# embeddings_queue

created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 614
encoding: FLOAT32
metadata:
{"title": "Targeted isolation of panels of diverse human protective broadly neutralizing antibodies against SARS-like viruses", "chroma:document": "donors and collected and processed plasma and PBMC samples. W.H., R.M., G.S., K.D., S.C., P.Y. and F.A. performed BLI, ELISA, \nvirus preparation, neutralization and isolation and characterization of monoclonal antibodies. Y.S. performed immunogenetic analysis \nof antibodies. P.Z. prepared virus mutant plasmids. J.L.T. and R.M.V. conducted negative stain electron microscopy studies. M.Y. and \nH.L. generated antibody-antigen structural models. L.V.T. performed live virus neutralizations assays and L.V.T., D.R.M., A.S., and \nL.E.G. conducted in vivo animal protection studies. W.H., R.M., G.S., K.D., L.V.T., D.R.M., A.S., S.C., P.Y., N.B., J.L.T., R.M.V., \nP.Z., M.Y. H.L., F.A., M.P., E.G., I.A.W., A.B.W., T.F.R., R.S.B., L.E.G., D.R.B. and R.A. designed the experiments and/or analyzed \nthe data. W.H., R.M., D.R.B. and R.A. wrote the paper, and all authors reviewed and edited the paper.\nCompeting interests: W.H., R.M., G.S., K.D., T.F.R., D.R.B. and R.A. are listed as inventors on pending patent applications describing \nthe sarbecovirus broadly neutralizing antibodies isolated in this study. A.B.W, I.A.W and D.R.B. receive research funding from \nAdagio. RSB and LEG have ongoing collaborations with Adagio. All other authors have no competing interests to declare.\nHHS Public Access\nAuthor manuscript\nNat Immunol. Author manuscript; available in PMC 2023 April 09.\nPublished in final edited form as:\nNat Immunol. 2022 June ; 23(6): 960\u2013970. doi:10.1038/s41590-022-01222-1.\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: 615
encoding: FLOAT32
metadata:
{"title": "The ventromedial prefrontal cortex and emotion regulation: lost in translation?", "chroma:document": "J Physiol 601.1 (2023) pp 37\u201350\n37\nThe Journal of Physiology\nREVIEW-SYMPOSIUM\nThe ventromedial prefrontal cortex and emotion\nregulation: lost in translation?\nLaith Alexander1,2\n, Christian M. Wood3,4\nand Angela C. Roberts3,4\n1St Thomas\u2019 Hospital, London, UK\n2Department of Psychological Medicine, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London,\nLondon, UK\n3Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK\n4Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK\nEdited by: Ian Forsythe & Michael Okun\nThe peer review history is available in the Supporting information section of this article\n(https://doi.org/10.1113/JP282627#support-information-section).\nAbstract Neuroimaging studies implicate the ventromedial prefrontal cortex (vmPFC) in a wide\nrange of emotional and cognitive functions, and changes in activity within vmPFC have been\nThis symposium review forms part of the \u2019Decoding Prefrontal Cortical Physiology: Circuits of Cognition\u2019 symposium held at Physiology 2021 in\nJuly 2021, and organised by Professor Matt Jones.\n\u00a9 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.\nDOI: 10.1113/JP282627\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution\nand reproduction in any medium, provided the original work is properly cited."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 616
encoding: FLOAT32
metadata:
{"title": "Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques", "chroma:document": "RESEARCH ARTICLE\nChronic immune activation and gut barrier\ndysfunction is associated with\nneuroinflammation in ART-suppressed SIV+\nrhesus macaques\nSarah J. Byrnes1, Kathleen Busman-Sahay2,3, Thomas A. Angelovich1,4,5,\nSkyler Younger2, Sol Taylor-Brill2, Michael Nekorchuk2, Stephen Bondoc2,\nRachel Dannay2, Margaret Terry2, Catherine R. Cochrane1, Trisha A. Jenkins1,\nMichael Roche1,5, Claire Deleage6, Steven E. Bosinger7,8, Mirko Paiardini7,8, Bruce\nJ. Brew9, Jacob D. Estes1,2,3\u262f, Melissa J. ChurchillID1,4,10\u262f*\n1 School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia, 2 Vaccine & Gene\nTherapy Institute, Oregon Health & Science University, Portland, Oregon, United States of America,\n3 Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health &\nScience University, Portland, Oregon, United States of America, 4 Life Science, Burnet Institute, Melbourne,\nAustralia, 5 Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, The\nUniversity of Melbourne, Melbourne, Australia, 6 AIDS and Cancer Virus Program, Leidos Biomedical\nResearch Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of\nAmerica, 7 Division of Microbiology and Immunology, Emory National Primate Research Center, Emory\nUniversity, Atlanta, Georgia, United States of America, 8 Department of Pathology and Laboratory Medicine,\nEmory University School of Medicine, Atlanta, Georgia, United States of America, 9 Peter Duncan\nNeurosciences Unit, Departments of Neurology and Immunology St Vincent\u2019s Hospital, University of New\nSouth Wales and University of Notre Dame, Sydney, New South Wales, Australia, 10 Departments of\nMicrobiology and Medicine, Monash University, Clayton, Australia\n\u262f These authors contributed equally to this work.\n* melissa.churchill@rmit.edu.au\nAbstract\nHIV-associated neurocognitive disorders (HAND) affect ~40% of virally suppressed people"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 617
