# embeddings_queue

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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 206
encoding: FLOAT32
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{"title": "Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19", "chroma:document": "cal source and presents as a novel explorative and diagnostical tool.\nMethods Patients with PCR\u2011verified COVID\u201119 infection (COV\u2011POS, n = 20), and patients with respiratory symptoms \nbut with > 2 negative polymerase chain reaction (PCR) tests (COV\u2011NEG, n = 16) and healthy controls (HCO, n = 12) \nwere prospectively recruited. EBPs were collected using a \u201cparticles in exhaled air\u201d (PExA 2.0) device. Particle per \nexhaled volume (PEV) and size distribution profiles were compared. Proteins were analyzed using liquid chromatog\u2011\nraphy\u2011mass spectrometry. A random forest machine learning classification model was then trained and validated on \nEBP data achieving an accuracy of 0.92.\nResults Significant increases in PEV and changes in size distribution profiles of EBPs was seen in COV\u2011POS and \nCOV\u2011NEG compared to healthy controls. We achieved a deep proteome profiling of EBP across the three groups \nwith proteins involved in immune activation, acute phase response, cell adhesion, blood coagulation, and known \ncomponents of the respiratory tract lining fluid, among others. We demonstrated promising results for the use of an \nintegrated EBP biomarker panel together with particle concentration for diagnosis of COVID\u201119 as well as a robust \nmethod for protein identification in EBPs.\nConclusion Our results demonstrate the promising potential for the use of EBP fingerprints in biomarker discovery \nand for diagnosing pulmonary diseases, rapidly and non\u2011invasively with minimal patient discomfort.\nKeywords Exhaled breath particles, Proteomics, COVID\u201119, LC\u2013MS/MS, Breath analysis\n*Correspondence:\nSandra Lindstedt\nsandra.lindstedt_ingemansson@med.lu.se\nFull list of author information is available at the end of the article"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 207
encoding: FLOAT32
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{"title": "A tripartite view of the posterior cingulate cortex", "chroma:document": "A tripartite view of the posterior cingulate cortex\nBrett L. Foster1, Seth R. Koslov1, Lyndsey Aponik-Gremillion2,3, Megan E. Monko4, \nBenjamin Y. Hayden4,5, Sarah R. Heilbronner4\n1Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, \nPhiladelphia, PA, USA.\n2Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.\n3Department of Health Sciences, Dumke College for Health Professionals, Weber State \nUniversity, Ogden, UT, USA.\n4Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.\n5Center for Magnetic Resonance Research and Center for Neural Engineering, University of \nMinnesota, Minneapolis, MN, USA.\nAbstract\nThe posterior cingulate cortex (PCC) is one of the least understood regions of the cerebral \ncortex. By contrast, the anterior cingulate cortex has been the subject of intensive investigation in \nhumans and model animal systems, leading to detailed behavioural and computational theoretical \naccounts of its function. The time is right for similar progress to be made in the PCC given \nits unique anatomical and physiological properties and demonstrably important contributions to \nhigher cognitive functions and brain diseases. Here, we describe recent progress in understanding \nthe PCC, with a focus on convergent findings across species and techniques that lay a foundation \nfor establishing a formal theoretical account of its functions. Based on this converging evidence, \nwe propose that the broader PCC region contains three major subregions \u2013 the dorsal PCC, ventral \nPCC and retrosplenial cortex \u2013 that respectively support the integration of executive, mnemonic \nand spatial processing systems. This tripartite subregional view reconciles inconsistencies in prior \nunitary theories of PCC function and offers promising new avenues for progress.\nIntroduction\nThe posterior cingulate cortex (PCC) is one of the most poorly understood regions of the \ncerebrum1-3. In general, the PCC has not received the consistent empirical and theoretical"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 208
encoding: FLOAT32
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{"title": "A tripartite view of the posterior cingulate cortex", "chroma:document": "Reprints and permissions information is available at www.nature.com/reprints.\nCorrespondence should be addressed to Brett L. Foster. brett.foster@pennmedicine.upenn.edu.\nAuthor contributions\nAll authors contributed to researching data for the article and writing the article. B.L.F., S.R.K., S.R.H. and B.Y.H. contributed \nsignificantly to discussion of article content and reviewed and/or edited the article.\nCompeting interests\nThe authors declare no competing interests.\nSupplementary information The online version contains supplementary material available at https://doi.org/10.1038/\ns41583-022-00661-x.\nHHS Public Access\nAuthor manuscript\nNat Rev Neurosci. Author manuscript; available in PMC 2023 March 27.\nPublished in final edited form as:\nNat Rev Neurosci. 2023 March ; 24(3): 173\u2013189. doi:10.1038/s41583-022-00661-x.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 209
encoding: FLOAT32
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{"title": "Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits", "chroma:document": "Cellular/Molecular\nInsufficient Oligodendrocyte Turnover in Optic Nerve\nContributes to Age-Related Axon Loss and Visual Deficits\nJun-Jie Zhi,1,2p Shuang-Ling Wu,2,3p Hao-Qian Wu,1,2p Qi Ran,1,2 Xing Gao,2 Jing-Fei Chen,2 Xing-Mei Gu,2,4\nTao Li,2 Fei Wang,2\nLan Xiao,2 Jian Ye,1 and Feng Mei2,3\n1Department of Ophthalmology and Institute of Surgery Research, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing,\n400042, China, 2Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Brain and Intelligence Research Key Laboratory of\nChongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing, 400038, China, 3School of Medicine,\nChongqing University, Chongqing, 400030, China, and 4Department of Medical English Teaching and Research, Third Military Medical University (Army\nMedical University), Chongqing, 400038, China\nAge-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available\nup-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-\n18months) and old (20-22months) mice of either sex compared with adult mice (3-8months), accompanied by functional deficits.\nOligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL\nturnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis dis-\nplayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and\nvisual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice.\nGenetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 210
encoding: FLOAT32
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{"title": "Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits", "chroma:document": "impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual func-\ntion. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clem-\nastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine\ntreatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved\nvisual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and\nvisual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function.\nKey words: clemastine; myelin; myelination; oligodendrogenesis; OPC; RGC\nSignificance Statement\nOligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional sig-\nnificance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manip-\nulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent\nmanner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration,\nalong with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin\ngeneration in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promot-\ning OL generation might be a promising strategy to preserve visual function from age-related decline.\nIntroduction\nAge-related decline in visual functions emerges irreversibly in\nthe elder population, such as impaired visual acuity and contrast\nsensitivity to visual signals (C. Zhang et al., 2008). The pathologic\nchanges underlying the functional damages are complicated and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 211
encoding: FLOAT32
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{"title": "Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits", "chroma:document": "remain elusive. The optic nerve (ON) is mainly made up of the\naxons of the retinal ganglion cells (RGCs) from the retina. The\naxons are susceptible to age and undergo irreversible degenera-\ntion with a ;40% decrease in axon number throughout the life-\nspan regardless of species (Cavallotti et al., 2002; Neufeld and\nGachie, 2003; Harwerth et al., 2008; Calkins, 2013; Fortune et al.,\nReceived Nov. 16, 2022; revised Jan. 16, 2023; accepted Jan. 27, 2023.\nAuthor contributions: J.-J.Z., S.-L.W., H.-Q.W., Q.R., X.G., J.-F.C., T.L., F.W., and F.M. performed research; J.-J.Z.,\nS.-L.W., H.-Q.W., Q.R., T.L., and F.W. analyzed data; H.-Q.W., X.-M.G., L.X., J.Y., and F.M. edited the paper; X.G., X.-M.G.,\nT.L., L.X., and J.Y. contributed unpublished reagents/analytic tools; F.M. designed research; F.M. wrote the paper.\nThis work was supported by the STI 2030\u2013Major Projects (2021ZD0201702), National Natural Science Foundation of\nChina (82171417, 81901378, 32000723, 31921003), Chongqing Education Commission Fund (CXQT19009), and Young Elite\nScientists Sponsorship Program by CAST (YESS 2019QNRC001). We thank Drs. J. Josh Lawrence (Texas Tech University) and\nSusumu Tonegawa (Massachusetts Institute of Technology) for the M1R floxed mice; Dr. Richard Lu (University of\nCincinnati) for the Olig2 floxed mice; and Dr. Sonia Mayoral (Brown University) for critical reading of the manuscript.\n*J.-J.Z., S.-L.W., and H.-Q.W. contributed equally to this work.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Jian Ye at yejian1979@163.com or Feng Mei at meif@tmmu.edu.cn.\nhttps://doi.org/10.1523/JNEUROSCI.2130-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, March 15, 2023 \u2022 43(11):1859\u20131870 \u2022 1859"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 212
encoding: FLOAT32
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{"title": "Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity", "chroma:document": "Cerebral blood flow and cardiovascular risk effects on resting \nbrain regional homogeneity\nBhim M. Adhikaria, L. Elliot Honga, Zhiwei Zhaob, Danny J.J. Wangc, Paul M. Thompsond, \nNeda Jahanshadd, Alyssa H. Zhud, Stefan Holigae, Jessica A. Turnerf, Theo G.M. van \nErpg,h, Vince D. Calhounf,i, Kathryn S. Hatcha, Heather Brucea, Stephanie M. Harea, Joshua \nChiappellia, Eric L. Goldwasera, Mark D. Kvartaa, Yizhou Maa, Xiaoming Dua, Thomas E. \nNicholsj, Alan R. Shuldinerk, Braxton D. Mitchellk, Juergen Dukartl,m, Shuo Chena, Peter \nKochunova,\u2217\naMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School \nof Medicine, Baltimore, MD 21228\nbUniversity of Maryland, College Park, MD 20742\nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)\n\u2217 Corresponding author at: Maryland Psychiatry Research Center, Department of Psychiatry, University of Maryland School of \nMedicine, Baltimore, MD 21228. pkochunov@som.umaryland.edu (P. Kochunov). \nCredit authorship contribution statement\nB. M. Adhikari: Formal analysis, Investigation, Methodology, Visualization, Writing \u2013 original draft, Writing \u2013 review and editing.\nP. Kochunov, L. E. Hong: Conceptualization, Research design and data acquisition, Funding acquisition and project administration, \nWriting \u2013 review and editing.\nS. Chen, Z. Zhao: Data analysis, Methodology, Writing \u2013 review and editing\nD. J. J. Wang, P. M. Thompson, N. Jahanshad, A. H. Zhu, J. A. Turner, T. G. M. van Erp, V. D. Calhoun, K. S. Hatch, H. Bruce, S. M. \nHare, J. Chiappelli, E. L. Goldwaser, M. D. Kvarta, Y. Ma, X. Du, T. E. Nichols, A. R. Shuldiner, B. D. Mitchell: Writing \u2013 review and \nediting\nJ. Dukart, S. Holiga: Resources, Writing \u2013 review and editing\nData and code availability\nRelevant data are made available in the manuscript. Imaging data and relevant codes will be made available upon request.\nCompeting Interests"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 213
encoding: FLOAT32
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{"title": "Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity", "chroma:document": "LEH has received or plans to receive research funding or consulting fees on research projects from Mitsubishi, Your Energy Systems \nLLC, Neuralstem, Taisho, Heptares, Pfizer, Luye Pharma, Sound Pharma, Takeda, and Regeneron. None was involved in the design, \nanalysis or outcomes of the study. NJ and PT received a research grant from Biogen, Inc., for research unrelated to this project. All \nother authors declare no conflicts of interest.\nCredit authorship contribution statement\nBhim M. Adhikari: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing \u2013 original draft, Writing \u2013 \nreview & editing. L. Elliot Hong: Conceptualization, Investigation, Funding acquisition, Project administration, Supervision, Writing \n\u2013 review & editing. Zhiwei Zhao: Formal analysis, Methodology, Writing \u2013 review & editing. Danny J.J. Wang: Writing \u2013 review \n& editing. Paul M. Thompson: Writing \u2013 review & editing. Neda Jahanshad: Writing \u2013 review & editing. Alyssa H. Zhu: Writing \n\u2013 review & editing. Stefan Holiga: Resources, Writing \u2013 review & editing. Jessica A. Turner: Writing \u2013 review & editing. Theo \nG.M. van Erp: Writing \u2013 review & editing. Vince D. Calhoun: Writing \u2013 review & editing. Kathryn S. Hatch: Writing \u2013 review & \nediting. Heather Bruce: Writing \u2013 review & editing. Stephanie M. Hare: Writing \u2013 review & editing. Joshua Chiappelli: Writing \n\u2013 review & editing. Eric L. Goldwaser: Writing \u2013 review & editing. Mark D. Kvarta: Writing \u2013 review & editing. Yizhou Ma: \nWriting \u2013 review & editing. Xiaoming Du: Writing \u2013 review & editing. Thomas E. Nichols: Writing \u2013 review & editing. Alan R. \nShuldiner: Writing \u2013 review & editing. Braxton D. Mitchell: Writing \u2013 review & editing. Juergen Dukart: Resources, Writing \n\u2013 review & editing. Shuo Chen: Formal analysis, Methodology, Writing \u2013 review & editing. Peter Kochunov: Conceptualization, \nInvestigation, Funding acquisition, Project administration, Supervision, Writing \u2013 review & editing.\nSupplementary materials"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 214
encoding: FLOAT32
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{"title": "Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity", "chroma:document": "Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.neuroimage.2022.119555.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 March 28.\nPublished in final edited form as:\nNeuroimage. 2022 November 15; 262: 119555. doi:10.1016/j.neuroimage.2022.119555.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 215
encoding: FLOAT32
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{"title": "Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications", "chroma:document": "Liu\u00a0et\u00a0al. Military Medical Research           (2023) 10:16  \nhttps://doi.org/10.1186/s40779-023-00448-w\nREVIEW\nOpen Access\n\u00a9 The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBiomimetic natural biomaterials for\u00a0tissue \nengineering and\u00a0regenerative medicine: \nnew biosynthesis methods, recent advances, \nand\u00a0emerging applications\nShuai Liu1, Jiang\u2011Ming Yu2, Yan\u2011Chang Gan1, Xiao\u2011Zhong Qiu1, Zhe\u2011Chen Gao2, Huan Wang3*, \nShi\u2011Xuan Chen4*, Yuan Xiong5, Guo\u2011Hui Liu5, Si\u2011En Lin6, Alec McCarthy7, Johnson V. John8, Dai\u2011Xu Wei2,9,10* and \nHong\u2011Hao Hou1*   \nAbstract \nBiomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and \nregenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based \non natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 216
encoding: FLOAT32
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{"title": "Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications", "chroma:document": "extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, \nand inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regen\u2011\nerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), \nincluding advances in their preparation, functionality, potential applications and future challenges. We highlight \nrecent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs \nwith various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent \nkey advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by \noffering our perspective on open challenges and future developments in this rapidly\u2011evolving field.\nKeywords Biomimic, Scaffold, Biosynthesis, Natural biomaterial, Tissue engineering\n*Correspondence:\nHuan Wang\nwangh679@mail.sysu.edu.cn\nShi\u2011Xuan Chen\nchensx@ucas.ac.cn\nDai\u2011Xu Wei\ndaviddxwei@163.com\nHong\u2011Hao Hou\nss.hhh89@hotmail.com\n1 Guangdong Provincial Key Laboratory of Construction and Detection \nin Tissue Engineering, The Fifth Affiliated Hospital, School of Basic Medical \nScience, Southern Medical University, Guangzhou 510900, China\n2 Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong \nUniversity, Shanghai 200336, China\n3 The Eighth Affiliated Hospital, Sun Yat\u2011Sen University, Shenzhen 518033, \nGuangdong, China\n4 Engineering Research Center of Clinical Functional Materials \nand Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou \nInstitute, University of Chinese Academy of Sciences, Wenzhou 325011, \nZhejiang, China\n5 Department of Orthopedics, Union Hospital, Tongji Medical College, \nHuazhong University of Science and Technology, Wuhan 430022, China\n6 Department of Orthopaedics and Traumatology, Faculty of Medicine,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 217
encoding: FLOAT32
metadata:
{"title": "Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications", "chroma:document": "the Chinese University of Hong Kong, Hong Kong SAR 999077, China\n7 Department of Functional Materials, Terasaki Institute for Biomedical \nInnovation, Los Angeles, CA 90064, USA\n8 Mary & Dick Holland Regenerative Medicine Program, College \nof Medicine, University of Nebraska Medical Center, Omaha, NE 68130, \nUSA\n9 Zigong Affiliated Hospital of Southwest Medical University, Zigong \nPsychiatric Research Center, Zigong Institute of Brain Science, \nZigong 643002, Sichuan, China\n10 Key Laboratory of Resource Biology and Biotechnology in Western \nChina, Ministry of Education, School of Medicine, Department of Life \nSciences and Medicine, Northwest University, Xi\u2019an 710127, China"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 218
encoding: FLOAT32
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{"title": "Visual Characteristics of Adults with Long-Standing History of Dietary Exposure to Mercury in Grassy Narrows First Nation, Canada", "chroma:document": "Citation: Tousignant, B.; Chatillon,\nA.; Philibert, A.; Da Silva, J.; Fillion,\nM.; Mergler, D. Visual Characteristics\nof Adults with Long-Standing\nHistory of Dietary Exposure to\nMercury in Grassy Narrows First\nNation, Canada. Int. J. Environ. Res.\nPublic Health 2023, 20, 4827. https://\ndoi.org/10.3390/ijerph20064827\nAcademic Editor: Paul B. Tchounwou\nReceived: 31 January 2023\nRevised: 23 February 2023\nAccepted: 7 March 2023\nPublished: 9 March 2023\nCopyright:\n\u00a9 2023 by the authors.\nLicensee MDPI, Basel, Switzerland.\nThis article is an open access article\ndistributed\nunder\nthe\nterms\nand\nconditions of the Creative Commons\nAttribution (CC BY) license (https://\ncreativecommons.org/licenses/by/\n4.0/).\nInternational  Journal  of\nEnvironmental Research\nand Public Health\nArticle\nVisual Characteristics of Adults with Long-Standing History\nof Dietary Exposure to Mercury in Grassy Narrows First\nNation, Canada\nBenoit Tousignant 1,2,*\n, Annie Chatillon 1, Aline Philibert 3, Judy Da Silva 4, Myriam Fillion 3,5\nand Donna Mergler 3\n1\nSchool of Optometry, Universit\u00e9 de Montr\u00e9al, 3744 Jean-Brillant, Montreal, QC H3T 1P1, Canada\n2\nDepartment of Social and Preventive Medicine, School of Public Health, Universit\u00e9 de Montr\u00e9al,\n7101 Avenue du Parc, Montreal, QC H3N 1X9, Canada\n3\nCentre de Recherche Interdisciplinaire sur le Bien-\u00eatre, la Sant\u00e9, la Soci\u00e9t\u00e9 et L\u2019environnement (Cinbiose),\nUniversit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, C.P. 8888, Succ. Centre-Ville, Montr\u00e9al, QC H3C 3P8, Canada\n4\nGrassy Narrows First Nation, General Delivery, Grassy Narrows, ON P0X 1B0, Canada\n5\nD\u00e9partement Science et Technologie, Universit\u00e9 T\u00c9LUQ, 5800, Rue Saint-Denis, Bureau 1105,\nMontr\u00e9al, QC H2S 3L5, Canada\n*\nCorrespondence: benoit.tousignant@umontreal.ca\nAbstract: Since the 1960s, Grassy Narrows First Nation (Ontario, Canada) has been exposed to methyl\nmercury (Hg) through \ufb01sh consumption, resulting from industrial pollution of their territorial waters.\nThis cross-sectional study describes the visual characteristics of adults with documented Hg exposure"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 219
encoding: FLOAT32
metadata:
{"title": "Visual Characteristics of Adults with Long-Standing History of Dietary Exposure to Mercury in Grassy Narrows First Nation, Canada", "chroma:document": "between 1970 and 1997. Oculo-visual examinations of 80 community members included visual acuity,\nautomated visual \ufb01elds, optical coherence tomography [OCT], color vision and contrast sensitivity.\nMedian age was 57 years (IQR 51\u201363) and 55% of participants were women. Median visual acuity was\n0.1 logMAR (Snellen 6/6.4; IQR 0\u20130.2). A total of 26% of participants presented a Visual Field Index\ninferior to 62%, and qualitative losses assessment showed concentric constriction (18%), end-stage\nconcentric loss (18%), and complex defects (24%). On OCT, retinal nerve \ufb01ber layer scans showed\n74% of participants within normal/green range. For color testing with the Hardy, Rand, and Rittler\ntest, 40% presented at least one type of color defect, and with the Lanthony D-15 test, median color\nconfusion index was 1.59 (IQR 1.33\u20131.96). Contrast sensitivity showed moderate loss for 83% of\nparticipants. These \ufb01ndings demonstrate important loss of visual \ufb01eld, color vision, and contrast\nsensitivity in older adults in a context of long-term exposure to Hg in Grassy Narrows First Nation.\nKeywords: methyl mercury; visual \ufb01eld; optical coherence tomography; color vision; contrast\nsensitivity; Indigenous peoples\n1. Introduction\nFor many Indigenous communities around the world, \ufb01sh is an important component\nof traditional food systems [1]; for some, \ufb01sh is not only a nutritious food [2], but also the\nheart of their culture and identity [3,4]. Colonization and dispossession have resulted in\nland degradation and pollution, with profound impacts on Indigenous food systems [5,6].\nMercury (Hg), from local and global sources, has polluted lakes, rivers, and oceans, bioac-\ncumulating and biomagnifying through the aquatic food chain [7]. While the bene\ufb01ts of\n\ufb01sh consumption have been widely documented [8,9], coastal and riverside Indigenous\ncommunities who rely on \ufb01sh for sustenance are often at risk from the toxic effects of\nmethyl Hg exposure [3,10,11]. In Northern Ontario, Canada, the Asubpeeschoseewagong"}


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id: 220
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{"title": "Visual Characteristics of Adults with Long-Standing History of Dietary Exposure to Mercury in Grassy Narrows First Nation, Canada", "chroma:document": "Anishinabek (also known as Grassy Narrows First Nation) people have been exposed to\nHg for 60 years through \ufb01sh consumption. Between 1962 and 1975, a chloralkali plant of a\npulp and paper mill discharged almost 10 tons of Hg into the \ufb02uvial lake system on their\ntraditional territories. In 1970, \ufb01sh was a dietary mainstay [12] and blood Hg concentrations\nInt. J. Environ. Res. Public Health 2023, 20, 4827. https://doi.org/10.3390/ijerph20064827\nhttps://www.mdpi.com/journal/ijerph"}


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{"title": "Changes Caused by Bisphenols in the Chemical Coding of Neurons of the Enteric Nervous System of Mouse Stomach", "chroma:document": "Citation: Makowska, K.; Gonkowski,\nS. Changes Caused by Bisphenols in\nthe Chemical Coding of Neurons of\nthe Enteric Nervous System of Mouse\nStomach. Int. J. Environ. Res. Public\nHealth 2023, 20, 5125. https://\ndoi.org/10.3390/ijerph20065125\nAcademic Editor: Mar\u00eda\nGemma Albend\u00edn\nReceived: 25 January 2023\nRevised: 4 March 2023\nAccepted: 13 March 2023\nPublished: 14 March 2023\nCopyright:\n\u00a9 2023 by the authors.\nLicensee MDPI, Basel, Switzerland.\nThis article is an open access article\ndistributed\nunder\nthe\nterms\nand\nconditions of the Creative Commons\nAttribution (CC BY) license (https://\ncreativecommons.org/licenses/by/\n4.0/).\nInternational  Journal  of\nEnvironmental Research\nand Public Health\nArticle\nChanges Caused by Bisphenols in the Chemical Coding of\nNeurons of the Enteric Nervous System of Mouse Stomach\nKrystyna Makowska 1,*\nand Slawomir Gonkowski 2\n1\nDepartment of Clinical Diagnostics, Faculty of Veterinary Medicine, University of Warmia and Mazury in\nOlsztyn, Oczapowskiego 14, 10-957 Olsztyn, Poland\n2\nDepartment of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in\nOlsztyn, Oczapowskiego 13, 10-957 Olsztyn, Poland\n*\nCorrespondence: krystyna.makowska@uwm.edu.pl\nAbstract: Bisphenol A (BPA), an organic chemical compound which is widely used in the production\nof plastics, can severely damage live organisms. Due to these \ufb01ndings, the plastic industry has\nstarted to replace it with other substances, most often with bisphenol S (BPS). Therefore, during\nthe present investigation, with the use of double immuno\ufb02uorescence labeling, we compared the\neffect of BPA and BPS on the enteric nervous system (ENS) in the mouse corpus of the stomach. The\nobtained results show that both studied toxins impact the amount of nerve cells immunoreactive to\nsubstance P (SP), galanin (GAL), vesicular acetylcholine transporter (VAChT is used here as a marker\nof cholinergic neurons) and vasoactive intestinal polypeptide (VIP). Changes observed under the"}


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id: 222
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{"title": "Changes Caused by Bisphenols in the Chemical Coding of Neurons of the Enteric Nervous System of Mouse Stomach", "chroma:document": "impact of both bisphenols depended on the neuronal factor, the type of the enteric ganglion and the\ndoses of bisphenols studied. Generally, the increase in the percentage of neurons immunoreactive\nto SP, GAL and/or VIP, and the decrease in the percentage of VAChT-positive neurons, was noted.\nSeverity of changes was more visible after BPA administration. However, the study has shown that\nlong time exposure to BPS also signi\ufb01cantly affects the ENS.\nKeywords: bisphenol A; bisphenol S; mice; enteric nervous system; stomach; neuroplasticity;\nimmuno\ufb02uorescence labeling\n1. Introduction\nBisphenol A (BPA) is an organic chemical compound of the phenol family that is\nwidely used in the production of plastics [1]. However, more and more studies have shown\nthe many negative effects of BPA on the living organism. Until now, the harmful effects of\nthis substance have been noticed in almost every internal system of the organism, \ufb01rst of\nall including the endocrine, reproductive and nervous systems [2].\nThese allegations have led to different ways of reducing the use of BPA in the plastic\nindustry. Therefore, many countries have introduced various restrictions on the use of\nBPA [1,3] and several substitutes of BPA have been implemented for the plastic production.\nThe substitute that is most commonly used is bisphenol S (BPS) [4]. Although at \ufb01rst\nBPS seemed safe for living organisms, more and more studies have featured its harmful\neffects on humans and animals [4\u20136]. It has been discovered that, as with BPA, BPS is also\nan endocrine disruptor with a negative impact on endocrine, digestive and reproductive\nsystems [7].\nBisphenols can get to the organism through several routes, namely through the di-\ngestive tract, airway or skin [8]. The main route of exposure is the gastrointestinal tract,\nwhich is connected with the penetration of bisphenols from food containers and bottles to\nfood and drinking water [1]. In the living organism, every alimentary toxin has to cross the"}


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id: 223
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{"title": "Changes Caused by Bisphenols in the Chemical Coding of Neurons of the Enteric Nervous System of Mouse Stomach", "chroma:document": "intestinal barrier formed with the immune system and enteric nervous system (ENS) [9].\nTherefore, the \ufb01rst subclinical signs of bisphenol intoxication can involve disturbances in\nthe digestive tract.\nInt. J. Environ. Res. Public Health 2023, 20, 5125. https://doi.org/10.3390/ijerph20065125\nhttps://www.mdpi.com/journal/ijerph"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 224
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{"title": "High-throughput screening of mutations affecting SARS-CoV-2 spike functions", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 225
encoding: FLOAT32
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{"title": "Safety and immunogenicity of the ChAdOx1, MVA-MERS-S, and GLS-5300 DNA MERS-CoV vaccines", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 226
encoding: FLOAT32
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{"title": "Repeatability and reproducibility of various 4D Flow CMR postprocessing software programs in a multi-software and multi-vendor cross-over comparison study", "chroma:document": "Oechtering\u00a0et\u00a0al. \nJournal of Cardiovascular Magnetic Resonance           (2023) 25:22  \nhttps://doi.org/10.1186/s12968-023-00921-4\nRESEARCH\nOpen Access\n\u00a9 The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nJournal of Cardiovascular\nMagnetic Resonance\nRepeatability and\u00a0reproducibility of\u00a0various \n4D Flow MRI postprocessing software programs \nin\u00a0a\u00a0multi-software and\u00a0multi-vendor cross-over \ncomparison study\nThekla H. Oechtering1,2,3*  , Andr\u00e9 Nowak1,2, Malte M. Sieren1,2, Andreas M. Stroth1,2, Nicolas Kirschke1,2, \nFranz Wegner1,2, Maren Balks1,2, Inke R. K\u00f6nig4, Ning Jin5, Joachim Graessner6, Hendrik Kooijman\u2011Kurfuerst7, \nAnja Hennemuth8,9, J\u00f6rg Barkhausen1,2 and Alex Frydrychowicz1,2 \nAbstract \nBackground Different software programs are available for the evaluation of 4D Flow cardiovascular magnetic reso\u2011\nnance (CMR). A good agreement of the results between programs is a prerequisite for the acceptance of the method."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 227
encoding: FLOAT32
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{"title": "Repeatability and reproducibility of various 4D Flow CMR postprocessing software programs in a multi-software and multi-vendor cross-over comparison study", "chroma:document": "Therefore, the goal was to compare quantitative results from a cross\u2011over comparison in individuals examined on two \nscanners of different vendors analyzed with four postprocessing software packages.\nMethods Eight healthy subjects (27 \u00b1 3 years, 3 women) were each examined on two 3T CMR systems (Ingenia, \nPhilips Healthcare; MAGNETOM Skyra, Siemens Healthineers) with a standardized 4D Flow CMR sequence. Six manu\u2011\nally placed aortic contours were evaluated with Caas (Pie Medical Imaging, SW\u2011A), cvi42 (Circle Cardiovascular Imag\u2011\ning, SW\u2011B), GTFlow (GyroTools, SW\u2011C), and MevisFlow (Fraunhofer Institute MEVIS, SW\u2011D) to analyze seven clinically \nused parameters including stroke volume, peak flow, peak velocity, and area as well as typically scientifically used wall \nshear stress values. Statistical analysis of inter\u2011 and intrareader variability, inter\u2011software and inter\u2011scanner comparison \nincluded calculation of absolute and relative error  (ER), intraclass correlation coefficient (ICC), Bland\u2013Altman analysis, \nand equivalence testing based on the assumption that inter\u2011software differences needed to be within 80% of the \nrange of intrareader differences.\nResults SW\u2011A and SW\u2011C were the only software programs showing agreement for stroke volume (ICC = 0.96; \n ER = 3 \u00b1 8%), peak flow (ICC: 0.97;  ER = \u22121 \u00b1 7%), and area (ICC = 0.81;  ER = 2 \u00b1 22%). Results from SW\u2011A/D and SW\u2011C/D \nwere equivalent only for area and peak flow. Other software pairs did not yield equivalent results for routinely used \nclinical parameters. Especially peak maximum velocity yielded poor agreement (ICC \u2264 0.4) between all software pack\u2011\nages except SW\u2011A/D that showed good agreement (ICC = 0.80). Inter\u2011 and intrareader consistency for clinically used \nparameters was best for SW\u2011A and SW\u2011D (ICC = 0.56\u201397) and worst for SW\u2011B (ICC = \u20110.01\u20130.71). Of note, inter\u2011scanner \ndifferences per individual tended to be smaller than inter\u2011software differences."}


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id: 228
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{"title": "Repeatability and reproducibility of various 4D Flow CMR postprocessing software programs in a multi-software and multi-vendor cross-over comparison study", "chroma:document": "Conclusions Of all tested software programs, only SW\u2011A and SW\u2011C can be used equivalently for determination of \nstroke volume, peak flow, and vessel area. Irrespective of the applied software and scanner, high intra\u2011 and interreader \n*Correspondence:\nThekla H. Oechtering\nThekla.Oechtering@uksh.de\nFull list of author information is available at the end of the article"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 229
encoding: FLOAT32
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{"title": "Strategies for modelling endometrial diseases", "chroma:document": "Strategies for modelling endometrial diseases\nAlina R. Murphy,\nHannes Campo,\nJ. Julie Kim\nDivision of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, \nNorthwestern University, Chicago, IL, USA.\nAbstract\nEach month during a woman\u2019s reproductive years, the endometrium undergoes vast changes to \nprepare for a potential pregnancy. Diseases of the endometrium arise for numerous reasons, many \nj-kim4@northwestern.edu .\nAuthor contributions\nThe authors contributed equally to all aspects of the article.\nCompeting interests\nThe authors declare no competing interests.\nPeer review information\nNature Reviews Endocrinology thanks Caroline Gargett, Virginia Pensabene and the other, anonymous, reviewer(s) for their \ncontribution to the peer review of this work.\nSpringer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other \nrightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such \npublishing agreement and applicable law.\nOrganoids\n3D cellular aggregates that self-assemble and form structural units that partially resemble the organ in both structure and function.\nMicrophysiological systems\nIntegrative, microfabricated platforms designed to recapitulate functional units of human organs in vitro; also known as organ-on-a-\nchip technology.\nThermoplastics\nA class of polymer that can be permanently deformed through the application of heat.\nCurettage\nScraping or removal of endometrial tissue for diagnostic or therapeutic purposes.\nSpheroids\n3D, simple clusters of cells that lack self-assembly or organization.\nSampson\u2019s retrograde menstruation theory\nTheory to explain the aetiology of endometriosis in which retrograde flow of sloughed endometrial cells during menstruation occurs \nthrough the fallopian tubes into the pelvic cavity promoting the establishment of ectopic lesions.\nChorioallantoic membrane"}


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id: 230
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{"title": "Strategies for modelling endometrial diseases", "chroma:document": "(CAM). A membrane in bird eggs that is the site of gas exchange for the embryo.\nTranswell\nA commercially available Boyden chamber device with a microporous membrane that inserts into a standard cell culture well and \nprovides a second compartment.\nMicropatterned\nSeeding and controlling the geometry and location of cells at the microscale level.\nM\u00fcllerian remnants\nPluripotent remains of the embryonic precursor to the uterus, which could undergo metaplasia into endometrial tissue during the \ndevelopment of adenomyosis.\nBiobanking\nCreating a repository of biological samples for use in future research.\nHHS Public Access\nAuthor manuscript\nNat Rev Endocrinol. Author manuscript; available in PMC 2023 March 29.\nPublished in final edited form as:\nNat Rev Endocrinol. 2022 December ; 18(12): 727\u2013743. doi:10.1038/s41574-022-00725-z.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 231
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{"title": "Using mesoscopic tract-tracing data to guide the estimation of fiber orientation distributions in the mouse brain from diffusion\\\r MRI", "chroma:document": "Using mesoscopic tract-tracing data to guide the estimation of \nfiber orientation distributions in the mouse brain from diffusion \nMRI\nZifei Liang,\nTanzil Mahmud Arefin,\nChoong H. Lee,\nJiangyang Zhang*\nDepartment of Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, New York \nUniversity School of Medicine, 660 First Ave, New York, NY 10016, USA\nAbstract\nDiffusion MRI (dMRI) tractography is the only tool for non-invasive mapping of macroscopic \nstructural connectivity over the entire brain. Although it has been successfully used to reconstruct \nlarge white matter tracts in the human and animal brains, the sensitivity and specificity of \ndMRI tractography remained limited. In particular, the fiber orientation distributions (FODs) \nestimated from dMRI signals, key to tractography, may deviate from histologically measured \nfiber orientation in crossing fibers and gray matter regions. In this study, we demonstrated that \na deep learning network, trained using mesoscopic tract-tracing data from the Allen Mouse \nBrain Connectivity Atlas, was able to improve the estimation of FODs from mouse brain dMRI \ndata. Tractography results based on the network generated FODs showed improved specificity \nwhile maintaining sensitivity comparable to results based on FOD estimated using a conventional \nspherical deconvolution method. Our result is a proof-of-concept of how mesoscale tract-tracing \ndata can guide dMRI tractography and enhance our ability to characterize brain connectivity.\nKeywords\nDiffusion MRI; Tractography; Mouse brain; Deep learning; Fiber orientation distribution; \nConnectivity\nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)\n*Corresponding author. Jiangyang.zhang@nyulangone.org (J. Zhang). \nCredit author statement\nThe project was conceived by Z.L. and J.Z.. T.A. was involved in discussion and tractography. C.L. acquired and analyzed most MR \nimages. Z.L. and J.Z. wrote and prepared the paper, C.L. and T.A. edited the paper."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 232
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{"title": "Using mesoscopic tract-tracing data to guide the estimation of fiber orientation distributions in the mouse brain from diffusion\\\r MRI", "chroma:document": "Declaration of Competing Interest\nThe authors declare no competing interest related to the work presented here.\nSupplementary materials\nSupplementary material associated with this article can be found, in the online version, at doi:10.1016/j.neuroimage.2023.119999.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 April 15.\nPublished in final edited form as:\nNeuroimage. 2023 April 15; 270: 119999. doi:10.1016/j.neuroimage.2023.119999.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 233
encoding: FLOAT32
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{"title": "Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment", "chroma:document": "Multiregion transcriptomic profiling of the primate brain reveals \nsignatures of aging and the social environment\nKenneth L. Chiou1,2,3,4,28, Alex R. DeCasien5,6,28, Katherina P. Rees2, Camille Testard7, \nCailyn H. Spurrell8, Aishwarya A. Gogate8,9, Hannah A. Pliner8, S\u00e9bastien Tremblay7, \nArianne Mercer3, Connor J. Whalen5, Josu\u00e9 E. Negr\u00f3n-Del Valle2, Mareike C. Janiak10, \nSamuel E. Bauman Surratt11, Olga Gonz\u00e1lez12, Nicole R. Compo11, Michala K. Stock13, \nAngelina V. Ruiz-Lambides11, Melween I. Mart\u00ednez11,\nCayo Biobank Research Unit*,\nMelissa A. Wilson1,2, Amanda D. Melin14,15,16, Susan C. Ant\u00f3n5,6, Christopher S. Walker17, \nJ\u00e9r\u00f4me Sallet18, Jason M. Newbern2, Lea M. Starita8,19, Jay Shendure8,19,20,21, James P. \nHigham5,6, Lauren J. N. Brent22, Michael J. Montague7, Michael L. Platt7,23,24, Noah Snyder-\nMackler1,2,3,4,25,26,27\n1Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA.\n2School of Life Sciences, Arizona State University, Tempe, AZ, USA.\n3Department of Psychology, University of Washington, Seattle, WA, USA.\n*A list of authors and their affiliations appears at the end of the paper.\nReprints and permissions information is available at www.nature.com/reprints.\nCorrespondence and requests for materials should be addressed to Kenneth L. Chiou, Alex R. DeCasien or Noah Snyder-Mackler. \nchiou@asu.edu; alex.decasien@nyu.edu; nsnyderm@asu.edu.\nAuthor contributions\nN.S.-M., M.L.P., M.J.M., J.P.H., L.J.N.B., K.L.C. and A.R.D. conceptualized the research. N.S.-M., J. Shendure, M.L.P., M.J.M., \nL.M.S. and K.L.C. conceptualized the single-cell sequencing studies. M.J.M., N.S.-M., K.L.C., A.R.D., O.G., N.R.C., S.E.B.S., \nM.C.J., C.J.W. and S.T. collected brain tissue, facilitated by M.I.M., A.V.R.-L., J. Sallet, C.S.W., S.C.A., M.K.S., A.D.M., J.P.H., \nM.L.P. and CBRU. M.A.W. contributed data. K.L.C., A.R.D., A.M. and C.H.S. performed genomic lab work. J.E.N.-D.V. collected"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 234
encoding: FLOAT32
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{"title": "Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment", "chroma:document": "behavioral data using a protocol designed by L.J.N.B. K.L.C., A.R.D., C.H.S., A.A.G. and H.A.P. performed genomic analysis \nwith input from N.S.-M. and J. Shendure. C.T. and L.J.N.B. performed behavioral analysis. K.P.R. and J.M.N. performed protein \nexperiments and analysis. K.L.C., A.R.D. and N.S.-M. wrote the manuscript. All authors reviewed and revised the manuscript. Full \nmembership of the CBRU: S. C. Ant\u00f3n, L. J. N. Brent, J. P. Higham, M. I. Mart\u00ednez, A. D. Melin, M. J. Montague, M. L. Platt, J. \nSallet and N. Snyder-Mackler\nCompeting interests\nJ. Shendure is a scientific advisory board member, consultant and/or cofounder of Cajal Neuroscience, Guardant Health, Maze \nTherapeutics, Camp4 Therapeutics, Phase Genomics, Adaptive Biotechnologies, Scale Biosciences and Sixth Street Capital. M.L.P. \nis a scientific advisory board member, consultant and/or cofounder of Blue Horizons International, NeuroFlow, Amplio, Cogwear \nTechnologies, Burgeon Labs and Ashurst Cognitive Health and receives research funding from AIIR Consulting, the SEB Group, Mars \nInc., Slalom Inc., the Lefkort Family Research Foundation, Sisu Capital and Benjamin Franklin Technology Partners. All other authors \ndeclare no competing interests.\nExtended data is available for this paper at https://doi.org/10.1038/s41593-022-01197-0.\nSupplementary information The online version contains supplementary material available at https://doi.org/10.1038/\ns41593-022-01197-0.\nReporting summary\nFurther information on research design is available in the Nature Portfolio Reporting Summary linked to this article.\nOnline content\nAny methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, \nacknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code \navailability are available at https://doi.org/10.1038/s41593-022-0n97-0.\nHHS Public Access\nAuthor manuscript\nNat Neurosci. Author manuscript; available in PMC 2023 June 01."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 235
encoding: FLOAT32
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{"title": "Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment", "chroma:document": "Published in final edited form as:\nNat Neurosci. 2022 December ; 25(12): 1714\u20131723. doi:10.1038/s41593-022-01197-0.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 236
encoding: FLOAT32
metadata:
{"title": "Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability", "chroma:document": "https://doi.org/10.1093/brain/awac031\nBRAIN 2023: 146; 359\u2013371 | 359\nStem cell-derived sensory neurons modelling \ninherited erythromelalgia: normalization of \nexcitability\nMatthew Alsaloum,1,2,3,4,5 Julie I. R. Labau,1,2,3,6,7 Shujun Liu,1,2,3 Philip R. Effraim2,3,8 \nand Stephen G. Waxman1,2,3\nEffective treatment of pain remains an unmet healthcare need that requires new and effective therapeutic ap-\nproaches. NaV1.7 has been genetically and functionally validated as a mediator of pain. Preclinical studies of \nNaV1.7-selective blockers have shown limited success and translation to clinical studies has been limited. The degree \nof NaV1.7 channel blockade necessary to attenuate neuronal excitability and ameliorate pain is an unanswered ques-\ntion important for drug discovery. Here, we utilize dynamic clamp electrophysiology and induced pluripotent stem \ncell-derived sensory neurons (iPSC-SNs) to answer this question for inherited erythromelalgia, a pain disorder caused \nby gain-of-function mutations in Nav1.7. We show that dynamic clamp can produce hyperexcitability in iPSC-SNs as-\nsociated with two different inherited erythromelalgia mutations, NaV1.7-S241T and NaV1.7-I848T. We further show \nthat blockade of approximately 50% of NaV1.7 currents can reverse neuronal hyperexcitability to baseline levels.\n1\nDepartment of Neurology, Yale School of Medicine, New Haven, CT 06510, USA\n2\nCenter for Neuroscience and Regeneration Research, Yale University, West Haven, CT 06516, USA\n3\nCenter for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA\n4\nYale Medical Scientist Training Program, Yale School of Medicine, New Haven, CT 06510, USA\n5\nInterdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA\n6\nDepartment of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University \nMedical Centre, Maastricht, The Netherlands\n7\nDepartment of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands\n8"}


