# embeddings_queue

created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 414
encoding: FLOAT32
metadata:
{"title": "Fatty acid amides as potential circulating biomarkers for sarcopenia", "chroma:document": "Fatty acid amides as potential circulating biomarkers\nfor sarcopenia\nYe An Kim1\u2020, Seung Hun Lee2\u2020, Jung-Min Koh2, Seung-hyun Kwon3, Young Lee3, Han Jin Cho4, Hanjun Kim4, Su Jung Kim5,\nJi Hyun Lee1, Hyun Ju Yoo5*\u2020 & Je Hyun Seo3*\u2020\n1Division of Endocrinology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, South Korea; 2Division of Endocrinology and Metabolism, Asan\nMedical Center, University of Ulsan College of Medicine, Seoul, South Korea; 3Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, South\nKorea; 4Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea; 5Department of Convergence Medicine, Asan Institute for Life\nSciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea\nAbstract\nBackground\nSarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age.\nGiven that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detec-\ntion are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform\nexperimental studies using metabolomics.\nMethods\nPlasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control\ngroup, were measured using global metabolome pro\ufb01ling. Muscle and plasma samples from an aging mouse model\nof sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted\nmetabolome pro\ufb01ling. Based on these experimental results, fatty acid amides were quanti\ufb01ed from human plasma as\nwell as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated.\nResults\nGlobal metabolome pro\ufb01ling showed that fatty acid amide levels were signi\ufb01cantly different in the plasma of\nelderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome pro-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 415
encoding: FLOAT32
metadata:
{"title": "Fatty acid amides as potential circulating biomarkers for sarcopenia", "chroma:document": "\ufb01ling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle\ntissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted\nmetabolome pro\ufb01ling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma\n(P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia pa-\nrameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively).\nThe area under the receiver-operating characteristic curve (AUC) for DHA EA level \u2264 4.60 fmol/\u03bcL for sarcopenia was\n0.618 (95% con\ufb01dence interval [CI]: 0.532\u20130.698). DHA EA level \u2264 4.60 fmol/\u03bcL was associated with a signi\ufb01cantly\ngreater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03\u20134.30), independent of HGS. The addition of\nDHA EA level to age and HGS signi\ufb01cantly improved the AUC from 0.620 to 0.691 (P = 0.0497).\nConclusions\nOur study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with\nsarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become\na reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the\nmetabolomic changes relevant to sarcopenia from an aging perspective.\nKeywords\nAging; Metabolomics; Sarcopenia; Biomarkers; Fatty acid amides\nReceived: 31 October 2022; Revised: 14 February 2023; Accepted: 3 April 2023\n*Correspondence to: Je Hyun Seo, Veterans Medical Research Institute, Veterans Health Service Medical Center, Jinhwangdo-ro 61-gil 53, Gangdong-gu, Seoul 05368, South\nKorea. Email: jazmin2@naver.com;\nHyun Ju Yoo, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Email:\nyoohyunju@amc.seoul.kr\n\u2020These authors contributed equally to this work.\nORIGINAL ARTICLE"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 416
encoding: FLOAT32
metadata:
{"title": "Fatty acid amides as potential circulating biomarkers for sarcopenia", "chroma:document": "\u00a9 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,\nprovided the original work is properly cited, the use is non-commercial and no modi\ufb01cations or adaptations are made.\nJournal of Cachexia, Sarcopenia and Muscle 2023; 14: 1558\u20131568\nPublished online 1 May 2023 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/jcsm.13244"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 417
encoding: FLOAT32
metadata:
{"title": "Stress-Induced Biological Aging: A Review and Guide for Research Priorities", "chroma:document": "Stress-Induced Biological Aging: A Review and Guide for \nResearch Priorities\nLilian R. Polsky1,\u2020, Kelly E. Rentscher, Ph.D.1,2,\u2020,*, Judith E. Carroll1\n1Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience & Human \nBehavior, University of California, Los Angeles\n2Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin\nAbstract\nExposure to chronic adverse conditions, and the resultant activation of the neurobiological \nresponse cascade, has been associated with an increased risk of early onset of age-related disease \nand, recently, with an older biological age. This body of research has led to the hypothesis that \nexposure to stressful life experiences, when occurring repeatedly or over a prolonged period, may \naccelerate the rate at which the body ages. The mechanisms through which chronic psychosocial \nstress influences distinct biological aging pathways to alter rates of aging likely involve multiple \nlayers in the physiological-molecular network. In this review, we integrate research using animal, \nhuman, and in vitro models to begin to delineate the distinct pathways through which chronic \npsychosocial stress may impact biological aging, as well as the neuroendocrine mediators (i.e., \nnorepinephrine, epinephrine, and glucocorticoids) that may drive these effects. Findings highlight \nkey connections between stress and aging, namely cellular metabolic activity, DNA damage, \ntelomere length, cellular senescence, and inflammatory response patterns. We conclude with a \nguiding framework and conceptual model that outlines the most promising biological pathways \nby which chronic adverse conditions could accelerate aging and point to key missing gaps in \nknowledge where future research could best answer these pressing questions.\nKeywords\npsychosocial stress; biological aging; cellular senescence; telomere length; DNA damage; \ninflammation\n*Corresponding author: Kelly E. Rentscher, Ph.D., Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 418
encoding: FLOAT32
metadata:
{"title": "Stress-Induced Biological Aging: A Review and Guide for Research Priorities", "chroma:document": "Clinical Cancer Center, 1000 N. 92nd St., Milwaukee, WI 53226, Phone: 414-955-4097, krentscher@mcw.edu.\n\u2020Co-first authorship\nAuthor Contributions\nAll authors made substantial contributions to and approved the final version of this manuscript. The manuscript was conceptualized, \ndrafted, and revised critically for intellectual content by L.R.P., K.E.R., and J.E.C.\nDeclarations of Interest\nNone\nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review \nof the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered \nwhich could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nBrain Behav Immun. Author manuscript; available in PMC 2023 October 23.\nPublished in final edited form as:\nBrain Behav Immun. 2022 August ; 104: 97\u2013109. doi:10.1016/j.bbi.2022.05.016.\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: 419
encoding: FLOAT32
metadata:
{"title": "The blue-light-hazard vs. blue-light-hype", "chroma:document": "The blue-light-hazard vs. blue-light-hype\nMartin A. Mainster, PhD, MD, FRCOphth1, Oliver Findl, MD, MBA, FEBO2, H. Burkhard Dick, \nMD, PhD3, Thomas Desmettre, MD, PhD4, Gerardo Ledesma-Gil, MD, FICO5, Christine A. \nCurcio, PhD, FARVO6, Patricia L. Turner, MD1\n1Department of Ophthalmology, University of Kansas School of Medicine, Prairie Village, Kansas, \nUSA\n2Vienna Institute for Research in Ocular Surgery, A Karl Landsteiner Institute, Hanusch Hospital, \nVienna, Austria\n3Department of Ophthalmology, Ruhr University Eye Hospital, Science, Bochum, Germany\n4Centre de Retine Medicale, Marquette-Lez-Lille, France\n5Retina Department, Institute of Ophthalmology, Fundaci\u00f3n Conde de Valenciana, Mexico City, \nMexico\n6Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, \nBirmingham, Alabama, USA\nAbstract\nPURPOSE:\u00a0The blue-light-hazard is the experimental finding that blue light is highly toxic \nto the retina (photic retinopathy), in brief abnormally intense exposures, including sungazing \nor vitreoretinal endoillumination. This term has been misused commercially to suggest, falsely, \nthat ambient environmental light exposure causes phototoxicity to the retina, leading to age-\nrelated macular degeneration (AMD). We analyze clinical, epidemiological and biophysical data \nregarding blue-filtering optical chromophores.\nDESIGN:\u00a0Multi-institutional perspective.\nMETHODS:\u00a0Analysis and integration of data regarding the blue-light-hazard and blue-blocking \nfilters in ophthalmology and related disciplines.\nRESULTS:\u00a0Large epidemiological studies show that blue-blocking intraocular lenses (IOLs) do \nnot decrease AMD risk or progression. Blue-filtering lenses cannot reduce disability glare because \nimage and glare illumination are decreased in the same proportion. Blue light essential for optimal \nrod and retinal ganglion photoreception is decreased by progressive age-related crystalline lens \nyellowing, pupillary miosis and rod and retinal ganglion photoreceptor degeneration. Healthful"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 420
encoding: FLOAT32
metadata:
{"title": "The blue-light-hazard vs. blue-light-hype", "chroma:document": "daily environmental blue light exposure decreases in older adults, especially women. Blue light is \nimportant in dim environments where inadequate illumination increases risk of falls and associated \nmorbidities.\nCorresponding author: Martin A. Mainster, PhD, MD, FRCOphth, Department of Ophthalmology, University of Kansas School of \nMedicine, 7400 State Line Road, Prairie Village, Kansas, 66208-3444, USA, mmainste@kumc.edu (no \u201cr\u201d in \u201cmmainste\u201d). \nHHS Public Access\nAuthor manuscript\nAm J Ophthalmol. Author manuscript; available in PMC 2023 June 06.\nPublished in final edited form as:\nAm J Ophthalmol. 2022 August ; 240: 51\u201357. doi:10.1016/j.ajo.2022.02.016.\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: 421
encoding: FLOAT32
metadata:
{"title": "Coccidioides undetected in soils from agricultural land and uncorrelated with time or the greater soil fungal community on undeveloped land", "chroma:document": "RESEARCH ARTICLE\nCoccidioides undetected in soils from\nagricultural land and uncorrelated with time\nor the greater soil fungal community on\nundeveloped land\nRobert WagnerID1*, Liliam Montoya1, Jennifer R. Head2, Simon Campo3, Justin Remais3,\nJohn W. Taylor1\n1 Department of Plant & Microbial Biology, University of California Berkeley, Berkeley, California, United\nStates of America, 2 Division of Epidemiology, University of California Berkeley, Berkeley, California, United\nStates of America, 3 Division of Environmental Health Sciences, University of California Berkeley, Berkeley,\nCalifornia, United States of America\n* robwagner@berkeley.edu\nAbstract\nCoccidioidomycosis is a typically respiratory fungal disease that, in the United States,\noccurs primarily in Arizona and California. In California, most coccidioidomycosis cases\noccur in the San Joaquin Valley, a primarily agricultural region where the disease poses a\nrisk for outdoor workers. We collected 710 soil samples and 265 settled dust samples from\nnine sites in the San Joaquin Valley and examined how Coccidioides detection varied by\nmonth, site, and the presence and abundance of other fungal species. We detected Cocci-\ndioides in 89 of 238 (37.4%) rodent burrow soil samples at five undeveloped sites and were\nunable to detect Coccidioides in any of 472 surface and subsurface soil samples at four agri-\ncultural sites. In what is the largest sampling effort undertaken on agricultural land, our\nresults provide no evidence that agricultural soils in the San Joaquin Valley harbor Cocci-\ndioides. We found no clear association between Coccidioides and the greater soil fungal\ncommunity, but we identified 19 fungal indicator species that were significantly associated\nwith Coccidioides detection in burrows. We also did not find a seasonal pattern in Cocci-\ndioides detection in the rodent burrow soils we sampled. These findings suggest both the\npresence of a spore bank and that coccidioidomycosis incidence may be more strongly"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 422
encoding: FLOAT32
metadata:
{"title": "Coccidioides undetected in soils from agricultural land and uncorrelated with time or the greater soil fungal community on undeveloped land", "chroma:document": "associated with Coccidioides dispersal than Coccidioides growth. Finally, we were able to\ndetect Coccidioides in only five of our 265 near-surface settled dust samples, one from agri-\ncultural land, where Coccidioides was undetected in soils, and four from undeveloped land,\nwhere Coccidioides was common in the rodent burrow soils we sampled. Our ability to\ndetect Coccidioides in few settled dust samples indicates that improved methods are likely\nneeded moving forward, though raises questions regarding aerial dispersal in Coccidioides,\nwhose key transmission event likely occurs over short distances in rodent burrows from soil\nto na\u00efve rodent lungs.\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011391\nMay 25, 2023\n1 / 29\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Wagner R, Montoya L, Head JR, Campo\nS, Remais J, Taylor JW (2023) Coccidioides\nundetected in soils from agricultural land and\nuncorrelated with time or the greater soil fungal\ncommunity on undeveloped land. PLoS Pathog\n19(5): e1011391. https://doi.org/10.1371/journal.\nppat.1011391\nEditor: Eva H. Stukenbrock, Max-Planck-Institut fur\nEvolutionsbiologie, GERMANY\nReceived: December 10, 2022\nAccepted: April 27, 2023\nPublished: May 25, 2023\nCopyright: \u00a9 2023 Wagner 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 supporting\nthe findings of this study have been deposited in\npublically available online repositories. All qPCR\ndata, environmental data and metadata have been\ndeposited in the Dryad repository (www.datadryad.\norg): https://doi.org/10.5061/dryad.p8cz8w9vx. All\nDNA sequencing data have been deposited in the\nNCBI Sequence Read Archive (www.ncbi.nlm.nih.\ngov/sra) with the following accession numbers:\nPRJNA736519, PRJNA736167 and PRJNA736543."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 423
encoding: FLOAT32
metadata:
{"title": "The association between air pollution and the severity at diagnosis and progression of systemic sclerosis-associated interstitial lung disease: results from the retrospective ScleroPol study", "chroma:document": "Roeser\u00a0et\u00a0al. Respiratory Research          (2023) 24:151  \nhttps://doi.org/10.1186/s12931-023-02463-w\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.\nRespiratory Research\nThe association between\u00a0air pollution \nand\u00a0the\u00a0severity at\u00a0diagnosis and\u00a0progression \nof\u00a0systemic sclerosis-associated interstitial lung \ndisease: results from\u00a0the\u00a0retrospective ScleroPol \nstudy\nAna\u00efs Roeser1, Lucile Sese1,9\u2020, Guillaume Chassagnon2\u2020, Benjamin Chaigne3\u2020, Bertrand Dunogue3, \nSt\u00e9phane Tran Ba4, Salma Jebri4, Pierre\u2011Yves Brillet4, Marie Pierre Revel2, Fr\u00e9d\u00e9rique Aubourg5, Robin Dhote6, \nFr\u00e9d\u00e9ric Caux7, Isabella Annesi\u2011Maesano8\u2020, Luc Mouthon3\u2020, Hilario Nunes1,9\u2020 and Yurdag\u00fcl Uzunhan1,9*\u2020 \nAbstract \nObjective To investigate the association of air pollution exposure with the severity of interstitial lung disease (ILD) at \ndiagnosis and ILD progression among patients with systemic sclerosis (SSc)\u2011associated ILD."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 424
encoding: FLOAT32
metadata:
{"title": "The association between air pollution and the severity at diagnosis and progression of systemic sclerosis-associated interstitial lung disease: results from the retrospective ScleroPol study", "chroma:document": "Methods We conducted a retrospective two\u2011center study of patients with SSc\u2011associated ILD diagnosed between \n2006 and 2019. Exposure to the air pollutants particulate matter of up to 10 and 2.5 \u00b5m in diameter  (PM10,  PM2.5), \nnitrogen dioxide  (NO2), and ozone  (O3) was assessed at the geolocalization coordinates of the patients\u2019 residential \naddress. Logistic regression models were used to evaluate the association between air pollution and severity at diag\u2011\nnosis according to the Goh staging algorithm, and progression at 12 and 24 months.\nResults We included 181 patients, 80% of whom were women; 44% had diffuse cutaneous scleroderma, and 56% \nhad anti\u2011topoisomerase I antibodies. ILD was extensive, according to the Goh staging algorithm, in 29% of patients. \n O3 exposure was associated with the presence of extensive ILD at diagnosis (adjusted OR: 1.12, 95% CI 1.05\u20131.21; p \nvalue = 0.002). At 12 and 24 months, progression was noted in 27/105 (26%) and 48/113 (43%) patients, respectively. \n O3 exposure was associated with progression at 24 months (adjusted OR: 1.10, 95% CI 1.02\u20131.19; p value = 0.02). We \nfound no association between exposure to other air pollutants and severity at diagnosis and progression.\nConclusion Our findings suggest that high levels of  O3 exposure are associated with more severe SSc\u2011associated ILD \nat diagnosis, and progression at 24 months.\n\u2020Lucile Sese, Guillaume Chassagnon and Benjamin Chaigne contributed \nequally to this work.\n\u2020Isabella Annesi\u2011Maesano, Luc Mouthon, Hilario Nunes and Yurdag\u00fcl \nUzunhan contributed equally to this work.\n*Correspondence:\nYurdag\u00fcl Uzunhan\nyurdagul.uzunhan@aphp.fr\nFull list of author information is available at the end of the article"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 425
encoding: FLOAT32
metadata:
{"title": "Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes", "chroma:document": "Shorey\u2011Kendrick\u00a0et\u00a0al. Clinical Epigenetics          (2023) 15:104  \nhttps://doi.org/10.1186/s13148\u2011023\u201101519\u20114\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.\nClinical Epigenetics\nPrenatal delta\u20119\u2011tetrahydrocannabinol \nexposure is\u00a0associated with\u00a0changes in\u00a0rhesus \nmacaque DNA methylation enriched for\u00a0autism \ngenes\nLyndsey E. Shorey\u2011Kendrick1*, Victoria H. J. Roberts2, Rahul J. D\u2019Mello3, Elinor L. Sullivan1,4,5, Susan K. Murphy6, \nOwen J. T. Mccarty7, Danny J. Schust6, Jason C. Hedges2,8, A. J. Mitchell1, Jose Juanito D. Terrobias2, \nCharles A. Easley IV9, Eliot R. Spindel1 and Jamie O. Lo2,3 \nAbstract \nBackground With the growing availability of cannabis and the popularization of additional routes of cannabis use \nbeyond smoking, including edibles, the prevalence of cannabis use in pregnancy is rapidly increasing. However, the \npotential effects of prenatal cannabis use on fetal developmental programming remain unknown."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 426
encoding: FLOAT32
metadata:
{"title": "Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes", "chroma:document": "Results We designed this study to determine whether the use of edible cannabis during pregnancy is deleterious \nto the fetal and placental epigenome. Pregnant rhesus macaques consumed a daily edible containing either delta\u2011\n9\u2011tetrahydrocannabinol (THC) (2.5 mg/7 kg/day) or placebo. DNA methylation was measured in 5 tissues collected \nat cesarean delivery (placenta, lung, cerebellum, prefrontal cortex, and right ventricle of the heart) using the Illumina \nMethylationEPIC platform and filtering for probes previously validated in rhesus macaque. In utero exposure to THC \nwas associated with differential methylation at 581 CpGs, with 573 (98%) identified in placenta. Loci differentially \nmethylated with THC were enriched for candidate autism spectrum disorder (ASD) genes from the Simons Founda\u2011\ntion Autism Research Initiative (SFARI) database in all tissues. The placenta demonstrated greatest SFARI gene enrich\u2011\nment, including genes differentially methylated in placentas from a prospective ASD study.\nConclusions Overall, our findings reveal that prenatal THC exposure alters placental and fetal DNA methylation at \ngenes involved in neurobehavioral development that may influence longer\u2011term offspring outcomes. The data from \nthis study add to the limited existing literature to help guide patient counseling and public health polices focused on \nprenatal cannabis use in the future.\nKeywords Delta\u20119\u2011tetrahydrocannabinol (THC), Cannabis, Marijuana, DNA methylation, Prenatal substance use\n*Correspondence:\nLyndsey E. Shorey\u2011Kendrick\nshorey@ohsu.edu\nFull list of author information is available at the end of the article"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 427
encoding: FLOAT32
metadata:
{"title": "Non-small cell lung cancers \\(NSCLCs\\) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors", "chroma:document": "ARTICLE\nOPEN\nNon-small cell lung cancers (NSCLCs) oncolysis using\ncoxsackievirus B5 and synergistic DNA-damage response\ninhibitors\nBopei Cui1,2, Lifang Song1,2, Qian Wang1, Kelei Li1,3, Qian He1, Xing Wu1, Fan Gao1, Mingchen Liu1, Chaoqiang An1,3, Qiushuang Gao1,\nChaoying Hu1, Xiaotian Hao1, Fangyu Dong1,4, Jiuyue Zhou4, Dong Liu1,5, Ziyang Song1,6, Xujia Yan1,5, Jialu Zhang1, Yu Bai1,\nQunying Mao1\u2709, Xiaoming Yang\n2,7\u2709 and Zhenglun Liang1\u2709\nWith the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising\ntool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy.\nHuman enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of\nsome enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/\nFaulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing\napoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated\nprotein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection\ntriggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded\nDNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting\nexacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and\ninhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by\nERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 428
encoding: FLOAT32
metadata:
{"title": "Non-small cell lung cancers \\(NSCLCs\\) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors", "chroma:document": "Conclusively, our study identi\ufb01es an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a\npotential therapy for NSCLCs.\nSignal Transduction and Targeted Therapy  (2023) 8:366 \n; https://doi.org/10.1038/s41392-023-01603-4\nINTRODUCTION\nThe disability-adjusted life years of tumors were approximately\n105 million years globally in 2019.1 Currently, immunotherapy is a\nhot spot for tumor treatment because of its targeting and security,\nincluding\nchimeric\nantigen\nreceptor\nT-cell\nimmunotherapy,\nimmune checkpoint blockade, and oncolytic virus (OV).2 OVs are\nnatural or genetically-modi\ufb01ed viruses that can only recognize\nand lyse tumor cells, but cannot mire normal cells.3 For instance,\nT-vec was constructed to treat melanoma and was approved by\nthe FDA in 2015.4 Moreover, many types of OVs, including DNA\nand RNA viruses, are in the research stage.5\nThe targeting and potency of an OV depend on many aspects.\nOn the one hand, it relies on the expression of speci\ufb01c receptors\non tumors but not on normal cells. However, signaling pathways\ncan assist or compromise this effect. Furthermore, neutralizing\nantibody levels at baseline or primed by OV causes concerns of a\nlimited \u201cone shot\u201d approach.6,7 Therefore, OV is required to be low\nseroprevalent and its de\ufb01nite receptor and oncolytic mechanism\nshould be determined.\nRecently, oncolytic enteroviruses have been reported to exert an\noncolytic effect on tumor cells in a receptor-dependent manner,\nincluding coxsackievirus A21 (CV-A21), Coxsackievirus B3 (CV-B3), and\nEchovirus 7.8\u201311 For CV-A21, melanoma is the most sensitive cell type\nwhich is highly prevalent in Europe and America, and a phase II\nclinical trial has been launched.8,12 Enteroviruses appear to be a safer\nmodality that replicates in the host cytosol without a DNA phase. As\na result, they are unlike a DNA virus and lack the genotoxicity caused\nby the integration of the viral genome into the host DNA.13\nEnteroviruses can utilize the internal ribosome entry site to conduct"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 429
encoding: FLOAT32
metadata:
{"title": "Non-small cell lung cancers \\(NSCLCs\\) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors", "chroma:document": "cap-independent translation.14 They can replicate rapidly, activate\nin\ufb02ammatory responses, upregulate the expression of cytokines and\nchemokines, and induce anti-tumor immune responses. However,\nenteroviruses are the main pathogens causing hand-foot-and-mouth\ndisease (HFMD) in infants and children, including Enterovirus A71,\nCoxsackievirus A16, Coxsackievirus A6, Coxsackievirus A10, CV-B3,\nCoxsackievirus B5 (CV-B5), Echovirus 30, and Echovirus 25, with a\nrelatively high seroprevalence, which may be an obstacle in its\napplication.15 Moreover, these common types of tumors in Asia,\nReceived: 10 January 2023 Revised: 18 July 2023 Accepted: 14 August 2023\n1Division of Hepatitis and Enterovirus Vaccines, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research\nand Evaluation of Biological Products, Institute of Biological Products, National Institutes for Food and Drug Control, Beijing, China; 2National Engineering Technology Research\nCenter for Combined Vaccines, Wuhan, China; 3Beijing Minhai Biotechnology Co., Ltd, Beijing, China; 4Taibang Biologic Group, Beijing, China; 5Changchun Institute of Biological\nProducts Co., Ltd, Changchun, China; 6Shanghai Institute of Biological Products Co., Ltd, Shanghai, China and 7China National Biotec Group Company Limited, Beijing, China\nCorrespondence: Qunying Mao (maoqunying@126.com) or Xiaoming Yang (yangxiaoming@sinopharm.com) or Zhenglun Liang (lzhenglun@126.com)\nThese authors contributed equally: Bopei Cui, Lifang Song\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 430
encoding: FLOAT32
metadata:
{"title": "exosomebased_regimen_rescues_endometrial_fibrosis_in_intrauterine_adhesions_via_targeting_clinical_fibrosis_biomarkers", "chroma:document": "Stem Cells Translational Medicine, 2023, 12, 154\u2013168\nhttps://doi.org/10.1093/stcltm/szad007\nAdvance access publication 8 March 2023\nOriginal Research\nReceived: 21 August 2022; Accepted: 17 January 2023.\n\u00a9 The Author(s) 2023. Published by Oxford University Press.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/\nlicenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For \ncommercial re-use, please contact journals.permissions@oup.com.\nExosome-Based Regimen Rescues Endometrial Fibrosis \nin Intrauterine Adhesions Via Targeting Clinical Fibrosis \nBiomarkers\nYifeng\u00a0Lin1,\u2021, Yaoshen\u00a0Li2,\u2021, Panpan\u00a0Chen1,\u2021, Yanye\u00a0Zhang3, Jiwei\u00a0Sun3, Xiao\u00a0Sun3, Jiaqun\u00a0Li3, \nJiani\u00a0Jin3, Jinglei\u00a0Xue3, Junyan\u00a0Zheng3, Xin-Chi\u00a0Jiang2,4, Chuan\u00a0Chen3, Xiaoqing\u00a0Li3, Yiqing\u00a0Wu3, \nWei\u00a0Zhao3, Juan\u00a0Liu3, Xiaohang\u00a0Ye3, Runju\u00a0Zhang*,1,3, Jianqing\u00a0Gao*,2,4,5,\n, Dan\u00a0Zhang*,1,3,\n1Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women\u2019s Hospital, Zhejiang \nUniversity School of Medicine, Hangzhou, Zhejiang, People\u2019s Republic of China\n2Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People\u2019s Republic of China\n3Key Laboratory of Women\u2019s Reproductive Health of Zhejiang Province and Department of Reproductive Endocrinology, Women\u2019s Hospital, \nZhejiang University School of Medicine, Hangzhou, Zhejiang, People\u2019s Republic of China\n4Dr Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, People\u2019s Republic of China\n5Jinhua Institute of Zhejiang University, Jinhua, People\u2019s Republic of China\n*Corresponding author: Dan Zhang, PhD, Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 431
encoding: FLOAT32
metadata:
{"title": "exosomebased_regimen_rescues_endometrial_fibrosis_in_intrauterine_adhesions_via_targeting_clinical_fibrosis_biomarkers", "chroma:document": "Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310006, People\u2019s Republic of China. Email: zhangdan@zju.edu.cn; \nor, Jianqing Gao, PhD, Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, People\u2019s \nRepublic of China. Email: gaojianqing@zju.edu.cn; or,\u00a0Runju Zhang, PhD, Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of \nReproductive Endocrinology, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310006, People\u2019s Republic of China. \nEmail:\u00a05311005@zju.edu.cn\n\u2021Contributed equally as co-first authors.\nAbstract \nIntrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility \nglobally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endo-\nmetrium of IUA patients. Mesenchymal stem cell\u2013derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis \ndiseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, \nherein, we reported an exosome\u2013based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently \npromote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and \nCOL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides \nthe theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery \nsystem in IUA patients.\nKey words: intrauterine adhesions; endometrial fibrosis; fibrosis biomarkers; exosomes; poloxamer hydrogel."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 432
encoding: FLOAT32
metadata:
{"title": "association_between_inflammatory_bowel_diseases_and_parkinsons_disease_systematic_review_and_metaanalysis", "chroma:document": "344  \uff5cNEURAL REGENERATION RESEARCH\uff5cVol 17\uff5cNo. 2\uff5cFebruary 2022\nAssociation between inflammatory bowel diseases \nand Parkinson\u2019s disease: systematic review and \nmeta-analysis\nYu Zhu#, Min Yuan#, Yue Liu, Fang Yang, Wen-Zhi Chen, Zhen-Zhen Xu, \nZheng-Bing Xiang*, Ren-Shi Xu*\nAbstract  \nGrowing evidence suggests that there are similar pathological mechanisms and closely \nrelated pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson\u2019s \ndisease (PD). However, the epidemiological features of these two diseases are different. \nThis review systematically evaluated the relationship between inflammatory bowel diseases \nand Parkinson\u2019s disease risk. We searched PubMed, Embase, and Cochrane databases to \nretrieve observational studies of IBD and PD published from inception to October 2019. \nNine observational studies, involving 12,177,520 patients, were included in the final \nanalysis. None of the studies had Newcastle\u2013Ottawa Scale scores that suggested a high \nrisk of bias. After adjusting for confounders and excluding heterogeneous studies, the \noverall risk of PD was significantly higher in IBD patients than in the general population \n(adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15\u20131.34, P < 0.001). A meta-\nanalysis of the temporal relationship revealed that the incidence of IBD was significantly \nincreased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18\u20131.35, P < 0.001) and \nafter (adjusted RR = 1.40, 95% CI: 1.20\u20131.80, P < 0.001) PD diagnosis. After excluding a \nheterogeneous study, the pooled risk of PD development in patients with ulcerative colitis \n(adjusted HR = 1.25, 95% CI: 1.13\u20131.38, P < 0.001) or Crohn\u2019s disease (adjusted HR = \n1.33, 95% CI: 1.21\u20131.45, P < 0.01) was significantly increased. Subgroup analysis revealed \nno significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10\u20131.39) \nand women (adjusted HR = 1.26, 95% CI: 1.10\u20131.43); however, older (> 65 years old) IBD"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 433
encoding: FLOAT32
metadata:
{"title": "association_between_inflammatory_bowel_diseases_and_parkinsons_disease_systematic_review_and_metaanalysis", "chroma:document": "patients (adjusted HR = 1.32, 95% CI: 1.17\u20131.48) may have a higher risk than younger (\u2264 65 \nyears old) patients (adjusted HR = 1.24, 95% CI: 1.08\u20131.42). Patients with IBD who were not \ntreated with anti-tumor necrosis factor-\u03b1 or azathioprine had significantly higher PD risk \n(adjusted HR = 1.6, 95% CI: 1.2\u20132.2). Thus, our meta-analysis indicates a certain correlation \nbetween IBD and PD, and suggests that IBD may moderately increase PD risk regardless of \nsex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies \nfor IBD might reduce the risk of developing PD. Our findings suggest an urgent need for \nan individualized screening strategy for patients with IBD. However, most studies included \nin this paper were observational, and more randomized controlled trials are needed to \nconfirm the precise association between IBD and PD.\nKey Words: brain-gut axis; central nervous system; Crohn\u2019s disease; inflammatory bowel \ndiseases; meta-analysis; neurodegenerative disease; neuroinflammation; Parkinson\u2019s \ndisease; systematic review; ulcerative colitis \nChinese Library Classification No. R452; R574; R741.04\nhttps://doi.org/10.4103/1673-5374.317981\nDate of submission: October 9, 2020 \nDate of decision: October 13, 2020 \nDate of acceptance: November 13, 2020 \nDate of web publication: July 8, 2021 \nIntroduction \nPa r k i n s o n \u2019s  d i s e a s e  ( P D )  i s  t h e  m o st  co m m o n \nneurodegenerative motor disorder (Park et al., 2020; Thomas \nBroome et al., 2020), with symptoms that include resting \ntremor, dyskinesia, ankylosis, and postural instability. Non-\nmotor symptoms (e.g., dementia, depression, and sleep \ndisorders) also occur, and can arise even before a motor \ndiagnosis is made. The pathology of PD is associated with a \nprofound loss of dopaminergic neurons in the substantia nigra \npars compacta, which is accompanied by filamentous protein \ninclusions, termed Lewy bodies, in the surviving neurons. \nLewy bodies are mainly composed of alpha-synuclein (\u03b1-syn),"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 434
encoding: FLOAT32
metadata:
{"title": "association_between_inflammatory_bowel_diseases_and_parkinsons_disease_systematic_review_and_metaanalysis", "chroma:document": "and these inclusions are the hallmark pathological feature \nof PD. However, their pathogenic relevance remains under \ndebate (Kalinderi et al., 2016; Obergasteiger et al., 2018). \nMuch evidence suggests that PD pathology starts from chronic \nlow-level inflammation in the gastrointestinal tract, thus \ninducing misfolded \u03b1-syn, which then propagates to the brain \nvia a dysfunctional blood-brain barrier (BBB) or the vagus \nnerve. This has been widely investigated in studies regarding \nthe association between PD and alterations of the intestinal \nenvironment (Houser and Tansey, 2017; Lionnet et al., 2018; \nSpielman et al., 2018).\nDepartment of Neurology, Jiangxi Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital of Nanchang University, Nanchang, Jiangxi Province, China\n*Correspondence to: Ren-Shi Xu, MD, PhD, 13767015770@163.com; Zheng-Bing Xiang, MD, xzbshawn@163.com.\nhttps://orcid.org/0000-0003-0313-3434 (Ren-Shi Xu); https://orcid.org/0000-0001-9003-0489 (Zheng-Bing Xiang)\n#Both authors contributed equally to this work.\nHow to cite this article: Zhu Y, Yuan M, Liu Y, Yang F, Chen WZ, Xu ZZ, Xiang ZB, Xu RS (2022) Association between inflammatory bowel diseases and Parkinson\u2019s \ndisease: systematic review and meta-analysis. Neural Regen Res 17(2):344-353. \nResearch Article"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 435
encoding: FLOAT32
metadata:
{"title": "Type C oncornavirus isolation studies in systemic lupus erythematosus", "chroma:document": "Annals of the Rheumatic Diseases, 1978, 37, 225-233\nType C oncornavirus isolation studies in systemic\nlupus erythematosus\nII. Attempted detection by viral RNA-dependent DNA polymerase assay\nPAUL E. PHILLIPS AND RITA HARGRAVE-GRANDA\nFrom the Department ofMedicine, The Hospitalfor Special Surgery, New York Hospitaland Cornell University\nMedical College, 535 East 70th Street, New York, NY 10021, USA\nSUMMARY\nIsolation of type C oncornavirus was attempted from 20 tissues and cell cultures of\npatients with systemic lupus erythematosus. Chemical inducers, cocultivation and fusion with cells\nfrom multiple other species, prolonged subculturing, and the RNA-dependent DNA polymerase\nassay for virus detection were used. A type C virus was isolated, but was shown to be the endogenous\nrat virus. Thus the methods, although generally appropriate, were not specifically permissive for\nreplication of a human type C virus. This agrees with the failure of other investigators to isolate a\nvirus of undisputed human origin. Combining available evidence, a fundamental role for type C\nviruses in lupus erythematosus remains an attractive hypothesis.\nIt has been postulated that viruses are involved in the\npathogenesis of systemic lupus erythematosus (SLE)\n(reviewed in Phillips and Christian, 1978). Particular\ninterest has been shown in type C oncornaviruses\nbecause of their role in the animal model of SLE,\nNew Zealand (NZ) mouse disease (Yoshiki et al.,\n1974; Levy et al., 1975). However, the evidence is\nconflicting as to whether type C expression is en-\nhanced, similar, or absent in SLE patients compared\nwith other humans (Markenson and Phillips, 1978).\nOur earlier study failed to isolate type C, or other\nRNA viruses, or mycoplasma from SLE cell cultures\nand tissues (Phillips et al., 1976). In this study we\nused more sensitive methods previously successful in\nisolating type C virsuses from other species, and the\nRNA-dependent DNA polymerase (RDDP) assay\nfor virus detection.\nMaterials and methods\nPATIENTS\nWe studied"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 436
encoding: FLOAT32
metadata:
{"title": "Type C oncornavirus isolation studies in systemic lupus erythematosus", "chroma:document": "13 patients with SLE (Cases\n1-13,\nTable 1) according to the American Rheumatism\nAssociation criteria (Cohen et al., 1971) and 6 with\nprobable or possible SLE (Cases 14-19). All were\nfemale, aged 15-65 years (mean 33 0 years), and had\nAccepted foi publication September 22, 1977\nCorrespondence to Dr P. E. Phillips\nbeen ill for 0-5-15 years (mean 6 7 years). 7 had\nclinically active disease and 12 were receiving pred-\nnisone, 1-60 mg daily (mean 27-0 mg); 5 were\nreceiving\nimmunosuppressive\ndrugs.\n20\ntissues\n(Table 1) were studied. Cases 1-5 had also been\ntested previously (Cases 2, 3, 5, 6, 7 respectively in\nPhillips et al., 1976).\nCELL CULTURES\nSLE tissues were obtained and the cells cultured as\ndescribed (Phillips et al., 1976) except for tissues\nfrom Cases 8 and 17, which were frozen at -70\u00b0C\nuntil testing.\n31 experiments were done: 5 with\nfrozen tissue homogenates, the remainder with SLE\ncells periodically subcultured for up to 18 months\nbefore testing (6 tested immediately or cultured for\n<1 month, 8 cultured for 1-6 months, 7 for 6-12\nmonths, and 5 for 12-18 months; Table 1).\nFor virus isolation, 6 cell lines from heterologous\nspecies were used: rabbit cornea (SIRC; CCL 60,\nAmerican Type Culture Collection, Rockville, MD),\nmink lung (Mv 1 Lu; CCL 64), bat lung (Tb 1 Lu;\nCCL 88), horse skin (E. Derm.; CCL 57), fetal\nrhesus monkey lung (DBS-FRhL-1; from Dr J. C.\nPetricciani, Food and Drug Administration, Rock-\nville, MD), and\nHarvey\nmurine sarcoma virus-\ntransformed\nnonvirus-producing\nrat\nkidney\n(H-NRK; from Dr T.\nPincus,\nMemorial-Sloan\n225"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 437
encoding: FLOAT32
metadata:
{"title": "Systemic lupus erythematosus, repeated abortions, and thrombocytopenia", "chroma:document": "Annals of the Rheumatic Diseases, 1978, 37, 476-478\nCase Report\nSystemic lupus erythematosus, repeated abortions, and\nthrombocytopenia\nM. H. PRITCHARD,\nJ. D. JESSOP, P. M. TRENCHARD, AND\nJ. A. WHITTAKER\nFrom the Departments ofRheumatology and Haematology, University Hospital of Wales, Heath Park, Cardiff\nSUMMARY A case is described of severe thrombocytopenia in a pregnant patient with mild SLE.\nThree previous pregnancies had ended in abortion. Attempts to reverse the thrombocytopenia\nwith steroids, plasmapheresis, and splenectomy failed, the platelet count returning to normal\nimmediately after the death of the fetus at 20 weeks gestation.\nIt is known that patients suffering from systemic\nlupus erythematosus (SLE) may show a deterioration\nin their disease during pregnancy, and that spontan-\neous abortions are frequent (Grigor et al., 1977).\nThis report describes a case in which for several\nyears the only significant symptom of SLE was mild\nthrombocytopenia;\nhowever,\nduring\nthis time 4\npregnancies ended in spontaneous abortion, and 2\nof these were complicated by severe, potentially life\nthreatening thrombocytopenia.\nHistory\nThe patient is a 31-year old woman. She gave a\nhistory of 3 previous pregnancies in 1970, 1971, and\n1975 all of which ended in spontaneous abortion\nbetween 18 and 24 weeks. The second pregnancy\nwas\ncomplicated\nby\nepisodes\nof\npurpura\nand\nthrombocytopenia with platelet counts of around\n20 x\n109/l. These responded to oral prednisone.\nThe platelet counts did not fall significantly during\nthe first and third pregnancies.\nWhen first seen in Cardiff in December 1973,\nSLE had already been diagnosed on the basis of a\npositive anti-nuclear factor and a DNA binding of\n70%. She had been prescribed 10 mg prednisone\non alternate days with 100 mg azathioprine daily.\nThe latter was stopped without any ill effects, and her\nonly symptoms were occasional attacks of arthralgia.\nHer platelet count varied between 70 and 140 x 109/l\nwith occasional episodes of mild purpura."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 438
encoding: FLOAT32
metadata:
{"title": "Systemic lupus erythematosus, repeated abortions, and thrombocytopenia", "chroma:document": "She was admitted to hospital in January 1977,\nAccepted for publication January 25, 1978\nduring the 14th week of her fourth pregnancy, at\nthe request of her obstetrician, because of a steadily\ndeteriorating thrombocytopenia, which had failed\nto respond to raising the prednisone dose to 80 mg\ndaily. On admission she was found to be in excellent\nphysical health, there was no bruising, purpura or\nbleeding from any source in spite of a platelet count\nof 20 x 109/l. It appeared from her notes that the\nplatelet count 3 weeks earlier had been in the region\nof 200 x 109/l, but had shown a steady decline since\nthen, in spite of massive increases in steroid dosage.\nThe fetus was\nalive, according\nto the Sonicaid\nfindings.\nInvestigations and management\nInvestigations showed a haemaglobin (Hb) of 15.2\ng/dl, normal urea, electrolytes and liver function\ntests, ESR 13 mm/h, DAT 1/32 and an active bone\nmarrow\nwith\nabundant\nmegakaryocytes.\nCom-\nplement studies showed low CH50, C. and C4 but\nnormal factor B. Complement fixing platelet anti-\nbodies were also found (Fig. 1) although, no cryo-\nprecipitate or anticomplementary activity could be\ndetected at any time.\nThe chances of a successful pregnancy in the\npresence\nof\nsevere thrombocytopenia\nand\nhigh\nsteroid dosage were considered to be very small.\nTwo further methods were therefore proposed to\nreverse the thrombocytopenia; plasmapheresis to\nremove the platelet autoantibodies and splenectomy.\nPlasmapheresis was tried first, as it has been success-\nfully used in pregnancy for the removal of anti-\nRhesus antibodies with no ill effects on the fetus\n476"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 439