encoding: FLOAT32
metadata:
{"title": "Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques", "chroma:document": "with HIV (PWH), however, the precise viral dependent and independent changes to the\nbrain are unclear. Here we characterized the CNS reservoir and immune environment of\nSIV-infected (SIV+) rhesus macaques during acute (n = 4), chronic (n = 12) or ART-sup-\npressed SIV infection (n = 11). Multiplex immunofluorescence for markers of SIV infection\n(vRNA/vDNA) and immune activation was performed on frontal cortex and matched colon\ntissue. SIV+ animals contained detectable viral DNA+ cells that were not reduced in the\nfrontal cortex or the gut by ART, supporting the presence of a stable viral reservoir in these\ncompartments. SIV+ animals had impaired blood brain barrier (BBB) integrity and height-\nened levels of astrocytes or myeloid cells expressing antiviral, anti-inflammatory or oxidative\nstress markers which were not abrogated by ART. Neuroinflammation and BBB dysfunction\ncorrelated with measures of viremia and immune activation in the gut. Furthermore, SIV-\nuninfected animals with experimentally induced gut damage and colitis showed a similar\nimmune activation profile in the frontal cortex to those of SIV-infected animals, supporting\nthe role of chronic gut damage as an independent source of neuroinflammation. Together,\nthese findings implicate gut-associated immune activation/damage as a significant\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011290\nMarch 29, 2023\n1 / 26\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Byrnes SJ, Busman-Sahay K, Angelovich\nTA, Younger S, Taylor-Brill S, Nekorchuk M, et al.\n(2023) Chronic immune activation and gut barrier\ndysfunction is associated with neuroinflammation\nin ART-suppressed SIV+ rhesus macaques. PLoS\nPathog 19(3): e1011290. https://doi.org/10.1371/\njournal.ppat.1011290\nEditor: Daniel C. Douek, Vaccine Research Center,\nUNITED STATES\nReceived: August 11, 2022\nAccepted: March 10, 2023\nPublished: March 29, 2023\nCopyright: This is an open access article, free of all\ncopyright, and may be freely reproduced,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 618
encoding: FLOAT32
metadata:
{"title": "Chronic immune activation and gut barrier dysfunction is associated with neuroinflammation in ART-suppressed SIV+ rhesus macaques", "chroma:document": "distributed, transmitted, modified, built upon, or\notherwise used by anyone for any lawful purpose.\nThe work is made available under the Creative\nCommons CC0 public domain dedication.\nData Availability Statement: All relevant data are\nwithin the manuscript and its Supporting\nInformation files.\nFunding: This research was funded by National\nHealth and Medical Research Council, Australia\ngrant 1157988 (M.J.C, J.D.E, T.A.A; https://www.\nnhmrc.gov.au/funding) and National Institutes of\nHealth, USA grants https://www.nih.gov/grants-\nfunding): R01AI143411 (J.D.E), P51OD011092\n(Oregon National Primate Research Center),"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 619
encoding: FLOAT32
metadata:
{"title": "Cortico&#x02010;thalamocortical interactions for learning, memory and decision&#x02010;making", "chroma:document": "J Physiol 601.1 (2023) pp 25\u201335\n25\nThe Journal of Physiology\nREVIEW-SYMPOSIUM\nCortico-thalamocortical interactions for learning, memory\nand decision-making\nBrook A. L. Perry1\n, Juan Carlos Mendez1,2\nand Anna S. Mitchell1\n1Department of Experimental Psychology, University of Oxford, Oxford, UK\n2College of Medicine and Health, University of Exeter, Exeter, UK\nHandling Editors: Ian Forsythe & Richard Carson\nThe peer review history is available in the Supporting information section of this article\n(https://doi.org/10.1113/JP282626#support-information-section).\nAbstract\nThe thalamus and cortex are interconnected both functionally and anatomically\nand share a common developmental trajectory. Interactions between the mediodorsal thalamus\n(MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as\nlearning and adaptive decision-making. Cortico-thalamocortical interactions involving other\ndorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these\ncognitive processes. Our work, and that of others, indicates a crucial influence of these inter-\ndependent cortico-thalamocortical neural networks that contributes actively to the processing\nof information within the cortex. Each of these thalamic nuclei also receives potent subcortical\nThis symposium review forms part of the \u2018Decoding Prefrontal Cortical Physiology: Circuits of Cognition\u2019 symposium held at Physiology 2021 in July\n2021, and organized by Professor Matt Jones.\n\u00a9 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.\nDOI: 10.1113/JP282626\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution\nand reproduction in any medium, provided the original work is properly cited."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 620