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id: 237
encoding: FLOAT32
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{"title": "Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability", "chroma:document": "8\nDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT 06510, USA\nCorrespondence to: Stephen G. Waxman  \nCenter for Neuroscience and Regeneration Research  \n950 Campbell Ave, Building 34, West Haven, CT 06516, USA  \nE-mail: Stephen.waxman@yale.edu\nKeywords: Inherited erythromelalgia; Nav1.7; dynamic clamp; iPSC; stem cell-derived sensory neurons\nReceived October 17, 2021. Revised December 30, 2021. Accepted January 6, 2022. Advance access publication January 28, 2022\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: \njournals.permissions@oup.com\nIntroduction\nChronic pain affects a significant percentage of the global \npopulation1\u20133 and contributes to multiple comorbidities and \nan impaired quality of life.4\u20136 Unfortunately, most pharma-\ncotherapies are only partially effective or ineffective and may \nbe associated with significant adverse effects.7\u20139 The develop-\nment of improved pain therapeutics is an urgent healthcare \nneed.\nVoltage-gated sodium (NaV) channels have emerged as promis-\ning targets for the development of novel pain therapeutics. Nine \ndifferent NaV channels (NaV1.1\u2013NaV1.9) have been described in hu-\nmans.10,11 Of these nine NaV channel isoforms, three\u2014NaV1.7, \nNaV1.8, and NaV1.9\u2014are preferentially expressed in dorsal root \nganglion (DRG) neurons, primary afferents responsible for trans-\nmitting pain information into the spinal cord.12 Hyperexcitability \nof DRG neurons is known to underlie the development and"}


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id: 238
encoding: FLOAT32
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{"title": "Temporopolar regions of the human brain", "chroma:document": "https://doi.org/10.1093/brain/awac339\nBRAIN 2023: 146; 20\u201341 | 20\nTemporopolar regions of the human brain\nM.-Marsel Mesulam\nFollowing prolonged neglect during the formative decades of behavioural neurology, the temporopolar region has be-\ncome a site of vibrant research on the neurobiology of cognition and conduct. This turnaround can be attributed to in-\ncreasing recognition of neurodegenerative diseases that target temporopolar regions for peak destruction. The \nresultant syndromes include behavioural dementia, associative agnosia, semantic forms of primary progressive aphasia \nand semantic dementia. Clinicopathological correlations show that object naming and word comprehension are critically \ndependent on the language-dominant (usually left) temporopolar region, whereas behavioural control and non-verbal \nobject recognition display a more bilateral representation with a rightward bias. Neuroanatomical experiments in maca-\nques and neuroimaging in humans show that the temporoparietal region sits at the confluence of auditory, visual and \nlimbic streams of processing at the downstream (deep) pole of the \u2018what\u2019 pathway. The functional neuroanatomy of \nthis region revolves around three axes, an anterograde horizontal axis from unimodal to heteromodal and paralimbic cor-\ntex; a radial axis where visual (ventral), auditory (dorsal) and paralimbic (medial) territories encircle temporopolar cortex \nand display hemispheric asymmetry; and a vertical depth-of-processing axis for the associative elaboration of words, ob-\njects and interoceptive states. One function of this neural matrix is to support the transformation of object and word re-\npresentations from unimodal percepts to multimodal concepts. The underlying process is likely to start at canonical \ngateways that successively lead to generic (superordinate), specific (basic) and unique levels of recognition. A first sign \nof left temporopolar dysfunction takes the form of taxonomic blurring where boundaries among categories are preserved"}


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id: 239
encoding: FLOAT32
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{"title": "Temporopolar regions of the human brain", "chroma:document": "but not boundaries among exemplars of a category. Semantic paraphasias and coordinate errors in word\u2013picture verifi-\ncation tests are consequences of this phenomenon. Eventually, boundaries among categories are also blurred and com-\nprehension impairments become more profound. The medial temporopolar region belongs to the amygdalocentric \ncomponent of the limbic system and stands to integrate exteroceptive information with interoceptive states underlying \nsocial interactions. Review of the pertinent literature shows that word comprehension and conduct impairments caused \nby temporopolar strokes and temporal lobectomy are far less severe than those seen in temporopolar atrophies. One ex-\nplanation for this unexpected discrepancy invokes the miswiring of residual temporopolar neurons during the many \nyears of indolently progressive neurodegeneration. According to this hypothesis, the temporopolar regions become \nnot only dysfunctional but also sources of aberrant outputs that interfere with the function of areas elsewhere in the lan-\nguage and paralimbic networks, a juxtaposition not seen in lobectomy or stroke.\nMesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University Feinberg School of \nMedicine, Chicago, IL 60611, USA\nCorrespondence to: M. Mesulam  \n330 East Superior St, Tarry-8, Chicago, IL 60611, USA  \nE-mail: mmesulam@northwestern.edu\nKeywords: temporal pole; semantics; word comprehension; object recognition; dementia; aphasia; TDP-C\nReceived April 8, 2022. Revised July 26, 2022. Accepted August 29, 2022. Advance access publication November 4, 2022\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: \njournals.permissions@oup.com\nIntroduction\nIn 1934, Karl Kleist1 published a detailed functional localization \nmap where every nook and cranny of the cerebral cortex but one \nwas assigned a consequential task. The temporopolar region was"}