encoding: FLOAT32
metadata:
{"title": "Viruses and lymphocytes in rheumatoid arthritis. Studies cultured rheumatoid lymphocytes", "chroma:document": "Annals of the Rheumatic Diseases, 1979, 38, 507-513\nViruses and lymphocytes in rheumatoid arthritis.\nI. Studies on cultured rheumatoid lymphocytes\nMARY NORVAL, HELENA HART, AND B. P. MARMION\nFrom the Department ofBacteriology, University ofEdinburgh Medical School, Edinburgh\nSUMMARY\nSynovial fluid lymphocytes from patients with rheumatoid arthritis have been examined\nfor evidence of a productive infection with retroviruses by electron microscopy, labelling with\n3H-uridine, growth in soft agar, and culturing in conditioned medium. No such viruses were detected.\nIn addition, the synovial lymphocytes were activated before fusion and cocultivation with several cell\nlines which have proved permissive for primate retroviruses. Monitoring these cultures subsequently\nby reverse transcriptase assay, labelling with 3H-uridine, and membrane immunofluorescence gave\nno indication that retroviruses were present.\nA possible viral aetiology for rheumatoid arthritis\n(RA) has been much canvassed and investigated\nduring the last 10 years but with negative results so\nfar. Much of the search has concentrated on the\nfibroblast-like cells cultured from the RA synovial\nmembrane or synovial fluid effusions and thought\nto be derived from type B or C lining cells (Smith\nand Hamerman,\n1969). However,\nthere\nis\nlittle\nevidence for viral genomes, productive viral in-\nfection, or neoantigens in such cells. For summaries\nand reviews see Hamerman (1975), Marmion and\nMackay (1977), and Marmion (in press).\nLess attention has been paid in RA to the possible\nproduction of disease as a result of the interaction\nof virus with cells of the immune and immuno-\nregulatory system (Denman,\n1975;\nTalal,\n1977;\nMarmion and Mackay, 1977; Marmion, in press).\nReports on the relative proportion and classes of\nlymphocytes\nin\nrheumatoid\nsynovial\nfluid\nand\nperipheral blood vary. Several investigations record\nan increase in T-cell numbers, a decrease in B-cell\nnumbers (Froland et al., 1973; Holborow et al.,\n1975), and the presence of a population of null cells,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 440
encoding: FLOAT32
metadata:
{"title": "Viruses and lymphocytes in rheumatoid arthritis. Studies cultured rheumatoid lymphocytes", "chroma:document": "up to 32% (Winchester et al., 1974). Others have\nfound an increase in B-cells (Mellbye et al., 1972).\nThe lymphocytes in RA synovial membranes, as\ndistinct from the synovial fluid, are predominantly\nT-cells (Loewi, 1975).\nThere may be a marked diminution in responsive-\nness of synovial lymphocytes of RA patients to\nAccepted for publication 19 December 1978.\nCorrespondence\nto\nDr\nMary\nNorval,\nDepartment\nof\nBacteriology,\nUniversity\nof Edinburgh\nMedical\nSchool,\nTeviot Place, Edinburgh EH8 9AG.\nvarious mitogens,\nespecially PHA (Stratton and\nPeter, 1972; Panayi, 1973; Holborow et al., 1975)\nbut reports are not consistent. Also the reactivity of\nperipheral blood lymphocytes in mixed lumphocyte\nculture may be depressed (Astorga and Williams,\n1969). It is possible that the cells may already be\nactivated or that the receptor sites for the antigen\nmay be blocked; such effects might be virally induced.\nIn view of these pointers to disordered lymphocyte\nfunction\nin RA we decided\nto\ninvestigate RA\nsynovial and\nperipheral\nblood lymphocytes\nfor\nevidence of viral infection or of viral gene products.\nWe were particularly interested in the association of\nretroviruses (type C or oncoviruses) with lympho-\ncytes. This interaction has been well studied in\nvarious mice strains in which the immune response\nto endogenous viruses is modified by genetic factors\ninvolved with infectivity and expression (review,\nIhle and Hanna, 1977). In human beings there have\nbeen\nextensive\nattempts\nto\ndetect\nretroviruses,\nespecially in association with leukaemia or lym-\nphoma. Several isolations have been made, one of\nwhich was from cultured myeloid leukaemia cells.\nThis virus was closely related to simian sarcoma\nvirus and baboon endogenous virus (Reitz et al.,\n1976), and it can be established as a chronic in-\nfection in various cell lines (Teich et al., 1975).\nA range of different cell-virus relationships exists\nwith retroviruses and extends from productive in-\nfection to an integrated 'silent' genome. In addition"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 441
encoding: FLOAT32
metadata:
{"title": "Viruses and lymphocytes in rheumatoid arthritis. Studies cultured rheumatoid lymphocytes", "chroma:document": "some viruses are unable to replicate in cells of the\nsame species from which they have been derived\n(xenotropic viruses). During the course of this study\nwe used methods described by other workers for\n507"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 442
encoding: FLOAT32
metadata:
{"title": "Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antiv\\\rirals", "chroma:document": "Characterization of an air-liquid interface primary human vaginal \nepithelium to study Ebola virus infection and testing of antivirals\nOlivier Escaffrea,c,*, Vsevolod Popova,b,c, Eldridge Hagera, Alexander N. Freiberga,b,c,**\naDepartment of Pathology, USA\nbCenter for Biodefense and Emerging Infectious Diseases, USA\ncInstitute for Human Infections & Immunity and Sealy & Smith Foundation, University of Texas \nMedical Branch, Galveston, TX, 77555, USA\nAbstract\nEbola virus (EBOV) is the causative agent of the often-fatal Ebola virus disease (EVD) \ncharacterized by hemorrhagic fever in humans and non-human primates. Sexual transmission \nfrom male survivors has been at the origin of multiple outbreak flare-ups between 2015 and \n2021. However, this route is still poorly understood and the resulting EVD from it is also \nunderstudied. To support epidemiological studies documenting sexual transmission to women, \nand as a transition from previously using monolayer vaginal epithelial cells (VK2/E6E7), we \nfirst determined the biological relevance of two similar air-liquid interface models of the human \nvaginal epithelium (VEC and VLC Epivaginal\u2122) and then characterized their susceptibility \nto EBOV and virus-induced inflammation. Finally, we evaluated toxicity of Polyphenylene \nCarboxymethylene (PPCM) microbicide in VLC and reassessed its antiviral effect.\nAs expected, the VEC, but also VLC model showed stratified layers including a lamina propria \nunder an epithelial structure similar to the full thickness of the human vaginal epithelium. \nHowever, we could not detect the immune cells featured in the most relevant model (VLC) of \nthe vaginal epithelium using the dendritic cell CD1a and CD11c markers. Consistent with our \nprevious work using the VK2/E6E7 cell line, infectious virus was detected from the apical side \nof both primary human cell systems, but only when using a high infective dose, with titers \nremaining at a constant level of 103\u20134 pfu/ml over 7 days suggesting lasting infectious virus"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 443
encoding: FLOAT32
metadata:
{"title": "Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antiv\\\rirals", "chroma:document": "shedding. In addition, infection caused disruption of the epithelium of both models and virus \nantigen was found from the apical superficial layers down to the lamina propria suggesting full \nvirus penetration and overall confirming the susceptibility of the human vaginal tissue for EBOV. \nJust like previously seen in VK2/E6E7 cells, VLC infection also caused significant increase \nThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).\n*Corresponding author. Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, \n77555-0609, USA. olescaff@utmb.edu (O. Escaffre). **Corresponding author. Department of Pathology, University of Texas Medical \nBranch, 301 University Boulevard, Galveston, TX, 77555-0609, USA. anfreibe@utmb.edu (A.N. Freiberg). \nDeclaration of competing interest\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to \ninfluence the work reported in this paper.\nAppendix A. Supplementary data\nSupplementary data to this article can be found online at https://doi.org/10.1016/j.antiviral.2023.105551.\nHHS Public Access\nAuthor manuscript\nAntiviral Res. Author manuscript; available in PMC 2023 June 22.\nPublished in final edited form as:\nAntiviral Res. 2023 March ; 211: 105551. doi:10.1016/j.antiviral.2023.105551.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 444
encoding: FLOAT32
metadata:
{"title": "Omnipresence of the sensorimotor-association axis topography in the\\nhuman connectome", "chroma:document": "Omnipresence of the sensorimotor-association axis topography \nin the human connectome\nKarl-Heinz Nenninga,*, Ting Xub, Alexandre R. Francoa,b,f, Khena M. Swallowc, Arielle \nTambinia,f, Daniel S. Marguliesd, Jonathan Smallwoode, Stanley J. Colcombea,f, Michael \nP. Milhama,b\naNathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States\nbChild Mind Institute, New York, NY, United States\ncCornell University, Ithaca, NY, United States\ndCNRS and Universit\u00e9 de Paris, Paris, France\neQueen\u2019s University, Kingston, Ontario, Canada\nfNew York University, New York, NY, United States\nAbstract\nLow-dimensional representations are increasingly used to study meaningful organizational \nprinciples within the human brain. Most notably, the sensorimotor-association axis consistently \nexplains the most variance in the human connectome as its so-called principal gradient, \nsuggesting that it represents a fundamental organizational principle. While recent work indicates \nthese low dimensional representations are relatively robust, they are limited by modeling \nonly certain aspects of the functional connectivity structure. To date, the majority of studies \nhave restricted these approaches to the strongest connections in the brain, treating weaker \nor negative connections as noise despite evidence of meaningful structure among them. The \npresent work examines connectivity gradients of the human connectome across a full range \nof connectivity strengths and explores the implications for outcomes of individual differences, \nidentifying potential dependencies on thresholds and opportunities to improve prediction tasks. \nInterestingly, the sensorimotor-association axis emerged as the principal gradient of the human \nconnectome across the entire range of connectivity levels. Moreover, the principal gradient of \nconnections at intermediate strengths encoded individual differences, better followed individual-\nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 445
encoding: FLOAT32
metadata:
{"title": "Omnipresence of the sensorimotor-association axis topography in the\\nhuman connectome", "chroma:document": "*Corresponding author. karl-heinz.nenning@nki.rfmh.org (K.-H. Nenning). \nDeclaration of Competing Interest None.\nCredit authorship contribution statement\nKarl-Heinz Nenning: Conceptualization, Formal analysis, Methodology, Software, Visualization, Writing \u2013 original draft, Writing \u2013 \nreview & editing. Ting Xu: Conceptualization, Methodology, Writing \u2013 review & editing. Alexandre R. Franco: Resources, Writing \n\u2013 review & editing. Khena M. Swallow: Writing \u2013 review & editing. Arielle Tambini: Writing \u2013 review & editing. Daniel S. \nMargulies: Writing \u2013 review & editing. Jonathan Smallwood: Writing \u2013 review & editing. Stanley J. Colcombe: Conceptualization, \nFunding acquisition, Resources, Writing \u2013 review & editing. Michael P. Milham: Conceptualization, Funding acquisition, Resources, \nWriting \u2013 review & editing.\nSupplementary materials\nSupplementary material associated with this article can be found, in the online version, at doi:10.1016/j.neuroimage.2023.120059.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 June 22.\nPublished in final edited form as:\nNeuroimage. 2023 May 15; 272: 120059. doi:10.1016/j.neuroimage.2023.120059.\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: 446
encoding: FLOAT32
metadata:
{"title": "Osteoarthritis: The result of joint failure?", "chroma:document": "Annals of the Rheumatic Diseases 1989; 48: 958-961\nHypothesis\nOsteoarthritis: The cause not result of joint failure?\nOsteoarthritis is an enigmatic condition as it is at\nonce simple and complex. It seems simple as trauma\nis sufficient to produce its major features, but it\nbecomes complex when we try to understand both\n'primary' osteoarthritis and why the processes that\nare features of osteoarthritis develop. An enormous\namount of information is available on the epidemi-\nology, clinical picture, pathology, and biochemistry\nof osteoarthritis, but the problem\nis to see the\npatterns linking that information. Observation has\nestablished a set of features of osteoarthritis that any\nsatisfactory hypothesis needs to explain.\nOsteoarthritis is characterised by joint destruction\nwith cartilage loss and occasional gross derange-\nment of the\njoint's\nintegrity. 1\nOsteoarthritis\nis\nhomogeneous, ubiquitous, and related to age.2 3\nThe anatomical, histological, and biochemical fea-\ntures are present and constant to a remarkable\ndegree in osteoarthritis at different sites and in\ndifferent animals and animal models, though they\nmay\nvary\nquantitatively.\nParadoxically\nalso,\nalthough osteoarthritis shows extraordinary diver-\nsity, it is heterogeneous, and this is shown in its\naetiology.\nJoint\ninsult of almost any kind may\nproduce osteoarthritis. Cartilage abnormality from\namino acid metabolism in ochronosis, trauma, and\npre-existing\ninflammatory\nosteoarthritis may\nall\nproduce this seemingly common pathway of a joint\nreacting to 'failure'. The clinical picture, pathology,\nand natural history are also very varied.\"4\nOsteoarthritis has a characteristic joint distribu-\ntion that is both spatial and temporal. Joints that are\nfrequently involved\ninclude\nthe\nfirst\nmetatarso-\nphalangeal,\nfirst\ncarpometacarpal,\ndistal\ninter-\nphalangeal, knee, and the apophyseal joints of the\nspine\nat the thoracolumbar and thoracocervical\njunctions. Conversely, others, such as the wrist,\nelbow, shoulder, ankle, and tarsal joints, are rarely"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 447
encoding: FLOAT32
metadata:
{"title": "Osteoarthritis: The result of joint failure?", "chroma:document": "involved. Usually the features are seen first at the\nmetatarsophalangeal joint, and the sequence\nof\ninvolvement reflects the common site distribution.2 5\nRemarkably, osteoarthritis is an anabolic as well\nas a destructive process. Bone sclerosis, capsular\nfibrosis, and osteophyte formation are the result of\nactive turn on of systems producing tissue growth.\nThe biochemistry of experimental osteoarthritis and\nof pathological specimens reflects this anabolism\nin an increase\nin\ncell activity and proteoglycan\nturnover.7 8 More remarkably, the proteoglycans\nare qualitatively different from those produced with\naging; they are similar to the profile of 'juvenile'\nyoung cartilage.9-i\nFinally, to make the whole process seem totally\ncontradictory some of its features may occur in\nisolation. Fibrillation of cartilage and 'age related\nosteophytes', which are features of osteoarthritis,\nmay occur alone.i 12\nCan a hypothesis be constructed to link these\nfeatures? The primary approach is to see osteo-\narthritis as joint failure. If the joint is considered as\na mechanical system, which it is, this allows an\nanalogy with man-made machines. Joint failure is\nthus a function of use, material, and design, and this\nconcept goes some way towards explaining the\nobserved features. The heterogeneity reflects the\nmultiple combinations of factors that interact to\nproduce the osteoarthritic process. The distribution\nand age association reflect underdesign of joints. i3\nThe homogeneity results from the triggering of the\nsame\nfinal common pathway,\nthe\nosteoarthritic\nprocess itself 6 (Fig. 1), and the anabolic response is\nthen seen as an attempt at repair. i4 15\nThe model though is not sufficient as it does not\nexplain the nature of the anabolic response or why\nsome features like osteophytes occur in isolation. It\nalso gives no explanation for primary osteoarthritis.\nIs it simply that the aetiological factors are unidenti-\nfied, or could the process develop in some other\nway? Possibly the process is a result of the failure of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 448
encoding: FLOAT32
metadata:
{"title": "Osteoarthritis: The result of joint failure?", "chroma:document": "the normal maintenance of the joint-that is, a\nfailure of remodelling.'6 17 This concept can be\ntaken further; rather than the process being driven\nMultiple aetiological factors\nJoint malfunction\nOsteoarthritic response\nJoint failure\nFig.\n1\nThe osteoarthritic process.\n958"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 449
encoding: FLOAT32
metadata:
{"title": "Advances toward precision medicine for bipolar disorder: mechanisms & molecules", "chroma:document": "Advances toward precision medicine for bipolar disorder: \nmechanisms & molecules\nStephen J. Haggarty1, Rakesh Karmacharya2,3, Roy H. Perlis4\n(1)Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General \nHospital, Departments of Psychiatry & Neurology, Harvard Medical School, Boston, USA\n(2)Center for Genomic Medicine, Massachusetts General Hospital, Department of Psychiatry, \nHarvard Medical School Boston, Boston, USA\n(3)Schizophrenia and Bipolar Disorder Program, McLean Hospital, Belmont, USA\n(4)Center for Quantitative Health, Center for Genomic Medicine and Department of Psychiatry, \nMassachusetts General Hospital, Harvard Medical School, Boston, USA\nAbstract\nGiven its chronicity, contribution to disability and morbidity, and prevalence of more than 2%, \nthe effective treatment, and prevention of bipolar disorder represents an area of significant \nunmet medical need. While more than half a century has passed since the introduction of \nlithium into widespread use at the birth of modern psychopharmacology, that medication \nremains a mainstay for the acute treatment and prevention of recurrent mania/hypomania and \ndepression that characterize bipolar disorder. However, the continued limited understanding of \nhow lithium modulates affective behavior and lack of validated cellular and animal models have \nresulted in obstacles to discovering more effective mood stabilizers with fewer adverse side \neffects. In particular, while there has been progress in developing new pharmacotherapy for \nmania, developing effective treatments for acute bipolar depression remain inadequate. Recent \nlarge-scale human genetic studies have confirmed the complex, polygenic nature of the risk \narchitecture of bipolar disorder, and its overlap with other major neuropsychiatric disorders. Such \ndiscoveries have begun to shed light on the pathophysiology of bipolar disorder. Coupled with \nbroader advances in human neurobiology, neuropharmacology, noninvasive neuromodulation, and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 450
encoding: FLOAT32
metadata:
{"title": "Advances toward precision medicine for bipolar disorder: mechanisms & molecules", "chroma:document": "clinical trial design, we can envision novel therapeutic strategies informed by defined molecular \nmechanisms and neural circuits and targeted to the root cause of the pathophysiology. Here, we \nreview recent advances toward the goal of better treatments for bipolar disorder, and we outline \nPublisher's Disclaimer: Disclaimer: This is a machine generated PDF of selected content from our products. This functionality \nis provided solely for your convenience and is in no way intended to replace original scanned PDF. Neither Cengage \nLearning nor its licensors make any representations or warranties with respect to the machine generated PDF. The PDF \nis automatically generated \u201cAS IS\u201d and \u201cAS AVAILABLE\u201d and are not retained in our systems. CENGAGE LEARNING \nAND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING \nWITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-\nINFRINGEMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the machine generated PDF \nis subject to all use restrictions contained in The Cengage Learning Subscription and License Agreement and/or the Gale Academic \nOneFile Terms and Conditions and by using the machine generated PDF functionality you agree to forgo any and all claims against \nCengage Learning or its licensors for your use of the machine generated PDF functionality and any output derived therefrom.\nHHS Public Access\nAuthor manuscript\nMol Psychiatry. Author manuscript; available in PMC 2023 June 24.\nPublished in final edited form as:\nMol Psychiatry. 2021 January ; 26(1): 168\u2013185. doi:10.1038/s41380-020-0831-4.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 451
encoding: FLOAT32
metadata:
{"title": "Sex specificity of pancreatic cancer cachexia phenotypes, mechanisms, and treatment in mice and humans: role of Activin", "chroma:document": "Sex speci\ufb01city of pancreatic cancer cachexia\nphenotypes, mechanisms, and treatment in mice and\nhumans: role of Activin\nXiaoling Zhong1,2, Ashok Narasimhan1, Libbie M. Silverman1, Andrew R. Young1, Sa\ufb01 Shahda3\u2020, Sheng Liu4,5, Jun Wan4,5,6,\nYunlong Liu4,5,6,7, Leonidas G. Koniaris1,2,6,7 & Teresa A. Zimmers1,2,5,6,7*\n1Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; 2Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA;\n3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 4Department of Medical and Molecular Genetics, Indiana University School of\nMedicine, Indianapolis, IN, USA; 5Center for Computational Biology and Bioinformatics, Indianapolis, IN, USA; 6Indiana University Melvin and Bren Simon Comprehensive\nCancer Center, Indianapolis, IN, USA; 7Indiana Center for Musculoskeletal Health, Indianapolis, IN, USA\nAbstract\nORIGINAL ARTICLE\nBackground\nCachexia is frequent, deadly, and untreatable for patients with pancreatic ductal adenocarcinoma\n(PDAC). The reproductive hormone and cytokine Activin is a mediator of PDAC cachexia, and Activin receptor targeting\nwas clinically tested for cancer cachexia therapy. However, sex-speci\ufb01c manifestations and mechanisms are poorly un-\nderstood, constraining development of effective treatments.\nMethods\nCachexia phenotypes, muscle gene/protein expression, and effects of the Activin blocker ACVR2B/Fc\nwere assessed in LSL-KrasG12D/+, LSL-Trp53R172H/+, and Pdx-1-Cre (KPC) mice with autochthonic PDAC. Effects of\nPDAC and sex hormones were modelled by treating C2C12 myotubes with KPC-cell conditioned medium (CM)\nand estradiol. Muscle gene expression by RNAseq and change in muscle from serial CT scans were measured in patients\nwith PDAC.\nResults\nDespite equivalent tumour latency (median 17 weeks) and mortality (24.5 weeks), male KPC mice showed\nearlier and more severe cachexia than females. In early PDAC, male gastrocnemius, quadriceps, and tibialis anterior"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 452
encoding: FLOAT32
metadata:
{"title": "Sex specificity of pancreatic cancer cachexia phenotypes, mechanisms, and treatment in mice and humans: role of Activin", "chroma:document": "muscles were reduced (\u000121.7%, \u000118.9%, and \u000120.8%, respectively, all P < 0.001), with only gastrocnemius reduced\nin females (\u000116%, P < 0.01). Sex differences disappeared in late PDAC. Plasma Activin A was similarly elevated be-\ntween sexes throughout, while oestrogen and testosterone levels suggested a virilizing effect of PDAC in females. Estra-\ndiol partially protected myotubes from KPC-CM induced atrophy and promoted expression of the potential Activin in-\nhibitor Fstl1. Early-stage female mice showed greater muscle expression of Activin inhibitors Fst, Fstl1, and Fstl3; this\nsex difference disappeared by late-stage PDAC. ACVR2B/Fc initiated in early PDAC preserved muscle and fat only in\nmale KPC mice, with increases of 41.2%, 52.6%, 39.3%, and 348.8%, respectively, in gastrocnemius, quadriceps,\ntibialis, and fat pad weights vs. vehicle controls, without effect on tumour. No protection was observed in females.\nAt protein and RNA levels, pro-atrophy pathways were induced more strongly in early-stage males, with sex differences\nless evident in late-stage disease. As with mass, ACVR2B/Fc blunted atrophy-associated pathways only in males. In pa-\ntients with resectable PDAC, muscle expression of Activin inhibitors FSTL1, FSLT3, and WFIKKN2/GASP2 were higher\nin women than men. Overall, among 124 patients on \ufb01rst-line gemcitabine/nab-paclitaxel for PDAC, only men\ndisplayed muscle loss (P < 0.001); average muscle wasting in men was greater (\u00016.63 \u00b1 10.70% vs.\n\u00011.62 \u00b1 12.00% mean \u00b1 SD, P = 0.038) and more rapid (\u00010.0098 \u00b1 0.0742%/day vs. \u00010.0466 \u00b1 0.1066%/day,\nP = 0.017) than in women.\nConclusions\nPancreatic ductal adenocarcinoma cachexia displays sex-speci\ufb01c phenotypes in mice and humans, with\nActivin a preferential driver of muscle wasting in males. Sex is a major modulator of cachexia mechanisms. Consider-\nation of sexual dimorphism is essential for discovery and development of effective treatments."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 453
encoding: FLOAT32
metadata:
{"title": "Sex specificity of pancreatic cancer cachexia phenotypes, mechanisms, and treatment in mice and humans: role of Activin", "chroma:document": "\u00a9 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,\nprovided the original work is properly cited, the use is non-commercial and no modi\ufb01cations or adaptations are made.\nJournal of Cachexia, Sarcopenia and Muscle 2022; 13: 2146\u20132161\nPublished online 5 May 2022 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/jcsm.12998"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 454
encoding: FLOAT32
metadata:
{"title": "Rift Valley fever in animals and humans: Current perspectives", "chroma:document": "Rift Valley fever in animals and humans: Current perspectives\nCynthia M. McMillen,\nAmy L. Hartman*\nCenter for Vaccine Research, Department of Infectious Diseases and Microbiology, University of \nPittsburgh Graduate School of Public Health, USA\nAbstract\nRift Valley fever (RVF) is an ecologically complex emerging arboviral disease that causes \nsignificant illness in both livestock and people. This review article is designed to assist the \nreader in understanding the varied aspects of RVF disease in animals and humans. The historical \nfacets of RVF disease, including the evolution of human outbreaks, are presented and discussed. \nThe different clinical presentations of human RVF disease and the underlying causes are then \naddressed. We explore the exposure and transmission potential of RVF in animals and people. In \nthe concluding section, we discuss the historical role of RVF as a biological weapon. We conclude \nwith an outline of the important unanswered questions for ongoing research into this important \nzoonotic disease.\n1. Introduction\nRift Valley fever (RVF) is a veterinary disease of livestock in Africa, and as such it \nexemplifies the One Health concept, in which animal and human health are inextricably \nintertwined. Infection of domesticated livestock (sheep, cattle, and goats) with RVF virus \n(RVFV) causes a highly lethal illness that results in dire economic consequences in affected \nregions. Initially a disease of the Rift Valley in eastern Africa, RVFV has spread through \ncontinental Africa as well as to Madagascar and the Arabian Peninsula. The World Health \nOrganization (WHO)\u2019s first Workshop on Prioritization of Pathogens assigned RVF to the \nlist of \u201csevere emerging diseases with potential to generate a public health emergency, \nand for which no, or insufficient, preventive and curative solutions exist\u201d (World Health \nOrganization, 2015, 2017). RVF remains on the World Organization for Animal Health \n(OIE)\u2019s list of notifiable animal diseases of concern World Organization for Animal Health"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 455
encoding: FLOAT32
metadata:
{"title": "Rift Valley fever in animals and humans: Current perspectives", "chroma:document": "(OIE), 2018. Veterinary and human vaccination strategies and development of therapeutic \ninterventions are the key to limiting spread and alleviating disease burden. Both have \nrecently been comprehensively reviewed (Dungu et al., 2018; Atkins and Freiberg, 2017) \nand are not discussed here. Instead, this review article is designed to assist laboratory \nresearchers, clinicians, and public health practitioners in understanding the manifold aspects \nof RVF disease in animals and humans. We first provide a historical perspective on the \n*Corresponding author. 8038 Biomedical Science Tower 3, 3501 Fifth Ave, Pittsburgh, PA 15213, USA. Hartman2@pitt.edu (A.L. \nHartman). \nAppendix A. Supplementary data\nSupplementary data related to this article can be found at http://dx.doi.org/10.1016/j.antiviral.2018.05.009.\nHHS Public Access\nAuthor manuscript\nAntiviral Res. Author manuscript; available in PMC 2023 July 03.\nPublished in final edited form as:\nAntiviral Res. 2018 August ; 156: 29\u201337. doi:10.1016/j.antiviral.2018.05.009.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 456
encoding: FLOAT32
metadata:
{"title": "Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review", "chroma:document": "Risk of Hepatocellular Carcinoma After Spontaneous \nClearance of Hepatitis C Virus and in Noncirrhosis \nChronic Hepatitis C Patients With Sustained Virological \nResponse: A Systematic Review\nChristine C. Hsu,1,a Harish Gopalakrishna,1,a Maria Mironova,1 Mei-Hsuan Lee,2 Chien-Jen Chen,3 Hwai-I Yang,3 Manfred Wiese,4,b Kyong-Mi Chang,5,6\nElizabeth C. Wright,7 Tomilowo Abijo,7 Jordan J. Feld,8,9 and David E. Kaplan5,6\n1Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA; 2Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, \nTaiwan; 3Genomics Research Center, Academia Sinica, Taipei, Taiwan; 4Department of Hepatology, University Hospital Leipzig, East German HCV Study Group, Leipzig, Germany; 5Division of \nGastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 6Division of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, \nPhiladelphia, Pennsylvania, USA; 7Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA; 8Department of Medicine, Division of \nGastroenterology, Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada; and 9Toronto Viral Hepatitis Care Network, Toronto, Canada\nIn a hepatitis C virus (HCV)\u2013controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then \ntreated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the \nCHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to \nHCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). \nFor noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 457
encoding: FLOAT32
metadata:
{"title": "Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review", "chroma:document": "and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not \naccounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may \nconfound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. \nAlthough it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.\nKeywords. hepatocellular carcinoma risk; hepatitis C; noncirrhosis.\naC. C. H. and H. G. contributed equally to this work.\nbEast German HCV Study Group members include K. Ende (Erfurt), U. G\u00f6bel (Cottbus), \nT. Heuchel (Chemnitz), U. Kullig (Dresden), K. Stein (Magdeburg), M. Wiese (Leipzig), \nS. Wollschl\u00e4ger (Dresden).\nCorrespondence: Christine C. Hsu, Liver Disease Branch, National Institute of Diabetes and \nDigestive and Kidney Diseases, 10 Center Drive, 10N248B, Bethesda, MD 20892 (christine. \nhsu@nih.gov ). J. Feld, Toronto Centre for Liver Disease (TCLD), Francis Family Liver Clinic, \nDepartment of Medicine, Division of Gastroenterology, Toronto General Hospital, 9EN-225, \n200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada (jordan.feld@uhn.ca).\nClinical Infectious Diseases\u00ae\n2023;77(S3):S245\u201356 \nPublished by Oxford University Press on behalf of Infectious Diseases Society of America 2023. \nThis work is written by (a) US Government employee(s) and is in the public domain in the US.\nhttps://doi.org/10.1093/cid/ciad380\nHepatitis C virus (HCV) is a single-stranded RNA virus trans-\nmitted to humans primarily via direct blood inoculation or trau-\nmatic percutaneous exposure [1]. About 25%\u201330% of acutely \ninfected individuals spontaneously clear the virus within 6\u201312 \nmonths of infection, while the majority progress to develop \nchronic HCV infection, after which spontaneous clearance is \nexceedingly rare [2]. Unlike chronic HCV that may cause pro-\ngressive liver damage, ultimately leading to cirrhosis, transient"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 458
encoding: FLOAT32
metadata:
{"title": "Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review", "chroma:document": "HCV infection is not associated with persistent liver injury \nor fibrosis. In patients with chronic infection who progress \nto cirrhosis, there is an increased risk of hepatocellular \ncarcinoma (HCC), which is reduced but not eliminated with \ntreatment-induced sustained virological response (SVR) [3]. \nThere is no known risk of HCC after spontaneously resolving \nacute HCV; however, data are limited. Recent studies have \nshown that HCV infection is associated with epigenetic changes \nin the host genome, leading to increased expression of cancer- \nrelated genes that persist even after viral clearance [4\u20136]. \nThese epigenetic changes were present in acute and chronic in-\nfections; they were demonstrated in patients with chronic HCV \ninfections (the majority with significant fibrosis or F2-F4 fibro-\nsis) but also in in vitro cell culture studies after hepatoma cell \nlines were briefly infected for 1\u20132 weeks and in primary human \nhepatocytes after shorter durations of infections [4, 6]. \nEpigenetic alterations similar to those seen in cell culture were \npresent in an 8-gene risk set associated with HCC in 7 liver bi-\nopsy samples from patients with active chronic HCV infection \nand were also present in 4 liver biopsy samples from patients \ncured of HCV with direct-acting antivirals (DAAs), raising con-\ncern that HCV infection may lead to a persistent change in cells \nthat could predispose to cancer [6]. However, it is notable that \nHCV-related HCC almost exclusively occurs in patients with \ncirrhosis, including in all cases of HCC described by Perez \nand colleagues and by Hamdane and colleagues [4, 6, 7]. It is fea-\nsible that the epigenetic changes can lead to pathways involved \nin hepatocarcinogenesis; however, these data suggest that \nHepatocellular Carcinoma Risk and Hepatitis C \u2022 CID 2023:77 (Suppl 3) \u2022 S245\nClinical Infectious Diseases                                          \nS U P P L E M E N T  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: 459
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates", "chroma:document": "RESEARCH ARTICLE\nBroadly neutralizing humanized SARS-CoV-2\nantibody binds to a conserved epitope on\nSpike and provides antiviral protection\nthrough inhalation-based delivery in non-\nhuman primates\nPaule HermetID1, Beno\u0131\u02c6t Delache2, Cecile Herate2, Esther Wolf3, Gaily Kivi1,\nErkki Juronen1, Karl Mumm1, Eva Z\u02c7usinaite4, Denis Kainov5, Eve Sankovski1,\nKai Viruma\u00a8e1, Anu Planken1, Andres Merits4, Jessica E. Besaw6, Ai Woon Yee6,\nTakefumi Morizumi6, Kyumhyuk Kim6, Anling Kuo6, Asma Berriche2, Nathalie Dereuddre-\nBosquet2, Quentin Sconosciuti2, Thibaut Naninck2, Francis Relouzat2,\nMariangela Cavarelli2, Mart Ustav1, Derek Wilson3, Oliver P. Ernst6,7, Andres Ma\u00a8nnik1,\nRoger LeGrand2, Mart Ustav, Jr.ID1*\n1 Icosagen Cell Factory OU\u00a8 ; Tartu, Estonia, 2 Universite\u00b4 Paris-Saclay, Inserm, CEA, Center for Immunology\nof Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT); Fontenay-aux-Roses,\nFrance, 3 York University; Toronto, Canada, 4 University of Tartu; Tartu, Estonia, 5 NTNU; Trondheim,\nNorway, 6 Department of Biochemistry, University of Toronto; Toronto, Canada, 7 Department of Molecular\nGenetics, University of Toronto; Toronto, Canada\n* mart.ustav.jr@icosagen.com\nAbstract\nThe COVID-19 pandemic represents a global challenge that has impacted and is expected\nto continue to impact the lives and health of people across the world for the foreseeable\nfuture. The rollout of vaccines has provided highly anticipated relief, but effective therapeu-\ntics are required to further reduce the risk and severity of infections. Monoclonal antibodies\nhave been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of\nconcern (VoC) continue to emerge, their utility and use have waned due to limited or no effi-\ncacy against these variants. Furthermore, cumbersome systemic administration limits easy\nand broad access to such drugs. As well, concentrations of systemically administered anti-\nbodies in the mucosal epithelium, a primary site of initial infection, are dependent on neona-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 460
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates", "chroma:document": "tal Fc receptor mediated transport and require high drug concentrations. To reduce the viral\nload more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2\nneutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-\nneutralizing properties. Administration of this antibody via a vibrating mesh nebulization\ndevice retained antibody integrity and resulted in effective distribution of the antibody in the\nupper and lower respiratory tract of non-human primates (NHP). In comparison with intrave-\nnous administration, significantly higher antibody concentrations can be obtained in the\nlung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This\napproach may reduce the barriers of access and uptake of antibody therapeutics in real-\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011532\nAugust 2, 2023\n1 / 32\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Hermet P, Delache B, Herate C, Wolf E,\nKivi G, Juronen E, et al. (2023) Broadly neutralizing\nhumanized SARS-CoV-2 antibody binds to a\nconserved epitope on Spike and provides antiviral\nprotection through inhalation-based delivery in\nnon-human primates. PLoS Pathog 19(8):\ne1011532. https://doi.org/10.1371/journal.\nppat.1011532\nEditor: Alexander E. Gorbalenya, Leiden University\nMedical Center: Leids Universitair Medisch\nCentrum, NETHERLANDS\nReceived: December 22, 2022\nAccepted: July 3, 2023\nPublished: August 2, 2023\nCopyright: \u00a9 2023 Hermet 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 available\nin the main text or the supplementary materials.\nThe X-ray diffraction data and X-ray crystal\nstructure have been deposited in PDB under\naccession code 8EL2. The cryo-EM map has been"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 461
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates", "chroma:document": "deposited in EMDB under accession code EMD-\n28228. The cryo-EM structure has been deposited\nin PDB under accession code 8ELJ."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 462
encoding: FLOAT32
metadata:
{"title": "The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and diseas\\\re susceptibility", "chroma:document": "The microgenderome revealed: sex differences in bidirectional \ninteractions between the microbiota, hormones, immunity and \ndisease susceptibility\nRavichandra Vemuri1, Kristyn E. Sylvia2, Sabra L. Klein2, Samuel C. Forster3,4, Magdalena \nPlebanski1,5, Raj Eri1, and Katie L. Flanagan1,5,6\n1School of Health Sciences, College of Health and Medicine, University of Tasmania, Hobart, \nTasmania, Australia\n2The W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns \nHopkins Bloomberg School of Public Health, Baltimore, Maryland, USA\n3Microbiota and Systems Biology Laboratory, Centre for Innate Immunity and Infectious Diseases, \nHudson Institute of Medical Research, Melbourne, Victoria, Australia\n4Department of Molecular and Translational Sciences, Monash University, Melbourne, Victoria, \nAustralia\n5School of Health and Biomedical Science, RMIT University, Melbourne, Victoria, Australia\n6Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia\nAbstract\nSex differences in immunity are well described in the literature and thought to be mainly driven by \nsex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the \nlargest immune organs in the body and contains multiple immune cells in the GIT-associated \nlymphoid tissue, Peyer\u2019s patches and elsewhere, which together have profound effects on local and \nsystemic inflammation. The GIT is colonised with microbial communities composed of bacteria, \nfungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple \ninteractions locally with immune cells that regulate the homeostatic environment and systemically \nin diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in \nanimal models and in humans, and these sex differences often lead to sex-dependent changes in \nlocal GIT inflammation, systemic immunity and susceptibility to a range of inflammatory"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 463
encoding: FLOAT32
metadata:
{"title": "The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and diseas\\\re susceptibility", "chroma:document": "diseases. The sexually dimorphic microbiome has been termed the \u2018microgenderome\u2019. Herein, we \nreview the evidence for the microgenderome and contemplate the role it plays in driving sex \ndifferences in immunity and disease susceptibility. We further consider the impact that biological \nsex might play in the response to treatments aimed at manipulating the GIT microbiota, such as \nprebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial \ntransplant. These alternative therapies hold potential in the treatment of both psychological (e.g., \nKatie L. Flanagan, katie.flanagan@ths.tas.gov.au. \nCompliance with ethical standards\nConflict of interest The authors declare that they have no conflict of interest.\nHHS Public Access\nAuthor manuscript\nSemin Immunopathol. Author manuscript; available in PMC 2019 May 04.\nPublished in final edited form as:\nSemin Immunopathol. 2019 March ; 41(2): 265\u2013275. doi:10.1007/s00281-018-0716-7.\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: 464
encoding: FLOAT32
metadata:
{"title": "The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial \\(RESET BRAIN\\", "chroma:document": "Vol:.(1234567890)\nJournal of Neurology (2023) 270:5600\u20135612\nhttps://doi.org/10.1007/s00415-023-11879-9\n1 3\nORIGINAL COMMUNICATION\nThe effect of\u00a0erenumab on\u00a0brain network function in\u00a0episodic \nmigraine patients: a\u00a0randomized, placebo\u2011controlled clinical trial \n(RESET BRAIN)\nMassimo\u00a0Filippi1,2,3,4,5 \u00a0\u00b7 Roberta\u00a0Messina1,2,5\u00a0\u00b7 Marta\u00a0Bartezaghi6\u00a0\u00b7 Ilaria\u00a0Cetta1,2,5\u00a0\u00b7 Bruno\u00a0Colombo2\u00a0\u00b7 \nLicia\u00a0Grazzi7\u00a0\u00b7 Daniele\u00a0Martinelli8,9\u00a0\u00b7 Raffaele\u00a0Ornello10\u00a0\u00b7 Anna\u00a0Pichiecchio9,11\u00a0\u00b7 Debora\u00a0Raimondi6\u00a0\u00b7 Antonio\u00a0Russo12\u00a0\u00b7 \nSimona\u00a0Sacco10\u00a0\u00b7 Alessandra\u00a0Splendiani10\u00a0\u00b7 Cristina\u00a0Tassorelli8,9\u00a0\u00b7 Renato\u00a0Turrini6\u00a0\u00b7 Paola\u00a0Valsasina1\u00a0\u00b7 \nMaria\u00a0Assunta\u00a0Rocca1,2,5\u00a0\u00b7 RESET BRAIN Study Group\nReceived: 8 June 2023 / Revised: 12 July 2023 / Accepted: 12 July 2023 / Published online: 8 August 2023 \n\u00a9 The Author(s) 2023\nAbstract\nBackground We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide \nreceptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect \nfollowing treatment discontinuation.\nMethods This was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in \nadult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12\u00a0weeks of erenumab \n140\u00a0mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain net-\nworks involved in migraine were investigated using a seed-based correlation approach.\nResults Sixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at \nweek 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major proto-\ncol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was \nperformed as a parallel comparison of erenumab vs placebo of the first 12\u00a0weeks of treatment. From baseline to week 12,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 465