encoding: FLOAT32
metadata:
{"title": "Major haemorrhage: past, present and future", "chroma:document": "Review Article\nMajor haemorrhage: past, present and future\nA. Shah,1\nV. Kerner,2\nS. J. Stanworth3\nand S. Agarwal4\n1 NIHR Academic Clinical Lecturer, Nuf\ufb01eld Department of Clinical Neurosciences, University of Oxford, Oxford, UK\n2 Specialist Registrar, Nuf\ufb01eld Department of Anaesthesia, Oxford University Hospitals NHS Foundation Trust,\nOxford, UK\n3 Professor, Radcliffe Department of Medicine, University of Oxford, Oxford, UK\n4 Consultant, Department of Anaesthesia, Manchester University NHS Foundation Trust, Manchester, UK\nSummary\nMajor haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires\nearly recognition, planned responses, readily available resources (such as blood products) and rapid access to\nsurgery or interventional radiology. Major haemorrhage is often accompanied by volume loss, haemodilution,\nacidaemia, hypothermia and coagulopathy (factor consumption and \ufb01brinolysis). Management of major\nhaemorrhage over the past decade has evolved to now deliver a `package\u00b4 of haemostatic resuscitation\nincluding: surgical or radiological control of bleeding; regular monitoring of haemostasis; advanced critical\ncare support; and avoidance of the lethal triad of hypothermia, acidaemia and coagulopathy. Recent trial data\nadvocate for a more personalised approach depending on the clinical scenario. Fresh frozen plasma should be\ngiven as early as possible in major trauma in a 1:1 ratio with red blood cells until the results of coagulation tests\nare available. Tranexamic acid is a cheap, life-saving drug and is advocated in major trauma, postpartum\nhaemorrhage and surgery, but not in patients with gastrointestinal bleeding. Fibrinogen levels should be\nmaintained > 2 g.l\u00011 in postpartum haemorrhage and > 1.5 g.l\u00011 in other haemorrhage. Improving outcomes\nafter major traumatic haemorrhage is now driving research to include extending blood-product resuscitation\ninto prehospital care."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 621
encoding: FLOAT32
metadata:
{"title": "Major haemorrhage: past, present and future", "chroma:document": ".................................................................................................................................................................\nCorrespondence to: A. Shah\nEmail: akshay.shah@linacre.ox.ac.uk\nAccepted: 29 August 2022\nKeywords: crystalloid resuscitation: coagulopathy; major haemorrhage; transfusion; trauma\nTwitter: @DocAShah; @OxCPD; @SimonStanworth; @SeemaMosca\nIntroduction\nA person dies from injury nearly every 3 min, and 40% of\nthese deaths are due to major haemorrhage or its\nconsequences [1]. Death from haemorrhage is early, with\nup to 60% of deaths occurring within the \ufb01rst 3 h of injury\n[2]. Haemorrhage continues to be the leading cause of\nmaternal death globally [3]. Causes of haemorrhage may\nalso vary geographically. In high-resource settings, the most\ncommon indications for massive transfusion are major\nsurgery (61.2%) followed by trauma (15.4%), whereas\nobstetric bleeding only constitutes 1.8% of cases [4].\nSince the publication of major haemorrhage guidelines\nfrom the British Society of Haematology in 2015 and\nAssociation of Anaesthetists in 2016, there have been\nnumerous randomised controlled trials in this \ufb01eld. A\nsummary of these trials is displayed in Table 1.\nThe aims of this article are to: describe the de\ufb01nitions of\nmajor haemorrhage; brie\ufb02y recap the mechanisms and\npathophysiology of bleeding; provide a contemporary\nnarrative review of transfusion support during major\nhaemorrhage across a range of clinical indications; and\nhighlight ongoing trials and areas of uncertainty.\n\u00a9 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.\n93\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use,\ndistribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.\nAnaesthesia 2023, 78, 93\u2013104\ndoi:10.1111/anae.15866"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 622
encoding: FLOAT32
metadata:
{"title": "The current status of stem cell-based therapies during ex vivo graft perfusion: an integrated review of four organs ", "chroma:document": "Am J Transplant. 2022;22:2723\u20132739. \n \n\u2003|\u20032723\nAJT\namjtransplant.com\nReceived: 3 May 2022\u2003|\u2003Revised: 26 June 2022\u2003|\u2003Accepted: 15 July 2022\nDOI: 10.1111/ajt.17161  \nM I N I R E V I E W\nThe current status of stem cell- based therapies during ex vivo \ngraft perfusion: An integrated review of four organs\nStefan H. Luijmes1\n\u2003|   Monique M. A. Verstegen1\n\u2003|   Martin J. Hoogduijn2\n\u2003|    \nLeonard Seghers3\n\u2003|   Robert C. Minnee1\n\u2003|   Edris A. F. Mahtab4\n\u2003|    \nYannick J. H. J. Taverne4\n\u2003|   Marlies E. J. Reinders2\n\u2003|   Luc J. W. van der Laan1\n\u2003|   \nJeroen de Jonge1\n1Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, \nRotterdam, The Netherlands\n2Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center Rotterdam, \nRotterdam, The Netherlands\n3Department of Pulmonology, Thorax Center, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands\n4Department of Cardiothoracic Surgery, Thorax Center, Erasmus MC Transplant Institute, University Erasmus Medical Center Rotterdam, Rotterdam, The \nNetherlands\nThis is an open access article under the terms of the Creative Commons Attribution- NonCommercial- NoDerivs License, which permits use and distribution in \nany medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.\n\u00a9 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the \nAmerican Society of Transplant Surgeons.\nAbbreviations: ADAR, adenosine deaminase, RNA- specific; AFC, alveolar fluid clearance; AKT1, v- akt murine thymoma viral oncogene homolog 1; AKT3, v- akt murine thymoma viral"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 623
encoding: FLOAT32
metadata:
{"title": "The current status of stem cell-based therapies during ex vivo graft perfusion: an integrated review of four organs ", "chroma:document": "oncogene homolog 3; ALP, alkaline phosphatase; ALT, alanine aminotransferase; A- MSC, adipose- derived mesenchymal stromal cell; ANG- 1, angiopoietin 1; AOX1, aldehyde oxidase 1; \nAST, aspartate aminotransferase; ATP, adenosine triphosphate; ATP6V0D2, vacuolar H\u2009+\u2009- ATPase d2 Subunit; BALF, bronchoalveolar lavage fluid; BCL2L11, BCL2- like 11; BICC1, \nbicaudal C homolog 1 gene; BID, BH3- interacting domain death agonist; BIRC5, baculoviral IAP repeat- containing 5; BM- MSC, bone marrow- derived mesenchymal stromal cell; BTLA, \nB-  and T- lymphocyte attenuator; BW, bodyweight; CALB1, calbindin 1; CASP2, caspase- 2; CASP8, caspase- 8; CAT, catalase; CCL11, chemokine (C\u2009\u2212\u2009C motif) ligand 11; CD40LG, CD40 \nligand; CFTR, cystic fibrosis transmembrane conductance regulator; CXCL2, chemokine C- X- C motif ligand 2; CXCL3, chemokine C- X- C motif ligand 3; CXCR4, C- X- C chemokine \nreceptor type 4; CXCR5, C- X- C chemokine receptor type 5; CXCR7, C- X- C chemokine receptor type 7; DCDC2, doublecortin domain- containing protein 2; DHCR24, \n24- Dehydrocholesterol reductase; DNM2, dynamin 2; dP/dtmax, maximal slope of systolic pressure increment; dP/dtmin, maximal slope of diastolic pressure decrement; E.coli, Escherichia \ncoli; EB, endobronchially; ECD, extended criteria donor; EGF, endothelial growth factor; EPX, eosinophil peroxidase; EV, extracellular vesicle; EVHP, ex vivo heart perfusion; EVLP, ex \nvivo lung perfusion; FADD, fas (TNFRSF6) associated via death domain; FASLG, Fas ligand; FBS, fetal bovine serum; FGF- 1, fibroblast growth factor- 1; FGF- 2, fibroblast growth factor- 2; \nFLT- 3 L, FMS- like tyrosine kinase 3 ligand; FOXG1, forkhead box G1; GCP, Good Clinical Practice; G- CSF, granulocyte colony- stimulating factor; GGT, gamma- glutamyltransferase; \nGITR, glucocorticoid- induced tumor necrosis factor receptor; GM- CSF, granulocyte- macrophage colony- stimulating factor; GPX, glutathione peroxidase; GPX4, anti- glutathione"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 624
encoding: FLOAT32
metadata:
{"title": "The current status of stem cell-based therapies during ex vivo graft perfusion: an integrated review of four organs ", "chroma:document": "peroxidase 4; GRB2, growth factor receptor- bound protein 2; GSH, glutathione; GZMB, granzyme B; HA, hyaluronic acid; HGF, hepatocyte growth factor; HIF1A, hypoxia- inducible \nfactor 1- \u03b1; HLA- G5, human leukocyte antigen- G5; HLSC, human liver stem cell; HLSC- EV, human liver stem cell extracellular vesicle; HMGB1, high- mobility group box 1; HMP, \nhypothermic machine perfusion; HO- 1, heme oxygenase 1; HO- 1/BMMSC, heme oxygenase 1- modified bone marrow- derived mesenchymal stromal cell; HOPE, hypothermic \noxygenated perfusion; HSP70, heat shock protein 70; HYOU1, hypoxia upregulated 1; IA, intra- arterially; ICAM- 1, intercellular adhesion molecule 1; IDH2, isocitrate dehydrogenase 2; \nIDO, Indolamine- 2,3- dioxygenase; IFN- \u03b3, interferon- gamma; IGF, insulin- like growth factor; IH, intrahepatic; IL, interleukin; IL- 1- RA, interleukin- 1 receptor antagonist; IP- 10, \ninterferon- inducible protein 10; IT, intratracheal; IV, intravenous; KRT19, cytokeratin- 19; KRT7, cytokeratin- 