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{"title": "Temporopolar regions of the human brain", "chroma:document": "the sole exception (Fig. 1A). A similar verdict came from Bogen \nand Bogen,2 who wrote: \u2018If you have \u2026 a cerebral lesion that pro-\nduces a loss of language \u2026 it is rather unlikely that the lesion will"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 241
encoding: FLOAT32
metadata:
{"title": "The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity", "chroma:document": "RESEARCH ARTICLE\nThe anti-immune dengue subgenomic\nflaviviral RNA is present in vesicles in\nmosquito saliva and is associated with\nincreased infectivity\nShih-Chia Yeh1\u262f\u00a4a, Tania Strilets2\u262f, Wei-Lian Tan1, David Castillo3, Hac\u00e8ne Medkour4,\nFe\u00b4lix Rey-Cadilhac4, Idalba M. Serrato-Pomar4, Florian Rachenne4, Avisha Chowdhury5\u00a4b,\nVanessa Chuo1, Sasha R. Azar6, Moirangthem Kiran Singh2, Rodolphe Hamel4,\nDorothe\u00b4e Misse\u00b4 4, R. Manjunatha Kini5,7, Linda J. Kenney2, Nikos Vasilakis6,8,9,10,11,12,13,\nMarc A. Marti-Renom3,14,15,16, Guy Nir2, Julien Pompon1,4\u2021*, Mariano A. Garcia-\nBlancoID1,2,17,18\u2021*\n1 Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 2 Department of\nBiochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States of\nAmerica, 3 CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and\nTechnology (BIST), Barcelona, Spain, 4 MIVEGEC, Univ. Montpellier, IRD, CNRS, Montpellier, France,\n5 Department of Biological Sciences, National University of Singapore, Singapore, 6 Department of\nPathology, University of Texas Medical Branch, Galveston, Texas, United States of America, 7 Department\nof Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 8 Center\nfor Biodefense and Emerging Infectious Diseases, University of University of Texas Medical Branch,\nGalveston, Texas, United States of America, 9 Center for Tropical Diseases, University of University of Texas\nMedical Branch, Galveston, Texas, United States of America, 10 Institute for Human Infection and Immunity,\nUniversity of University of Texas Medical Branch, Galveston, Texas, United States of America, 11 Center for\nVector-Borne and Zoonotic Diseases, University of University of Texas Medical Branch, Galveston, Texas,\nUnited States of America, 12 Department of Preventive Medicine and Population Health, University of\nUniversity of Texas Medical Branch, Galveston, Texas, United States of America, 13 World Reference"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 242
encoding: FLOAT32
metadata:
{"title": "The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity", "chroma:document": "Center for Emerging Viruses and Arboviruses, University of University of Texas Medical Branch, Galveston,\nTexas, United States of America, 14 Centre for Genomic Regulation (CRG), Barcelona Institute of Science\nand Technology (BIST), Barcelona, Spain, 15 Universitat Pompeu Fabra (UPF), Barcelona, Spain,\n16 ICREA, Barcelona, Spain, 17 Department of Internal Medicine, University of Texas Medical Branch,\nGalveston, Texas, United States of America, 18 Department of Microbiology, Immunology and Cancer\nBiology, University of Virginia, Charlottesville, Virginia, United States of America\n\u262f These authors contributed equally to this work.\n\u00a4a Current address: Cancer Science Institute of Singapore, National University of Singapore, Singapore\n\u00a4b Current address: Toronto Centre for Liver Disease, University Health Network, Princess Margaret Cancer\nResearch Tower, Toronto, Canada\n\u2021 JP and MAG-B also contributed equally to this work.\n* julien.pompon@ird.fr (JP); marianogb@virginia.edu, maragarc@utmb.edu (MAGB)\nAbstract\nMosquito transmission of dengue viruses to humans starts with infection of skin resident\ncells at the biting site. There is great interest in identifying transmission-enhancing factors in\nmosquito saliva in order to counteract them. Here we report the discovery of high levels of\nthe anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito\nsaliva. We established that sfRNA is present in saliva using three different methods: north-\nern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in\ndetergent-sensitive compartments, likely extracellular vesicles. In support of this\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011224\nMarch 30, 2023\n1 / 29\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Yeh S-C, Strilets T, Tan W-L, Castillo D,\nMedkour H, Rey-Cadilhac F, et al. (2023) The anti-\nimmune dengue subgenomic flaviviral RNA is\npresent in vesicles in mosquito saliva and is"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 243
encoding: FLOAT32
metadata:
{"title": "The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity", "chroma:document": "associated with increased infectivity. PLoS Pathog\n19(3): e1011224. https://doi.org/10.1371/journal.\nppat.1011224\nEditor: Amy L. Hartman, University of Pittsburgh,\nUNITED STATES\nReceived: August 4, 2022\nAccepted: February 20, 2023\nPublished: March 30, 2023\nCopyright: \u00a9 2023 Yeh et al. This is an open access\narticle distributed under the terms of the Creative\nCommons Attribution License, which permits\nunrestricted use, distribution, and reproduction in\nany medium, provided the original author and\nsource are credited.\nData Availability Statement: All relevant data are\nwithin the manuscript and its Supporting\nInformation files. The link https://github.com/\nGarcia-BlancoGroup/Yehetal2022 describes in\nhouse macros.\nFunding: Support for this research came from a\nfellowship from the McLauglin Family Foundation\nto TS, scholarships from the Fondation pour la\nRecherche Me\u00b4dicale (FRM project\nSPF202110013925) to HM, from the Institut"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 244
encoding: FLOAT32
metadata:
{"title": "Vector-based SARS-CoV-2 vaccination is associated with improved T-cell responses in hematological neoplasia", "chroma:document": "Vector-based SARS-CoV-2 vaccination is associated with improved\nT-cell responses in hematological neoplasia\nRobby Engelmann,1 Nadja Jaekel,2 Sabrina Jotschke,3 Beatrice Ludwig-Kraus,4 Frank Bernhard Kraus,4 Neha Kumari,1 Susann Schulze,3\nMichael Hecker,5 Christina Zahn,2 Haifa Kathrin Al-Ali,3 Christian Junghanss,1 and Sebastian B\u00f6ttcher1\n1Clinic III\u2014Hematology, Oncology, and Palliative Care, Rostock University Medical Center, Rostock, Germany; 2University Clinic and Outpatient Clinic for Internal Medicine IV,\n3Krukenberg Cancer Center Halle and 4Central Laboratory, University Hospital Halle (Saale), Halle (Saale), Germany; and 5Division of Neuroimmunology, Department of\nNeurology, Rostock University Medical Center, Rostock, Germany\nKey Points\n\u2022 Vector-based SARS-\nCoV-2 vaccines are\nadvantageous for the\ngeneration of T-cell\nresponses in patients\nwith hematological\nneoplasia.\n\u2022 CD4+ and CD8+ T-cell\nresponses cooccur in\nhematological\nneoplasms, whereas\nIgG titers are CD4+ T\ncells associated in\nmyeloid neoplasia only.\nIn order to elucidate mechanisms for severe acute respiratory syndrome coronavirus\n2 vaccination success in hematological neoplasia, we, herein, provide a\ncomprehensive characterization of the spike-speci\ufb01c T-cell and serological immunity\ninduced in 130 patients in comparison with 91 healthy controls. We studied 121\ndistinct T-cell subpopulations and the vaccination schemes as putative response\npredictors. In patients with lymphoid malignancies an insuf\ufb01cient immunoglobulin G\n(IgG) response was accompanied by a healthy CD4+ T-cell function. Compared with\ncontrols, a spike-speci\ufb01c CD4+ response was detectable in fewer patients with myeloid\nneoplasia whereas the seroconversion rate was normal. Vaccination-induced CD4+\nresponses were associated to CD8+ and IgG responses. Vector-based AZD1222 vaccine\ninduced more frequently detectable speci\ufb01c CD4+ responses in study participants\nacross all cohorts (96%; 27 of 28), whereas fully messenger RNA-based vaccination"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 245
encoding: FLOAT32
metadata:
{"title": "Vector-based SARS-CoV-2 vaccination is associated with improved T-cell responses in hematological neoplasia", "chroma:document": "schemes resulted in measurable CD4+ cells in only 102 of 168 participants (61%;\nP < .0001). A similar bene\ufb01t of vector-based vaccination was observed for the\ninduction of spike-speci\ufb01c CD8+ T cells. Multivariable models con\ufb01rmed vaccination\nschemes that incorporated at least 1 vector-based vaccination as key feature to mount\nboth a spike-speci\ufb01c CD4+ response (odds ratio, 10.67) and CD8+ response (odds ratio,\n6.56). Multivariable analyses identi\ufb01ed a speci\ufb01c CD4+ response but not the vector-\nbased immunization as bene\ufb01cial for a strong, speci\ufb01c IgG titer. Our study reveals\nfactors associated with a T-cell response in patients with hematological neoplasia and\nmight pave the way toward tailored vaccination schemes for vaccinees with these\ndiseases. The study was registered at the German Clinical Trials Register as\n#DRKS00027372.\nSubmitted 29 September 2022; accepted 13 March 2023; prepublished online on\nBlood\nAdvances\nFirst\nEdition\n22\nMarch\n2023.\nhttps://doi.org/10.1182/\nbloodadvances.2022009054.\nAll R scripts and accompanying raw data are available upon reasonable request to the\ncorresponding author, Sebastian B\u00f6ttcher (sebastian.boettcher@med.uni-rostock.de).\nThe full-text version of this article contains a data supplement.\n\u00a9 2023 by The American Society of Hematology. Licensed under Creative Commons\nAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0),\npermitting only noncommercial, nonderivative use with attribution. All other rights\nreserved.\nREGULAR ARTICLE\n25 JULY 2023 \u2022 VOLUME 7, NUMBER 14\n3403"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 246
encoding: FLOAT32
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{"title": "Pramipexole modulates fronto-subthalamic pathway in sequential working memory", "chroma:document": "ARTICLE\nOPEN\nPramipexole modulates fronto-subthalamic pathway\nin sequential working memory\nMarcus Heldmann1,2, Eliana M\u00f6nch1, Antonia Kesseb\u00f6hmer1, Norbert Br\u00fcggemann1,3, Thomas F. M\u00fcnte1,2\u2709 and Zheng Ye4\u2709\n\u00a9 The Author(s) 2022\nBrain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of\ndopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist\npramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a\ndouble-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI\nscanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance,\nregional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance,\nleading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related\nsubthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole\nupregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for\nmanipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic\nfunctional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This\nstudy con\ufb01rms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2\ntransmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.\nNeuropsychopharmacology (2023) 48:716\u2013723; https://doi.org/10.1038/s41386-022-01494-z\nINTRODUCTION\nBrain dopamine is known to regulate visuospatial working memory\n[1\u20133]. It may also regulate sequential working memory as patients"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 247
encoding: FLOAT32
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{"title": "Pramipexole modulates fronto-subthalamic pathway in sequential working memory", "chroma:document": "with Parkinson\u2019s disease (PD) exhibit dif\ufb01culties in arranging items\nin a speci\ufb01c order [4, 5], understanding stories that are told\nbackward [6, 7], and planning sequential steps to achieve goals\n[8\u201310]. To better understand the role of dopaminergic innervation,\nthis study investigates whether and how the D2/3 receptor agonist\npramipexole modulates the fronto-subthalamic hyperdirect or\nfronto-striatal indirect pathway during sequential working memory.\nIn visuospatial working memory, the dual-state theory of prefrontal\ndopamine function [11] assumes that a cortical D2-dominated state\n(e.g., D2 receptor activation) facilitates \ufb02exible manipulation, whereas\na cortical D1-dominated state (e.g., D2 receptor blockade) favors\npersistent maintenance of information. The tonic-phasic dopamine\nhypothesis emphasizes a balance of tonic and phasic dopamine\nfunction in the frontal and subcortical regions [12, 13]. Namely,\nincreased phasic and reduced tonic dopamine transmission sub-\ncortically and reduced dopamine concentration cortically (i.e.,\nincreased D2 and reduced D1 transmission) may facilitate \ufb02exible\nmanipulation but impair persistent maintenance of information. In\ncontrast, reduced phasic and increased tonic dopamine transmission\nsubcortically and increased dopamine concentration cortically (i.e.,\nincreased D1 and reduced D2 transmission) may have opposite\neffects on visuospatial working memory [14].\nDistinct roles of D1 versus D2 transmission in sequential working\nmemory are less understood. Human pharmacological and genetic\nstudies had inconsistent \ufb01ndings. In healthy adults, the D2 receptor\nantagonist sulpiride (D2 receptor blockade) can improve perfor-\nmance in reordering sequential items [15] but impair performance\nin planning sequential steps [16, 17]. In patients with PD, both the\nD2 receptor agonist bromocriptine (predominant D2 receptor\nactivation) and levodopa (predominant D1 receptor activation)\ncan improve performance in maintaining or reordering sequential"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 248
encoding: FLOAT32
metadata:
{"title": "Pramipexole modulates fronto-subthalamic pathway in sequential working memory", "chroma:document": "items [18, 19]. The Val allele of the COMT Val158Met polymorphism\n(high COMT activity, increased D2 and reduced D1 transmission)\nimproves performance in planning sequential steps [20]. But the Val\nallele of the BDNF Val66Met polymorphism (high BDNF secretion\nand increased D3 transmission) impairs performance in planning\nsequential steps [21]. These \ufb01ndings don\u2019t \ufb01t well with current\ndopaminergic models of visuospatial working memory.\nWe have put forward a fronto-basal ganglia model for sequential\nworking memory [22]. We assume that the prefrontal cortex encodes\nand retrieves sequential items through a competitive queuing\nmechanism [23\u201325]. The competitive queuing mechanism comprises\na parallel planning layer, which represents the serial position of items\nas the relative strength of node activations, and a competitive choice\nlayer, which forms reciprocal connections which the parallel\nplanning layer and selects the node with the strongest activation.\nThe basal ganglia may interact with the competitive choice layer to\nReceived: 20 June 2022 Revised: 23 October 2022 Accepted: 26 October 2022\nPublished online: 9 November 2022\n1Department of Neurology, University of L\u00fcbeck, L\u00fcbeck 23538, Germany. 2Institute of Psychology II, University of L\u00fcbeck, L\u00fcbeck 23538, Germany. 3Institute of Neurogenetics,\nUniversity of L\u00fcbeck, L\u00fcbeck 23538, Germany. 4Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences,\nShanghai 200031, China. \u2709email: thomas.muente@neuro.uni-luebeck.de; yez@ion.ac.cn\nwww.nature.com/npp\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 249
encoding: FLOAT32
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{"title": "Correction: A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque \\(Macaca mulatta\\) model", "chroma:document": "CORRECTION\nCorrection: A time-course comparative clinical\nand immune response evaluation study\nbetween the human pathogenic Orientia\ntsutsugamushi strains: Karp and Gilliam in a\nrhesus macaque (Macaca mulatta) model\nManutsanun Inthawong, Piyanate Sunyakumthorn, Sirima Wongwairot,\nTippawan Anantatat, Susanna J. Dunachie, Rawiwan Im-Erbsin, James W. Jones, Carl\nJ. Mason, Luis A. Lugo, Stuart D. Blacksell, Nicholas P. J. Day, Piengchan Sonthayanon,\nAllen L. Richards, Daniel H. Paris\nThere is an error in the affiliation order for author Manutsanun Inthawong. The correct affilia-\ntion order is:\nManutsanun Inthawong1,2\n1 Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine,\nMahidol University, Bangkok, Thailand\n2 Department of Veterinary Medicine, United States Army Medical Directorate, Armed\nForces Research Institute of Medical Sciences (USAMD-AFRIMS), Bangkok, Thailand\nReference\n1.\nInthawong M, Sunyakumthorn P, Wongwairot S, Anantatat T, Dunachie SJ, Im-Erbsin R, et al. (2022) A\ntime-course comparative clinical and immune response evaluation study between the human patho-\ngenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.\nPLoS Negl Trop Dis 16(8): e0010611. https://doi.org/10.1371/journal.pntd.0010611 PMID: 35925895\nPLOS NEGLECTED TROPICAL DISEASES\nPLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011277\nApril 12, 2023\n1 / 1\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Inthawong M, Sunyakumthorn P,\nWongwairot S, Anantatat T, Dunachie SJ, Im-\nErbsin R, et al. (2023) Correction: A time-course\ncomparative clinical and immune response\nevaluation study between the human pathogenic\nOrientia tsutsugamushi strains: Karp and Gilliam in\na rhesus macaque (Macaca mulatta) model. PLoS\nNegl Trop Dis 17(4): e0011277. https://doi.org/\n10.1371/journal.pntd.0011277\nPublished: April 12, 2023\nCopyright: This is an open access article, free of all\ncopyright, and may be freely reproduced,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 250
encoding: FLOAT32
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{"title": "Correction: A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque \\(Macaca mulatta\\) model", "chroma:document": "distributed, transmitted, modified, built upon, or\notherwise used by anyone for any lawful purpose.\nThe work is made available under the Creative\nCommons CC0 public domain dedication."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 251
encoding: FLOAT32
metadata:
{"title": "Orexinergic neurons in the hypothalami of an Asiatic lion, an African lion, and a Southeast African cheetah", "chroma:document": "Received: 1 September 2022\nRevised: 17 October 2022\nAccepted: 19 October 2022\nDOI: 10.1002/cne.25431\nR E S E A R C H A R T I C L E\nOrexinergic neurons in the hypothalami of an Asiatic lion, an\nAfrican lion, and a Southeast African cheetah\nDemi Oddes1\nAyanda Ngwenya1\nIllke B. Malungo1\nAnita Burkevica2\nTherese H\u00e5rd3\nMads. F. Bertelsen4\nMuhammad A. Spocter1,5\nD. Michael Scantlebury6\nPaul R. Manger1\n1School of Anatomical Sciences, Faculty of\nHealth Sciences, University of the\nWitwatersrand, Johannesburg, South Africa\n2Parken Zoo i Eskilstuna AB, Eskilstuna,\nSweden\n3Bor\u00e5s Zoo, Bor\u00e5s, Sweden\n4Centre for Zoo and Wild Animal Health,\nCopenhagen Zoo, Frederiksberg, Denmark\n5Department of Anatomy, Des Moines\nUniversity, Des Moines, Iowa, USA\n6School of Biological Sciences, Queen\u2019s\nUniversity Belfast, Belfast, UK\nCorrespondence\nPaul Manger, School of Anatomical Sciences,\nFaculty of Health Sciences, University of the\nWitwatersrand, 7 York Road, Parktown,\nJohannesburg, 2193, South Africa.\nEmail: Paul.Manger@wits.ac.za\nFunding information\nCarnegie Corporation of New York; South\nAfrican National Research Foundation;\nseed-funding from Queen\u2019s University, Belfast,\nand the University of the Witwatersrand\nAbstract\nEmploying orexin-A immunohistochemistry, we describe the distribution, morphology,\nand nuclear parcellation of orexinergic neurons within the hypothalami of an Asiatic\nlion (Panthera leo subsp. persica), an African lion (Panthera leo subsp. melanochaita),\nand a Southeast African cheetah (Acinonyx jubatus subsp. jubatus). In all three felids,\nthe clustering of large, bipolar, and multipolar hypothalamic orexinergic neurons pri-\nmarily follows the pattern observed in other mammals. The orexinergic neurons were\nfound, primarily, to form three distinct clusters\u2014the main, zona incerta, and optic tract\nclusters. In addition, large orexinergic neurons were observed in the ventromedial\nsupraoptic region of the hypothalamus, where they are not typically observed in other"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 252
encoding: FLOAT32
metadata:
{"title": "Orexinergic neurons in the hypothalami of an Asiatic lion, an African lion, and a Southeast African cheetah", "chroma:document": "species. As has been observed in cetartiodactyls and the African elephant, a cluster of\nsmall, multipolar orexinergic neurons, the parvocellular cluster, was observed in the\nmedial zone of the hypothalamus in all three felids, although this parvocellular cluster\nhas not been reported in other carnivores. In both subspecies of lions, but not the chee-\ntah, potential orexin-immunopositive neurons were observed in the paraventricular\nhypothalamic nucleus, supraoptic nucleus, the lateral part of the retrochiasmatic area,\nand the inner layer of the median eminence. The distribution and parcellation of orexin-\nergic neurons in the hypothalami of the three felids studied appear to be more complex\nthan observed in many other mammals and for the two subspecies of lion may be even\nmore complex. These findings are discussed in terms of potential technical concerns,\nphylogenetic variations of this system, and potentially associated functional aspects of\nthe orexinergic system.\nKEY WO RDS\nCarnivora, Felidae, hypocretin, immunohistochemistry, orexin, RRID:AB_91545, stereology\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any\nmedium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.\n\u00a9 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.\n366\nwileyonlinelibrary.com/journal/cne\nJ Comp Neurol. 2023;531:366\u2013389."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 253
encoding: FLOAT32
metadata:
{"title": "Complete meiosis in rat prepubertal testicular tissue under in vitro sequential culture conditions", "chroma:document": "Received: 23 June 2022\nRevised: 25 September 2022\nAccepted: 9 October 2022\nDOI: 10.1111/andr.13325\nO R I G I N A L A R T I C L E\nComplete meiosis in rat prepubertal testicular tissue under\nin vitro sequential culture conditions\nJustine Saulnier1\nMathilde Soirey1\nNasreddine K\u00e9bir2\nMarion Delessard1\nAur\u00e9lie Rives-Feraille1\nLaura Moutard1\nLudovic Dumont1\nNathalie Rives1\nChristine Rondanino1\n1INSERM, U1239, Adrenal and Gonadal\nPathophysiology team, Laboratory of\nNeuroendocrine Endocrine and Germinal\nDifferentiation and Communication, Rouen\nUniversity Hospital, Rouen Normandy\nUniversity, Rouen, France\n2Normandie Univ, INSA Rouen Normandie,\nLaboratoire PBS, Saint-Etienne-du-Rouvray,\nFrance\nCorrespondence\nChristine Rondanino, INSERM, U1239,\nAdrenal and Gonadal Pathophysiology team,\nLaboratory of Neuroendocrine Endocrine and\nGerminal Differentiation and Communication,\nRouen University Hospital, Rouen Normandy\nUniversity, Rouen, France.\nEmail: christine.rondanino@univ-rouen.fr\nFunding information\nRouen Normandy University\nAbstract\nBackground: Testicular tissue cryopreservation before gonadotoxic treatments allows\nfertility preservation in children suffering from cancer. Fertility restoration strategies,\nin particular in vitro maturation of prepubertal testicular tissue, are being developed\nmainly in animal models. The rat, widely used in biomedical research, including in\nreproductive biology, is a relevant model.\nObjectives: To determine whether sequential two-step culture protocols can improve\nthe efficiency of rat in vitro spermatogenesis.\nMaterials and methods: Rat prepubertal testicular tissues were cultured on agarose\ngels with either a one-step or two-step protocol with or without polydimethyl-\nsiloxane (PDMS) ceiling chips. The progression of spermatogenesis, germ/Sertoli\ncell ratio, cell proliferation, seminiferous tubule area, and intratubular cell density\nwere assessed by histological and immunohistochemical analyses. Terminal deoxynu-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 254
encoding: FLOAT32
metadata:
{"title": "Complete meiosis in rat prepubertal testicular tissue under in vitro sequential culture conditions", "chroma:document": "cleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays and Peanut\nAgglutinin (PNA) lectin labeling were performed to analyze the Deoxyribonucleic Acid\n(DNA) integrity and differentiation step of in vitro-produced spermatids.\nResults: Sequential two-step protocols allowed the production of spermatids with\na higher efficiency compared with the one-step culture protocol. However, the effi-\nciency was low, as less than 1.5% of tubules contained spermatids. Most of the in\nvitro-produced spermatids contained unfragmented DNA and were at an early step of\ndifferentiation. Rare elongating spermatids could be detected in the cultured explants.\nAlthough complete in vitro spermatogenesis could not be obtained with PDMS ceiling\nchips, entry into meiosis was promoted in one-step organotypic cultures.\nDiscussion and conclusion: Complete in vitro meiosis and the beginning of the elon-\ngation phase of spermiogenesis were obtained in a rat model using sequential culture\nmethods. Because of their low efficiency, further work will be necessary to identify\nthe culture conditions allowing the completion of spermiogenesis. These optimizations\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided\nthe original work is properly cited.\n\u00a9 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.\nAndrology. 2023;11:167\u2013176.\nwileyonlinelibrary.com/journal/andr\n167"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 255
encoding: FLOAT32
metadata:
{"title": "Neuronal activity patterns in microcircuits of the cerebellar cortical C3 zone during reaching", "chroma:document": "J Physiol 600.23 (2022) pp 5077\u20135099\n5077\nThe Journal of Physiology\nNeuronal activity patterns in microcircuits of the cerebellar\ncortical C3 zone during reaching\nNadia L. Cerminara1\n, Martin Garwicz2, Henry Darch1, Conor Houghton3\n, Dilwyn E. Marple-Horvat4\nand Richard Apps1\n1School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK\n2Neuronano Research Centre and Birgit Rausing Centre for Medical Humanities, Department of Experimental Medical Science, Lund University, Lund,\nSweden\n3Department of Computer Science, University of Bristol, Bristol, UK\n4Department of Life Sciences, Manchester Metropolitan University, Manchester, UK\nHandling Editors: Richard Carson & Vatsala Thirumalai\nThe peer review history is available in the Supporting Information section of this article\n(https://doi.org/10.1113/JP282928#support-information-section).\nNadia Cerminara is a Research Fellow at the University of Bristol, UK. She obtained her PhD in neurophysiology from Monash University, Australia,\nin 2002. Using an in vivo systems-level approach, a key aim of her work is to determine the information processing that occurs in cerebellar circuits\nduring the performance of both new and well-rehearsed movements.\nN. L. Cerminara, M. Garwicz, D. E. Marple-Horvat and R. Apps contributed as senior authors.\nThis article was first published as a preprint. Cerminara NL, Garwicz M, Darch H, Houghton C, Marple-Horvat DE, Apps R. 2020. Action-based\norganization and function of cerebellar cortical microcircuits. bioRxiv. https://doi.org/10.1101/2020.04.04.025387\n\u00a9 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.\nDOI: 10.1113/JP282928\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution\nand reproduction in any medium, provided the original work is properly cited."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 256
encoding: FLOAT32
metadata:
{"title": "Characterizing microglial gene expression in a model of secondary progressive MS", "chroma:document": "R E S E A R C H A R T I C L E\nCharacterizing microglial gene expression in a model\nof secondary progressive multiple sclerosis\nIlia D. Vainchtein1\n|\nAstrid M. Alsema1\n|\nMarissa L. Dubbelaar1\n|\nCorien Grit1\n|\nJonathan Vinet2\n|\nHilmar R. J. van Weering1\n|\nSarah Al-Izki3\n|\nGiuseppe Biagini2\n|\nNieske Brouwer1\n|\nSandra Amor3,4\n|\nDavid Baker3\n|\nBart J. L. Eggen1\n|\nErik W. G. M. Boddeke1,5\n|\nSusanne M. Kooistra1\n1Department of Biomedical Sciences of Cells &\nSystems, Section Molecular Neurobiology,\nUniversity of Groningen, University Medical\nCenter Groningen, Groningen,\nThe Netherlands\n2Department of Biomedical, Metabolic and\nNeural Sciences, University of Modena and\nReggio Emilia, Modena, Italy\n3Department of Neuroimmunology, Blizard\nInstitute, Barts and the London School of\nMedicine and Dentistry, Queen Mary\nUniversity of London, London, UK\n4Department of Pathology, VUMC,\nAmsterdam, The Netherlands\n5Department of Cellular and Molecular\nMedicine, Center for Healthy Ageing,\nUniversity of Copenhagen, Copenhagen,\nDenmark\nCorrespondence\nIlia D. Vainchtein and Susanne M. Kooistra,\nDepartment of Biomedical Sciences of Cells &\nSystems, Section Molecular Neurobiology,\nUniversity of Groningen, University Medical\nCenter Groningen, Groningen,\nThe Netherlands.\nEmail: ilia.vainchtein@gmail.com and s.m.\nkooistra@umcg.nl\nFunding information\nItalian MS Foundation, Grant/Award Number:\n2011/B/7; Stichting MS Research,\nGrant/Award Numbers: 10-723, 16-947\nAbstract\nMultiple sclerosis (MS) is the most common inflammatory, demyelinating and neuro-\ndegenerative disease of the central nervous system in young adults. Chronic-\nrelapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is\nan experimental model of MS. This crEAE model is characterized by an acute phase\nwith severe neurological disability, followed by remission of disease, relapse of neu-\nrological disease and remission that eventually results in a chronic progressive phase\nthat mimics the secondary progressive phase (SPEAE) of MS. In both MS and SPEAE,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 257
encoding: FLOAT32
metadata:
{"title": "Characterizing microglial gene expression in a model of secondary progressive MS", "chroma:document": "the role of microglia is poorly defined. We used a crEAE model to characterize micro-\nglia in the different phases of crEAE phases using morphometric and RNA sequencing\nanalyses. At the initial, acute inflammation phase, microglia acquired a pro-\ninflammatory phenotype. At the remission phase, expression of standard immune\nactivation genes was decreased while expression of genes associated with lipid\nmetabolism and tissue remodeling were increased. Chronic phase microglia partially\nregain inflammatory gene sets and increase expression of genes associated with pro-\nliferation. Together, the data presented here indicate that microglia obtain different\nfeatures at different stages of crEAE and a particularly mixed phenotype in the\nchronic stage. Understanding the properties of microglia that are present at the\nchronic phase of EAE will help to understand the role of microglia in secondary pro-\ngressive MS, to better aid the development of therapies for this phase of the disease.\nK E Y W O R D S\nexperimental autoimmune encephalitis, microglia, RNA sequencing, secondary progressive MS\n1\n|\nINTRODUCTION\nMicroglia are the tissue-resident macrophages of the central nervous\nsystem\n(CNS)\nand\nrecent\ngenome-wide\nassociation\nanalysis\n(International Multiple Sclerosis Genetics Consortium, 2019) and\nIlia D. Vainchtein and Astrid M. Alsema contributed equally to this study.\nReceived: 16 March 2022\nRevised: 30 September 2022\nAccepted: 26 October 2022\nDOI: 10.1002/glia.24297\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any\nmedium, provided the original work is properly cited and is not used for commercial purposes.\n\u00a9 2022 The Authors. GLIA published by Wiley Periodicals LLC.\n588\nGlia. 2023;71:588\u2013601.\nwileyonlinelibrary.com/journal/glia"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 258
encoding: FLOAT32
metadata:
{"title": "Complosome \u0084 the intracellular complement system", "chroma:document": "Nature Reviews Nephrology\nnature reviews nephrology\nhttps://doi.org/10.1038/s41581-023-00704-1\nReview article\n Check for updates\nComplosome \u2014 the intracellular \ncomplement system\nErin E. West\u2009\n \u2009 & Claudia Kemper\u2009\n \u2009 \nAbstract\nThe complement system is a recognized pillar of host defence against \ninfection and noxious self-derived antigens. Complement is traditionally \nknown as a serum-effective system, whereby the liver expresses and  \nsecretes most complement components, which participate in the \ndetection of bloodborne pathogens and drive an inflammatory reac -\ntion\u00a0to safely remove the microbial or antigenic threat. However, pertur-\nbations in normal complement function can cause severe disease and,  \nfor reasons that are currently not fully understood, the kidney is\u00a0parti-\ncularly vulnerable to dysregulated complement activity. Novel insights  \ninto complement biology have identified cell-autonomous and intra-\ncellularly active complement \u2014 the complosome \u2014 as an unexpected central \norchestrator of normal cell physiology. For example, the\u00a0complo some \ncontrols mitochondrial activity, glycolysis, oxidative phosphorylation, \ncell survival and gene regulation in innate and adaptive immune cells, and \nin non-immune cells, such as fibroblasts and endothelial and epithelial \ncells. These unanticipated complosome contributions to basic cell \nphysiological pathways make it a novel and central player in the control \nof cell homeostasis and effector responses. This discovery, together with \nthe realization that an increasing number of human diseases involve \ncomplement perturbations, has renewed interest in the complement \nsystem and its therapeutic targeting. Here, we summarize the current \nknowledge about the complosome across healthy cells and tissues, \nhighlight contributions from dysregulated complosome activities  \nto human disease and discuss potential therapeutic implications.\nSections\nIntroduction\nClassical functions of systemic \nand local extracellular \ncomplement\nIntracellular complement and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 259
encoding: FLOAT32
metadata:
{"title": "Complosome \u0084 the intracellular complement system", "chroma:document": "its role in cell physiology\nThe complosome across cells \nand tissues\nThe complosome in human \ndisease\nTherapeutic implications\nConclusions\nNational Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Complement and \nInflammation Research Section (CIRS), Bethesda, MD, USA. \n\u2009e-mail: claudia.kemper@nih.gov"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 260
encoding: FLOAT32
metadata:
{"title": "Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant", "chroma:document": "RESEARCH ARTICLE\nSyrian hamster convalescence from prototype\nSARS-CoV-2 confers measurable protection\nagainst the attenuated disease caused by the\nOmicron variant\nKathryn A. RyanID*, Kevin R. Bewley, Robert J. Watson, Christopher Burton,\nOliver Carnell, Breeze E. Cavell, Amy Challis, Naomi S. Coombes, Elizabeth R. Davies,\nJack Edun-Huges, Kirsty Emery, Rachel Fell, Susan A. Fotheringham, Karen E. Gooch,\nKathryn Gowan, Alastair Handley, Debbie J. Harris, Richard Hesp, Laura Hunter,\nRichard Humphreys, Rachel Johnson, Chelsea Kennard, Daniel Knott, Sian Lister,\nDaniel Morley, Didier Ngabo, Karen L. Osman, Jemma Paterson, Elizabeth J. Penn, Steven\nT. Pullan, Kevin S. Richards, Sian Summers, Stephen R. Thomas, Thomas Weldon,\nNathan R. Wiblin, Emma L. Rayner, Richard T. Vipond, Bassam Hallis, Francisco\nJ. Salguero, Simon G. P. Funnell, Yper Hall\nUK Health Security Agency, Salisbury, United Kingdom\n* kathryn.ryan@ukhsa.gov.uk\nAbstract\nThe mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern\nfor naturally acquired and vaccine-induced immunity. We investigated the ability of prior\ninfection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to pro-\ntect against disease caused by BA.1. We established that BA.1 infection in na\u00efve Syrian\nhamsters resulted in a less severe disease than a comparable dose of the ancestral virus,\nwith fewer clinical signs including less weight loss. We present data to show that these clini-\ncal observations were almost absent in convalescent hamsters challenged with the same\ndose of BA.1 50 days after an initial infection with ancestral virus. These data provide evi-\ndence that convalescent immunity against ancestral SARS-CoV-2 is protective against\nBA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and\nclinical data supports consistency of the model and its predictive value for the outcome in\nhumans. Further, the ability to detect protection against the less severe disease caused by"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 261
encoding: FLOAT32
metadata:
{"title": "Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant", "chroma:document": "BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-spe-\ncific countermeasures.\nAuthor summary\nThe Golden Syrian hamster model has proved to be a robust model for SARS-CoV-2, with\nclinical signs, pathological changes and viral load outputs providing endpoints for an ani-\nmal model of COVID-19, suitable for the assessment of interventions that may serve to\nprevent infection, transmission and/or disease. Following wild type virus infection in the\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011293\nApril 4, 2023\n1 / 25\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Ryan KA, Bewley KR, Watson RJ, Burton\nC, Carnell O, Cavell BE, et al. (2023) Syrian hamster\nconvalescence from prototype SARS-CoV-2\nconfers measurable protection against the\nattenuated disease caused by the Omicron variant.\nPLoS Pathog 19(4): e1011293. https://doi.org/\n10.1371/journal.ppat.1011293\nEditor: Jacob S. Yount, The Ohio State University,\nUNITED STATES\nReceived: August 23, 2022\nAccepted: March 11, 2023\nPublished: April 4, 2023\nCopyright: \u00a9 2023 Ryan et al. This is an open\naccess article distributed under the terms of the\nCreative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: All relevant data are\nwithin the manuscript and its Supporting\nInformation files.\nFunding: This work was funded by the Coalition for\nEpidemic Preparedness Innovations\u2019 (CEPI) Agility\nProgramme. The funders had no role in study\ndesign, data collection and analysis, decision to\npublish, or preparation of the manuscript.\nCompeting interests: The authors have declared\nthat no competing interests exist."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 262
encoding: FLOAT32
metadata:
{"title": "Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants", "chroma:document": "ARTICLE\nOPEN\nIntranasal booster using an Omicron vaccine confers broad\nmucosal and systemic immunity against SARS-CoV-2 variants\nQian Wang1, Chenchen Yang2,3, Li Yin4,5, Jing Sun1, Wei Wang3, Hengchun Li4,5, Zhengyuan Zhang4,5, Si Chen3, Bo Liu2,3, Zijian Liu4,5,\nLinjing Shi4,5, Xiaolin Liu2,3, Suhua Guan2,3, Chunhua Wang2,3, Linbing Qu4, Ying Feng3, Xuefeng Niu1, Liqiang Feng4,\nJincun Zhao\n1,3\u2709, Pingchao Li4\u2709, Ling Chen1,3,4\u2709 and Nanshan Zhong1,3\nThe highly contagious SARS-CoV-2 Omicron subvariants severely attenuated the effectiveness of currently licensed SARS-CoV-2\nvaccines based on ancestral strains administered via intramuscular injection. In this study, we generated a recombinant, replication-\nincompetent human adenovirus type 5, Ad5-S-Omicron, that expresses Omicron BA.1 spike. Intranasal, but not intramuscular\nvaccination, elicited spike-speci\ufb01c respiratory mucosal IgA and residential T cell immune responses, in addition to systemic\nneutralizing antibodies and T cell immune responses against most Omicron subvariants. We tested intranasal Ad5-S-Omicron as a\nheterologous booster in mice that previously received intramuscular injection of inactivated ancestral vaccine. In addition to\ninducing serum broadly neutralizing antibodies, there was a signi\ufb01cant induction of respiratory mucosal IgA and neutralizing\nactivities against Omicron subvariants BA.1, BA.2, BA.5, BA.2.75, BF.7 as well as pre-Omicron strains Wildtype, Beta, and Delta. Serum\nand mucosal neutralizing activities against recently emerged XBB, BQ.1, and BQ.1.1 could also be detected but were much lower.\nNasal lavage \ufb02uids from intranasal vaccination contained multimeric IgA that can bind to at least 10 spike proteins, including\nOmicron subvariants and pre-Omicron strains, and possessed broadly neutralizing activities. Intranasal vaccination using Ad5-S-\nOmicron or instillation of intranasal vaccinee\u2019s nasal lavage \ufb02uids in mouse nostrils protected mice against Omicron challenge."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 263
encoding: FLOAT32
metadata:
{"title": "Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants", "chroma:document": "Taken together, intranasal Ad5-S-Omicron booster on the basis of ancestral vaccines can establish effective mucosal and systemic\nimmunity against Omicron subvariants and multiple SARS-CoV-2 variants. This candidate vaccine warrants further development as a\nsafe, effective, and user-friendly infection and transmission-blocking vaccine.\nSignal Transduction and Targeted Therapy  (2023) 8:167 \n; https://doi.org/10.1038/s41392-023-01423-6\nINTRODUCTION\nIt has been over 3 years since the beginning of the COVID-19\npandemic that is caused by SARS-CoV-2, which is an enveloped\nsingle-stranded RNA virus. Vaccines are the most effective way to\nminimize infection and associated morbidity and mortality. The\nspike protein of SARS-CoV-2 is the principal target for antibody\nand vaccine countermeasures. SARS-CoV-2 enters and replicates in\nepithelial cells through the binding of spike with the cell-surface\nreceptor angiotensin-converting enzyme 2 (ACE2). As of March 06,\n2023, over two-thirds of the world\u2019s population has received at\nleast one dose of a COVID-19 vaccine, and 13.23 billion doses have\nbeen administered globally.1 Although infection or vaccine-\ninduced neutralizing antibodies can inhibit the binding and\ninfection of SARS-CoV-2, the virus mutates rapidly. An increasing\nlist of lineages is designated variants of concern (VOCs) due to\nincreased transmission and evasion of vaccine-induced immunity,\nincluding Beta, Delta, and Omicron subvariants.\nSince the end of 2021, the dominant variants have become and\nremained thus far the Omicron subvariants, including BA.1, BA.2,\nBA.2.12.1, BA.2.75, BA.4, BA.5, BF.7, BQ.1, BQ.1.1, and XBB. These\nsubvariants contain multiple mutations with the capability of\nstrong immune escape and rapid transmission. The effectiveness\nof the 2-dose mRNA-1273 vaccine against Omicron infection was\n30.4% between 14\u201390 days and declined to 0% by 180 days post-\nvaccination.2 Even with the 4th dose of mRNA vaccine of ancestral\nstrain, vaccine ef\ufb01cacy against symptomatic infection was 30% for"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 264
encoding: FLOAT32
metadata:
{"title": "Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants", "chroma:document": "BNT162b2 and 11% for mRNA-1273, and people had a high viral\nload in the nasopharyngeal tract that can be highly transmissible.3\nThe outcome of reduced vaccine ef\ufb01cacy against new variants and\nlack of mucosal immunity may provide conditions for further\nselection of highly resistant and transmissible variants in the\nupper airway. Thus, there is a need to establish an immune barrier\nthat can provide front-line immunity to block infection and\ntransmission of Omicron subvariants.\nSARS-CoV-2 infection starts in the upper respiratory system,\nwhere the nasopharyngeal tract is at the forefront. To prevent\nviruses from attaching and replicating at the mucosal epithelium,\neffective mucosal immunity in the airway is critically important.\nEarlier studies have shown that mucosal booster vaccination with\nadenovirus-vectored ancestral vaccines after mRNA priming can\nReceived: 26 November 2022 Revised: 14 March 2023 Accepted: 22 March 2023\n1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Af\ufb01liated Hospital of Guangzhou Medical University, Guangzhou, China;\n2Guangzhou nBiomed Ltd., Guangzhou, China; 3Guangzhou Laboratory & Bioland Laboratory, Guangzhou, China; 4Guangdong Laboratory of Computational Biomedicine,\nGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China and 5University of Chinese Academy of Sciences, Beijing, China\nCorrespondence: Jincun Zhao (zhaojincun@gird.cn) or Pingchao Li (li_pingchao@gibh.ac.cn) or Ling Chen (chen_ling@gibh.ac.cn)\nThese authors contributed equally: Qian Wang, Chenchen Yang, Li Yin, Jing Sun, Wei Wang.\nThe original online version of this article was revised: The error in"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 265
encoding: FLOAT32
metadata:
{"title": "Antiviral neutralizing antibodies: from in vitro to in vivo activity", "chroma:document": "Nature Reviews Immunology\nnature reviews immunology\nhttps://doi.org/10.1038/s41577-023-00858-w\nReview article\n Check for updates\nAntiviral neutralizing antibodies: \nfrom in vitro to in vivo activity\nDennis R. Burton\u2009\n \u20091,2 \nAbstract\nNeutralizing antibodies (nAbs) are being increasingly used as passive \nantiviral reagents in prophylactic and therapeutic modalities and to \nguide viral vaccine design. In vivo, nAbs can mediate antiviral functions \nthrough several mechanisms, including neutralization, which is defined \nby in vitro assays in which nAbs block viral entry to target cells, and \nantibody effector functions, which are defined by in vitro assays that \nevaluate nAbs against viruses and infected cells in the presence of \neffector systems. Interpreting in vivo results in terms of these  \nin vitro assays is challenging but important in choosing optimal passive \nantibody and vaccine strategies. Here, I review findings from many \ndifferent viruses and conclude that, although some generalizations are \npossible, deciphering the relative contributions of different antiviral \nmechanisms to the in vivo efficacy of antibodies currently requires \nconsideration of individual antibody\u2013virus interactions.\nSections\nIntroduction\nMechanisms of neutralization \nin vitro\nNeutralization stoichiometry\nAntibody effector assays\nAntiviral antibody activities \nin vivo\nConcluding remarks\n1Department of Immunology and Microbiology, Consortium for HIV/AIDS Vaccine Development, International \nAIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. 2Ragon \nInstitute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, \nCambridge, MA, USA. \n\u2009e-mail: burton@scripps.edu"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 266
encoding: FLOAT32
metadata:
{"title": "The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito", "chroma:document": "RESEARCH ARTICLE\nThe E2 glycoprotein holds key residues for\nMayaro virus adaptation to the urban Aedes\naegypti mosquito\nChelsea Cereghino1,2\u262f, Ferdinand Roesch3,4\u262f, Luc\u0131\u00b4a Carrau3,5, Alexandra Hardy3, Helder\nV. Ribeiro-Filho6, Annabelle Henrion-Lacritick7, Cassandra Koh7, Jeffrey M. Marano1,8,\nTyler A. Bates1, Pallavi Rai1, Christina Chuong1, Shamima Akter1,9, Thomas Vallet3,\nHerve\u00b4 Blanc7, Truitt J. Elliott10,11,12, Anne M. Brown10, Pawel Michalak1,13,14,15,\nTanya LeRoith1, Jesse D. Bloom16,17, Rafael Elias Marques6, Maria-Carla Saleh7,\nMarco Vignuzzi3, James Weger-LucarelliID1,2,3*\n1 Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine,\nVirginia Tech, Blacksburg, Virginia, United States of America, 2 Center for Emerging, Zoonotic, and\nArthropod-borne Pathogens, Virginia Tech, Blacksburg, Virginia, United States of America, 3 Institut Pasteur,\nViral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris,\nFrance, 4 UMR 1282 ISP, INRAE Centre Val de Loire, Nouzilly, France, 5 Department of Microbiology, New\nYork University Langone Medical Center, New York, New York, United States of America, 6 Brazilian\nBiosciences National Laboratory, Brazilian Center for Research in Energy and Materials (CNPEM),\nCampinas, S\u00e3o Paulo, Brazil, 7 Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la\nRecherche Scientifique UMR 3569, Paris, France, 8 Translational Biology, Medicine, and Health Graduate\nProgram, Virginia Tech, Roanoke, Virginia, United States of America, 9 Department of Bioinformatics and\nComputational Biology, School of Systems Biology, George Mason University, Fairfax, Virginia, United States\nof America, 10 Program in Genetics, Bioinformatics, and Computational Biology (GBCB), Virginia Tech,\nBlacksburg, Virginia, United States of America, 11 Research and Informatics, University Libraries, Virginia\nTech, Blacksburg, Virginia, United States of America, 12 Department of Biochemistry, Virginia Tech,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 267
encoding: FLOAT32
metadata:
{"title": "The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito", "chroma:document": "Blacksburg, Virginia, United States of America, 13 Edward Via College of Osteopathic Medicine, Monroe,\nLouisiana, United States of America, 14 Center for One Health Research, VA-MD Regional College of\nVeterinary Medicine, Blacksburg, Virginia, Untied States of Ameria, 15 Institute of Evolution, University of\nHaifa, Haifa, Israel, 16 Basic Sciences Division and Computational Biology Program, Fred Hutchinson\nCancer Research Center, Seattle, Washington, United States of America, 17 Howard Hughes Medical\nInstitute, Chevy Chase, Maryland, United States of America\n\u262f These authors contributed equally to this work.\n* weger@vt.edu\nAbstract\nAdaptation to mosquito vectors suited for transmission in urban settings is a major driver in\nthe emergence of arboviruses. To better anticipate future emergence events, it is crucial to\nassess their potential to adapt to new vector hosts. In this work, we used two different exper-\nimental evolution approaches to study the adaptation process of an emerging alphavirus,\nMayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses.\nWe identified E2-T179N as a key mutation increasing MAYV replication in insect cells and\nenhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this muta-\ntion decreased viral replication and binding in human fibroblasts, a primary cellular target of\nMAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and\ndisplays less severe tissue pathology in vivo in a mouse model. We found evidence in\nmouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replica-\ntion than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1010491\nApril 5, 2023\n1 / 32\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Cereghino C, Roesch F, Carrau L, Hardy\nA, Ribeiro-Filho HV, Henrion-Lacritick A, et al.\n(2023) The E2 glycoprotein holds key residues for"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 268
encoding: FLOAT32
metadata:
{"title": "The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito", "chroma:document": "Mayaro virus adaptation to the urban Aedes aegypti\nmosquito. PLoS Pathog 19(4): e1010491. https://\ndoi.org/10.1371/journal.ppat.1010491\nEditor: Thomas E. Morrison, University of Colorado\nDenver, UNITED STATES\nReceived: April 4, 2022\nAccepted: March 13, 2023\nPublished: April 5, 2023\nPeer Review History: PLOS recognizes the\nbenefits of transparency in the peer review\nprocess; therefore, we enable the publication of\nall of the content of peer review and author\nresponses alongside final, published articles. The\neditorial history of this article is available here:\nhttps://doi.org/10.1371/journal.ppat.1010491\nCopyright: \u00a9 2023 Cereghino et al. This is an open\naccess article distributed under the terms of the\nCreative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: Raw sequencing data\nwas deposited under the Sequence Read Archive\n(SRA, NCBI) under bioproject number"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 269
encoding: FLOAT32
metadata:
{"title": "Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity", "chroma:document": "1\u2011O\u2011Octadecyl-2\u2011O\u2011benzyl-sn-glyceryl-3-phospho-GS-441524\n(V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV\u20112\nInfection and Synthesis and Antiviral Evaluation of Additional\nPhospholipid Esters with Enhanced Anti-SARS-CoV\u20112 Activity\nAaron F. Carlin,# James R. Beadle,# Alex E. Clark, Kendra L. Gully, Fernando R. Moreira, Ralph S. Baric,\nRachel L. Graham, Nadejda Valiaeva, Sandra L. Leibel, William Bray, Rachel E. McMillan,\nJonathan E. Freshman, Aaron F. Garretson, Rachael N. McVicar, Tariq Rana, Xing-Quan Zhang,\nJoyce A. Murphy, Robert T. Schooley, and Karl Y. Hostetler*\nCite This: J. Med. Chem. 2023, 66, 5802\u22125819\nRead Online\nACCESS\nMetrics & More\nArticle Recommendations\n*\ns\u0131\nSupporting Information\nABSTRACT: Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused\nby COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we\ndescribe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which\nallow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-\nbenzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by\n1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs\nthat have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-\nmethoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn\nphospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.\n\u25a0 INTRODUCTION\nSince its emergence in late 2019, SARS-CoV-2 has resulted in\nthe deaths of more than a million people in the United States"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 270
encoding: FLOAT32
metadata:
{"title": "Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity", "chroma:document": "and over 6.5 million people globally.1 Despite the dramatic\nimpact of SARS-CoV-2 vaccines on COVID-19-related\nmorbidity, COVID-19 remains the third most frequent cause\nof death in the U.S. behind only cardiovascular disease and\ncancer.2 The emergence of novel SARS-CoV-2 variants\ncoupled with the natural decay of coronavirus immunity has\ncontributed to successive waves of new and breakthrough\ninfections since the advent of COVID-19 vaccines. Vaccine\nhesitancy and the partial vaccine protection provided to older\nand immunocompromised populations further compromise\nvaccine efficacy at the population level.3\u22125 Viral evolution has\nalso severely compromised the efficacy of all currently available\nSARS-CoV-2-specific monoclonal antibodies for the preven-\ntion or treatment of the infection.6\nTwo orally bioavailable antiviral drugs are currently\navailable, nirmatrelvir/ritonavir and molnupiravir.7,8 Nirma-\ntrelvir/ritonavir reduces hospitalization and death, but the\nsubstantial number of ritonavir-related drug\u2212drug interactions\nrelated to its effects on hepatic metabolism and gut transport\nmechanisms, as well as the physician reticence to dose-adjust\nother medications in patients who are otherwise stable,\nReceived:\nJanuary 9, 2023\nPublished: April 11, 2023\nArticle\npubs.acs.org/jmc\n\u00a9 2023 The Authors. Published by\nAmerican Chemical Society\n5802\nhttps://doi.org/10.1021/acs.jmedchem.3c00046\nJ. Med. Chem. 2023, 66, 5802\u22125819"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 271
encoding: FLOAT32
metadata:
{"title": "Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 272
encoding: FLOAT32
metadata:
{"title": "Efficient and Precise Processing of the Optimized Primary Artificial MicroRNA in a Huntingtin-Lowering Adeno-Associated Viral Gene Therapy In Vitro and in Mice and Nonhuman Primates", "chroma:document": "Ef\ufb01cient and Precise Processing of the Optimized Primary\nArti\ufb01cial MicroRNA in a Huntingtin-Lowering Adeno-Associated\nViral Gene Therapy In Vitro and in Mice and Nonhuman Primates\nWei Wang,1,{,{ Pengcheng Zhou,1,{,x Xin Wang,1 Fen Chen,1,** Emily Christensen,1,{{ Jeffrey Thompson,1\nXiaoqin Ren,1 Adrian Kells,1,{{ Lisa Stanek,2,xx Todd Carter,1 Jay Hou,1,*** and Dinah W.Y. Sah1,*,i\n1Voyager Therapeutics, Cambridge, Massachusetts, USA; 2Sano\ufb01-Genzyme, Framingham, Massachusetts, USA.\n{Both these authors are co-\ufb01rst authors.\nCurrent af\ufb01liations: {Tome Biosciences, Cambridge, Massachusetts, USA.\nxFrontera Therapeutics, Bedford, Massachusetts, USA.\n**Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA.\n{{IDEXX Laboratories, Westbrook, Maine, USA.\n{{Asklepios BioPharmaceutical, Columbus, Ohio, USA.\nxxAf\ufb01nia Therapeutics, Waltham, Massachusetts, USA.\n***Skyline Therapeutics, Shanghai, China.\niORCID ID (https://orcid.org/0000-0003-2598-5881).\nHuntington\u2019s disease is a fatal neurodegenerative disorder caused by an inherited mutation in the huntingtin (HTT) gene\ncomprising an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat sequence that results in a pathogenic hun-\ntingtin protein. Adeno-associated viral (AAV) gene therapy containing a primary arti\ufb01cial microRNA (pri-amiRNA)\nspeci\ufb01cally targeting HTT messenger RNA (mRNA) has the potential to provide long-lasting therapeutic bene\ufb01t, through\ndurable reduction of mutant HTT expression after a single administration. The ef\ufb01ciency and precision of processing of the\npri-amiRNA precursor to the mature guide (G) strand by transduced cells are critical for speci\ufb01c and potent HTT mRNA\nlowering. The selection of the optimized pri-amiRNA comprised a series of in vitro studies followed by in vivo studies in\nsmall and then large mammals. Our studies demonstrate the predictivity of certain cell culture systems and rodent models for\nnonhuman primates with respect to some, but not all key features of pri-amiRNA processing. In addition, our results show"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 273
encoding: FLOAT32
metadata:
{"title": "Efficient and Precise Processing of the Optimized Primary Artificial MicroRNA in a Huntingtin-Lowering Adeno-Associated Viral Gene Therapy In Vitro and in Mice and Nonhuman Primates", "chroma:document": "that the processing of pri-amiRNAs to the mature guide strand can differ greatly across different scaffolds and sequences\nwhile providing the same levels of target lowering. Importantly, our data demonstrate that there is a combinatorial effect of\nguide and passenger (P) strand sequences, together with the scaffold, on pri-amiRNA processing, with different guide and\npassenger strand sequences within the same scaffold dramatically altering pri-amiRNA processing. Taken together, our\nresults highlight the importance of optimizing not only target lowering but also the ef\ufb01ciency and precision of pri-amiRNA\nprocessing in vitro, in rodents and in large mammals to identify the most potent and selective AAV gene therapy that\nharnesses the endogenous microRNA (miRNA) biogenesis pathway for target lowering without perturbing the endogenous\ncellular miRNA pro\ufb01le. The optimized pri-amiRNA was selected with this focus on ef\ufb01ciency and precision of pri-amiRNA\nprocessing in addition to its pharmacological activity on HTT mRNA lowering and general tolerability in vivo.\nKeywords: RNAi, arti\ufb01cial microRNA, Huntington\u2019s disease, huntingtin lowering, in vivo\nINTRODUCTION\nHUNTINGTON\u2019S DISEASE (HD) is a rare, autosomal-dominant,\ndebilitating, and fatal neurodegenerative disorder charac-\nterized by progressive motor, cognitive, and neuropsychi-\natric impairment. There are no effective therapies. Clinical\nonset based on motor diagnosis occurs at *40 years of age\non average, with death typically 15\u201320 years later, preceded\nby profound physical deterioration and dementia.\nHD is caused by a mutation in the huntingtin (HTT)\ngene, in which an expansion of more than *39 cytosine\n*Correspondence: Dr. Dinah W.Y. Sah, Voyager Therapeutics, 75 Sidney Street, Cambridge, MA 02139, USA. E-mail: dinah@vygr.com\nThe abstract portion of this article was presented at the ESGCT XXV Anniversary Congress in Collaboration with the German Society for Gene Therapy October 17\u201320, 2017"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 274
encoding: FLOAT32
metadata:
{"title": "Efficient and Precise Processing of the Optimized Primary Artificial MicroRNA in a Huntingtin-Lowering Adeno-Associated Viral Gene Therapy In Vitro and in Mice and Nonhuman Primates", "chroma:document": "Berlin, Germany; and also presented at the 21st Annual ASGCT Meeting, May 16\u201319, 2018, Chicago, IL, USA.\n\u00aa Wei Wang et al., 2021; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY]\n(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nHUMAN GENE THERAPY, VOLUME 33, NUMBERS 1\u20132\nDOI: 10.1089/hum.2021.221 j 37\nMary Ann Liebert, Inc."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 275
encoding: FLOAT32
metadata:
{"title": "Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition", "chroma:document": "Clinical Infectious Diseases                                          \nM A J O R  A R T I C L E\nNon-Lactobacillus-Dominant and Polymicrobial Vaginal \nMicrobiomes Are More Common in Younger South \nAfrican Women and Predictive of Increased Risk of \nHuman Immunodeficiency Virus Acquisition\nYiran Wang,1,a Laura No\u00ebl-Romas,1,2,a Michelle Perner,3,a Samantha Knodel,1,2,a Refilwe Molatlhegi,4 Sarah Hoger,5 Kenzie Birse,1,2 Christina Farr Zuend,1\nLyle R. McKinnon,5 and Adam D. Burgener1,2,6\n1Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; 2Department of Obstetrics and Gynecology, University of Manitoba, Winnipeg, \nCanada; 3Sexually Transmitted Infectious and Bloodborne Pathogens Section, JC Wilt Infectious Disease Research Center, Public Health Agency of Canada, Winnipeg, Canada; 4Department of \nMedical Microbiology, University of KwaZulu-Natal, Durban, South Africa; 5Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada; and 6Unit of \nInfectious Diseases, Department of Medicine Solna, Center for Molecular, Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden\nBackground. Adolescent girls and young women aged 15\u201224 years in sub-Saharan Africa are at disproportionate risk of human \nimmunodeficiency virus (HIV) infection. Given the known association between vaginal microbial dysbiosis and HIV susceptibility, we \nperformed an age-stratified analysis of the vaginal microbiome in South African women and compared this to their risk of HIV acquisition.\nMethods. Vaginal microbiome data were generated by mass spectrometry\u2013based proteomic analysis of cervicovaginal lavages \ncollected from participants (n = 688) in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial. \nParticipants were grouped by age (18\u201319 years, n = 93; 20\u201324 years, n = 326; 25\u201341 years, n = 269)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 276
encoding: FLOAT32
metadata:
{"title": "Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition", "chroma:document": "Results. Four microbiome types were identified based on predominant taxa, including Lactobacillus crispatus (CST-LC, 12.2%), \nLactobacillus iners (CST-LI, 43.6%), Gardnerella vaginalis (CST-GV, 26.6%), or polymicrobial (CST-PM, 15.1%). Women aged 18\u2013 \n19 and 20\u201324 years had increased CST-PM and a non-Lactobacillus-dominant microbiome compared to those 25\u201341 years (odds \nratio [OR], 3.14 [95% confidence interval {CI}, 1.12\u20137.87], P = .017; OR, 2.81 [95% CI, 1.07\u20137.09], P = .038, respectively; and OR, \n1.65 [95% CI, 1.02\u20132.65], P = .028; OR, 1.40 [95% CI, 1.01\u20131.95], P = .030, respectively). The HIV incidence rate of women with \nCST-PM microbiome was 7.19-fold higher compared to women with CST-LC (hazard ratio [HR], 7.19 [95% CI, 2.11\u201324.5], P = \n.00162), which was also consistent in women aged 20\u201324 years (HR, 4.90 [95% CI, 1.10\u201321.9], P = .0375).\nConclusions. Younger women were more likely to have a higher-risk polymicrobial microbiome suggesting that vaginal \nmicrobiota are contributing to increased HIV-1 susceptibility in this group.\nClinical Trials Registration. NCT00441298.\nKeywords. HIV transmission; vaginal microbiome; young women.\nReceived 02 September 2022; editorial decision 04 December 2022; published online 12 \nDecember 2022\naY. W., L. N.-R., M. P., and S. K. contributed equally to this work.\nCorrespondence: A. Burgener, Center for Global Health and Diseases, Case Western Reserve \nUniversity, 2109 Adelbert Rd, Biomedical Research Bldg, Cleveland, OH 44106 (adam. \nburgener@case.edu).\nClinical Infectious Diseases\u00ae\n2023;76(8):1372\u201381 \n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution- \nNonCommercial-NoDerivs \nlicence \n(https://creativecommons.org/licenses/by-nc-nd/4.0/), \nwhich permits non-commercial reproduction and distribution of the work, in any medium, pro-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 277
encoding: FLOAT32
metadata:
{"title": "Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition", "chroma:document": "vided the original work is not altered or transformed in any way, and that the work is properly \ncited. For commercial re-use, please contact journals.permissions@oup.com\nhttps://doi.org/10.1093/cid/ciac938\nIn sub-Saharan Africa, adolescent girls and young women \n(AGYW) aged 15\u201324 years are twice as likely to have human \nimmunodeficiency virus (HIV) than males of the same age \n[1]. Compared to their male counterparts, they acquire HIV in-\nfection at least 5\u20137 years earlier [1]. AGYW aged 15\u201319 years \nare especially vulnerable to becoming infected [2, 3]. In high- \nburden areas within South Africa, new infections are alarming-\nly high in AGYW, including 7.8% in those 15\u201319 years and \n8.6% in those 20\u201324 years of age based on a recent meta- \nanalysis [4]. Antiretroviral agents formulated as vaginal gels \n[5], rings [6, 7], and pills [8\u201310] have shown lower efficacy in \nthose with lower adherence, and lower adherence rates are \ncommon in younger age groups [6, 11]. Recent trials of newer \ntechnologies such as long-acting injectables, including HIV \nPrevention Trials Network study 084, have shown high efficacy \n[12] and provide further HIV prevention options for AGYW. \nNevertheless, intensifying HIV prevention efforts, specifically \nin young women, could have significant public health impact, \nand lessons learned in studying young women would have rel-\nevance for epidemic regions like these in Africa and the global \neffort to stop HIV. Although social, high-risk behavior, access \nto or utilization of healthcare services, and economic factors \nmay all contribute to increased susceptibility to HIV infection \n1372 \u2022 CID 2023:76 (15 April) \u2022 Wang et al"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 278
encoding: FLOAT32
metadata:
{"title": "Evaluating the seroprevalence of SARS-CoV-2 IgG in five different districts of Bangladesh. A seroepidemiological study", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 279
encoding: FLOAT32
metadata:
{"title": "Mice Humanized for MHC and hACE2 with High Permissiveness to SARS-CoV-2 Omicron Replication", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 280
encoding: FLOAT32
metadata:
{"title": "Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE", "chroma:document": "ARTICLE\nOPEN\nMale-selective effects of oxytocin agonism on alcohol intake:\nbehavioral assessment in socially housed prairie voles and\ninvolvement of RAGE\nSheena Potretzke1, Yangmiao Zhang1, Ju Li1, Kristopher M. Fecteau2, David W. Erikson2, Marcel Hibert3 and Andrey E. Ryabinin\n1\u2709\n\u00a9 The Author(s) 2022\nTargeting the oxytocin (OXT) peptide system has emerged as a promising new approach for the treatment of alcohol use disorder\n(AUD). However, further advancements in this development depend on properly modeling various complex social aspects of AUD\nand its treatment. Here we examined behavioral and molecular underpinnings of OXT receptor (OXTR) agonism in prairie voles, a\nrodent species with demonstrated translational validity for neurobiological mechanisms regulating social af\ufb01liations. To further\nimprove translational validity of these studies, we examined effects of intranasal (IN) OXT administration in male and female prairie\nvoles socially housed in the presence of untreated cagemates. IN OXT selectively inhibited alcohol drinking in male, but not female,\nanimals. Further, we con\ufb01rmed that exogenously administered OXT penetrates the prairie vole brain and showed that Receptor for\nAdvanced Glycation End-products assists this penetration after IN, but not intraperitoneal (IP), OXT administration. Finally, we\ndemonstrated that IP administration of LIT-001, a small-molecule OXTR agonist, inhibits alcohol intake in male, but not female,\nprairie voles socially housed in the presence of untreated cagemates. Taken together, results of this study support the promise of\nselectively targeting OXTR for individualized treatment of AUD.\nNeuropsychopharmacology (2023) 48:920\u2013928; https://doi.org/10.1038/s41386-022-01490-3\nINTRODUCTION\nThe prevalence and negative impacts of alcohol use disorder\n(AUD) demand ef\ufb01cacious treatment options. Currently approved\nAUD pharmacotherapies show limited success clinically [1\u20134],\ndespite demonstrated ef\ufb01cacy in preclinical models [5\u201310]."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 281
encoding: FLOAT32
metadata:
{"title": "Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE", "chroma:document": "Oxytocin (OXT), a hormone with essential roles in social behaviors\n[11, 12], has drawn interest as a potential pharmacotherapy for\nAUD. Previous research indicated a role for OXT in mediating the\nprocesses associated with alcohol use [13]. In particular, OXT\u2019s\nsocial effects [14, 15] may serve to bolster abstinence through\nsocial support\u2014a key mediator of treatment outcomes [16, 17].\nThis idea is in line with the previously proposed overarching role\nof OXT in the regulation of social-cue saliency [18].\nOptimization of animal models for testing pharmacotherapies\nfor AUD may help to bridge the gap between preclinical and\nclinical ef\ufb01cacy. In the current studies, we administered OXT\nintranasally (IN)\u2014a translationally relevant route exclusively used\nin clinical trials in human patients. Among the obstacles in\ndevelopment of ef\ufb01cacious therapies for AUD that current\ntherapies have inadequately addressed are the complex interac-\ntions of alcohol-related behaviors with the social environment\n[19\u201321]. Here we examined the effect of pharmacologically\ntargeting the OXT system in socially housed prairie voles given\nunrestricted access to the other animals in the cage and alcohol in\na continuous-access two-bottle choice paradigm (CA-2BC). Prairie\nvoles are facultatively monogamous rodents with demonstrated\ntranslational validity for mechanisms regulating social behaviors,\nin which the OXT system has been extensively explored [22\u201324].\nAs animals that voluntarily consume alcohol, and show social\nin\ufb02uences on alcohol consumption similar to humans, prairie voles\nserve as an ideal animal model for these studies [25, 26]. Finally,\nwe used a mixed-cage design, with treated and control animals in\nthe same cage. This design better recapitulates scenarios human\npatients experience during medication-assisted maintenance of\nabstinence from alcohol.\nDespite previous demonstrations of OXT\u2019s ef\ufb01cacy in decreasing\nmeasures associated with AUD preclinically [27\u201332] and clinically"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 282
encoding: FLOAT32
metadata:
{"title": "Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE", "chroma:document": "[33\u201335], the molecular mechanisms of OXT\u2019s effects remain elusive\nincluding its transport into the brain. OXT is thought to cross the\nblood-brain barrier (BBB) [36]. Evidence indicates that OXT acts\ncentrally to inhibit alcohol intake. In rats, centrally administered\nOXT decreased reinstatement of alcohol self-administration, and\ncentral, but not peripheral, administration of a BBB non-penetrant\noxytocin receptor (OXTR) antagonist prevented OXT\u2019s inhibitory\neffects on alcohol self-administration [31, 33]. In mice, a centrally-\nbut not peripherally acting- OXTR antagonist prevented a\ndecrease in alcohol intake following chemogenetic activation of\nhypothalamic OXT neurons [37]. Recent studies in rodents and\nnon-human\nprimates\n(NHPs)\nshowed\nsmall\nproportions\nof\nexogenous OXT in the brain when administered peripherally,\nReceived: 3 August 2022 Revised: 20 October 2022 Accepted: 25 October 2022\nPublished online: 11 November 2022\n1Department of Behavioral Neuroscience, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. 2Endocrine Technologies Core, Oregon National\nPrimate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. 3Laboratoire d\u2019Innovation Th\u00e9rapeutique, Facult\u00e9 de Pharmacie,\nUMR7200 CNRS/Universit\u00e9 de Strasbourg, 74 Route du Rhin, F-67412 Illkirch, France. \u2709email: ryabinin@ohsu.edu\nwww.nature.com/npp\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 283
encoding: FLOAT32
metadata:
{"title": "Systemic kappa opioid receptor antagonism accelerates reinforcement learning via augmentation of novelty processing in male mice", "chroma:document": "ARTICLE\nOPEN\nSystemic kappa opioid receptor antagonism accelerates\nreinforcement learning via augmentation of novelty processing\nin male mice\nZahra Z. Farahbakhsh1, Keaton Song1, Hannah E. Branthwaite1, Kirsty R. Erickson\n1, Snigdha Mukerjee1, Suzanne O. Nolan\n1 and\nCody A. Siciliano\n1\u2709\n\u00a9 The Author(s) 2023\nSelective inhibition of kappa opioid receptors (KORs) is highly anticipated as a pharmacotherapeutic intervention for substance use\ndisorders and depression. The accepted explanation for KOR antagonist-induced amelioration of aberrant behaviors posits that\nKORs globally function as a negative valence system; antagonism thereby blunts the behavioral in\ufb02uence of negative internal states\nsuch as anhedonia and negative affect. While effects of systemic KOR manipulations have been widely reproduced, explicit\nevaluation of negative valence as an explanatory construct is lacking. Here, we tested a series of falsi\ufb01able hypotheses generated a\npriori based on the negative valence model by pairing reinforcement learning tasks with systemic pharmacological KOR blockade in\nmale C57BL/6J mice. The negative valence model failed to predict multiple experimental outcomes: KOR blockade accelerated\ncontingency learning during both positive and negative reinforcement without altering innate responses to appetitive or aversive\nstimuli. We next proposed novelty processing, which in\ufb02uences learning independent of valence, as an alternative explanatory\nconstruct. Hypotheses based on novelty processing predicted subsequent observations: KOR blockade increased exploration of a\nnovel, but not habituated, environment and augmented the reinforcing ef\ufb01cacy of novel visual stimuli in a sensory reinforcement\ntask. Together, these results revise and extend long-standing theories of KOR system function.\nNeuropsychopharmacology (2023) 48:857\u2013868; https://doi.org/10.1038/s41386-023-01547-x\nINTRODUCTION\nCentral and peripheral kappa opioid receptors (KORs) are targets\nof a wide variety of pharmacotherapeutics. Most currently"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 284
encoding: FLOAT32
metadata:
{"title": "Systemic kappa opioid receptor antagonism accelerates reinforcement learning via augmentation of novelty processing in male mice", "chroma:document": "approved compounds are multi-target drugs, with varying\npharmacodynamic actions and selectivity for KORs. These drugs\nare used for the treatment of a diverse array of disorders\nincluding, but not limited to, nalfura\ufb01ne for pruritus [1],\nalfentanil for nociceptive [2] and levorphanol for neuropathic\npain [3], naltrexone for substance use disorders [4], and\neluxadoline for irritable bowel syndrome [5, 6]. Development\nof selective KOR compounds has been a longstanding goal in\nmedicinal chemistry and recent breakthroughs have produced\nclinically viable, highly selective KOR agonists and antagonists,\nseveral of which are in various stages of clinical evaluation\n(National Clinical Trial number: NCT02800928, NCT02218736,\nNCT01913535, NCT02641028, NCT02475447) [1, 7, 8]. In parti-\ncular, clinically viable selective KOR antagonists have been\nhighly anticipated due to wide consensus in the preclinical\nliterature that systemic blockade of KORs holds great promise\nfor the treatment of several neuropsychiatric disorders including\ndepression, substance use disorders, and anxiety [9\u201312].\nIn preclinical models, KOR activity has been causally linked to\nthe underlying behavioral symptomatology of multiple neuropsy-\nchiatric diseases. For example, systemic administration of KOR\nantagonists in model species reliably reverses escalated drug and\nalcohol consumption resulting from chronic exposure [13\u201317],\nameliorates depression-like phenotypes [18, 19], and can prevent\nthe behavioral consequences of chronic stress [20\u201323]. It is\nthought that KOR modulation of addiction-, depression-, and\nanxiety-related behaviors stems from its endogenous function as a\nnegative valence system. Indeed, the prevailing and widely\naccepted model of KOR\u2019s role in neuropsychiatric disease posits\nthat acute activation of KORs produces dysphoria and that\nexperience-dependent upregulation of this system drives aberrant\nbehavioral states such as anhedonia in depression and negative\naffect during periods of drug abstinence in addiction [24\u201341]. This"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 285
encoding: FLOAT32
metadata:
{"title": "Systemic kappa opioid receptor antagonism accelerates reinforcement learning via augmentation of novelty processing in male mice", "chroma:document": "model of the KOR\u2019s primary role in neurobehavioral processes\ncenters on negative valence processing and motivated behaviors\ndriven by aversive internal states, which are both critical but latent\nconstructs (i.e., cannot be directly observed). Though the latent\nnature of the variables involved does not allow for a straightfor-\nward operationalized de\ufb01nition, the theory has been semantically\nformalized by multiple literatures. The theory states that KOR\nactivity is involved in negative valence domains (e.g., acute threat,\npotential threat, sustained threat, loss, and frustrative nonreward)\nand is critical for the development of subsequent behavioral\nresponses to aversive stimuli, such as negative reinforcement\n[12, 22, 25, 42, 43]. The role of KORs in these constructs are\nReceived: 13 September 2022 Revised: 20 January 2023 Accepted: 2 February 2023\nPublished online: 17 February 2023\n1Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.\n\u2709email: cody.siciliano@vanderbilt.edu\nwww.nature.com/npp\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 286
encoding: FLOAT32
metadata:
{"title": "Iron and the Pathophysiology of Diabetes", "chroma:document": "Iron and the Pathophysiology of Diabetes\nAlexandria V Harrison1, Felipe Ramos Lorenzo1,2, Donald A. McClain1,2\n1Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, \nNorth Carolina, USA\n2Department of Veterans Affairs, W.G. (Bill) Hefner Veterans Affairs Medical Center, Salisbury, \nNorth Carolina, USA\nAbstract\nHigh iron is a risk factor for type 2 diabetes mellitus (T2DM) and affects most of its cardinal \nfeatures: decreased insulin secretion, insulin resistance, and increased hepatic gluconeogenesis. \nThis is true across the normal range of tissue iron levels and in pathologic iron overload. Because \nof iron\u2019s central role in metabolic processes (e.g., fuel oxidation) and metabolic regulation (e.g., \nhypoxia sensing), iron levels participate in determining metabolic rates, gluconeogenesis, fuel \nchoice, insulin action, and adipocyte phenotype. The risk of diabetes related to iron is evident \nin most or all tissues that determine diabetes phenotypes, with the adipocyte, beta cell, and liver \nplaying central roles. Molecular mechanisms for these effects are diverse, although there may be \nintegrative pathways at play. Elucidating these pathways has implications not only for diabetes \nprevention and treatment, but also for the pathogenesis of other diseases that are, like T2DM, \nassociated with aging, nutrition, and iron.\nKeywords\ndiabetes; iron; hepcidin; hemochromatosis; adipocyte; insulin\n1. INTRODUCTION\nMacronutrients play an undisputed role in conferring an increased risk of type 2 diabetes \nmellitus (T2DM), but the micronutrient iron is also a risk determinant, not only in pathologic \nexcess or deficiency, but also within its very broad range of normal levels. This review \naddresses the evidence for a connection between iron and diabetes risk, first providing a \nbrief review of iron homeostasis and the evidence linking tissue iron levels with diabetes \nin humans. Because in many cases the aforementioned topics have been the subject of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 287
encoding: FLOAT32
metadata:
{"title": "Iron and the Pathophysiology of Diabetes", "chroma:document": "detailed reviews, this review concentrates on mechanistic studies addressing how iron \nThis work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, \nand reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party \nmaterial in this article for license information.\ndmcclain@wakehealth.edu . \nDISCLOSURE STATEMENT\nThe authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the \nobjectivity of this review.\nHHS Public Access\nAuthor manuscript\nAnnu Rev Physiol. Author manuscript; available in PMC 2023 May 05.\nPublished in final edited form as:\nAnnu Rev Physiol. 2023 February 10; 85: 339\u2013362. doi:10.1146/annurev-physiol-022522-102832.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 288
encoding: FLOAT32
metadata:
{"title": "Fourth mRNA vaccination increases cross-neutralizing antibody titers against SARS-CoV-2 variants, including BQ.1.1 and XBB, in a very elderly population", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 289
encoding: FLOAT32
metadata:
{"title": "Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain", "chroma:document": "Article\nMolecular and cognitive signatures of ageing\npartially restored through synthetic delivery of IL2\nto the brain\nPierre Lemaitre1,2,\u2020\n, Samar HK Tareen3,\u2020, Emanuela Pasciuto1,2,\u2020\n, Loriana Mascali1,2,\nAraks Martirosyan1,4, Zsuzsanna Callaerts-Vegh5\n, Suresh Poovathingal1, James Dooley3,6\n,\nMatthew G Holt1,4,7,*,\u2021\n, Lidia Yshii1,2,4,**,\u2021\n& Adrian Liston1,2,3,6,***,\u2021\nAbstract\nCognitive decline is a common pathological outcome during aging,\nwith an ill-defined molecular and cellular basis. In recent years,\nthe concept of inflammaging, defined as a low-grade inflammation\nincreasing with age, has emerged. Infiltrating T cells accumulate in\nthe brain with age and may contribute to the amplification of\ninflammatory cascades and disruptions to the neurogenic niche\nobserved with age. Recently, a small resident population of regula-\ntory T cells has been identified in the brain, and the capacity of\nIL2-mediated expansion of this population to counter neuroinflam-\nmatory disease has been demonstrated. Here, we test a brain-\nspecific IL2 delivery system for the prevention of neurological\ndecline in aging mice. We identify the molecular hallmarks of\naging in the brain glial compartments and identify partial restora-\ntion of this signature through IL2 treatment. At a behavioral level,\nbrain IL2 delivery prevented the age-induced defect in spatial\nlearning, without improving the general decline in motor skill or\narousal. These results identify immune modulation as a potential\npath to preserving cognitive function for healthy aging.\nKeywords Aging; Brain; Gene Therapy; Interleukin 2; Regulatory T cells\nSubject Categories Immunology; Neuroscience\nDOI 10.15252/emmm.202216805 | Received 28 August 2022 | Revised 8 March\n2023 | Accepted 10 March 2023 | Published online 28 March 2023\nEMBO Mol Med (2023) 15: e16805\nIntroduction\nAging is an irreversible process associated with physical deteriora-\ntion and hence especially noticeable in organs containing mainly\npostmitotic cells, such as the brain. The progressive decline in mem-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 290
encoding: FLOAT32
metadata:
{"title": "Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain", "chroma:document": "ory, orientation, attention, motivation, and cognition seen in\nhumans is thought to stem largely from aging-related processes (Hof\n& Morrison, 2004). Although cognitive aging research generally\nfocuses on neurons, which are widely held to be the computational\nunits of the brain, there is an increasing realization that reciprocal\ninteractions between neurons and non-neuronal cells (collectively\nreferred to as glia) play key roles in all aspects of nervous system\nfunction. These include the regulation of synapse formation and\nfunction by astrocytes, as well as myelination and provision of tro-\nphic support to neurons by oligodendrocytes. Once thought of as\nsolely immune cells, which protect the CNS against injury and dis-\nease, there is increasing evidence that the same systems used by\nmicroglia to remove invading pathogens from the brain have also\nbeen co-opted to remove weak and/or inappropriate neuronal syn-\napses, establishing precise patterns of neuronal connectivity in the\nbrain (Allen & Lyons, 2018). It should not be surprising, therefore,\nthat aging-related cognitive decline has been associated with several\nmolecular processes, including chronic inflammation, impaired\nautophagy, macromolecular damage, and mitochondrial dysfunction\nand senescence (Hou et al, 2019), which impact the function of all\nCNS cell types (Jurk et al, 2012; Bussian et al, 2018; Chinta\net al, 2018; Ogrodnik et al, 2019).\nIn addition to the shared cellular phenotypes of aging, unique\nphenotypes emerge among the individual glial cell types with aging.\n1\nVIB Center for Brain and Disease Research, Leuven, Belgium\n2 Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium\n3 Immunology Programme, The Babraham Institute, Babraham, UK\n4 Department of Neurosciences, KU Leuven, Leuven, Belgium\n5 Laboratory of Biological Psychology, Faculty of Psychology, KU Leuven, Leuven, Belgium\n6 Department of Pathology, The University of Cambridge, Cambridge, UK"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 291
encoding: FLOAT32
metadata:
{"title": "Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain", "chroma:document": "7 Instituto de Investiga\u00e7\u0001ao e Inova\u00e7\u0001ao em Sa\u0003ude (i3S), University of Porto, Porto, Portugal\n*Corresponding author. Tel: +351 226 074 900; E-mail: mholt@i3s.up.pt\n**Corresponding author. Tel: +32 16 32 33 67; E-mail: lidia.yshii@kuleuven.be\n***Corresponding author. Tel: +44 1223 333690; E-mail: al989@cam.ac.uk\n\u2020These authors contributed equally to this work\n\u2021These authors contributed equally to this work\n\u0001 2023 The Authors. Published under the terms of the CC BY 4.0 license\nEMBO Molecular Medicine\n15: e16805 | 2023\n1 of 18"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 292
encoding: FLOAT32
metadata:
{"title": "Computational complexity drives sustained deliberation", "chroma:document": "Nature Neuroscience | Volume 26 | May 2023 | 850\u2013857\n850\nnature neuroscience\nArticle\nhttps://doi.org/10.1038/s41593-023-01307-6\nComputational complexity drives  \nsustained deliberation\nTao Hong\u2009\n \u20091,2,3 & William R. Stauffer\u2009\n \u20091,2,3 \nEconomic deliberations are slow, effortful and intentional searches for \nsolutions to difficult economic problems. Although such deliberations are \ncritical for making sound decisions, the underlying reasoning strategies and \nneurobiological substrates remain poorly understood. Here two nonhuman \nprimates performed a combinatorial optimization task to identify valuable \nsubsets and satisfy predefined constraints. Their behavior revealed \nevidence of combinatorial reasoning\u2014when low-complexity algorithms \nthat consider items one at a time provided optimal solutions, the animals \nadopted low-complexity reasoning strategies. When greater computational \nresources were required, the animals approximated high-complexity \nalgorithms that search for optimal combinations. The deliberation \ntimes reflected the demands created by computational complexity\u2014\nhigh-complexity algorithms require more operations and, concomitantly, \nthe animals deliberated for longer durations. Recurrent neural networks \nthat mimicked low- and high-complexity algorithms also reflected the \nbehavioral deliberation times and were used to reveal algorithm-specific \ncomputations that support economic deliberation. These findings reveal \nevidence for algorithm-based reasoning and establish a paradigm for \nstudying the neurophysiological basis for sustained deliberation.\nDifficult economic decisions\u2014whether to buy a house or not, what to \nstudy at school or how to invest for retirement\u2014require slow, effortful \nand intentional consideration1. Decision-makers must determine the \nbest outcomes by considering combinations of economic factors, \nincluding immediate needs, available resources, environmental con-\nstraints and future consequences. These combinatorial considera-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 293
encoding: FLOAT32
metadata:
{"title": "Computational complexity drives sustained deliberation", "chroma:document": "tions generate substantial computational demands and render the \nfinding of satisfactory solutions to a hard problem. Economic delib-\neration is, therefore, a cognitive process of identifying subjectively \noptimal solutions to hard economic problems. This mode of slow \nand effortful thinking is rarely evoked with traditional neuroeco-\nnomic paradigms. Even when choosing between items with similar \nvalues, a context that is considered to drive hard economic choices, \nboth human and nonhuman primate (NHP) neuronal and behavioral \nresponses evolve in hundreds of milliseconds2,3. In contrast to stand-\nard neuroeconomic tasks, combinatorial optimization problems \nrequire extended deliberations. These problems can be designed to \nreflect the combinatorial nature of difficult economic decisions, as \ndefined above, and possess a normative scale of difficulty\u2014compu-\ntational complexity. Recent studies of human decision-makers have \nshown that computational complexity modulates effort, response \ntimes (RTs) and performance4,5. Thus, combinatorial optimization \ntasks have the capacity to model difficult economic decisions, and \nto reveal the mental algorithms for economic deliberation.\nComputational difficulty, or complexity, is manifested in numer-\nous routine tasks, including scheduling, route planning and, as men-\ntioned above, economic decision making6. Therefore, understanding \nhow the brain manages computational complexity is vital for build-\ning computationally plausible models of cognition and behavior7,8. \nComputational complexity theory is a branch of computer science \nthat focuses on characterizing the difficulty of solving computational \nproblems9, defining the complexity of individual problems10 and \nReceived: 26 April 2022\nAccepted: 16 March 2023\nPublished online: 24 April 2023\n Check for updates\n1Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA. 2Program in Neural Computation, Carnegie Mellon University, Pittsburgh, PA,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 294
encoding: FLOAT32
metadata:
{"title": "Computational complexity drives sustained deliberation", "chroma:document": "USA. 3Center for the Neural Basis of Cognition, Pittsburgh, PA, USA. \n\u2009e-mail: wrs@pitt.edu"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 295
encoding: FLOAT32
metadata:
{"title": "Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines", "chroma:document": "REVIEW ARTICLE\nOPEN\nTargetable elements in SARS-CoV-2 S2 subunit for the design\nof pan-coronavirus fusion inhibitors and vaccines\nLiyan Guo1, Sheng Lin1, Zimin Chen1, Yu Cao1,2, Bin He1\u2709 and Guangwen Lu\n1\u2709\nThe ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2\n(SARS\u2010CoV\u20102), has caused devastating impacts on the public health and the global economy. Rapid viral antigenic evolution has led\nto the continual generation of new variants. Of special note is the recently expanding Omicron subvariants that are capable of\nimmune evasion from most of the existing neutralizing antibodies (nAbs). This has posed new challenges for the prevention and\ntreatment of COVID-19. Therefore, exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In\nsharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain (RBD), the S2 fusion\nsubunit has remained highly conserved among variants. Hence, S2-based therapeutics may provide effective cross-protection\nagainst new SARS-CoV-2 variants. Here, we summarize the most recently developed broad-spectrum fusion inhibitors (e.g., nAbs,\npeptides, proteins, and small-molecule compounds) and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2\nsubunit. The main focus includes all the targetable S2 elements, namely, the fusion peptide, stem helix, and heptad repeats 1 and 2\n(HR1-HR2) bundle. Moreover, we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-\nreactive fusion inhibitors, which should guide and promote future design of S2-based inhibitors and vaccines against new\ncoronaviruses.\nSignal Transduction and Targeted Therapy  (2023) 8:197 \n; https://doi.org/10.1038/s41392-023-01472-x\nINTRODUCTION\nCoronaviruses\n(CoVs)\nare\nenveloped,\npositive-sense,\nsingle-\nstranded RNA viruses, classi\ufb01ed in the family of Coronaviridae.1\nThey exist widely in nature and can infect humans, other"}