encoding: FLOAT32
metadata:
{"title": "The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial \\(RESET BRAIN\\", "chroma:document": "compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal \ngray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a \n50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed \nwhen erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.\nConclusion Erenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, \nerenumab-induced brain RS FC changes tend to reverse when treatment is stopped.\nKeywords Headache\u00a0\u00b7 Prevention\u00a0\u00b7 Therapy\u00a0\u00b7 Neuroimaging\nIntroduction\nMigraine is a common and highly disabling neurological \ndisease [1]. Increased recognition of the huge personal and \nsocial impact of migraine has increased interest in the devel-\nopment of new treatments. Based on evidence supporting \na key role of calcitonin gene-related peptide (CGRP) in \nmigraine neurobiology, new migraine-specific preventive \ndrugs targeting the CGRP pathway have been developed \n[2]. Erenumab is a monoclonal antibody (mAb) targeting \nthe CGRP receptor. Previous randomized controlled trials \n(RCTs) showed the efficacy, safety and tolerability of ere-\nnumab in episodic and chronic migraine [3\u20135]. Erenumab \nis believed to exert its antimigraine effect in the periphery, \nmore precisely at the trigeminovascular level. This belief \nis sustained by the large size of anti-CGRP mAbs and their \npoor blood\u2013brain barrier (BBB) penetrability (1:1000 ratio) \n[6]. In this context, modulation of the trigeminal ganglion \nand fibers may limit the recruitment of pain signaling at \nthe meningeal tissues and inhibit pain transmission at the \ntrigeminal ganglion and nucleus [2]. On the other hand, the \nMembers of the RESET BRAIN Study Group are present in the \nAcknowledgement section.\nExtended author information available on the last page of the article"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 466
encoding: FLOAT32
metadata:
{"title": "Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments", "chroma:document": "Potential Anti-Mpox Virus Activity of Atovaquone, \nMefloquine, and Molnupiravir, and Their Potential  \nUse as Treatments\nDaisuke Akazawa,1,a Hirofumi Ohashi,1,a Takayuki Hishiki,1,b Takeshi Morita,1,b Shoya Iwanami,2,c Kwang Su Kim,2,3,4,c Yong Dam Jeong,2,4,c Eun-Sil Park,5\nMichiyo Kataoka,6 Kaho Shionoya,7,8 Junki Mifune,1 Kana Tsuchimoto,1 Shinjiro Ojima,1 Aa Haeruman Azam,1 Shogo Nakajima,7 Hyeongki Park,2\nTomoki Yoshikawa,9 Masayuki Shimojima,9 Kotaro Kiga,1 Shingo Iwami,2,10,11,12,13,14,15 Ken Maeda,5 Tadaki Suzuki,6 Hideki Ebihara,9\nYoshimasa Takahashi,1 and Koichi Watashi1,2,7,8,15\n1Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan; 2Interdisciplinary Biology Laboratory, Graduate School of Science, Nagoya University, \nNagoya, Japan; 3Department of Science System Simulation, Pukyong National University, Busan, South Korea; 4Department of Mathematics, Pusan National University, Busan, South Korea; \n5Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan; 6Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan; 7Department of \nVirology II, National Institute of Infectious Diseases, Tokyo, Japan; 8Department of Applied Biological Science, Tokyo University of Science, Noda, Japan; 9Department of Virology I, National \nInstitute of Infectious Diseases, Tokyo, Japan; 10Institute of Mathematics for Industry, Kyushu University, Fukuoka, Japan; 11Institute for the Advanced Study of Human Biology, Kyoto University, \nKyoto, Japan; 12Interdisciplinary Theoretical and Mathematical Sciences Program, RIKEN, Saitama, Japan; 13NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan; \n14Science Groove, Inc, Fukuoka, Japan; and 15MIRAI, Japan Science and Technology Agency, Saitama, Japan\nBackground. Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 467
encoding: FLOAT32
metadata:
{"title": "Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments", "chroma:document": "brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, \nby a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts \nby mathematical modeling.\nMethods. We screened 132 approved drugs using an MPXV infection cell system. We quantified antiviral activities of potential \ndrug candidates by measuring intracellular viral DNA and analyzed the modes of action by time-of-addition assay and electron \nmicroscopic analysis. We further predicted the efficacy of drugs under clinical concentrations by mathematical simulation and \nexamined combination treatment.\nResults. Atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of \n0.51\u20135.2 \u03bcM, which was more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and \nmolnupiravir targeted postentry processes. Atovaquone was suggested to exert its activity through inhibiting dihydroorotate \ndehydrogenase. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative \nmathematical simulations predicted that atovaquone can promote viral clearance in patients by 7 days at clinically relevant drug \nconcentrations.\nConclusions. These data suggest that atovaquone would be a potential candidate for treating mpox.\nKeywords. mpox; antiviral; atovaquone; dihydroorotate dehydrogenase; mefloquine; molnupiravir; pan-orthopoxvirus.\nReceived 23 November 2022; editorial decision 28 February 2023; accepted 08 March 2023; \npublished online 9 March 2023\naD. A. and H. O. contributed equally.\nbT. H. and T. M. contributed equally.\ncS. I., K. S. K., and Y. D. J contributed equally.\nCorrespondence: Koichi Watashi, PhD, Research Center for Drug and Vaccine Development, \nNational Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan \n(kwatashi@niid.go.jp).\nThe Journal of Infectious Diseases\u00ae\n2023;228:591\u2013603"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 468
encoding: FLOAT32
metadata:
{"title": "Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments", "chroma:document": "\u00a9 The Author(s) 2023. 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/jiad058\nMpox virus (MPXV) is a zoonotic virus classified in the \nOrthopoxvirus genus of the Poxviridae family that causes \nsmallpox-like diseases including rash, scab, fever, and head \nand body aches in humans [1\u20133]. After the first cases of human \ninfection were reported in Congo in 1970, mpox cases have \nbeen primarily reported in Central and West African countries, \nwith rare reports in other countries that have been linked with \nimportation and travel from endemic African regions. In May \n2022, an outbreak of human mpox was reported and involved \nmore than 80 000 cases in over 100 countries, mainly in Europe \nand North America at the time of writing of this article [4]. The \nWorld Health Organization declared this mpox outbreak a \nglobal health emergency on 23 July 2022.\nTecovirimat and brincidofovir are approved by the US Food \nand Drug Administration (FDA) for the treatment of smallpox \n[5]. Tecovirimat targets the viral-encoded VP37 protein to in-\nhibit the envelopment of intracellular mature virions, whereas \nbrincidofovir is a lipid conjugate prodrug of the nucleotide an-\nalogue cidofovir, which inhibits viral DNA replication [6\u20138]. \nAlthough these 2 drugs have been approved for smallpox \nAnti-Mpox Virus Activity of Atovaquone \u2022 JID 2023:228 (1 September) \u2022 591\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: 469
encoding: FLOAT32
metadata:
{"title": "Discordance for ankylosing spondylitis in monozygotic twins", "chroma:document": "Annals of the Rheumatic Diseases, 1977, 36, 360-364\nDiscordance for ankylosing spondylitis in\nmonozygotic twins\nC. J. EASTMOND* AND J. C. WOODROW\nFrom the Nuffield Unit ofMedical Genetics, Department of Medicine, University ofLiverpool, Ashton Street,\nP.O. Box 147, Liverpool L69 3BX\nSUMMARY\nThree monozygotic twin pairs, each over the age of 45 years, with ankylosing spondylitis\nare described. In two pairs there is discordance for this disease and in the third pair there is a marked\ndifference in the severity of this disease. These findings provide evidence that environmental factors\nare necessary not only for the initial development of ankylosing spondylitis, but possibly also for\ndetermining its future severity.\nGenetic factors are known to be important in the\naetiology\nof\nthe\nseronegative\nspondarthritides\n(Emery and Lawrence, 1967; Moll and Wright, 1973;\nLawrence,\n1974).\nThe\nfinding\nof an\nincreased\nfrequency of the histocompatibility antigen B27 in\nankylosing spondylitis by Brewerton et al. (1973a)\nand Schlosstein et al. (1973) suggested that at least\npart of the genetic\nsusceptibility\nto ankylosing\nspondylitis is due to genes in the HLA chromosomal\nregion. Associations have also been found between\nHLA B27 and Reiter's syndrome (Brewerton et al.,\n1973b; Woodrow et\nal.,\n1974) and the reactive\narthropathies (Aho\net\nal.,\n1973). While genetic\nfactors are known to be important in predisposing\nto Reiter's syndrome (Lawrence,\n1974) and the\nreactive arthropathies, there is also evidence that\ninfective micro-organisms\nare necessary\nfor the\ninitial development of these diseases. Similar direct\nevidence of an environmental factor being necessary\nfor the development of ankylosing spondylitis\nis\nFig. 1\nPedigree offamily\nP showing discordance for\nankylosing spondylitis in\nmonozygotic twins.\nII\nAll, B12\nA9, BD\nlacking. Moesmann (1960), reviewing the published\ndata on monozygous twins and ankylosing spondy-\nlitis, found nine reported twin pairs of which three\nt\nt\n2\n\\~~~~2\nII\n/\nA2,9; B7, 27\nFig. 2\nPedigree offamily"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 470
encoding: FLOAT32
metadata:
{"title": "Discordance for ankylosing spondylitis in monozygotic twins", "chroma:document": "R showing discordance for\nankylosing spondylitis in\nmonozygotic twins.\nt\nI\nt\n2\nII\nA2, B27\n,A2Bw15\nIII\nA2, B27\n/A2, B27\nA9, Bw 17\nA 2, Bw IS\n[J Ankylosing spondylitis\n[\nRadiological socroiliitic\nF\nUveitis\nAccepted for publication November 20, 1977\n* Present address: Department of Rheumatology & Rehabili-\nFilg 3\nPedigree offamily E showing concordance for\ntation, School of Medicine,\n36 Clarendon Road, Leeds\nradiological sacroilitis and discordance for clinical\nLS2 9PJ\nankylosing spondylitis and anterior uveitis in\nCorrespondence to Dr. J. C. Woodrow\nmonozygotic twins.\n360"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 471
encoding: FLOAT32
metadata:
{"title": "Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease", "chroma:document": "Endocrinology, 2022, 163, 1\u20138\nhttps://doi.org/10.1210/endocr/bqab254\nAdvance access publication 20 December 2021\nMini-Review\nSex and Gender Differences in Lung Cancer and Chronic \nObstructive Lung\u00a0Disease\nJill\u00a0M.\u00a0Siegfried,\n1Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA, and \n2Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA\nCorrespondence: Jill M.\u00a0Siegfried, PhD, Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church, Street SE, Minneapolis MN \n55455, USA. Email: jsiegfri@umn.edu.\nAbstract\nTwo highly prevalent pulmonary diseases, lung cancer and chronic obstructive lung disease (COPD), show both sex and gender differences in their \npresentations and outcomes. Sex differences are defined as biological differences associated with the male vs female genotype, and gender differ-\nences are defined as behavioral or social differences that primarily arise because of gender identity. The incidence of both lung cancer and COPD has \nincreased dramatically in women over the past 50\u00a0years, and both are associated with chronic pulmonary inflammation. Development of COPD is also \na risk factor for lung cancer. In this review, the main differences in lung cancer and COPD biology observed between men and women will be sum-\nmarized. Potential causative factors will be discussed, including the role of estrogen in promoting pro-growth and inflammatory phenotypes which \nmay contribute to development of both lung cancer and COPD. Response of the innate and adaptive immune system to estrogen is a likely factor in \nthe biology of both lung cancer and COPD. Estrogen available from synthesis by reproductive organs as well as local pulmonary estrogen synthesis \nmay be involved in activating estrogen receptors expressed by multiple cell types in the lung. Estrogenic actions, although more pronounced in"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 472
encoding: FLOAT32
metadata:
{"title": "Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease", "chroma:document": "women, may also have importance in the biology of lung cancer and COPD in men. Effects of estrogen are also timing and context dependent; the \nmultiple cell types that mediate estrogen action in the lungs may confer both positive and negative effects on disease processes.\nKey Words: lung cancer, chronic obstructive pulmonary disease, estrogen, estrogen receptor, sex difference, gender difference\nAbbreviations: COC, combined oral contraceptive; COPD, chronic obstructive pulmonary disease; EGFR, epidermal growth factor receptor; ER\u03b2, estrogen re-\nceptor beta; HRT, hormone replacement therapy; TAM, tumor-associated macrophage; TP53, tumor protein 53.\nLung cancer has been the number 1 cause of death from cancer \nin U.S.\u00a0women as well as men for over a decade (1), and chronic \nobstructive lung disease (COPD) has now emerged as the number \none overall cause of death in U.S.\u00a0women who smoke (2-4). COPD \nis also the second largest cause of death in men who smoke, be-\nhind heart disease (4, 5). Although the disease burden in women \noccurred in parallel with increased female smoking rates since the \nmid-twentieth century, for both COPD and lung cancer, the disease \narising in women shows distinctions from disease arising in men. \nTo better inform screening and treatment for individual patients, \nit is important to appreciate both the scope of burden in women \nfrom these 2 diseases, and how the presentation and outcome for \nlung cancer and COPD differs between men and women. In the \npreparation of this review, a PubMed literature search was con-\nducted for articles from 1990 onward using terms such as lung \ncancer, chronic obstructive pulmonary disease, COPD, emphy-\nsema, women, female, sex difference, gender difference, estrogen \nreceptor, and inflammation; this was followed by a selection, \nbased on expert opinion, of the relevance, soundness, and import-\nance of the studies for inclusion in a mini-review. Relevant refer-\nences cited by selected publications were also included.\nDifferences in Lung Cancer Presentation"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 473
encoding: FLOAT32
metadata:
{"title": "Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease", "chroma:document": "Between Women and\u00a0Men\nFor both lung cancer and COPD, diagnosis is more frequent at \na younger age in women than in men (1, 6-10), and diagnosis \nis also associated with lower exposure to tobacco in women \nthan in men (7-13). Population studies show in general a 20% \nto 25% lower average pack-years of smoking for women \ndiagnosed with COPD (9, 10, 13) or lung cancer (11, 12) \ncompared with men, and comparisons in early onset or low \nexposure groups show similar associations (13). Examination \nof age-specific incidence of lung cancer in U.S.\u00a0 men and \nwomen diagnosed before age 50 showed a crossover to an \nincrease in diagnoses in women born since 1965, even though \nsmoking prevalence and number of cigarettes per day among \nwomen remained lower than that of men (7). There has also \nbeen a specific increase in lung cancer incidence rates in pre-\nmenopausal women (7, 14). Rising trends are found in the \nproportion of new lung cancer diagnoses in never smokers \n(increasing to 15% in 2011-2013 from 8% in 1990-1995), \nwith twice the rate of new diagnosis in women compared to \nmen (7, 8). In general, both COPD and lung cancer diagnosed \nin never smokers is more common in women than in men \n(15-17). These differences, as well as those discussed below, \nare summarized in Table 1.\nFor lung cancer, histological presentation in women is more \nfrequently adenocarcinoma (2:1 ratio of adenocarcinoma to \nsquamous cell carcinoma), while men show a much higher \nprevalence of squamous cell carcinoma (1:1 ratio) (18). \nAdenocarcinoma of the lung in general is less associated with \nsmoking than other histological types, and risk for adeno-\ncarcinoma also declines more slowly after smoking cessation \nReceived: 17 May 2021. Editorial Decision: 11 December 2021. Corrected and Typeset: 13 January 2022\n\u00a9 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: \njournals.permissions@oup.com"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 474
encoding: FLOAT32
metadata:
{"title": "Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease", "chroma:document": "Downloaded from https://academic.oup.com/endo/article/163/2/bqab254/6470418 by guest on 15 August 2023"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 475
encoding: FLOAT32
metadata:
{"title": "Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function", "chroma:document": "ARTICLE\nOPEN\nGestational ethanol exposure impairs motor skills in female\nmice through dysregulated striatal dopamine and acetylcholine\nfunction\nSebastiano Bariselli\n1\u2709, Yolanda Mateo1, Noa Reuveni1 and David M. Lovinger1\nThis is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023\nFetal alcohol exposure has deleterious consequences on the motor skills of patients affected by Fetal Alcohol Spectrum Disorder\n(FASD) and in pre-clinical models of gestational ethanol exposure (GEE). De\ufb01cits in striatal cholinergic interneurons (CINs) and\ndopamine function impair action learning and execution, yet the effects of GEE on acetylcholine (ACh) and striatal dopamine\nrelease remain unexplored. Here, we report that alcohol exposure during the \ufb01rst ten postnatal days (GEEP0-P10), which mimics\nethanol consumption during the last gestational trimester in humans, induces sex-speci\ufb01c anatomical and motor skill de\ufb01cits in\nfemale mice during adulthood. Consistent with these behavioral impairments, we observed increased stimulus evoked-dopamine\nlevels in the dorsolateral striatum (DLS) of GEEP0-P10 female, but not male, mice. Further experiments revealed sex-speci\ufb01c de\ufb01cits in\n\u03b22-containing nicotinic ACh receptor (nAChR)-modulation of electrically evoked dopamine release. Moreover, we found a reduced\ndecay of ACh transients and a decreased excitability of striatal CINs in DLS of GEEP0-P10 females, indicating striatal CIN dysfunctions.\nFinally, the administration of varenicline, a \u03b22-containing nAChR partial agonist, and chemogenetic-mediated increase in CIN\nactivity improved motor performance in adult GEEP0-P10 females. Altogether, these data shed new light on GEE-induced striatal\nde\ufb01cits and establish potential pharmacological and circuit-speci\ufb01c interventions to ameliorate motor symptoms of FASD.\nNeuropsychopharmacology (2023) 48:1808\u20131820; https://doi.org/10.1038/s41386-023-01594-4\nINTRODUCTION\nAlcohol exposure during development leads to heterogeneous"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 476
encoding: FLOAT32
metadata:
{"title": "Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function", "chroma:document": "anatomical and neurobehavioral conditions, collectively known as\nFetal Alcohol Spectrum Disorder (FASD) [1]. While a signi\ufb01cant\nnumber of women with Alcohol Use Disorder (AUD) abstain\nduring early pregnancy, a large proportion of them report alcohol\nuse during perinatal periods [2, 3]. The teratogenic effects of\nethanol include impaired cognitive \ufb02exibility and motor de\ufb01cits\n[4, 5], severely affecting patient\u2019s everyday life and resulting in\nhigh socioeconomic costs [6]. Despite a reduced overall survival\nrate and higher prevalence of FASD in males during infancy [7],\nthe higher severity of dysmorphology and cognitive symptoms\nreported in females [8] points to sex-related differences in the\nneurobehavioral effects of FASD.\nIn animal models of gestational ethanol exposure (GEE), female\noffspring show decreased behavioral inhibition [9] and impaired\nextinction of aversive memories compared to males [10]. While GEE\ninterferes with cognitive and motor skill learning [11\u201314], sex-speci\ufb01c\neffects on motor function remain unclear. Considering the high rate\nof alcohol relapse during perinatal periods [2] and the developmental\nsimilarities between the last trimester of human pregnancy and the\n\ufb01rst 10 postnatal days (P0-P10) in mice [15], we implemented a\nmouse model of binge-like and late-term gestational ethanol\nexposure that would cover this developmental period (GEEP0-P10).\nWe have previously hypothesized that the behavioral de\ufb01cits\ninduced by GEE might derive from synaptic and circuit de\ufb01cits in the\nstriatum [16], a brain region involved in cognitive and motor function\n[17\u201319] and particularly vulnerable to the teratogenic effects of fetal\nalcohol exposure [13, 20]. Dorsal striatal circuits contain different\nneuronal populations, including medium spiny neurons (MSNs), the\nprimary striatal projection neurons, acetylcholine (ACh)-releasing\ninterneurons (CINs), as well as dopaminergic inputs from the\nmidbrain. Recent simultaneous in vivo \ufb01ber photometry experiments"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 477
encoding: FLOAT32
metadata:
{"title": "Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function", "chroma:document": "revealed coordinated ACh and dopamine signaling during decision-\nmaking [21] and spontaneous locomotion [22, 23] in the dorsal\nstriatum. These data support previous evidence that ACh dysregula-\ntion impairs cognitive function and motor skills [24\u201326], the latter\ntypically assessed with rotarod tasks in rodents. Moreover, Fast Scan\nCyclic Voltammetry (FSCV) experiments demonstrate that pre-\nsynaptic nAChR and glutamatergic receptor activation modulates\nelectrically evoked or ACh-driven striatal dopamine release [27\u201330].\nWhile previous experiments show that GEE impairs dopamine\nreceptor expression and binding in rodents [31, 32] and monkeys\n[33], whether GEE alters striatal dopamine dynamics remains an open\nquestion.\nIn addition to striatal dopamine dysregulation, GEE impairs ACh\nfunction\nin\nseveral\nbrain\nregions.\nIn\nrats,\nGEE\nalters\nthe\ndevelopmental expression of choline acetyltransferase (ChAT)\n[34], the enzyme that catalyzes ACh synthesis, with no obvious\nchanges in the expression of acetylcholinesterase (AChE), the\nenzyme that catalyzes ACh degradation, in nucleus basalis of\nMeynert (NBM), neocortex, or striatum [35, 36]. Along with\nReceived: 14 December 2022 Revised: 29 March 2023 Accepted: 21 April 2023\nPublished online: 15 May 2023\n1Laboratory for Integrative Neuroscience (LIN), NIH-NIAAA, 5625 Fishers Lane, Bethesda, MD 20892, USA. \u2709email: sebastiano.bariselli@nih.gov\nwww.nature.com/npp\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 478
encoding: FLOAT32
metadata:
{"title": "Taking stock of value in the orbitofrontal cortex", "chroma:document": "Taking stock of value in the orbitofrontal cortex\nEric B. Knudsen1, Joni D. Wallis2\n1Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.\n2Department of Psychology and Helen Wills Neuroscience Institute, University of California \nBerkeley, Berkeley, California, USA.\nAbstract\nPeople with damage to the orbitofrontal cortex (OFC) have specific problems making decisions, \nwhereas their other cognitive functions are spared. Neurophysiological studies have shown that \nOFC neurons fire in proportion to the value of anticipated outcomes. Thus, a central role of the \nOFC is to guide optimal decision-making by signalling values associated with different choices. \nUntil recently, this view of OFC function dominated the field. New data, however, suggest that the \nOFC may have a much broader role in cognition by representing cognitive maps that can be used \nto guide behaviour and that value is just one of many variables that are important for behavioural \ncontrol. In this Review, we critically evaluate these two alternative accounts of OFC function and \nexamine how they might be reconciled.\nIn the 1990s, Damasio brought attention to the fascinating deficits exhibited by people with \ndamage to the orbitofrontal cortex (OFC)1. These individuals would make terrible choices \nand their everyday lives lurched from one catastrophic decision to another, yet they would \nperform normally on standard laboratory tests of cognition2. Damasio developed new tests \nbased on real-world decision-making3. Participants were given play money and had to make \nchoices across a series of gambles based on reward history. People with OFC damage \nperformed poorly, quickly losing all their money as they failed to learn from the outcomes \nassociated with each gamble. These impairments had gone unnoticed for years, simply \nbecause no one thought to assess individuals\u2019 decision-making in a neuropsychological \nexam. Inspired by Damasio\u2019s findings, many labs started to record OFC neurons in non-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 479
encoding: FLOAT32
metadata:
{"title": "Taking stock of value in the orbitofrontal cortex", "chroma:document": "human primates during decision-making tasks. In a seminal study, Padoa-Schioppa and \nAssad presented monkeys with choices between different amounts of various juices4. OFC \nneurons encoded the amount of juice, weighted by how much the monkey liked it, consistent \nwith how valuable the option was to the animal. This made a neat and compelling story: \nindividuals with OFC damage made poor decisions because they were missing the neurons \nthat would signal the value of each option.\nwallis@berkeley.edu .\nAuthor contributions\nThe authors contributed equally to all aspects of the article.\nCompeting interests\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nNat Rev Neurosci. Author manuscript; available in PMC 2023 September 20.\nPublished in final edited form as:\nNat Rev Neurosci. 2022 July ; 23(7): 428\u2013438. doi:10.1038/s41583-022-00589-2.\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: 480
encoding: FLOAT32
metadata:
{"title": "Knife\u0090s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines", "chroma:document": "REVIEW ARTICLE\nOPEN\nKnife\u2019s edge: Balancing immunogenicity and reactogenicity in\nmRNA vaccines\nJisun Lee1,6, Matthew C. Woodruff2,3,6, Eui Ho Kim4\u2709 and Jae-Hwan Nam\n1,5\u2709\n\u00a9 The Author(s) 2023\nSince the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of\ntherapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were developed and approved in record-breaking\ntime, revolutionizing the vaccine development landscape. Although \ufb01rst-generation COVID-19 mRNA vaccines have demonstrated\nover 90% ef\ufb01cacy, alongside strong immunogenicity in humoral and cell-mediated immune responses, their durability has lagged\ncompared to long-lived vaccines, such as the yellow fever vaccine. Although worldwide vaccination campaigns have saved lives\nestimated in the tens of millions, side effects, ranging from mild reactogenicity to rare severe diseases, have been reported. This\nreview provides an overview and mechanistic insights into immune responses and adverse effects documented primarily for\nCOVID-19 mRNA vaccines. Furthermore, we discuss the perspectives of this promising vaccine platform and the challenges in\nbalancing immunogenicity and adverse effects.\nExperimental & Molecular Medicine (2023) 55:1305\u20131313; https://doi.org/10.1038/s12276-023-00999-x\nINTRODUCTION\nFor more than 100 years, public vaccination campaigns have\nremained our most successful interdictions into the prevention of\nhuman infectious diseases. Prophylactic vaccination has been\nimplemented to increase life expectancy and improve public\nhealth, thereby saving countless lives1,2. However, while vaccine\ntechnology has signi\ufb01cantly advanced over the past century3, the\nconceptualization of an \u201coptimal\u201d vaccine has only grown more\ncomplicated with the rapid progress in our understanding of the\ncellular components associated with protective immunity. Con-\nventional vaccines have often failed against dif\ufb01cult-to-target and\nantigenically variable viruses such as human immunode\ufb01ciency"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 481
encoding: FLOAT32
metadata:
{"title": "Knife\u0090s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines", "chroma:document": "virus (HIV) and hepatitis C virus (HCV)4, and due to both the time\nrequired for development processes and rapid mutation of the\nviral genome, some traditional vaccine technologies are poorly\nsuited for sudden outbreaks that threaten global health and\nsecurity, such as the recent coronavirus disease (COVID-19)\npandemic. Considering these constraints, messenger RNA (mRNA)\nvaccines have represented an attractive alternative to conven-\ntional\nvaccines\ndue\nto\ntheir\ncell-free,\nrapid,\nand\nscalable\ndevelopment and production5.\nmRNA vaccine technology has been extensively studied for\ncancer treatment owing to its ability to trigger a potent T-cell\nresponse, well-tolerated nature, and suitability for personalized\ndesign. The details of mRNA-based cancer vaccine development\nare comprehensively described in recent reviews6\u20138. However, it\nwas the COVID-19 pandemic that incited interest in mRNA for\nmedical application, leading to expedited licensure of two mRNA\nvaccines9,10, with several others at various stages of development\nor in clinical trials11. The unprecedented pace of the SARS-CoV-2\nvaccine rollout was accomplishable only because of the unique\nproperties of mRNA vaccine platforms. Tremendous advance-\nments have been made in the ef\ufb01cient delivery and expression of\nantigenic mRNA for current COVID-19 mRNA vaccines. Modi\ufb01ca-\ntions such as N1-methylpseudouridine, 5\u2032 capping, and codon\noptimization have been used to optimize mRNA production to\nmaximize antigen availability12,13. To enable ef\ufb01cient delivery of\nmRNA to the cytosol of target cells, lipid nanoparticles (LNPs)\ncomprised of ionizable cationic lipids, cholesterol, phospholipids,\nand polyethylene glycol (PEG) have been used. The LNP\u2013mRNA\ncomplex is neutral at physiological pH but becomes positively\ncharged when the LNP is sequestered and acidi\ufb01ed in the\nendosome; this process is followed by fusion with the endosomal\nmembrane and the release of mRNA into the cytosol13\u201315.\nComposed\nsolely\nof\nmodi\ufb01ed\nmRNA\nencapsulated\nby\nan"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 482
encoding: FLOAT32
metadata:
{"title": "Knife\u0090s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines", "chroma:document": "by\nan\nengineered LNP16, this approach eliminates the need for the\nmassive pathogen culturing efforts required for attenuated or\nkilled/split vaccines, such as the polio17 or in\ufb02uenza vaccine18. De\nnovo DNA template synthesis and basic molecular biology\npropagation allow this technology to signi\ufb01cantly outpace even\nprotein subunit-based approaches, resulting in nimble, cost-\neffective platforms capable of rapidly deploying to the front line\nto improve public health19.\nThe COVID-19 pandemic has allowed for a real-time assessment\nof the strong potential of mRNA vaccines to rapidly reshape the\nworldwide landscape of a deadly emerging infectious disease.\nFirst-generation SARS-CoV-2 vaccines were fully designed within a\nfew weeks of the publication of the full-length Wuhan strain spike\nReceived: 30 November 2022 Revised: 26 February 2023 Accepted: 27 March 2023\nPublished online: 10 July 2023\n1Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea. 2Department of Medicine, Division of\nRheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA. 3Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.\n4Viral Immunology Laboratory, Institut Pasteur Korea, Seongnam 13488, Republic of Korea. 5BK Plus Department of Biotechnology, The Catholic University of Korea, Bucheon,\nGyeonggi-do 14662, Republic of Korea. 6These authors contributed Equally: Jisun Lee, Matthew C. Woodruff. \u2709email: euiho.kim@ip-korea.org; jhnam@catholic.ac.kr\nwww.nature.com/emm\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 483
encoding: FLOAT32
metadata:
{"title": "Pathological Bergmann glia alterations and disrupted calcium dynamics in ataxic Canavan disease mice", "chroma:document": "Pathological Bergmann glia alterations and disrupted calcium \ndynamics in ataxic Canavan disease mice\nVanessa L. Hull1,2, Yan Wang1,2, Travis Burns1,2, Sarah Sternbach3, Shuaishuai Gong1,2, \nJennifer McDonough3, Fuzheng Guo1,2, Laura N. Borodinsky2,4, David Pleasure1,2\n1Department of Neurology, University of California Davis School of Medicine, Sacramento, \nCalifornia, USA\n2Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, Sacramento, \nCalifornia, USA\n3Department of Biological Sciences, Kent State University, Kent, Ohio, USA\n4Department of Physiology & Membrane Biology, University of California Davis School of \nMedicine, Sacramento, California, USA\nAbstract\nCanavan disease (CD) is a recessively inherited pediatric leukodystrophy resulting from \ninactivating mutations to the oligodendroglial enzyme aspartoacylase (ASPA). ASPA is \nresponsible for hydrolyzing the amino acid derivative N-acetyl-L-aspartate (NAA), and without \nit, brain NAA concentrations increase by 50% or more. Infants and children with CD present with \nprogressive cognitive and motor delays, cytotoxic edema, astroglial vacuolation, and prominent \nspongiform brain degeneration. ASPA-deficient CD mice (Aspanur7/nur7) present similarly with \nelevated NAA, widespread astroglial dysfunction, ataxia, and Purkinje cell (PC) dendritic atrophy. \nBergmann glia (BG), radial astrocytes essential for cerebellar development, are intimately \nintertwined with PCs, where they regulate synapse stability, functionality, and plasticity. BG \ndamage is common to many neurodegenerative conditions and frequently associated with PC \ndysfunction and ataxia. Here, we report that, in CD mice, BG exhibit significant morphological \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which \npermits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no \nmodifications or adaptations are made."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 484
encoding: FLOAT32
metadata:
{"title": "Pathological Bergmann glia alterations and disrupted calcium dynamics in ataxic Canavan disease mice", "chroma:document": "Correspondence Vanessa L. Hull and David Pleasure, Institute for Pediatric Regenerative Medicine, UC Davis, c/o Shriners Hospital \nfor Children, 2425 Stockton Blvd, Sacramento, CA 95817, USA. vhull@mednet.ucla.edu and depleasure@ucdavis.edu.\nAUTHOR CONTRIBUTIONS\nDavid Pleasure and Vanessa Hull conceived and designed the study. Vanessa Hull performed the immunohistochemistry, confocal \nimaging, morphological analyses and calcium imaging/analysis. Yan Wang performed the qPCR. Yan Wang and Vanessa Hull \ncompleted the cell culture experiments with help from Shuaishuai Gong. Fuzheng Guo provided required materials and guidance for \nqPCR and cell culture experiments. Laura Borodinsky designed the calcium imaging experiments and provided required materials and \nequipment. Sarah Sternbach and Jenny McDonough performed and analyzed NAA assays. Travis Burns performed rotarod testing. \nVanessa Hull and David Pleasure wrote the manuscript. All authors reviewed and approved the manuscript.\nPresent address\nVanessa L. Hull, Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, \nCalifornia, USA.\nSUPPORTING INFORMATION\nAdditional supporting information can be found online in the Supporting Information section at the end of this article.\nCONFLICT OF INTEREST STATEMENT\nNone.\nHHS Public Access\nAuthor manuscript\nGlia. Author manuscript; available in PMC 2023 December 01.\nPublished in final edited form as:\nGlia. 2023 December ; 71(12): 2832\u20132849. doi:10.1002/glia.24454.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 485
encoding: FLOAT32
metadata:
{"title": "Stem cell therapy in retinal diseases", "chroma:document": "1478  \uff5cNEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nReview\nAbstract  \nAlteration of the outer retina leads to various diseases such as age-related macular degeneration \nor retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness. Despite \nintensive research in the field of retinal disorders, there is currently no curative treatment. Several \ntherapeutic approaches such as cell-based replacement and gene therapies are currently in \ndevelopment. In the context of cell-based therapies, different cell sources such as embryonic stem \ncells, induced pluripotent stem cells, or multipotent stem cells can be used for transplantation. In the \nvast majority of human clinical trials, retinal pigment epithelial cells and photoreceptors are the cell \ntypes considered for replacement cell therapies. In this review, we summarize the progress made in \nstem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.\nKey Words: age-related macular degeneration; cell transplantation; clinical trial; retinal disease; \nretinal dystrophy; stem cell\nIntroduction \nThe progressive degeneration of photoreceptors characterizes various \nretinal diseases such as age-related macular degeneration (AMD) and \nretinitis pigmentosa (RP), leading to progressive vision and visual field \nloss and ultimately to blindness (Verbakel et al., 2018; Voisin et al., 2022). \nIn AMD, there is geographic atrophy (called atrophic AMD form) and \nabnormal and excessive growth of blood vessels in the eye called choroidal \nneovascularization (the exudative AMD form). Anti-vascular endothelial \ngrowth factor intravitreal therapy, which is the only effective treatment for \nexudative AMD, targets choroidal neovascularization but not the disease \nitself. To date, aside from some positive advances in gene therapy for very \nfew particular forms of retinal dystrophy (i.e., voretigene neparvovec), there"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 486
encoding: FLOAT32
metadata:
{"title": "Stem cell therapy in retinal diseases", "chroma:document": "is no curative treatment for these retinal diseases (Stingl et al., 2022). In this \ncontext, over the past two decades, the development of cell-based therapy \nhas been investigated as a means of replacing apoptotic or dystrophic cells \nand restoring visual function. Mammalian retinas have limited regenerative \ncapacity, and stem cells in regenerative strategy seem to be a promoting \napproach (Salas et al., 2021). Despite encouraging results, stem cell therapy \nneeds to be optimized to improve its effectiveness in the treatment of retinal \ndiseases. This review focuses on the retinal dystrophies and the different stem \ncell populations and their use for transplantation in retinal diseases. \nSearch Strategy and Selection Criteria\nStudies cited in this review were published between 2000 and 2022 and \nsearched from PubMed or Google Scholar databases. The following keywords \nwere used for this research: stem cell transplantation, retinal disease, retinal \ndegeneration, retinal dystrophy, stem cell therapy, age-related macular \ndegeneration, retina, retinitis pigmentosa, Stargardt disease, bone marrow-\nderived stem cells, retinal precursor cells, clinical trials, retinal pigment \nepithelial cells, mesenchymal stem cells, embryonic stem cells, and induced \npluripotent stem cells.\n1Laboratoire de Neurosciences Exp\u00e9rimentales et Cliniques, Universit\u00e9 de Poitiers, INSERM 1084, Poitiers, France; 2Department of Ophthalmology, CHU Poitiers, Poitiers, France; \n3Laboratoires Thea, Clermont-Ferrand, France\n*Correspondence to: Audrey Voisin, PhD, audrey.voisin@univ-poitiers.fr.\nhttps://orcid.org/0000-0002-9766-5759 (Audrey Voisin) \nHow to cite this article: Voisin A, P\u00e9naguin A, Gaillard A, Leveziel N (2023) Stem cell therapy in retinal diseases. Neural Regen Res 18(7):1478-1485. \nFrom the Contents\nIntroduction\n1478\nSearch Strategy and Selection Criteria\n1478\nRetinal Degeneration\n1478\nCell-Based Therapy\n1479\nCell Source\n1479\nPreclinical Model \n1480\nClinical Trials\n1481\nConclusion\n1483\nStem cell therapy in retinal diseases"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 487
encoding: FLOAT32
metadata:
{"title": "Stem cell therapy in retinal diseases", "chroma:document": "https://doi.org/10.4103/1673-5374.361537\nDate of submission: July 27, 2022 \nDate of decision: September 14, 2022 \nDate of acceptance: October 24, 2022 \nDate of web publication: November 25, 2022 \nAudrey Voisin1, 2, *, Amaury P\u00e9naguin1, 3, Afsaneh Gaillard1, Nicolas Leveziel1, 2\nRetinal Degeneration\nThe human adult retina is organized in ten histological layers with one glial \ncell type, the M\u00fcller glial cells, and six major types of neurons: two main cell \ntypes of photoreceptors (PRs; rods and cones), bipolar cells, amacrine cells, \nhorizontal cells, and ganglion cells. Retinal cell bodies are organized into three \nlayers from apical to basal; the outer nuclear layer, the inner nuclear layer, and \nthe ganglion cell layer. Aside from these layers, the outer and inner plexiform \nlayers contain axons and dendrites of neuronal cells. The outer part of the \nretina is limited by the retinal pigment epithelium (RPE) layer. These cells \nfulfill many functions such as epithelial transport, visual cycle, phagocytosis, \nsecretion, and immune modulation (Voisin et al., 2019). \nRecessive Stargardt macular degeneration\nRecessive Stargardt macular degeneration (STGD1) is common retinal \ndystrophy of varying severity, the most common and severe form during \nchildhood, and the less common form during adulthood (Tanna et al., 2017). \nSTGD1 is an autosomal recessive disease with an incidence of 1:8000 to \n1:10,000, caused by mutations in the ATP binding cassette subfamily A \nmember 4 (ABCA4) gene (Spiteri Cornish et al., 2017; Cicinelli et al., 2019). The \nprotein encoded by ABCA4 is involved in the visual cycle and localized in the \nphotoreceptor outer segments. The disease is characterized by choriocapillaris \natrophy and by accumulation of lipofuscin, an age-related pigment, in RPE, \nleading to PR degeneration (Figure 1A). Patients affected by STGD1 usually \nexperience a rapid bilateral central visual loss with dyschomatopsia and central \nscotoma. Disease-causing variants of ABCA4 are also associated with cone, rod,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 488
encoding: FLOAT32
metadata:
{"title": "Stem cell therapy in retinal diseases", "chroma:document": "and rod-cone dystrophies (Cremers et al., 2020).\nRP \nRP is the most frequent hereditary (30\u201340% autosomal dominant, 40\u201360% \nautosomal recessive, and 5\u201315% X-linked) retinal disease with an incidence \nof approximately 1:4000 (Verbakel et al., 2018). Patients suffering from RP \nfrequently report night blindness and progressive visual field loss beginning \naround the age of 20\u201330 years, and finally are complete blindness at the \nlate stage. The disease is characterized by primary degeneration of PR rods \n(eventually secondary degeneration of cones in case of complete blindness) \n(Ali et al., 2017). At fundus examination, the disease is clinically characterized \nby dark bone-spicule pigmentation and attenuated blood vessels (Figure 1B; \nVerbakel et al., 2018). \nAMD\nAMD is a complex multifactorial disease characterized by degeneration of the \nmacula usually preceded by drusen formation made up of the extracellular \naccumulation of proteins and lipids (Voisin et al., 2022). The disease usually \naffects older adult individuals and is the leading cause of blindness in \nindustrialized countries. The pathogenesis of this retinal disease is associated \nwith both genetic (CFH, ARMS2, etc.) and environmental factors (smoking \nand light exposure). AMD is classified in an atrophic form (Figure 1C) with the \nprogressive development of macular atrophy and an exudative form (Figure \n1D) with the development of choroidal neovascularization (Nashine, 2021). \nBoth forms are clinically characterized by visual acuity decrease, central \nscotoma, and metamorphopsia."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 489
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues", "chroma:document": "Sex Differences in Gene Expression and Regulatory Networks \nacross 29 Human Tissues\nCamila M. Lopes-Ramos1, Cho-Yi Chen2, Marieke L. Kuijjer3, Joseph N. Paulson4, Abhijeet \nR. Sonawane5, Maud Fagny6, John Platig5, Kimberly Glass1,5, John Quackenbush1,5,7,*, \nDawn L. DeMeo5,8,9,*\n1Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA\n2Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan\n3Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, \nOslo, Norway\n4Department of Biostatistics, Product Development, Genentech Inc., San Francisco, CA, USA\n5Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s \nHospital and Harvard Medical School, Boston, MA, USA\n6Genetique Quantitative et Evolution-Le Moulon, Universite Paris-Saclay, Institut National de \nRecherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement, Centre National de la Recherche \nScientifique, AgroParisTech, Gif-sur-Yvette, France\n7Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, \nMA, USA\n8Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Boston, MA, \nUSA\n9Lead Contact\nSUMMARY\nSex differences manifest in many diseases and may drive sex-specific therapeutic responses. To \nunderstand the molecular basis of sex differences, we evaluated sex-biased gene regulation by \nconstructing sample-specific gene regulatory networks in 29 human healthy tissues using 8,279 \nwhole-genome expression profiles from the Genotype-Tissue Expression (GTEx) project. We find \nsex-biased regulatory network structures in each tissue. Even though most transcription factors \n*Correspondence: johnq@hsph.harvard.edu (J.Q.), dawn.demeo@channing.harvard.edu (D.L.D.).\nAUTHOR CONTRIBUTIONS\nConceptualization, C.M.L.-R., C.-Y.C., M.L.K., J.N.P., A.R.S., M.F., J.P., K.G., J.Q., and D.L.D.; Methodology, C.M.L.-R., C.-Y.C.,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 490
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues", "chroma:document": "M.L.K., K.G., J.Q., and D.L.D.; Formal Analysis, C.M.L.-R. and C.-Y.C.; Investigation, C.M.L.-R. and C.-Y.C.; Resources, J.Q. and \nD.L.D.; Data Curation, J.N.P. and J.Q.; Writing \u2013 Original Draft, C.M.L.-R. and C.-Y.C.; Writing \u2013 Review & Editing, C.M.L.-R., C.-\nY.C., M.L.K., J.N.P., A.R.S., M.F., J.P., K.G., J.Q., and D.L.D.; Visualization, C.M.L.-R. and C.-Y.C.; Supervision, J.Q. and D.L.D.; \nFunding Acquisition, M.L.K., K.G., J.Q., and D.L.D.\nSUPPLEMENTAL INFORMATION\nSupplemental Information can be found online at https://doi.org/10.1016/j.celrep.2020.107795.\nDECLARATION OF INTERESTS\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nCell Rep. Author manuscript; available in PMC 2021 February 22.\nPublished in final edited form as:\nCell Rep. 2020 June 23; 31(12): 107795. doi:10.1016/j.celrep.2020.107795.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 491
encoding: FLOAT32
metadata:
{"title": "Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure", "chroma:document": "ARTICLE\nOPEN\nAltered behavior, brain structure, and neurometabolites in a rat\nmodel of autism-speci\ufb01c maternal autoantibody exposure\nMatthew R. Bruce\n1, Amalie C. M. Couch2, Simone Grant3, Janna McLellan1, Katherine Ku3, Christina Chang3, Angelica Bachman3,\nMatthew Matson3, Robert F. Berman4,5, Richard J. Maddock\n3, Douglas Rowland\n6, Eugene Kim\n7, Matthew D. Ponzini7,\nDanielle Harvey8, Sandra L. Taylor8, Anthony C. Vernon\n2,9,10, Melissa D. Bauman3,5,10 and Judy Van de Water\n1,5\u2709\n\u00a9 The Author(s) 2023\nMaternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant\nconnection exists between in\ufb02ammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In\nthis study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce\nneuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure\nin rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following con\ufb01rmation of aAb\nproduction in rat dams and antigen-speci\ufb01c immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain\nstructure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced de\ufb01cit in\nsocial play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic\nresonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-speci\ufb01c\ndifferences in total and regional brain volume. Treatment-speci\ufb01c effects by region appeared to converge on midbrain and\ncerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were\ncollected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 492
encoding: FLOAT32
metadata:
{"title": "Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure", "chroma:document": "decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control\nanimals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and\nneurometabolites; reminiscent of \ufb01ndings observed in clinical ASD.\nMolecular Psychiatry (2023) 28:2136\u20132147; https://doi.org/10.1038/s41380-023-02020-3\nINTRODUCTION\nAutism spectrum disorder (ASD) is clinically de\ufb01ned by a collection\nof symptoms including alterations in social, communicative, and\nstereotyped behaviors [1]. Despite these well-de\ufb01ned behaviorally\ndiagnostic criteria, the molecular basis of these behaviors remains\nunclear.\nHowever,\nevidence\nexists\nfor the dysregulation\nof\nimportant brain signaling molecules and pathways in ASD etiology;\nincluding imbalances in key neurotransmitters, gamma aminobu-\ntyric acid (GABA) and glutamate [2], or alterations in cellular\nmetabolism including mitochondrial function [3] and one-carbon\nsignaling [4]. Understanding which physiological systems and\nrelated signaling molecules are impacted, as well as the roles of\ndevelopmental timing and biological sex on individual outcomes\nwill aid in early diagnosis and therapeutic strategies in ASD.\nGenetic in\ufb02uence is also an important factor in ASD, and studies\ninvestigating genetic risk have identi\ufb01ed a multitude of candidate\ngene networks associated with diagnosis [5]. These include gene\nnetworks important for synaptic function [6], cellular metabolism\n[7], and immune signaling [8, 9]. The development of ASD,\nhowever, likely results from a combination of genetic and\nenvironmental factors, with early-life exposure to environmental\ninsults playing an important role in some cases [10, 11]. In support\nof this view, numerous studies provide evidence that changes in\nmaternal immune signaling during pregnancy associate with ASD\ndiagnosis in offspring [12\u201315]. Prominent among these \ufb01ndings is\nthat ~20% of mothers of children subsequently diagnosed with"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 493
encoding: FLOAT32
metadata:
{"title": "Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure", "chroma:document": "ASD possess circulating aAbs directed against proteins known to\nbe important for early development. This phenomenon has been\ntermed maternal autoantibody-related (MAR) ASD [16, 17]. We\nhave previously shown that exposure to clinically relevant patterns\nof these aAbs results in changes to behavior, brain structure (as\nmeasured by sMRI), and neural progenitor cell proliferation in\nmice [18\u201320]. What remains to be understood are the effects of\nMAR-ASD aAb exposure on offspring across the lifespan, the\nimpact of aAbs on cell signaling and target proteins, and the\nin\ufb02uence of sex as a biological variable.\nReceived: 15 August 2022 Revised: 23 February 2023 Accepted: 27 February 2023\nPublished online: 27 March 2023\n1Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, CA, USA. 2Department of Basic and Clinical\nNeuroscience, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, UK. 3Department of Psychiatry and Behavioral Sciences, University of\nCalifornia, Davis, CA, USA. 4Department of Neurological Surgery, University of California, Davis, CA, USA. 5MIND Institute, University of California, Davis, CA, USA. 6Center for\nMolecular and Genomic Imaging, University of California, Davis, CA, USA. 7Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College\nLondon, London, UK. 8Department of Public Health Sciences, University of California, Davis, CA, USA. 9MRC Centre for Neurodevelopmental Disorders, King\u2019s College London,\nLondon, UK. 10These authors contributed equally: Anthony C. Vernon, Melissa D. Bauman. \u2709email: javandewater@ucdavis.edu\nwww.nature.com/mp\nMolecular Psychiatry\n1234567890();,:"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 494
encoding: FLOAT32
metadata:
{"title": "Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys", "chroma:document": "Resource\nCaloric Restriction Engages Hepatic RNA Processing\nMechanisms in Rhesus Monkeys\nGraphical Abstract\nHighlights\nd Caloric restriction reprograms hepatic metabolism in\nmonkeys independently of aging\nd The response to CR involves recruitment of RNA processing\nmechanisms\nd Integrative analysis reveals a multi-pathway core CR\nmetabolic network\nd The core CR metabolic network is regulated at the level of\nRNA processing\nAuthors\nTimothy W. Rhoads,\nMaggie S. Burhans, Vincent B. Chen, ...,\nJoshua J. Coon, Ricki J. Colman,\nRozalyn M. Anderson\nCorrespondence\nrozalyn.anderson@wisc.edu\nIn Brief\nRhoads et al. use multi-platform high-\nresolution molecular pro\ufb01ling to\ndemonstrate that caloric restriction (CR)\nreprograms hepatic metabolism in rhesus\nmonkeys. They identify a role for RNA\nprocessing in the mechanisms of CR and\nshow that the CR metabolic network is\nsubject to substantial regulation at the\nRNA level.\nO\nOH\nH2N\nHO\nO\nO\nOH\nOH\nO\nHO\nO\nO\n-\nHN\nN\nH\nO\nO\nO\nO\nO\nO\nO\nO\nO\nAcetylation\nHepatic CR-responsive\nmolecular network\nmRNA\nmetabolites\nlipids\nproteins\nPTMs\nRhoads et al., 2018, Cell Metabolism 27, 677\u2013688\nMarch 6, 2018 \u00aa 2018 Elsevier Inc.\nhttps://doi.org/10.1016/j.cmet.2018.01.014"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 495
encoding: FLOAT32
metadata:
{"title": "Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys", "chroma:document": "Meng\u00a0et\u00a0al. BMC Neurosci            (2020) 21:2  \nhttps://doi.org/10.1186/s12868-020-0550-4\nRESEARCH ARTICLE\nProteomics profiling and\u00a0pathway analysis \nof\u00a0hippocampal aging in\u00a0rhesus monkeys\nShu Meng1\u2020, Wenchao Xia1\u2020, Meng Pan1\u2020, Yangjie Jia1\u2020, Zhanlong He2* and Wei Ge1,3* \nAbstract \nBackground: Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive \nresearch has been carried out on the characteristics of human hippocampal aging, there is still very little scientific \nunderstanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics \nprofiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high \nthroughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged \n6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinfor-\nmatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios \nof 20-years vs. 6-years, \u2265 1.20 or \u2264 0.83).\nResults: In total, 3260 proteins were identified with a high level of confidence in rhesus hippocampus. We found \n367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we \nfound these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal \nadhesion\u2013PI3K\u2013AKT\u2013mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeX-\nchange with identifier PXD011398.\nConclusion: This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. \nThese findings should make an important contribution to further mechanistic studies, marker selection and drug \ndevelopment for the prevention and treatment of aging or age-related neurodegeneration.\nKeywords: Aging, Proteomics, Hippocampus, Rhesus monkey, Neurodegeneration"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 496
encoding: FLOAT32
metadata:
{"title": "Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys", "chroma:document": "\u00a9 The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, \nadaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material \nin this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material \nis not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the \npermitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco \nmmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/\nzero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\nRhesus macaques are a nonhuman primate species that \nis closely related to humans and share a common ances-\ntor that lived over 25 million years ago [1\u20133]. Rhesus \nmacaques are also one of the most commonly used ani-\nmal models in basic and applied biomedical research on \nhuman disease [1, 2]. Previous research has also estab-\nlished that rhesus macaques and humans share approxi-\nmately 95% genetic homology and have very similar \nage-associated conditions including diabetes, osteoar-\nthritis, endometriosis, visual accommodation, hyper-\ntension, osteoporosis, and amyloidosis [2]. The brain \narchitecture of the rhesus macaque is also very similar to \nthat in humans and displays comparable age-related cog-\nnitive decline [2\u20134]. Investigating the molecular mecha-\nnism of the normal aging of rhesus brain has received \nconsiderable critical attention.\nThe hippocampus plays a pivotal role in cerebral learn-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 497
encoding: FLOAT32
metadata:
{"title": "Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys", "chroma:document": "ing and memory and is particularly susceptible to normal \nOpen Access\nBMC Neuroscience\n*Correspondence:  hzl612@126.com; wei.ge@chem.ox.ac.uk\n\u2020Shu Meng, Wenchao Xia, Meng Pan and Yangjie Jia contributed equally \nto this work\n1 State Key Laboratory of Medical Molecular Biology & Department \nof Immunology, Institute of Basic Medical Sciences Chinese Academy \nof Medical Sciences, School of Basic Medicine Peking Union Medical \nCollege, Dongdan Santiao 5# Dongcheng District, Beijing 100005, China\n2 Yunnan Key Laboratory of Vaccine Research and Development \non Severe Infectious Disease, Institute of Medical Biology, Chinese \nAcademy of Medical Sciences and Peking Union Medical College, \nKunming 650118, Yunnan, China\nFull list of author information is available at the end of the article"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 498
encoding: FLOAT32
metadata:
{"title": "3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis", "chroma:document": "Article\n3D Genome of macaque fetal brain reveals\nevolutionary innovations during primate\ncorticogenesis\nGraphical Abstract\nHighlights\nd Construction of a high-resolution Hi-C map of macaque\nfetal brain\nd Cross-species 3D genome analyses uncover human-speci\ufb01c\nchromatin structures\nd The subplate lamina shows human-speci\ufb01c regulatory\nchanges during corticogenesis\nd The human-speci\ufb01c loop regulating EPHA7 affects neuron\ndendrite development\nAuthors\nXin Luo, Yuting Liu, Dachang Dang, ...,\nShihua Zhang, Cheng Li, Bing Su\nCorrespondence\nzsh@amss.ac.cn (S.Z.),\ncheng_li@pku.edu.cn (C.L.),\nsub@mail.kiz.ac.cn (B.S.)\nIn Brief\nHigh-resolution map of developing\nrhesus macaque brain genome\narchitecture during corticogenesis\nreveals human-speci\ufb01c chromatin\nstructure and regulatory changes that\nimpact dendrite development.\nLuo et al., 2021, Cell 184, 723\u2013740\nFebruary 4, 2021 \u00aa 2021 Elsevier Inc.\nhttps://doi.org/10.1016/j.cell.2021.01.001\nll"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 499
encoding: FLOAT32
metadata:
{"title": "2019 Alzheimer's disease facts and figures", "chroma:document": "Alzheimer\u2019s Association Report\n2019 Alzheimer\u2019s disease facts and \ufb01gures\nAlzheimer\u2019s Association*\nAbstract\nThis article describes the public health impact of Alzheimer\u2019s disease (AD), including incidence\nand prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers\nand society. The Special Report examines the use of brief cognitive assessments by primary care\nphysicians as a tool for improving early detection of dementia. An estimated 5.8 million Americans\nhave Alzheimer\u2019s dementia. By mid-century, the number of people living with Alzheimer\u2019s dementia\nin the United States may grow to 13.8 million, fueled in large part by the aging baby boom generation.\nIn 2017, of\ufb01cial death certi\ufb01cates recorded 121,404 deaths from AD, making AD the sixth leading\ncause of death in the United States and the \ufb01fth leading cause of death among Americans age\n\u000165 years. Between 2000 and 2017, deaths resulting from stroke, heart disease, and prostate cancer\ndecreased, whereas reported deaths from AD increased 145%. In 2018, more than 16 million family\nmembers and other unpaid caregivers provided an estimated 18.5 billion hours of care to people\nwith Alzheimer\u2019s or other dementias. This care is valued at nearly $234 billion, but its costs extend\nto family caregivers\u2019 increased risk for emotional distress and negative mental and physical health\noutcomes. Average per-person Medicare payments for services to bene\ufb01ciaries age \u000165 years with\nAlzheimer\u2019sorotherdementiasaremorethanthreetimesasgreataspaymentsforbene\ufb01ciarieswithout\nthese conditions. Total payments in 2019 for health care, long-term care and hospice services for peo-\nple age \u000165 years with dementia are estimated to be $290billion. Early detection of Alzheimer\u2019s offers\nnumerous medical, emotional and \ufb01nancial bene\ufb01ts\u2014bene\ufb01ts that accrue to affected individuals and\ntheir families as well as to society at large. Alzheimer\u2019s Association surveys regarding brief cognitive"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 500
encoding: FLOAT32
metadata:
{"title": "2019 Alzheimer's disease facts and figures", "chroma:document": "assessments for detection of dementia found that while a large majority of seniors and primary care\nphysicians say the assessments are important, only half of seniors have received an assessment, and\nonly 16 percent of seniors receive regular cognitive assessments. Many educational opportunities exist\nto facilitate increased use of brief cognitive assessments in the primary care setting.\nKeywords:\nAlzheimer\u2019s disease; Alzheimer\u2019s dementia; Dementia; Diagnostic criteria; Risk factors; Prevalence; Incidence;\nMortality; Morbidity; Caregivers; Family caregiver; Spouse caregiver; Health care professional; Health care costs;\nHealth care expenditures; Long-term care costs; Medicare spending; Medicaid spending; Brief cognitive assess-\nment; Primary care physician; Medicare Annual Wellness Visit; Early detection\n1. About this report\n2019 Alzheimer\u2019s Disease Facts and Figures is a\nstatistical resource for U.S. data related to Alzheimer\u2019s\ndisease, the most common cause of dementia. Background\nand context for interpretation of the data are contained in\nthe overview. Additional sections address prevalence,\nmortality and morbidity, caregiving and use and costs of\nhealth care, long-term care and hospice. A Special\nReport discusses Alzheimer\u2019s detection in the primary care\nsetting.\n1.1. Speci\ufb01c information in this report\nSpeci\ufb01c information in this year\u2019s Alzheimer\u2019s Disease\nFacts and Figures includes:\n\u0003 Brain changes that occur with Alzheimer\u2019s disease.\n\u0003 Risk factors for Alzheimer\u2019s disease.\n\u0003 Number of Americans with Alzheimer\u2019s dementia\nnationally and for each state.\n\u0003 Lifetime risk for developing Alzheimer\u2019s dementia.\n\u0003 Proportion of women and men with Alzheimer\u2019s and\nother dementias.\n*Tel.: 11-312-335-5893; Fax: 11-866-521-8007.\nE-mail address: sciencestaff@alz.org\nhttps://doi.org/10.1016/j.jalz.2019.01.010\n1552-5260\nAlzheimer\u2019s & Dementia 15 (2019) 321-387"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 501
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Lifespan", "chroma:document": "Sex Differences in Lifespan\nSteven N. Austad1,* and Kathleen E. Fischer1\n1Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294-1170, USA\nSUMMARY\nSex differences in longevity can provide insights into novel mechanisms of aging, yet they have \nbeen little studied. Surprisingly, sex-specific longevity patterns are better known in wild animals. \nEvolutionary hypotheses accounting for longevity patterns in natural populations include \ndifferential vulnerability to environmental hazards, differential intensity of sexual selection and \ndistinct patterns of parental care. Mechanistic hypotheses focus on asymmetric inheritance of sex \nchromosomes and mitochondria. Virtually all intensively studied species show conditional sex \ndifferences in longevity. Humans are the only species in which one sex is known to have a \nubiquitous survival advantage. Paradoxically, although women live longer, they suffer greater \nmorbidity particularly late in life. This mortality-morbidity paradox may be a consequence of \ngreater connective tissue responsiveness to sex hormones in women. Human females\u2019 longevity \nadvantage may result from hormonal influences on inflammatory and immunological responses, or \ngreater resistance to oxidative damage; current support for these mechanisms is weak.\n INTRODUCTION\nThe vast majority of animal species have two sexes and those sexes often differ in many \naspects of their biology. Most obviously, males range from a tiny fraction of the size of \nfemales to considerably larger and live considerably shorter to substantially longer lives \n(Austad, 2006; Finch, 1990). Sex differences in longevity can potentially be exploited to \nhelp understand mechanisms underlying variation in longevity within a species. Yet these \ndifferences remain little studied despite considerable variation among different genotypes of \ncommonly used laboratory species such as C. elegans (McCulloch and Gems, 2003), \nDrosophila melanogaster (Malick and Kidwell, 1966), and Mus musculus (Austad, 2011)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 502
encoding: FLOAT32
metadata:
{"title": "Sex Differences in Lifespan", "chroma:document": "Surprisingly, much more has been reported about sex differences in longevity among wild \npopulations than among captive populations because numerous long-term field studies have \ntried to understand the evolutionary forces underlying sex differences in behavior and a host \nof life history traits such as rates of development, mating systems, and reproductive patterns. \nThus we know that female short-finned pilot whales live nearly twice as long as males \n(Kasuya and Marsh, 1984); and that female African lions, red deer, black-tailed prairie dogs, \n*Correspondence: austad@uab.edu. \nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of \nthe resulting proof before it is published in its final citable form. Please note that during the production process errors may be \ndiscovered which could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nCell Metab. Author manuscript; available in PMC 2017 June 14.\nPublished in final edited form as:\nCell Metab. 2016 June 14; 23(6): 1022\u20131033. doi:10.1016/j.cmet.2016.05.019.\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: 503
encoding: FLOAT32
metadata:
{"title": "A meta-analysis of sex differences in human brain structure", "chroma:document": "Neuroscience\n and\n Biobehavioral\n Reviews\n 39\n (2014)\n 34\u201350\nContents\n lists\n available\n at\n ScienceDirect\nNeuroscience\n and\n Biobehavioral\n Reviews\njournal\n h\n om\n epa\n ge:\n www.elsevier.com/locate/neubiorev\nA\n meta-analysis\n of\n sex\n differences\n in\n human\n brain\n structure\u0002\nAmber\n N.V.\n Ruigrok a,\u2217,  Gholamreza\n Salimi-Khorshidi b,  Meng-Chuan\n Lai a,c,\nSimon\n Baron-Cohen a,d, Michael\n V.\n Lombardo a,e,  Roger\n J.  Tait f,g,  John\n Suckling d,f,g\na Autism\n Research\n Centre,\n Department\n of\n Psychiatry,\n University\n of\n Cambridge,\n Douglas\n House,\n 18B\n Trumpington\n Road,\n Cambridge\n CB2\n 8AH,\n United\n Kingdom\nb Centre\n for\n Functional\n MRI\n of\n the\n Brain\n (FMRIB),\n Nuf\ufb01eld\n Department\n of\n Clinical\n Neurosciences,\n University\n of\n Oxford,\n John\n Radcliffe\n Hospital,\n Oxford\n OX3\n9DU,\n United\n Kingdom\nc Department\n of\n Psychiatry,\n College\n of\n Medicine,\n National\n Taiwan\n University,\n No.\n 1\n Jen-Ai\n Road\n Section\n 1,\n Taipei\n 10051,\n Taiwan\nd Cambridgeshire\n and\n Peterborough\n NHS\n Foundation\n Trust,\n Elizabeth\n House,\n Fulbourn\n Hospital,\n Cambridge\n CB21\n 5EF,\n United\n Kingdom\ne Department\n of\n Psychology,\n University\n of\n Cyprus,\n P.O.\n Box\n 20537,\n CY\n 1678\n Nicosia,\n Cyprus\nf Brain\n Mapping\n Unit,\n School\n of\n Clinical\n Medicine,\n University\n of\n Cambridge,\n Herchel\n Smith\n Building,\n Robinson\n Way,\n Cambridge\n CB2\n 0SP,\n United\n Kingdom\ng Behavioural\n and\n Clinical\n Neuroscience\n Institute,\n Department\n of\n Psychology,\n University\n of\n Cambridge,\n Downing\n Street,\n Cambridge\n CB2\n 3EB,\n United\n Kingdom\na\n r  t\n i c  l e  \ni  n  f  o\nArticle\n history:\nReceived\n 15\n June\n 2013\nReceived\n in\n revised\n form\n13\n December\n 2013\nAccepted\n 17\n December\n 2013\nKeywords:\nBrain\nSex\n differences\nMeta-analysis\nGaussian-process\n regression\n (GPR)\nVoxel-based\n morphometry\nVolume\na\n b\n s\n t  r  a\n c  t\nThe  prevalence,\n age  of onset,\n and  symptomatology\n of  many  neuropsychiatric\n conditions\n differ\n between\nmales\n and\n females.\n To  understand\n the  causes  and  consequences\n of  sex  differences\n it is  important"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 504
encoding: FLOAT32
metadata:
{"title": "A meta-analysis of sex differences in human brain structure", "chroma:document": "to  estab-\nlish\n where\n they  occur\n in  the  human  brain.  We  report  the  \ufb01rst  meta-analysis\n of  typical  sex  differences\n on\nglobal\n brain\n volume,\n a  descriptive\n account\n of the  breakdown\n of studies\n of  each\n compartmental\n volume\nby\n six  age  categories,\n and\n whole-brain\n voxel-wise\n meta-analyses\n on  brain\n volume  and  density.  Gaussian-\nprocess\n regression\n coordinate-based\n meta-analysis\n was  used  to examine  sex  differences\n in voxel-based\nregional\n volume\n and  density.  On  average,\n males  have  larger  total\n brain\n volumes\n than\n females.\n Exami-\nnation\n of the  breakdown\n of  studies\n providing\n total\n volumes\n by  age  categories\n indicated  a bias  towards\nthe\n 18\u201359  year-old\n category.\n Regional\n sex  differences\n in  volume\n and  tissue  density\n include  the  amyg-\ndala,\n hippocampus\n and  insula,\n areas  known\n to be  implicated\n in  sex-biased\n neuropsychiatric\n conditions.\nTogether,\n these  results  suggest\n candidate\n regions\n for  investigating\n the  asymmetric\n effect  that\n sex  has  on\nthe\n developing\n brain,\n and\n for  understanding\n sex-biased\n neurological\n and  psychiatric\n conditions.\n\u00a9\n 2014  The  Authors.  Published\n by  Elsevier\n Ltd.\n All  rights\n reserved.\nContents\n1.\n \nIntroduction\n . . .  . . .  . . . . .  . . . .  . . .  .  . . .  . . .  .  .  . .  .  . . . . . . .  .  . . .  . . .  .  . . .  .  .  . .  . . . .  . . . . .  . . .  .  . . .  . . . .  . .  .  . .  . . .  . . .  . . . .  .  . .  .  .  . .  .  . . .  . . .  . . .  .  . . .  .  . . . . .  . . . .  . . .\n .  .  .  . . . . . . . . . .  .  .  .  .  \n35\n2.\n \nMethods.  .  . .  .  . .  .  . . . .  .  . . .  .  . . .  .  . . .  .  . . .  .  . . .  . . . .  .  . . .  . . .  .  . . .  .  . . .  .  . . .  . . .  .  . . .  . . . .  . . .  .  . .  . . . .  . . .  .  . . . .  .  . . .  .  .  . . .  .  . . .  . . . .  . . .  . . . .  . . .  .  . . . . . .  . .  .  . .  .  . . . . .\n .  .  . . .  . . .  . . . .  .  .  \n35\n2.1.\n \nSystematic\n literature\n search"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 505
encoding: FLOAT32
metadata:
{"title": "A meta-analysis of sex differences in human brain structure", "chroma:document": "search\n . . .  . . .  . . . .  .  . . . .  . . .  .  . . .  . . .  .  . . .  . . .  .  .  . . .  . .  . . .  . .  .  . .  .  . .  . . .  . . . .  .  . .  .  .  .  . .  . . .  .  .  . . .  . . . . .  . .  . .  .  .  . . .  .  . . .  .  . . .  . . . . .\n .  .  . . .  .  .  .\n . . .  . . .  \n35\n2.2.\n \nSelection\n criteria  . . . .  . . . . . . . .  . . . .  . . .  .  .  . .  .  . . .  .  . . .  . . . .  . . .  . . .  .  . . .  .  . . .  . .  .  .  . . .  . . .  . . . .  .  .  . . . .  . .  . . .  .  .  .  . .  . . .  .  . . . .  . .  .  . .  .  . . .  .  . . .  .  .  . . .  .  . . . . .  .  . . .  .  .  .  . . .  .  . . .  .  \n35\n2.3.\n \nData analysis\n . .  .  . . .  .  . . .  .  . . .  . . . . . . .  . . .  .  . . .  .  . . . .  . . .  .  . . .  . . .  . . . .  . . .  . . . .  . . .  .  . . .  . . . .  . .  . . .  . . .  . . .  . . .  .  .  . . .  . . . .  .  . .  . . .  . . .  . . . .  .  . .  .  .  .  . . .  .  . . .  .  .  .  . . . . . . . . . .  . . . \n36\n2.3.1.\n \nOverall\n volumes\n meta-analysis\n . . . . .  .  . . .  .  . . .  . . . .  . . .  . . . .  . . . . . .  .  . .  . . . . . .  . . .  .  .  . .  .  .  .  . .  . . .  .  .  . . .  . . . . . . .  . . . .  . . .  .  .  . .  .  . . .  .  .  . .  .  .  . . . .\n .  .  . . .  .  . .  .  .  \n36\n2.3.2.\n \nRegional\n coordinate-based\n meta-analysis\n . .  .  . .  .  . . .  . .  . .  .  . .  .  . . .  . . . . .  . . .  .  . . .  . . . . .  . .  . . .  .  . . .  .  . . .  .  . . . .  . . . . .  . . .  . .  . . .  .  . . . . .\n .  .  . . .  .  .  .  . . .  .  .  . .  . \n36\n3.\n \nResults\n . . . . .  . . . .  . .  .  . . . .  .  . . . .  . . . .  . . .  .  . . .  .  . . .  .  . . .  .  . .  .  . . .  .  . .  .  .  . .  .  .  .  .  .  . .  .  . . .  .  . .  . .  . . .  .  .  . . . .  . . .  . . . .  . .  . . .  .  .  . . .  .  . . .  . . . .  . .  .  . .  .  . . .  .  . . .  .  . . .  .  .  .  . . .  .  . . . . .  .  . . .  .  .  .  . . .  .  \n37\n3.1.\n \nLiterature\n search"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 506
encoding: FLOAT32
metadata:
{"title": "A meta-analysis of sex differences in human brain structure", "chroma:document": "search\n . . .  . . . . . . . .  . . . .  . . .  .  .  . .  .  . . .  . . .  .  . . .  .  . . .  .  . .  .  .  . .  . . .  .  .  . . .  .  . . .  . . . .  . .  .  . .  .  . .  . . .  . . . .  .  . . .  .  .  . .  .  . . .  .  . . .  . . . . . . . .  . .  . . . .  .  .  .\n .  . .  . . .  .  .  . .  . . .  .  . . . . \n37\n3.2.\n \nSex  differences\n in  overall  volumes\n . . .  . . . .  .  . . .  . . . .  . . . . . .  . . . .  .  . . .  .  . .  . . . .  . . .  . .  . . .  . . . .  .  .  . .  . . .  . . .  . . . .  .  . .  .  .  . . .  . .  .  . . .  . . . . . .  . . . .  . . .\n .  . .  . . . . . . . .  . . .  .  .  .  . \n37\n3.2.1.\n \nBreakdown\n of  studies  looking  at  overall  volume\n .  . . .  . . .  . . . .  . . .  . . .  . . .  . . . .  .  . .  . . .  .  . . . .  . . .  . . . . .  . . .  . . . .  . . .  .  . . .  .  .  .  . . . . . . . . .  .  . . .  .  .  .  . . . .  .  . .  \n37\n3.3.\n \nRegional\n sex differences\n in  volume\n and  tissue  density.  .  .  .  . . .  .  . .  .  .  . . .  .  . .  . .  . . .  .  .  . . .  . . .  . . .  . . .  .  . . .  .  .  . . .  . . .  .  .  . . .  . . . .  . . .  .  . . . . .  . . .  .  .  .  .  . . . . . .  . . . .  . .  .  \n41\n3.3.1.\n \nRegional\n volume\n meta-analysis\n . . . . .  . . . .  .  . .  . . . .  . . .  . . . . . . .  .  .  . .  . . .  .  .  .  . . . .  . . . . . . .  .  . .  . . .  .  . . . .  . .  .  . .  . . . .  .  . . .  .  . . . .  .  . . .  .  .  . . . . .  .  . . . .  .  .  . .  . .  . . .  \n41\n3.3.2.\n \nRegional\n tissue  density\n meta-analysis\n . .  .  .  . . .  .  .  . .  . . .  .  .  . . .  . .  .  .  . . .  . . .  . . . .  . . .  . . .  .  . . . .  . . .  . . . .  .  . .  .  . . .  . . .  .  . . .  .  . .  .  . . .  . . .  .  . . . . . .  .  . .  .  . .  .  . .  .  . . \n43\n4.\n \nDiscussion"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 507
encoding: FLOAT32
metadata:
{"title": "A meta-analysis of sex differences in human brain structure", "chroma:document": ". .  .  . . . .  .  . . .  . .  .  .  . .  .  . . .  .  . . . . . . . . . .  . . .  .  . . .  .  .  . .  .  . .  .  .  . .  . .  . .  .  . .  .  .  .  . . .  . . . .  . .  .  . .  .  .  . . .  . . . . .  . . .  . .  .  . .  . .  .  . . .  . . . .  .  . .  . .  . . .  . . .  . .  . . .  . . . .  . .  . . . .  .  .  .  .  . .  .\n . . . .  . . . \n43\n4.1.  \nBrain  development\n . .  .  . .  . . . .  . . . .  . . . .  . . .  .  . . .  .  . . .  .  . . .  .  . . .  . . .  . . .  .  . . . .  . .  .  . . .  .  . . .  . . . . .  . . .  . .  .  . .  . .  . . .  . . .  . .  .  . . . .  .  . . .  .  . . .  . . .  . .  . . .  .  .  . . .  .  .  .\n .  . .  . . . . . . .  . . .  . .  \n43\n\u0002 This\n is\n an\n open-access\n article\n distributed\n under\n the\n terms\n of\n the\n Creative\n Commons\n Attribution\n License,\n which\n permits\n unrestricted\n use,\n distribution,\n and\n reproduction\nin\n any\n medium,\n provided\n the\n original\n author\n and\n source\n are\n credited.\n\u2217 Corresponding\n author.\n Tel.:\n +44\n 1223\n 746030/746057;\n fax:\n +44\n 1223\n 746033.\nE-mail\n address:\n ar560@cam.ac.uk\n (A.N.V.\n Ruigrok).\n0149-7634/$\n \u2013\n see\n front\n matter\n \u00a9\n 2014\n The\n Authors.\n Published\n by\n Elsevier\n Ltd.\n All\n rights\n reserved.\nhttp://dx.doi.org/10.1016/j.neubiorev.2013.12.004"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 508
encoding: FLOAT32
metadata:
{"title": "Polymyositis in Chagas's disease", "chroma:document": "Annals ofthe Rheumatic Diseases, 1978, 37, 277-280\nCase report\nPolymyositis in Chagas's disease\nW. COSSERMELLI, H. FRIEDMAN, E. H. PASTOR, M. R. NOBRE,\nA. MANZIONE, M. E. CAMARGO, AND M. SHIROMA\nFrom the Rheumatology Research Unit and Department of Pathology, Faculty of Medicine, University of\nSao Paulo, Brazil\nsuMMARY\nPolymyositis marked the clinical onset of Chagas's disease in a patient with rheumatoid\narthritis. This is unusual, although clinically unimportant muscle involvement in trypanosomiasis\nhas been described. The plasma cell infiltrate and vascular deposition of IgM and C3 suggest that\nthe humoral immune system may play a role in the pathogenesis of chagasic polymyositis. It is not\nknown whether the rheumatoid diseases predisposed to the polymyositis.\nThere are few reports of myositis\nin Chagas's\ndisease, although this is commonly seen in experi-\nmental models (Wolf et al., 1952; Andrade and\nAndrade,\n1968).\nMyositis\nassociated\nwith\nthe\npresence of parasites was demonstrated by Ponce\n(1972) in sequential biopsies of the gastrocnemius\nmuscle in patients with chronic and acute Chagas's\ndisease and cardiopathy. Cenget and Rojas (1959)\nobserved deltoid myositis in 96-3% of 27 chagasic\npatients, but did not mention parasites in the muscle\nlesions.\nCossio et al. (1974a, b) described a circulating\nautoantibody that reacts against endocardium, as\nwell as vessels and interstitium of skeletal muscle\nand myocardium and interacts with complement\n(EVI antibody). It was found in 95% ofpatients with\nChagas's heart disease and in 45 % of asymptomatic\nindividuals infected with Trypanosoma cruzi. In the\nearly stage of acute heart disease EVI antibody is of\nIgM class but one month later both IgM and IgG\nantibodies are found. We report a patient with\ndefinite rheumatoid arthritis who developed chagasic\npolymyositis.\nCase report\nA 43-year-old\nwhite female had\nsuffered from\nrheumathoid arthritis from age 17 years. Early in\nthe course of the disease she received gold salts with\nremarkable improvement. After a 15-year period"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 509
encoding: FLOAT32
metadata:
{"title": "Polymyositis in Chagas's disease", "chroma:document": "without symptoms, she then started to complain of\nAccepted for publication September 5, 1977\nCorrespondence\nto\nDr W.\nCossermelli,\nFaculdade\nde\nMedicina, Universidade de Sao Paulo, SP 2921, Sao Paulo-\nSP Brazil.\njoint pain in both hands, shoulders, and knees, with\nmorning stiffness and fever of 38\u00b0C. Nonsteroidal\nanti-inflammatory drugs provided some relief. At\nthis time she had her tonsils removed. Postoperatively\nshe received 500 ml of fresh blood. 10 days after\nsurgery her joint pains increased and were accom-\npanied by muscle weakness and pain in the shoulders,\nthighs, and legs, fever of 40\u00b0C ,and tachycardia. She\nwas wholly incapacitated by the muscle weakness.\nRaised values of transaminases and LDH isoenzymes\nand positive antinuclear factor were recorded. Pred-\nnisone 80 mg bd was started, but 20 days later she\nwas no better and was admitted to the Hospital das\nClinicas da Universidade de Sao Paulo.\nHer general condition was fair, blood pressure\n110/70 mmHg, pulse rate 100/min, respiratory rate\n30/min, and temperature 38\u00b0C. No cardiac murmurs\nor changes in heart sounds or rhythm disturbances\nwere found. The lungs were normal on examination.\nThe spleen was not palpable, but the liver was\nenlarged about 3 cm. There was pain on joint move-\nment in both hands, shoulders, knees, and ankles.\nThe left ankle was swollen without limited movement.\nMuscle\nweakness\nin\na\nsymmetrical,\nproximal\ndistribution was the prominent feature, and the\naffected muscles were tender to pressure. Tendon\nreflexes were well preserved.\nThe erythrocyte sedimentation rate was 49 mm/h,\nRA latex fixation test 1:80, negative LE-cell test,\nantinuclear antibodies (ANA) positive at a 1:5000\ndilution (rat liver preparation),\ntotal haemolytic\ncomplement 15 U (normal: 166-333), C3 0-6 g/l\n(normal 0 8-1 * 2 g/l). Total protein measured 102 g/l,\ngammaglobulin 44 g/l. Serum muscle enzymes were\nmarkedly raised:\ncreatine phosphokinase (CPK)\n277"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 510
encoding: FLOAT32
metadata:
{"title": "Aging hallmarks exhibit organ-specific temporal signatures", "chroma:document": "Aging hallmarks exhibit organ-specific temporal signatures\nNicholas Schaum1,#, Benoit Lehallier2,#, Oliver Hahn2,#, R\u00f3bert P\u00e1lovics2, Shayan \nHosseinzadeh3, Song E. Lee2, Rene Sit3, Davis P. Lee4, Patricia Mor\u00e1n Losada2, Macy E. \nZardeneta4, Tobias Fehlmann5, James Webber3, Aaron McGeever3, Kruti Calcuttawala2, Hui \nZhang4, Daniela Berdnik4, Vidhu Mathur2, Weilun Tan3, Alexander Zee3, Michelle Tan3, The \nTabula Muris Consortium\u2020, Angela Pisco3, Jim Karkanias3, Norma F. Neff3, Andreas \nKeller2,5,*, Spyros Darmanis3, Stephen R. Quake3,6,*, Tony Wyss-Coray2,4,7,8,*\n1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of \nMedicine, Stanford, California, USA.\n2Department of Neurology and Neurological Sciences, Stanford University School of Medicine, \nStanford, California, USA.\n3Chan Zuckerberg Biohub, San Francisco, California, USA.\n4Veterans Administration Palo Alto Healthcare System, Palo Alto, California, USA.\n5Clinical Bioinformatics, Saarland University, Saarbr\u00fccken, Germany.\n6Department of Bioengineering, Stanford University, Stanford, California, USA.\n7Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, \nCalifornia, USA.\n8Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, California, \nUSA.\nUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, \nsubject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#termsAuthor Information \nReprints and permissions information is available at www.nature.com/reprints. Readers are welcome to comment on the online version \nof the paper.\n*Correspondence to twc@stanford.edu or quake@stanford.edu.\n#These authors contributed equally.\n\u2020A full list of authors and affiliations appears in the online version of the paper.\nAuthor Contributions"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 511
encoding: FLOAT32
metadata:
{"title": "Aging hallmarks exhibit organ-specific temporal signatures", "chroma:document": "N.S., B.L., S.R.Q., and T.W.-C. conceptualized the study. N.S., O.H., B.L., R.P., and T.W.-C. conceptualized the analysis. O.H., B.L., \nand R.P. with contributions from A.K., and T.F. conducted the transcriptomic analyses. N.S., S.E.L., D.P.L., M.E.Z., H.Z., and D.B. \ncollected samples and extracted RNA. S.H., A.Z., and W.T. conducted cDNA and library preparation. P.M.L. created the Shiny web \ninterface. R.S. and M.T. performed sequencing and library quality control. S.H., A.O.P., J.W., and A.M. processed raw sequencing \ndata. The Tabula Muris Senis Consortium generated the single-cell sequencing database. N.S. and K.C. performed and analyzed FACS \nand RNAscope experiments. N.S., B.L., O.H., T.W.-C., and S.R.Q. wrote and edited the manuscript. T.W.-C., S.R.Q., S.D., N.F.N. and \nJ.K. supervised the work.\nSupplementary Information is available in the online version of the paper.\nThe authors declare no competing financial interests.\nCode Availability\nAll code was limited to the commercial software listed in the methods and reporting summary.\nData Availability\nRaw data are available on GEO (GSE132040).\nReviewer Information Nature thanks the anonymous reviewers for their contributions to the peer review of this work.\nHHS Public Access\nAuthor manuscript\nNature. Author manuscript; available in PMC 2021 January 15.\nPublished in final edited form as:\nNature. 2020 July ; 583(7817): 596\u2013602. doi:10.1038/s41586-020-2499-y.\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: 512
encoding: FLOAT32
metadata:
{"title": "Alzheimer\\220s Pathogenic Mechanisms and Underlying Sex Difference", "chroma:document": "Alzheimer\u2019s Pathogenic Mechanisms and Underlying Sex \nDifference\nDonghui Zhu1,2,*, Axel Montagne3,4, Zhen Zhao3,4\n1Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States\n2Neuroscience Graduate Program, Renaissance School of Medicine, Stony Brook University, \nStony Brook, NY, United States\n3Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern \nCalifornia, Los Angeles, CA, United States\n4Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los \nAngeles, CA, United States\nAbstract\nBoth men and women can have Alzheimer\u2019s disease (AD), and there might be sex differences. \nAD is a neurodegenerative disease, and its frequency is often reported to be higher for women \nthan men: almost two-thirds of patients with AD are women. One prevailing view is that women \nlive longer than men on average of 4.5 years, plus there are more women aged 85 years or \nolder than men in most global subpopulations; and older age is the greatest risk factor for \nAD. However, the differences in the actual risk of developing AD for men and women of \nthe same age is difficult to assess, and the findings have been mixed. An increasing body of \nevidence from preclinical and clinical studies as well as the complications in estimating incidence \nsupport the sex-specific biological mechanisms in diverging AD risk as an important adjunct \nexplanation to the epidemiologic perspective. While some of the sex differences in AD prevalence \nare due to differences in longevity, other distinct biological mechanisms increase the risk and \nprogression of AD in women. These risk factors include 1) deviations in brain structure and \nbiomarkers, 2) psychosocial stress responses, 3) pregnancy, menopause, and sex hormones, 4) \ngenetic background (i.e., APOE), 5) inflammation, gliosis, and immune module (i.e., TREM2), \nand 6) vascular disorders. More studies focusing on the underlying biological mechanisms for this"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 513
encoding: FLOAT32
metadata:
{"title": "Alzheimer\\220s Pathogenic Mechanisms and Underlying Sex Difference", "chroma:document": "phenomenon are needed to better understand AD. This review presents the most recent data in \nsex differences in AD \u2013 the gateway to precision medicine, therefore, shaping expert perspectives, \ninspiring researchers to go in new directions, and driving development of future diagnostic tools \nand treatments for AD in a more customized way.\nKeywords\naging; dementia; gender difference; cognition; hormones; estrogen; menopause\n*Corresponding author: Donghui.Zhu@stonybrook.edu (D. Zhu). \nConflicts of Interest\nThe authors declare no conflicts of interest.\nHHS Public Access\nAuthor manuscript\nCell Mol Life Sci. Author manuscript; available in PMC 2022 January 02.\nPublished in final edited form as:\nCell Mol Life Sci. 2021 June ; 78(11): 4907\u20134920. doi:10.1007/s00018-021-03830-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: 514
encoding: FLOAT32
metadata:
{"title": "The times they are a-changin\u00e2\u00a0\u0092: a proposal on how brain flexibility goes beyond the obvious to include the concepts of \u00e2\u00a0\u009cupward\u00e2\u00a0\u0080 and \u00e2\u00a0\u009cdownward\u00e2\u00a0\u0080 to neuroplasticity", "chroma:document": "REVIEW ARTICLE\nOPEN\nThe times they are a-changin\u2019: a proposal on how brain\n\ufb02exibility goes beyond the obvious to include the concepts\nof \u201cupward\u201d and \u201cdownward\u201d to neuroplasticity\nCassiano Ricardo Alves Faria Diniz\n1,2\u2709 and Ana Paula Crestani\n1,2\u2709\n\u00a9 The Author(s) 2022\nSince the brain was found to be somehow \ufb02exible, plastic, researchers worldwide have been trying to comprehend its\nfundamentals to better understand the brain itself, make predictions, disentangle the neurobiology of brain diseases, and \ufb01nally\npropose up-to-date treatments. Neuroplasticity is simple as a concept, but extremely complex when it comes to its mechanisms.\nThis review aims to bring to light an aspect about neuroplasticity that is often not given enough attention as it should, the fact\nthat the brain\u2019s ability to change would include its ability to disconnect synapses. So, neuronal shrinkage, decrease in spine\ndensity or dendritic complexity should be included within the concept of neuroplasticity as part of its mechanisms, not as an\nimpairment of it. To that end, we extensively describe a variety of studies involving topics such as neurodevelopment, aging,\nstress, memory and homeostatic plasticity to highlight how the weakening and disconnection of synapses organically permeate\nthe brain in so many ways as a good practice of its intrinsic physiology. Therefore, we propose to break down neuroplasticity\ninto two sub-concepts, \u201cupward neuroplasticity\u201d for changes related to synaptic construction and \u201cdownward neuroplasticity\u201d\nfor changes related to synaptic deconstruction. With these sub-concepts, neuroplasticity could be better understood from a\nbigger landscape as a vector in which both directions could be taken for the brain to \ufb02exibly adapt to certain demands. Such a\nparadigm shift would allow a better understanding of the concept of neuroplasticity to avoid any data interpretation bias, once\nit makes clear that there is no morality with regard to the organic and physiological changes that involve dynamic biological"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 515
encoding: FLOAT32
metadata:
{"title": "The times they are a-changin\u00e2\u00a0\u0092: a proposal on how brain flexibility goes beyond the obvious to include the concepts of \u00e2\u00a0\u009cupward\u00e2\u00a0\u0080 and \u00e2\u00a0\u009cdownward\u00e2\u00a0\u0080 to neuroplasticity", "chroma:document": "systems as seen in the brain.\nMolecular Psychiatry (2023) 28:977\u2013992; https://doi.org/10.1038/s41380-022-01931-x\nINTRODUCTION\nThe etymology of neuroplasticity breaks it down into two basic\nmorphemes: neuro- plastic; with the \u201cplastic\u201d originally meaning\n\u201csuitable for molding\u201d as it comes \ufb01rst from the Greek term\n\u201cplastik\u00f3s\u201d and later from the Latin \u201cplasticus\u201d. As a concept,\nneuroplasticity means the nervous system\u2019s ability to reorganize its\nstructure and functioning in response to some stimuli, either\nintrinsic or extrinsic [1]. Although simple in de\ufb01nition, the historical\nground behind this concept relies entirely on the shoulders of\nmagni\ufb01cent and pioneering scientists. From a philosophical\nperspective, plasticity roots, as a reference to the nervous system,\nare still a matter of debate and have been tracked back to Willian\nJames (1890), Santiago Ram\u00f3n y Cajal (1894) and Demor (1896) in\nthe late 1800s or Lugaro (1906) and Minea (1909) in the early 1900s\n[2\u20134]. However, the practical relevance of the neuroplasticity only\nbegan to be unveiled in the mid-20th century by Paul Bach-y-Rita\nwho built the concept of sensory substitution by proposing that\nother brain areas may assume functions previously mediated by a\nlost neural tissue [5]. Similarly, based on Wilder Pen\ufb01eld works that\nshowed a motor and sensory cortical representation of the body [6],\nMichael Merzenich noted that the adult brain is actually a dynamic\nstructure, with the cortical body representations constantly shifting\nits boundaries [7]. Intriguing, Merzenich\u2019s \ufb01ndings were initially\ncriticized by David Hubel and Torsten Wiesel, two eminent\nneuroscientists at Johns Hopkins who had found a critical period\nfor visual cortex plasticity to allow visual processing input to be\nreplaced by the non-deprived eye at the expense of the deprived\none [8, 9].\nAll\nthe\n\ufb01eld\nadvancement\nhas\nnot\ncome\nwithout\nthe\ncontroversy of the unknown and, not surprisingly, for so long\nthe adult brain was considered hard-wired, incapable of any"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 516
encoding: FLOAT32
metadata:
{"title": "The times they are a-changin\u00e2\u00a0\u0092: a proposal on how brain flexibility goes beyond the obvious to include the concepts of \u00e2\u00a0\u009cupward\u00e2\u00a0\u0080 and \u00e2\u00a0\u009cdownward\u00e2\u00a0\u0080 to neuroplasticity", "chroma:document": "accommodation. However, after some breakthroughs, neuroplas-\nticity is now well recognized as a fundamental and lifelong brain\nproperty. Although partially compromised, compared to early\nneurodevelopment, adult brain remodeling is still salient and\nfairly required for learning/experience- and internal milieu-based\nbehavioral adjustments [10].\nBearing in mind a broader perspective of a \ufb02exible brain, we will\ngo through studies related to early neurodevelopment, aging,\nstress, memory, and homeostatic plasticity to propose that brain\n\ufb02exibility goes beyond the obvious to include the concepts of\n\u201cupward\u201d and \u201cdownward\u201d to neuroplasticity. Such sub-concepts\naim to clarify how neuroplasticity is not only about building, but\nalso about dismantling.\nReceived: 21 September 2022 Revised: 7 December 2022 Accepted: 14 December 2022\nPublished online: 27 December 2022\n1School of Medicine, Campus USP, Ribeir\u00e3o Preto, SP, Brazil. 2Center for Neuroscience, University of California, Davis, CA, USA. \u2709email: crafd87@gmail.com;\npaula.crestani@gmail.com\nwww.nature.com/mp\nMolecular Psychiatry\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 517
encoding: FLOAT32
metadata:
{"title": "Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolate\\\rral amygdala that project to the dorsal striatum", "chroma:document": "Chronic intermittent ethanol exposure differentially alters the \nexcitability of neurons in the orbitofrontal cortex and basolateral \namygdala that project to the dorsal striatum\nSudarat Nimitvilai-Roberts1, Dominic Gioia1, Marcelo F. Lopez2, Christina M. Glaser1, John \nJ. Woodward1,2,*\n1Department of Neuroscience\n2Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical \nUniversity of South Carolina, Charleston, SC 29425\nAbstract\nAlcohol use disorder is associated with altered neuronal function including those in orbitofrontal \ncortex (OFC) and basolateral amygdala (BLA) that send glutamatergic inputs to areas of the dorsal \nstriatum (DS) that mediate goal and habit directed actions. Previous studies reported that chronic \nintermittent (CIE) exposure to ethanol alters the electrophysiological properties of OFC and BLA \nneurons, although projection targets for these neurons were not identified. In this study, we used \nmale and female mice and recorded current-evoked spiking of retrobead labeled DS-projecting \nOFC and BLA neurons in the same animals following air or CIE treatment. DS-projecting OFC \nneurons were hyperexcitable 3- and 7-days following CIE exposure and spiking returned to \ncontrol levels after 14 days of withdrawal. In contrast, firing was decreased in DS-projecting \nBLA neurons at 3-days withdrawal, increased at 7- and 14-days and returned to baseline at 28 \ndays post-CIE. CIE exposure enhanced the amplitude and frequency of spontaneous excitatory \npostsynaptic currents (sEPSCs) of DS-projecting OFC neurons but had no effect on inhibitory \npostsynaptic currents (sIPSCs). In DS-projecting BLA neurons, the amplitude and frequency of \nsIPSCs was enhanced 3 days post-CIE with no change in sEPSCs while at 7-days post-withdrawal, \nsEPSC amplitude and frequency were increased and sIPSCs had returned to normal. Finally, \nin CIE-treated mice, acute ethanol no longer inhibited spike firing of DS-projecting OFC and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 518
encoding: FLOAT32
metadata:
{"title": "Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolate\\\rral amygdala that project to the dorsal striatum", "chroma:document": "BLA neurons. Overall, these results suggest that CIE-induced changes in the excitability of \nDS-projecting OFC and BLA neurons could underlie deficits in behavioral control often observed \nin alcohol-dependent individuals.\nKeywords\nOrbitofrontal cortex; basolateral amygdala; dorsal medial striatum; chronic ethanol exposure; \nintrinsic excitability; spontaneous postsynaptic currents\n*Corresponding author: John J. Woodward, PhD, Dept. of Neuroscience, 30 Courtenay Drive, STB627B, Charleston, SC 29425, Tel: \n843-792-5225, woodward@musc.edu.\nAuthor contributions\nParticipated in research design: S. Nimitvilai-Roberts, J.J. Woodward; Conducted experiments: S. Nimitvilai-Roberts, D. Gioia, M.F. \nLopez; C.M. Glaser; Performed data analysis: S. Nimitvilai-Roberts, J.J. Woodward; Wrote or contributed to the writing of the \nmanuscript: S. Nimitvilai-Roberts, J.J. Woodward.\nHHS Public Access\nAuthor manuscript\nNeuropharmacology. Author manuscript; available in PMC 2023 May 01.\nPublished in final edited form as:\nNeuropharmacology. ; 228: 109463. doi:10.1016/j.neuropharm.2023.109463.\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: 519
encoding: FLOAT32
metadata:
{"title": "Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development", "chroma:document": "REVIEW ARTICLE\nOPEN\nSynthetic biology-inspired cell engineering in diagnosis,\ntreatment, and drug development\nNinglin Zhao1, Yingjie Song2, Xiangqian Xie3, Ziqi Zhu1, Chenxi Duan1, Cheng Nong1, Huan Wang\n3\u2709 and Rui Bao\n1\u2709\nThe fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved\nperformance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and\ndevelopment of novel therapeutics. However, there are certain limitations and challenges in applying genetically engineered cells\nin clinical practice. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment,\nand drug development, of SB-inspired cell engineering. It describes technologies and relevant examples in a clinical and\nexperimental setup that may signi\ufb01cantly impact the biomedicine \ufb01eld. At last, this review concludes the results with future\ndirections to optimize the performances of synthetic gene circuits to regulate the therapeutic activities of cell-based tools in speci\ufb01c\ndiseases.\nSignal Transduction and Targeted Therapy  (2023) 8:112 \n; https://doi.org/10.1038/s41392-023-01375-x\nINTRODUCTION\nModern science is becoming highly multidisciplinary to promote\nthe innovation of new theories and technologies. Synthetic biology\n(SB) is one of the fastest-growing and most dynamic multi-\ndisciplinary \ufb01elds comprising different projects, approaches, and\nde\ufb01nitions.1\u20133 SB applies engineering principles to genetically\ndesign and transform cells or living organisms by constructing\nbiological functional components, devices, and systems, creating or\nreinventing biological modules to meet human needs, or even\ncreating novel biological systems.4 SB-inspired cell factory engi-\nneering for industrial applications, in a narrow concept, is about\nusing renewable biomass resources as raw materials and synthetic\nassembly of existing components from microbial or animal cells to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 520
encoding: FLOAT32
metadata:
{"title": "Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development", "chroma:document": "produce various products.5\u20137 Engineered and standardized func-\ntional modules are the strengths of SB. Appropriate interface design\nmakes modules detachable, improving their stability and compat-\nibility in different environments. Whole-genome synthesis, redesign,\nand reconstruction allow generating of arti\ufb01cial biomimetic/\nminimal cells, while atomic or module/domain-level protein\nengineering offers high speci\ufb01city and controllability over more\ncomplex functions. Meanwhile, innovative modi\ufb01cation and crea-\ntive assembly of signaling and communication systems can further\noptimize cell engineering. In addition, mathematical models for\nfunctional module simulation and prediction help streamline circuit\ndesign for the development of invaluable research tools.8\u201310\nEngineered cells can have various applications, including the\nproduction of industrial or pharmaceutical compounds and\nincreasing agricultural productivity by alleviating pathogens and\nenvironmental challenges.11,12 SB-inspired cell engineering can be\ncommercialized for medical and healthcare. The main goal of\nmedical SB is to genetically modify cells and redesign/synthesize\nregulatory systems to assist in disease diagnosis and treat-\nment.13,14 Such cell-based sensors and therapies could achieve\nmore speci\ufb01c detection and treat diseases on a much broader\nscale.12,15,16 Medical SB utilizes rationally designed therapeutic\ngene circuits, which can be implanted into the human body via\nvectors to correct the targeted defect. SB-inspired cell engineering\nwith ef\ufb01cient design, speci\ufb01city, and control can maximize\ntherapeutic effects while minimizing side effects.\nThere are several reviews on SB technologies for developing\ntherapeutic strategies or improving clinical effectiveness; most of\nthem covered different aspects or speci\ufb01c approaches of SB in\nmedical applications (Fig. 1).17\u201326 The ongoing development of\nengineered cells-derived tools has attracted substantial public\nattention.\nAccordingly,\nthis\nreview\nsummarizes\nthe\nrecent"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 521
encoding: FLOAT32
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{"title": "Synthetic biology-inspired cell engineering in diagnosis, treatment, and drug development", "chroma:document": "recent\npreclinical, clinical, and experimental data to discuss the bene\ufb01ts\nand\nlimitations\nof SB\ntechniques\nin\ncell\nengineering\nand\nbiomedical research. Here, we elaborate on various SB-driven cell\ndevices in diagnosis, treatment, and drug development. Also, we\naddress the current and potential future challenges for SB and cell\nengineering in medical applications.\nENGINEERED CELLS FOR DIAGNOSIS\nAccurate disease characterization and monitoring are critical for\ntherapeutic planning and epidemiological records. However, most\ntraditional diagnostic procedures involving pathological examina-\ntion of biopsies cannot precisely detect the disease state in real-\ntime and are time-consuming. Thus, there is an urgent need to\nenhance current medical diagnostics capabilities. SB-inspired cell\nengineering and programmable biosensors have focused on high-\nthroughput biomolecular/pathogens identi\ufb01cation and probing,\nReceived: 5 September 2022 Revised: 31 January 2023 Accepted: 15 February 2023\n1Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China; 2College of Life\nScience, Sichuan Normal University, Chengdu, China and 3State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center of Nanjing University,\nJiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China\nCorrespondence: Huan Wang (wanghuan@nju.edu.cn) or Rui Bao (baorui@scu.edu.cn)\nThese authors contributed equally: Ninglin Zhao, Yingjie Song, Xiangqian Xie.\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: 522
encoding: FLOAT32
metadata:
{"title": "Distinct platelet crosstalk with adaptive and innate immune&nbsp;cells after adenoviral and mRNA vaccination against SARS-CoV-2", "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: 523
encoding: FLOAT32
metadata:
{"title": "Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on MRI in very pret\\\rerm infants", "chroma:document": "Acute histologic chorioamnionitis independently and directly \nincreases the risk for brain abnormalities seen on MRI in very \npreterm infants\nViral G Jain, MD1,2, Julia E. Kline, PhD2, Lili He, PhD2, Beth Kline-Fath, MD3,4, Mekibib \nAltaye, PhD5, Louis J. Muglia, MD PhD2,6,7, Emily A DeFranco, DO8, Namasivayam \nAmbalavanan, MD1, Nehal A. Parikh, DO, MS*,2,7,9,\nCincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators\n1.Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, \nBirmingham, AL\n2.Perinatal Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH\n3.Radiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH\n4.Department of Radiology, University of Cincinnati, College of Medicine, Cincinnati, OH\n5.Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center, \nCincinnati, OH\n6.Burroughs Wellcome Fund, Research Triangle Park, NC\n7.Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH\n8.Department of Obstetrics & Gynecology, University of Cincinnati, College of Medicine, \nCincinnati, OH\n9.Center for Prevention of Neurodevelopmental Disorders, Cincinnati Children\u2019s Hospital Medical \nCenter, Cincinnati, OH\nAbstract\nBackground:\u00a0The independent risk for neurodevelopmental impairments attributed to \nchorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury \nidentified on magnetic resonance imaging (MRI) at term-equivalent age can be used as a surrogate \nmeasure of neurodevelopmental impairments that is less confounded by post neonatal intensive \ncare unit (NICU) environmental factors to more clearly investigate this relationship.\n*Correspondence: Nehal A. Parikh, DO, MS, Cincinnati Children\u2019s Hospital Medical Center, 3333 Burnet Avenue, MLC 7009, \nCincinnati, OH, 45229, United States, nehal.parikh@cchmc.org, Phone: 513.636.7584.\nAuthor Contribution Statement"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 524
encoding: FLOAT32
metadata:
{"title": "Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on MRI in very pret\\\rerm infants", "chroma:document": "Conceptualization - VGJ, NAP. Methodology \u2013 NAP, VGJ, EAD, NA, LJM. Formal Analysis - VGJ, NAP, MA, JK, LH, BKF. Data \ncuration & Investigation \u2013 NAP, JK, BFK, LH. Writing- Original draft preparation - VGJ. Writing-Reviewing and Editing \u2013 NAP, MA, \nEAD, NM, LJM. Supervision - NAP. All authors have reviewed and approved the final version of this manuscript.\nConflict of Interest: None declared\nPublisher's Disclaimer: This is a PDF fle of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review \nof the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered \nwhich could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nAm J Obstet Gynecol. Author manuscript; available in PMC 2023 October 01.\nPublished in final edited form as:\nAm J Obstet Gynecol. 2022 October ; 227(4): 623.e1\u2013623.e13. doi:10.1016/j.ajog.2022.05.042.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 525
encoding: FLOAT32
metadata:
{"title": "Activation of immune signals during organ transplantation", "chroma:document": "REVIEW ARTICLE\nOPEN\nActivation of immune signals during organ transplantation\nQingwen Li1,2 and Peixiang Lan1,2\u2709\nThe activation of host\u2019s innate and adaptive immune systems can lead to acute and chronic graft rejection, which seriously impacts\ngraft survival. Thus, it is particularly signi\ufb01cant to clarify the immune signals, which are critical to the initiation and maintenance of\nrejection generated after transplantation. The initiation of response to graft is dependent on sensing of danger and stranger\nmolecules. The ischemia and reperfusion of grafts lead to cell stress or death, followed by releasing a variety of damage-associated\nmolecular patterns (DAMPs), which are recognized by pattern recognition receptors (PRRs) of host immune cells to activate\nintracellular immune signals and induce sterile in\ufb02ammation. In addition to DAMPs, the graft exposed to \u2018non-self\u2019 antigens\n(stranger molecules) are recognized by the host immune system, stimulating a more intense immune response and further\naggravating the graft damage. The polymorphism of MHC genes between different individuals is the key for host or donor immune\ncells to identify heterologous \u2018non-self\u2019 components in allogeneic and xenogeneic organ transplantation. The recognition of \u2018non-\nself\u2019 antigen by immune cells mediates the activation of immune signals between donor and host, resulting in adaptive memory\nimmunity and innate trained immunity to the graft, which poses a challenge to the long-term survival of the graft. This review\nfocuses on innate and adaptive immune cells receptor recognition of damage-associated molecular patterns, alloantigens and\nxenoantigens, which is described as danger model and stranger model. In this review, we also discuss the innate trained immunity\nin organ transplantation.\nSignal Transduction and Targeted Therapy  (2023) 8:110 \n; https://doi.org/10.1038/s41392-023-01377-9\nINTRODUCTION\nTransplantation rejection has always been the most critical\nproblem affecting the long-term survival of allografts, which"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 526
encoding: FLOAT32
metadata:
{"title": "Activation of immune signals during organ transplantation", "chroma:document": "involves many biological processes. During transplantation, the\ngraft experiences hypoxia/ischemia during preservation, leading\nto dysmetabolism and stress response. On the one hand, it\ninduces the production of mediators related to in\ufb02ammation and\nexpands the in\ufb02ammatory damage of cells. On the other hand, it\nmediates cells death. Damage-associated molecular patterns\n(DAMPs) from cells are exposed on the cell surface or released\nextracellular due to cellular stress or death. Graft reperfusion\nallows exposed DAMPs to be recognized by pattern recognition\nreceptors (PRRs) of the host circulating immune cells. The\ninteraction between DAMPs and PRRs activates PRRs, transmits\nactivation signals intracellular, and stimulates immune cells to\nsecrete pro-in\ufb02ammatory cytokines and chemokines, resulting in\naggravated graft injury. In addition to inducing innate immune\nresponse, the DAMPs produced by ischemia/reperfusion can be\ninvolved in the initiation of adaptive immunity as signal 0 via\nDendritic cells (DCs).1 However, it is important to note that\ncompared to allogeneic transplantation, DAMPs from syngeneic\ngraft induce DCs production and promote T lymphocyte cloning\nand proliferation, but they are not enough to induce DCs to\nproduce IL-12 and cannot drive T cells to differentiate into\nlymphocytes capable of producing IFN-\u03b3.2,3 Therefore, it\u2019s not\nsuf\ufb01cient to activate adaptive immune signals.\nThe host immune system distinguishes self and \u2018non-self\u2019\ncomponents, tolerates its healthy cells, and eliminates cells with\n\u2018non-self\u2019 antigens, which inevitably lead to graft rejection. To\nrecognition of \u2018non-self\u2019 antigens, the host immune system\nrequires the participation of receptors of immune cells. TCR of T\nand BCR of B lymphocytes can recognize allogeneic \u2018non-self\u2019 MHC\nantigens, leading to the activation of T and B lymphocyte-\nmediated rejection. However, the mere involvement of adaptive\nimmune cells in recognizing \u2018non-self\u2019 MHC molecules cannot\nexplain the fact that the depletion of lymphocytes still produces"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 527
encoding: FLOAT32
metadata:
{"title": "Activation of immune signals during organ transplantation", "chroma:document": "immune rejection of \u2018non-self\u2019 antigens.3 Multiple evidences reveal\nthat receptors expressed in innate immune NK and myeloid cells\ncan also recognize allogeneic antigens. These receptors belong to\na family of immunoglobulin-like receptors (ILRs), which recognize\nMHC molecules including classical and non-classical MHC and are\ninvolved in the regulation of transplant tolerance and immune\nresponse. Based on the release of DAMPs induced by metabolic\nreprogramming and stress responses during transplantation, as\nwell as the exposure of allogenic molecules to the host, this review\nmainly discusses the role of DAMPs, allogenic and xenogeneic\n\u2018non-self\u2019 component in immune recognition and induction of\npositive immune signals during transplantation.\nHISTORY OF ORGAN TRANSPLANTATION RESEARCH\nThe history of organ transplantation is inevitably associated with\nthe development of immunology. Advancements in our under-\nstanding of immune rejection have also driven clinical application\nof organ transplantation. Organ transplantation, as a powerful\ntreatment for end-stage diseases, has gone through a long and\nReceived: 26 October 2022 Revised: 10 February 2023 Accepted: 15 February 2023\n1Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China and 2Key Laboratory of Organ\nTransplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan,\nChina\nCorrespondence: Peixiang Lan (lansong9783@126.com)\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 528
encoding: FLOAT32
metadata:
{"title": "Opioid Withdrawal Abruptly Disrupts Amygdala Circuit Function by Reducing Peptide Actions", "chroma:document": "Cellular/Molecular\nOpioid Withdrawal Abruptly Disrupts Amygdala Circuit\nFunction by Reducing Peptide Actions\nGabrielle C. Gregoriou, Sahil D. Patel, Sebastian Pyne,\nBryony L. Winters, and Elena E. Bagley\nSydney Pharmacy School, Faculty of Medicine and Health and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia, 2111\nWhile the physical signs of opioid withdrawal are most readily observable, withdrawal insidiously drives relapse and contrib-\nutes to compulsive drug use, by disrupting emotional learning circuits. How these circuits become disrupted during with-\ndrawal is poorly understood. Because amygdala neurons mediate relapse, and are highly opioid sensitive, we hypothesized\nthat opioid withdrawal would induce adaptations in these neurons, opening a window of disrupted emotional learning circuit\nfunction. Under normal physiological conditions, synaptic transmission between the basolateral amygdala (BLA) and the neigh-\nboring main island (Im) of GABAergic intercalated cells (ITCs) is strongly inhibited by endogenous opioids. Using patch-clamp\nelectrophysiology in brain slices prepared from male rats, we reveal that opioid withdrawal abruptly reduces the ability of these\npeptides to inhibit neurotransmission, a direct consequence of a protein kinase A (PKA)-driven increase in the synaptic activity\nof peptidases. Reduced peptide control of neurotransmission in the amygdala shifts the excitatory/inhibitory balance of inputs\nonto accumbens-projecting amygdala cells involved in relapse. These findings provide novel insights into how peptidases control\nsynaptic activity within the amygdala and presents restoration of endogenous peptide activity during withdrawal as a viable option\nto mitigate withdrawal-induced disruptions in emotional learning circuits and rescue the relapse behaviors exhibited during opioid\nwithdrawal and beyond into abstinence.\nKey words: addiction; amygdala; opioids; peptidase; withdrawal\nSignificance Statement"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 529
encoding: FLOAT32
metadata:
{"title": "Opioid Withdrawal Abruptly Disrupts Amygdala Circuit Function by Reducing Peptide Actions", "chroma:document": "We find that opioid withdrawal dials down inhibitory neuropeptide activity in the amygdala. This disrupts both GABAergic\nand glutamatergic transmission through amygdala circuits, including reward-related outputs to the nucleus accumbens. This\nlikely disrupts peptide-dependent emotional learning processes in the amygdala during withdrawal and may direct behavior\ntoward compulsive drug use.\nIntroduction\nOpioid addiction is characterized by cycles of compulsive drug-\nuse, withdrawal and relapse (Koob and Volkow, 2016). During\nwithdrawal, relapse is strongly motivated by disrupted emotional\nlearning processes. Maladaptive reinforcement mechanisms drive\nrelapse triggered by the desire to alleviate the aversive withdrawal\nstate (Wikler and Pescor, 1967; Kenny et al., 2006) and by expo-\nsure to cues/contexts previously associated with drug use or with-\ndrawal (Wikler and Pescor, 1967; Childress et al., 1993; Hellemans\net al., 2006; Crombag et al., 2008). Then, if opioid reuse during\nwithdrawal does occur, disrupted reward learning processes ele-\nvate the incentive value of opiates, which persistently escalates\nreward-seeking and taking behaviors (Hutcheson et al., 2001;\nWassum et al., 2016). The cellular adaptions that underlie these\ndisruptions likely develop in the basolateral amygdala (BLA), as\nneural circuits within this area are associated with reinforce-\nment-driven relapse (Stinus et al., 1990; Fuchs and See, 2002;\nFrenois et al., 2005) and disrupted reward learning during with-\ndrawal (Wassum et al., 2016).\nEndogenous opioids acting at m-opioid receptors (MORs) in the\nBLA mediate the aversive opioid withdrawal state (Frenois et al.,\n2002) and learning changes in incentive value during withdrawal\n(Wassum et al., 2016). While their involvement in cue/context-\ninduced reinstatement of opiates is unresolved, endogenous opioids\nare also implicated in cue/context-driven relapse to other drugs\nsuch as nicotine (Liu et al., 2009), alcohol (Ciccocioppo et al., 2002),"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 530
encoding: FLOAT32
metadata:
{"title": "Opioid Withdrawal Abruptly Disrupts Amygdala Circuit Function by Reducing Peptide Actions", "chroma:document": "and cocaine (Burattini et al., 2008). This suggests that changes to en-\ndogenous opioid activity in the BLA during withdrawal may under-\nlie the disruptions to emotional learning processes that support and\nescalate drug use. Whether BLA endogenous opioid actions are\nchanged by opioid withdrawal is unknown.\nThe endogenous opioids that disrupt BLA processes during\nopioid withdrawal are likely sourced from neighboring GABAergic\nReceived July 3, 2022; revised Oct. 18, 2022; accepted Nov. 21, 2022.\nAuthor contributions: E.E.B. designed research; G.C.G., S.D.P., S.P., B.L.W., and E.E.B. performed research;\nG.C.G., S.D.P., S.P., and B.L.W. analyzed data; G.C.G. wrote the first draft of the paper; G.C.G. and E.E.B. edited\nthe paper; E.E.B. wrote the paper.\nThis work was supported by the National Health and Medical Research Council Grant APP1047372.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Elena E. Bagley at elena.bagley@sydney.edu.au.\nhttps://doi.org/10.1523/JNEUROSCI.1317-22.2022\nCopyright \u00a9 2023 the authors\n1668 \u2022 The Journal of Neuroscience, March 8, 2023 \u2022 43(10):1668\u20131681"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 531
encoding: FLOAT32
metadata:
{"title": "Model-Based Approach Shows ON Pathway Afferents Elicit a Transient Decrease of V1 Responses", "chroma:document": "Systems/Circuits\nModel-Based Approach Shows ON Pathway Afferents Elicit a\nTransient Decrease of V1 Responses\nDavid St-Amand and Curtis L. Baker Jr\nMcGill Vision Research Unit, Department of Ophthalmology & Visual Sciences, McGill University, Montreal, Quebec H3G 1A4, Canada\nNeurons in the primary visual cortex (V1) receive excitation and inhibition from distinct parallel pathways processing light-\nness (ON) and darkness (OFF). V1 neurons overall respond more strongly to dark than light stimuli, consistent with a pre-\nponderance of darker regions in natural images, as well as human psychophysics. However, it has been unclear whether this\n\u201cdark-dominance\u201d is because of more excitation from the OFF pathway or more inhibition from the ON pathway. To under-\nstand the mechanisms behind dark-dominance, we record electrophysiological responses of individual simple-type V1 neurons\nto natural image stimuli and then train biologically inspired convolutional neural networks to predict the neurons\u2019 responses.\nAnalyzing a sample of 71 neurons (in anesthetized, paralyzed cats of either sex) has revealed their responses to be more\ndriven by dark than light stimuli, consistent with previous investigations. We show that this asymmetry is predominantly\nbecause of slower inhibition to dark stimuli rather than to stronger excitation from the thalamocortical OFF pathway.\nConsistent with dark-dominant neurons having faster responses than light-dominant neurons, we find dark-dominance to\nsolely occur in the early latencies of neurons\u2019 responses. Neurons that are strongly dark-dominated also tend to be less orien-\ntation-selective. This novel approach gives us new insight into the dark-dominance phenomenon and provides an avenue to\naddress new questions about excitatory and inhibitory integration in cortical neurons.\nKey words: dark dominance; neurophysiology; receptive field; system identification; V1; visual cortex\nSignificance Statement"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 532
encoding: FLOAT32
metadata:
{"title": "Model-Based Approach Shows ON Pathway Afferents Elicit a Transient Decrease of V1 Responses", "chroma:document": "Neurons in the early visual cortex respond on average more strongly to dark than to light stimuli, but the mechanisms behind\nthis bias have been unclear. Here we address this issue by combining single-unit electrophysiology with a novel machine\nlearning model to analyze neurons\u2019 responses to natural image stimuli in primary visual cortex. Using these techniques, we\nfind slower inhibition to light than to dark stimuli to be the leading mechanism behind stronger dark responses. This slower\ninhibition to light might help explain other empirical findings, such as why orientation selectivity is weaker at earlier response\nlatencies. These results demonstrate how imbalances in excitation versus inhibition can give rise to response asymmetries in\ncortical neuron responses.\nIntroduction\nThe early thalamocortical visual system is separated into two dis-\ntinct pathways: an ON pathway, which responds more to lighter\nparts of images; and an OFF pathway, which encodes darker\nimage regions. Neurons in primary visual cortex (V1) combine\ninputs from these two pathways, but the nature of this integra-\ntion is still poorly understood.\nV1 neurons evidently receive asymmetrical inputs from the\ntwo pathways, since they are on average more responsive to dark\nthan light stimuli (Jin et al., 2008; Yeh et al., 2009), especially at\nlow spatial frequencies (Kremkow et al., 2014; Jansen et al., 2019)\nand shorter time latencies (Komban et al., 2014). This asymmetry\nis presumably adaptive because of the preponderance of dark\nregions in natural images (Ratliff et al., 2010), which is also more\npronounced at lower spatial frequencies (Cooper and Norcia,\n2015). These asymmetries may influence human perception,\nsince dark stimuli are processed faster and more reliably than\nlight stimuli (Buchner and Baumgartner, 2007; Komban et al.,\n2011).\nThere are more OFF than ON excitatory inputs from the\nLGN to layer 4 of V1, which could help explain why responses to\ndark stimuli are stronger in V1 (Jin et al., 2008). However, this"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 533
encoding: FLOAT32
metadata:
{"title": "Model-Based Approach Shows ON Pathway Afferents Elicit a Transient Decrease of V1 Responses", "chroma:document": "does not explain why more dark-dominant neurons are found in\nlayers 2/3 than in layer 4 (Yeh et al., 2009). This discrepancy\ncould be explained by stronger ON than OFF intracortical\nReceived June 21, 2022; revised Jan. 29, 2023; accepted Jan. 30, 2023.\nAuthor contributions: D.S.-A. and C.L.B. designed research; D.S.-A. performed research; D.S.-A. analyzed\ndata; D.S.-A. wrote the first draft of the paper; D.S.-A. and C.L.B. edited the paper.\nThis work was supported by Canadian Institutes of Health Research Grant MOP-119498 to C.L.B. We thank\nGuangxing Li for contributions to software and technical support in experiments; and Philippe Nguyen and\nAmol Gharat for important contributions to data collection and spike-sorting.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Curtis L. Baker at curtis.baker@mcgill.ca.\nhttps://doi.org/10.1523/JNEUROSCI.1220-22.2023\nCopyright \u00a9 2023 the authors\n1920 \u2022 The Journal of Neuroscience, March 15, 2023 \u2022 43(11):1920\u20131932"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 534
encoding: FLOAT32
metadata:
{"title": "Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial", "chroma:document": "ORIGINAL RESEARCH\nAxial Shortening in Myopic Children after Repeated\nLow-Level Red-Light Therapy: Post Hoc Analysis\nof a Randomized Trial\nWei Wang . Yu Jiang . Zhuoting Zhu . Shiran Zhang .\nMeng Xuan . Xingping Tan . Xiangbin Kong . Hui Zhong .\nGabriella Bulloch . Ruilin Xiong . Yixiong Yuan . Yanping Chen .\nJian Zhang . Junwen Zeng . Ian G. Morgan . Mingguang He\nReceived: January 1, 2023 / Accepted: January 31, 2023 / Published online: February 15, 2023\n\u0002 The Author(s) 2023\nABSTRACT\nIntroduction: Axial length (AL) elongation in\nmyopia is considered irreversible. We aimed to\nsystemically report unexpected AL shortening\nobserved in a randomized clinical trial (RCT)\nafter repeated low-level red-light (RLRL) therapy.\nMethods: This is a post hoc analysis of a multi-\ncenter, single-masked RCT. Two hundred sixty-\nfour myopic children aged 8\u201313 years allocated\nto RLRL treatment (intervention group) or a sin-\ngle vision spectacle (SVS, control group) were\nincluded. AL was measured using an IOL-master\n500 at baseline, 1-, 3-, 6-, and 12-month follow-\nup visits. AL shortening was de\ufb01ned as AL\nreduction from baseline to follow-up visits at\nthree\ncutoffs: [ 0.05 mm, [ 0.10 mm,\nand [\n0.20 mm. Frequency of AL shortening at differ-\nent cutoffs was calculated. Analysis was done\nwith intent to treat (ITT).\nResults: At 12-months follow up, frequency of\nAL shortening [ 0.05 mm was 26/119 (21.85%)\nWei Wang, Yu Jiang, Zhuoting Zhu, and Shiran Zhang\ncontributed equally and share the \ufb01rst authorship.\nSupplementary Information\nThe online version\ncontains supplementary material available at https://\ndoi.org/10.1007/s40123-023-00671-7.\nW. Wang \u0002 Y. Jiang \u0002 Z. Zhu \u0002 S. Zhang \u0002 M. Xuan \u0002\nR. Xiong \u0002 Y. Yuan \u0002 Y. Chen \u0002 J. Zhang \u0002 J. Zeng \u0002\nM. He\nState Key Laboratory of Ophthalmology, Zhongshan\nOphthalmic Center, Sun Yat-Sen University,\nGuangzhou, China\nZ. Zhu \u0002 G. Bulloch \u0002 M. He (&)\nCentre for Eye Research Australia, Royal Victorian\nEye and Ear Hospital, University of Melbourne,\nLevel 7, 32 Gisborne Street, East Melbourne, VIC"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 535
encoding: FLOAT32
metadata:
{"title": "Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial", "chroma:document": "3004, Australia\ne-mail: mingguang.he@unimelb.edu.au\nX. Tan\nOphthalmology, Xiangya Hospital, Central South\nUniversity, Changsha, Hunan, China\nX. Kong\nOphthalmology, Department of Surgery, The\nSecond People\u2019s Hospital of Foshan, Foshan,\nGuangdong, China\nH. Zhong\nDepartment of Ophthalmology, Shenzhen\nChildren\u2019s Hospital, Shenzhen, Guangdong, China\nG. Bulloch \u0002 M. He\nOphthalmology, Department of Surgery, University\nof Melbourne, Melbourne, Australia\nI. G. Morgan\nResearch School of Biology, Australian National\nUniversity, Canberra, Australia\nOphthalmol Ther (2023) 12:1223\u20131237\nhttps://doi.org/10.1007/s40123-023-00671-7"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 536
encoding: FLOAT32
metadata:
{"title": "Advances in the Rehabilitation of Hemispatial Inattention", "chroma:document": "Vol.:(0123456789)\n1 3\nCurrent Neurology and Neuroscience Reports (2023) 23:33\u201348 \nhttps://doi.org/10.1007/s11910-023-01252-8\nAdvances in\u00a0the\u00a0Rehabilitation of\u00a0Hemispatial Inattention\nNeena\u00a0R.\u00a0Singh1,2\u00a0\u00b7 Alexander\u00a0P.\u00a0Leff1 \nAccepted: 22 December 2022 / Published online: 4 March 2023 \n\u00a9 The Author(s) 2023\nAbstract\nPurpose of Review There continue to be a plethora of approaches to the rehabilitation of hemispatial inattention, from dif-\nferent forms of sensory stimulation (visual, auditory and somatosensory feedback), through all major modes of non-invasive \nbrain stimulation to drug therapies. Here we summarise trials published in the years 2017\u20132022 and tabulate their effect \nsizes, with the aim of drawing on common themes that may serve to inform future rehabilitative studies.\nRecent Findings Immersive virtual reality approaches to visual stimulation seem well tolerated, although they have yet to \nyield any clinically relevant improvements. Dynamic auditory stimulation looks very promising and has high potential for \nimplementation. Robotic interventions are limited by their cost and are perhaps best suited to patients with a co-occurring \nhemiparesis. Regarding brain stimulation, rTMS continues to demonstrate moderate effects but tDCS studies have yielded \ndisappointing results so far. Drugs, primarily aimed at the dopaminergic system, often demonstrate beneficial effects of a \nmedium size, but as with many of the approaches, it seems difficult to predict responders and non-responders.\nSummary Our main recommendation is that researchers consider incorporating single-case experimental designs into their \nstudies as rehabilitation trials are likely to remain small in terms of patient numbers, and this is the best way to deal with all \nthe factors that cause large between-subject heterogeneity.\nKeywords Hemispatial inattention\u00a0\u00b7 Neglect\u00a0\u00b7 Sensory stimulation\u00a0\u00b7 Brain stimulation\u00a0\u00b7 Dopaminergic therapy\u00a0\u00b7 \nRehabilitation\nIntroduction\nHemispatial inattention, also known as \u2018neglect\u2019, is an"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 537