7; LDH, lactate dehydrogenase; LLL, left lower lobe; MAPC, multipotent \nadult progenitor cell; MAPK3, mitogen- activated protein kinase 3; MAPK4, extracellular signal- regulated kinase 4; MCP- 1, monocyte chemoattractant protein- 1; MCP- 3, monocyte \nchemoattractant protein- 3; M- CSF, macrophage colony- stimulating factor; MDA, malondialdehyde; MDC, macrophage- derived chemokine; MIP, macrophage inflammatory protein; MP, \nmachine perfusion; MPO, myeloperoxidase; MSC, mesenchymal stromal cell; MSC- CM, mesenchymal stromal cell- conditioned medium; MSC- EV, mesenchymal stem cell- derived \nextracellular vesicle; mTOR, mechanistic target of rapamycin; MV, microvesicle; MVB, multivesicular body; NDUFS8, NADH dehydrogenase Fe- S protein 8; NGAL, neutrophil \ngelatinase- associated lipocalin; NK, natural killer; NMP, normothermic machine perfusion; NO, nitric oxide; NOX4, NADPH oxidase 4; NOXO1, NADPH oxidase organizer; PAK1, p21"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 625
encoding: FLOAT32
metadata:
{"title": "The current status of stem cell-based therapies during ex vivo graft perfusion: an integrated review of four organs ", "chroma:document": "protein (Cdc42/Rac)- activated kinase; PAP, pulmonary arterial pressure; PAR, pulmonary artery resistance; PBG, peribiliary gland; PCNA, proliferating cell nuclear antigen; PD- 1, \nprogrammed cell death protein- 1; PDHB, pyruvate dehydrogenase beta; PGE2, prostaglandin E2; PTGS2, prostaglandin- endoperoxide synthase 2; PV, portal vein; PVR, pulmonary \nvascular resistance; RAI, rejection activity index; RANTES, regulated on activation, normal T expressed and secreted; RBC, red blood cell; RML, right middle lobe; RNA, ribonucleic acid; \nROS, reactive oxidative species; SDF- 1\u03b1, stromal cell- derived factor- 1\u03b1; Serpinb1b, Serine (or cysteine) peptidase inhibitor, clade B, member 1b; SLC16A1, monocarboxylate transporter \n1; sNMP, subnormothermic machine perfusion; SOCS3, suppressor of cytokine signaling 3; SOD, superoxide dismutase; SOD2, superoxide dismutase 2, mitochondrial; SOX4, \nsex- determining region Y- related high- mobility group box transcription factor 4; STC- 1, stanniocalcin- 1; STIP1, transformation- sensitive protein IEF SSP 3521; Tau- w, time constant of \nthe left ventricular pressure decay; TCL1a, T- cell leukemia/lymphoma 1A; TGF, transforming growth factor; TIMP- 1, tissue inhibitor of metalloproteinase- 1; TNF- \u03b1, tumor necrosis \nfactor- \u03b1; TPN, total parenteral nutrition; TPO, thyroid peroxidase; TPVR, total pulmonary vascular resistance; T- reg, regulatory T cell; TUNEL, terminal deoxynucleotidyl transferase \ndUTP nick end labeling; TXNRD2, thioredoxin reductase 2; UC- MSC, umbilical cord- derived mesenchymal stromal cell; UW- MPS, University of Wisconsin machine perfusion solution; \nVEGF, vascular endothelial growth factor."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 626
encoding: FLOAT32
metadata:
{"title": "Neural bases of the bodily self as revealed by electrical brain stimulation: a systematic review", "chroma:document": "R E V I E W A R T I C L E\nNeural bases of the bodily self as revealed by electrical brain\nstimulation: A systematic review\nZo\u00e9 Dary1\n|\nBigna Lenggenhager2,3\n|\nStanislas Lagarde4,5\n|\nSamuel Medina Villalon4,5\n|\nFabrice Bartolomei4,5\n|\nChristophe Lopez1\n1Aix Marseille University, CNRS, LNC, FR3C,\nMarseille, France\n2Department of Psychology, University of\nZurich, Zurich, Switzerland\n3Department of Psychology, University of\nKonstanz, Konstanz, Germany\n4Aix Marseille University, APHM, Inserm, INS,\nTimone Hospital, Marseille, France\n5APHM, Timone Hospital, Epileptology and\nCerebral Rhythmology, Marseille, France\nCorrespondence\nChristophe Lopez, Laboratoire de\nNeurosciences Cognitives \u2013 UMR 7291, Aix\nMarseille University & Centre National de la\nRecherche Scientifique (CNRS), Centre Saint-\nCharles, F\u00e9d\u00e9ration de Recherche 3C \u2013 Case\nB. 3, Place Victor Hugo. 13331 Marseille\nCedex 03, France.\nEmail: christophe.lopez@univ-amu.fr\nFunding information\nAgence Nationale de la Recherche,\nGrant/Award Number: ANR-19-CE37-0027\nAbstract\nAn increasing amount of recent research has focused on the multisensory and neural\nbases of the bodily self. This pre-reflective form of self is considered as multifaceted,\nincorporating phenomenal components, such as self location, body ownership, first-\nperson perspective, agency, and the perceptual body image. Direct electrical brain\nstimulation (EBS) during presurgical evaluation of epilepsy and brain tumor re-\nsection is a unique method to causally relate specific brain areas to the various phe-\nnomenal components of the bodily self. We conducted a systematic review of the\nliterature describing altered phenomenal experience of the bodily self evoked by\nEBS. We included 42 articles and analyzed self reports from 221 patients. Three-\ndimensional density maps of EBS revealed that stimulation in the middle cingulum,\ninferior parietal lobule, supplementary motor area, posterior insula, hippocampal\ncomplex/amygdala, and precuneus most consistently altered one or several compo-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 627