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id: 296
encoding: FLOAT32
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{"title": "Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines", "chroma:document": "mammals, or various avian species, causing different acute and\nchronic diseases.2,3 Coronaviruses are a highly diverse family\ncomprising four genera: alphacoronavirus (\u03b1-CoV), betacorona-\nvirus (\u03b2-CoV), gammacoronavirus (\u03b3-CoV) and deltacoronavirus (\u03b4-\nCoV).4 The four annually circulating human coronaviruses (HCoVs),\nnamely HCoV-229E and HCoV-NL63 of \u03b1-CoV and HCoV-OC43 and\nHCoV-HKU1 of \u03b2-CoV, are endemic to humans and generally cause\nmild upper respiratory illness.5\u20138 However, there are also three\nhighly pathogenic \u03b2-CoVs, including severe acute respiratory\nsyndrome coronavirus (SARS-CoV), Middle East respiratory syn-\ndrome coronavirus (MERS-CoV), and severe acute respiratory\nsyndrome\ncoronavirus\n2\n(SARS\u2010CoV\u20102).9\u201311\nAll\nthree\nhighly\npathogenic HCoVs can cause severe pneumonia in humans and\nhave led to numerous infections and deaths worldwide.12\u201314 The\nastonishingly high transmissibility of SARS-CoV-2 has resulted in a\nglobal coronavirus disease 2019 (COVID-19) pandemic that\nsigni\ufb01cantly impacted the global economy and public health,\ncausing more than 763,740,140 con\ufb01rmed infections and over\n6,908,554 deaths as of 19 April 2023 (https://covid19.who.int).\nCoronavirus infection begins with virus entry, which depends\non the intact trimetric spike (S) protein located on the surface of\nthe virion.15\u201319 The S protein, a class I viral fusion glycoprotein, is\nfunctionally\ndivided\ninto\nS1\nand\nS2\nsubunits,\nwhich\nare\nresponsible for receptor binding and membrane fusion, respec-\ntively. Speci\ufb01cally, S1 relies on receptor-binding domain (RBD) to\ninteract with human angiotensin-converting enzyme 2 (ACE2).16,20\nAs a major antigenic determinant, RBD is a critical target for the\ndevelopment of vaccines and fusion inhibitors. Currently, most\ntherapeutic neutralizing antibodies (nAbs) and promising vaccine\ncandidates are designed to target the RBD or use RBD as the sole\nantigen.21\u201325 However, RBD is poorly conserved, with the newly\nemerged Omicron subvariants harboring multiple mutations in"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 297
encoding: FLOAT32
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{"title": "Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines", "chroma:document": "RBD that are capable of immune evasion from the majority of\nexisting neutralizing antibodies (nAbs). Consequently, vaccine\nef\ufb01cacy has markedly reduced, thus, posing new challenges for\nthe prevention and treatment of SARS-CoV-2.26\u201330 Although\nefforts have been made to design nAbs and vaccines against\nOmicron subvariants, new variants might continue to emerge due\nto the progressive accumulation of mutations and the increasing\nimmune selective pressure.31 Moreover, SARS-CoV-2 and MERS-\nCoV coinfection has been reported and may occur more\nfrequently as the virus evolves.32 Given that \u03b2-CoVs infect the\nsame target cells and use identical transcriptional regulatory\nsequences, genetic recombination between coronaviral coinfec-\ntion\nin\nCOVID-19\nmay\nresult\nin\nnew\nclades\nwith\nhigher\ntransmissibility and lethality.33 Although many nAbs and vaccines\nagainst each class of \u03b2-CoVs have been developed with proven\nef\ufb01cacy, they show weak cross-neutralization activity, thus, limit-\ning their ability to prevent or treat highly pathogenic new HCoV\ninfections.34,35\nReceived: 18 February 2023 Revised: 4 April 2023 Accepted: 23 April 2023\n1Department of Emergency Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China and 2Disaster Medicine\nCenter, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China\nCorrespondence: Bin He (hb40400387@163.com) or Guangwen Lu (lugw@scu.edu.cn)\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


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id: 298
encoding: FLOAT32
metadata:
{"title": "HIV replication and latency in monocytes and macrophages", "chroma:document": "HIV replication and latency in monocytes and macrophages\nRebecca T. Veenhuisa, Celina M. Abreua, Erin N. Shirka, Lucio Gamaa,d, Janice E. \nClementsa,b,c,*\naDepartment of Molecular and Comparative Biology, Johns Hopkins University School of \nMedicine, Baltimore, MD, United States\nbDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United \nStates\ncDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United \nStates\ndVaccine Research Center, NIAID, NIH, Bethesda, MD, United States\nAbstract\nThe relevance of monocyte and macrophage reservoirs in virally suppressed people with HIV \n(vsPWH) has previously been debatable. Macrophages were assumed to have a moderate life \nspan and lack self-renewing potential. However, recent studies have challenged this dogma and \nnow suggest an important role of these cell as long-lived HIV reservoirs. Lentiviruses have a \nlong-documented association with macrophages and abundant evidence exists that macrophages \nare important target cells for HIV in vivo. A critical understanding of HIV infection, replication, \nand latency in macrophages is needed in order to determine the appropriate method of measuring \nand eliminating this cellular reservoir. This review provides a brief discussion of the biology and \nacute and chronic infection of monocytes and macrophages, with a more substantial focus on \nreplication, latency and measurement of the reservoir in cells of myeloid origin.\nKeywords\nMacrophages; HIV; SIV; Latency; Replication\n1. Introduction\nSince the emergence of AIDS, it was demonstrated that both CD4 + T cells and \nmacrophages were susceptible to HIV infection and were involved in disease progression. \nEarly studies classified the virus as macrophage tropic, as it was able to induce syncytia \nin culture [1]. HIV isolates that could infect healthy donor CD4 + T cells in vitro were \nalso able to infect tissue macrophages in several organs, including brain and lung [2,3]."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 299
encoding: FLOAT32
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{"title": "HIV replication and latency in monocytes and macrophages", "chroma:document": "Indeed, some of the direct manifestations of viral pathogenesis were directly associated with \ninfection of tissue macrophages, leading to neurological and lung symptoms. Combined \n*Corresponding author at: Department of Molecular and Comparative Biology, Johns Hopkins University School of Medicine, 733 N. \nBroadway, Baltimore, MD, 21205, United States. jclements@jhmi.edu (J.E. Clements). \nHHS Public Access\nAuthor manuscript\nSemin Immunol. Author manuscript; available in PMC 2023 May 10.\nPublished in final edited form as:\nSemin Immunol. 2021 January ; 51: 101472. doi:10.1016/j.smim.2021.101472.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 300
encoding: FLOAT32
metadata:
{"title": "Adenoviral-vectored next-generation respiratory mucosal vaccines against COVID-19", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 301
encoding: FLOAT32
metadata:
{"title": "An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor-binding domain vaccine in aged mice", "chroma:document": "An aluminum hydroxide:CpG adjuvant enhances protection \nelicited by a SARS-CoV-2 receptor-binding domain vaccine in \naged mice\nEtsuro Nanishi1,2,\u2020, Francesco Borriello1,2,3,19,\u2020, Timothy R. O\u2019Meara1,\u2021, Marisa E. \nMcGrath4,\u2021, Yoshine Saito1, Robert E. Haupt4, Hyuk-Soo Seo5,6, Simon D. van Haren1,2, \nCecilia B. Cavazzoni7, Byron Brook1,2, Soumik Barman1,2, Jing Chen8, Joann Diray-\nArce1,2, Simon Doss-Gollin1, Maria De Leon1, Alejandra Prevost-Reilly1, Katherine Chew1, \nManisha Menon1, Kijun Song5, Andrew Z. Xu5, Timothy M. Caradonna9, Jared Feldman9, \nBlake M. Hauser9, Aaron G. Schmidt9,10, Amy C. Sherman1,11, Lindsey R. Baden11, \nRobert K. Ernst12, Carly Dillen4, Stuart M. Weston4, Robert M. Johnson4, Holly L. \nHammond4, Romana Mayer13, Allen Burke13, Maria E. Bottazzi14,15, Peter J. Hotez14,15, \nUlrich Strych14,16, Aiquan Chang17, Jingyou Yu17, Peter T. Sage7, Dan H. Barouch17, Sirano \nDhe-Paganon5,6, Ivan Zanoni2,3, Al Ozonoff1,2, Matthew B. Frieman4,\u00a7, Ofer Levy1,2,18,\u00a7, \nDavid J. Dowling1,2,\u00a7,*\n1Precision Vaccines Program, Division of Infectious Diseases, Boston Children\u2019s Hospital, Boston, \nMA, USA 02115.\n2Department of Pediatrics, Harvard Medical School, Boston, MA, USA 02115.\n3Division of Immunology, Boston Children\u2019s Hospital, Boston, MA, USA 02115.\n4Department of Microbiology and Immunology, University of Maryland School of Medicine, \nBaltimore, MD, USA 21201.\n*Corresponding author: David J. Dowling, Precision Vaccines Program, Division of Infectious Diseases, Boston Children\u2019s Hospital; \nHarvard Medical School, Rm 842, Boston, MA 02115, USA. Tel: +1 617-919-6890. david.dowling@childrens.harvard.edu.\n\u2020These authors contributed equally to this manuscript.\n\u00a7Co-senior authors.\n\u2021These authors contributed equally to this manuscript.\nAUTHOR CONTRIBUTIONS\nEN and FB conceived, designed, performed, analyzed the experiments and wrote the paper; TRO performed mouse serological \nassays, splenocyte restimulation, human in vitro experiments and their analysis; YS performed mouse in vivo experiments, serological"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 302
encoding: FLOAT32
metadata:
{"title": "An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor-binding domain vaccine in aged mice", "chroma:document": "readouts, splenocyte restimulation; BB, MDL, APR, KC, MM, SDG, and SDvH performed in vitro PBMC or T cell co-culture \nexperiments; SB performed splenocyte restimulation; JC and JD-A performed the analysis of the qPCR data; KS, AZX, HSS, SDP, \nTMC, JF, BMH, and AGS expressed and purified SARS-CoV-2 RBD and spike protein; MEM, REH, CD, SMW, RMJ, HLH, \nRM, AB, and MBF performed and analyzed SARS-CoV-2 neutralization experiments and mouse challenge study; AC, JY, and \nDHB performed and analyzed pseudovirus neutralization experiments; ACS and LRB contributed to the human older adult in vitro \nanalysis; CBC and PTS performed and analyzed lymph node immunophenotyping; MEB, PJH, and US edited and critically reviewed \nthe manuscript; RKE and IZ contributed to the design of experiments; AO provided study design feedback and contributed to the \nstatistical analysis; OL and DJD conceived the project, designed the experiments, and wrote the manuscript.\nCOMPETING INTERESTS STATEMENT\nEN, FB, TRO, YS, SVH, IZ, OL and DJD are named inventors on vaccine adjuvant patents assigned to Boston Children\u2019s Hospital \n(\u201cAdjuvants For Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV) Vaccines\u201d, PCT/US21/34919). FB has signed \nconsulting agreements with Merck Sharp & Dohme Corp. (a subsidiary of Merck & Co., Inc.), Sana Biotechnology, Inc., and F. \nHoffmann-La Roche Ltd. IZ reports compensation for consulting services with Implicit Biosciences. MF is on the advisory board \nof Aikido Pharma. The Baylor College of Medicine (BCM) authors declare they are developers of a recombinant RBD technology. \nBCM recently licensed the technology to Biological E, an Indian manufacturer, for advancement and licensure. OL served as a paid \nconsultant to Moody\u2019s analytics. These commercial or financial relationships are unrelated to the current study.\nHHS Public Access\nAuthor manuscript\nSci Transl Med. Author manuscript; available in PMC 2023 May 12.\nPublished in final edited form as:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 303
encoding: FLOAT32
metadata:
{"title": "An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor-binding domain vaccine in aged mice", "chroma:document": "Sci Transl Med. 2022 January 26; 14(629): eabj5305. doi:10.1126/scitranslmed.abj5305.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 304
encoding: FLOAT32
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{"title": "Paroxysmal alien hand syndrome", "chroma:document": "7ournal ofNeurology, Neurosurgery, and Psychiaty 1993;56:788-792\nParoxysmal alien hand syndrome\nRamon Leiguarda, Sergio Starkstein, Martin Nogues, Marcelo Berthier, Roberto Arbelaiz\nAbstract\nFour patients are described who presen-\nted with a paroxysmal form of the alien\nhand syndrome. Two patients with dam-\nage to one frontomedial cortex had brief\nepisodes of abnormal motor behaviour of\nthe contralateral arm that featured grop-\ning, grasping, and apparently purposeful\nbut\nperseverative\nmovements,\nwhich\nboth\npatients\ninterpreted\nas\nalien\nor\nforeign. The other two patients, with\nposterior parietal damage, reported a\nparoxysmal feeling of unawareness of the\nlocation of the contralateral arm, lack of\nrecognition of the arm as their own, pur-\nposeless movements, and personification\nof the arm. These cases represent a new\nform of the alien hand syndrome mani-\nfested by\nbrief, paroxysmal\nepisodes,\nwhich may be due to ictal mechanisms.\n(7 Neurol Neurosurg Psychiatty 1993;56:788-792)\nwith an infarction in the territory of the right\nposterior\ncerebral\nartery spontaneous arm\nmovements such as those related to gestures\nor postural adjustment, are felt as out of con-\ntrol due to opticosensory ataxia and as alien\ndue to the severe sensory loss.\" The alien\nhand syndrome in patients with unilateral\nhemispheric lesions, unlike those with callosal\ndamage, is always present in the hand con-\ntralateral to the lesion, regardless of the pat-\ntern of cerebral speech dominance and not\nnecessarily triggered by volitional movements\nof the normal hand.4 69\nThe alien hand syndrome may last for days\nor weeks but has not been described as a\nparoxysmal manifestation. We\nreport four\npatients who showed a paroxysmal alien hand\nsyndrome probably caused by seizures origi-\nnating in the contralateral frontomedial cor-\ntex (two patients) and in the contralateral\nposterior parietal region (two patients).\nInstitute of\nNeurological Research\nRafil Carrea, Buenos\nAires, Argentina\nRam6n Leiguarda\nSergio Starkstein\nMartin Nogues\nMarcelo Berthier"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 305
encoding: FLOAT32
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{"title": "Paroxysmal alien hand syndrome", "chroma:document": "Roberto Arbelaiz\nCorrespondence to:\nDr Leiguarda, Fleni,\nAyacucho 2166, (1112)\nBuenos Aires, Argentina.\nReceived 23 June 1992\nand in revised form\n13 October 1992.\nAccepted 16 October 1992\nThe alien hand sign or syndrome is a psy-\nchomotor disorder characterised by a dissoci-\nation between intention and action. One of\nthe patient's hands performs apparently pur-\nposeful movements, which are independent of\nvolitional control, as if the hand is driven by\nan\nexternal\nagent.'-9 The\nsymptoms\nvary\naccording to location of the lesion. In patients\nwith either surgical\nor spontaneous lesions\nrestricted to the corpus callosum, the hand\nipsilateral to the language and motor domi-\nnant hemisphere acts in a manner opposite to\nwhat the patient voluntarily does with the\ndominant\nhand,\na\nphenomenon\ncalled\ndiagonistic dyspraxia by Akelaitis' and inter-\nmanual conflict by Bogen.3 This abnormal\nmotor behaviour is always triggered by voli-\ntional movements of the normal hand.58'0\nWhen a medial callosal lesion affects adjacent\nparietotemporal\nregions,\nthe non-dominant\narm may not be recognised as the patient's\nown when held by the\ncontralateral\narm\nbehind the back in the absence of sensory\nloss7 or, altematively, the hand \"behaves in a\nway which the patient finds 'foreign', 'alien'\nor\nat\nleast uncooperative\".'\nPatients\nwith\nmedial frontal lobe damage affecting the sup-\nplementary\nmotor\narea and\nthe\ncingulate\ngyrus may show a seemingly purposeful and\nuncontrollable tendency of the hand\ncon-\ntralateral\nto the lesion to grope and grasp\nobjects, sometimes accompanied by motor\nperseveration or compulsive manipulation of\ntools placed before them.469 Among patients\nCase reports\nCase 1\nA 65 year old right handed man reported the\nfollowing: \"While I was travelling on a bus I\nnoticed that a hand was approaching me on\nthe right from behind, trying to catch me.\nAfter grasping my trouser leg, the hand did\nnot release it. First, I thought somebody was\nassaulting me, but then I realised that it was\nmy own right hand, although I did not feel it"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 306
encoding: FLOAT32
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{"title": "Paroxysmal alien hand syndrome", "chroma:document": "belonged to me. Thereafter, the fingers devel-\noped\ncreeping movements,\nand\nrepetitive\njerks involving the whole arm soon followed. I\nwas unable to control my right hand and I\nhad to grasp and hold it with my left hand.\nMy right arm felt heavy and awkward.\nI was\nvery anguished, anxious and frightened, and\nhad palpitations.\n. .\" The episode lasted for a\nfew\nminutes,\nand\nrecurred\nbriefly\nthat\nevening at the patient's home: \"I couldn't\nsleep at all that night because I was terrified\nmy right hand would assault me while sleep-\ning.\"\nNeurological,\nneuropsychiatric,\nand\ngeneral examinations yielded normal results.\nLaboratory analyses (haemoglobin concentra-\ntion, white 7 blood cell count, erythrocyte\nsedimentation\nrate,\nblood\nglucose,\nblood\nurea,\nplasma\nelectrolytes,\ncalcium\nions,\nVenereal Disease Research Laboratory test,\nlipids,\nliver\nfunction\ntest,\nprotein\nelec-\ntrophoresis, coagulation studies, T3 and T4,\nurinalysis, electrocardiography, doppler ultra-\nsound\nof\nneck\nand\nintracranial\nvessels,\nechocardiogram,\nand\ninterictal\nelectroen-\ncephalography) also yielded normal results.\n788"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 307
encoding: FLOAT32
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{"title": "Regional cerebral blood flow abnormalities in depressed patients with", "chroma:document": "7Journal of Neurology, Neurosurgery, and Psychiatry 1992;55:768-773\nRegional cerebral blood flow abnormalities in\ndepressed patients with cognitive impairment\nR J Dolan, C J Bench, R G Brown, L C Scott, K J Friston, R S J Frackowiak\nAcademic Department\nof Psychiatry, Royal\nFree Hospital and\nSchool of Medicine,\nLondon\nR J Dolan*\nC J Bench*\nL C Scott\nMRC Cyclotron Unit,*\nHammersmith\nHospital, London\nK J Friston\nR S J Frackowiak\nMRC Human\nMovement and\nBalance Unit, National\nHospital for Neurology\nand Neurosurgery,\nLondon\nR G Brown\nAcademic Department\nof Psychiatry,\nWestminster and\nCharing Cross\nMedical School,\nLondon\nK J Friston\nNational Hospital for\nNeurology and\nNeurosurgery, London\nR J Dolan\nR S J Frackowiak\nCorrespondence to:\nDr Dolan, Royal Free\nHospital School of\nMedicine, Rowland Hill\nStreet, London NW3 2PF,\nUK.\nReceived 30 September\n1991\nand in final revised form\n5 March 1992.\nAccepted 16 March 1992\nAbstract\nDepression with cognitive impairment, so\ncalled\ndepressive\npseudodementia,\nis\ncommonly mistaken for a neurodegener-\native dementia. Using positron emission\ntomography (PET) derived measures of\nregional cerebral blood flow (rCBF) a\ncohort of 33 patients with major depres-\nsion was studied. Ten patients displayed\nsignificant\nand\nreversible\ncognitive\nimpairment. The patterns of rCBF of\nthese\npatients\nwere compared\nwith\na\ncohort of equally depressed non-cogni-\ntively impaired depressed patients. In the\ndepressed cognitively impaired patients a\nprofile of rCBF abnormalities was identi-\nfied consisting of decreases in the left\nanterior medial prefrontal\ncortex and\nincreases in the cerebellar vermis. These\nchanges were additional to those seen in\ndepression alone and are distinct from\nthose\ndescribed\nin\nneurodegenerative\ndementia. The cognitive impairment seen\nin a proportion\nof depressed patients\nwould seem to be associated with dysfimc-\ntion of neural systems distinct from those\nimplicated in depression alone or the\nneurodegenerative dementias.\n(7 Neurol Neurosurg Psychiatry 1992;55:768-773)"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 308
encoding: FLOAT32
metadata:
{"title": "Regional cerebral blood flow abnormalities in depressed patients with", "chroma:document": "Primary depression with significant cognitive\nimpairment, commonly referred to as depres-\nsive\npseudodementia\nor\nthe\ndementia\nof\ndepression, may be mistaken for a progressive\nneurodegenerative\ndementia. 1\nDepression\nitself may also be a concomitant of a progres-\nsive degenerative dementia, particularly in its\nearly phases.2 The conjunction of depression\nand cognitive impairment frequently poses a\nclinical diagnostic problem which may hamper\npatient management. Recognition of a primary\ndepression masquerading as a neurodegener-\native dementia is clinically important because\nof its treatability. Depression with cognitive\nimpairment can lead to misdiagnosis of pri-\nmary degenerative dementia even in specialist\ncentres.3 Misdiagnosis, more common in the\nelderly, may also occur in the presenium.4\nThe extent of misdiagnosis may be inferred\nfrom\na study which reported\nthat 8%\nof\npatients with an index diagnosis of dementia\nwere rediagnosed as depression on subsequent\nadmission.6 Depressed patients with cognitive\nimpairment demonstrate a significant improve-\nment on quantitative assessments of cognition\nfollowing treatment or on follow-up.78\nThe\nneurobiological\nbasis\nof depression\nrelated cognitive impairment remains obscure.\nDistinct patterns of focal cerebral metabolic\nabnormalities have been described in primary\ndepression.9\"0 The most consistent change\ndescribed is a decrease in rCBF or metabolism\nin\nthe\nleft\ndorsolateral\nprefrontal\ncortex\n(DLPFC). We report a study of depressed\npatients,\nusing PET\nderived\nmeasures\nof\nrCBF, which reveals a profile of abnormality,\ndistinct from that seen in depression alone, in\ndepression related cognitive impairment.\nSubjects and methods\nPatients included in the study were recruited\nfrom\ndistrict\npsychiatric\nservices\nin\nnorth\nLondon and the National Hospital for Neurol-\nogy and Neurosurgery. Potential participants\nindicating willingness to cooperate with the\nstudy and ability to give informed consent were\nadministered The Schedule for Affective Dis-\norders and Schizophrenia (SADS)."}