encoding: FLOAT32
metadata:
{"title": "Advances in the Rehabilitation of Hemispatial Inattention", "chroma:document": "acquired neurological deficit affecting attention with a bias \ntowards one side of space. This is usually manifested in \nextra-personal space but can also affect the patient\u2019s own \nbody parts or intra-personal space. This causes significant \ndisability and, when stroke is the cause, often reduces the \neffectiveness of attempts to rehabilitate co-occurring deficits \nsuch as hemiparesis, causing increased in-patient stays and \nreduced functional independence [1]. It occurs in 25\u201330% \nof people hospitalised by a stroke and despite a degree of \nspontaneous recovery it can persist into the chronic phase \n(>3 months) in a third of cases [2].\nGiven its significant impact on stroke recovery, there \nhas been a considerable focus on the rehabilitation of hem-\nispatial inattention, with a variety of approaches trialled \nover the past 60 years employing either sensory stimula-\ntion, indirect brain stimulation, or drugs. Here we review \nthe most recent studies in the field. Given the diversity \nof approaches, it can be challenging to compare results \nacross studies. This is compounded by the lack of stand-\nardisation of outcome measures (summarised in Table\u00a01). \nWe have addressed this by tabulating unstandardised (raw) \nand standardised (usually Cohen\u2019s d) effects for all the \nreviewed studies, where these have been reported or can be \ncalculated from the data or figures provided (Table\u00a02). We \nhave limited ourselves to primary outcome measures in the \nmain text and split these into measures of impairment (e.g. \ncancellation tasks) or function (e.g. the Catherine Bergego \nScale (CBS)). There is no accepted Minimally Important \nClinical Difference (MICD) for cancellation tasks. For the \nCBS, a reduction of four points is considered meaningful \n[3].\n * Alexander P. Leff \n \na.leff@ucl.ac.uk\n1 \nUCL Queen Square institute of\u00a0Neurology, University \nCollege London, London, UK\n2 \nDepartment of\u00a0Neurology, Neurosciences Institute, Cleveland \nClinic London, London, UK"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 538
encoding: FLOAT32
metadata:
{"title": "Clinically Significant Axial Shortening in Myopic Children After Repeated Low-Level Red Light Therapy: A Retrospective Multicenter Analysis", "chroma:document": "ORIGINAL RESEARCH\nClinically Signi\ufb01cant Axial Shortening in Myopic\nChildren After Repeated Low-Level Red Light Therapy:\nA Retrospective Multicenter Analysis\nWei Wang . Yu Jiang . Zhuoting Zhu . Shiran Zhang .\nMeng Xuan . Yanping Chen . Ruilin Xiong . Gabriella Bulloch .\nJunwen Zeng . Ian G. Morgan . Mingguang He\nReceived: October 22, 2022 / Accepted: December 14, 2022 / Published online: January 7, 2023\n\u0002 The Author(s) 2023\nABSTRACT\nIntroduction: Myopia is recognized as a pro-\ngressive eye disease. The aim of this study was to\nevaluate the frequency and associated factors of\nclinically signi\ufb01cant axial length (AL) shorten-\ning among myopic children following repeated\nlow-level red light (RLRL) therapy.\nMethods: The clinical data that were collected\nfor the myopic children aged 3\u201317 years who\nreceived an RLRL therapy delivered by home-\nuse desktop light device that emitted light at\n650 nm for at least 1 year, were reviewed. The\nclinical data included AL, spherical equivalent\nrefraction (SER), and visual acuity measured at\nbaseline and follow-up. The primary outcomes\nwere\nfrequency\nof\nAL\nshortening\nof [ 0.05 mm, [ 0.10 mm, and [ 0.20 mm per\nyear, and associated factors of AL shortening per\nyear.\nResults: A total of 434 myopic children with at\nleast 12 months of follow-up data were inclu-\nded. The mean age of participants was 9.7 (2.6)\nyears with SER of -3.74 (2.60) diopters. There\nwere 115 (26.50%), 76 (17.51%), and 20 (4.61%)\nchildren with AL shortening based on cutoffs of\n0.05 mm/year,\n0.10 mm/year,\nand\n0.20 mm/\nyear, respectively. In the multivariable model,\nAL shortening was signi\ufb01cantly associated with\nolder baseline age, female gender, and longer\nbaseline AL\nor greater spherical\nequivalent\nWei Wang, Yu Jiang, Zhuoting Zhu, and Shiran Zhang\ncontributed equally.\nSupplementary Information\nThe online version\ncontains supplementary material available at https://\ndoi.org/10.1007/s40123-022-00644-2.\nW. Wang \u0002 Y. Jiang \u0002 Z. Zhu \u0002 S. Zhang \u0002 M. Xuan \u0002\nY. Chen \u0002 R. Xiong \u0002 J. Zeng \u0002 M. He (&)"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 539
encoding: FLOAT32
metadata:
{"title": "Clinically Significant Axial Shortening in Myopic Children After Repeated Low-Level Red Light Therapy: A Retrospective Multicenter Analysis", "chroma:document": "State Key Laboratory of Ophthalmology,\nGuangdong Provincial Key Laboratory of\nOphthalmology and Visual Science, Zhongshan\nOphthalmic Center, Sun Yat-Sen University,\nGuangzhou 510060, China\ne-mail: mingguang.he@unimelb.edu.au\nG. Bulloch \u0002 M. He\nCentre for Eye Research Australia, Royal Victorian\nEye and Ear Hospital, University of Melbourne,\nLevel 7, 32 Gisborne Street, East Melbourne, VIC\n3004, Australia\nI. G. Morgan\nResearch School of Biology, Australian National\nUniversity, Canberra, Australia\nM. He\nOphthalmology, Department of Surgery, University\nof Melbourne, Melbourne, Australia\nOphthalmol Ther (2023) 12:999\u20131011\nhttps://doi.org/10.1007/s40123-022-00644-2"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 540
encoding: FLOAT32
metadata:
{"title": "Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils", "chroma:document": "RESEARCH ARTICLE\nNeisseria gonorrhoeae co-opts C4b-binding\nprotein to enhance complement-independent\nsurvival from neutrophils\nLacie M. Werner1, Allison Alcott1\u00a4a, Frida Mohlin2, Jocelyn C. Ray1, Meagan Belcher\nDufrisne3, Asya Smirnov1\u00a4b, Linda Columbus3, Anna M. Blom2, Alison K. CrissID1*\n1 Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville,\nVirginia, United States of America, 2 Department of Translational Medicine, Lund University, Malmo,\nSweden, 3 Department of Chemistry, University of Virginia, Charlottesville, Virginia, United States of America\n\u00a4a Current address: Thermo Fisher Scientific, Gaithersburg, Maryland, United States of America\n\u00a4b Current address: Department of Molecular Microbiology, Washington University School of Medicine,\nSt. Louis, Missouri, United States of America\n* akc2r@virginia.edu\nAbstract\nNeisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmit-\nted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered\nbacteria predominantly express phase-variable, surface-expressed opacity-associated\n(Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc sur-\nvival when exposed to human neutrophils ex vivo. Here, we made the unexpected observa-\ntion that incubation with normal human serum, which is found in inflamed mucosal\nsecretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly\nlinked this phenomenon to a novel complement-independent function for C4b-binding pro-\ntein (C4BP). When bound to the bacteria, C4BP was necessary and sufficient to suppress\nGc-induced neutrophil reactive oxygen species production and prevent neutrophil phagocy-\ntosis of Opa+ Gc. This research identifies for the first time a complement-independent role\nfor C4BP in enhancing the survival of a pathogenic bacterium from phagocytes, thereby\nrevealing how Gc exploits inflammatory conditions to persist at human mucosal surfaces.\nAuthor summary"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 541
encoding: FLOAT32
metadata:
{"title": "Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils", "chroma:document": "Gonorrhea is considered an urgent threat to public health with an estimated 87 million\ncases occurring annually worldwide, growing antimicrobial resistance, and the absence of\na gonococcal vaccine. Currently, we do not understand how N. gonorrhoeae expressing\nopacity (Opa) proteins survive neutrophil defenses and are recovered viable from infected\npatients.\nHere, we investigated how soluble elements of gonorrhea infection, present in human\nserum, contribute to N. gonorrhoeae survival from neutrophils. We found that the serum\ncomponent C4b-binding protein (C4BP) protects N. gonorrhoeae from neutrophil killing\nand suppresses neutrophil activation. C4BP limited neutrophil phagocytosis of N.\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011055\nMarch 2, 2023\n1 / 27\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Werner LM, Alcott A, Mohlin F, Ray JC,\nBelcher Dufrisne M, Smirnov A, et al. (2023)\nNeisseria gonorrhoeae co-opts C4b-binding protein\nto enhance complement-independent survival from\nneutrophils. PLoS Pathog 19(3): e1011055. https://\ndoi.org/10.1371/journal.ppat.1011055\nEditor: H. Steven Seifert, Northwestern University\nFeinberg School of Medicine, UNITED STATES\nReceived: December 8, 2022\nAccepted: February 7, 2023\nPublished: March 2, 2023\nCopyright: \u00a9 2023 Werner 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: Data for the results\npresented in this manuscript are deposited in the\nOpen Science Framework repository: https://osf.io/\n6smfu/?view_only=f870019813d04cd38b6f89a94\n21f3788. Raw imaging flow cytometry data are\nuploaded to the MyFlowCyt repository as follows:\nPhagocytosis and association of bacteria with\nneutrophils: https://flowrepository.org/id/RvFrI1\nRnnCQSpSV7q5tLgTflvbNzVfC8Edq5I9pyOU8"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 542
encoding: FLOAT32
metadata:
{"title": "Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils", "chroma:document": "BOPRNuxMrLinIOVpmKGZ2 Detecting C4BP on\nthe bacterial surface: https://flowrepository.org/id/\nRvFrDE8iJvnxTCQOq0MD65s5vgpRts4oRz1oo7C"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 543
encoding: FLOAT32
metadata:
{"title": "Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications", "chroma:document": "REVIEW ARTICLE\nOPEN\nMetabolic landscape in cardiac aging: insights into molecular\nbiology and therapeutic implications\nSaiyang Xie1, Si-Chi Xu2, Wei Deng\n3 and Qizhu Tang1\u2709\nCardiac aging is evident by a reduction in function which subsequently contributes to heart failure. The metabolic\nmicroenvironment has been identi\ufb01ed as a hallmark of malignancy, but recent studies have shed light on its role in cardiovascular\ndiseases (CVDs). Various metabolic pathways in cardiomyocytes and noncardiomyocytes determine cellular senescence in the aging\nheart. Metabolic alteration is a common process throughout cardiac degeneration. Importantly, the involvement of cellular\nsenescence in cardiac injuries, including heart failure and myocardial ischemia and infarction, has been reported. However,\nmetabolic complexity among human aging hearts hinders the development of strategies that targets metabolic susceptibility.\nAdvances over the past decade have linked cellular senescence and function with their metabolic reprogramming pathway in\ncardiac aging, including autophagy, oxidative stress, epigenetic modi\ufb01cations, chronic in\ufb02ammation, and myocyte systolic\nphenotype regulation. In addition, metabolic status is involved in crucial aspects of myocardial biology, from \ufb01brosis to hypertrophy\nand chronic in\ufb02ammation. However, further elucidation of the metabolism involvement in cardiac degeneration is still needed.\nThus, deciphering the mechanisms underlying how metabolic reprogramming impacts cardiac aging is thought to contribute to the\nnovel interventions to protect or even restore cardiac function in aging hearts. Here, we summarize emerging concepts about\nmetabolic landscapes of cardiac aging, with speci\ufb01c focuses on why metabolic pro\ufb01le alters during cardiac degeneration and how\nwe could utilize the current knowledge to improve the management of cardiac aging.\nSignal Transduction and Targeted Therapy  (2023) 8:114 \n; https://doi.org/10.1038/s41392-023-01378-8\nINTRODUCTION"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 544
encoding: FLOAT32
metadata:
{"title": "Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications", "chroma:document": "In the past few decades, improved pharmacological and surgical\ntreatments have contributed to increased life expectancy and\nan aging population in certain industrialized countries.1 In\naddition, the proportion of the retired population is rapidly\nincreasing; retirees are much more likely to slide into sedentary\nlifestyles,\nwhich\nfurther\naccelerates\ncardiac\naging.2\u20135\nThe\nincidence of age-associated disorders, especially cardiovascular\ndiseases (CVDs), has increased dramatically; in elderly indivi-\nduals, these age-related disorders correlate with high hospita-\nlization, increased mortality rates, as well as elevated cost.4,5\nEven without disease, aging is accompanied with functional\ndecline of multiple organs. It is characterized by unique\nhistological and biochemical features, including oxidative stress,\nprotein misfolding, cell death, and mitochondrial abnormal-\nities.6,7 Similar to other group of organs, the heart function\ndeclines gradually with age, which is evident by the reduced\npump function and myocardial compliance resulting from\nincreased afterload and insuf\ufb01cient coronary perfusion/oxyge-\nnation.8\u201310 Conventional wisdom suggests that the aging heart\nmanifests increased left ventricular mass, while considerable\nevidence from autopsies and magnetic resonance imaging\ndemonstrate that cardiac mass tends to be decreased in older\nadults and remain the same in women in the absence of\nhypertension.11,12 In line with the reduced performance of other\norgan systems, the age-related cardiac decline dramatically\naccelerates after 50 years of age.10\nIn elderly individuals, the metabolic landscape during cellular\nsenescence can increase the risk of cardiac function dysregulation\nand cardiac repair dysfunction.13 For example, the stroke volume of\nthe aging heart is mildly increased during moderate aerobic\nexercise. This is partly due to the strength of the Frank-Starling\nmechanism (cardiac preload), in which the metabolic demand of the\nwork rate is substantially enhanced.14,15 In addition, a recent study"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 545
encoding: FLOAT32
metadata:
{"title": "Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications", "chroma:document": "involving metabolic pro\ufb01ling of serum and urine in healthy subjects\nsuggested that aging induces impaired catabolism in glycoproteins,\namino acids, and several lipids, among which cumulative metabo-\nlites contribute to the cardiac aging process.16 Importantly,\naccumulated evidence from multiomics exploration has highlighted\nthe complex alterations of metabolic status during aging. In this\nregard, we review and outline the recent advancements of the\nmechanisms and therapeutic implications of the metabolic land-\nscape in aging hearts since this information in\ufb02uences the\nprogression of the cardiac dysfunction and lifespan.\nDISTINCT SUBSTRATE METABOLISM DURING CARDIAC AGING\nAging hearts are accompanied by several pathological changes in\nmetabolism (Fig. 1). Below, we outline the major alterations in\nmetabolism and their involvement in developing cardiac aging.\nReceived: 12 September 2022 Revised: 6 February 2023 Accepted: 20 February 2023\n1Department of Cardiology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Metabolic and Chronic Diseases, Cardiovascular Research Institute of Wuhan\nUniversity, Wuhan, PR China; 2State Key Laboratory of Complex Severe and Rare Diseases, Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of\nMedical Science and Peking Union Medical College, Beijing, PR China and 3Department of Cardiology, Renmin Hospital of Wuhan University, Department of Cardiology, The Fifth\nAf\ufb01liated Hospital of Xinjiang Medical University, \u00dcr\u00fcmqi, PR China\nCorrespondence: Qizhu Tang (qztang@whu.edu.cn)\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: 546
encoding: FLOAT32
metadata:
{"title": "Time-resolved transcriptomic profiling of the developing rabbit\u0090s lungs: impact of premature birth and implications for modelling bronchopulmonary dysplasia", "chroma:document": "Storti\u00a0et\u00a0al. Respiratory Research           (2023) 24:80  \nhttps://doi.org/10.1186/s12931-023-02380-y\nRESEARCH\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.\nOpen Access\nRespiratory Research\nTime-resolved transcriptomic profiling \nof\u00a0the\u00a0developing rabbit\u2019s lungs: impact \nof\u00a0premature birth and\u00a0implications \nfor\u00a0modelling bronchopulmonary dysplasia\nMatteo Storti1, Maria Laura Faietti2, Xabier Murgia3, Chiara Catozzi1, Ilaria Minato4,5, Danilo Tatoni4,9, \nSimona Cantarella4,8, Francesca Ravanetti6, Luisa Ragionieri6, Roberta Ciccimarra6, Matteo Zoboli6, \nMar Vilanova7, Ester S\u00e1nchez\u2011Jim\u00e9nez7, Marina Gay7, Marta Vilaseca7, Gino Villetti1, Barbara Pioselli2, \nFabrizio Salomone1, Simone Ottonello4,5, Barbara Montanini4,5* and Francesca Ricci1,10* \nAbstract \nBackground Premature birth, perinatal inflammation, and life\u2011saving therapies such as postnatal oxygen and \nmechanical ventilation are strongly associated with the development of bronchopulmonary dysplasia (BPD); these"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 547
encoding: FLOAT32
metadata:
{"title": "Time-resolved transcriptomic profiling of the developing rabbit\u0090s lungs: impact of premature birth and implications for modelling bronchopulmonary dysplasia", "chroma:document": "risk factors, alone or combined, cause lung inflammation and alter programmed molecular patterns of normal lung \ndevelopment. The current knowledge on the molecular regulation of lung development mainly derives from mecha\u2011\nnistic studies conducted in newborn rodents exposed to postnatal hyperoxia, which have been proven useful but \nhave some limitations.\nMethods Here, we used the rabbit model of BPD as a cost\u2011effective alternative model that mirrors human lung \ndevelopment and, in addition, enables investigating the impact of premature birth per se on the pathophysiology of \nBPD without further perinatal insults (e.g., hyperoxia, LPS\u2011induced inflammation). First, we characterized the rabbit\u2019s \nnormal lung development along the distinct stages (i.e., pseudoglandular, canalicular, saccular, and alveolar phases) \nusing histological, transcriptomic and proteomic analyses. Then, the impact of premature birth was investigated, \ncomparing the sequential transcriptomic profiles of preterm rabbits obtained at different time intervals during their \nfirst week of postnatal life with those from age\u2011matched term pups.\nResults Histological findings showed stage\u2011specific morphological features of the developing rabbit\u2019s lung and \nvalidated the selected time intervals for the transcriptomic profiling. Cell cycle and embryo development, oxidative \nphosphorylation, and WNT signaling, among others, showed high gene expression in the pseudoglandular phase. \nAutophagy, epithelial morphogenesis, response to transforming growth factor \u03b2, angiogenesis, epithelium/endothe\u2011\nlial cells development, and epithelium/endothelial cells migration pathways appeared upregulated from the 28th \nday of gestation (early saccular phase), which represents the starting point of the premature rabbit model. Premature \nbirth caused a significant dysregulation of the inflammatory response. TNF\u2011responsive, NF\u2011\u03baB regulated genes were \n*Correspondence:\nBarbara Montanini\nbarbara.montanini@unipr.it\nFrancesca Ricci\nF.RICCI@chiesi.com"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 548
encoding: FLOAT32
metadata:
{"title": "Time-resolved transcriptomic profiling of the developing rabbit\u0090s lungs: impact of premature birth and implications for modelling bronchopulmonary dysplasia", "chroma:document": "Full 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: 549
encoding: FLOAT32
metadata:
{"title": "A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants", "chroma:document": "ARTICLE\nOPEN\nA new generation Mpro inhibitor with potent activity against\nSARS-CoV-2 Omicron variants\nChong Huang1, Huiping Shuai2,3, Jingxin Qiao1, Yuxin Hou2,3, Rui Zeng1, Anjie Xia\n1, Lingwan Xie1, Zhen Fang\n1, Yueyue Li1,\nChaemin Yoon2,3, Qiao Huang4, Bingjie Hu2,3, Jing You1, Baoxue Quan1, Xiu Zhao1, Nihong Guo4, Shiyu Zhang4, Ronggang Ma1,\nJiahao Zhang1, Yifei Wang1, Ruicheng Yang1, Shanshan Zhang1, Jinshan Nan1, Haixing Xu1, Falu Wang1, Jian Lei\n1\u2709,\nHin Chu\n2,3\u2709 and Shengyong Yang1\u2709\nEmerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health.\nSmall molecule antivirals are an effective treatment strategy to \ufb01ght against the virus. However, the \ufb01rst-generation antivirals either\nshow limited clinical ef\ufb01cacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these\ndrugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a new\ngeneration antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). This\ncompound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, but\nalso other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2\nmouse model, oral treatment with SY110 signi\ufb01cantly lowered the viral burdens in lung and alleviated the virus-induced pathology.\nImportantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstanding\nsafety pro\ufb01le. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigation\nprovides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.\nSignal Transduction and Targeted Therapy  (2023) 8:128 \n; https://doi.org/10.1038/s41392-023-01392-w\nINTRODUCTION"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 550
encoding: FLOAT32
metadata:
{"title": "A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants", "chroma:document": "Since the outbreak of the Coronavirus Disease 2019 (COVID-19)\npandemic\ndue\nto\nthe\nsevere\nacute\nrespiratory\nsyndrome\ncoronavirus 2 (SARS-CoV-2) in late 2019, more than three years\nhave passed.1,2 In the battle against this virus, vaccines have\nplayed a decisive role. However, continuous viral mutations, from\nAlpha, Beta, to the latest Omicron, bring challenges to the\nprotection effect of existing vaccines.3\u20137 Especially, the Omicron\nvariant and its sublineages have more than 30 mutations on the\nspike protein, which is the main target of vaccines, and have\nshown much higher transmissibility and escape of immune\nelicited by natural infection or vaccines than other SARS-CoV-2\nvariants.8\u201311 Furthermore, historical experiences tell us that the\nlong-term existence of SARS-CoV-2 is perhaps inevitable.12 There-\nfore, besides vaccines, effective antivirals are also an important\nstrategy to address the current epidemic and future threats.\nSARS-CoV-2 is a positive-sense single stranded (+ss) RNA\nvirus.2,13 It belongs to the genus \u03b2-coronavirus of the family\nCoronaviridae.2 The SARS-CoV-2 genome encodes 14 open reading\nframes (ORFs) with a length of around 30 kb. These ORFs encodes\ntwo long polyproteins, pp1a and pp1ab, four structural proteins\nand nine accessory proteins. The two polyproteins, pp1a and\npp1ab, are self-catalyzed and cleaved into 16 non-structural\nproteins (NSPs) by two cysteine proteases, the main protease\n(Mpro, also referred to as 3CLpro) and the papain-like protease\n(PLpro).14,15 Mpro is a conserved gene in SARS-CoV-2 and its\nvariants, as well as other highly pathogenic coronavirus, including\nSARS-CoV-1, MERS-CoV.15\u201318 This protease is responsible for the\ngeneration of 13 NSPs by cleaving pp1a and pp1ab, including\nRNA-dependent RNA polymerase (RdRp), helicase, exoribonu-\ncleases, 2\u2032-O-methyltransferase and uridine-speci\ufb01c endoribonu-\nclease.15,19 Of note is that Mpro recognizes and cleaves amino acid\nsequence of the substrate with speci\ufb01city and its most cleavage"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 551
encoding: FLOAT32
metadata:
{"title": "A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants", "chroma:document": "sites at sequences Leu-Gln \u2193 (Ser, Ala, or Gly) (\u2193 represents the\ncleavage site), while no known human proteases have the similar\nspeci\ufb01city.20 The critical role of Mpro in viral replication and its high\nconservation, combined with no known human proteases with\nsimilar cleavage speci\ufb01city, render it an attractive target for the\ndevelopment of antivirals. The RdRp, a highly versatile enzyme\nthat assists in RNA synthesis by catalyzing the RNA-template-\ndependent\nformation\nof\nphosphodiester\nbonds,\nis\nanother\nimportant\nantiviral\ntarget,\nand\nhas\nalso\nbeen\nextensively\nstudied.18,19\nCurrently, several small-molecule antivirals targeting Mpro or\nRdRp have been approved to use in some countries and regions\nworldwide. For example, three small-molecule antivirals, Remde-\nsivir, Molnupiravir, and Paxlovid (a combination of Nirmatrelvir\nand Ritonavir), have been approved to use clinically by US Food\nReceived: 4 February 2023 Revised: 27 February 2023 Accepted: 5 March 2023\n1State Key Laboratory of Biotherapy and Cancer Center and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041,\nChina; 2State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region,\nChina; 3Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China and 4Key\nLaboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China\nCorrespondence: Jian Lei (leijian@scu.edu.cn) or Hin Chu (hinchu@hku.hk) or Shengyong Yang (yangsy@scu.edu.cn)\nThese authors contributed equally: Chong Huang, Huiping Shuai, Jingxin Qiao, Yuxin Hou, Rui Zeng, Anjie Xia, Lingwan Xie, Zhen Fang\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: 552
encoding: FLOAT32
metadata:
{"title": "Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex", "chroma:document": "Vol.:(0123456789)\n1 3\nActa Neuropathologica (2023) 145:439\u2013459 \nhttps://doi.org/10.1007/s00401-023-02541-9\nORIGINAL PAPER\nAssociations of\u00a0psychiatric disease and\u00a0ageing with\u00a0FKBP5 expression \nconverge on\u00a0superficial layer neurons of\u00a0the\u00a0neocortex\nNatalie\u00a0Matosin1,2,3 \u00a0\u00b7 Janine\u00a0Arloth1,4\u00a0\u00b7 Darina\u00a0Czamara1\u00a0\u00b7 Katrina\u00a0Z.\u00a0Edmond2,3\u00a0\u00b7 Malosree\u00a0Maitra6\u00a0\u00b7 \nAnna\u00a0S.\u00a0Fr\u00f6hlich1,5\u00a0\u00b7 Silvia\u00a0Martinelli1,5\u00a0\u00b7 Dominic\u00a0Kaul2,3\u00a0\u00b7 Rachael\u00a0Bartlett2,3\u00a0\u00b7 Amber\u00a0R.\u00a0Curry2,3\u00a0\u00b7 Nils\u00a0C.\u00a0Gassen1,8\u00a0\u00b7 \nKathrin\u00a0Hafner1\u00a0\u00b7 Nikola\u00a0S.\u00a0M\u00fcller4\u00a0\u00b7 Karolina\u00a0Worf4\u00a0\u00b7 Ghalia\u00a0Rehawi1,4\u00a0\u00b7 Corina\u00a0Nagy6,9\u00a0\u00b7 Thorhildur\u00a0Halldorsdottir7\u00a0\u00b7 \nCristiana\u00a0Cruceanu1,20\u00a0\u00b7 Miriam\u00a0Gagliardi10\u00a0\u00b7 Nathalie\u00a0Gerstner1,4,5\u00a0\u00b7 Maik\u00a0K\u00f6del1\u00a0\u00b7 Vanessa\u00a0Murek1,10\u00a0\u00b7 \nMichael\u00a0J.\u00a0Ziller1,10\u00a0\u00b7 Elizabeth\u00a0Scarr11,17\u00a0\u00b7 Ran\u00a0Tao12\u00a0\u00b7 Andrew\u00a0E.\u00a0Jaffe12\u00a0\u00b7 Thomas\u00a0Arzberger13,14\u00a0\u00b7 Peter\u00a0Falkai1,13\u00a0\u00b7 \nJoel\u00a0E.\u00a0Kleinmann12,15\u00a0\u00b7 Daniel\u00a0R.\u00a0Weinberger12,15\u00a0\u00b7 Naguib\u00a0Mechawar6,9\u00a0\u00b7 Andrea\u00a0Schmitt13,16\u00a0\u00b7 Brian\u00a0Dean11,17\u00a0\u00b7 \nGustavo\u00a0Turecki6,9,18\u00a0\u00b7 Thomas\u00a0M.\u00a0Hyde12,15\u00a0\u00b7 Elisabeth\u00a0B.\u00a0Binder1,19\nReceived: 19 December 2022 / Revised: 18 January 2023 / Accepted: 19 January 2023 / Published online: 2 February 2023 \n\u00a9 The Author(s) 2023\nAbstract\nIdentification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with \ndecades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a \ntherapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expres-\nsion is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical \nareas of the human brain this occurs. This knowledge is critical to propel FKBP5/1-targeted treatment development. Here, \nwe performed an extensive, large-scale postmortem study (n = 1024) of FKBP5/1, examining neocortical areas (BA9, BA11 \nand ventral BA24/BA24a) derived from subjects that lived with schizophrenia, major depression or bipolar disorder. With"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 553
encoding: FLOAT32
metadata:
{"title": "Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex", "chroma:document": "an extensive battery of RNA (bulk RNA sequencing, single-nucleus RNA sequencing, microarray, qPCR, RNAscope) and \nprotein (immunoblot, immunohistochemistry) analysis approaches, we thoroughly investigated the effects of disease state, \nageing and genotype on cortical FKBP5/1 expression including in a cell type-specific manner. We identified consistently \nheightened FKBP5/1 levels in psychopathology and with age, but not genotype, with these effects strongest in schizophrenia. \nUsing single-nucleus RNA sequencing (snRNAseq; BA9 and BA11) and targeted histology (BA9, BA24a), we established \nthat these disease and ageing effects on FKBP5/1 expression were most pronounced in excitatory superficial layer neurons \nof the neocortex, and this effect appeared to be consistent in both the granular and agranular areas examined. We then found \nthat this increase in FKBP5 levels may impact on synaptic plasticity, as FKBP5 gex levels strongly and inversely correlated \nwith dendritic mushroom spine density and brain-derived neurotrophic factor (BDNF) levels in superficial layer neurons in \nBA11. These findings pinpoint a novel cellular and molecular mechanism that has potential to open a new avenue of FKBP51 \ndrug development to treat cognitive symptoms in psychiatric disorders.\nKeywords FKBP5\u00a0\u00b7 FKBP51\u00a0\u00b7 Psychosis\u00a0\u00b7 Depression\u00a0\u00b7 Ageing\u00a0\u00b7 Stress\u00a0\u00b7 Single cell\u00a0\u00b7 Postmortem brain\nIntroduction\nSevere psychiatric disorders\u2014including schizophrenia, \nmajor depression and bipolar disorder\u2014present a huge \nburden for individuals, society and the healthcare system. \nWhile there are efficacious treatments, relapse, resistance \nand chronicity are common, and cognitive symptoms in par-\nticular are not adequately treated [28, 58]. A major issue \nis that the approved use of available drugs and treatments \nfor specific psychiatric diagnoses, and their prescription \n * Natalie Matosin \n \nnmatosin@uow.edu.au\n * Elisabeth B. Binder \n \nbinder@psych.mpg.de\nExtended author information available on the last page of the article"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 554
encoding: FLOAT32
metadata:
{"title": "Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology", "chroma:document": "The Journal of Infectious Diseases                                \nS U P P L E M E N T  A R T I C L E\nBiotypes of Central Nervous System Complications in \nPeople With Human Immunodeficiency Virus: \nVirology, Immunology, and Neuropathology\nSarah B. Joseph,1,a, Sara Gianella,2,a Tricia H. Burdo,3 Paola Cinque,4 Magnus Gisslen,5,6 Scott Letendre,2 Avindra Nath,7, Susan Morgello,8\nLishomwa C. Ndhlovu,9,b and Serena Spudich10,b\n1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 2Department of Medicine, Division of Infectious Disease and Global \nPublic Health, University of California, San Diego, La Jolla, California, USA; 3Department of Microbiology, Immunology and Inflammation, Center for NeuroVirology and Gene Editing, Lewis Katz \nSchool of Medicine, Temple University, Philadelphia, Pennsylvania, USA; 4Unit of Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy; 5Department of Infectious Diseases, Institute of \nBiomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 6Department of Infectious Diseases, Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Gothenburg, \nSweden; 7National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA; 8Departments of Neurology, Neuroscience, and Pathology, Icahn School \nof Medicine at Mount Sinai, New York, New York, USA; 9Department of Medicine, Division of Infectious Diseases, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, \nUSA; and 10Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA\nDespite viral suppression with antiretroviral therapy (ART), people with human immunodeficiency virus (HIV) continue to \nexperience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health \ndisorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis and heterogeneity of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 555
encoding: FLOAT32
metadata:
{"title": "Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology", "chroma:document": "mechanisms likely underlying CNS complications must be addressed in the development of preventive interventions and \neffective treatments. The biotyping approach has previously been useful to define phenotypes of other CNS diseases based on \nunderlying mechanisms and could be translated to the field of neuroHIV. The purpose of the Biotype Workshop series, and the \nVirology, Immunology and Neuropathology Working Group in particular, is to capitalize on current and new technologies and \nguide future research efforts using the wealth of available immunological, virologic, and neuropathological data collected from \npeople with HIV on and off ART.\nKeywords. HIV-associated cognitive disorder; HAND; neuroHIV; biomarkers; inflammation; biotype.\naS. B. J. and S. G. contributed equally to this work (shared first authors).\nbL. C. N. and S. S. contributed equally to this work (shared last authors).\nCorrespondence: Sarah B. Joseph, PhD, Department of Microbiology and Immunology, \nUniversity of North Carolina at Chapel Hill, 22-062 Lineberger Comprehensive Cancer Center \nCB# 7295, Chapel Hill, NC 27510 (sbjoseph@email.unc.edu).\nThe Journal of Infectious Diseases\u00ae\n2023;227(S1):S3\u201315 \n\u00a9 The Author(s) 2023. 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 licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which \npermits non-commercial reproduction and distribution of the work, in any medium, provided \nthe original work is not altered or transformed in any way, and that the work is properly cited. \nFor commercial re-use, please contact journals.permissions@oup.com\nhttps://doi.org/10.1093/infdis/jiac370\nHuman immunodeficiency virus type 1 (HIV) can be detected \nin the central nervous system (CNS) days after infection [1] and \nis associated with cognitive, neurological, and mental health \ncomplications [2]. Antiretroviral therapy (ART) has dramat-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 556
encoding: FLOAT32
metadata:
{"title": "Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology", "chroma:document": "ically reduced CNS morbidity; however, many people with \nHIV (PWH) continue to experience CNS complications, pri-\nmarily in the form of mild cognitive impairment and mental \nhealth disorders (eg, depression, anxiety, other neuropsychi-\natric problems) [3\u20135]. Understanding the complex relation-\nship between HIV infection and neuropathogenesis remains \na research priority even though ART that suppresses HIV \nreplication reduces how HIV directly and indirectly affects \nthe CNS.\nDecades-long research efforts have not generated a complete \nunderstanding of the mechanisms by which HIV infection gen-\nerates and maintains CNS complications during ART, and no \neffective therapies exist to reverse these complications. \nInflammation has long been viewed as one of the primary driv-\ners of CNS complications. While an early-stage study aimed at \nreducing monocyte activation in the CNS showed promise for \nimproving cognition in PWH [6], several clinical trials aimed at \nreducing neuroinflammation in ART-treated PWH generated \nminimal or no improvement in cognition [7, 8]. Such findings \nmay be explained by the following, not mutually exclusive, pos-\nsibilities: (1) neuroinflammation is not the exclusive driver of \nadverse CNS outcomes; (2) clinical trials included interven-\ntions that were unable to sufficiently inhibit the type of inflam-\nmation responsible for CNS complications; (3) participants had \naccumulated irreversible CNS damage prior to the intervention \n(so-called legacy effect); (4) these trials only examined differ-\nences in specific subgroups, which might not be representative \nof the entire populations of PWH; and/or (5) most studies fo-\ncused on global cognition and it is possible that certain drugs \ninfluence some, but not all, domains. These findings highlight \nthe need for new approaches for studying neuroHIV.\nBiotypes of CNS Complications in People With HIV \u2022 JID 2023:227 (Suppl 1) \u2022 S3"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 557
encoding: FLOAT32
metadata:
{"title": "Sulindac", "chroma:document": "Annals of the Rheumatic Diseases, 1978, 37, 89-92\nSulindac\nTrials of a new anti-inflammatory drug\nE. C. HUSKISSON AND JANE SCOTT\nFrom the Department ofRheumatology, St Bartholomew's Hospital, London ECI\nSUMMARY\nTrials in patients with rheumatoid arthritis and osteoarthritis showed sulindac to be an\nanalgesic with anti-inflammatory properties and at least as effective as aspirin. It was effective\nwithin 24 hours in doses of 300-400 mg daily. It had the advantages of twice daily administration\nand a lower incidence of gastric side effects than aspirin. Constipation, usually mild, occurred in\n20-30% of cases. Like other anti-inflammatory drugs, it was effective in only a proportion of the\npatients.\nThere is no shortage of nonsteroidal anti-inflamma-\ntory drugs. A new compound should therefore have\nsome advantage to justify its introduction. Sulindac\nis related to indomethacin and would have such an\nadvantage\nif\nit combined the anti-inflammatory\nactivity of indomethacin with a more acceptable\nincidence ofside effects.\nSulindac is an indene analogue of indomethacin\nwith similar anti-inflammatory potency in animal\nmodels but less tendency to cause gastric bleeding\nand ulceration (Van Arman et al., 1972). It is well\nabsorbed after oral administration with a plasma\nhalf,life of about 8 hours, it is excreted mainly in\nthe urine as unchanged drug and sulphone metabo-\nlite.\nAnother\nmetabolite,\nthe\nsulphide,\ncan\nbe\ndetected in plasma and has a long half-life of about\n18 hours. It is more active than sulindac in animal\nmodels of inflammation and may account for a\nmajor part of the anti-inflammatory effect (Hucker\netal., 1973).\nMethods\nThree double-blind trials were carried out, a short-\nterm\nthree-way\ncrossover\ntrial\nin\nrheumatoid\narthritis (RA) and long-term studies in both RA and\nosteoarthritis (OA).\nCROSSOVER STUDY\nTwenth-four outpatients with RA entered a cross-\nover study, each receiving one week of treatment\nwith aspirin (3-6 g daily in 4 divided doses), sulindac\nAccepted for publication June 20, 1977"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 558
encoding: FLOAT32
metadata:
{"title": "Sulindac", "chroma:document": "Correspondence to Dr E. C. Huskisson\n(400 mg daily in 2 divided doses), and placebo. The\norder of treatment was randomised and balanced.\nMeasurements made at the end of each week of\ntreatment by a single observer included pain (visual\nanalogue\nscale),\nduration\nof morning\nstiffness,\nproximal\ninterphalangeal\njoint\ncircumference\n(Boardman and Hart, 1967), articular index (Ritchie\net al., 1968), and drug preference. The patients com-\npleted a daily visual analogue pain relief scale which\nwas used to determine the time course of the actions\nof the drugs.\nLONG-TERM STUDY IN OA\nThirty outpatients with OA of the hip or knee were\nallocated randomly to two treatment groups.\n14\npatients received sulindac in an initial dose of 100 mg\ntwice daily with the possibility of increasing up to a\ntotal daily dose of 400 mg.\n16 patients received\naspirin in an initial dose of 500 mg four times daily\nwith the possibility of increasing up to a total daily\ndose of 4 g. Measurements were made by a single\nobserver before the start of treatment and after 1, 2,\n3, 4, 6, and 8 weeks of treatment. They included pain\nseverity (visual analogue scale), duration of stiffness\nafter inactivity, and side effects. The dose of trial\ndrugs was noted at each visit and checked by\nreturned tablet counting. Side effects were recorded,\nscored as either mild (1), moderate (2), or severe (3),\nand used to calculate side effect scores. The side\neffect score represented the sum of all side effects at\nall assessment visits. Urinalysis and full haematolo-\ngical and biochemical monitoring were performed.\nAn\nelectrocardiogram\nand\nan\nophthalmological\nassessment were carried out at the beginning and\nend of the study.\n89"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 559
encoding: FLOAT32
metadata:
{"title": "Potential RNA-dependent RNA polymerase \\(RdRp\\) inhibitors as prospective drug candidates for SARS-CoV-2", "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: 560
encoding: FLOAT32
metadata:
{"title": "Altered dendritic morphology in dorsolateral prefrontal cortex of nonhuman primates prenatally exposed to maternal immune activa\\\rtion", "chroma:document": "Altered dendritic morphology in dorsolateral prefrontal cortex \nof nonhuman primates prenatally exposed to maternal immune \nactivation\nKari L. Hansona,b,1, Ruth K. Weirc,1, Ana-Maria Iosifd, Judy Van de Waterb,f, Cameron S. \nCartera,g, A. Kimberley McAllisterg, Melissa D. Baumana,b,e,*, Cynthia M. Schumanna,b,*\naDepartment of Psychiatry and Behavioral Sciences, University of California, Davis School of \nMedicine, United States\nbMIND Institute, University of California, Davis, United States\ncInnovation & Enterprise Department, University College London, United Kingdom\ndDivision of Biostatistics, Department of Public Health Sciences, University of California, Davis, \nUnited States\neCalifornia National Primate Research Center, University of California, Davis, United States\nfRheumatology/Allergy and Clinical Immunology, University of California, Davis, United States\ngCenter for Neuroscience, University of California, Davis, United States\nAbstract\nWomen who contract a viral or bacterial infection during pregnancy have an increased risk of \ngiving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal \ninfection are likely mediated by the maternal immune response, as preclinical animal models have \nconfirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain \nand behavior development. The present study sought to determine the impact of MIA-exposure \nduring the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex \n(DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus \nmonkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased \nneuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative \nto controls, with no significant differences observed between offspring exposed to maternal \ninfection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 561
encoding: FLOAT32
metadata:
{"title": "Altered dendritic morphology in dorsolateral prefrontal cortex of nonhuman primates prenatally exposed to maternal immune activa\\\rtion", "chroma:document": "infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, \nirrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology \nof MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune \n*Corresponding authors at: Department of Psychiatry and Behavioral Sciences, University of California, Davis School of Medicine, \nUnited States. mdbauman@ucdavis.edu (M.D. Bauman), cschumann@ucdavis.edu (C.M. Schumann).\n1Authors contributed equally.\nDeclaration of Competing Interest\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to \ninfluence the work reported in this paper.\nHHS Public Access\nAuthor manuscript\nBrain Behav Immun. Author manuscript; available in PMC 2023 March 18.\nPublished in final edited form as:\nBrain Behav Immun. 2023 March ; 109: 92\u2013101. doi:10.1016/j.bbi.2023.01.003.\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: 562
encoding: FLOAT32
metadata:
{"title": "The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates", "chroma:document": "Systems/Circuits\nThe Neural Basis for Biased Behavioral Responses Evoked by\nGalvanic Vestibular Stimulation in Primates\nPatrick A. Forbes,1p Annie Kwan,2p Diana E. Mitchell,3 Jean-S\u00e9bastien Blouin,4 and\nKathleen E. Cullen3,5,6,7,8\n1Department of Neuroscience, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands, 2Departments of\nBiomedical Engineering and, 3Physiology, McGill University, Montr\u00e9al, Qu\u00e9bec H3G 1Y6, Canada, 4School of Kinesiology, University of British\nColumbia, Vancouver, British Colombia V6T 1Z1, Canada, 5Departments of Biomedical Engineering, 6Otolaryngology-Head and Neck Surgery, and,\n7Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, and 8Kavli Neuroscience Discovery Institute, Johns Hopkins University,\nBaltimore, Maryland 21205\nNoninvasive electrical stimulation of the vestibular system in humans has become an increasingly popular tool with a broad\nrange of research and clinical applications. However, common assumptions regarding the neural mechanisms that underlie\nthe activation of central vestibular pathways through such stimulation, known as galvanic vestibular stimulation (GVS), have\nnot been directly tested. Here, we show that GVS is encoded by VIIIth nerve vestibular afferents with nonlinear dynamics\nthat differ markedly from those predicted by current models. GVS produced asymmetric activation of both semicircular canal\nand otolith afferents to the onset versus offset and cathode versus anode of applied current, that in turn produced asymmet-\nric eye movement responses in three awake-behaving male monkeys. Additionally, using computational methods, we demon-\nstrate that the experimentally observed nonlinear neural response dynamics lead to an unexpected directional bias in the net\npopulation response when the information from both vestibular nerves is centrally integrated. Together our findings reveal\nthe neural basis by which GVS activates the vestibular system, establish that neural response dynamics differ markedly from"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 563
encoding: FLOAT32
metadata:
{"title": "The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates", "chroma:document": "current predictions, and advance our mechanistic understanding of how asymmetric activation of the peripheral vestibular\nsystem alters vestibular function. We suggest that such nonlinear encoding is a general feature of neural processing that will\nbe common across different noninvasive electrical stimulation approaches.\nKey words: asymmetry; galvanic vestibular stimulation; modeling; nonlinear; vestibular afferent\nSignificance Statement\nHere, we show that the application of noninvasive electrical currents to the vestibular system (GVS) induces more complex\nresponses than commonly assumed. We recorded vestibular afferent activity in macaque monkeys exposed to GVS using a\nsetup analogous to human studies. GVS evoked notable asymmetries in irregular afferent responses to cathodal versus anodal\ncurrents. We developed a nonlinear model explaining these GVS-evoked afferent responses. Our model predicts that GVS\ninduces directional biases in centrally integrated head motion signals and establishes electrical stimuli that recreate physiolog-\nically plausible sensations of motion. Altogether, our findings provide new insights into how GVS activates the vestibular sys-\ntem, which will be vital to advancing new clinical and biomedical applications.\nIntroduction\nVestibular sensory signals encode head movement and orienta-\ntion in space to shape our actions and perception in everyday life\nas we move and interact within our environment. During such\nself-motion, the vestibular system is inevitably activated in con-\ncert with other sensory modalities (e.g., vision, proprioception).\nAs such, studying the vestibular system requires techniques that\nallow for independent investigation from other sources of sen-\nsory feedback. A promising approach to target and understand\nthe functional role of the vestibular system is the application of\nlocalized currents via surface electrodes placed bilaterally behind\nthe ears on the mastoid process (Fitzpatrick and Day, 2004;\nForbes et al., 2015; Dlugaiczyk et al., 2019). This noninvasive"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 564
encoding: FLOAT32
metadata:
{"title": "The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates", "chroma:document": "Received May 23, 2022; revised Jan. 25, 2023; accepted Jan. 30, 2023.\nAuthor contributions: P.A.F., A.K., J.-S.B., and K.E.C. designed research; P.A.F., A.K., and D.E.M. performed\nresearch; P.A.F. and A.K. analyzed data; and P.A.F., A.K., J.-S.B., and K.E.C. wrote the paper.\nThis work was supported by National Institutes of Health\u2013National Institute on Deafness and Other\nCommunication Disorders Grants R01-DC002390, R01-DC013069, and 1UF1NS111695 to K.E.C. P.A.F. was\nsupported by Dutch Research Council Grants 016.Veni.188.049 and VI.Vidi.203.066, and J.-S.B. was supported\nby Natural Sciences and Engineering Research Council of Canada Grant RGPIN-2020-05438. We thank Maurice\nChacron for critical feedback on the manuscript.\n*P.A.F. and A.K. contributed equally to this work.\nThe authors declare no competing financial interests.\nCorrespondence should be addressed to Kathleen E. Cullen at kathleen.cullen@jhu.edu.\nhttps://doi.org/10.1523/JNEUROSCI.0987-22.2023\nCopyright \u00a9 2023 the authors\nThe Journal of Neuroscience, March 15, 2023 \u2022 43(11):1905\u20131919 \u2022 1905"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 565
encoding: FLOAT32
metadata:
{"title": "ZIKV RNA and IgM Persistence in blood compartments and body fluids: a\\nprospective observational study", "chroma:document": "ZIKV RNA and IgM Persistence in blood compartments and body \nfluids: a prospective observational study\nMars Stone, PhD1,2, Sonia Bakkour, PhD1,2, Marion C. Lanteri, PhD1,2, Donald Brambilla, \nPhD3, Prof. Graham Simmons, PhD1,2, Roberta Bruhn, PhD1,2, Zhanna Kaidarova, PhD1, \nTzong-Hae Lee, MD1, Jose Orlando Alsina, MS4, Phillip C. Williamson, PhD5, Susan A. \nGalel, MD6, Lisa Lee Pate, MD6, Jeffrey M. Linnen7, Prof. Steve Kleinman, MD8, Prof. \nMichael P. Busch, MD1,2,\nNHLBI Recipient Epidemiology Donor Evaluation Study REDS-III Program\n1.Vitalant Research Institute (formerly Blood Systems Research Institute), San Francisco, CA, \nUnited States.\n2.Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, \nUnited States\n3.RTI International, Rockville, MD, United States\n4.Banco de Sangre de Servicios Mutuos, San Juan, Puerto Rico, United States\n5.Creative Testing Solutions, Tempe, AZ, United States\n6.Roche Molecular Systems, Inc., Pleasanton, CA, United States\n7.Grifols Diagnostic Solutions Inc., San Diego, CA, United States\n8.Department of Pathology, University of British Columbia, Victoria, British Columbia, Canada\nAbstract\nBackground:\u00a0Characterization of the dynamics of Zika virus (ZIKV) persistence following acute \ninfection is needed to inform blood donor and diagnostic testing policies and understand the \nnatural history of ZIKV infection. We characterized the natural history, persistence, and clinical \noutcomes of ZIKV infection through prospective study of initially asymptomatic ZIKV RNA+ \nblood donors.\nCorresponding author: Mars Stone PhD. Address: Vitalant Research Institute, 270 Masonic Avenue, San Francisco, CA, United States \n94118. Phone: 1-415-354-1389. Fax: 1-415-567-5899. mstone@vitalant.org. \nConflicts of interest\nDr Linnen is an employee of Grifols Diagnostic Solutions Inc. and shareholder of Grifols. Drs Galel and Lee are employees and \nshareholder of Roche Diagnostics, which sponsored the clinical trial that identified the potential subjects for this study."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 566
encoding: FLOAT32
metadata:
{"title": "ZIKV RNA and IgM Persistence in blood compartments and body fluids: a\\nprospective observational study", "chroma:document": "Conflicts of interest\nDr Linnen is an employee of Grifols Diagnostic Solutions Inc. and shareholder of Grifols. Drs Galel and Lee are employees of Roche \nMolecular Systems. The remaining coauthors declare no conflicts of interest.\nMCL is now an employee of Cerus Corporation\nPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our \ncustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review \nof the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered \nwhich could affect the content, and all legal disclaimers that apply to the journal pertain.\nHHS Public Access\nAuthor manuscript\nLancet Infect Dis. Author manuscript; available in PMC 2023 March 21.\nPublished in final edited form as:\nLancet Infect Dis. 2020 December ; 20(12): 1446\u20131456. doi:10.1016/S1473-3099(19)30708-X.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 567
encoding: FLOAT32
metadata:
{"title": "Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19", "chroma:document": "Vol:.(1234567890)\nJournal of Clinical Immunology (2023) 43:882\u2013893\nhttps://doi.org/10.1007/s10875-023-01459-x\n1 3\nORIGINAL ARTICLE\nNeutrophil Activation and\u00a0Immune Thrombosis Profiles Persist \nin\u00a0Convalescent COVID\u201119\nHakim\u00a0Hocini1\u00a0\u00b7 Aur\u00e9lie\u00a0Wiedemann1\u00a0\u00b7 Fabiola\u00a0Blengio1\u00a0\u00b7 C\u00e9cile\u00a0Lefebvre1\u00a0\u00b7 Minerva\u00a0Cervantes\u2011Gonzalez4,5,6\u00a0\u00b7 \nEmile\u00a0Foucat1\u00a0\u00b7 Pascaline\u00a0Tisserand1\u00a0\u00b7 Mathieu\u00a0Surenaud1\u00a0\u00b7 S\u00e9verin\u00a0Col\u00e9on1\u00a0\u00b7 M\u00e9lanie\u00a0Prague1,2\u00a0\u00b7 Lydia\u00a0Guillaumat1\u00a0\u00b7 \nCorinne\u00a0Krief1\u00a0\u00b7 Craig\u00a0Fenwick3\u00a0\u00b7 C\u00e9dric\u00a0Laou\u00e9nan4,5\u00a0\u00b7 Lila\u00a0Bouadma5,6\u00a0\u00b7 Jade\u00a0Ghosn5,7\u00a0\u00b7 Giuseppe\u00a0Pantaleo1,8\u00a0\u00b7 \nRodolphe\u00a0Thi\u00e9baut1,2,9\u00a0\u00b7 the French COVID cohort study group\u00a0\u00b7 Yves\u00a0L\u00e9vy1,10 \nReceived: 23 December 2022 / Accepted: 24 February 2023 / Published online: 21 March 2023 \n\u00a9 The Author(s) 2023, corrected publication 2023\nAbstract\nPurpose Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated \nthe immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19.\nMethods We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole \nblood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6\u00a0months following hospital discharge.\nResults We observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and \nendothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory  CD4+ and \neffector  CD8+ T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of \ngenes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identi-\nfied a \u201ccore gene signature\u201d associated with a history of thrombotic events, with upregulation of a set of genes involved in \nneutrophil activation, platelet, hematopoiesis, and blood coagulation."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 568
encoding: FLOAT32
metadata:
{"title": "Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19", "chroma:document": "Conclusion The lack of restoration of gene expression to a normal profile after up to 6\u00a0months of follow-up, even in asymp-\ntomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose \npreventive measures.\nKeywords COVID-19 disease\u00a0\u00b7 post-acute COVID-19 syndrome\u00a0\u00b7 thrombosis\nIntroduction\nFollowing a severe acute respiratory syndrome coronavirus 2 \n(SARS-CoV-2) infection, a significant proportion of individ-\nuals develop prolonged symptoms, including predominantly \nfatigue, headache, and upper respiratory and multi-system \n * Yves L\u00e9vy \n \nyves.levy@aphp.fr\n1 \nVaccine Research Institute, Universit\u00e9 Paris-Est Cr\u00e9teil,  \nFacult\u00e9 de M\u00e9decine, INSERM U955, Team 16, Cr\u00e9teil, \nFrance\n2 \nDepartment of\u00a0Public Health, Univ. Bordeaux, Inserm \nBordeaux Population Health Research Centre, Inria SISTM, \nUMR 1219, Bordeaux, France\n3 \nService of\u00a0Immunology and\u00a0Allergy, Department \nof\u00a0Medicine, Lausanne University Hospital and\u00a0University \nof\u00a0Lausanne, Lausanne, Switzerland\n4 \nD\u00e9partement \u00c9pid\u00e9miologie Biostatistiques Et Recherche \nClinique, AP-HP, H\u00f4pital Bichat, INSERM, Centre \nd\u2019Investigation Clinique-Epid\u00e9miologie Clinique 1425, \n75018\u00a0Paris, France\n5 \nUMR 1137, Universit\u00e9 de Paris, INSERM, IAME, \n75018\u00a0Paris, France\n6 \nAPHP- H\u00f4pital Bichat \u2013 M\u00e9decine Intensive et R\u00e9animation \ndes Maladies Infectieuses, Paris, France\n7 \nAP-HP, H\u00f4pital Bichat, Service de Maladies Infectieuses Et \nTropicales, 75018\u00a0Paris, France\n8 \nSwiss Vaccine Research Institute, Lausanne University \nHospital, University of\u00a0Lausanne, Lausanne, Switzerland\n9 \nCHU de Bordeaux, P\u00f4le de Sant\u00e9 Publique, Service \nd\u2019Information M\u00e9dicale, Bordeaux, France\n10 Assistance Publique-H\u00f4pitaux de Paris, Service Immunologie \nClinique, Groupe Henri-Mondor Albert-Chenevier, Cr\u00e9teil, France"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 569
encoding: FLOAT32
metadata:
{"title": "Severe COVID-19 versus multisystem inflammatory syndrome: comparing two critical outcomes of SARS-CoV-2 infection", "chroma:document": "Severe COVID-19 versus multisystem inflammatory syndrome:\ncomparing two critical outcomes of SARS-CoV-2 infection\nRupsha Fraser1, Aurelio Orta-Resendiz\n2, David Dockrell1, Michaela M\u00fcller-Trutwin2 and\nAlexander Mazein3\n1The University of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, UK.\n2Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, HIV,\nInflammation and Persistence Unit, Paris, France. 3Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux,\nLuxembourg.\nCorresponding author: Rupsha Fraser (rupsha.fraser@ed.ac.uk)\nShareable abstract (@ERSpublications)\nDevelopment of severe COVID-19 versus multisystem inflammatory syndrome relies on distinct\naetiological factors that lead to variable host immune responses and inflammatory manifestations,\ndespite following a common trajectory of immune dysregulation. https://bit.ly/3Xtsa7P\nCite this article as: Fraser R, Orta-Resendiz A, Dockrell D, et al. Severe COVID-19 versus multisystem\ninflammatory syndrome: comparing two critical outcomes of SARS-CoV-2 infection. Eur Respir Rev\n2023; 32: 220197 [DOI: 10.1183/16000617.0197-2022].\nAbstract\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with diverse host\nresponse immunodynamics and variable inflammatory manifestations. Several immune-modulating risk\nfactors can contribute to a more severe coronavirus disease 2019 (COVID-19) course with increased\nmorbidity and mortality. The comparatively rare post-infectious multisystem inflammatory syndrome (MIS)\ncan develop in formerly healthy individuals, with accelerated progression to life-threatening illness. A\ncommon trajectory of immune dysregulation forms a continuum of the COVID-19 spectrum and MIS;\nhowever, severity of COVID-19 or the development of MIS is dependent on distinct aetiological factors\nthat produce variable host inflammatory responses to infection with different spatiotemporal manifestations,\na comprehensive understanding of which is necessary to set better targeted therapeutic and preventative"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 570
encoding: FLOAT32
metadata:
{"title": "Severe COVID-19 versus multisystem inflammatory syndrome: comparing two critical outcomes of SARS-CoV-2 infection", "chroma:document": "strategies for both.\nIntroduction\nThe management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing the\ncoronavirus disease 2019 (COVID-19) pandemic, has been a major new challenge to healthcare and\nresearch. SARS-CoV-2 infection is associated with diverse host response immunodynamics with variable\ninflammatory manifestations. The development of severe COVID-19 can typically be linked to a number of\nrisk factors (e.g. age-related susceptibility, pre-existing chronic diseases or an immunosuppressed status,\namongst others) that cause altered immune profiles [1\u20137], while another potentially fatal syndrome can\ndevelop in previously\nhealthy individuals following SARS-CoV-2 infection, termed multisystem\ninflammatory syndrome (MIS) [8\u201310]. Despite a significant overlap in their dysregulated immune\nresponses, these two hyperinflammatory disease phenotypes can be distinguished by a range of distinct\nspatiotemporal adaptations and clinical profiles. Understanding how different aetiological factors underpin\nthe immunopathogenic pathways and timeline of events in the development of severe COVID-19 and MIS\nwill guide patient stratification and more targeted therapeutic or vaccination strategies. Here, we pinpoint\nsevere COVID-19 as an early acute hyperinflammatory response predominantly affecting the respiratory\ntract, but also with systemic involvement that is influenced by various risk factors to cause impairment of\nthe primary innate response to infection, as well as dysregulation of downstream innate and adaptive\ndefence mechanisms, and MIS as a delayed acute hyperinflammatory response to SARS-CoV-2 infection\nwith systemic but minimal or no respiratory symptoms and low pulmonary viral loads, which might\ndevelop due to genetic susceptibility traits that trigger the activation of systemic autoimmune and\nhyperinflammatory pathways upon SARS-CoV-2 infection.\nCopyright \u00a9The authors 2023\nThis version is distributed under\nthe terms of the Creative\nCommons Attribution Non-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 571
encoding: FLOAT32
metadata:
{"title": "Severe COVID-19 versus multisystem inflammatory syndrome: comparing two critical outcomes of SARS-CoV-2 infection", "chroma:document": "Commercial Licence 4.0. For\ncommercial reproduction rights\nand permissions contact\npermissions@ersnet.org\nReceived: 14 Oct 2022\nAccepted: 31 Dec 2022\nhttps://doi.org/10.1183/16000617.0197-2022\nEur Respir Rev 2023; 32: 220197\nEUROPEAN RESPIRATORY REVIEW\nREVIEW\nR. FRASER ET AL."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 572
encoding: FLOAT32
metadata:
{"title": "The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota", "chroma:document": "The balance between protective and pathogenic immune \nresponses to pneumonia in the neonatal lung is enforced by gut \nmicrobiota\nJoseph Stevens1,2, Shelby Steinmeyer3,4, Madeline Bonfield1, Laura Peterson3,4, Timothy \nWang3,4, Jerilyn Gray3, Ian Lewkowich4,5, Yan Xu3,4,6, Yina Du3, Minzhe Guo3,4, James \nL. Wynn7, William Zacharias3,4, Nathan Salomonis4,6, Lisa Miller8,9, Claire Chougnet4,5, \nDennis Hartigan O\u2019Connor9,10,11, Hitesh Deshmukh3,4,5,*\n1Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH \n45229, USA.\n2Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH \n45267, USA.\n3Division of Neonatology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, \nUSA.\n4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, \nUSA.\n5Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, \nUSA.\n6Division of Bioinformatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, \nUSA.\n7Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA.\n8Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University \nof California, Davis, Davis, CA 95616, USA.\n9California National Primate Research Center, Davis, CA 95616, USA.\n10Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA \n95616, USA.\n*Corresponding author. hitesh.deshmukh@cchmc.org.\nAuthor contributions: H.D., J.G., C.C., L.M., and D.H.O. designed the experiments. I.L. and W.Z. provided tools. J.L.W. provided \nthe patient-related metadata. N.S., J.S., Y.X., Y.D., M.G., L.P., and H.D. analyzed the single-cell and bulk transcriptomic data. J.G. \nand H.D. analyzed the cytometry data. J.S., S.S., T.W., M.B., and H.D. wrote the manuscript with inputs from M.G., Y.X., C.C., I.L., \nJ.L.W., D.H.O., and L.M.\nCompeting interests: The authors declare that they have no competing interests."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 573
encoding: FLOAT32
metadata:
{"title": "The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota", "chroma:document": "SUPPLEMENTARY MATERIALS\nwww.science.org/doi/10.1126/scitranslmed.abl3981 \nMaterials and Methods \nFigs. S1 to S12\nTables S1 to S33\nMDAR Reproducibility Checklist \nHHS Public Access\nAuthor manuscript\nSci Transl Med. Author manuscript; available in PMC 2023 March 22.\nPublished in final edited form as:\nSci Transl Med. 2022 June 15; 14(649): eabl3981. doi:10.1126/scitranslmed.abl3981.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 574
encoding: FLOAT32
metadata:
{"title": "Tuberculosis vaccines update: Is an RNA-based vaccine feasible for tuberculosis?", "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: 575
encoding: FLOAT32
metadata:
{"title": "A Modular Approach to Vocal Learning: Disentangling the Diversity of a Complex Behavioral Trait", "chroma:document": "A Modular Approach to Vocal Learning: Disentangling the \nDiversity of a Complex Behavioral Trait\nMorgan Wirthlin1, Edward F. Chang2, Mirjam Kn\u00f6rnschild3, Leah A. Krubitzer4,5, Claudio V. \nMello6, Cory T. Miller7, Andreas R. Pfenning1, Sonja C. Vernes8,9, Ofer Tchernichovski10, \nMichael M. Yartsev11\n1.Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA\n2.Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, \nUSA\n3.Animal Behavior Lab, Free University Berlin, Takustrasse 6, 14195, Berlin, Germany\n4.Center for Neuroscience, University of California, Davis, CA, USA\n5.Department of Psychology, University of California, Davis, CA, USA\n6.Department of Behavioral Neuroscience, OHSU, Portland, OR, USA\n7.Cortical Systems and Behavior Laboratory, Neurosciences Graduate Program, University of \nCalifornia San Diego, La Jolla, CA, USA\n8.Neurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics, \nNijmegen, The Netherlands\n9.Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands\n10.Department of Psychology, Hunter College, The City University of New York, New York, NY, \nUSA\n11.Helen Wills Neuroscience Institute and Department of Bioengineering, UC Berkeley, Berkeley, \nCA USA\nAbstract\nVocal learning is a behavioral trait in which the social and acoustic environment shapes the vocal \nrepertoire of individuals. Over the past century, the study of vocal learning has progressed at the \nintersection of neuroscience, genomics, molecular biology, physiology, ecology, and evolution. \nYet, despite the complexity of this trait, vocal learning is most frequently described as a binary \ntrait, with species being classified as either vocal learners or vocal non-learners. As a result, \nstudies have largely focused on a handful of vocal learner species. Recent studies, however, \nsuggest a continuum in vocal learning capacity across taxa. Here, we further suggest that"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 576
encoding: FLOAT32
metadata:
{"title": "A Modular Approach to Vocal Learning: Disentangling the Diversity of a Complex Behavioral Trait", "chroma:document": "vocal learning is a multidimensional behavioral phenotype comprised of distinct, interconnected \nmodules. Discretizing the vocal learning phenotype into its constituent components would \nfacilitate integration of findings across a diversity of species, taking advantage of the ways in \nwhich each excels in a particular component, or in a specific combination of features. Such \ncomparative studies can improve understanding of the mechanisms and evolutionary origins of \nvocal learning. We propose an initial set of vocal learning modules supported by behavioral \nHHS Public Access\nAuthor manuscript\nNeuron. Author manuscript; available in PMC 2023 April 01.\nPublished in final edited form as:\nNeuron. 2019 October 09; 104(1): 87\u201399. doi:10.1016/j.neuron.2019.09.036.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 577
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques", "chroma:document": "Broadly neutralizing antibodies to SARS-related viruses can be \nreadily induced in rhesus macaques\nWan-ting He1,2,3,\u2020, Meng Yuan4,\u2020, Sean Callaghan1,2,3,\u2020, Rami Musharrafieh1,2,3, Ge \nSong1,2,3, Murillo Silva3,5, Nathan Beutler1, Wen-Hsin Lee4, Peter Yong1,2,3, Jonathan \nL. Torres4, Mariane Melo3,5, Panpan Zhou1,2,3, Fangzhu Zhao1,2,3, Xueyong Zhu4, \nLinghang Peng1, Deli Huang1, Fabio Anzanello1,2,3, James Ricketts1, Mara Parren1, Elijah \nGarcia1, Melissa Ferguson6, William Rinaldi6, Stephen A. Rawlings7, David Nemazee1, \nDavey M. Smith7, Bryan Briney1,2,3, Yana Safonova8, Thomas F. Rogers1,7, Jennifer M. \nDan7,9, Zeli Zhang9, Daniela Weiskopf9, Alessandro Sette7,9, Shane Crotty3,7,9, Darrell \nJ. Irvine3,5,10,11,12, Andrew B. Ward2,3,4, Ian A. Wilson2,3,4,13,*, Dennis R. Burton1,2,3,12,*, \nRaiees Andrabi1,2,3,*\n1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA \n92037, USA.\n2IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.\n3Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La \nJolla, CA 92037, USA.\n4Department of Integrative Structural and Computational Biology, The Scripps Research Institute, \nLa Jolla, CA 92037, USA.\n5Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, \nCambridge, MA 02139, USA.\nThis work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, \ndistribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit \nhttp://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the \narticle that is credited to a third party; obtain authorization from the rights holder before using this material. The Authors, some rights \nreserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 578
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques", "chroma:document": "Distributed under a Creative Commons Attribution License 4.0 (CC BY).\n*Corresponding author. wilson@scripps.edu (I.A.W.); burton@scripps.edu, (D.R.B.); andrabi@scripps.edu (R.A.).\n\u2020These authors contributed equally to this work.\nAuthor contributions: W.-t.H., M.Y., S. Callaghan, S. Crotty, D.J.I., A.B.W., I.A.W., D.R.B., and R.A. conceived and designed \nthe study. W.-t.H., S. Callaghan, G.S., D.H., M.F., and W.R. conducted animal immunization studies. M.S. and M.M. prepared \nthe SMNP adjuvant. N.B., J.R., M.P., E.G., S.A.R., D.M.S., T.F.R., J.M.D., Z.Z., D.W., A.S., and S. Crotty recruited donors and \ncollected and processed plasma samples. W.-t.H., S. Callaghan, R.M., G.S., F.A., P.Y., and P.Z. performed BLI assays, ELISAs, virus \npreparations, neutralization assays, and isolation and characterization of monoclonal antibodies. F.Z. prepared the human antibodies. \nL.P. and D.H. prepared virus mutant plasmids. R.M., B.B., and Y.S. performed immunogenetic analysis of the antibodies. W.-H.L. and \nJ.L.T. conducted nSEM studies. M.Y. and X.Z. determined the crystal structures of the antibody-antigen complexes. W.-t.H., M.Y., \nS. Callaghan, R.M., G.S., N.B., W.-H.L., P.Y., J.L.T., P.Z., X.Z., L.P., D.H., F.A., D.N., B.B., Y.S., T.F.R., S. Crotty, D.J.I., A.B.W., \nI.A.W., D.R.B., and R.A. designed the experiments or analyzed the data. W.-t.H., M.Y., R.M., I.A.W., D.R.B., and R.A. wrote the \npaper, and all authors reviewed and edited the paper.\nCompeting interests: W.-t.H., M.Y., S. Callaghan, I.A.W., D.R.B., and R.A. are listed as inventors on a pending patent application \ndescribing the macaque sarbecovirus bnAbs reported in this study. D.J.I., S. Crotty, and M.S. are inventors on a patent filed by MIT \nand the La Jolla Institute for Immunology relating to the SMNP adjuvant. A.S. is a consultant for Gritstone Bio, Flow Pharma, \nImmunoScape, Avalia, Moderna, Fortress, Repertoire, Gerson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. S. Crotty has"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 579
encoding: FLOAT32
metadata:
{"title": "Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques", "chroma:document": "consulted for GSK, JP Morgan, Citi, Morgan Stanley, Avalia NZ, Nutcracker Therapeutics, University of California, California State \nUniversities, United Airlines, Adagio, and Roche. D.R.B. is a consultant for IAVI, Adagio, Adimab, Mabloc, VosBio, Nonigenex, and \nRadiant. The other authors declare that they have no competing interests.\nHHS Public Access\nAuthor manuscript\nSci Transl Med. Author manuscript; available in PMC 2023 August 10.\nPublished in final edited form as:\nSci Transl Med. 2022 August 10; 14(657): eabl9605. doi:10.1126/scitranslmed.abl9605.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 580
encoding: FLOAT32
metadata:
{"title": "Shared and independent roles of CGRP and PACAP in migraine pathophysiology", "chroma:document": "Kuburas\u00a0and Russo  \nThe Journal of Headache and Pain           (2023) 24:34  \nhttps://doi.org/10.1186/s10194-023-01569-2\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.\nThe Journal of Headache\n                           and Pain\nShared and\u00a0independent roles of\u00a0CGRP \nand\u00a0PACAP in\u00a0migraine pathophysiology\nAdisa Kuburas1 and Andrew F. Russo1,2* \nAbstract \nThe neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypep-\ntide (PACAP) have emerged as mediators of migraine pathogenesis. Both are vasodilatory peptides that can cause \nmigraine-like attacks when infused into people and migraine-like symptoms when injected into rodents. In this \nnarrative review, we compare the similarities and differences between the peptides in both their clinical and preclini-\ncal migraine actions. A notable clinical difference is that PACAP, but not CGRP, causes premonitory-like symptoms"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 581
encoding: FLOAT32
metadata:
{"title": "Shared and independent roles of CGRP and PACAP in migraine pathophysiology", "chroma:document": "in patients. Both peptides are found in distinct, but overlapping areas relevant to migraine, most notably with the \nprevalence of CGRP in trigeminal ganglia and PACAP in sphenopalatine ganglia. In rodents, the two peptides share \nactivities, including vasodilation, neurogenic inflammation, and nociception. Most strikingly, CGRP and PACAP cause \nsimilar migraine-like symptoms in rodents that are manifested as light aversion and tactile allodynia. Yet, the peptides \nappear to act by independent mechanisms possibly by distinct intracellular signaling pathways. The complexity of \nthese signaling pathways is magnified by the existence of multiple CGRP and PACAP receptors that may contribute to \nmigraine pathogenesis. Based on these differences, we suggest PACAP and its receptors provide a rich set of targets \nto complement and augment the current CGRP-based migraine therapeutics.\nKeywords CGRP, PACAP, Migraine, Intracellular signaling, Receptors\nBackground\nMigraine is one of the most disabling neurological dis-\norders in the world [1]. It affects over one billion people \nwith 3:1 prevalence in women. Migraine is a headache \nlasting 4\u201372\u00a0 h with characteristics that often include \nunilateral pulsating pain of moderate to severe intensity \nthat is aggravated by routine physical activity and is asso-\nciated with vomiting or nausea and/or photophobia and \nphonophobia [2]. While the mechanisms of migraine are \nstill poorly understood, insights from clinical and pre-\nclinical studies over the past three decades have focused \nattention on two neuropeptides: calcitonin gene-related \npeptide (CGRP) and pituitary adenylate cyclase-activat-\ning polypeptide (PACAP).\nThe importance of CGRP in migraine was first real-\nized in reports that CGRP is upregulated during migraine \nattacks and between attacks in chronic migraine patients \n[3\u20135], although this is not seen in all studies [6\u20138]. Even \nmore striking was the finding that infusion of CGRP can \ninduce migraine-like attacks in migraine patients, as"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 582
encoding: FLOAT32
metadata:
{"title": "Shared and independent roles of CGRP and PACAP in migraine pathophysiology", "chroma:document": "described below. The importance of CGRP has been fully \nestablished over the past 5\u00a0years with the efficacy of eight \nFDA approved CGRP-based therapeutics [9\u201313]. These \ndrugs include monoclonal antibodies against CGRP or its \nreceptor and small molecule receptor antagonists that are \neffective for prevention and treatment of migraine. How-\never, in general only about 40\u201360% of migraine patients \nare significantly helped by these agents [12, 14, 15], which \nsuggests involvement of other factors beyond CGRP in \nmigraine pathophysiology, such as PACAP [16]. In this \n*Correspondence:\nAndrew F. Russo\nandrew-russo@uiowa.edu\n1 Department of Molecular Physiology and Biophysics and Department \nof Neurology, University of Iowa, Iowa City, IA 52242, USA\n2 Veterans Affairs Medical Center, Iowa City, IA 52246, USA"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 583
encoding: FLOAT32
metadata:
{"title": "Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis", "chroma:document": "Vol:.(1234567890)\nJournal of Neurology (2023) 270:2826\u20132852\nhttps://doi.org/10.1007/s00415-023-11684-4\n1 3\nREVIEW\nPosterior reversible encephalopathy syndrome and\u00a0reversible cerebral \nvasoconstriction syndrome in\u00a0patients with\u00a0COVID\u201119 infection: \nis\u00a0there a\u00a0link? A\u00a0systematic review and\u00a0case report analysis\nAdriano\u00a0Bonura1,2\u00a0\u00b7 Gianmarco\u00a0Iaccarino1,2\u00a0\u00b7 Sergio\u00a0Soeren\u00a0Rossi1,2\u00a0\u00b7 Fioravante\u00a0Capone1,2\u00a0\u00b7 Francesco\u00a0Motolese1,2\u00a0\u00b7 \nRosalinda\u00a0Calandrelli3\u00a0\u00b7 Vincenzo\u00a0Di\u00a0Lazzaro1,2\u00a0\u00b7 Fabio\u00a0Pilato1,2 \nReceived: 15 January 2023 / Revised: 26 February 2023 / Accepted: 21 March 2023 / Published online: 4 April 2023 \n\u00a9 The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2023\nAbstract\nDuring the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Revers-\nible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these \nsyndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for \nSystematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used \nto treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles \n(60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical \ncharacteristics of the two populations separately, then performed an inferential analysis to search for other independent risk \nfactors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-\n19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional \nrisk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of \nendothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 584
encoding: FLOAT32
metadata:
{"title": "Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis", "chroma:document": "Keywords RCVS\u00a0\u00b7 PRES\u00a0\u00b7 SARS-CoV2\u00a0\u00b7 COVID-19\u00a0\u00b7 Antiviral drugs\u00a0\u00b7 Endothelial dysfunction\nIntroduction\nCOVID-19 is a disease caused by Severe Acute Respiratory \nSyndrome Corona Virus 2 (SARS-CoV2), a single-stranded \nRNA beta coronavirus. Most patients develop mild to mod-\nerate respiratory symptoms, while others require medi-\ncal assistance and hospitalization due to respiratory tract \ninvolvement. Several long-term complications have been \nreported including diabetes mellitus, kidney injury, myo-\ncarditis, heart failure, and venous thromboembolism [1, 2]. \nNeurological complications have been described as well: \nmyalgia, dizziness, headache, anosmia, ageusia, encepha-\nlitis, stroke, seizures, and myelitis [3\u20135] but also Posterior \nReversible Encephalopathy Syndrome (PRES) and Revers-\nible Cerebral Vasoconstriction Syndrome (RCVS) [6\u20138].\nPRES and RCVS [9\u201311] are relatively new clinical-radio-\nlogical syndromes. More and more cases of these syndromes \nhave been described so far, mainly due to increased aware-\nness of their clinical signs and the widespread use of MRI \nthat allows catching their signs at an early stage. Although \ntheir etiologies remain unclear, several studies pointed out \nthe role of intracranial vessels and endothelium in their \ndevelopment [12].\nPRES, first described by Hinchey et\u00a0al. in 1996 [13], \ncauses encephalopathy, disorders of consciousness, seizures, \nvisual disturbances, and headache [14]. It is more common \nin females and the most frequently recognized risk factors \nare: hypertension, pre-eclampsia, renal disease, immuno-\nsuppressive state, infections, steroids, dialysis, and blood \n * Fabio Pilato \n \nf.pilato@policlinicocampus.it\n1 \nDepartment of\u00a0Medicine and\u00a0Surgery, Unit of\u00a0Neurology, \nNeurophysiology, Neurobiology and\u00a0Psychiatry, Universit\u00e0 \nCampus Bio-Medico di Roma, Via Alvaro del Portillo, 21, \n00128\u00a0Rome, Italy\n2 \nInstitute of\u00a0Neurology, Fondazione Policlinico Universitario \nCampus Bio-Medico, Via Alvaro del Portillo, 200, \n00128\u00a0Rome, Italy\n3"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 585
encoding: FLOAT32
metadata:
{"title": "Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis", "chroma:document": "3 \nInstitute of\u00a0Radiology, Fondazione Policlinico Universitario \nAgostino Gemelli IRCCS, Largo A. Gemelli, 1, 00168\u00a0Rome, \nItaly"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 586
encoding: FLOAT32
metadata:
{"title": "Forever Connected: The Lifelong Biological Consequences of Fetomaternal and Maternofetal Microchimerism", "chroma:document": "Forever Connected: The Lifelong Biological Consequences of \nFetomaternal and Maternofetal Microchimerism\nDiana W. Bianchia,*, Kiarash Khosrotehranib, Sing Sing Wayc, Tippi C. MacKenzied, \nIngeborg Bajemae, Keelin O\u2019Donoghuef\naNational Human Genome Research Institute and Eunice Kennedy Shriver National Institute of \nChild Health and Human Development, National Institutes of Health, Bethesda, MD, USA;\nbExperimental Dermatology Group, The University of Queensland, UQ Diamantina Institute, \nBrisbane, Queensland, Australia;\ncDivision of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children\u2019s \nHospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA;\ndCenter for Maternal-Fetal Precision Medicine and the Department of Surgery, University of \nCalifornia, San Francisco, CA, USA;\neDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands;\nfIrish Centre for Maternal and Child Health (INFANT), University College Cork, Cork, Ireland.\nAbstract\nBACKGROUND:\u00a0Originally studied as a mechanism to understand eclampsia-related deaths \nduring pregnancy, fetal cells in maternal blood have more recently garnered attention as a \nnoninvasive source of fetal material for prenatal testing. In the 21st century, however, intact \nfetal cells have been largely supplanted by circulating cell-free placental DNA for aneuploidy \nscreening. Instead, interest has pivoted to the ways in which fetal cells influence maternal biology. \nIn parallel, an increasing appreciation of the consequences of maternal cells in the developing \nfetus has occurred.\nCONTENT:\u00a0In this review, we highlight the potential clinical applications and functional \nconsequences of the bidirectional trafficking of intact cells between a pregnant woman and her \nfetus. Fetal cells play a potential role in the pathogenesis of maternal disease and tissue repair. \nMaternal cells play an essential role in educating the fetal immune system and as a factor in"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 587
encoding: FLOAT32
metadata:
{"title": "Forever Connected: The Lifelong Biological Consequences of Fetomaternal and Maternofetal Microchimerism", "chroma:document": "transplant acceptance. Naturally occurring maternal microchimerism is also being explored as a \nsource of hematopoietic stem cells for transplant in fetal hematopoietic disorders.\n*Address correspondence to this author at: Eunice Kennedy Shriver National Institute of Child Health and Human Development, 31 \nCenter Drive, Room 2A03, National Institutes of Health, Bethesda, MD 20892, USA. Fax 301-402-1104; Diana.Bianchi@nih.gov.\nAuthor Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the \nfollowing 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation \nof data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be \naccountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are \nappropriately investigated and resolved.\nK. Khosrotehrani, administrative support, provision of study material or patients; I. Bajema, provision of study material or patients; K. \nO\u2019Donoghue, administrative support, provision of study material or patients.\nAuthors\u2019 Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.\nHHS Public Access\nAuthor manuscript\nClin Chem. Author manuscript; available in PMC 2023 April 04.\nPublished in final edited form as:\nClin Chem. 2021 January 30; 67(2): 351\u2013362. doi:10.1093/clinchem/hvaa304.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 588
encoding: FLOAT32
metadata:
{"title": "COVID-19 therapeutics: Small-molecule drug development targeting SARS-CoV-2 main protease", "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: 589
encoding: FLOAT32
metadata:
{"title": "Bystanders or not? Microglia and lymphocytes in aging and stroke", "chroma:document": "NEURAL REGENERATION RESEARCH\uff5cVol 18\uff5cNo. 7\uff5cJuly 2023\uff5c1397\nNEURAL REGENERATION RESEARCH\nwww.nrronline.org\nReview\nAbstract  \nAs the average age of the world population increases, more people will face debilitating aging-\nassociated conditions, including dementia and stroke. Not only does the incidence of these conditions \nincrease with age, but the recovery afterward is often worse in older patients. Researchers and \nhealth professionals must unveil and understand the factors behind age-associated diseases to \ndevelop a therapy for older patients. Aging causes profound changes in the immune system including \nthe activation of microglia in the brain. Activated microglia promote T lymphocyte transmigration \nleading to an increase in neuroinflammation, white matter damage, and cognitive impairment in both \nolder humans and rodents. The presence of T and B lymphocytes is observed in the aged brain and \ncorrelates with worse stroke outcomes. Preclinical strategies in stroke target either microglia or the \nlymphocytes or the communications between them to promote functional recovery in aged subjects. \nIn this review, we examine the role of the microglia and T and B lymphocytes in aging and how they \ncontribute to cognitive impairment. Additionally, we provide an important update on the contribution \nof these cells and their interactions in preclinical aged stroke.\nKey Words: age; B lymphocytes; brain; central nervous system; cognition; inflammation; microglia; \nmiddle cerebral artery occlusion; neuroinflammation; stroke; T lymphocytes; white matter injury\nIntroduction \nThe advancement of technology and medicine increased the individual\u2019s \naverage age. With a decreasing fertility and mortality rate, a significant \nproportion of the population is becoming older (Kowal et al., 2016). Older \nindividuals are more susceptible to age-associated diseases including stroke, \ndementia, diabetes, cardiovascular disease, and cancer (Jaul and Barron, \n2017). The anatomy and homeostasis of the brain change with aging (Juraska"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 590