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id: 309
encoding: FLOAT32
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{"title": "Regional cerebral blood flow abnormalities in depressed patients with", "chroma:document": "\" Patients\nwho\nmet\nResearch\nDiagnostic\nCriteria\n(RDC)12 for major depressive disorder were\nconsidered further. Exclusion criteria were a\npast or present history of neurological disease,\ndrug or alcohol abuse (based on the SADS) or\nany significant past medical illness. Subjects\nwere also excluded if they scored over 4 on the\nHachinski ischaemic scale.13 Patients on psy-\nchotropic medication (19 of the 33) entered\nthe study on the hypothesis that patterns of\nrCBF would reflect their depressed mental\nstate rather than medication. The study was\napproved by the\nethical committees of all\nreferring hospitals and by the local committee\nofthe Hammersmith Hospital, where the scans\nwere performed.\nPermission\nto\nadminister\n\"5Oxygen was granted by the Administration of\nRadioactive Substances Advisory Committee\n(ARSAC). All subjects gave informed written\nconsent.\nA total of 33 patients met entry criteria for\nthe study. All patients had moderate to severe\ndepression as rated on the 17 item Hamilton\nRating Scale for Depression14 (range 17-32,\nmean = 25). Cognitive finction, assessed using\na clinical neuropsychological battey as well as\nthe Mini Mental State Examination (MMSE)\nand CAMCOG\nscale\nof the CAMDEX,\nshowed that 10 patients had marked cognitive\nimpairment and scored in the impaired range.\nCognitive impairment was determined using\ncut-points of < 25 on the MMSE and < 85 on\nthe CAMCOG.\"5 16 Subsequent follow up of\nthese patients revealed a clinical course con-\n768"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 310
encoding: FLOAT32
metadata:
{"title": "Transient neurogenesis in ischemic cortex from Sox2 astrocytes", "chroma:document": "NEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\uff5c1521\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nResearch Article\nTransient neurogenesis in ischemic cortex from Sox2+ \nastrocytes\nAbstract  \nThe adult cortex has long been regarded as non-neurogenic. Whether injury can induce neurogenesis in the adult cortex is still controversial. Here, we report \nthat focal ischemia stimulates a transient wave of local neurogenesis. Using 5\u2032-bromo-2\u2032-deoxyuridine labeling, we demonstrated a rapid generation of \ndoublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia. Nestin-CreER-based cell ablation and fate mapping showed a \nsmall contribution of neuroblasts by subventricular zone neural stem cells. Using a mini-photothrombotic ischemia mouse model and retrovirus expressing \ngreen fluorescent protein labeling, we observed maturation of locally generated new neurons. Furthermore, fate tracing analyses using PDGFR\u03b1-, GFAP-, \nand Sox2-CreER mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major \nneurogenic cells in adult cortex. In addition, a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca \nmulatta. Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex, which suggests the possibility of inducing \nneuronal regeneration by amplifying this intrinsic response in the future.  \nKey Words: adult; astrocyte; cortex; fate-mapping; ischemia; local neurogenesis; neural stem cells; Sox2\nhttps://doi.org/10.4103/1673-5374.357910\nDate of submission: April 20, 2022 \nDate of decision: June 23, 2022 \nDate of acceptance: August 23, 2022 \nDate of web publication: October 13, 2022 \nIntroduction \nOnce development ends, the neurogenic potential of the neocortex becomes \nlatent. Because of the importance of the neocortex in brain function and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 311
encoding: FLOAT32
metadata:
{"title": "Transient neurogenesis in ischemic cortex from Sox2 astrocytes", "chroma:document": "its vulnerability to injuries (such as ischemia), extensive investigations have \nbeen conducted to seek and promote neurogenesis in adult cortex after \ninjury (Kernie and Parent, 2010; Ceanga et al., 2021). In the past decade, \nseveral studies have documented cortical neurogenesis under physiological \nand pathophysiological conditions, particularly following cerebral ischemia, \nwhereas others have detected no neurogenesis in adult cortex (Jiang et \nal., 2001; Pekcec et al., 2006; Kernie and Parent, 2010; Ohira et al., 2010; \nVessal and Darian-Smith, 2010; Ohira, 2011; Huttner et al., 2014). Cortical \nneurogenesis, if indeed occurs, is minimal. Adult neural stem cells (aNSCs) in \nthe subventricular zone (SVZ) respond to cerebral ischemia, so it is generally \nthought that the observed cortical neurogenesis is mainly derived from SVZ \naNSCs (Li et al., 2010). \nSome studies have indicated that there may exist potential neurogenic \ncells in the cortex, such as GABAnergic progenitors (Ohira et al., 2010), \noligodendrocyte progenitors (Guo et al., 2010) and reactive astrocytes (Buffo \net al., 2008). In particular, reactive astrocytes have been speculated to be \nneurogenic because (1) SVZ aNSCs and hippocampal aNSCs are astrocyte-like \ncells, and (2) reactive astrocytes can upregulate neural progenitor markers, \nform neurospheres, and are multi-potent in vitro (Robel et al., 2011; Shimada \net al., 2012; Gotz et al., 2015). Recent studies have reported that in the \nstriatum, where postischemic neurogenesis is thought to be solely derived \nfrom SVZ aNSCs, local astrocytes also give rise to neurons (Luzzati et al., 2014; \nMagnusson et al., 2014). These observations indicate the possibility of cortical \nneurogenesis from local astrocytes. However, in vivo neurogenic evidence is \nstill lacking.\nRecently, Chunli Zhang\u2019s group reported that a subpopulation of cortical \nastrocytes maintains a low level of Sox2 expression (Chen et al., 2019). Our \nprevious study revealed that Sox2-positive glia in dorsal root ganglion give rise"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 312
encoding: FLOAT32
metadata:
{"title": "Transient neurogenesis in ischemic cortex from Sox2 astrocytes", "chroma:document": "to nociceptive neurons under chronic pain (Zhang et al., 2019). In the present \nstudy, using 5\u2032-bromo-2\u2032-deoxyuridine (BrdU) labeling, retrovirus expressing \ngreen fluorescent protein (GFP; Retro-GFP) labeling and Cre-mediated cell \nfate tracing, we demonstrated transient neurogenesis in adult mouse cortex \nafter ischemia and further explored the neurogenic potential of Sox2-positive \nastrocytes. \n1Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi\u2019an, Shaanxi Province, China; 2China National Clinical \nResearch Center for Neurological Diseases, Department of Neurology, Beijing Tiantan Hospital, Beijing, China; 3Department of Neurology, The Second Affiliated Hospital of Xi\u2019an \nJiaotong University, Xi\u2019an, Shaanxi Province, China; 4State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, Fudan \nUniversity, Shanghai, China; 5Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, \nChinese Academy of Sciences, Kunming, Yunnan Province, China\n*Correspondence to: Ya-Zhou Wang, PhD, yazhouw@fmmu.edu.cn; Ying-Zhou Hu, PhD, huyingzhou@mail.kiz.ac.cn; Kun Zhang, PhD, Kunyang1028@126.com.\nhttps://orcid.org/0000-0002-7116-2395 (Ya-Zhou Wang); https://orcid.org/0000-0001-7220-7607 (Ying-Zhou Hu); https://orcid.org/0000-0003-2928-8178 (Kun Zhang)\n#These authors contribute equally to the work. \nFunding: This work was supported by the National Natural Science Foundation of China, Nos. 82171346 (to YZW), 82171269 (to JLY), 82171471 (to HF); Beijing Nova Program, No. \nZ201100006820076 (to JLY).\nHow to cite this article: Yang JL, Fan H, Fu FF, Guo BL, Huang Y, Sun L, Wang WT, Xing JL, Hu XT, Ding YQ, Zhang K, Hu YZ, Wang YZ (2023) Transient neurogenesis in ischemic cortex \nfrom Sox2+ astrocytes. Neural Regen Res 18(7):1521-1526. \nGraphical Abstract\nTransient wave of local neurogenesis\nFrom the Contents\nIntroduction"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 313
encoding: FLOAT32
metadata:
{"title": "Transient neurogenesis in ischemic cortex from Sox2 astrocytes", "chroma:document": "1521\nMethods  \n1522\nResults\n1523\nDiscussion\n1526\nJia-Lei Yang1, 2, #, Hong Fan1, 3, #, Fan-Fan Fu1, #, Bao-Lin Guo1, Ying Huang4, Li Sun1, Wen-Ting Wang1, Jun-Ling Xing1, Xin-Tian Hu5, \nYu-Qiang Ding4, Kun Zhang1, *, Ying-Zhou Hu5, *, Ya-Zhou Wang1, *"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 314
encoding: FLOAT32
metadata:
{"title": "Damage to endothelial barriers and its contribution to long COVID", "chroma:document": "Vol.:(0123456789)\n1 3\nAngiogenesis \nhttps://doi.org/10.1007/s10456-023-09878-5\nREVIEW PAPER\nDamage to\u00a0endothelial barriers and\u00a0its contribution to\u00a0long COVID\nXiaoming\u00a0Wu1\u00a0\u00b7 Mengqi\u00a0Xiang1\u00a0\u00b7 Haijiao\u00a0Jing1\u00a0\u00b7 Chengyue\u00a0Wang1\u00a0\u00b7 Valerie\u00a0A.\u00a0Novakovic2\u00a0\u00b7 Jialan\u00a0Shi1,2,3 \nReceived: 1 August 2022 / Accepted: 16 April 2023 \n\u00a9 The Author(s), under exclusive licence to Springer Nature B.V. 2023\nAbstract\nThe world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset \nof convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, \nautopsy, animal and in\u00a0vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial \ndysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs \ncontain different types of endothelia, each with specific features, forming different endothelial barriers and executing different \nphysiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of \nglycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged \nendothelial cells promote diffuse microthrombi and destroy the endothelial (including blood\u2013air, blood\u2013brain, glomerular \nfiltration and intestinal\u2013blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset \nof patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an \nimportant knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, \nwe mainly focus on these endothelial barriers and their contribution to long COVID.\nKeywords Long COVID\u00a0\u00b7 Endothelial barrier\u00a0\u00b7 Vaccination\u00a0\u00b7 Antithrombotic therapy\nAbbreviations\nACE2 \n Angiotensin converting enzyme 2\nAKI \n Acute kidney injury\nAPCs \n Antigen presenting cells\nBBB \n Blood\u2013brain barrier"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 315
encoding: FLOAT32
metadata:
{"title": "Damage to endothelial barriers and its contribution to long COVID", "chroma:document": "BAL \n Bronchoalveolar lavage\nCNS \n Central nervous system\nDOAC \n Direct oral anticoagulation\nECs \n \u00a0Endothelial cells\neGFR \n Estimated glomerular filtration rate\nFCV \n Forced vital capacity\nFEV1 \n Forced expiratory volume in the first \nsecond\nGFB \n Glomerular filtration barrier\nGIS \n Gastrointestinal symptoms\nRBC \n Erythrocyte\nRBD \n Receptor-binding domain\nRCT \n Randomized clinical trial\nVE-cadherin  Vascular endothelial cadherin\nVE-PTP \n \u00a0Vascular endothelial-protein tyrosine \nphosphatase\nVEGF \n Vascular endothelial growth factor\nVEGF A \n Vascular endothelial growth factor A\nZO \n Zonula occludens\nIntroduction\nAs of March 3, 2023, more than 758\u00a0million confirmed cases \nof COVID-19 have been reported to WHO [1]. Although \nmost patients return to their baseline state of health after \ninfection, a subset of patients have ongoing health prob-\nlems, known as post-acute sequelae of COVID-19 or long \nCOVID. The WHO defines long COVID as the continuation \nor development of new symptoms 3 months after the initial \nSARS-CoV-2 infection, with these symptoms lasting for at \nleast 2 months without other explanation [2]. The persis-\ntent symptoms can occur even after an oligosymptomatic \ninfection [3]. These symptoms include fatigue, shortness of \n * Jialan Shi \n \njialan_shi@dfci.harvard.edu; shi73661@gmail.com\n1 \nDepartment of\u00a0Hematology,  The First Hospital, Harbin \nMedical University, 150001\u00a0Harbin, China\n2 \nDepartment of\u00a0Research, VA Boston Healthcare System, \nHarvard Medical School, Boston, MA, USA\n3 \nDepartment of\u00a0Medical Oncology, Dana-Farber Cancer \nInstitute, Harvard Medical School, MA, Boston, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 316
encoding: FLOAT32
metadata:
{"title": "Antiretroviral drug exposure in urethral and glans surface sampling of the penis", "chroma:document": "Antiretroviral drug exposure in urethral and glans surface \nsampling of the penis\nRichard E. Haaland1,*, Jeffrey Fountain1, Chuong Dinh1, L. Davis Lupo1, Amy Martin1, \nChristopher Conway-Washington2, LaShonda Hall2, Colleen F. Kelley2,3, J. Gerardo Garcia-\nLerma1, Walid Heneine1\n1Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA;\n2The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of \nMedicine, Emory University School of Medicine, Atlanta, GA, USA;\n3Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, \nUSA\nAbstract\nBackground:\u00a0HIV exposure to penile tissues provides a risk of acquisition among men, yet \nstudies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured \nARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, \nemtricitabine, elvitegravir, darunavir and cobicistat.\nMethods:\u00a0Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal \nswabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/\nelvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography\u2013mass \nspectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for \nplasma and urine. Concentrations are reported as median and range.\nResults:\u00a0Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for \nemtricitabine (36 ng/swab; 3\u2013307 ng/swab) and 8 h for darunavir (25 ng/swab; 2\u201352 ng/swab). \nGlans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine \n14 ng/swab, <LOD\u2013328 ng/swab; darunavir 6 ng/swab, <LOD\u2013149 ng/swab). Estimated peak \nurethral secretion emtricitabine and darunavir concentrations are between 10 and 20 lg/mL, similar \nto rectal secretions, 4-fold greater than in plasma, but 2-fold lower than in urine. Tenofovir and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 317
encoding: FLOAT32
metadata:
{"title": "Antiretroviral drug exposure in urethral and glans surface sampling of the penis", "chroma:document": "elvitegravir were detected on less than 20% of urethral or glans swabs collected within 24 h of \ndosing.\nThis work is written by (a) US Government employee(s) and is in the public domain in the US.\n*Corresponding author. hyw9@cdc.gov. \nTransparency declarations\nJ.G.G.-L. and W.H. are named in a US Government patent application related to methods for HIV prophylaxis. All other authors: none \nto declare.\nDisclaimer\nThe findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the \nUnited States Centers for Disease Control and Prevention or the Department of Health and Human Services.\nHHS Public Access\nAuthor manuscript\nJ Antimicrob Chemother. Author manuscript; available in PMC 2023 April 27.\nPublished in final edited form as:\nJ Antimicrob Chemother. 2021 August 12; 76(9): 2368\u20132374. doi:10.1093/jac/dkab155.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 318
encoding: FLOAT32
metadata:
{"title": "Post-ictal Kliuver-Bucy syndrome temporal lobectomy", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatry 1993;56:31 1-313\nSHORT REPORT\nPost-ictal Kliuver-Bucy syndrome after temporal\nlobectomy\nJohn A Anson, Donald T Kuhlman\nAbstract\nIn both animals and humans, Kluver-\nBucy syndrome is produced by bilateral\ntemporal lobectomy. It is characterised\nby hypersexuality, visual agnosia, strong\noral\ntendencies,\ndietary\nchanges,\nand\nhypermetamorphosis. Recurrent, postic-\ntal\nKluver-Bucy\nsyndrome\noccurred\ntransiently after seizures in a female who\nhad\nundergone\nunilateral\ntemporal\nlobectomy.\nThe\npathophysiological\nmechanism may have been postictal dys-\nfunction of the remaining temporal lobe,\nproducing a transient functional bilateral\ntemporal lobectomy.\n(7 Neurol Neurosurg Psychiatry 1993;56:31 1-313)\nDivision of\nNeurological Surgery,\nUniversity of\nNew Mexico Hospital,\nAlbuquerque, New\nMexico, USA\nJ A Anson\nDepartment of\nNeurology, Mt Sinal\nHospital, Chicago,\nIllinois, USA\nJ D T Kuhlman\nCorrespondence to:\nDr Anson, c/o Division of\nNeurosurgery, University of\nNew Mexico Hospital, 2211\nLomas NE, Albuquerque,\nNew Mexico 87131, USA\nReceived 8 April 1992\nand in revised form\n16 June 1992.\nAccepted 7 July 1992\nIn 1939, Kliiver and Bucy described a behav-\nioural syndrome in rhesus monkeys that fol-\nlowed\nbilateral\ntemporal\nlobectomy.'\nThe\nsyndrome\nwas\ncharacterised by prominent\nand indiscriminate hypersexuality, excessive\noral tendencies, loss of normal fear and anger,\nhypermetamorphosis (excessive attentiveness\nto visual stimuli), psychic blindness (inability\nto recognise objects without loss of gross visu-\nal discrimination), and dietary changes.\nIn 1955 Terzian\nfirst reported the same\nsyndrome in humans after bilateral temporal\nlobectomy.\nKliiver-Bucy syndrome\nis\nalso\nassociated with a variety of neurological disor-\nders, including herpes encephalitis, Pick's dis-\nease,\nAlzheimer's\ndisease,\ncerebrovascular\naccidents, cerebral trauma, and temporal lobe\nepilepsy. The common feature of all aetiolo-\ngies\nwas\nbilateral\nmesial\ntemporal\nlobe\ndestruction or dysfunction."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 319
encoding: FLOAT32
metadata:
{"title": "Post-ictal Kliuver-Bucy syndrome temporal lobectomy", "chroma:document": "We report an unusual\ncase of recurrent\ntransient Kluver-Bucy syndrome\nthat\nonly\noccurred during the\npostictal\nperiod\nin\na\npatient who had occasional seizures after a\nunilateral temporal lobectomy.\nCase report\nIn 1984 a 24 year old female sought treat-\nment\nafter generalised\nseizures\nfollowed\na.\nweek-long fever. A CT scan showed a nonen-\nhancing radioluscent\narea between the\nleft\nmedial temporal lobe and the\nleft cerebral\npeduncle that suggested atrophy of the left\nmedial\ntemporal\nlobe\n(Fig). Two\nlumbar\npunctures\nwere normal.\nShe\ncontinued\nto\nhave frequent seizures and a week later devel-\noped\nstatus\nepilepticus\ndespite\ntherapeutic\nlevels of phenytoin, phenobarbitone, and val-\nproic acid. A 24 hour EEG demonstrated that\nbilateral frontotemporal\nictal patterns were\noccurring every 30 minutes and lasting 70 to\n90 seconds. These EEG patterns were associ-\nated with\nthe\nclinically observed\nseizures.\nEighty one per cent of the ictal events origi-\nnated from the left side.\nMRI showed increased signal intensity of\nthe left temporal lobe. Status epilepticus was\npersistent and refractory to maximal medical\ntherapy. The patient therefore had a left tem-\nporal craniotomy 2 weeks after admission.\nElectrocorticography showed many indepen-\ndent spike discharges from the inferior and\nmiddle temporal gyri. A temporal lobectomy\nremoved the anterior 4 cm of the left tempo-\nral lobe, the amygdala, and the anterior 1 to\n1g5 cm of the hippocampus.\nPostoperatively, the patient did well. She\nexperienced no further seizures while receiv-\ning phenytoin, phenobarbitone, and carba-\nmazepine in the hospital. An EEG showed\nspike and wave complexes and sharp waves\nfrom the left frontotemporal region. Because\nof the unusual need for temporal lobectomy\nto control status epilepticus, this case was\nreported\nin the neurosurgical\nliterature\nin\n1986.3 The patient was then lost to follow up\nseveral months after surgery.\nFive years later after a generalised seizure,\nthe patient sought treatment in a local emer-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 320
encoding: FLOAT32
metadata:
{"title": "Post-ictal Kliuver-Bucy syndrome temporal lobectomy", "chroma:document": "gency room. On examination, she was lethar-\ngic and unresponsive but medically stable\nwithout further seizure activity. She was left\nunattended in an examination room. About\n30 minutes later, she was found in an adja-\ncent room performing fellatio on an elderly\nmale cardiac patient. The patient was easily\nled back to her room. She was placid and\napparently did not recognise family members\nwho arrived soon after. An hour later she was\nalert and neurologically intact with no memo-\nry of the episode.\nWhen\nquestioned,\nthe\npatient's\nfamily\nrevealed that she still had occasional seizures\ndespite the temporal lobectomy. Typically,\nthe seizures occurred after she had run out of\nanticonvulsant medication. After the seizures,\nthe family reported that she exhibited abnor-\nmal sexual behaviour, which included mastur-\nbating in public and\nsoliciting intercourse\nwith family members and neighbours. During\nthese episodes, she did not recognise family\nmembers and was subdued and apathetic.\nShe also exhibited bulimia, eating voraciously\nwhatever food was available. These behav-\nioural changes lasted 1 to 2 hours; afterwards,\nshe was amnestic for the entire event. During\n31"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 321
encoding: FLOAT32
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{"title": "Smooth pursuit eye movement deficits after pontine nuclei lesions in humans", "chroma:document": "Journal ofNeurology, Neurosurgery, and Psychiatty 1993;56:799-807\nSmooth pursuit eye movement deficits after\npontine nuclei lesions in humans\nB Gaymard, C Pierrot-Deseilligny, S Rivaud, S Velut\nAbstract\nEye movements were recorded electro-\noculographically\nin four patients with\nbasal pontine lesions, demonstrated by\nMRI. The most prominent eye move-\nment abnormality observed was mild to\nsevere impairment\nof smooth pursuit\nand optokinetic nystagmus, mainly ipsi-\nlateral to the lesion. This abnormality is\nthought to result from damage to the\npontine\nnuclei, which form a\ncrucial\nrelay between the cerebral cortex and the\ncerebellum controlling smooth pursuit.\nAbnormalities\nof\nsaccades\nand\nthe\nvestibulo-ocular reflex in one patient are\nalso discussed.\n(9Neurol Neurosurg Psychiatry 1993;56:799-807)\nClinique Neurologique\nand Unit6 INSERM\n289, Hopital de la\nSalpetriere, Paris, and\nService de\nNeurochirurgie,\nH6pital Bretonneau,\nTours, France\nB Gaymard\nC Pierrot-Deseilligny\nS Rivaud\nS Velut\nCorrespondence to:\nB Gaymard, INSERM 289,\nH6pital de la Salpetriere, 47\nBd de l'H6pital, 75651\nParis, Cedex 13, France\nReceived 30 March 1992\nand in revised from\n11 August 1992.\nAccepted 25 September 1992\nThe pontine nuclei (PN) consist of several\ngroups of neurons in the basis pontis relaying\nsignals from the cerebral cortex towards the\ncerebellum. Some of them, namely the dorso-\nlateral, the lateral, and the dorsomedian PN,\ncould be specifically involved in smooth pur-\nsuit eye movements, and represent a crucial\nlink in the corticopontine pathways mediating\nthis eye movement.'23 However, the location\nand function of the PN involved in smooth\npursuit still have to be precisely determined\nin humans. The first human case with a selec-\ntive PN lesion and including eye movement\nrecordings was recently reported.4 It provided\ndata consistent with the results of experimen-\ntal lesion studies involving the dorsolateral\npontine nuclei (DLPN) in the monkey. We\nreport\nfour patients with\ndiverse vascular"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 322
encoding: FLOAT32
metadata:
{"title": "Smooth pursuit eye movement deficits after pontine nuclei lesions in humans", "chroma:document": "lesions affecting the basis pontis, resulting in\nvarious impairments of smooth pursuit and\noptokinetic nystagnus (OKN). The relation\nbetween smooth pursuit impairment and the\nlocation of the lesions is discussed.\nCase reports\nPATENT 1\nA 73 year old woman had been complaining\nfor a year and a half of a right trigeminal neu-\nralgia despite carbamazepine\ntherapy.\nShe\nthus agreed to a neurosurgical procedure, and\na microvascular decompression of the fifth\nnerve\nwas\nperformed.\nAfter\nsurgery,\nthe\npatient awoke with left hemiplegia.\nThere\nwas no cerebellar symptoms, no sensory loss,\nand no diplopia. MRI showed a right pontine\nlesion, compatible with a haematoma (fig 1).\nThis lesion was located along the lateral edge\nof the basis pontis, and affected about two\nthirds of the rostrocaudal extent of the pons\n(fig 2). When eye movement recordings were\nmade, one week after surgery, the left hemi-\nplegia had not improved, though the patient\nwas alert and cooperative.\nPATENT 2\nA 59 year old woman was hospitalised after\nthe sudden onset of right hemiplegia. On ini-\ntial examination, severe right hemiplegia was\nobserved. On the left side, strength was nor-\nmal but there was dysmetria in the finger to\nnose test. All sensory examination was nor-\nmal. MRI showed a left pontine lesion, com-\npatible with an infarct (fig 3). A transverse\nsection showed that the lesion affected almost\nall the left basis pontis, and slightly crossed\nthe midline (fig 3A). The pontine tegmentum\nwas spared, excepc-for a limited part of the\nmedian structures, on which a very narrow\nposterior extent of the lesion impinged (fig 2).\nSagittal\nsections\nclearly\nshowed\nthat\nthe\nlesion had a short rostrocaudal extent, and\nconsisted of a thin horizontal slice (about\n5 mm) at the mid-pons level (fig 3B). MRI\ndid not show any lesions in the superior or\ninferior cerebellar peduncles or in the cerebel-\nlum. Eye movement recordings were per-\nformed five months after the stroke. At that\ntime, the motor deficit and the cerebellar\nsyndrome persisted. The patient was\nalert"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 323
encoding: FLOAT32
metadata:
{"title": "Smooth pursuit eye movement deficits after pontine nuclei lesions in humans", "chroma:document": "alert\nand cooperative.\nPATENT 3\nA 34 year old woman with no medical back-\nground was\nhospitalised\nafter the sudden\nonset of pure left hemiparesis. MRI showed a\nlesion restricted to the basis pontis, compati-\nble with an infarct. It was located just below\nthe mid-pons level, along the midline, with a\nlimited extent on the right side (fig 2). On\nsagittal sections,\nit occupied approximately\n30% of the whole rostrocaudal extent of the\npons. Eye movement recordings were per-\nformed one month after the stroke. At that\ntime, there was no improvement in the motor\ndeficit, though\nthe\npatient was\nalert and\ncooperative.\nPATINT 4\nA 66 year old woman with a long history of\nhypertension suddenly experienced isolated\nleft hemiplegia. MRI showed a lesion com-\npatible with an infarct, located on the right\nside of the brainstem, at the mid-pons level.\nThe lesion was restricted to the basis pontis,\n799"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 324
encoding: FLOAT32
metadata:
{"title": "Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation", "chroma:document": "Impact of GVHD prophylaxis on CMV reactivation and disease after\nHLA-matched peripheral blood stem cell transplantation\nMasumi Ueda Oshima,1,2 Hu Xie,1 Danniel Zamora,1,3 Mary E. Flowers,1,2 Geoffrey R. Hill,1,2 Marco B. Mielcarek,1,2\nBrenda M. Sandmaier,1,2 Ted A. Gooley,1 and Michael J. Boeckh1,3\n1Fred Hutchinson Cancer Center, Seattle, WA; 2Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA; and 3Division of Allergy and\nInfectious Diseases, University of Washington, Seattle, WA\nKey Points\n\u2022 Despite higher risk of\nearly CMV reactivation\nusing PTCy, 1-year viral\nburden and CMV\ndisease are\ncomparable with MTX-\nbased prophylaxis.\n\u2022 MMF is associated\nwith higher risk of early\nand late CMV\nreactivation and higher\n1-year viral burden than\nMTX-based\nprophylaxis.\nThe kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell\ntransplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are\npoorly de\ufb01ned. We retrospectively compared CMV reactivation and disease among 780\nseropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and\ncalcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44),\nmycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation\noccurred between 2007 and 2018; CMV monitoring/management followed uniform standard\npractice. Hazards of CMV reactivation at various thresholds were compared. Spline curves\nwere \ufb01t over average daily viral load and areas under the curve (AUC) within 1 year were\ncalculated. PTCy and MMF were associated with an increased risk of early (day \u2264100) CMV\nreactivation \u2265250 IU/mL after multivariate adjustment. The viral load AUC at 1 year was\nhighest with MMF (mean difference = 0.125 units vs MTX group) and similar between PTCy\nand MTX (mean difference = 0.016 units vs MTX group). CMV disease risk was similar across\ngroups. There was no interaction between GVHD prophylaxis and CMV reactivation on"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 325
encoding: FLOAT32
metadata:
{"title": "Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation", "chroma:document": "chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the\nCMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast,\nMMF was associated with higher overall CMV viral burden in the 1 year posttransplant.\nAlthough different mechanisms of immunosuppressive agents may affect CMV reactivation\nrisk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate\ninfection risk over time.\nIntroduction\nCytomegalovirus (CMV) reactivation at any level after allogeneic stem cell transplantation is strongly\nassociated with inferior overall and nonrelapse mortality. The differential impact of various pharmaco-\nlogic graft-versus-host disease (GVHD) prophylaxis regimens on CMV infection is poorly de\ufb01ned. In\nrecent years, the use of posttransplantation cyclophosphamide (PTCy) has been shown to signi\ufb01cantly\nreduce both severe acute and chronic GVHD risk after HLA-haploidentical (haplo)1 and HLA-matched\nrelated and unrelated donor stem cell transplantation.2 Single-center retrospective studies have\nreported a higher incidence of CMV infection after haplo transplantation using PTCy than historically\nSubmitted 23 December 2022; accepted 28 December 2022; prepublished\nonline on Blood Advances First Edition 3 January 2023. https://doi.org/10.1182/\nbloodadvances.2022009112.\nData are available on request from the corresponding author, Masumi Ueda Oshima\n(mueda@fredhutch.org).\nThe full-text version of this article contains a data supplement.\n\u00a9 2023 by The American Society of Hematology. Licensed under Creative Commons\nAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0),\npermitting only noncommercial, nonderivative use with attribution. All other rights\nreserved.\nTRANSPLANTATION\n1394\n25 APRIL 2023 \u2022 VOLUME 7, NUMBER 8"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 326
encoding: FLOAT32
metadata:
{"title": "Effect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity", "chroma:document": "Effect of antiplatelet agents and tyrosine kinase inhibitors on\noxLDL-mediated procoagulant platelet activity\nTony J. Zheng,1 Tia C. L. Kohs,1 Paul A. Mueller,2 Jiaqing Pang,1 St\u00b4ephanie E. Reitsma,1 Iv\u00b4an Parra-Izquierdo,1,2 Alexander R. Melrose,2\nLiping Yang,3 Jaewoo Choi,4 Keith D. Zientek,5 Denis O. Sviridov,6 Mark K. Larson,7 Craig D. Williams,8 Nathalie Pamir,2\nJoseph J. Shatzel,1,9 Ashok P. Reddy,5 Paul Kievit,4 Alan T. Remaley,6 Jan F. Stevens,8,10 Monica T. Hinds,1 Owen J. T. McCarty,1,9,11 and\nJoseph E. Aslan1,2,12\n1Department of Biomedical Engineering and 2Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR; 3Department of Chemistry, Oregon State\nUniversity, Corvallis, OR; 4Oregon National Primate Research Center and 5Proteomics Shared Resource, Oregon Health & Science University, Portland, OR; 6Lipoprotein\nMetabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; 7Department of\nBiology, Augustana University, Sioux Falls, SD; 8College of Pharmacy, Oregon State University, Corvallis, OR; 9Division of Hematology & Medical Oncology, Oregon Health &\nScience University, Portland, OR; 10Linus Pauling Institute, Oregon State University, Corvallis, OR; and 11Department of Cell, Developmental & Cancer Biology and\n12Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR\nKey Points\n\u2022 OxLDL enhances\nGPVI-driven platelet\nprocoagulant activity\nex vivo.\n\u2022 P2YR antagonists and\ntyrosine kinase\ninhibitors may reduce\noxLDL-enhanced\nplatelet procoagulant\nactivity more so than\naspirin.\nLow-density lipoprotein (LDL) contributes to atherogenesis and cardiovascular disease through\ninteractions with peripheral blood cells, especially platelets. However, mechanisms by which\nLDL affects platelet activation and atherothrombosis, and how to best therapeutically target\nand safely prevent such responses remain unclear. Here, we investigate how oxidized low-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 327
encoding: FLOAT32
metadata:
{"title": "Effect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity", "chroma:document": "density lipoprotein (oxLDL) enhances glycoprotein VI (GPVI)-mediated platelet hemostatic and\nprocoagulant responses, and how traditional and emerging antiplatelet therapies affect oxLDL-\nenhanced platelet procoagulant activity ex vivo. Human platelets were treated with oxLDL and\nthe GPVI-speci\ufb01c agonist, crosslinked collagen-related peptide, and assayed for hemostatic and\nprocoagulant responses in the presence of inhibitors of purinergic receptors (P2YR),\ncyclooxygenase (COX), and tyrosine kinases. Ex vivo, oxLDL enhanced GPVI-mediated platelet\ndense granule secretion, \u03b1-granule secretion, integrin activation, thromboxane generation and\naggregation, as well as procoagulant phosphatidylserine exposure and \ufb01brin generation.\nStudies of washed human platelets, as well as platelets from mouse and nonhuman primate\nmodels of hyperlipidemia, further determined that P2YR antagonists (eg, ticagrelor) and Bruton\ntyrosine kinase inhibitors (eg, ibrutinib) reduced oxLDL-mediated platelet responses and\nprocoagulant activity, whereas COX inhibitors (eg, aspirin) had no signi\ufb01cant effect. Together,\nour results demonstrate that oxLDL enhances GPVI-mediated platelet procoagulant activity in a\nmanner that may be more effectively reduced by P2YR antagonists and tyrosine kinase\ninhibitors compared with COX inhibitors.\nIntroduction\nDyslipidemia and lipoprotein accumulation drive atherogenesis and cardiovascular disease, a leading\npreventable cause of mortality worldwide.1-3 Lipoprotein levels are established risk factors for\nSubmitted 28 January 2022; accepted 11 September 2022; prepublished online on\nBlood\nAdvances\nFirst\nEdition\n11\nOctober\n2022.\nhttps://doi.org/10.1182/\nbloodadvances.2022007169.\nFull material/reagents list and reproducible methods are provided in supplemental\nMethods.\nData are available on request from the corresponding author, Joseph E. Aslan (aslanj@\nohsu.edu).\nThe full-text version of this article contains a data supplement.\nLicensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 328
encoding: FLOAT32
metadata:
{"title": "Effect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity", "chroma:document": "International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use\nwith attribution.\nREGULAR ARTICLE\n1366\n25 APRIL 2023 \u2022 VOLUME 7, NUMBER 8"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 329
encoding: FLOAT32
metadata:
{"title": "Lacunar thalamic stroke with cerebellar and proprioceptive deficits", "chroma:document": "54ournal of Neurology, Neurosurgery, and Psychiatry 1992;55:854-856\nSHORT REPORT\nLacunar thalamic stroke with pure cerebellar and\nproprioceptive deficits\nJose A Gutrecht, Amir A Zamani, Deepak N Pandya\nAbstract\nCase reports of two patients with cere-\nbellar ataxia and proprioceptive sensory\nloss\nare presented. MRI of the brain\nrevealed lesions of the ventroposterior\npart of the thalamus. These patients illus-\ntrate clinically the anatomical independ-\nence ofcerebelkar and sensory pathways in\nthe thalamus. We suggest that the ataxic\ndeficit is caused by interruption of cere-\nbellar outflow pathways in the thalamus\nand not secondary to sensory deaffer-\nentation.\n(3 Neurol Neurosurg Psychiatry 1992;55:854-856)\nDepartment of\nNeurology, Lahey\nClinic Medical Center,\nBurlington,\nMassachusetts\nJ A Gutrecht\nDepartment of\nRadiology, Brigham\nand Women's Hospital,\nBoston, Massachusetts\nA A Zamani\nDepartment of\nAnatomy and\nNeurology, Boston\nUniversity Medical\nSchool, Boston,\nMassachusetts, and\nthe Bedford Veterans\nAdministration\nHospital, Bedford,\nMassachusetts, USA\nD N Pandya\nCorrespondence to:\nDr Gutrecht, Department of\nNeurology, Lahey Clinic\nMedical Center, 41 Mall\nRoad, Burlington, MA\n01805.\nReceived 12 September\n1991\nand in revised form\n6 December 1991.\nAccepted 18 December\n1991\nIschaemic lacunar strokes occur frequently in\nthe thalamus.' 2 Small haemorrhages in the\nthalamus may also produce lacunar strokes3 4\nwith similar clinical deficits.5 The lateral syn-\ndrome is the most common and has one of the\nbest known cluster of findings of the thalamic\nsyndromes.6This syndrome and its anatomical\nlocation of the responsible lesion were first\ndescribed by Dejerine and Roussy7 in 1906.\nReported cases of \"pure\" thalamic\nsyn-\ndromes with deficits in only one or two tracts\nor systems deficits are rare.8-\" We report two\ncases of lacunar thalamic stroke that produced\na contralateral combination of a cerebellar\ndeficit and proprioceptive sensory loss.\nCase reports\nA 63 year old right handed man was seen at the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 330
encoding: FLOAT32
metadata:
{"title": "Lacunar thalamic stroke with cerebellar and proprioceptive deficits", "chroma:document": "Lahey Clinic Medical Center because of the\nsudden onset of dysaesthesia of the right side\nof the face and distal right limbs and an\ninability to walk that lasted for one hour. Three\ndays earlier, he had had an episode of nausea,\ndecreased concentration, and an inability to\nread that lasted for a few hours. The patient has\ndiabetes mellitus and hypertension, and he was\ntaking tolbutamide and metoprolol. Neuro-\nlogical examination demonstrated dysdiado-\nchokinesis and dysmetria with terminal tremor\nin the right limbs that did not worsen with\nclosed eyes. A mild subjective decreased pain\nsensation was observed in the right side of the\nface and right hand, but touch, position, and\ntemperature sensation were normal. Two-point\ndiscrimination and stereognosis were greatly\ndecreased in the right hand. No weakness was\nnoted. Stretch reflexes were hypoactive but\nsymmetrical.\nPlantar reflexes were normal.\nMRI of the brain showed a small lesion in the\nlateral posterior aspect of the left thalamus (fig\n1). No source of an embolus was found.\nCerebral angiography was not performed. The\ndeficits abated in several days.\nA 74 year old right handed man complained\nof sudden onset of inability to control the right\narm and leg despite normal strength, unsteadi-\nness, and a \"frozen feeling\" in the right side of\nthe face and right hand. History included\nhypertension\ntreated with methyldopa and\ntriamterene/hydrochlorothiazide. Mild dysar-\nthria, inconsistently decreased pain sensation,\ndysdiadochokinesis,\nand\ndecomposition\nof\nmovements in the right limbs were noted. CT\nof the head showed a small left lateral thalamic\nhaemorrhage. The findings improved in a few\nweeks. Neurological examination at the Lahey\nClinic seven months\nlater revealed\nslightly\ndecreased touch and pain sensations but nor-\nmal temperature sensation and position sense\nwith moderately diminished two-point\ndis-\ncrimination and graphaesthesia in the right\nhand. Mild dysmetria, terminal tremor, and\ndecreased finger and foot tapping ability were"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 331
encoding: FLOAT32
metadata:
{"title": "Lacunar thalamic stroke with cerebellar and proprioceptive deficits", "chroma:document": "present on the right side. No weakness was\npresent,\nand\nthe\nstretch\nreflexes\nwere\nnormoactive and symmetrical. Plantar reflexes\nwere normal. MRI of the brain performed\n.5\n.\n*A4~~~~~~~~~~~..\n...\n....S.\n...S..;...:\nFigure 1\n(Case 1). Coronal T,-weighted (Magneton 1 *0\nT, TR 065 s, TE 17 ms, 3 mm slice) image through\nposterior thalamic regions demonstrates a well-defined\nirregular area of low intensity in the lateral portion of the\nleft thalamus.\n854"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 332
encoding: FLOAT32
metadata:
{"title": "The Orienting Reflex Reveals Behavioral States Set by Demanding Contexts: Role of the Superior Colliculus", "chroma:document": "Behavioral/Cognitive\nThe Orienting Reflex Reveals Behavioral States Set by\nDemanding Contexts: Role of the Superior Colliculus\nJi Zhou, Sebastian Hormigo,\nNatan Busel, and\nManuel A. Castro-Alamancos\nDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut 06001\nSensory stimuli can trigger an orienting reflex (response) by which animals move the head to position their sensors (e.g., eyes,\npinna, whiskers). Orienting responses may be important to evaluate stimuli that call for action (e.g., approach, escape, ignore),\nbut little is known about the dynamics of orienting responses in the context of goal-directed actions. Using mice of either sex, we\nfound that, during a signaled avoidance action, the orienting response evoked by the conditioned stimulus (CS) consisted of a\nfast head movement containing rotational and translational components that varied substantially as a function of the behavioral\nand underlying brain states of the animal set by different task contingencies. Larger CS-evoked orienting responses were associ-\nated with high-intensity auditory stimuli, failures to produce the appropriate signaled action, and behavioral states resulting from\nuncertain or demanding situations and the animal\u2019s ability to cope with them. As a prototypical orienting neural circuit, we con-\nfirmed that the superior colliculus controls and codes the direction of spontaneous exploratory orienting movements. In addition,\nsuperior colliculus activity correlated with CS-evoked orienting responses, and either its optogenetic inhibition or excitation\npotentiated CS-evoked orienting responses, which are likely generated downstream in the medulla. CS-evoked orienting responses\nmay be a useful probe to assess behavioral and related brain states, and state-dependent modulation of orienting responses may\ninvolve the superior colliculus.\nKey words: avoidance; behavioral states; escape; midbrain; orienting\nSignificance Statement"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 333
encoding: FLOAT32
metadata:
{"title": "The Orienting Reflex Reveals Behavioral States Set by Demanding Contexts: Role of the Superior Colliculus", "chroma:document": "Humans and other animals produce an orienting reflex (also known as orienting response) by which they rapidly orient their\nhead and sensors to evaluate novel or salient stimuli. Spontaneous orienting movements also occur during exploration of the\nenvironment in the absence of explicit, salient stimuli. We monitored stimulus-evoked orienting responses in mice perform-\ning signaled avoidance behaviors and found that these responses reflect the behavioral state of the animal set by contextual\ndemands and the animal\u2019s ability to cope with them. Various experiments involving the superior colliculus revealed a well-\nestablished role in spontaneous orienting but only an influencing effect over orienting responses. Stimulus-evoked orienting\nresponses may be a useful probe of behavioral and related brain states.\nIntroduction\nIn alert animals, an unexpected, novel, or salient sensory stimu-\nlus leads to a well-known orienting response by which animals\nmove their head and sensors in an apparent effort to evaluate the\nstimulus (Sokolov, 1963). Spontaneous orienting also occurs dur-\ning active exploration of the environment in the absence of sa-\nlient overt stimuli, but it is not clear whether stimulus-evoked\nand spontaneous orienting share the same neural substrate. Since\nPavlov identified orienting responses, they have been intensely\ninvestigated in humans as a functional unconditioned response\nsystem that comprises numerous motor and physiological (e.g.,\nvascular, respiratory, skin conductance, EEG) reactions (e.g.,\nRanganath and Rainer, 2003; Friedman et al., 2009). However,\nless is known about stimulus-evoked orienting responses in\nmice, an animal model amenable to studying the underlying\nneural circuits.\nA decision to act usually follows stimulus-evoked orienting\nresponses. For instance, during a learned sensory guided loco-\nmotor behavior in rodents, known as signaled active avoidance,\nthe conditioned stimulus (CS) onset typically evokes a head ori-\nenting response that is dissociable from the ensuing avoidance"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 334
encoding: FLOAT32
metadata:
{"title": "The Orienting Reflex Reveals Behavioral States Set by Demanding Contexts: Role of the Superior Colliculus", "chroma:document": "action (e.g., Hormigo et al., 2021b; Zhou et al., 2022). However,\nlittle is known about CS-evoked orienting responses in the con-\ntext of signaled avoidance behaviors. One possibility is that ori-\nenting responses adapt to changes in the meaning of the evoking\nCS, reflecting the significance of the stimulus. Alternatively, ori-\nenting responses may vary in relation to the demands of the\nReceived Aug. 29, 2022; revised Jan. 26, 2023; accepted Feb. 1, 2023.\nAuthor contributions: J.Z., S.H., N.B., and M.A.C.-A. performed research; J.Z., S.H., and M.A.C.-A. analyzed\ndata; J.Z., S.H., N.B., and M.A.C.-A. edited the paper; M.A.C.-A. designed research; M.A.C.-A. wrote the first\ndraft of the paper; M.A.C.-A. wrote the paper.\nThis work was supported by National Institutes of Health grants R35 NS097272 and R01 NS104810 to M.A.C.-A.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Manuel A. Castro-Alamancos at mcastro@uchc.edu.\nhttps://doi.org/10.1523/JNEUROSCI.1643-22.2023\nCopyright \u00a9 2023 the authors\n1778 \u2022 The Journal of Neuroscience, March 8, 2023 \u2022 43(10):1778\u20131796"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 335
encoding: FLOAT32
metadata:
{"title": "Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses", "chroma:document": "Horizontal Transmission of Cytomegalovirus in a Rhesus\nModel Despite High-Level, Vaccine-Elicited Neutralizing\nAntibody and T-Cell Responses\nJulia Li,1 Sabine Wellnitz,1 Xiaoyuan S. Chi,1 Yujuan Yue,2 Kimberli A. Schmidt,3 Nancy Nguyen,3 Wei Chen,1 Irina Yurgelonis,1 Eduardo Rojas,1\nYuhang Liu,3 Jakob Loschko,1 Eneida Pollozi,1 Yury V. Matsuka,1 Elie Needle,1 Eugene Vidunas,1 Robert G. K. Donald,1 Justin Moran,1\nKathrin U. Jansen,1 Philip R. Dormitzer,1 Peter A. Barry,2,4,5 and Xinzhen Yang1\n1Vaccine Research and Development, P\ufb01zer, Inc, Pearl River, New York, USA; 2Center for Comparative Medicine, University of California Davis, Davis, California, USA; 3Groton Center for Chemistry,\nP\ufb01zer, Inc, Groton, Connecticut, USA; 4Department of Pathology and Laboratory Medicine, University of California Davis, Davis, California, USA; and 5California National Primate Research Center,\nUniversity of California Davis, Davis, California, USA\nThe development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested\nrhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a seronegative macaque oral challenge model. Immunogens\nincluded a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA\nplasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing\ntiters comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-speci\ufb01c\ncytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and\nwas detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV\nevades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity\nsuperior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.\nKeywords."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 336
encoding: FLOAT32
metadata:
{"title": "Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses", "chroma:document": "Keywords.\ncytomegalovirus; vaccine; neutralizing antibody; protective ef\ufb01cacy; rhesus macaque; RhCMV.\nHuman\ncytomegalovirus\n(HCMV)\ninfection\nof\nimmune-\ncompetent individuals generally manifests with an acute phase\nfollowed by a life-long latent phase and is often asymptomatic.\nHowever, new infection or reactivation from latent HCMV infec-\ntion in immunosuppressed patients, such as transplant recipients\nor those with AIDS, can cause serious disease and even death.\nPrimary HCMV infection of a seronegative pregnant woman re-\nsults in transmission to her fetus in approximately 30% of cases\n[1, 2]. Approximately 10% of congenitally infected infants will\nhave symptoms at birth, with approximately 30%\u201340% of those\nexhibiting severe disease, which can include hearing loss, vision\nloss, microcephaly, and developmental delay. Nonprimary infec-\ntion of a seropositive pregnant woman or reactivation of her la-\ntent HCMV also can result in transplacental transmission. The\nprobability of transmission to the fetus and severe sequelae\nmay be substantially lower after nonprimary maternal infection,\nthough studies of the outcomes of nonprimary maternal infection\nare inconsistent [1, 2]. A prophylactic HCMV vaccine is urgently\nneeded to prevent congenital HCMV disease, as well as HCMV\ndisease in immunosuppressed patients.\nAt least 3 viral glycoproteins or glycoprotein complexes me-\ndiate HCMV entry into cells: glycoprotein B (gB), which is re-\nquired for CMV entry into all target cells [3]; the gH/gL/\npUL128/pUL130/pUL131 heteropentamer complex (PC) [3],\nwhich is important for entry into epithelial and endothelial\ncells; and gH/gL/gO, which is important for entry into \ufb01bro-\nblasts [4\u20137]. The viral fusion glycoprotein, gB, transitions\nfrom a metastable prefusion conformation to a stable postfu-\nsion conformation as it fuses membranes during cell entry [8,\n9]. Postfusion gB has been isolated in a well-characterized\nform stable enough to test its immunogenicity. Postfusion gB\nelicits strong nonneutralizing antibody responses, strong"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 337
encoding: FLOAT32
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{"title": "Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses", "chroma:document": "complement-dependent neutralizing responses, and much\nweaker complement-independent neutralizing responses [10,\n11]. A subunit vaccine candidate containing an adjuvanted, re-\ncombinant, postfusion CMV gB antigen has demonstrated stat-\nistically signi\ufb01cant protection from horizontal transmission of\nCMV to seronegative new mothers [12], and a trend toward\nprotection of seronegative adolescent girls [13]. Although the\nobserved level of protection was insuf\ufb01cient to justify further\ndevelopment of a postfusion gB-based vaccine, the \ufb01ndings\nsuggest that mechanisms other than virus neutralization may\nhave some protective capacity. Prefusion HCMV gB has been\nReceived 07 December 2021; editorial decision 01 March 2022; accepted 07 April 2022;\npublished online 12 April 2022\nCorrespondence: Xiaoyuan S. Chi, PhD, P\ufb01zer Vaccine Research and Development, 401\nN. Middletown Road, Pearl River, NY 10965 (schi01@yahoo.com).\nThe Journal of Infectious Diseases\u00ae\n2022;226:585\u201394\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases\nSociety of America. All rights reserved. For permissions, please e-mail: journals.permissions\n@oup.com\nhttps://doi.org/10.1093/infdis/jiac129\nCMV Infection Despite Vaccination \u2022 JID 2022:226 (15 August) \u2022 585\nThe Journal of Infectious Diseases\nM A J O R A R T I C L E"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 338
encoding: FLOAT32
metadata:
{"title": "Episodic memory deficit in HIV infection: common phenotype with Parkinson\u0090s disease, different neural substrates", "chroma:document": "Vol.:(0123456789)\n1 3\nBrain Structure and Function (2023) 228:845\u2013858 \nhttps://doi.org/10.1007/s00429-023-02626-x\nORIGINAL ARTICLE\nEpisodic memory deficit in\u00a0HIV infection: common phenotype \nwith\u00a0Parkinson\u2019s disease, different neural substrates\nRosemary\u00a0Fama1,2 \u00a0\u00b7 Eva\u00a0M.\u00a0M\u00fcller\u2011Oehring1,2 \u00a0\u00b7 Taylor\u00a0F.\u00a0Levine3 \u00a0\u00b7 Edith\u00a0V.\u00a0Sullivan1 \u00a0\u00b7 \nStephanie\u00a0A.\u00a0Sassoon2 \u00a0\u00b7 Priya\u00a0Asok1,2\u00a0\u00b7 Helen\u00a0M.\u00a0Bront\u00eb\u2011Stewart3,4 \u00a0\u00b7 Kathleen\u00a0L.\u00a0Poston3,4 \u00a0\u00b7 Kilian\u00a0M.\u00a0Pohl1,2 \u00a0\u00b7 \nAdolf\u00a0Pfefferbaum1,2 \u00a0\u00b7 Tilman\u00a0Schulte2,5 \nReceived: 3 November 2022 / Accepted: 3 March 2023 / Published online: 18 April 2023 \n\u00a9 The Author(s) 2023\nAbstract\nEpisodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson\u2019s disease (PD). Given \nknown effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunc-\ntion. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may \nalso contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, \nassessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed \nwith a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were \nexamined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hip-\npocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall \ntrials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account \nfor the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in \nHIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 339
encoding: FLOAT32
metadata:
{"title": "Episodic memory deficit in HIV infection: common phenotype with Parkinson\u0090s disease, different neural substrates", "chroma:document": "and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learn-\ning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller \nthalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates \nin HIV and PD suggest different pathogenic mechanisms.\nKeywords HIV infection\u00a0\u00b7 Episodic memory processes\u00a0\u00b7 Regional brain volume\u00a0\u00b7 Parkinson\u2019s disease\nIntroduction\nEven in the current era of antiretroviral therapies (ART), \nmild to moderate cognitive deficits can be observed in peo-\nple living with HIV infection (PLWH) (Heaton et\u00a0al. 2010). \nAs PLWH live longer, the most susceptible cognitive defi-\ncits to the progression of impairment in aging include epi-\nsodic memory and motor functions, which may be associ-\nated with hippocampal (Maki et\u00a0al. 2009) and basal ganglia \n(Goodkin et\u00a0al. Sep 2017) dysfunction. The behavioral- and \nbrain-related impairments observed in HIV infection are \nmore often consistent with age-related diseases that affect \nsubcortical regions such as Parkinson\u2019s disease (PD) than \nage-related diseases that affect cortical regions, such as Alz-\nheimer\u2019s disease (Scott et\u00a0al. Aug 2011), although the his-\ntorical and heuristic dissociation between \u201csubcortical\u201d and \n\u201ccortical\u201d dementia has continued to diminish. For example, \nRosemary Fama and Eva M. M\u00fcller-Oehring are the Joint first \nauthorship.\n * Eva M. M\u00fcller-Oehring \n \nevamoe@stanford.edu\n1 \nDepartment of\u00a0Psychiatry and\u00a0Behavioral Sciences, Stanford \nUniversity School of\u00a0Medicine, 401 Quarry Rd, Stanford, \nCA\u00a094305, USA\n2 \nNeuroscience Program, Center for\u00a0Health Sciences, \nBioscience Division, SRI International, 333 Ravenswood \nAve, Menlo\u00a0Park, CA\u00a094025, USA\n3 \nDepartment of\u00a0Neurology and\u00a0Neurological Sciences, \nStanford University School of\u00a0Medicine, Stanford, \nCA\u00a094305, USA\n4 \nDepartment of\u00a0Neurosurgery, Stanford University School \nof\u00a0Medicine, Stanford, CA\u00a094305, USA\n5"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 340
encoding: FLOAT32
metadata:
{"title": "Episodic memory deficit in HIV infection: common phenotype with Parkinson\u0090s disease, different neural substrates", "chroma:document": "5 \nClinical Psychology, Palo Alto University, 1791 Arastradero \nRd, Palo\u00a0Alto, CA\u00a094304, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 341
encoding: FLOAT32
metadata:
{"title": "An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques", "chroma:document": "LETTER\nOPEN\nAn RBD virus-like particle vaccine for SARS-CoV-2 induces\ncross-variant antibody responses in mice and macaques\nSignal Transduction and Targeted Therapy  (2023) 8:173 \n; https://doi.org/10.1038/s41392-023-01425-4\nDear Editor,\nSince early 2020, severe acute respiratory syndrome coronavirus\n2 (SARS-CoV-2) has spread globally infecting over 500 million\npeople and causing over 6 million deaths. The massive worldwide\nimmunisation programmes and the arising clinical trial data\npresent a unique opportunity to compare the vaccines and\nvarious delivery platforms (i.e. viral vector platform, mRNA\nplatform and virus-like particle platform). As reviewed from the\npublished clinical data,1 it is evident that the mRNA vaccines\n(mRNA-1273 from Moderna, BNT162b2 from P\ufb01zer) and subunit\nprotein/adjuvant vaccine (NVAX-CoV2373 from Novavax) were\nable to induce an average 2\u20134 fold greater neutralizing antibody\n(nAb) titer as compared to the human convalescent serum (HCS)\ncontrol.\nOn\nthe\nother\nhand,\nthe\nviral\nvectored\nvaccines\n(Ad26.COV2.S from Johnson & Johnson, ChAdOx1 nCoV-19 from\nAstraZeneca) and the inactivated vaccine (CoronaVac from\nSinovac) induced less nAb than the HCS. Interestingly, CoVLP\nfrom Medicago, which uses a plant-based virus-like particle (VLP)\nplatform technology, was able to induce a >10-fold increase in the\nnAb response as compared to HCS;2 suggesting VLP vaccine or\narrayed antigen delivery is highly immunogenic.\nWe designed a vaccine, named RBDM, targeting the receptor-\nbinding domain (RBD) of the SARS-CoV-2 Spike glycoprotein (S-\nprotein), whereby the wild-type (WT; Wuhan strain) RBD is\ndelivered in an array on a VLP (an RBD-VLP vaccine) produced\nusing a split protein Tag/Catcher technology as described\npreviously.3 The RBD protein and VLP carrier, depicted in Fig. 1a,\nwere expressed at high titres in CHO cells (>4 g/L) and E. coli BL21\n(DE3) cells (>3 g/L) respectively. Using a good manufacturing\npractice (GMP) compatible puri\ufb01cation process, RBDM achieved a"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 342
encoding: FLOAT32
metadata:
{"title": "An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques", "chroma:document": "purity of >95% and endotoxin level of <5EU/mL (Fig. 1b).\nFurthermore, RBDM robustly formed particles as con\ufb01rmed by\ndynamic\nlight\nscattering\n(DLS)\nreading\nat\n35.86 nm;\nhigh-\nperformance liquid chromatography size exclusion chromatogra-\nphy (HPLC-SEC) analysis at 26.4 min retention time; as well as\ntransmission electron microscopy (TEM) analysis (Fig. 1c, d, e). The\naf\ufb01nity between RBD antigen and human Angiotensin-converting\nenzyme 2 (hACE2) was measured in vitro using a Biolayer\nInterferometry (BLI) assay. RBDM demonstrated the strongest\nbinding af\ufb01nity constant to hACE2 among all other designs, likely\ndue to the avidity of the interaction when arraying antigen on a\nVLP (Supplementary Fig. S1). The S protein trimer (S-trimer),\ndepicted in Fig. 1a, was selected as a \u201creference vaccine\u201d since\nmost \ufb01rst-generation SARS-CoV-2 subunit vaccines were designed\nbased on S-protein antigen.\nWe\nimmunised\nBALB/c\nmice\nwith\ntwo\ndoses\nof\nRBDM\nformulated in Alhydrogel to evaluate its immunogenicity (Fig.\n1f). RBDM was able to induce a signi\ufb01cantly higher IgG response\nas compared to the soluble RBD; although it was not signi\ufb01cantly\ndifferent as compared to the larger S-trimer immunogen at each\ntimepoint (Supplementary Fig. S2a). RBD-speci\ufb01c IgG subclasses\nwere also measured in day 28 samples. Here, RBDM induced a\nsigni\ufb01cantly higher and more balanced IgG1, IgG2a and IgG2b\nresponse than the soluble RBD. A similar trend was observed\nwhen compared to S-trimer (Supplementary Fig. S2b). Neutralizing\nantibody (nAb) was measured using an ACE2-RBD binding\ncompetition ELISA. RBDM induced signi\ufb01cantly higher nAb\nresponses against most variants (Fig. 1g). For RBDM, the reduction\nof nAb titers from WT to variants were no more than 3-fold, expect\nfor Omicron BA.1 where a >20-fold reduction was observed\n(Fig. 1g). To understand if the higher nAb response of the RBDM\ngroup was solely due to a higher total IgG response as\ndemonstrated in the endpoint titre ELISA (Supplementary Fig\nS2a), we calculated the ratio of ELISA-measured nAb to IgG"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 343
encoding: FLOAT32
metadata:
{"title": "An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques", "chroma:document": "endpoint titer for individual animals. Per unit of endpoint titer,\nthere were signi\ufb01cantly more anti-WT, Alpha, Beta, Delta and\nLambda nAbs in the RBDM vaccinated group than the S-trimer\ngroup. The nAb response against Gamma and Omicron BA.1\nvariant followed the same trend but was not statistically different\n(Fig. 1h). These data indicate the RBDM vaccine induced a\nqualitatively superior antibody response against most variants in\nour study.\nTo test if RBDM is effective against viral challenges, K18-hACE2\ntransgenic mice were immunised three times with 10 \u03bcg or 20 \u03bcg\nRBDM formulated in Alhydrogel adjuvant on days 0, 21 and 42 as\ndepicted in Fig. 1i. Serum from individual mice was taken on days\n21, 42 and 49. The IgG titers were measured and the vaccines at\nboth doses induced signi\ufb01cantly higher IgG response as compared\nto the saline and adjuvant control groups; while no signi\ufb01cant\ndifference\nwas\nobserved\nbetween\nthe\ntwo\nvaccine\ndoses\n(Supplementary\nFig.\nS3a).\nNeutralizing\nantibody\n(nAb)\nwas\nmeasured by pseudovirus assay and the nAb response against\nboth the WT and Delta stains of pseudovirus were detected\n(Supplementary Fig. S3b, c). The mice were then challenged with\nthe WT or Delta variant of SARS-CoV-2 live virus on day 49\nfollowed by dissection on day 52. The viral loads in the lung tissue\nwere measured by plaque assay and no live virus was detected in\nany of the vaccinated groups challenged with either strain of\nSARS-CoV-2 (Fig. 1k).\nTo test if RBDM is immunogenic in non-human primates (NHP),\nrhesus macaques were immunised three times with 50 or 25 \u03bcg\nRBDM or adjuvant control on days 0, 28 and 56; the immunisation\nstrategy is depicted in Fig. 1j. The anti-Spike glycoprotein IgG was\nmeasured by ELISA and both dosage groups induced high\nantibody titers with similar trend, and both peaked after the\nsecond immunisation (Fig. 1l). Pseudovirus neutralization assay\n(Supplementary Fig. S4a) and live virus neutralization assay\n(Fig. 1m) were performed. Both tests con\ufb01rmed induction of high"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 344
encoding: FLOAT32
metadata:
{"title": "An RBD virus-like particle vaccine for SARS-CoV-2 induces cross-variant antibody responses in mice and macaques", "chroma:document": "nAb titers against the WT and Delta variant of SARS-CoV-2. The live\nvirus\nneutralization\nassay\nagainst\nWT\nSARS-CoV-2\nrevealed\nrelatively high nAb responses, with a geometric mean titer\n(GMT) of 3547 on day 56 after two vaccinations and 5552 on day\nReceived: 18 November 2022 Revised: 15 March 2023 Accepted: 29 March 2023\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 345
encoding: FLOAT32
metadata:
{"title": "Biliatresone: progress in biliary atresia study", "chroma:document": "Vol.:(0123456789)\n1 3\nWorld Journal of Pediatrics (2023) 19:417\u2013424 \nhttps://doi.org/10.1007/s12519-022-00619-0\nREVIEW ARTICLE\nBiliatresone: progress in\u00a0biliary atresia study\nJia\u2011Jie\u00a0Zhu1\u00a0\u00b7 Yi\u2011Fan\u00a0Yang1\u00a0\u00b7 Rui\u00a0Dong1\u00a0\u00b7 Shan\u00a0Zheng1 \nReceived: 24 March 2022 / Accepted: 5 September 2022 / Published online: 27 September 2022 \n\u00a9 The Author(s) 2022\nAbstract\nBackground Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis \nand treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current \ntheorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still \nlargely unknown. Recently, biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we \nsummarized the latest progress of biliatresone research in BA and tried to answer the question of whether it could provide \nfurther clues to the etiology of human BA.\nData sources We conducted a PubMed search for any published articles related to the topic using search terms including \n\u201cbiliary atresia\u201d, \u201cbiliatresone\u201d, \u201cGSH\u201d, and \u201cHSP90\u201d. Relevant data were extracted from the original text or supplementary \nmaterials of the corresponding articles.\nResults Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors \ninvolved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epide-\nmiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occur-\nrence of biliary atresia is partly due to biliatresone or its structure-like compounds depositing in human body via vegetables \nor/and the altered intestinal flora structure can be tentatively established.\nConclusions Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 346
encoding: FLOAT32
metadata:
{"title": "Biliatresone: progress in biliary atresia study", "chroma:document": "and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered \nintestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. \nHowever, the evidence from large sample epidemiological research is necessary.\nKeywords Biliary atresia\u00a0\u00b7 Biliatresone\u00a0\u00b7 Glutathione\u00a0\u00b7 Gut flora\nIntroduction\nBiliary atresia (BA), characterized by fibro-inflammation \nand obstruction of extrahepatic bile ducts (EHBD) that can \nlead to liver fibrosis [1], remains the most common reason \nfor liver transplantation in infants, and its clinical presen-\ntations include high levels of direct or conjugated serum \nbilirubin, acholic stool, dark urine, and progressive hepatic \nfailure [2]. Typical pathophysiological features of BA liv-\ners include EHBD obstruction, portal tract fibrosis, ductular \nproliferation, and cholestasis with the appearance of bile \nplugs [3]. BA occurs variably worldwide, affecting all ethnic \ngroups, and has a higher incidence in Asia and the Pacific \nregion [4, 5]. To date, there are still no consistently cura-\ntive treatment options for BA, and nearly 70% of children \nstill cannot escape the fate of requiring liver transplantation \neven after undergoing a Kasai portoenterostomy (KPE), a \nprocedure that removes fibrotic EHBD and reestablishes the \nbile drainage pathway [6]. Therefore, to transfer from effec-\ntive but symptom-only treatments (such as KPE) to origin-\nrelated treatment and/or prevention methods, unraveling the \netiology of BA must be a top priority.\nStudies conducted on specimen samples (acquired dur-\ning surgery or tissue biopsy) or experimental animal mod-\nels, especially the Rhesus rotavirus (RRV)-induced mouse \nmodel, which replicates the key pathological features of \nhuman BA, such as EHBD damage, portal tract fibrosis and \nductular proliferation [7], are trying to answer the ques-\ntion of what causes BA, and some of the factors have been \n * Shan Zheng \n \nszheng@shmu.edu.cn\n1"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 347
encoding: FLOAT32
metadata:
{"title": "Biliatresone: progress in biliary atresia study", "chroma:document": "1 \nDepartment of\u00a0Pediatric Surgery, Shanghai Key Laboratory \nof\u00a0Birth Defect, and\u00a0Key Laboratory of\u00a0Neonatal Disease, \nMinistry of\u00a0Health, Children\u2019s Hospital of\u00a0Fudan University, \n399 Wan Yuan Road, Shanghai\u00a0201102, China"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 348
encoding: FLOAT32
metadata:
{"title": "A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned", "chroma:document": "RESEARCH ARTICLE\nA replicon RNA vaccine can induce durable\nprotective immunity from SARS-CoV-2 in\nnonhuman primates after neutralizing\nantibodies have waned\nMegan A. O\u2019Connor1,2, David W. Hawman3,4, Kimberly Meade-White3, Shanna Leventhal3,\nWenjun Song5, Samantha Randall1,6, Jacob Archer1,6, Thomas B. Lewis1,2,\nBrieann Brown1,2, Megan N. Fredericks1,2, Kaitlin R. Sprouse7, Hillary C. Tunggal1,2,\nMara Maughan1,2, Naoto Iwayama2, Chul Ahrens2, William Garrison2, Solomon Wangari2,\nKathryn A. Guerriero2, Patrick Hanley4, Jamie Lovaglio4, Greg Saturday4, David Veesler7,\nPaul T. Edlefsen5, Amit P. Khandhar6, Heinz Feldmann3, Deborah\nHeydenburg FullerID1,2*, Jesse H. ErasmusID1,6*\n1 Department of Microbiology, University of Washington, Seattle, Washington, United States of America,\n2 Washington National Primate Research Center, University of Washington, Seattle, Washington, United\nStates of America, 3 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and\nInfectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, United\nStates of America, 4 Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute\nof Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton,\nMontana, United States of America, 5 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer\nResearch Center, Seattle, Washington, United States of America, 6 HDT Bio, Seattle, Washington, United\nStates of America, 7 Department of Biochemistry, University of Washington, United States of America\n* fullerdh@uw.edu (DHF); jesse.erasmus@hdt.bio (JHE)\nAbstract\nThe global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines.\nAlthough several vaccines have received emergency approval through various public health\nagencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning\nimmunity in the vaccinated, evidence that vaccines may not prevent transmission and ineq-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 349
encoding: FLOAT32
metadata:
{"title": "A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned", "chroma:document": "uity in vaccine distribution have driven continued development of vaccines against SARS-\nCoV-2 to address these public health needs. In this report, we evaluated a novel self-ampli-\nfying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19\ndisease. We found that this vaccine elicited strong binding and neutralizing antibody\nresponses against homologous virus. We also observed broad binding antibody against het-\nerologous contemporary and ancestral strains, but neutralizing antibody responses were\nprimarily targeted to the vaccine-homologous strain. While binding antibody responses\nwere sustained, neutralizing antibody waned to undetectable levels in some animals after\nsix months but were rapidly recalled and conferred protection from disease when the ani-\nmals were challenged 7 months after vaccination as evident by reduced viral replication and\npathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower\nconcentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demon-\nstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and\nprotective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011298\nApril 19, 2023\n1 / 24\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: O\u2019Connor MA, Hawman DW, Meade-\nWhite K, Leventhal S, Song W, Randall S, et al.\n(2023) A replicon RNA vaccine can induce durable\nprotective immunity from SARS-CoV-2 in\nnonhuman primates after neutralizing antibodies\nhave waned. PLoS Pathog 19(4): e1011298.\nhttps://doi.org/10.1371/journal.ppat.1011298\nEditor: Alexander Bukreyev, University of Texas\nMedical Branch / Galveston National Laboratory,\nUNITED STATES\nReceived: September 5, 2022\nAccepted: April 11, 2023\nPublished: April 19, 2023\nCopyright: This is an open access article, free of all\ncopyright, and may be freely reproduced,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 350
encoding: FLOAT32
metadata:
{"title": "A replicon RNA vaccine can induce durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned", "chroma:document": "distributed, transmitted, modified, built upon, or\notherwise used by anyone for any lawful purpose.\nThe work is made available under the Creative\nCommons CC0 public domain dedication.\nData Availability Statement: All data are available\nin the main text or the supplementary materials.\nFunding: This work was supported in part by the\nIntramural Research Program of NIAID/NIH to HF\nand by the National Institute of Health (NIH) (P51\nOD010425 to DHF and MAO; 27220140006C to\nJHE; K01-MH123258 to MAO; U42OD011123),\nand HDT Bio internal funds. JHE, APK, SR, JA\nreceive salary from HDT Bio.The funders had no"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 351
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{"title": "Fiber photometry in striatum reflects primarily nonsomatic changes in calcium", "chroma:document": "Fiber photometry in striatum reflects primarily nonsomatic \nchanges in calcium\nAlex A. Legaria1, Bridget A. Matikainen-Ankney2, Ben Yang3, Biafra Ahanonu4, Julia A. \nLicholai5, Jones G. Parker3,\u2709, Alexxai V. Kravitz1,2,6,\u2709\n1Department of Neuroscience, Washington University School of Medicine, St Louis, MO, USA.\n2Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.\n3Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, \nUSA.\n4Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.\n5Department of Neuroscience, Brown University, Providence, RI, USA.\n6Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA.\nAbstract\nFiber photometry enables recording of population neuronal calcium dynamics in awake mice. \nWhile the popularity of fiber photometry has grown in recent years, it remains unclear whether \nphotometry reflects changes in action potential firing (that is, \u2018spiking\u2019) or other changes in \nneuronal calcium. In microscope-based calcium imaging, optical and analytical approaches can \nhelp differentiate somatic from neuropil calcium. However, these approaches cannot be readily \napplied to fiber photometry. As such, it remains unclear whether the fiber photometry signal \nreflects changes in somatic calcium, changes in nonsomatic calcium or a combination of the two. \n\u2709Correspondence and requests for materials should be addressed to Jones G. Parker or Alexxai V. Kravitz. \njones.parker@northwestern.edu; alexxai@wustl.edu.\nAuthor contributions\nA.A.L. contributed to conceptualization, methodology, software, formal analysis, investigation, data curation, writing of the original \ndraft, reviewing and editing the article and visualization. B.A.M.-A. contributed to the investigation and reviewing and editing the \narticle. B.Y. contributed to data curation and formal analysis. B.A. contributed to software, methodology and reviewing and editing the"}


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id: 352
encoding: FLOAT32
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{"title": "Fiber photometry in striatum reflects primarily nonsomatic changes in calcium", "chroma:document": "article. J.A.L. contributed to conceptualization and the methodology. J.G.P. contributed to the methodology, data curation, writing of \nthe original draft, reviewing and editing the article, resources and supervision. A.V.K. contributed to conceptualization, investigation, \nwriting of the original draft, reviewing and editing the article, resources and supervision.\nCompeting interests\nThe authors declare no competing interests.\nReporting summary. Further information on research design is available in the Nature Research Reporting Summary linked to this \narticle.\nCode availability\nAll custom code generated to analyze the datasets used in the current study are available in the Open Science Framework repository, at \nhttps://osf.io/8j7g2/.\nExtended data is available for this paper at https://doi.org/10.1038/s41593-022-01152-z.\nPeer review information Nature Neuroscience thanks Bernardo Sabatini, Garret Stuber, and the other, anonymous, reviewer(s) for \ntheir contribution to the peer review of this work.\nReprints and permissions information is available at www.nature.com/reprints.\nSupplementary information The online version contains supplementary material available at https://doi.org/10.1038/\ns41593-022-01152-z.\nHHS Public Access\nAuthor manuscript\nNat Neurosci. Author manuscript; available in PMC 2023 May 02.\nPublished in final edited form as:\nNat Neurosci. 2022 September ; 25(9): 1124\u20131128. doi:10.1038/s41593-022-01152-z.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 353
encoding: FLOAT32
metadata:
{"title": "G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders", "chroma:document": "REVIEW ARTICLE\nOPEN\nG protein-coupled receptors in neurodegenerative diseases and\npsychiatric disorders\nThian-Sze Wong1,2, Guangzhi Li3, Shiliang Li\n4,5, Wei Gao1,5, Geng Chen1, Shiyi Gan1, Manzhan Zhang4,5, Honglin Li\n4,5\u2709,\nSong Wu3,6\u2709 and Yang Du\n1\u2709\nNeuropsychiatric disorders are multifactorial disorders with diverse aetiological factors. Identifying treatment targets is challenging\nbecause the diseases are resulting from heterogeneous biological, genetic, and environmental factors. Nevertheless, the increasing\nunderstanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge of\nmolecular mechanisms and structural information of GPCRs will be advantageous for developing effective drugs. This review\nprovides an overview of the role of GPCRs in various neurodegenerative and psychiatric diseases. Besides, we highlight the\nemerging opportunities of novel GPCR targets and address recent progress in GPCR drug development.\nSignal Transduction and Targeted Therapy  (2023) 8:177 \n; https://doi.org/10.1038/s41392-023-01427-2\nINTRODUCTION\nThe nervous system employs membrane receptors to detect\nextracellular stimuli and transmit signals across the cell mem-\nbrane. As the largest membrane protein family, G protein-coupled\nreceptors (GPCRs) allow the nervous system to respond accurately\nto external stimuli and internal states. GPCRs are structurally\nsimilar transmembrane proteins containing seven transmembrane\n(TM) \u03b1-helices linked by three extracellular loops and three\nintracellular loops.1 The unique ligand binding pockets formed by\nthe 7TM regions allow the receptor to engage with various stimuli,\nincluding neurotransmitters, nucleotides, amines, peptides, cyto-\nkines, and hormones in the extracellular environment (Fig. 1).2\nThrough expressing GPCRs with different ligand-recognizing\nabilities, the nervous system could \ufb01lter and select particular\nsignals to respond.3 Furthermore, the intrinsic ligand selectivity of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 354
encoding: FLOAT32
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{"title": "G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders", "chroma:document": "neuronal GPCRs allows crosstalk and proper integration between\nsignal transduction pathways. GPCRs drive signal transduction via\ntwo major modulators: heterotrimeric G protein and arrestins.\nCharacterizing the physiological functions of GPCRs in the nervous\nsystem and pathological mechanisms in disease models could\naccelerate GPCR-targeted drug development.\nThe progressive dysfunction of neural tissues in the central and\nperipheral nervous systems is the hallmark feature of neurode-\ngenerative diseases. Neurodegenerative diseases are increasing in\nthe elderly population.4 It is estimated that neurodegenerative\ndiseases affect over\n50 million people across the globe.5\nAlzheimer\u2019s disease, Huntington\u2019s disease, Parkinson\u2019s disease,\nand Multiple sclerosis are representative examples. Currently,\nthere is no effective cure. The pathogenesis and underlying\nmechanisms\nof\nneurodegenerative\ndiseases\nremain\npoorly\nunderstood. At present, symptom control is the primary treatment\nobjective.6 It is estimated that neurodegenerative diseases will\nbecome the second most common cause of death.7\nAlzheimer\u2019s disease and dementias are in the top-ten ranking\nleading cause of death globally.8 Deposition of the insoluble and\nphosphorylated \u03b2-amyloid peptide (derived from amyloid precursor\nprotein) in the brain parenchyma of Alzheimer\u2019s disease patients\naffects functions/regeneration of various forms of neurons.9 The\nresulting widespread neuron damage affects synaptic communication\nleading to cognitive de\ufb01cits, regional brain shrinkage, and brain\natrophy;10 Huntington\u2019s disease could appear in childhood or\nadolescence. Aberrant expansion of DNA segment containing CAG\ntrinucleotide repeats in the huntingtin gene is a hallmark feature.11\nLarge CAG repeat is associated with early symptoms manifestation.12\nSymptoms include poor coordination, chorea (involuntary dance-like\nmovements), slow movement, seizures, and slurred speech; Parkin-\nson\u2019s disease affects motion control. Rigidity, tremor, and slow"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 355
encoding: FLOAT32
metadata:
{"title": "G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders", "chroma:document": "movement (bradykinesia) are frequently observed. Risk factors include\ngenetic polymorphism, chronic in\ufb02ammation, and metabolic dis-\norders.13 Multiple sclerosis is a relapsing-remitting disease caused by\nan autoimmune attack in the central nervous system. Damage of\nmyelin sheath in multiple areas by immune cells causes cognitive\nimpairment, fatigue, muscle weakness, tremor, and vision problems.14\nBrain disorders are frequently associated with mental/psychia-\ntric illnesses.15 Mental illness is burdening the healthcare system\nwith enormous unmet medical needs.16,17 Serious mental illness is\nclosely linked to reduced life expectancy due to a higher risk of\ncardiovascular morbidity and mortality.18 Common mental ill-\nnesses include anxiety, depression, bipolar disorder, attention\nde\ufb01cit hyperactivity disorder, and schizophrenia. Both children\nReceived: 8 July 2022 Revised: 17 February 2023 Accepted: 30 March 2023\n1Kobilka Institute of Innovative Drug Discovery, Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong,\n518172 Shenzhen, Guangdong, China; 2School of Medicine, Tsinghua University, 100084 Beijing, China; 3Institute of Urology, The Af\ufb01liated Luohu Hospital of Shenzhen\nUniversity, Shenzhen University, 518000 Shenzhen, Guangdong, China; 4Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and\nTechnology, 200237 Shanghai, China; 5Innovation Center for AI and Drug Discovery, East China Normal University, 200062 Shanghai, China and 6Department of Urology, South\nChina Hospital, Health Science Center, Shenzhen University, 518116 Shenzhen, Guangdong, China\nCorrespondence: Honglin Li (hlli@ecust.edu.cn) or Song Wu (wusong@szu.edu.cn) or Yang Du (yangdu@cuhk.edu.cn)\nThese authors contributed equally: Thian-Sze Wong, Guangzhi Li, Shiliang Li.\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 356
encoding: FLOAT32
metadata:
{"title": "Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development", "chroma:document": "Lessons from Acquired Natural Immunity and Clinical Trials \nto Inform Next-Generation Human Cytomegalovirus Vaccine \nDevelopment\nXintao Hu1, Hsuan-Yuan Wang1,2, Claire E. Otero1,2, Jennifer A. Jenks2, Sallie R. Permar1\n1Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA;\n2Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA\nAbstract\nHuman cytomegalovirus (HCMV) infection, the most common cause of congenital disease \nglobally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in \ninfants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to \na significant disease burden in immunocompromised individuals. Hence, an effective HCMV \nvaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, \ndespite more than five decades of vaccine development, no successful HCMV vaccine is available. \nThis review summarizes what we have learned from acquired natural immunity, including innate \nand adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the \nprogress in related animal models; and the analysis of protective immune responses during natural \ninfection and vaccination settings. Finally, we propose novel vaccine strategies that will harness \nthe knowledge of protective immunity and employ new technology and vaccine concepts to inform \nnext-generation HCMV vaccine development.\nKeywords\nhuman cytomegalovirus; acquired natural immunity; clinical trial; animal model; immune \ncorrelates of protection; next-generation vaccine\n1. INTRODUCTION\nHuman cytomegalovirus (HCMV), a double-stranded DNA virus with the largest genome \n(around 235 kbp) of known human viruses, belongs to the human betaherpesvirus family (1). \nHCMV infection causes persistent, life-long infection in broad types of host cells mediated \nby four major envelope glycoprotein complexes (GCs): glycoprotein B (gB) oligomer,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 357
encoding: FLOAT32
metadata:
{"title": "Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development", "chroma:document": "gM/gN dimer, gH/gL/gO trimer, and gH/gL/UL128/UL130/UL131 pentamer complex (PC) \nthrough distinct entry mechanisms (1, 2).\nsallie.permar@med.cornell.edu . \nDISCLOSURE STATEMENT\nS.R.P. is a consultant to Moderna, Merck, Pfizer, GSK, Dynavax, and Hoopika CMV vaccine programs and leads sponsored programs \nwith Moderna and Merck. S.R.P. also serves on the board of the National CMV Foundation and as an educator on CMV for Medscape. \nThe other authors have no financial conflicts of interest.\nHHS Public Access\nAuthor manuscript\nAnnu Rev Virol. Author manuscript; available in PMC 2023 September 29.\nPublished in final edited form as:\nAnnu Rev Virol. 2022 September 29; 9(1): 491\u2013520. doi:10.1146/annurev-virology-100220-010653.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 358
encoding: FLOAT32
metadata:
{"title": "Single-cell transcriptomics of the ocular anterior segment: a comprehensive review", "chroma:document": "REVIEW ARTICLE\nOPEN\nSingle-cell transcriptomics of the ocular anterior segment: a\ncomprehensive review\nSo\ufb01a Ahsanuddin\n1,2,3 and Albert Y. Wu\n1\u2709\n\u00a9 The Author(s) 2023\nElucidating the cellular and genetic composition of ocular tissues is essential for uncovering the pathophysiology of ocular diseases.\nSince the introduction of single-cell RNA sequencing (scRNA-seq) in 2009, vision researchers have performed extensive single-cell\nanalyses to better understand transcriptome complexity and heterogeneity of ocular structures. This technology has revolutionized\nour ability to identify rare cell populations and to make cross-species comparisons of gene expression in both steady state and\ndisease conditions. Importantly, single-cell transcriptomic analyses have enabled the identi\ufb01cation of cell-type speci\ufb01c gene\nmarkers and signalling pathways between ocular cell populations. While most scRNA-seq studies have been conducted on retinal\ntissues, large-scale transcriptomic atlases pertaining to the ocular anterior segment have also been constructed in the past three\nyears. This timely review provides vision researchers with an overview of scRNA-seq experimental design, technical limitations, and\nclinical applications in a variety of anterior segment-related ocular pathologies. We review open-access anterior segment-related\nscRNA-seq datasets and illustrate how scRNA-seq can be an indispensable tool for the development of targeted therapeutics.\nEye (2023) 37:3334\u20133350; https://doi.org/10.1038/s41433-023-02539-3\nINTRODUCTION\nTechnological advances in mRNA phenotyping methods have\nenabled unprecedented access to transcriptomic data in ophthal-\nmology [1]. As a proxy to the proteome, the \u201ctranscriptome\u201d offers\ninsight into how gene expression correlates with cellular physiology\nand function, thereby revealing previously unknown cellular\ndynamics in ensembles of large cell numbers [2, 3]. Prior to\ntranscriptomics, the earliest applications of immunohistochemistry\nin ophthalmic pathology enabled researchers to de\ufb01ne cellular"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 359
encoding: FLOAT32
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{"title": "Single-cell transcriptomics of the ocular anterior segment: a comprehensive review", "chroma:document": "phenotype by protein expression, while in-situ hybridization\nenabled precise spatial RNA sequence localization in a select tissue\nsample [4]. To construct gene expression pro\ufb01les at different time-\npoints, researchers harnessed subtractive hybridization to create\ncomplementary DNA (cDNA) libraries of various ocular structures\nsuch as retina, retinal pigment epithelial (RPE), and ciliary epithelium\n[5\u20138]. This technique has been demonstrated to be effective for\ninvestigating gene expression in complex disease states such as\nuveal melanoma [9].\nExpression studies involving differential display, expressed\nsequence tags (EST), serial analysis of gene expression (SAGE),\nand hybridization-based microarray technologies have similarly\nfacilitated differentially expressed gene identi\ufb01cation in ophthal-\nmology [10]. Eventually, the development of next-generation\nsequencing (NGS) techniques like RNA-sequencing (RNA-Seq)\npooled large cell numbers and allowed researchers to generate\nmore comprehensive cell atlases comprised of both known and\nunknown mRNA transcripts, a feat that was previously limited to\nknown transcripts [11, 12]. The high throughput of this technology\nallowed for novel gene marker detection and provided insight\ninto alternative splicing as an important regulatory factor of\ncellular heterogeneity and pathogenesis in many disease states\n[13]. Nonetheless, all of these technologies involve analysis of\nlarge numbers of aggregated cells, which hinders more granular\nassessments of gene expression dynamics in highly heterogenous\ntissues like those found in the eye. Because it lacks individual cell-\ntype resolution, pooled RNA-seq analyses also cannot provide\ninsight into each cell type\u2019s relative abundance and how gene\nexpression differs by cell type within a sample [14].\nSince the \ufb01rst single-cell RNA sequencing (scRNA-seq) study was\ndescribed by Tang et al. in 2009, the technology has generated\nunprecedented levels of interest in the vision research community"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 360
encoding: FLOAT32
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{"title": "Single-cell transcriptomics of the ocular anterior segment: a comprehensive review", "chroma:document": "[3, 15]. It has proven to be a versatile and powerful tool for\nunderstanding the transcriptional heterogeneity of ocular tissues\nat single-cell resolution. ScRNA-seq studies have rapidly expanded\nfrom pro\ufb01ling eight cells to 1.3 million cells [3]. In comparison to\nbulk RNA-seq, scRNA-seq enables the identi\ufb01cation of rare cell\npopulations, stem cells, novel biomarkers, lineage tracing between\nvarious cellular states, and transcriptional responses to drug\ntherapy over time, all of which allow researchers to understand\nthe molecular mechanisms driving disease processes at high-\nresolution [16]. Importantly, scRNA-seq has been demonstrated\nto be useful for developing targeted therapeutic interventions in\nhighly heterogenous tissues because it enables investigations\nof cell type, monoallelic gene expression, gene co-expression,\nsplicing patterns, and gene regulatory networks in a parallelized\nmanner.\nIn the vision research community, scRNA-seq has primarily been\nutilized to elucidate the different cell types in the retina, RPE, and\nReceived: 21 November 2022 Revised: 7 March 2023 Accepted: 11 April 2023\nPublished online: 3 May 2023\n1Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Stanford, CA, USA. 2Department of Ophthalmology, New York Eye and Ear In\ufb01rmary\nof Mount Sinai, New York City, NY, USA. 3Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA. \u2709email: awu1@stanford.edu\nwww.nature.com/eye\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 361
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{"title": "Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 362
encoding: FLOAT32
metadata:
{"title": "Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma", "chroma:document": "Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 \nPeptide Vaccine for Prevention of Recurrent Colorectal Adenoma\nRobert E. Schoen1, Lisa A. Boardman2, Marcia Cruz-Correa3, Ajay Bansal4, David \nKastenberg5, Chin Hur6, Lynda Dzubinski1, Sharon F. Kaufman2, Luz M. Rodriguez7, Ellen \nRichmond7, Asad Umar7, Eva Szabo7, Andres Salazar8, John McKolanis9, Pamela Beatty9, \nReetesh K. Pai10, Aatur D. Singhi10, Camille M. Jacqueline9, Riuye Bao11,12, Brenda \nDiergaarde12,13, Ryan P. McMurray2, Carrie Strand2, Nathan R. Foster2, David M. Zahrieh2, \nPaul J. Limburg2, Olivera J. Finn9\nCorresponding authors: Robert E. Schoen, MD, MPH. Address: Division of Gastroenterology, Hepatology, and Nutrition, 200 \nLothrop St., Mezzanine Level, C Wing, PUH Pittsburgh, PA 15213-2582 Email: rschoen@pitt.edu, Olivera J. Finn, PhD. Address: \nDepartment of Immunology, Biomedical Science Tower, 200 Lothrop St., Pittsburgh, PA, 15213. ojfinn@pitt.edu.\nStudy concept and design: RES, LMR, PJL, OJF\nAcquisition of data: RES, LAB, MCC, AB, DK, CH, LD, SFK, JM, PB, RP, AS, CMJ, RB, BD, OJF\nAnalysis and interpretation of data: RES, PB, RKP, ADS, CMJ, RB, BD, RPM, CS, NRF, DMZ, PJL, OJF\nDrafting of the manuscript: RES, OJF\nCritical revision of the manuscript for important intellectual content: RES, LAB, MCC, AB, DK, CH, LMR, ER, AU, ES, RKP, AS, \nBD, RPM, CS, NRF, DMZ, PJL, OJF\nStatistical analysis: RB, RPM, CS, NRF, DMZ\nObtained funding: RES, PJL, OJF\nAdministrative, technical, or material support: LD, SFK, LMR, ER, AU, ES, AS, JM, PB, RP, ADS, CMJ, RB, BD\nStudy supervision: LMR, ER, AU, ES, PJL\nDisclosures of Potential conflict of interest:\nRES: Research support from Freenome, Immunovia, and Exact Sciences\nLAB: None\nMCC: None\nAB: Research support from Freenome and Stella Diagnostics\nDK: Consultant Medtronic, Research support - Exact Sciences and Freenome\nCH: None\nLD: None\nSFK: None\nLMR: None\nER: None\nAU: None\nES: None\nAS: Founder, CEO and CSO of Oncovir\nJM: None\nPB: None\nRKP: Consultant for Alimentiv\nADS: None\nCMJ: None"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 363
encoding: FLOAT32
metadata:
{"title": "Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma", "chroma:document": "CMJ: None\nRB: RB declares patents: (all provisional) PCT/US15/612657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers \nfor Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof), PCT/US63/055227 (Methods and \nCompositions for Treating Autoimmune and Allergic Disorders)\nBD: None\nRPM: None\nCS: None\nNRF: None\nDMZ: None\nPJL: Chief Medical Officer for Screening at Exact Sciences through a contracted services agreement with the Mayo Clinic. Dr. \nLimburg and Mayo Clinic have contractual rights to receive royalties through this agreement.\nOJF: Consultant: PDS Biotech, GeoVax, Immodulon, Ardigen, Invectys, Sparc, Isa Therapeutics\nClinicalTrials.gov Identifier: NCT02134925.\nhttps://clinicaltrials.gov/ct2/show/NCT02134925 \nHHS Public Access\nAuthor manuscript\nClin Cancer Res. Author manuscript; available in PMC 2023 November 01.\nPublished in final edited form as:\nClin Cancer Res. 2023 May 01; 29(9): 1678\u20131688. doi:10.1158/1078-0432.CCR-22-3168.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 364
encoding: FLOAT32
metadata:
{"title": "Myostatin: A Skeletal Muscle Chalone", "chroma:document": "Myostatin: A Skeletal Muscle Chalone\nSe-Jin Lee1,2\n1Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, \nFarmington, Connecticut, USA\n2The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA\nAbstract\nMyostatin (GDF-8) was discovered 25 years ago as a new transforming growth factor-\u03b2 family \nmember that acts as a master regulator of skeletal muscle mass. Myostatin is made by skeletal \nmyofibers, circulates in the blood, and acts back on myofibers to limit growth. Myostatin appears \nto have all of the salient properties of a chalone, which is a term proposed over a half century ago \nto describe hypothetical circulating, tissue-specific growth inhibitors that control tissue size. The \nelucidation of the molecular, cellular, and physiological mechanisms underlying myostatin activity \nsuggests that myostatin functions as a negative feedback regulator of muscle mass and raises the \nquestion as to whether this type of chalone mechanism is unique to skeletal muscle or whether it \nalso operates in other tissues.\nKeywords\nGDF-8; transforming growth factor-\u03b2; activin; latency; growth; tissue size\nTHE CHALONE HYPOTHESIS FOR THE REGULATION OF TISSUE MASS\nSubstances of the kind under discussion do not fall within the usual definition \nof a hormone as a systemically distributed chemical substance \u2018produced by one \ntissue with the primary function of exerting a specific effect of functional value \non another tissue\u2019 (Huxley 1935) (1). On the contrary, these are substances each \nof which is produced by a tissue with the primary function of controlling the \ngrowth, and perhaps the differentiation, of that same tissue\u2026. It is suggested that \nthe members of this complex of chemical messengers, which may possibly prove to \nbe a family of proteins, should be called chalones.\n(2, p. 332)\nThis work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 365
encoding: FLOAT32
metadata:
{"title": "Myostatin: A Skeletal Muscle Chalone", "chroma:document": "and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party \nmaterial in this article for license information.\nSe-Jin.Lee@jax.org . \nDISCLOSURE STATEMENT\nThe author is a consultant to Biohaven Pharmaceuticals, Inc., and an inventor on a patent application titled \u201cTherapeutics Targeting \nTransforming Growth Factor Beta Family Signaling.\u201d\nHHS Public Access\nAuthor manuscript\nAnnu Rev Physiol. Author manuscript; available in PMC 2023 May 06.\nPublished in final edited form as:\nAnnu Rev Physiol. 2023 February 10; 85: 269\u2013291. doi:10.1146/annurev-physiol-012422-112116.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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id: 366
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{"title": "Potential Protective Function of Adiponectin in Diabetic Retinopathy", "chroma:document": "REVIEW\nPotential Protective Function of Adiponectin\nin Diabetic Retinopathy\nHui Deng . Meichen Ai . Yuchen Cao . Liyang Cai . Xi Guo .\nXiongyi Yang . Guoguo Yi . Min Fu\nReceived: February 15, 2023 / Accepted: March 6, 2023 / Published online: March 31, 2023\n\u0002 The Author(s) 2023\nABSTRACT\nAdiponectin,\none\nof\nthe\nmost\nubiquitous\nadipokines found in the blood, plays a major\nrole\nin\nglucolipid\nmetabolism\nand\nenergy\nmetabolism and regulation. In recent years, a\ngrowing body of research indicates that adipo-\nnectin also plays a signi\ufb01cant role in diabetic\nretinopathy. In the present review, we speci\ufb01-\ncally\naddress\nthe\nprotective\neffects\nof\nadiponectin on the development and progres-\nsion of diabetic retinopathy through improve-\nment\nin\ninsulin\nresistance,\nalleviation\nof\noxidative stress, limiting of in\ufb02ammation, and\nprevention of vascular remodeling, with the\naim to explore new potential approaches and\ntargets for the prevention and treatment of\ndiabetic retinopathy.\nKeywords: Adiponectin; Diabetic retinopathy;\nTherapy targets\nHui Deng, Meichen Ai, and Yuchen Cao have\ncontributed equally to this review.\nH. Deng \u0002 M. Ai \u0002 Y. Cao \u0002 L. Cai \u0002 X. Yang \u0002 M. Fu\n(&)\nDepartment of Ophthalmology, Zhujiang Hospital,\nSouthern Medical University, No. 253, Industrial\nAvenue Middle, Haizhu, Guangzhou 510280,\nGuangdong, China\ne-mail: min_fu1212@163.com\nH. Deng \u0002 M. Ai \u0002 Y. Cao \u0002 L. Cai \u0002 X. Yang \u0002 M. Fu\nThe Second Clinical School of Southern Medical\nUniversity, Guangzhou 510280, Guangdong, China\nY. Cao\nPlastic Surgery Hospital, Peking Union Medical\nCollege, Chinese Academy of Medical Sciences,\nBeijing 100144, China\nX. Guo\nSchool of Rehabilitation Sciences, Southern Medical\nUniversity, Guangzhou 510280, Guangdong, China\nG. Yi (&)\nDepartment of Ophthalmology, The Sixth Af\ufb01liated\nHospital of Sun Yat-Sen University, No. 26, Erheng\nRoad, Yuancun, Tianhe, Guangzhou 510230,\nGuangdong, China\ne-mail: yigg@mail.sysu.edu.cn\nOphthalmol Ther (2023) 12:1519\u20131534\nhttps://doi.org/10.1007/s40123-023-00702-3"}