encoding: FLOAT32
metadata:
{"title": "Bystanders or not? Microglia and lymphocytes in aging and stroke", "chroma:document": "and Lowry, 2012) and the aged brain respond differently to injury and stress \nthan the brain of a young adult. Interestingly, the neuronal density remains \nstable throughout the lifespan however, 30% of individuals suffer from severe \ncognitive impairment without meeting the criteria of Alzheimer\u2019s disease (AD) \nor dementia (Harada et al., 2013). Results from MRI and histological analysis \nstudies demonstrate a decline in white matter volume which corroborated \nwith cognitive impairment in healthy aged individuals (Fjell and Walhovd, \n2010; Coelho et al., 2021). The myelin sheath damage leads to white matter \nvulnerability resulting in axonal damage producing disconnect that could \nattribute to cognitive impairment (Kohama et al., 2012; Peters and Kemper, \n2012; Faizy et al., 2020). A complex interplay between myelin plasticity, \noligodendrocyte maturation, removal and clearance of myelin debris, and \nremyelination supports myelin maintenance and homeostasis and these \nprocesses decline with age (Soreq et al., 2017; Spitzer et al., 2019; Sams, \n2021). Experimental studies have shown that oligodendrocyte precursor \ncells fail to mature into myelinating oligodendrocytes and aged animals \ndemonstrate limited ability to replenish oligodendrocyte precursor cells pool \nthus is partially responsible for age-related reduced remyelination and myelin \nrepair (Shields et al., 2000; Neumann et al., 2019; Ito et al., 2021). Microglia \nplays an important role in oligodendrocyte precursor cell differentiation \ninto mature oligodendrocytes, removes myelin debris, and promotes \nremyelination, however, this function declines with age (Kalafatakis and \nKaragogeos, 2021; Luan et al., 2021), thus prompting cognitive dysfunction. \nSeveral genes are expressed by microglia that promote lymphocyte infiltration \nin the aged brain exacerbating the white matter injury and contributing \nto cognitive impairments in aged individuals. Thus an interplay between \nmicroglia and lymphocytes not only contributes to age-associated brain injury"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 591
encoding: FLOAT32
metadata:
{"title": "Bystanders or not? Microglia and lymphocytes in aging and stroke", "chroma:document": "but their precise role in stroke pathophysiology in older subjects has not been \nfully explored. \nThe objective of this review is to summarize the evidence that both microglia \nand lymphocytes are involved in the process of aging. The interplay of \nmicroglia and lymphocytes negatively modulates cognition in older subjects \nafter stroke. Finally, we present the studies targeting therapeutic strategies \ntoward microglia or lymphocytes in older animals after stroke. The review will \naid in better understanding the contribution of microglia and lymphocytes in \npost-stroke functional outcomes that happen to be a major concern in older \nindividuals. \nRetrieval Strategy \nThe studies cited in this review were retrieved from Google scholar and \nPubMed databases. The relevant literature published from January 1994 \nto September 2022 was screened. A combination of the following words \n(MeSH terms) was used to maximize search specificity and sensitivity: age, \ncognition, microglia, T lymphocytes, B lymphocytes, stroke, white matter, \nneuroinflammation, and brain. The results were further screened by title \nand abstract and studies exploring the relationship between microglia, and \nlymphocytes in aging were included. Furthermore, the role of microglia and \nlymphocytes and their contribution to stroke neuroinflammation was included. \nNo language or study type restrictions were applied. Articles involving studies \ninvestigating the contribution of young microglia and lymphocytes in stroke \nwere excluded. No limit was used on the year of publication or authorship. \nAged Microglia Contributes to Cognitive \nImpairment\nOne of the cell types that is profoundly affected by age is brain resident \nmacrophages- microglia. Microglia are primary immune cells that constitute \n10% of all cells in the adult brain (Pessac et al., 2001). Microglia acquire \na dystrophic and dysfunctional phenotype with age (Safaiyan et al., 2016; \nCantuti-Castelvetri et al., 2018; Deczkowska et al., 2018). A multitude"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 592
encoding: FLOAT32
metadata:
{"title": "Bystanders or not? Microglia and lymphocytes in aging and stroke", "chroma:document": "of factors including cellular aging, transcriptomic changes, senescence-\nassociated secretory phenotype, dysregulated microglia metabolism, and \nthe milieu that these cells reside could influence the microglia behavior \n(Minhas et al., 2021). Activated microglia secrete multiple pro-inflammatory \n1University of Texas McGovern Medical School at Houston, Houston, TX, USA; 2Department of Neurology, University of Texas McGovern Medical School at Houston, Houston, TX, USA\n*Correspondence to: Anjali Chauhan, PhD, anjali.chauhan@uth.tmc.edu. \nhttps://orcid.org/0000-0002-9825-8100 (Anjali Chauhan)\nFunding: This work was supported by 16POST27490032 American Heart Association post-doctoral fellowship and National Institute of Neurological Disorders and Stroke Exploratory \nNeuroscience Research Grant R21 NS114836-01A1 (to AC).\nHow to cite this article: Nguyen JN, Chauhan A (2023) Bystanders or not? Microglia and lymphocytes in aging and stroke. Neural Regen Res 18(7):1397-1403. \nFrom the Contents\nIntroduction\n1397\nRetrieval Strategy\n1397\nAged Microglia Contributes to Cognitive Impairment\n1397\nMicroglia and Lymphocytes Interact with Age\n1398\nRole of T Lymphocytes in Aging and Cognition\n1398\nRole of B Lymphocytes in Aging\n1399\nAged Microglia in Stroke\n1399\nT and B Lymphocytes in Aged Stroke\n1400\nConclusion\n1400\nBystanders or not? Microglia and lymphocytes in aging \nand stroke\nhttps://doi.org/10.4103/1673-5374.360345\nDate of submission: September 17, 2022 \nDate of decision: October 18, 2022 \nDate of acceptance: October 24, 2022\nDate of web publication: November 9, 2022 \nJustin N. Nguyen1, Anjali Chauhan2, *"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 593
encoding: FLOAT32
metadata:
{"title": "A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus", "chroma:document": "RESEARCH ARTICLE\nA whole blood intracellular cytokine assay\noptimised for field site studies demonstrates\npolyfunctionality of CD4+ T cells in acute scrub\ntyphus\nManutsanun InthawongID1,2,3, Nattapon Pinthong4, Areerat Thaiprakhong2,\nTri Wangrangsimakul2,5, Piyanate Sunyakumthorn3, Jennifer Hill5,\nPiengchan Sonthayanon1,2, Daniel H. Paris2,6,7, Susanna J. Dunachie2,5,\nBarbara KronsteinerID2,5*\n1 Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University,\nBangkok, Thailand, 2 Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Faculty of Tropical\nMedicine, Mahidol University, Bangkok, Thailand, 3 Department of Veterinary Medicine, United States Army\nMedical Directorate, Armed Forces Research Institute of Medical Sciences (USAMD-AFRIMS), Bangkok,\nThailand, 4 Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok,\nThailand, 5 NDM Center for Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford,\nOxford, United Kingdom, 6 Department of Medicine, Swiss Tropical and Public Health Institute, Allschwil,\nSwitzerland, 7 Department of Clinical Research, University of Basel, Basel, Switzerland\n* barbara.kronsteiner-dobramysl@ndm.ox.ac.uk\nAbstract\nBackground\nAssessment of cellular immune responses by combining intracellular cytokine staining and\nimmunophenotyping using flow cytometry enables the simultaneous measurement of T cell\nphenotype and effector function in response to pathogens and vaccines. The use of whole\nblood samples rather than peripheral blood mononuclear cells avoids both the need for\nimmediate processing and loss of functional antigen presenting cells due to processing and\ncryopreservation. Using whole blood provides the possibility to stimulate peripheral T cells\nin situ, and is more suitable for studies where sample volume is limited, such as those involv-\ning children, the elderly and critically ill patients. The aim of this study was to provide a robust"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 594
encoding: FLOAT32
metadata:
{"title": "A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus", "chroma:document": "tool for the assessment of antigen-specific T cell responses in a field site setting with limited\nresources.\nMethodology/principle findings\nWe optimised a flow cytometry-based whole blood intracellular cytokine assay (WBA) with\nrespect to duration of antigen stimulation and intracellular protein retention time. We demon-\nstrate the ability of the WBA to capture polyfunctional T cell responses in the context of\nacute scrub typhus infection, by measuring IFN-\u03b3, TNF and IL-2 in CD4+ and CD8+ T cells\nin response to the causative agent O. tsutsugamushi (OT). Using an optimised OT antigen\npreparation, we demonstrate the presence of polyfunctional antigen-specific memory CD4+\nT cells in the blood of scrub typhus patients.\nPLOS NEGLECTED TROPICAL DISEASES\nPLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0010905\nMarch 24, 2023\n1 / 19\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Inthawong M, Pinthong N, Thaiprakhong\nA, Wangrangsimakul T, Sunyakumthorn P, Hill J, et\nal. (2023) A whole blood intracellular cytokine\nassay optimised for field site studies demonstrates\npolyfunctionality of CD4+ T cells in acute scrub\ntyphus. PLoS Negl Trop Dis 17(3): e0010905.\nhttps://doi.org/10.1371/journal.pntd.0010905\nEditor: Allen L. Richards, Uniformed Services\nUniversity of the Health Sciences, UNITED STATES\nReceived: October 28, 2022\nAccepted: February 25, 2023\nPublished: March 24, 2023\nCopyright: This is an open access article, free of all\ncopyright, and may be freely reproduced,\ndistributed, 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: The data that support\nthe findings of this study are publicly available from\nMendeley Data under https://data.mendeley.com/\ndatasets/4jj4dfd6b7/1.\nFunding: MI, BK and SJD were funded by the\nWellcome Trust (WT100174/Z/12/Z awarded to\nSJD, https://wellcome.org/). JH, BK and SJD are"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 595
encoding: FLOAT32
metadata:
{"title": "A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus", "chroma:document": "supported by the NIHR Global Research\nProfessorship (NIHR300791 awarded to SJD,\nhttps://www.nihr.ac.uk/). MI, NP, AT, TW, PSu and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 596
encoding: FLOAT32
metadata:
{"title": "Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials", "chroma:document": "Received: 4 April 2022\n-\nRevised: 1 July 2022\n-\nAccepted: 3 August 2022\nDOI: 10.1002/rmv.2385\nR E V I E W\nSafety and immunogenicity of Zika virus vaccine:\nA systematic review of clinical trials\nMahmuda Yeasmin1\n|\nMd. Maruf Ahmed Molla1,2\n|\nH. M. Abdullah Al Masud3\n|\nK. M. Saif\u2010Ur\u2010Rahman4,5,6\n1Department of Virology, National Institute of\nLaboratory Medicine and Referral Center,\nDhaka, Bangladesh\n2College of Graduate Studies, State University\nof New York Upstate Medical University,\nSyracuse, New York, USA\n3Department of Microbiology, Faculty of\nBiological Sciences, University of Chittagong,\nChattogram, Bangladesh\n4Health Systems and Population Studies\nDivision, icddr, b, Dhaka, Bangladesh\n5Evidence Synthesis Ireland and Cochrane\nIreland, Galway, Ireland\n6College of Medicine, Nursing and Health\nSciences, National University of Ireland,\nGalway, Ireland\nCorrespondence\nK. M. Saif\u2010Ur\u2010Rahman, College of Medicine,\nNursing and Health Sciences, National\nUniversity of Ireland, Galway, Ireland and\nHealth Systems and Population Studies\nDivision, icddr, b, Dhaka, Bangladesh.\nEmail: su.rahman@icddrb.org\nFunding information\nOpen access funding provided by IReL.\nAbstract\nSeveral phase\u20101 clinical trials have been performed to evaluate the safety and effi-\ncacy of candidate anti\u2010Zika vaccines. In this systematic review, we systematically\nevaluated the safety and immunogenicity of candidate vaccines, which would aid\nresearchers in formulating an effective vaccination strategy for phase\u20102 trials based\non current evidence. A literature search was conducted using the electronic data-\nbases MEDLINE through Pubmed, Web of Science, and Cochrane Database for\nrelevant studies on candidate anti\u2010zika vaccines. Studies on animal models were\nexcluded from our study. Healthy individuals who were administered candidate Zika\nvaccines to evaluate the immune response and adverse events (AEs) compared to\nplacebo were considered. Data were extracted, tabulated, and analysed using"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 597
encoding: FLOAT32
metadata:
{"title": "Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials", "chroma:document": "Microsoft Excel, while the risk of bias plots were generated using tidyverse and\nRobvis packages in R\u2010studio. A total of five phase\u20101 clinical trials were included in our\nanalysis comprising of studies on inactivated, viral vector, and DNA vaccines.\nImmunogenicity ranged from 10% to 100% after vaccination with the lowest sero-\nconversion rate (10%) and geometric mean titre (GMT) (6.3; 95% confidence interval\n(CI):3.7\u201310.8) observed among recipients of single\u2010dose inactivated anti\u2010zika vaccine\n(ZPIV). For DNA vaccines, the seroconversion rate ranged from 60% to 100% with\nthe highest seroconversion rate (100%) and GMT (2871; 95% CI:705.3\u201311688)\nobserved among recipients of three shots of high dose GLS\u20105700 vaccine. For viral\nvector vaccine (Ad26.ZIKV.001) seroconversion rate (100%) and GMT peaked after\ntwo shots with both low and high\u2010dose vaccines. In all those studies AEs were mostly\nlocal including injection site pain, erythema, and itching. The most common systemic\nAEs included fever, myalgia, nausea, and fatigue. In phase\u20101 clinical trials, all candi-\ndate vaccines were found to be highly immunogenic and relatively safe, especially\nwhen administered in higher doses and with the help of needle\u2010free devices.\nAbbreviations: AE, Adverse Event; COVID\u201019, Coronavirus Disease 2019; CZS, Congenital Zika Syndrome; ELISPOT, Enzyme\u2010linked Immune Absorbent Spot; GBS, Gullain Barrie Syndrome;\nGMT, Geometric Mean Titre; HD, Higher dose; LD, Lower Dose; MN50, 50% Microneutralisation; NHP, Nonhuman primtaes; PL, Placebo; PRISMA, Preferred Reporting Project for Systematic\nEvaluation and Meta\u2010Analysis; RCT, Randomised Controlled Trial; SARS\u2010CoV\u20102, Severe Acute Respiratory Syndrome Coronavirus\u20102; ZPIV, Zika Virus Purified Inactivated Vaccine.\nMahmuda Yeasmin, Md. Maruf Ahmed Molla contributed equally.\nThis is an open access article under the terms of the Creative Commons Attribution\u2010NonCommercial License, which permits use, distribution and reproduction in any"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 598
encoding: FLOAT32
metadata:
{"title": "Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials", "chroma:document": "medium, provided the original work is properly cited and is not used for commercial purposes.\n\u00a9 2022 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.\nRev Med Virol. 2023;33:e2385.\nwileyonlinelibrary.com/journal/rmv\n-\n1 of 10\nhttps://doi.org/10.1002/rmv.2385"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 599
encoding: FLOAT32
metadata:
{"title": "Porcine reproductive and respiratory syndrome virus infection triggers autophagy via ER stress-induced calcium signaling to facilitate virus replication", "chroma:document": "RESEARCH ARTICLE\nPorcine reproductive and respiratory\nsyndrome virus infection triggers autophagy\nvia ER stress-induced calcium signaling to\nfacilitate virus replication\nFeifei Diao1, Chenlong Jiang1, Yangyang Sun1, Yanni Gao1, Juan Bai1,2, Hans Nauwynck3,\nXianwei Wang1,2, Yuanqi Yang1, Ping Jiang1,2*, Xing LiuID1,2*\n1 Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International\nJoint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine,\nNanjing Agricultural University, Nanjing, PR China, 2 Jiangsu Co-innovation Center for Prevention and\nControl of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, PR China,\n3 Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium\n* jiangp@njau.edu.cn (PJ); xingliu@njau.edu.cn (XL)\nAbstract\nCalcium (Ca2+), a ubiquitous second messenger, plays a crucial role in many cellular func-\ntions. Viruses often hijack Ca2+ signaling to facilitate viral processes such as entry, replica-\ntion, assembly, and egress. Here, we report that infection by the swine arterivirus, porcine\nreproductive and respiratory syndrome virus (PRRSV), induces dysregulated Ca2+ homeo-\nstasis, subsequently activating calmodulin-dependent protein kinase-II (CaMKII) mediated\nautophagy, and thus fueling viral replication. Mechanically, PRRSV infection induces endo-\nplasmic reticulum (ER) stress and forms a closed ER\u2013plasma membrane (PM) contacts,\nresulting the opening of store operated calcium entry (SOCE) channel and causing the ER\nto take up extracellular Ca2+, which is then released into the cytoplasm by inositol trispho-\nsphate receptor (IP3R) channel. Importantly, pharmacological inhibition of ER stress or\nCaMKII mediated autophagy blocks PRRSV replication. Notably, we show that PRRSV pro-\ntein Nsp2 plays a dominant role in the PRRSV induced ER stress and autophagy, interacting"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 600
encoding: FLOAT32
metadata:
{"title": "Porcine reproductive and respiratory syndrome virus infection triggers autophagy via ER stress-induced calcium signaling to facilitate virus replication", "chroma:document": "with stromal interaction molecule 1 (STIM1) and the 78 kDa glucose-regulated protein 78\n(GRP78). The interplay between PRRSV and cellular calcium signaling provides a novel\npotential approach to develop antivirals and therapeutics for the disease outbreaks.\nAuthor summary\nPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in a seri-\nous swine disease and causes a severe economic threat to the global swine industry. How-\never, commercial vaccines do not provide satisfactory protection against PRRSV due to its\ngenetic variation. Well understanding the mechanism of PRRSV replication is helpful to\ndevelop the effective strategies to control the disease. Calcium signaling has been reported\nto play an important role in the life cycles of viruses. In this study, we describe the picture\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011295\nMarch 27, 2023\n1 / 27\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Diao F, Jiang C, Sun Y, Gao Y, Bai J,\nNauwynck H, et al. (2023) Porcine reproductive\nand respiratory syndrome virus infection triggers\nautophagy via ER stress-induced calcium signaling\nto facilitate virus replication. PLoS Pathog 19(3):\ne1011295. https://doi.org/10.1371/journal.\nppat.1011295\nEditor: Balaji Manicassamy, University of Iowa,\nUNITED STATES\nReceived: August 28, 2022\nAccepted: March 13, 2023\nPublished: March 27, 2023\nCopyright: \u00a9 2023 Diao 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: The authors confirm\nthat all data underlying the findings are fully\navailable without restriction. All relevant data are\nwithin the paper and its Supporting Information\nfiles.\nFunding: This work was supported by the National\nNatural Science Foundation (32230103), the\nEarmarked Fund for CARS-35, the Jiangsu"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 601
encoding: FLOAT32
metadata:
{"title": "Porcine reproductive and respiratory syndrome virus infection triggers autophagy via ER stress-induced calcium signaling to facilitate virus replication", "chroma:document": "Independent Innovation Fund Project (CX(22)\n1006), the Priority Academic Program"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 602
encoding: FLOAT32
metadata:
{"title": "Systemic inflammation exacerbates developmental neurotoxicity induced by sevoflurane in neonatal rats", "chroma:document": "Systemic in\ufb02ammation exacerbates developmental neurotoxicity\ninduced by sevo\ufb02urane in neonatal rats\nNemanja Useinovic1,*, Stefan Maksimovic1, Cole Liechty1, Omar H. Cabrera1,\nNidia Quillinan1,2 and Vesna Jevtovic-Todorovic1,3\n1Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2Neuronal Injury\nand Plasticity Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA and 3Department of\nPharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA\n*Corresponding author. E-mail: nemanja.useinovic@cuanschutz.edu\nAbstract\nBackground: General anaesthesia in the neonatal period has detrimental effects on the developing mammalian brain.\nThe impact of underlying in\ufb02ammation on anaesthesia-induced developmental neurotoxicity remains largely unknown.\nMethods: Postnatal day 7 (PND7) rats were randomly assigned to receive sevo\ufb02urane (3 vol% for 3 h) or carrier gas 12 h\nafter bacterial lipopolysaccharide (LPS; 1 mg g\u00011) or vehicle injection. Pharmacological inhibition of caspase-1 by Vx-765\n(two doses of 50 mg g\u00011 body weight) was used to investigate mechanistic pathways of neuronal injury. Histomorpho-\nlogical injury and molecular changes were quanti\ufb01ed 2 h after the end of anaesthesia. Long-term functional de\ufb01cits were\ntested at 5e8 weeks of age using a battery of behavioural tests in the memory and anxiety domains.\nResults: Sevo\ufb02urane or LPS treatment increased activated caspase-3 and caspase-9 expression in the hippocampal\nsubiculum and CA1, which was greater when sevo\ufb02urane was administered in the setting of LPS-induced in\ufb02ammation.\nNeuronal injury induced by LPS\u00fesevo\ufb02urane treatment resulted in sex-speci\ufb01c behavioural outcomes when rats were\ntested at 5e8 weeks of age, including learning and memory de\ufb01cits in males and heightened anxiety-related behaviour in\nfemales. Hippocampal caspase-1 and NLRP1 (NLR family pyrin domain containing 1), but not NLRP3, were upregulated by"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 603
encoding: FLOAT32
metadata:
{"title": "Systemic inflammation exacerbates developmental neurotoxicity induced by sevoflurane in neonatal rats", "chroma:document": "LPS or LPS\u00fesevo\ufb02urane treatment, along with related proin\ufb02ammatory cytokines, interleukin (IL)-1b, and IL-18. Pre-\ntreatment with Vx-765, a selective caspase-1 inhibitor, led to reduced IL-1b in LPS and LPS\u00fesevo\ufb02urane groups. Caspase-\n1 inhibition by Vx-765 signi\ufb01cantly decreased activated caspase-3 and caspase-9 immunoreactivity in the subiculum.\nConclusions: Systemic in\ufb02ammation promotes developmental neurotoxicity by worsening anaesthesia-induced\nneuronal damage with sex-speci\ufb01c behavioural outcomes. This highlights the importance of studying anaesthesia-\ninduced neurotoxicity in more clinically relevant settings.\nKeywords: apoptosis; caspase-1; hippocampus; in\ufb02ammasome; in\ufb02ammation; lipopolysaccharide; neonatal anaesthesia\nEditor\u2019s key points\n\u0003 General anaesthetics alone can enhance apoptotic\nneuronal and glial death and produce long-term\nbehavioural de\ufb01cits in animal models, but whether\nthis\nis\nmodi\ufb01ed\nby\nunderlying\nin\ufb02ammation\nis\nunclear.\n\u0003 Systemic in\ufb02ammation induce with bacterial lipo-\npolysaccharide (LPS) worsened neuroapoptosis and\nsex-speci\ufb01c behavioural de\ufb01cits produced by sevo-\n\ufb02urane anaesthesia exposure in neonatal rats.\n\u0003 These \ufb01ndings demonstrate effects of both sex and\nsystemic in\ufb02ammation on developmental anaes-\nthetic neurotoxicity in rats.\n\u0003 These \ufb01ndings highlight the potential impact of un-\nderlying pathological conditions on developmental\nanaesthetic neurotoxicity, which will require clinical\nvalidation.\nReceived: 21 September 2021; Accepted: 8 May 2022\n\u00a9 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.\nFor Permissions, please email: permissions@elsevier.com\n555\nBritish Journal of Anaesthesia, 129 (4): 555e566 (2022)\ndoi: 10.1016/j.bja.2022.05.008\nAdvance Access Publication Date: 11 June 2022\nNeuroscience and Neuroanaesthesia"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 604
encoding: FLOAT32
metadata:
{"title": "Scientific rationale for the use of \u00ce\u00b12A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders", "chroma:document": "EXPERT REVIEW\nOPEN\nScienti\ufb01c rationale for the use of \u03b12A-adrenoceptor agonists in\ntreating neuroin\ufb02ammatory cognitive disorders\nAmy F. T. Arnsten\n1\u2709, Yumiko Ishizawa2 and Zhongcong Xie2\n\u00a9 The Author(s) 2023\nNeuroin\ufb02ammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This\nincludes such challenging disorders as delirium, perioperative neurocognitive disorder, and the sustained cognitive de\ufb01cits from\n\u201clong-COVID\u201d or traumatic brain injury. There are no FDA-approved treatments for these symptoms; thus, understanding their\netiology is important for generating therapeutic strategies. The current review describes the molecular rationale for why PFC circuits\nare especially vulnerable to in\ufb02ammation, and how \u03b12A-adrenoceptor (\u03b12A-AR) actions throughout the nervous and immune\nsystems can bene\ufb01t the circuits in PFC needed for higher cognition. The layer III circuits in the dorsolateral PFC (dlPFC)\nthat generate and sustain the mental representations needed for higher cognition have unusual neurotransmission and\nneuromodulation. They are wholly dependent on NMDAR neurotransmission, with little AMPAR contribution, and thus are\nespecially vulnerable to kynurenic acid in\ufb02ammatory signaling which blocks NMDAR. Layer III dlPFC spines also have unusual\nneuromodulation, with cAMP magni\ufb01cation of calcium signaling in spines, which opens nearby potassium channels to rapidly\nweaken connectivity and reduce neuronal \ufb01ring. This process must be tightly regulated, e.g. by mGluR3 or \u03b12A-AR on spines, to\nprevent loss of \ufb01ring. However, the production of GCPII in\ufb02ammatory signaling reduces mGluR3 actions and markedly diminishes\ndlPFC network \ufb01ring. Both basic and clinical studies show that \u03b12A-AR agonists such as guanfacine can restore dlPFC network \ufb01ring\nand cognitive function, through direct actions in the dlPFC, but also by reducing the activity of stress-related circuits, e.g. in the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 605
encoding: FLOAT32
metadata:
{"title": "Scientific rationale for the use of \u00ce\u00b12A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders", "chroma:document": "locus coeruleus and amygdala, and by having anti-in\ufb02ammatory actions in the immune system. This information is particularly\ntimely, as guanfacine is currently the focus of large clinical trials for the treatment of delirium, and in open label studies for the\ntreatment of cognitive de\ufb01cits from long-COVID.\nMolecular Psychiatry; https://doi.org/10.1038/s41380-023-02057-4\nINTRODUCTION\nStress and in\ufb02ammation can profoundly alter the nervous and\nimmune systems, creating long-term impairments in cognitive\nfunctioning. In particular, the cognitive functions of the prefrontal\ncortex (PFC) are impaired in a wide range of neuroin\ufb02ammatory\ndisorders, including in Alzheimer\u2019s disease (AD) [1], traumatic brain\ninjury (TBI) [2], and perioperative neurocognitive disorder (PND)\n[3]. The PFC subserves abstract reasoning and the executive\nfunctions, where de\ufb01cits can be remarkably debilitating, interfer-\ning with the ability to work or care for families [4]. There is a great\nneed for treatment, especially in the wake of COVID-19 infection,\nwhere cognitive de\ufb01cits from \u201clong-COVID\u201d are prevalent [5].\nHowever, there are no FDA-approved medications for treating\nneuroin\ufb02ammatory cognitive disorders.\nNew research has shown that the recently evolved circuits in\nthe primate PFC have unusual molecular needs that support\nhigher cognitive operations, but render these circuits particularly\nvulnerable to disruption from neuroin\ufb02ammation [6]. In particular,\nthese circuits express the molecular machinery for cAMP to\nmagnify calcium signaling to help sustain prolonged neuron\n\ufb01ring needed to represent information without sensory stimula-\ntion. However, magni\ufb01ed cAMP-calcium signaling is readily\ndysregulated by stress and in\ufb02ammation, leading to atrophy, tau\nphosphorylation and impaired PFC cognitive functioning. Thus,\nmedications that can restore regulation of cAMP-calcium signaling\nmay be especially helpful in restoring cognitive abilities.\nAs will be described in detail below, research has shown that"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 606
encoding: FLOAT32
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{"title": "Scientific rationale for the use of \u00ce\u00b12A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders", "chroma:document": "the selective noradrenergic \u03b12A-adrenoceptor (\u03b12A-AR) agonist,\nguanfacine,\ncan\nstrengthen\nPFC\nnetwork\nconnections\nand\nimprove PFC cognitive functioning by regulating cAMP-calcium\nsignaling [7]. Based on this research, extended release guanfacine\nwas approved by the FDA in 2009 for the treatment of Attention\nDe\ufb01cit Hyperactivity Disorder, which is characterized by PFC\nde\ufb01cits. Guanfacine is also being used off-label and/or being\ntested to treat cognitive de\ufb01cits in a variety of neuroin\ufb02ammatory\ndisorders including traumatic brain injury (TBI), delirium (post-\nanesthetic or infectious), and cognitive de\ufb01cits from long-COVID\n(\u201cbrain fog\u201d). However, the scienti\ufb01c bases for guanfacine\u2019s actions\nin these disorders are generally not understood, as this research\nhas arisen from multiple, and often disparate, disciplines. While\nmany scientists and physicians are aware of how stimulation of\npresynaptic \u03b12A-AR autoreceptors reduces NE release from the\nsympathetic nervous system [8], they are often unaware of\nimportant,\npost-synaptic\n\u03b12A-AR\nactions\nin\nbrain\nthat\nare\nReceived: 20 November 2022 Revised: 22 March 2023 Accepted: 24 March 2023\n1Department Neuroscience, Yale University School of Medicine, New Haven, CT 056510, USA. 2Department Anesthesiology, Critical Care and Pain Medicine, Massachusetts\nGeneral Hospital, Harvard Medical School, Boston, MA 02114, USA. \u2709email: amy.arnsten@yale.edu\nwww.nature.com/mp\nMolecular Psychiatry\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 607
encoding: FLOAT32
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{"title": "Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases", "chroma:document": "REVIEW ARTICLE\nOPEN\nViral vectored vaccines: design, development, preventive and\ntherapeutic applications in human diseases\nShen Wang1, Bo Liang1, Weiqi Wang1,2, Ling Li3, Na Feng1, Yongkun Zhao1, Tiecheng Wang1, Feihu Yan1\u2709, Songtao Yang1\u2709 and\nXianzhu Xia1\u2709\nHuman diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the\nglobal economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized\ncountermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and\nrepresent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches.\nCurrently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against\nhuman diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parain\ufb02uenza\nvirus, measles virus, Newcastle disease virus, in\ufb02uenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors\nthat differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective ef\ufb01cacy. This\nreview summarized the overall pro\ufb01le of the design strategies, progress in advance and steps taken to address barriers to the\ndeployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application\nin cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate\ntechnological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs\nin novel vaccines and facilitate a rapid response to public health emergencies.\nSignal Transduction and Targeted Therapy  (2023) 8:149 \n; https://doi.org/10.1038/s41392-023-01408-5\nINTRODUCTION\nThe outbreak of infectious diseases and the occurrence of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 608
encoding: FLOAT32
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{"title": "Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases", "chroma:document": "cancers cause a huge impact on humans throughout history.\nHemorrhagic fever, including Ebola, Marburg, and Lassa fever,\ncause fatality rates of up to 50%.1\u20133 In addition, there have been\nthree waves of beta coronavirus emergence since 2003, of which\ncoronavirus disease 2019 (COVID-19) has caused billions of\ncon\ufb01rmed cases and millions of deaths since 2019.4\u20136 Globally,\nan estimated 19.3 million new cancer cases and almost 10.0\nmillion cancer deaths occur every year,7 which pose as the\nleading health threat.\nFor infectious diseases, vaccination and establishment of herd\nimmunity\nare\nof\nprimary\nimportance.\nAmong\nall\nvaccine\ntechnologies, recombinant viral vectors represent promising\nvaccine platforms due to their ability to express heterologous\nantigens and induction of cellular immune responses and\nhumoral immune responses without exogenous adjuvants. Viral\nvector vaccines consist of viral particles whose genomes have\nbeen modi\ufb01ed to contain one or more foreign genes encoding\nthe targeted antigens. The rationale for using viruses to deliver\nthe \u2018vaccine gene\u2019 is in several folds. Viral vectored vaccines are\nsafe and induce both arm of innate and adaptive immune\nresponses without involvement of the complete hazardous\npathogen.8 Moreover, viral vectors have intrinsic adjuvant proper-\nties due to the expression of diverse pathogen-associated\nmolecular\npatterns\n(PAMPs)\nand\nthe\nactivation\nof\ninnate\nimmunity.9 In addition, viral vectors can be engineered to deliver\nantigens to speci\ufb01c cells or tissues. Similarly, they can be rendered\nreplication-competent or replication-de\ufb01cient to increase their\nsafety and reduce reactogenicity. Notably, the viral vector vaccine\ncan recapitulate the natural infection process of speci\ufb01c patho-\ngens, thus triggering classical acute in\ufb02ammation and immune\ndetection through the natural production of PAMPs, enabling\nmucosal delivery and induction of local-mucosal and systemic\nimmunity. Several viral vector-based prophylactic vaccines have"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 609
encoding: FLOAT32
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{"title": "Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases", "chroma:document": "entered Phase III clinical trials or have been approved.10\u201315 In the\n\ufb01eld of cancers, viral vectors are ideal oncolytic viruses (OVs)\nsince they can trigger cellular immunity and could be armed,\nshielded and targeting tumor cells. The release of tumorasso-\nciated antigens (TAAs) could activate and regulate the anti-tumor\nimmune response. Several OV preparations have been approved\nfor marketing, which present promising directions for immu-\nnotherapy of tumors.\nNevertheless, the systematic and comparative review of these\nviral vectors is less well established. Moreover, the generality and\nindividuality of these viral vectors are not fully elucidated. In this\nreview, the general overview of vesicular stomatitis virus (VSV),\nrabies virus (RABV), parain\ufb02uenza virus (PIV), measles virus (MeV),\nNewcastle disease virus (NDV), in\ufb02uenza virus (IFV), adenovirus\n(AdV), and poxvirus vector vaccines was summarized in terms of\nReceived: 8 November 2022 Revised: 6 March 2023 Accepted: 14 March 2023\n1Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China;\n2College of Veterinary Medicine, Jilin University, Changchun, China and 3China National Research Center for Exotic Animal Diseases, China Animal Health and Epidemiology\nCenter, Qingdao, China\nCorrespondence: Feihu Yan (yanfh1990@163.com) or Songtao Yang (yst62041@163.com) or Xianzhu Xia (xiaxzh@cae.cn)\nThese authors contributed equally: Shen Wang, Bo Liang, Weiqi Wang, Ling Li\nwww.nature.com/sigtrans\nSignal Transduction and Targeted Therapy\n\u00a9 The Author(s) 2023\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 610
encoding: FLOAT32
metadata:
{"title": "Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus", "chroma:document": "RESEARCH ARTICLE\nFrequent first-trimester pregnancy loss in\nrhesus macaques infected with African-\nlineage Zika virus\nJenna R. RosinskiID1\u262f, Lauren E. Raasch1\u262f, Patrick Barros Tiburcio1, Meghan\nE. Breitbach1, Phoenix M. Shepherd1, Keisuke Yamamoto1, Elaina Razo2, Nicholas\nP. Krabbe2, Mason I. Bliss3, Alexander D. Richardson3, Morgan A. Einwalter3, Andrea\nM. Weiler3, Emily L. Sneed3, Kerri B. Fuchs3, Xiankun Zeng4, Kevin K. Noguchi5, Terry\nK. Morgan6,7, Alexandra J. Alberts1, Kathleen M. Antony8, Sabrina Kabakov9, Karla\nK. Ausderau9,10, Ellie K. Bohm11, Julia C. Pritchard11, Rachel V. Spanton9, James N. Ver\nHoove12, Charlene B. Y. Kim12, T. Michael Nork12, Alex W. Katz12, Carol A. Rasmussen12,\nAmy Hartman13, Andres Mejia3, Puja Basu3, Heather A. Simmons3, Jens C. Eickhoff14,\nThomas C. Friedrich15, Matthew T. Aliota11, Emma L. Mohr2, Dawn M. Dudley1, David\nH. O\u2019Connor1,3\u2021, Christina M. Newman1\u2021*\n1 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, Wisconsin,\nUnites States of America, 2 Department of Pediatrics, University of Wisconsin-Madison; Madison, Wisconsin,\nUnites States of America, 3 Wisconsin National Primate Research Center, University of Wisconsin-Madison;\nMadison, Wisconsin, Unites States of America, 4 United States Army Medical Research Institute of Infectious\nDiseases; Fort Detrick, Maryland, Unites States of America, 5 Department of Psychiatry, Washington\nUniversity School of Medicine; St. Louis, Washington, Unites States of America, 6 Department of Pathology,\nOregon Health and Science University; Portland, Oregon, Unites States of America, 7 Department of\nObstetrics and Gynecology, Oregon Health and Science University; Portland, Oregon, Unites States of\nAmerica, 8 Department of Obstetrics and Gynecology, University of Wisconsin-Madison; Madison,\nWisconsin, Unites States of America, 9 Department of Kinesiology, University of Wisconsin-Madison;\nMadison, Wisconsin, Unites States of America, 10 Waisman Center, University of Wisconsin-Madison;"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 611
encoding: FLOAT32
metadata:
{"title": "Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus", "chroma:document": "Madison, Wisconsin, Unites States of America, 11 Department of Veterinary and Biomedical Science,\nUniversity of Minnesota; St. Paul, Minnesota, Unites States of America, 12 Department of Ophthalmology\nand Visual Sciences, University of Wisconsin-Madison; Madison, Wisconsin, Unites States of America,\n13 Department of Communication Sciences and Disorders, University of Wisconsin-Madison; Madison,\nWisconsin, Unites States of America, 14 Department of Biostatistics & Medical Informatics, University of\nWisconsin-Madison; Madison, Wisconsin, Unites States of America, 15 Department of Pathobiological\nSciences, University of Wisconsin-Madison; Madison, Wisconsin, Unites States of America\n\u262f These authors contributed equally to this work.\n\u2021 DHO and CMN also contributed equally to this work.\n* ccondon2@wisc.edu\nAbstract\nIn the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects sur-\nfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy.\nLess is known about the impacts of gestational African-lineage ZIKV infections. Given high\nhuman immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circu-\nlates, we evaluated whether pregnant rhesus macaques infected with simian immunodefi-\nciency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects.\nRemarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused\na high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings sug-\ngest a significant risk for early pregnancy loss associated with African-lineage ZIKV infection\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011282\nMarch 28, 2023\n1 / 23\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Rosinski JR, Raasch LE, Barros Tiburcio\nP, Breitbach ME, Shepherd PM, Yamamoto K, et al.\n(2023) Frequent first-trimester pregnancy loss in\nrhesus macaques infected with African-lineage Zika"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 612
encoding: FLOAT32
metadata:
{"title": "Frequent first-trimester pregnancy loss in rhesus macaques infected with African-lineage Zika virus", "chroma:document": "virus. PLoS Pathog 19(3): e1011282. https://doi.\norg/10.1371/journal.ppat.1011282\nEditor: Helen M. Lazear, University of North\nCarolina at Chapel Hill School of Medicine, UNITED\nSTATES\nReceived: January 11, 2023\nAccepted: March 8, 2023\nPublished: March 28, 2023\nCopyright: This is an open access article, free of all\ncopyright, and may be freely reproduced,\ndistributed, 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 relevant data are\nwithin the manuscript and the Supporting\nInformation files. Primary data that support this\nstudy are also available at GitHub https://github.\ncom/lraasch/Frequent-first-trimester-pregnancy-\nloss-in-rhesus-macaques-infected-with-African-\nlineage-Zika-virus. ISH images are available at\nhttps://go.wisc.edu/23d838.\nFunding: This work was supported by NIH Grants\nR01AI138647, P01AI132132, K08AI139341,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 613
encoding: FLOAT32
metadata:
{"title": "Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses", "chroma:document": "Targeted isolation of panels of diverse human protective broadly \nneutralizing antibodies against SARS-like viruses\nWan-ting He1,2,3,\u2020, Rami Musharrafieh1,2,3,\u2020, Ge Song1,2,3,\u2020, Katharina Dueker1,2,3,\u2020, \nLongping V. Tse4, David R. Martinez4, Alexandra Sch\u00e4fer4, Sean Callaghan1,2,3, Peter \nYong1,2,3, Nathan Beutler1, Jonathan L. Torres5, Reid M. Volk5, Panpan Zhou1,2,3, Meng \nYuan5, Hejun Liu5, Fabio Anzanello1,2,3, Tazio Capozzola1,2,3, Mara Parren1, Elijah Garcia1, \nStephen A. Rawlings6, Davey M. Smith6, Ian A. Wilson2,3,5,7, Yana Safonova8, Andrew \nB. Ward2,3,5, Thomas F. Rogers1,6, Ralph S. Baric4,9,*, Lisa E. Gralinski4,*, Dennis R. \nBurton1,2,3,10,*, Raiees Andrabi1,2,3,*\n1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA \n92037, USA.\n2IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA\n3Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La \nJolla, CA 92037, USA.\n4Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC \n27599, USA.\n5Department of Integrative Structural and Computational Biology, The Scripps Research Institute, \nLa Jolla, CA 92037, USA.\n6Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La \nJolla, CA 92037, USA.\n7Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 9203\n8Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA\n9Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, \nChapel Hill, NC 27599, USA.\n*Corresponding author. rbaric@email.unc.edu (R.S.B.); lgralins@email.unc.edu (L.E.G.); burton@scripps.edu (D.R.B.); \nandrabi@scripps.edu (R.A.).\n\u2020These authors contributed equally to this work.\nAuthor contributions\nW.H., R.M., G.S., K.D., D.R.B. and R.A. conceived and designed the study. N.B., M.P., E.G., S.A.R., D.M.S., and T.F.R. recruited"}