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{"title": "Evolutionary psychiatry: foundations, progress and challenges", "chroma:document": "World Psychiatry 22:2 - June 2023 \n177\nSPECIAL ARTICLE\nEvolutionary psychiatry: foundations, progress and challenges\nRandolph M.\u00a0Nesse\nDepartments of Psychiatry and Psychology, University of Michigan, Ann Arbor, MI, USA; Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA\nEvolutionary biology provides a crucial foundation for medicine and behavioral science that has been missing from psychiatry. Its absence helps to ex-   \nplain slow progress; its advent promises major advances. Instead of offering a new kind of treatment, evolutionary psychiatry provides a scientific foun-\ndation useful for all kinds of treatment. It expands the search for causes from mechanistic explanations for disease in some individuals to evolutionary \nexplanations for traits that make all members of a species vulnerable to disease. For instance, capacities for symptoms such as pain, cough, anxiety \nand low mood are universal because they are useful in certain situations. Failing to recognize the utility of anxiety and low mood is at the root of \nmany problems in psychiatry. Determining if an emotion is normal and if it is useful requires understanding an individual\u2019s life situation. Conducting \na review of social systems, parallel to the review of systems in the rest of medicine, can help achieve that understanding. Coping with substance abuse \nis advanced by acknowledging how substances available in modern environments hijack chemically mediated learning mechanisms. Understanding \nwhy eating spirals out of control in modern environments is aided by recognizing the motivations for caloric restriction and how it arouses famine \nprotection mechanisms that induce binge eating. Finally, explaining the persistence of alleles that cause serious mental disorders requires evolutionary \nexplanations of why some systems are intrinsically vulnerable to failure. The thrill of finding functions for apparent diseases is evolutionary psychiatry\u2019s"}


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id: 368
encoding: FLOAT32
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{"title": "Evolutionary psychiatry: foundations, progress and challenges", "chroma:document": "greatest strength and weakness. Recognizing bad feelings as evolved adaptations corrects psychiatry\u2019s pervasive mistake of viewing all symptoms as if \nthey were disease manifestations. However, viewing diseases such as panic disorder, melancholia and schizophrenia as if they are adaptations is an \nequally serious mistake in evolutionary psychiatry. Progress will come from framing and testing specific hypotheses about why natural selection left \nus vulnerable to mental disorders. The efforts of many people over many years will be needed before we will know if evolutionary biology can provide \na new paradigm for understanding and treating mental disorders.\nKey words:\u00a0Evolutionary psychiatry, natural selection, vulnerability to diseases, evolutionary medicine, depression, anxiety, substance use dis \u00ad\norders, eating disorders, schizophrenia\n(World Psychiatry 2023;22:177\u2013202)\nCalls for new directions in psychiatry have echoed for dec\u00ad\nades, but only now is recognition growing that the field has been \nhobbled by using only one half of biology. Almost all effort has \ngone into research on mechanisms, while the rest of medicine \nand behavioral science have long also investigated the evolution\u00ad\nary origins and functions of those mechanisms. Evolutionary \nmedicine goes further to ask why natural selection left some traits \nvulnerable to malfunction. Evolutionary psychiatry answers that \nquestion for mental disorders.\nResearch on animal behavior was transformed when it adopted \nan evolutionary foundation in the final decades of the 20th cen\u00ad\ntury1\u00ad 4. Recognition that brains are shaped by natural selection to \nmaximize gene transmission expanded ethology from a descrip\u00ad\ntive science to one grounded in theory that predicts behavior. For \ninstance, the assumption that birds lay as many eggs as possible \nwas replaced when theoretically inspired studies showed that \nbirds adjust egg laying in ways that maximize the number of sur\u00ad\nviving fledglings in the current environment5. Animal behavior"}


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id: 369
encoding: FLOAT32
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{"title": "Evolutionary psychiatry: foundations, progress and challenges", "chroma:document": "textbooks are now all grounded on evolutionary biology.\nMedicine has long relied on knowledge about adaptive func\u00ad\ntions as well as mechanisms. Knowing the functions of the pan\u00ad\ncreas, the mitral valve, and the cough reflex is crucial for under\u00ad\nstanding their malfunctions. Internal medicine textbooks describe \npathology in the context of normal physiological functions. Psy\u00ad\nchiatry textbooks, instead, describe pathology with little reference \nto normal functions.\nExplaining traits that leave a species vulnerable to a disease \nposes special challenges, because most evolutionary explana\u00ad\ntions describe how traits give advantages. Webbed feet make \nducks paddle faster. Sweating stabilizes body temperature. Cough \nclears foreign matter from the airways. So, it seems natural to try \nto explain mental disorders by proposing ways they could offer \nadvantages. That approach is essential for negative emotions, to \ncorrect the pervasive error of viewing adaptations as if they were \ndiseases. However, viewing true diseases as if they were adapta\u00ad\ntions is an even more serious error that is common in evolution\u00ad\nary psychiatry. It is tempting to try to explain schizophrenia, ano\u00ad\nrexia nervosa or autism by proposing ways that they might offer \nadvantages, but such hypotheses are almost always wrong. Dis\u00ad\neases are not adaptations shaped by natural selection. They are \nnot universal traits. They harm fitness. Trying to explain diseases \nas if they were somehow useful gives rise to a conceptual fog, \nwhich will be dispelled, not by global debates about adaptation\u00ad\nism, but by systematically considering specific hypotheses in the \nlight of rigorous evolutionary theory.\nEvolutionary medicine does not explain diseases; it explains \ntraits that make bodies vulnerable to disease. Examples include \nthe narrow birth canal, the windpipe opening into the pharynx, \nand the tendency for immune responses to attack the body\u2019s own \ntissues. The usual explanation for disease vulnerability has been"}


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id: 370
encoding: FLOAT32
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{"title": "Evolutionary psychiatry: foundations, progress and challenges", "chroma:document": "that natural selection cannot prevent all mutations. That is an \nimportant explanation, but several others are equally important6\u00ad 10. \nNatural selection is too slow to keep up with rapid environmen\u00ad\ntal change or fast\u00ad evolving pathogens. It can\u2019t start fresh to cor\u00ad\nrect a suboptimal design. It increases the performance of traits at \nthe cost of reduced robustness. It maximizes gene transmission, \nat the expense of health and happiness. And it shapes useful \ndefenses such as pain and anxiety that feel awful and are prone \nto excessive expression. Evolutionary medicine frames and tests \nhypotheses based on these explanations."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 371
encoding: FLOAT32
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{"title": "Potential application of let-7a antagomir in injured peripheral nerve regeneration", "chroma:document": "1584  \uff5cNEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nResearch Article\nPotential application of let-7a antagomir in injured \nperipheral nerve regeneration\nAbstract  \nNeurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely \nlimited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. \nConsidering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we \nevaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of \nendogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety \nassessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively \nachieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-\nhydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our \nstudy provides an experimental basis for potential in vivo application of let-7a.\nKey Words: chitosan; chitosan-hydrogel scaffold; let-7; let-7a antagomir; miRNA; nerve graft; peripheral nerve injury; peripheral nerve regeneration; Schwann \ncells\nhttps://doi.org/10.4103/1673-5374.357914\nDate of submission: April 27, 2022 \nDate of decision: July 26, 2022 \nDate of acceptance: August 23, 2022 \nDate of web publication: October 13, 2022 \nIntroduction \nPeripheral nerve injury is a common clinical problem that affects"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 372
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{"title": "Potential application of let-7a antagomir in injured peripheral nerve regeneration", "chroma:document": "approximately 13\u201323 per 100,000 persons per year  (Li et al., 2014; Lolis et \nal., 2018). Currently, the gold standard treatment for peripheral nerve injury \nis autologous nerve grafting. The application of autologous nerve grafts, \nhowever, is largely limited by its intrinsic disadvantages, such as limited donor \nnerve sources, donor nerve functional loss, and size differences between the \ndonor nerve and recipient nerve (Gu et al., 2011; Luo et al., 2021). Therefore, \nthere is an urgent need to develop and construct tissue-engineered nerve \ngrafts with better clinical application to repair injured peripheral nerves.\nTissue-engineered nerve grafts have been designed as a prospective \nalternative for regenerative medicine. Tissue-engineered nerve grafts \ngenerally contain scaffolds and embedded supporting cells or biological \ncues. Morphological and cellular molecular studies have demonstrated that \naxonal regeneration involves the precise coordination of numerous cells to \nprovide an optimal regeneration microenvironment (Wang et al., 2022a). \nMacrophages, fibroblasts, and Schwann cells gather at the injury site to \nperform different functions and help establish a regenerative pathway to \nrepair peripheral nerve function (Qian et al., 2018; Wang et al., 2022a). Many \ngrowth factors with neurotrophic effects, especially nerve growth factor \n(NGF), promote myelin sheath formation, enhance axonal regeneration, and \nhave been used in neural tissue engineering (Gu et al., 2011, 2014). However, \nthe in vivo applications of these growth factors are largely restricted by their \nlow stability, short half-life periods, and high costs (Chen and Mooney, 2003; \nChen et al., 2012). Recent studies have reported that a variety of microRNAs \n(miRNAs) regulate peripheral nerve injury and regeneration (Li et al., 2015b; \nJi et al., 2019; Lopez-Leal et al., 2020; Wang et al., 2022c). Therefore, it is \nfeasible to incorporate miRNAs into biomaterial scaffolds to reshape the"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 373
encoding: FLOAT32
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{"title": "Potential application of let-7a antagomir in injured peripheral nerve regeneration", "chroma:document": "microenvironment, so as to promote injured nerve regeneration (Krutzfeldt \net al., 2005; Gu et al., 2014; Yu et al., 2015; Ou et al., 2019; Leng et al., 2020). \nMany reviews have discussed the possibilities of various miRNA applications, \nespecially the therapeutic application of miRNA for tissue engineering \n(Hutchison et al., 2013; Zhao et al., 2014; Caputo et al., 2015; Chew, 2015; \nLi et al., 2015a; Miller et al., 2015; Raschzok et al., 2015; Sabirzhanov et al., \n2016; Yao et al., 2016). \nLet-7, the first identified human miRNA, is involved in many important \nbiological processes (Shell et al., 2007; Roush and Slack, 2008; Su et al., \n2012; Yuan et al., 2012). Previous studies showed that decreased let-7 \nlevels elevated NGF secretion from Schwann cells, increased Schwann cell \nproliferation and migration in vitro, and promoted Schwann cell migration and \naxon outgrowth in vivo (Li et al., 2015b; Zhang et al., 2020). Another study \nshowed that let-7 miRNAs were core regulators affecting peripheral nerve \nrepair and regeneration (Wang et al., 2019). Considering these studies, we \nselected let-7a as a suitable member of the let-7 family, performed a safety \nassessment for potential application, and investigated its morphological and \nfunctional effects on peripheral nerve injury repair. \n1State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical \nSchool, Nanjing University, Nanjing, Jiangsu Province, China; 2NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Key Laboratory of \nNeuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China\n*Correspondence to: Shi-Ying Li, PhD, lisy0379@ntu.edu.cn.\nhttp://orcid.org/0000-0001-5150-7299 (Shi-Ying Li)"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 374
encoding: FLOAT32
metadata:
{"title": "Potential application of let-7a antagomir in injured peripheral nerve regeneration", "chroma:document": "Funding: This work was supported by the National Natural Science Foundation of China, No. 31970968 (to SYL), the Collegiate Natural Science Foundation of Jiangsu Province, \nNo.16KJA310005 (to SYL), Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD] and the Natural Science Foundation of Jiangsu Province, No. \nBK20200976 (to XHW).\nHow to cite this article: Chen QQ, Liu QY, Wang P, Qian TM, Wang XH, Yi S, Li SY (2023) Potential application of let-7a antagomir in injured peripheral nerve regeneration. Neural \nRegen Res 18(7):1584-1590. \nGraphical Abstract\nIn vivo application of let-7a antagomir in the repair of peripheral nerve injury\nFrom the Contents\nIntroduction\n1584\nMethods  \n1585\nResults\n1586\nDiscussion\n1589\nQian-Qian Chen1, 2 Qian-Yan Liu2, Pan Wang2, Tian-Mei Qian2, Xing-Hui Wang2, Sheng Yi2, Shi-Ying Li2, *"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 375
encoding: FLOAT32
metadata:
{"title": "Conservative Management of Alloimmune Hemolysis and Cholestasis With Extreme Laboratory Abnormalities", "chroma:document": "Conservative Management of Alloimmune Hemolysis and \nCholestasis With Extreme Laboratory Abnormalities\nChelsea Kotch, MDa, David F. Friedman, MDa,b,c, Benjamin J. Wilkins, MD,PhDb,c, Benjamin \nJ. Samelson-Jones, MD,PhD,FAAPa,c\naDivision of Hematology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania;\nbDepartment of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, \nPhiladelphia, Pennsylvania;\ncPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania\nAbstract\nAlloimmune hemolytic disease of the fetus or newborn (HDFN) is a rare cause of neonatal \ncholestasis. HDFN-associated cholestasis has most often been reported secondary to anti-D \nalloimmunization. In utero transfusions are also an identified risk factor. A variety of diagnostic \nand therapeutic strategies have been described, mostly in case reports. Here, we report 2 cases \nof HDFN-associated cholestasis that were notable for extreme laboratory abnormalities including \na peak ferritin of 24 700 ng/mL and a peak alanine aminotransferase of 1406 U/L (33.5-fold \nupper limit of normal). One case was due to alloimmunization other than anti-D. These cases help \ndefine the range of laboratory derangements that are consistent with HDFN-associated cholestasis, \nincluding extreme hyperferritinemia. Although in a number of cases, researchers have reported \nthe use of iron chelation in these infants, herein, we describe successful management without iron \nchelation.\nAlloimmune hemolytic disease of the fetus or newborn (HDFN)1 is a rare cause of \nneonatal cholestasis.2,3 Infants with HDFN and in utero or postnatal red blood cell (RBC) \ntransfusions are at increased risk for cholestasis. The diagnostic workup and management \nof these infants relies principally on experiences from case reports and small series (Table \n1).4\u201323 Herein, we describe the successful management, without iron chelation, of 2 infants \nwith HDFN-associated cholestatic liver disease and substantial laboratory abnormalities,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 376
encoding: FLOAT32
metadata:
{"title": "Conservative Management of Alloimmune Hemolysis and Cholestasis With Extreme Laboratory Abnormalities", "chroma:document": "including extreme hyperferritinemia. One case is also a rare example of cholestasis \noccurring with HDFN not due to anti-D alloimmunization.\nAddress correspondence to Benjamin J. Samelson-Jones, MD, PhD, FAAP, Children\u2019s Hospital of Philadelphia, 3501 Civic Center \nBlvd, 5028 Colket Translational Research Center, Philadelphia, PA 19104, samelsonjonesb@email.chop.edu.\nDrs Kotch and Samelson-Jones conceptualized and designed the report, collected and interpreted data, and drafted and revised the \nmanuscript; Drs Friedman and Wilkins collected and interpreted data and critically revised the manuscript; and all authors approved \nthe final manuscript as submitted and agree to be accountable for all aspects of the work.\nFINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.\nPOTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.\nHHS Public Access\nAuthor manuscript\nPediatrics. Author manuscript; available in PMC 2023 May 10.\nPublished in final edited form as:\nPediatrics. 2021 February ; 147(2): . doi:10.1542/peds.2019-3367.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 377
encoding: FLOAT32
metadata:
{"title": "Factors relating to circulating immune complexes in rheumatoid arthritis", "chroma:document": "Ann. rheum. Dis. (1976), 35, 314\nFactors relating to circulating immune\ncomplexes in rheumatoid arthritis\nP. J. ROBERTS-THOMSON, B. L. HAZLEMAN,*\nI. G. BARNETT,t\nI. C. M. MAcLENNAN, AND A. G. MOWAT\nFrom the Nuffield Department of Clinical Medicine, Radcliffe Infirmary, and\nthe Rheumatology Unit, Nuffield Orthopaedic Centre, Oxford\nRoberts-Thomson, P. J., Hazleman, B. L., Barnett,\nI. G., MacLennan,\nI. C. M., and\nMowat, A. G. (1976). Annals of the Rheumatic Diseases, 35, 314-320. Factors relating\nto circulating immune complexes in rheumatoid arthritis. Evidence has been presented\nsuggesting that circulating immune complexes occur in over half of the sera of patients\nwith rheumatoid arthritis. These IgG-containing complexes were small, eluting between\nIgG and IgM on gel filtration on Sepharose 6B and were not seen in the sera of healthy\ncontrol subjects. These complexes were detected in the sera of both seronegative and\nseropositive patients and their quantity did not correlate with IgM rheumatoid factor\ntitre. The quantity of complexed IgG was estimated from a ratio derived from the IgG\nprofile obtained by gel filtration of the serum. This quantity correlated significantly\nwith the degree of inhibition by the rheumatoid sera of cytolysis in vitro of IgG sensi-\ntized target cells by K cells from human peripheral blood. A significant inverse cor-\nrelation was observed between the quantity of serum complexes and the chemotactic\nindex of the circulating polymorphonuclear leucocytes obtained from the same rheuma-\ntoid patient. It is suggested that ingestion of these complexes may be implicated in the\nreduction in chemotaxis observed in patients with rheumatoid arthritis. There was no\ncorrelation between the quantity of the complexes in the sera and other clinical,\nhaematological, and biochemical measurements.\nThe presence of circulating IgG complexes of small\nsize (i.e. sedimenting between 7 and 19S) has now\nbeen shown in the sera of patients with a wide\nvariety\nof\ndiseases.\nThese\ninclude\nrheumatoid"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 378
encoding: FLOAT32
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{"title": "Factors relating to circulating immune complexes in rheumatoid arthritis", "chroma:document": "arthritis and hypergammaglobulinaemic purpura of\nWaldenstrom (Kunkel and others, 1961), systemic\nlupus\nerythematosus\nand\nSj0gren's\nsyndrome\n(Blaylock, Waller, and Normansell, 1974; Alarcon-\nSegovia and\nothers,\n1974),\ninflammatory\nbowel\ndisease (Jewell and MacLennan, 1973), and some\nthyroid disorders (Calder and others,\n1974). The\nnature\nof\nthese\nimmune\ncomplexes\nand\ntheir\nrelationship to the pathogenesis of these diseases is\nobscure.\nIn\nrheumatoid\narthritis\nsmall immune\ncomplexes\nare\nfrequently\nfound and\nare\noften\npresent in considerable quantity (Winchester and\nothers, 1971; Norberg, 1974).\nIn this study two techniques have been used to\ndetect and quantitate small immune complexes in\nthe sera of 35 patients with rheumatoid arthritis.\nThe first technique involves the separation of serum\nIgG using Sepharose 6B column chromatography\n(Jewell and MacLennan,\n1973).\nIn\nthis method\ncomplexed IgG separates in higher molecular size\nfractions\nthan noncomplexed\nIgG.\nThe\nsecond\ntechnique is a functional assay which can detect\ncertain immune complexes and aggregates of IgG.\nThis technique\nis based upon the principle that\nantibody-dependent\ncell-mediated\ncytotoxicity\nor\nK cell mediated cytotoxicity can be competitively\ninhibited\nby immune\ncomplexes\noccupying\nthe\nreceptors for antibody on K cells and so preventing\nK cell access to target cells sensitized with antibody.\nA ratio derived from gel filtration chromato-\ngraphy has been described for estimating the amount\nof these complexes found circulating in the sera of\nAccepted for publication December 21, 1975.\n* Present address: Department of Rlleumatology, Addenbrooke's Hospital, Cambridge.\nt Deceased.\nCorrespondence to: Dr. A. G. Mowat, Dept. of Rheumatology, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 379
encoding: FLOAT32
metadata:
{"title": "HLA-A, B antigens and a1-antitrypsin phenotypes in nodal generalised osteoarthritis and osteoarthritis", "chroma:document": "Annals of the Rheumatic Diseases 1989; 48: 470-475\nHLA-A, B antigens and a1-antitrypsin phenotypes in\nnodal generalised osteoarthritis and erosive\nosteoarthritis\nMARTIN\nPATTRICK,'\nADRIAN\nMANHIRE,2\nA\nMILFORD\nWARD,3\nAND\nMICHAEL DOHERTY1\nFrom the 'Rheumatology\nUnit and the 2Radiology Department,\nCity Hospital, Nottingham; and the\n3Department of Immunology, Royal Hallamshire Hospital, Sheffield\nSUMMARY\nHLA-A, B and a1-antitrypsin phenotypes were studied in 90 unrelated patients with\nestablished nodal generalised osteoarthritis (OA). Compared with standard reference popula-\ntions, independently increased frequency of the HLA-A1B8 and MZ ac-antitrypsin phenotypes\nwere observed (27% v 11-5%, relative risk 2-79, and 12% v 3-6%, relative risk 3.73 respectively).\nThese associations related to development of nodal generalised OA rather than to severity as\njudged by the summated radiographic scores for hand OA. Ten patients had marked subchondral\nradiographic erosions and were further classified as erosive OA; these patients had an increased\nfrequency of the MS a,-antitrypsin phenotype (30% v 9%) and higher radiographic OA scores\ncorrected for presence of erosions. This first report of two independent genetic markers in nodal\ngeneralised OA is of interest in relation to the increasingly recognised inflammatory component\nof the osteoarthritis process.\nSymptomatic osteoarthritis (OA) is a common but\nill understood condition with a spectrum of clinical\npresentation\nand\noutcome.' 2\nMultiple\nfactors\n(genetic,\nconstitutional,\nenvironmental) may be\ninvolved\nin\nits development.-5 To\nunderstand\nbetter its pathogenesis OA has been divided into\nsubsets on the basis of distribution, radiographic\nfeatures, associated crystal deposition, and recog-\nnised aetiological factors.2 Nodal generalised OA is\na subset characterised by polyarticular interpha-\nlangeal and thumb base OA, female preponderance,\nearly inflammatory component, and Heberden node\nformation6; of all OA subsets, familial tendency is\nparticularly\nrecognised.4 Erosive OA"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 380
encoding: FLOAT32
metadata:
{"title": "HLA-A, B antigens and a1-antitrypsin phenotypes in nodal generalised osteoarthritis and osteoarthritis", "chroma:document": "is an un-\ncommon form of generalised OA sharing many\nfeatures of nodal generalised OA but differing by\nhaving marked subchondral erosive change and a\nflorid inflammatory component.7 8\nGenetic factors have been extensively studied in\nrheumatic diseases4 and may be associated with\neither development or severity.9'2 Despite marked\nfamilial predisposition few studies have investigated\nAccepted for publication 9 November 1988.\nCorrespondence to Dr Martin Pattrick. Rheumatology Unit. City\nHospital. Hucknall Road. Nottingham NG5 IPB.\ngenetic markers in nodal generalised OA.4 Only\nfour report the frequencies of HLA antigens, with\nconflicting\nresults 1-6:\none\nreporting\nincreased\nfrequency\nof HLA-A1B8, 13\none\nan\nincreased\nfrequency\nof HLA-B8, 14\nand\ntwo\nfinding\nno\nassociations. 15 16 To our knowledge ac-antitrypsin\nphenotypes,\nwell\nstudied\nin\nother\nrheumatic\ndiseases,'7-21 have not been examined in OA.\nWe\ntherefore\ninvestigated\nthe\nprevalence\nof\nHLA-A, B antigens and a,-antitrypsin phenotypes\nin patients with well characterised nodal generalised\nOA to define genetic markers predisposing to either\nOA development or severity of radiographic change.\nPatients and methods\nNinety unrelated, English born, white patients (79\nwomen, 11 men; mean age 67, range 42-90 years)\npresenting\nto\nthe Nottingham\nunit\nwith\nnodal\ngeneralised OA were studied. Each had symptoma-\ntic polyarticular interphalangeal OA affecting more\nthan three rays of each hand with Heberden node\nformation unrelated to obvious trauma. Each under-\nwent full clinical and radiographic assessment. All\nhad radiographic and\nin some\ncases\nadditional\nclinical evidence of OA\nat other\nsites, but no\n470"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 381
encoding: FLOAT32
metadata:
{"title": "Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis", "chroma:document": "NEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\uff5c1535\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nResearch Article\nEmodin attenuates inflammation and demyelination in \nexperimental autoimmune encephalomyelitis\nAbstract  \nEmodin, a substance extracted from herbs such as rhubarb, has a protective effect on the central nervous system. However, the potential therapeutic effect \nof emodin in the context of multiple sclerosis remains unknown. In this study, a rat model of experimental autoimmune encephalomyelitis was established by \nimmune induction to simulate multiple sclerosis, and the rats were intraperitoneally injected with emodin (20 mg/kg/d) from the day of immune induction \nuntil they were sacrificed. In this model, the nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and the \nmicroglia exacerbated neuroinflammation, playing an important role in the development of multiple sclerosis. In addition, silent information regulator of \ntranscription 1 (SIRT1)/peroxisome proliferator-activated receptor-alpha coactivator (PGC-1\u03b1) was found to inhibit activation of the NLRP3 inflammasome, and \nSIRT1 activation reduced disease severity in experimental autoimmune encephalomyelitis. Furthermore, treatment with emodin decreased body weight loss \nand neurobehavioral deficits, alleviated inflammatory cell infiltration and demyelination, reduced the expression of inflammatory cytokines, inhibited microglial \naggregation and activation, decreased the levels of NLRP3 signaling pathway molecules, and increased the expression of SIRT1 and PGC-1\u03b1. These findings \nsuggest that emodin improves the symptoms of experimental autoimmune encephalomyelitis, possibly through regulating the SIRT1/PGC-1\u03b1/NLRP3 signaling \npathway and inhibiting microglial inflammation. These findings provide experimental evidence for treatment of multiple sclerosis with emodin, enlarging the \nscope of clinical application for emodin."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 382
encoding: FLOAT32
metadata:
{"title": "Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis", "chroma:document": "Key Words: demyelination; emodin; experimental autoimmune encephalomyelitis; microglia; multiple sclerosis; neuroinflammation; NLRP3 inflammasome; \nPGC-1\u03b1; pyroptosis; SIRT1\nhttps://doi.org/10.4103/1673-5374.358612\nDate of submission: May 12, 2022 \nDate of decision: August 2, 2022 \nDate of acceptance: September 28, 2022 \nDate of web publication: October 24, 2022\nIntroduction \nMultiple sclerosis (MS) is a demyelinating autoimmune disease of the central \nnervous system (CNS) (Filippi et al., 2018). MS affects more than two million \npeople worldwide (Browne et al., 2014) and is more common in young adults. \nThe pathological features of MS include focal demyelinating plaques in the \nbrain, spinal cord, and optic nerve, as well as diffuse changes such as axonal \ninjury and astrogliosis (Lassmann, 2018). Although the etiology of MS has not \nbeen fully elucidated, environmental, genetic, and epigenetic factors have \nbeen implicated in its pathogenesis (Olsson et al., 2017). Existing drugs for \nMS, such as interferon beta, dimethyl fumarate, and fingolimod, have strong \nside effects and cannot reverse the chronic progressive disabilities associated \nwith this condition (Tintore et al., 2019; Bhargava, 2021; D\u2019Amico et al., 2022). \nTherefore, there is an urgent need to develop effective and safe therapeutic \ndrugs for MS. Experimental autoimmune encephalomyelitis (EAE) is currently \nthe most widely used animal model of MS (Lassmann and Bradl, 2017); it \npartially simulates MS pathogenesis and is a useful tool for exploring the \nunderlying molecular mechanisms of MS. \nInflammasomes are signaling complexes that sense injury and stress signals \nand induce inflammatory cytokine maturation and secretion. The nucleotide-\nbinding domain-like receptor family pyrin domain containing 3 (NLRP3) \ninflammasome is the most widely studied inflammasome and is involved \nin many autoimmune and inflammatory diseases (Duewell et al., 2010; \nHeneka et al., 2013). NLRP3 inflammasome-related molecules are involved"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 383
encoding: FLOAT32
metadata:
{"title": "Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis", "chroma:document": "in MS pathogenesis, as indicated by altered levels of NLRP3 inflammasome \ncomplex components in patients with MS and in animal knockout models \n(Gris et al., 2010; Walsh et al., 2014; Burm et al., 2016; McKenzie et al., \n2018). Inflammasome component expression is increased in the CNS tissues \nof MS patients. Furthermore, inflammasome activation and pyroptosis occur \nin human glial cells, which may affect the occurrence and development of \nMS. Moreover, abnormal microglial activation leads to demyelination and \nneurodegenerative changes (Baecher-Allan et al., 2018). Microglia, which \nare the intrinsic immune cells of the CNS, can exacerbate neuroinflammation \nby secreting chemokines, which in turn recruit immune cells to the CNS, \nand can also act as antigen-presenting cells to activate immune cells (Ferrari \net al., 2004; Mallucci et al., 2015). In addition, microglia can be activated \nby pro-inflammatory cytokines such as interleukin (IL)-1\u03b2, thus creating a \nvicious cycle (Correale and Farez, 2015). These studies illustrate the key roles \nof inflammasome and microglial activation in MS. In addition, studies have \ndemonstrated that silent information regulator of transcription 1 (SIRT1) and \nthe downstream molecule peroxisome proliferator-activated receptor-alpha \ncoactivator (PGC-1\u03b1) can inhibit NLRP3 inflammasome activation (Park et al., \n2020; Wang et al., 2021b; Zhang et al., 2021). Research has shown that SIRT1-\nmediated responses are involved in a variety of physiological processes, such \nas oxidative stress, inflammation, and apoptosis (Yang et al., 2022). Several \nstudies have reported the inhibitory effect of SIRT1 on the inflammatory \nresponse (Yeung et al., 2004; Planavila et al., 2011; Bai et al., 2020). These \nresults suggest that SIRT1 can reduce neuroinflammation by inhibiting NLRP3 \ninflammasome activation. Moreover, related studies have found that activation \nDepartment of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 384
encoding: FLOAT32
metadata:
{"title": "Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis", "chroma:document": "*Correspondence to: Juan Feng, MD, PhD, juanfeng@cmu.edu.cn.\nhttps://orcid.org/0000-0002-1815-7036 (Juan Feng)\nFunding: This study was supported by the National Natural Science Foundation of China, No. 81771271; Key Research and Development Program of Liaoning Province, No. \n2020JH2/10300047; and Outstanding Scientific Fund of Shengjing Hospital (all to JF).\nHow to cite this article: Cui YR, Bu ZQ, Yu HY, Yan LL, Feng J (2023) Emodin attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis. Neural Regen \nRes 18(7):1535-1541. \nGraphical Abstract\nEmodin inhibits the NLRP3 signaling pathway and suppresses microglial activation in \nexperimental autoimmune encephalomyelitis\nFrom the Contents\nIntroduction\n1535\nMethods  \n1536\nResults\n1537\nDiscussion\n1539\nYue-Ran Cui, Zhong-Qi Bu, Hai-Yang Yu, Li-Li Yan, Juan Feng*"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 385
encoding: FLOAT32
metadata:
{"title": "Prevalence of Parvovirus B19 Viremia Among German Blood Donations and the Relationship to ABO and Rhesus Blood Group Antigens", "chroma:document": "The Journal of Infectious Diseases                                \nB R I E F  R E P O R T\nPrevalence of Parvovirus B19 Viremia \nAmong German Blood Donations and \nthe Relationship to ABO and Rhesus \nBlood Group Antigens\nKatie Healy,1,2 Linda B. S. Aulin,3,4 Urban Freij,5 Marie Ellerstad,5 Lena Br\u00fcckle,6\nHelen Hillmering,5 Tor-Einar Svae,7 Kristina Broliden,8 and Rasmus Gustafsson5,9\n1Division of Clinical Diagnostics and Surgery, Department of Dental Medicine, Karolinska \nInstitutet, Stockholm, Sweden; 2Division of Clinical Microbiology, Department of Laboratory \nMedicine, Karolinska Institutet, Stockholm, Sweden; 3Leiden Academic Centre for Drug \nResearch, Leiden University, Leiden, The Netherlands; 4Clinical Pharmacy and Biochemistry, \nFreie Universit\u00e4t Berlin, Berlin, Germany; 5Octapharma AB, Stockholm, Sweden; 6Octapharma \nPlasma GmbH, Langenfeld, Germany; 7Octapharma Handelsges.m.b.H, Vienna, Austria; \n8Karolinska Institutet, Department of Medicine Solna, Center for Molecular Medicine, \nDivision of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; \nand 9Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska \nInstitutet, Stockholm, Sweden\nBackground. Asymptomatic blood donors can transmit \nhuman parvovirus B19 (B19V).\nMethods. We assessed the B19V prevalence among a large \ncohort of blood donations collected in Germany during 2015\u2013 \n2018.\nResults. In total, 167 123 donations were screened for B19V \ndeoxyribonucleic acid with 22 cases of viremia identified (0.013% \npositive). Infections peaked at a 4-year interval and the highest \nnumber of cases occurred in the summer months. All 22 \ninfections were found in rhesus D-antigen-positive donations, \nsuggesting a protective factor in donors who lack this antigen.\nConclusions. These \nfindings \ncontribute \nto \nour \nunderstanding of risk factors for B19V infection among central \nEuropean blood and plasma donors.\nKeywords. ABO; b19V; blood donations; blood group; \nrhesus."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 386
encoding: FLOAT32
metadata:
{"title": "Prevalence of Parvovirus B19 Viremia Among German Blood Donations and the Relationship to ABO and Rhesus Blood Group Antigens", "chroma:document": "rhesus.\nReceived 01 July 2022; editorial decision 15 November 2022; accepted 18 November 2022; \npublished online 21 November 2022\nCorrespondence: Rasmus Gustafsson, PhD, Octapharma AB, 11251 Stockholm, Sweden \n(Rasmus.Gustafsson@ki.se).\nThe Journal of Infectious Diseases\u00ae\n2023;227:1214\u20138 \n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution- \nNonCommercial-NoDerivs \nlicence \n(https://creativecommons.org/licenses/by-nc-nd/4.0/), \nwhich permits non-commercial reproduction and distribution of the work, in any medium, pro-\nvided the original work is not altered or transformed in any way, and that the work is properly \ncited. For commercial re-use, please contact journals.permissions@oup.com\nhttps://doi.org/10.1093/infdis/jiac456\nThe human erythroparvovirus B19 (B19V) is a small, single- \nstranded, nonenveloped deoxyribonucleic acid (DNA) virus \nbelonging to the Parvoviridae family. The B19V replicates in \nhuman progenitor cells, leading to a decline in red blood cells \nthat can cause an accompanying anemia [1]. Although it is pri-\nmarily considered a respiratory disease, B19V can also be \ntransmitted through contaminated blood components as well \nas plasma-derived medicinal products [2, 3].\nIn epidemic seasons, blood and plasma donations with high \nB19V viral load have been reported, posing a risk for vulnerable \ngroups and B19V-naive individuals alike [4]. For example, \nB19V infection during pregnancy increases the risk of fetal \nloss, although the incidence rates are low [5]. It is known that \nthe risk of infection through blood products and plasma- \nderived medicinal products is correlated to the level of viremia, \nand the exclusion of plasma manufacturing pools containing \nB19V DNA levels above 104 IU/mL prevents transmission \nthrough the latter products [6].\nThe primary B19V receptor has been identified as the P"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 387
encoding: FLOAT32
metadata:
{"title": "Prevalence of Parvovirus B19 Viremia Among German Blood Donations and the Relationship to ABO and Rhesus Blood Group Antigens", "chroma:document": "blood group antigen [7]. Although the P antigen is necessary \nfor B19V binding, it alone is not sufficient for viral entry, which \nimplies that there is an additional surface coreceptor involved \n[8]. Integrin \u03b15\u03b21 and Ku80 have been suggested as coreceptors, \nbut the low expression on B19V-permissive cells indicates that \nthe exact mechanisms underlying B19V entry remain to be elu-\ncidated [9]. More recently, antibody-mediated mechanisms of \nviral entry have been proposed [10]. However, the exact core-\nceptor that enables B19V entry, and its subsequent endocytosis, \nis not yet known.\nGiven the importance of the P blood group antigens in B19V \nentry and the well documented importance of ABO and rhesus \nD-antigen [Rh(D)] blood groups in other virus infections in-\ncluding norovirus, human immunodeficiency virus (HIV), \nand hepatitis B virus [11], we hypothesized that other blood \ngroup antigens may play a role in virus susceptibility. In this \nstudy, we aimed to investigate the relationship between ABO \nblood group, Rh(D), and B19V prevalence in a large cohort \nof blood donations in Germany. Furthermore, we also investi-\ngated B19V infection dynamics among these central European \nblood and plasma donations over a 4-year period.\nMETHODS\nEthical Statement\nThis study was performed within the ethical standards of the \nDeclaration of Helsinki.\nAll data included in this study were pseudonymized and the \noriginal donor identities could not be traced back. Therefore, \nno ethical permit was required according to the Regional \nEthical Review Board in Stockholm.\nHuman Erythroparvovirus B19 Screening and Blood Group Typing of \nPlasma Donors\nAt Octapharma AB (Stockholm, Sweden) plasma donations \n(n = 167 123) from Germany were dispensed into 96-well \n1214 \u2022 JID 2023:227 (15 May) \u2022 BRIEF REPORT"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 388
encoding: FLOAT32
metadata:
{"title": "Accelerating antiviral drug discovery: lessons from COVID-19", "chroma:document": "Nature Reviews Drug Discovery\nnature reviews drug discovery\nhttps://doi.org/10.1038/s41573-023-00692-8\nPerspective\n Check for updates\nAccelerating antiviral drug \ndiscovery: lessons from COVID-19\nAnnette von Delft\u2009\n \u20091,2,11 \n, Matthew D. Hall\u2009\n \u20093, Ann D. Kwong4, Lisa A. Purcell\u2009\n \u20095, Kumar Singh Saikatendu6, Uli Schmitz7, \nJohn A. Tallarico8 & Alpha A. Lee9,10,11 \nAbstract\nDuring the coronavirus disease 2019 (COVID-19) pandemic, a wave of \nrapid and collaborative drug discovery efforts took place in academia \nand industry, culminating in several therapeutics being discovered, \napproved and deployed in a 2-year time frame. This article summarizes \nthe collective experience of several pharmaceutical companies and \nacademic collaborations that were active in severe acute respiratory \nsyndrome coronavirus 2 (SARS-CoV-2) antiviral discovery. We outline \nour opinions and experiences on key stages in the small-molecule \ndrug discovery process: target selection, medicinal chemistry, \nantiviral assays, animal efficacy and attempts to pre-empt resistance. \nWe propose strategies that could accelerate future efforts and argue \nthat a key bottleneck is the lack of quality chemical probes around \nunderstudied viral targets, which would serve as a starting point for \ndrug discovery. Considering the small size of the viral proteome, \ncomprehensively building an arsenal of probes for proteins in viruses \nof pandemic concern is a worthwhile and tractable challenge for the \ncommunity.\nSections\nIntroduction\nTarget selection and validation\nClinically validated targets\nTargets with chemical probe \nvalidation\nTargets with genetic evidence\nMedicinal chemistry\nCell culture models\nAnimal models\nHuman viral challenge models\nPre-empting resistance\nConcluding remarks\n1Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 2Oxford \nBiomedical Research Centre, National Institute for Health Research, University of Oxford, Oxford, UK. 3National"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 389
encoding: FLOAT32
metadata:
{"title": "Accelerating antiviral drug discovery: lessons from COVID-19", "chroma:document": "Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA. 4Pardes Biosciences, \nCarlsbad, CA, USA. 5Vir Biotechnology, San Francisco, CA, USA. 6Drug Discovery Sciences, Takeda California, Inc., \nSan Diego, CA, USA. 7Gilead Sciences, Inc., Foster City, CA, USA. 8Novartis Institutes for Biomedical Research, \nCambridge, MA, USA. 9PostEra, Inc., Cambridge, MA, USA. 10Cavendish Laboratory, University of Cambridge, \nCambridge, UK. 11These authors contributed equally: Annette von Delft, Alpha A.\u00a0Lee. \n\u2009e-mail: Annette.vondelft@\ncmd.ox.ac.uk; alpha.lee@postera.ai"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 390
encoding: FLOAT32
metadata:
{"title": "Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity", "chroma:document": "Homotopic local-global parcellation of the human cerebral \ncortex from resting-state functional connectivity\nXiaoxuan Yana,b,c,d, Ru Konga,b,c, Aihuiping Xuea,b,c, Qing Yanga,b,c, Csaba Orbana,b,c, Lijun \nAna,b,c, Avram J. Holmese, Xing Qiana, Jianzhong Chena,b,c, Xi-Nian Zuof,g, Juan Helen \nZhoua,b,d, Marielle V Fortierh,i, Ai Peng Tani,j, Peter Gluckmank, Yap Seng Chongi,l, Michael J \nMeaneyi,m, Danilo Bzdokn,o, Simon B. Eickhoffp,q, B.T. Thomas Yeoa,b,c,d,r,*\naCentre for Sleep and Cognition (CSC) & Centre for Translational Magnetic Resonance Research \n(TMR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore\nbDepartment of Electrical and Computer Engineering, National University of Singapore, \nSingapore\ncN.1 Institute for Health and Institute for Digital Medicine (WisDM), National University of \nSingapore, Singapore\ndIntegrative Sciences and Engineering Programme (ISEP), National University of Singapore, \nSingapor\neYale University, Departments of Psychology and Psychiatry, New Haven, CT, Unites States of \nAmerica\nfState Key Laboratory of Cognitive Neuroscience and Learning/IDG McGovern Institute for Brain \nResearch, Beijing Normal University, Beijing, China\ngNational Basic Public Science Data Center, China\nhDepartment of Diagnostic and Interventional Imaging, KK Women\u2019s and Children\u2019s Hospital, \nSingapore\niSingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research \n(A*STAR), Singapore\njDepartment of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of \nSingapore, Singapore\nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)\n*Corresponding author. thomas.yeo@nus.edu.sg (B.T.T. Yeo). \nCredit authorship contribution statement\nXiaoxuan Yan: Conceptualization, Methodology, Software, Writing \u2013 original draft, Visualization, Ru Kong: Conceptualization, \nMethodology; Aihuiping Xue: Conceptualization, Methodology, Validation; Qing Yang: Methodology; Csaba Orban: Writing,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 391
encoding: FLOAT32
metadata:
{"title": "Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity", "chroma:document": "Validation Lijun An: Software; Avram J Holmes: Writing, Validation; Xing Qian: Data processing; Jianzhong Chen: Software; \nXi-Nian Zuo: Writing, Validation; Juan Helen Zhou: Writing, Validation; Marielle V Fortier: Data collection; Ai Peng Tan: \nData collection; Peter Gluckman: Data collection; Yap Seng Chong: Data collection; Michael J Meaney: Data collection; Danilo \nBzdok: Writing, Validation; Simon B. Eickhoff: Writing, Validation; B.T. Thomas Yeo: Supervision, Conceptualization, Validation, \nWriting review and editing.\nSupplementary materials\nSupplementary material associated with this article can be found, in the online version, at doi:10.1016/j.neuroimage.2023.120010.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 June 01.\nPublished in final edited form as:\nNeuroimage. 2023 June ; 273: 120010. doi:10.1016/j.neuroimage.2023.120010.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 392
encoding: FLOAT32
metadata:
{"title": "Human Cytomegalovirus IE2 Disrupts Neural Progenitor Development and Induces Microcephaly in Transgenic Mouse", "chroma:document": "Vol.:(0123456789)\n1 3\nMolecular Neurobiology (2023) 60:3883\u20133897 \nhttps://doi.org/10.1007/s12035-023-03310-1\nHuman Cytomegalovirus IE2 Disrupts Neural Progenitor Development \nand\u00a0Induces Microcephaly in\u00a0Transgenic Mouse\nDelei\u00a0Niu1\u00a0\u00b7 Xianjuan\u00a0Zhang1\u00a0\u00b7 Shuyun\u00a0Zhang1\u00a0\u00b7 Tianyu\u00a0Fan2\u00a0\u00b7 Xiaoqiong\u00a0Zhou1\u00a0\u00b7 Hui\u00a0Wang3\u00a0\u00b7 Xueming\u00a0Zhang1\u00a0\u00b7 \nFulong\u00a0Nan3\u00a0\u00b7 Shasha\u00a0Jiang1\u00a0\u00b7 Fengjun\u00a0Liu3\u00a0\u00b7 Yunyang\u00a0Wang4\u00a0\u00b7 Bin\u00a0Wang1,3 \nReceived: 4 October 2022 / Accepted: 25 February 2023 / Published online: 29 March 2023 \n\u00a9 The Author(s) 2023\nAbstract \nHuman cytomegalovirus (HCMV) is a significant contributor to congenital birth defects. Limited by the lack of animal mod-\nels, the pathogenesis of neurological damage in\u00a0vivo caused by HCMV infection and the role of individual viral genes remain \nto be elucidated. Immediate early (IE2) protein may play a function in neurodevelopmental problems caused by HCMV \ninfection. Here, this study intended to investigate IE2\u2019s long-term effects on development of the brain in IE2-expressing \ntransgenic mice (Rosa26-LSL-IE2+/\u2212, Camk2\u03b1-Cre) aimed to observe the phenotype of postnatal mice. The expression of \nIE2 in transgenic mice was confirmed by PCR and Western blot technology. We collected mouse brain tissue at 2, 4, 6, 8, \nand 10 days postpartum to analyze the developmental process of neural stem cells by immunofluorescence. We discovered \nthat transgenic mice (Rosa26-LSL-IE2+/\u2212, Camk2\u03b1-Cre) can reliably produce IE2 in the brain at various postpartum phases. \nFurthermore, we also observed the symptoms of microcephaly in postnatal transgenic mice, and IE2 can damage the amount \nof neural stem cells, prevent them from proliferating and differentiating, and activate microglia and astrocytes, creating an \nunbalanced environment in the brain\u2019s neurons. In conclusion, we demonstrate that long-term expression of HCMV-IE2 \ncan cause microcephaly through molecular mechanisms affecting the differentiation and development of neural stem cells"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 393
encoding: FLOAT32
metadata:
{"title": "Human Cytomegalovirus IE2 Disrupts Neural Progenitor Development and Induces Microcephaly in Transgenic Mouse", "chroma:document": "in\u00a0vivo. This work establishes a theoretical and experimental foundation for elucidating the molecular mechanism of fetal \nmicrocephaly brought by HCMV infection in throughout the period of neural development of pregnancy.\nKeywords Human cytomegalovirus\u00a0\u00b7 IE2\u00a0\u00b7 Neural progenitor cells development\u00a0\u00b7 Microcephaly\u00a0\u00b7 Transgenic mouse\nIntroduction\nHuman cytomegalovirus (HCMV), belonging to the \n\u03b2-herpesvirus subfamily, is a ubiquitous and adaptable \nhuman pathogen that can remain latent for life in infected \nindividuals [1]. HCMV is a kind of opportunistic pathogens, \nmainly in immunocompromised patients cause significant \nmorbidity and mortality. During pregnancy, HCMV can be \ntransmitted to the developing fetus, thus globally affecting \n0.5\u20132% of newborns [2]. Approximately, 10\u201315% of neo-\nnates with congenital HCMV infection are symptomatic at \nbirth with defects, such as microcephaly (the most serious \nbrain diseases), hearing impairment, mental deficiency, and \nventricular calcification [3]. However, the mechanism by \nwhich HCMV affects neuropathogenesis has not yet been \nfully understood.\nThe correct timing of neural progenitor cell (NPC) pro-\nliferation/self-renewal and differentiation, neuronal migra-\ntion, and maturation is important for appropriate mammalian \nDelei Niu and Xianjuan Zhang contributed equally to this work.\n * Yunyang Wang \n \nwangyy_09@outlook.com\n * Bin Wang \n \nwangbin532@126.com\n1 \nDepartment of\u00a0Pathogenic Biology, College of\u00a0Basic \nMedicine, Qingdao University, Qingdao\u00a0266000, Shandong, \nChina\n2 \nDepartment of\u00a0Immunology, College of\u00a0Basic Medicine, \nQingdao University, Qingdao\u00a0266000, Shandong, China\n3 \nDepartment of\u00a0Special Medicine, College of\u00a0Basic Medicine, \nQingdao University, Qingdao\u00a0266000, Shandong, China\n4 \nDepartment of\u00a0Endocrinology and\u00a0Metabolism, the Affiliated \nHospital of\u00a0Qingdao University, Qingdao\u00a0266000, Shandong, \nChina"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 394
encoding: FLOAT32
metadata:
{"title": "Cell death in the lateral geniculate nucleus, and its possible relationship with nicotinic receptors and sudden infant death syndrome \\(SIDS\\", "chroma:document": "Vol:.(1234567890)\nMolecular Neurobiology (2023) 60:4120\u20134131\nhttps://doi.org/10.1007/s12035-023-03332-9\n1 3\nORIGINAL ARTICLE\nCell death in\u00a0the\u00a0lateral geniculate nucleus, and\u00a0its possible \nrelationship with\u00a0nicotinic receptors and\u00a0sudden infant death \nsyndrome (SIDS)\nCynthia\u00a0Chang1\u00a0\u00b7 Arunnjah\u00a0Vivekanandarajah2\u00a0\u00b7 Karen\u00a0A\u00a0Waters1,3\u00a0\u00b7 Rita\u00a0Machaalani1,3 \nReceived: 15 June 2022 / Accepted: 28 March 2023 / Published online: 11 April 2023 \n\u00a9 The Author(s) 2023\nAbstract\nThe role of the lateral geniculate nucleus (LGN) in vision has been extensively studied, yet its extraretinal capacities are \nstill being investigated, including its role in arousal from sleep. The \u03b22 nicotinic acetylcholine receptor (nAChR) subunit is \ninvolved in the laminal organisation of the LGN with magnocellular (MC) and parvocellular (PC) neurons. Sudden infant death \nsyndrome (SIDS) occurs during a sleep period and, neuropathologically, is associated with increased neuronal cell death and \naltered nAChRs. A recent qualitative pilot study from our group implicates the possibility of increased neuronal death/apop-\ntosis in the SIDS LGN. The present study used quantitative analysis to report the baseline expression of apoptotic and nAChR \nsubunits \u03b17 and \u03b22 in the PC and MC layers of the LGN, to determine correlations amongst these markers within layers and \nacross layers, and to evaluate changes in the expression of these markers in the LGN of SIDS infants, along with associations \nwith SIDS risk factors, such as age, sex, cigarette smoke exposure, bed-sharing, and presence of an upper respiratory tract \ninfection (URTI). Tissue was immunohistochemically stained for cell death markers of active caspase-3 (Casp-3) and TUNEL, \nand for the \u03b17 and \u03b22 nAChR subunits. Amongst 43 cases of sudden and unexpected deaths in infancy (SUDI), classifications \nincluded explained deaths (eSUDI, n = 9), SIDS I (n = 5) and SIDS II (n = 29). Results indicated a strong correlation of the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 395
encoding: FLOAT32
metadata:
{"title": "Cell death in the lateral geniculate nucleus, and its possible relationship with nicotinic receptors and sudden infant death syndrome \\(SIDS\\", "chroma:document": "apoptotic markers and \u03b22 nAChR subunit between the LGN layers, but not across the markers within the layers. Amongst the \ndiagnostic groups, compared to eSUDI, the SIDS II cases had decreased Casp-3 expression while \u03b22 nAChR expression was \nincreased in both PC and MC layers. Amongst the SIDS risk factors, URTI and bed-sharing were associated with changes in \nneuronal death but not in the \u03b17 and \u03b22 markers. In conclusion, our findings do not support a role for the \u03b17 and \u03b22 nAChRs in \napoptotic regulation of the LGN layers during infancy. However, for SIDS victims, an inverse correlation between the changes \nfor markers of apoptosis and the \u03b22 nAChR subunit expression suggests altered LGN function.\nKeywords Apoptosis\u00a0\u00b7 Acetylcholine\u00a0\u00b7 Cholinergic\u00a0\u00b7 LGN\u00a0\u00b7 SUDI\u00a0\u00b7 Sleep\nAbbreviations\nACh \n Acetylcholine\nCasp-3 \n Caspase 3\nLC \n Locus coeruleus\nLGN  \n Lateral Geniculate Nucleus\nLSD \n Least Significant Difference\nMC \n Magnocellular\nnAChR \n Nicotinic acetylcholine receptor\nPC \n Parvocellular\nSEM \n Standard Error of the Mean\nSIDS \n Sudden Infant Death Syndrome\nSUDI \n Sudden Unexpected Death in Infancy\nTUNEL  Terminal Deoxynucleotidyl Transferase (Tdt)-\nMediated dUTP Nick End\nREM \n Rapid Eye Movement sleep\nURTI \n Upper Respiratory Tract Infection\n * Rita Machaalani \n \nrita.machaalani@sydney.edu.au\n1 \nSydney Medical School, Faculty of\u00a0Medicine and\u00a0Health, \nThe University of\u00a0Sydney, Camperdown, NSW\u00a02006, \nAustralia\n2 \nDiscipline of\u00a0Medicine, Central Clinical School, Faculty \nof\u00a0Medicine and\u00a0Health, The University of\u00a0Sydney, \nCamperdown, NSW, Australia\n3 \nDiscipline of\u00a0Child and\u00a0Adolescent Health, Children\u2019s \nHospital at\u00a0Westmead Clinical School, Faculty of\u00a0Medicine \nand\u00a0Health, The University of\u00a0Sydney, Camperdown, NSW, \nAustralia"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 396
encoding: FLOAT32
metadata:
{"title": "Comparison of the Ct-values for genomic and subgenomic SARS-CoV-2 RNA reveals limited predictive value for the presence of replication competent virus", "chroma:document": "Since January 2020 Elsevier has created a COVID-19 resource centre with \nfree information in English and Mandarin on the novel coronavirus COVID-\n19. The COVID-19 resource centre is hosted on Elsevier Connect, the \ncompany's public news and information website. \n \nElsevier hereby grants permission to make all its COVID-19-related \nresearch that is available on the COVID-19 resource centre - including this \nresearch content - immediately available in PubMed Central and other \npublicly funded repositories, such as the WHO COVID database with rights \nfor unrestricted research re-use and analyses in any form or by any means \nwith acknowledgement of the original source. These permissions are \ngranted for free by Elsevier for as long as the COVID-19 resource centre \nremains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 397
encoding: FLOAT32
metadata:
{"title": "Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection", "chroma:document": "Persistence of Immunogenicity of a Purified Inactivated \nZika Virus Vaccine Candidate in Healthy Adults:  \n2 Years of Follow-up Compared With Natural Infection\nCamilo J. Acosta,1 Clemente Diaz,2 Francesco Nordio,1 Htay-Htay Han,1 Kelley J. Moss,1 Kelly Bohning,1 Pradeep Kumar,3 Mengya Liu,1 Hetal Patel,1\nFilippo Pacciarini,1 Vincent Mwangi,1 Elke Walter,3 Tim D. Powell,1 Hana M. El Sahly,4 Whitney R. Baldwin,1 Joseph Santangelo,1 Evan J. Anderson,5,\nand Gary Dubin3\n1Takeda Vaccines Inc, Cambridge, Massachusetts, USA; 2Puerto Rico Clinical and Translational Research Consortium, San Juan, Puerto Rico; 3Takeda Pharmaceuticals International AG, Z\u00fcrich, \nSwitzerland; 4Baylor College of Medicine, Houston, Texas, USA; and 5Emory University School of Medicine, Atlanta, Georgia, USA\nBackground. We report 2-year persistence of immune response to Takeda\u2019s prophylactic purified formalin-inactivated whole \nZika virus vaccine candidate (TAK-426) compared with that observed after natural infection.\nMethods. A randomized, observer-blind, placebo-controlled, dose-selection, phase 1 trial was conducted in 18\u201349-year-old \nadults at 9 centers (7 in the United States, 2 in Puerto Rico) from 13 November 2017 to 24 November 2020. Primary objectives \nwere safety, tolerability, and immunogenicity of 3 increasing doses of TAK-426 administered as 2 doses 28 days apart to \nflavivirus (FV)\u2013naive and FV-primed adults. Here, we report on safety and persistence of immunity up to 2 years after primary \nvaccination with 10-\u03bcg TAK-426, the highest dose, and compare neutralizing antibody responses with those observed after \nnatural infection.\nResults. TAK-426 at 10-\u03bcg had an acceptable safety profile in FV-naive and FV-primed adults up to 24 months after dose 2. \nSeropositivity for neutralizing antibodies was 100% at 1 year, and 93.8% and 76.2% at 2 years in FV-naive and FV-primed \ngroups, respectively. TAK-426 responses were comparable in magnitude and kinetics with those elicited by natural Zika virus \ninfection."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 398
encoding: FLOAT32
metadata:
{"title": "Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection", "chroma:document": "Conclusions. These results support the further clinical development of TAK-426 for both FV-naive and FV-primed \npopulations.\nClinical Trials Registration. NCT03343626\nKeywords. Zika virus; natural infection; neutralizing antibody response; persistence; safety; vaccine.\nReceived 25 August 2022; editorial decision 01 December 2022; accepted 09 December \n2022; published online 9 December 2022\nPresented in part: Eighth Northern European Conference on Travel Medicine, Rotterdam, the \nNetherlands, June 2022 (abstract 4291-A-2209).\nCorrespondence: Camilo J. Acosta, MD, PhD, MSc, Vaccines Clinical Development, Vaccine \nBusiness Unit, Takeda Vaccines, 40 Landsdowne St, Cambridge, MA 02139 (camiloj.acosta@ \ntakeda.com).\nThe Journal of Infectious Diseases\u00ae\n2023;227:1303\u201312 \n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution- \nNonCommercial-NoDerivs \nlicence \n(https://creativecommons.org/licenses/by-nc-nd/4.0/), \nwhich permits non-commercial reproduction and distribution of the work, in any medium, pro-\nvided the original work is not altered or transformed in any way, and that the work is properly \ncited. For commercial re-use, please contact journals.permissions@oup.com\nhttps://doi.org/10.1093/infdis/jiac482\nZika virus (ZIKV) is a mosquito and sexually transmitted flavi-\nvirus (FV) first identified in Uganda in 1947; it has since been \nresponsible for sporadic outbreaks of self-limited illness in \nAfrica, Asia, and French Polynesia [1\u20134]. ZIKV spread to \nSouth and Central America, and circulation has occurred in \nother regions, including the United States and Europe [5, 6]. \nThe incidence of ZIKV infections has since declined, but low \nsustained circulation occurs in Thailand [7], India [8], and \nSouth America [9]. Global awareness of ZIKV increased in \n2015 when clusters of Guillain-Barr\u00e9 syndrome in adults and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 399
encoding: FLOAT32
metadata:
{"title": "Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection", "chroma:document": "neurological disorders and congenital anomalies in newborns, \nincluding microcephaly, were temporally associated with a \nlarge ZIKV outbreak in Northeast Brazil [10] that subsequently \nspread to several countries in the Americas [11]. The World \nHealth Organization declared ZIKV a public health emergency \nof international concern in February 2016 [12] and has includ-\ned it as one of the priority diseases listed in its 2018 research \nand development blueprint [13]. Therefore, the threat of dis-\nease caused by ZIKV infection exists not only for human pop-\nulations living in and traveling to currently endemic countries \nbut also for those living in nonendemic countries where trans-\nmission of disease could occur in the future owing to the pres-\nence of the mosquito vector.\nBecause there is no effective therapy, a ZIKV vaccine is an \nimportant unmet medical need both for inhabitants of affected \nregions and for travelers to those countries. Takeda Vaccines is \ndeveloping TAK-426, a purified formalin-inactivated whole \nZIKV vaccine (PIZV) based on a plaque-purified subisolate \nZika Virus Vaccine Candidate After 2 Years \u2022 JID 2023:227 (1 June) \u2022 1303\nThe Journal of Infectious Diseases                                \nM A J O R  A R T I C L E"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 400
encoding: FLOAT32
metadata:
{"title": "Coordinated reset deep brain stimulation of subthalamic nucleus produces long-lasting, dose-dependent motor improvements in the \\\r1- methyl -4- phenyl -1,2,3,6-tetrahydropyridine non-human primate model of parkinsonism", "chroma:document": "Coordinated reset deep brain stimulation of subthalamic nucleus \nproduces long-lasting, dose-dependent motor improvements in \nthe 1- methyl -4- phenyl -1,2,3,6-tetrahydropyridine non-human \nprimate model of parkinsonism\nJing Wanga, Shane Nebeckb, Abirami Muralidharanc, Matthew D. Johnsond, Jerrold L. \nViteke, Kenneth B. Bakerf\naDepartment of Neurology, University of Minnesota, Minneapolis, MN, USA 55455\nbDepartment of Neurology, University of Minnesota, Minneapolis, MN, USA 55455\ncDepartment of Neurology, University of Minnesota, Minneapolis, MN, USA 55455\ndDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA 55455\neDepartment of Neurology, University of Minnesota, Minneapolis, MN, USA 55455\nfDepartment of Neuroscience, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA \n44195\nAbstract\nBackground:\u00a0Novel deep brain stimulation (DBS) paradigms are being explored in an effort to \nfurther optimize therapeutic outcome for patients with Parkinson\u2019s disease (PD). One approach, \ntermed \u2018Coordinated Reset\u2019 (CR) DBS, was developed to target pathological oscillatory network \nactivity; with desynchronizing effects and associated therapeutic benefit hypothesized to endure \nbeyond cessation of stimulus delivery.\nObjective:\u00a0To characterize the acute and carry-over effects of low-intensity CR DBS versus \ntraditional DBS (tDBS) in the region of the subthalamic nucleus (STN).\nMethods:\u00a0A within-subjects, block treatment design involving the 1-methyl-4-phenyl-1,2,3,6-\ntetrahydropyridine (MPTP) non-human primate model of parkinsonism was used. Each treatment \nblock consisted of five days of daily DBS delivery followed by a one week minimum post-\ntreatment observation window. Motor behavior was quantified using a modified rating scale for \nboth animals combined with an objective, upper-extremity reach task in one animal.\nResults:\u00a0Both animals demonstrated significant motor improvements during acute tDBS;"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 401
encoding: FLOAT32
metadata:
{"title": "Coordinated reset deep brain stimulation of subthalamic nucleus produces long-lasting, dose-dependent motor improvements in the \\\r1- methyl -4- phenyl -1,2,3,6-tetrahydropyridine non-human primate model of parkinsonism", "chroma:document": "however within-session and post-treatment carry-over were limited. Acute motor improvements \nalso were observed in response to low-intensity CR DBS, however both within- and between-\nsession therapeutic carry-over enhanced progressively following each daily treatment. Moreover, \nCorresponding Author: Kenneth B. Baker, Department of Neurology, University of Minnesota, 2873H, 2001 6th St SE, Minneapolis, \nMN 55455, phone: 612-626-8065, fax: 612-626-5685, bakerk6@ccf.org.\nAuthor Contributions:\nKBB, JLV and MDJ conceived and designed the experiments. JW, SN, AM, and KBB acquired and analyzed the data. All authors \nwere involved in drafting the article and have approved the final version for submission.\nHHS Public Access\nAuthor manuscript\nBrain Stimul. Author manuscript; available in PMC 2023 May 29.\nPublished in final edited form as:\nBrain Stimul. 2016 ; 9(4): 609\u2013617. doi:10.1016/j.brs.2016.03.014.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 402
encoding: FLOAT32
metadata:
{"title": "Characterization of the expression of gastrin-releasing peptide and its receptor in the trigeminal and spinal somatosensory syst\\\rems of Japanese macaque monkeys: Insight into humans", "chroma:document": "Characterization of the expression of gastrin-releasing peptide \nand its receptor in the trigeminal and spinal somatosensory \nsystems of Japanese macaque monkeys: Insight into humans\nKeiko Takanami1,2,3,4, Takumi Oti1,5, Yasuhisa Kobayashi1,6, Koki Hasegawa7,8, Takashi \nIto1, Naoaki Tsutsui1,9, Yasumasa Ueda10,11, Earl Carstens4, Tatsuya Sakamoto1, Hirotaka \nSakamoto1\n1Ushimado Marine Institute (UMI), Okayama University, Okayama, Japan\n2Department of Genetics, Mouse Genomics Resources Laboratory, National Institute of Genetics, \nSokendai (The Graduate University for Advanced Studies), Shizuoka, Japan\n3Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, \nJapan\n4Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California, \nUSA\n5Department of Biological Sciences, Faculty of Science, Kanagawa University, Kanagawa, Japan\n6Department of Aquatic Biology, Fisheries, Faculty of Agriculture, Kindai University, Nara, Japan\n7Center for Instrumental Analysis, Kyoto Pharmaceutical University, Kyoto, Japan\n8Theranostic Pharmaceuticals Laboratory, Department of Radiological Sciences, School of Health \nSciences, Fukushima Medical University, Fukushima, Japan\n9Department of Marine Bioresources, Mie University, Mie, Japan\n10Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan\n11Department of Physiology, Kansai Medical University, Osaka, Japan\nAbstract\nGastrin-releasing peptide (GRP) and its receptor (GRPR) have been identified as itch mediators \nin the spinal and trigeminal somatosensory systems in rodents. In primates, there are few reports \nof GRP/GRPR expression or function in the spinal sensory system and virtually nothing is known \nThis is an open access article under the terms of the Creative Commons Attribution-Noncommercial License, which permits use, \ndistribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 403
encoding: FLOAT32
metadata:
{"title": "Characterization of the expression of gastrin-releasing peptide and its receptor in the trigeminal and spinal somatosensory syst\\\rems of Japanese macaque monkeys: Insight into humans", "chroma:document": "Correspondence: Keiko Takanami, Present address: Department of Environmental Health, Faculty of Human Life and Environmental \nSciences, Nara Women\u2019s University, Nara, Japan. takanami@cc.nara-wu.ac.jp.\nAUTHORS CONTRIBUTION\nK.T. and H.S. designed research. K.T., T.O., Y.K., K.H., T.I., N.T., Y.U., and H.S. performed research. K.H., T.S., and H.S. contributed \nnew reagents or analytic tools. K.T., T.O., Y.K., K.H., T.I., N.T., Y.U., E.C., T.S., and H.S. analyzed data. K.T. wrote the article with \nassistance from K.H., E.C., T.S., and H.S. The whole study was supervised by K.T. All authors discussed the results and commented \non the manuscript.\nCONFLICT OF INTEREST\nThe authors declare no conflict of interest.\nHHS Public Access\nAuthor manuscript\nJ Comp Neurol. Author manuscript; available in PMC 2023 May 30.\nPublished in final edited form as:\nJ Comp Neurol. 2022 November ; 530(16): 2804\u20132819. doi:10.1002/cne.25376.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 404
encoding: FLOAT32
metadata:
{"title": "Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins", "chroma:document": "RESEARCH ARTICLE\nPathogenicity, tissue tropism and potential\nvertical transmission of SARSr-CoV-2 in\nMalayan pangolins\nXianghui Liang1\u262f, Xiaoyuan Chen1\u262f, Junqiong Zhai2\u262f, Xiaobing Li1,3\u262f, Xu Zhang1\u262f,\nZhipeng Zhang1, Ping Zhang1, Xiao Wang1, Xinyuan Cui1, Hai Wang1, Niu Zhou2, Zu-\nJin Chen2, Renwei Su1, Fuqing Zhou4, Edward C. Holmes5, David M. Irwin6,7, Rui-\nAi Chen1,8, Qian He1, Ya-Jiang Wu2, Chen Wang2, Xue-Qing Du2, Shi-Ming Peng2, Wei-\nJun Xie2, Fen Shan2, Wan-Ping Li2, Jun-Wei Dai2, Xuejuan Shen1, Yaoyu Feng1,\nLihua Xiao1, Wu Chen2*, Yongyi ShenID1,9*\n1 State Key Laboratory for Animal Disease Control and Prevention, Guangdong Laboratory for Lingnan\nModern Agriculture, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South\nChina Agricultural University, Guangzhou, China, 2 Guangzhou Zoo & Guangzhou Wildlife Research Center,\nGuangzhou, China, 3 College of Life Sciences, Longyan University, Longyan, China, 4 Department of\nRadiology, the First Affiliated Hospital, Nanchang University, Nanchang, China, 5 Sydney Institute for\nInfectious Diseases, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia,\n6 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, 7 Banting\nand Best Diabetes Centre, University of Toronto, Toronto, Canada, 8 Zhaoqing Branch Center of Guangdong\nLaboratory for Lingnan Modern Agricultural Science and Technology, Zhaoqing, China, 9 Guangdong\nProvincial Key Laboratory of Zoonosis Prevention and Control, Guangzhou, China\n\u262f These authors contributed equally to this work.\n* guangzhouchenwu@sina.com (WC); shenyy@scau.edu.cn (YS)\nAbstract\nMalayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to\nSARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans\nwe show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral\nground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 405
encoding: FLOAT32
metadata:
{"title": "Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins", "chroma:document": "examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple\norgans in pangolins, with the lungs the major target, and histological expression data\nrevealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome anal-\nysis indicated that virus-positive pangolins were likely to have inadequate interferon\nresponses, with relative greater cytokine and chemokine activity in the lung and spleen.\nNotably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing\ninitial evidence for vertical virus transmission. In sum, our study outlines the biological\nframework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in\nhumans.\nAuthor summary\nSARS-CoV-2 has caused a severe and ongoing global pandemic. To date, bats and pango-\nlins are the only groups of mammals known carry SARS-CoV-2-related coronaviruses\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011384\nMay 17, 2023\n1 / 14\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Liang X, Chen X, Zhai J, Li X, Zhang X,\nZhang Z, et al. (2023) Pathogenicity, tissue tropism\nand potential vertical transmission of SARSr-CoV-2\nin Malayan pangolins. PLoS Pathog 19(5):\ne1011384. https://doi.org/10.1371/journal.\nppat.1011384\nEditor: Vineet D. Menachery, University of Texas\nMedical Branch at Galveston, UNITED STATES\nReceived: January 9, 2023\nAccepted: April 24, 2023\nPublished: May 17, 2023\nCopyright: \u00a9 2023 Liang et al. This is an open\naccess article distributed under the terms of the\nCreative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: All data are in the\nmanuscript and supporting information files.\nSequence reads generated in this study are\navailable from the NCBI Sequence Read Archive\n(SRA) database under BioProject accession\nnumber PRJNA939083.\nFunding: YS is funded by the Guangdong"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 406
encoding: FLOAT32
metadata:
{"title": "Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins", "chroma:document": "Provincial Key R&D Program (2022B1111040001),\nBasic and Applied Basic Research Foundation of\nGuangdong Province (2020B0301030007),\nLaboratory of Lingnan Modern Agriculture Project"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 407
encoding: FLOAT32
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{"title": "In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury", "chroma:document": "RESEARCH ARTICLE\nIn vitro evidence against productive SARS-\nCoV-2 infection of human testicular cells:\nBystander effects of infection mediate\ntesticular injury\nStefanos Giannakopoulos1, Daniel P. Strange2, Boonyanudh Jiyarom2, Omar Abdelaal3,4,\nAaron W. Bradshaw3,5, Vivek R. Nerurkar2, Monika A. Ward6, Jackson Bakse6,\nJonathan Yap7, Selena Vanapruks7, William A. Boisvert7, Michelle D. Tallquist7,\nCecilia Shikuma2, Hooman Sadri-Ardekani3,5, Philip Clapp3, Sean V. Murphy3,\nSaguna VermaID1,2*\n1 Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at\nManoa, Honolulu, Hawaii, United States of America, 2 Department of Tropical Medicine, Medical\nMicrobiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa,\nHonolulu, Hawaii, United States of America, 3 Wake Forest Institute for Regenerative Medicine, Wake Forest\nSchool of Medicine, Winston-Salem, North Carolina, United States of America, 4 Department of Urology,\nFaculty of Medicine, Zagazig University, Egypt, 5 Department of Urology, Wake Forest School of Medicine,\nWinston-Salem, North Carolina, 6 Institute for Biogenesis Research, John A Burns School of Medicine,\nUniversity of Hawaii at Manoa, Honolulu, Hawaii, United States of America, 7 Center for Cardiovascular\nResearch, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa,\nHonolulu, Hawaii, United States of America\n* saguna@hawaii.edu\nAbstract\nThe hallmark of severe COVID-19 involves systemic cytokine storm and multi-organ injury\nincluding testicular inflammation, reduced testosterone, and germ cell depletion. The ACE2\nreceptor is also expressed in the resident testicular cells, however, SARS-CoV-2 infection\nand mechanisms of testicular injury are not fully understood. The testicular injury could be\ninitiated by direct virus infection or exposure to systemic inflammatory mediators or viral\nantigens. We characterized SARS-CoV-2 infection in different human testicular 2D and 3D"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 408
encoding: FLOAT32
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{"title": "In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury", "chroma:document": "culture systems including primary Sertoli cells, Leydig cells, mixed seminiferous tubule cells\n(STC), and 3D human testicular organoids (HTO). Data shows that SARS-CoV-2 does not\nproductively infect any testicular cell type. However, exposure of STC and HTO to inflamma-\ntory supernatant from infected airway epithelial cells and COVID-19 plasma decreased cell\nviability and resulted in the death of undifferentiated spermatogonia. Further, exposure to\nonly SARS-CoV-2 Envelope protein caused inflammatory response and cytopathic effects\ndependent on TLR2, while Spike 1 or Nucleocapsid proteins did not. A similar trend was\nobserved in the K18-hACE2 transgenic mice which demonstrated a disrupted tissue archi-\ntecture with no evidence of virus replication in the testis that correlated with peak lung\ninflammation. Virus antigens including Spike 1 and Envelope proteins were also detected in\nthe serum during the acute stage of the disease. Collectively, these data strongly suggest\nthat testicular injury associated with SARS-CoV-2 infection is likely an indirect effect of\nexposure to systemic inflammation and/or SARS-CoV-2 antigens. Data also provide novel\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011409\nMay 18, 2023\n1 / 24\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Giannakopoulos S, Strange DP, Jiyarom\nB, Abdelaal O, Bradshaw AW, Nerurkar VR, et al.\n(2023) In vitro evidence against productive SARS-\nCoV-2 infection of human testicular cells:\nBystander effects of infection mediate testicular\ninjury. PLoS Pathog 19(5): e1011409. https://doi.\norg/10.1371/journal.ppat.1011409\nEditor: Stanley Perlman, University of Iowa,\nUNITED STATES\nReceived: January 6, 2023\nAccepted: May 8, 2023\nPublished: May 18, 2023\nPeer Review History: PLOS recognizes the\nbenefits of transparency in the peer review\nprocess; therefore, we enable the publication of\nall of the content of peer review and author\nresponses alongside final, published articles. The"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 409
encoding: FLOAT32
metadata:
{"title": "In vitro evidence against productive SARS-CoV-2 infection of human testicular cells: Bystander effects of infection mediate testicular injury", "chroma:document": "editorial history of this article is available here:\nhttps://doi.org/10.1371/journal.ppat.1011409\nCopyright: \u00a9 2023 Giannakopoulos et al. This is an\nopen access article distributed under the terms of\nthe Creative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: All relevant data are\nwithin the manuscript and its Supporting\nInformation files."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 410
encoding: FLOAT32
metadata:
{"title": "Neurophysiological mechanisms of error monitoring in human and non-human primates", "chroma:document": "Neurophysiological mechanisms of error monitoring in human \nand non-human primates\nZhongzheng Fu1,2, Amirsaman Sajad3,4,5, Steven P. Errington3,4,5, Jeffrey D. Schall3,5,6,7,8, \nUeli Rutishauser1,9,10\n1Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.\n2Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA, \nUSA.\n3Center for Integrative & Cognitive Neuroscience, Vanderbilt University, Nashville, TN, USA.\n4Vanderbilt Vision Research Center, Vanderbilt University, Nashville, TN, USA.\n5Department of Psychology, Vanderbilt University, Nashville, TN, USA.\n6Centre for Vision Research, York University, Toronto, Ontario, Canada.\n7Vision: Science to Applications (VISTA), York University, Toronto, Ontario, Canada.\n8Department of Biology, Faculty of Science, York University, Toronto, Ontario, Canada.\n9Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, \nUSA.\n10Center for Neural Science and Medicine, Department of Biomedical Sciences, Cedars-Sinai \nMedical Center, Los Angeles, CA, USA.\nAbstract\nPerformance monitoring is an important executive function that allows us to gain insight into \nour own behaviour. This remarkable ability relies on the frontal cortex, and its impairment is an \naspect of many psychiatric diseases. In recent years, recordings from the macaque and human \nmedial frontal cortex have offered a detailed understanding of the neurophysiological substrate \nthat underlies performance monitoring. Here we review the discovery of single-neuron correlates \nof error monitoring, a key aspect of performance monitoring, in both species. These neurons are \nthe generators of the error-related negativity, which is a non-invasive biomarker that indexes error \ndetection. We evaluate a set of tasks that allows the synergistic elucidation of the mechanisms \nof cognitive control across the two species, consider differences in brain anatomy and testing"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 411
encoding: FLOAT32
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{"title": "Neurophysiological mechanisms of error monitoring in human and non-human primates", "chroma:document": "Reprints and permissions information is available at www.nature.com/reprints.\nCorrespondence should be addressed to Zhongzheng Fu, Jeffrey D. Schall or Ueli Rutishauser. zzbrooksfu@gmail.com; \nschalljd@yorku.edu; rutishauseru@csmc.edu.\nAuthor contributions\nThe authors all contributed to all aspects of preparing the article.\nCompeting interests\nThe authors declare no competing interests.\nSupplementary information The online version contains supplementary material available at https://doi.org/10.1038/\ns41583-022-00670-w.\nHHS Public Access\nAuthor manuscript\nNat Rev Neurosci. Author manuscript; available in PMC 2023 September 01.\nPublished in final edited form as:\nNat Rev Neurosci. 2023 March ; 24(3): 153\u2013172. doi:10.1038/s41583-022-00670-w.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 412
encoding: FLOAT32
metadata:
{"title": "Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates", "chroma:document": "https://doi.org/10.1093/brain/awac428\nBRAIN 2023: 146; 2524\u20132534 | 2524\nTau seeds from patients induce progressive \nsupranuclear palsy pathology and symptoms \nin primates\nMorgane Darricau,1 Taxiarchis Katsinelos,2 Flavio Raschella,3,4,5 \nTomislav Milekovic,3,4,5 Louis Crochemore,1 Qin Li,6 \nGr\u00e9goire Courtine,3,4,5 \nWilliam A. McEwan,2 \nBenjamin Dehay,1 \nErwan Bezard1,6,\u2020 and Vincent Planche1,7,\u2020\n\u2020These authors contributed equally to this work.\nProgressive supranuclear palsy is a primary tauopathy affecting both neurons and glia and is responsible for both mo-\ntor and cognitive symptoms. Recently, it has been suggested that progressive supranuclear palsy tauopathy may \nspread in the brain from cell to cell in a \u2018prion-like\u2019 manner. However, direct experimental evidence of this phenom-\nenon, and its consequences on brain functions, is still lacking in primates.\nIn this study, we first derived sarkosyl-insoluble tau fractions from post-mortem brains of patients with progressive \nsupranuclear palsy. We also isolated the same fraction from age-matched control brains. Compared to control extracts, \nthe in vitro characterization of progressive supranuclear palsy-tau fractions demonstrated a high seeding activity in \nP301S-tau expressing cells, displaying after incubation abnormally phosphorylated (AT8- and AT100-positivity), mis-\nfolded, filamentous (pentameric formyl thiophene acetic acid positive) and sarkosyl-insoluble tau. We bilaterally in-\njected two male rhesus macaques in the supranigral area with this fraction of progressive supranuclear palsy-tau \nproteopathic seeds, and two other macaques with the control fraction. The quantitative analysis of kinematic features \nrevealed that progressive supranuclear palsy-tau injected macaques exhibited symptoms suggestive of parkinsonism \nas early as 6 months after injection, remaining present until euthanasia at 18 months. An object retrieval task showed \nthe progressive appearance of a significant dysexecutive syndrome in progressive supranuclear palsy-tau injected ma-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 413
encoding: FLOAT32
metadata:
{"title": "Tau seeds from patients induce progressive supranuclear palsy pathology and symptoms in primates", "chroma:document": "caques compared to controls. We found AT8-positive staining and 4R-tau inclusions only in progressive supranuclear \npalsy-tau injected macaques. Characteristic pathological hallmarks of progressive supranuclear palsy, including glo-\nbose and neurofibrillary tangles, tufted astrocytes and coiled bodies, were found close to the injection sites but also \nin connected brain regions that are known to be affected in progressive supranuclear palsy (striatum, pallidum, thal-\namus). Interestingly, while glial AT8-positive lesions were the most frequent near the injection site, we found mainly \nneuronal inclusions in the remote brain area, consistent with a neuronal transsynaptic spreading of the disease.\nOur results demonstrate that progressive supranuclear palsy patient-derived tau aggregates can induce motor and \nbehavioural impairments in non-human primates related to the prion-like seeding and spreading of typical pathologic-\nal progressive supranuclear palsy lesions. This pilot study paves the way for supporting progressive supranuclear palsy- \ntau injected macaque as a relevant animal model to accelerate drug development targeting this rare and fatal neurode-\ngenerative disease.\n1\nUniversity of Bordeaux, CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, UMR 5293, F-33000 Bordeaux, France\n2\nUK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge, CB2 0AH \nCambridge, UK\n3\nSwiss Federal Institute of Technology (EPFL), CH-1011 Lausanne, Switzerland\n4\nDefitech Center for Interventional Neurotherapies (NeuroRestore), CH-1011 Lausanne, Switzerland\nReceived August 27, 2022. Revised October 26, 2022. Accepted November 04, 2022. Advance access publication November 16, 2022\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: \njournals.permissions@oup.com"}