encoding: FLOAT32
metadata:
{"title": "Neural bases of the bodily self as revealed by electrical brain stimulation: a systematic review", "chroma:document": "nents of the bodily self. In addition, we found that only EBS in the parietal cortex\ninduced disturbances of all five components of the bodily self considered in this\nreview article. These findings inform current neuroscientific models of the bodily self.\nK E Y W O R D S\nself consciousness, bodily self, electrical brain stimulation, epilepsy, parietal cortex\n1\n|\nINTRODUCTION\nThe functionality, morphology, and state of our body have shown to\nplay a major role in many cognitive, affective, and social processes\nand crucially define our self consciousness. Such bodily self is consid-\nered to result from a constant multisensory integration and fine-\ntuning of bottom-up signals (visual, somatosensory, interoceptive, and\nvestibular\nsignals)\nand\ntop-down\nexpectancy\n(Blanke,\n2012;\nLenggenhager & Lopez, 2015; Park & Blanke, 2019; Tsakiris, 2010).\nVarious phenomenal components of the bodily self have been\ndescribed in the literature, of which five main components will be\ndifferentiated in the present review article: self location, body owner-\nship, the first-person perspective, the sense of agency, and the per-\nceptual body image (Table 1). Self location refers to the experience of\noccupying a volume of space, typically localized within one's own\nphysical body boundaries (Blanke & Metzinger, 2009). Body owner-\nship is the experience of owning a physical body (Tsakiris et al., 2007).\nThe first-person perspective refers to \u201cthe experience from where I\nperceive the world\u201d (Blanke, 2012). The first-person perspective is\nusually centered on the body and corresponds to an egocentric per-\nspective/viewpoint (Vogeley & Fink, 2003). Agency is the sense of\nbeing in control of one's own actions (Jeannerod, 2006). The\nReceived: 17 October 2022\nRevised: 8 February 2023\nAccepted: 13 February 2023\nDOI: 10.1002/hbm.26253\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 628
encoding: FLOAT32
metadata:
{"title": "Neural bases of the bodily self as revealed by electrical brain stimulation: a systematic review", "chroma:document": "medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.\n\u00a9 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.\n2936\nHum Brain Mapp. 2023;44:2936\u20132959.\nwileyonlinelibrary.com/journal/hbm"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 629
encoding: FLOAT32
metadata:
{"title": "Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies", "chroma:document": "Single-Administration Long-Acting Microarray Patch with Ultrahigh\nLoading Capacity and Multiple Releases of Thermally Stable\nAntibodies\nKhanh T. M. Tran, Thinh T. Le, Vivek Agrahari, M. Melissa Peet, Louise A. Ouattara,\nSharon M. Anderson, Trang Huyen Le-Kim, Onkar N. Singh, Gustavo F. Doncel,*\nand Thanh D. Nguyen*\nCite This: Mol. Pharmaceutics 2023, 20, 2352\u22122361\nRead Online\nACCESS\nMetrics & More\nArticle Recommendations\n*\ns\u0131\nSupporting Information\nABSTRACT: Current antibody (Ab) therapies require development of\nstable formulations and an optimal delivery system. Here, we present a new\nstrategy to create a single-administration long-lasting Ab-delivery microarray\n(MA) patch, which can carry high doses of thermally stabilized Abs. The\nMA fabricated by an additive three-dimensional manufacturing technology\ncan be fully embedded into the skin via a single application to deliver doses\nof Abs at multiple programmable time points, thus sustaining Ab\nconcentrations in systemic circulation. We developed an MA formulation\nthat stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and\nfunctionality. As an example, the b12 Ab\u0001a broadly neutralizing Ab against HIV-1\u0001maintained antiviral activity in vitro after MA\nmanufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of\nconcept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded\nprotection against viral infections or combination HIV therapy and prevention.\nKEYWORDS: microarray patch, fabrications, therapeutic antibodies, protein stabilization, long-acting delivery\n1. INTRODUCTION\nAntibodies (Abs) are an important class of therapeutic agents\nand are being used to treat a wide variety of diseases including\ncancer, autoimmune disorders, and infectious diseases.1 More\nthan 100 monoclonal Ab (mAb)-based therapeutics have been\napproved by regulatory authorities for treatment of cancer, skin"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 630
encoding: FLOAT32
metadata:
{"title": "Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies", "chroma:document": "disorders, human immunodeficiency virus (HIV-1), COVID-\n19, Alzheimer\u2019s, and other diseases,2 and several others are\nactively under clinical development.3 Specifically, potent\nbroadly neutralizing antibodies (bnAbs) have emerged as\npotential alternatives or adjuvants to HIV antiretroviral therapy\n(ART).4 Although combination ART is highly effective, it\nrequires lifelong medication, which is associated with\nsignificant side effects.5 In contrast, bnAbs uniquely target\nand bind to specific parts of the HIV envelope, preventing new\ninfections through a different mechanism of action, and thus\ncan be used to suppress viral rebound in the absence of\nART.6,7 As such, Ab treatments are being explored as\nalternative/supplementary tools to antiretrovirals (ARVs) for\nthe long-acting treatment or prevention of HIV infection.8\nAdditionally, administration of a combination of bnAbs\ntargeting different neutralizing epitopes could expand\nprotection and treatment effectiveness.9 However, the delivery\nof Abs into the human body faces many challenges that have\nyet to be overcome.\nThe efficacy of therapeutic or prophylactic Abs is critically\ndependent on circulatings serum concentrations, which are\ndifficult to maintain at high levels for a long period. In order to\nachieve high and persistent serum levels of Abs for optimal\nefficacy, Ab therapies typically require frequent and repeated\nadministrations of relatively large doses (subgrams or grams).10\nIntravenous infusion remains the most popular delivery route\nof choice; however, it involves pain, discomfort, high costs,\nrepeated visits to medical facilities, intervention of highly\ntrained personnel, and use of hypodermic needles, which cause\nstress on patients, ultimately resulting in a high burden on the\nhealthcare system, especially in resource-constrained regions of\nthe world.11 While there is an unmet need for minimally\ninvasive, controlled-release, and easy-to-administer delivery\nsystems for mAb-based therapies, protein-based therapeutic"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 631
encoding: FLOAT32
metadata:
{"title": "Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies", "chroma:document": "agents frequently suffer from formulation challenges, and Abs\nare no exception. Formulations of Abs in polymeric carriers\noften include the use of organic solvents or high-temperature\nReceived:\nNovember 2, 2022\nRevised:\nMarch 15, 2023\nAccepted:\nMarch 15, 2023\nPublished: April 4, 2023\nArticle\npubs.acs.org/molecularpharmaceutics\n\u00a9 2023 The Authors. Published by\nAmerican Chemical Society\n2352\nhttps://doi.org/10.1021/acs.molpharmaceut.2c00919\nMol. Pharmaceutics 2023, 20, 2352\u22122361"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 632
encoding: FLOAT32
metadata:
{"title": "Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization", "chroma:document": "Analysis of antibodies from HCV elite neutralizers identifies \ngenetic determinants of broad neutralization\nTimm Weber1,16, Julian Potthoff1,16, Sven Bizu2, Maurice Labuhn3, Leona Dold1,4,5, \nTill Schoofs1,17, Marcel Horning1, Meryem S. Ercanoglu1, Christoph Kreer1, Lutz \nGieselmann1,5, Kanika Vanshylla1, Bettina Langhans4,5, Hanna Janicki1, Luisa J. Str\u00f6h9, \nElena Knops6, Dirk Nierhoff7, Ulrich Spengler4,5, Rolf Kaiser5,6, Pamela J. Bjorkman8, \nThomas Krey9,10,11,12,13, Dorothea Bankwitz3, Nico Pfeifer2, Thomas Pietschmann3,13,14, \nAndrew I. Flyak8, Florian Klein1,5,6,15,18,*\n1Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University \nHospital Cologne, University of Cologne, 50931 Cologne, Germany\n2Methods in Medical Informatics, Department of Computer Science, University of T\u00fcbingen, \n72076 T\u00fcbingen, Germany\n3Twincore, Centre for Experimental and Clinical Infection Research, Institute of Experimental \nVirology, 30625 Hannover, Germany\n4Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany\n5German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50931 Cologne, \nGermany\n6Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, \n50931 Cologne, Germany\n7Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital \nCologne, 50931 Cologne, Germany\n8Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA \n91125, USA\n9Institute of Virology, Hannover Medical School, 30625 Hannover, Germany\n10Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of L\u00fcbeck, \n23562 Luebeck, Germany\n11Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany\n*Correspondence: florian.klein@uk-koeln.de.\nAUTHOR CONTRIBUTIONS\nConceptualization, T.W., T.P., A.I.F., and F.K.; methodology, T.W., J.P., S.B., M.L., L.D., T.S., M.H., M.S.E., C.K., L.G., K.V., P.J.B.,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 633
encoding: FLOAT32
metadata:
{"title": "Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization", "chroma:document": "T.K., D.B., N.P., T.P., A.I.F., and F.K.; investigation, T.W., J.P., S.B., M.L., L.D., T.S., M.H., M.S.E., C.K., L.G., K.V., H.J., D.B., and \nA.I.F.; software, S.B., C.K., and N.P.; formal analysis, T.W., J.P., L.D., T.S., M.H., C.K., N.P., A.I.F., and F.K.; resources, B.L., L.S., \nE.K., D.N., U.S., R.K., P.J.B., T.K., T.P., and F.K.; writing\u2013original draft, T.W., J.P., A.I.F., and F.K.; supervision, P.J.B., T.K., N.P., \nT.P., and F.K.\nSUPPLEMENTAL INFORMATION\nSupplemental information can be found online at https://doi.org/10.1016/j.immuni.2021.12.003.\nDECLARATION OF INTERESTS\nReported antibodies are in the process of being patented.\nHHS Public Access\nAuthor manuscript\nImmunity. Author manuscript; available in PMC 2023 April 11.\nPublished in final edited form as:\nImmunity. 2022 February 08; 55(2): 341\u2013354.e7. doi:10.1016/j.immuni.2021.12.003.\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: 634
encoding: FLOAT32
metadata:
{"title": "Regional precuneus cortical hyperexcitability in Alzheimer's disease patients", "chroma:document": "RESEARCH ARTICLE\nRegional Precuneus Cortical\nHyperexcitability in Alzheimer\u2019s Disease\nPatients\nElias P. Casula, PhD\n,1,2 Ilaria Borghi, MSc,1,3 Michele Maiella, MSc,1\nMaria C. Pellicciari, PhD,1 Sonia Bonn\u00ec, PhD,1 Lucia Mencarelli, PhD,1\nMartina Assogna, MD,1 Alessia D\u2019Acunto, BSc,1 Francesco Di Lorenzo, MD,1\nDanny A. Spampinato, PhD,1 Emiliano Santarnecchi, PhD,4\nAlessandro Martorana, MD, PhD,5 and Giacomo Koch, MD, PhD\n1,6\nObjective: Neuronal excitation/inhibition (E/I) imbalance is a potential cause of neuronal network malfunctioning in\nAlzheimer\u2019s disease (AD), contributing to cognitive dysfunction. Here, we used a novel approach combining trans-\ncranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain\nareas known to be directly involved in AD pathology.\nMethods: We performed TMS-EEG recordings targeting the left dorsolateral prefrontal cortex (l-DLPFC), the left pos-\nterior parietal cortex (l-PPC), and the precuneus (PC) in a large sample of patients with mild-to-moderate AD (n = 65)\nthat were compared with a group of age-matched healthy controls (n = 21).\nResults: We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to\nsome extent, in the frontal lobe, as measured by TMS-evoked potentials. Notably, cortical excitability assessed over\nthe l-PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability\nwas associated with the level of cognitive impairment, as measured with Mini-Mental State Examination, and with\ncorticospinal \ufb02uid levels of A\u03b242.\nInterpretation: Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic\ndysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel prom-\nising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to\nstage disease severity and evaluate response to novel therapies."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 635
encoding: FLOAT32
metadata:
{"title": "Regional precuneus cortical hyperexcitability in Alzheimer's disease patients", "chroma:document": "ANN NEUROL 2023;93:371\u2013383\nAbbreviations\nA\u03b2\namyloid beta\nAD\nAlzheimer\u2019s disease\nCDR\nclinical dementia score\nChAT\ncholine acetyltransferase\nCSF\ncerebrospinal \ufb02uid\nDLPFC\ndorso-lateral prefrontal cortex\nDMN\ndefault mode network\nE/I\nexcitation/inhibition\nEEG\nelectroencephalography\nView this article online at wileyonlinelibrary.com. DOI: 10.1002/ana.26514\nReceived Jun 10, 2022, and in revised form Sep 5, 2022. Accepted for publication Sep 12, 2022.\nAddress correspondence to Dr Koch, Experimental Neuropsychophysiology Lab, Department of Behavioral and Clinical Neurology, Santa Lucia Founda-\ntion IRCCS, Via Ardeatina, 306, 00179, Rome, Italy. E-mail: g.koch@hsantalucia.it\nFrom the 1Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy; 2Department of Psychology, La Sapienza\nUniversity, Rome, Italy; 3Center for Translational Neurophysiology of Speech and Communication (CTNSC), Italian Institute of Technology (IIT), Ferrara,\nItaly; 4Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 5Memory\nClinic, Department of Systems Medicine, University of Tor Vergata, Rome, Italy; and 6Department of Neuroscience and Rehabilitation, University of\nFerrara, Ferrara, Italy\n\u00a9 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.\n371\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution\nand reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 636
encoding: FLOAT32
metadata:
{"title": "The role of oestrogen in determining sexual dimorphism in energy balance", "chroma:document": "J Physiol 601.3 (2023) pp 435\u2013449\n435\nThe Journal of Physiology\nREVIEW-SYMPOSIUM\nThe role of oestrogen in determining sexual dimorphism in\nenergy balance\nAnne Nicole De Jesus and Belinda A. Henry\nMetabolism, Obesity and Diabetes Program, Biomedicine, Discovery Institute, Department of Physiology, Monash University, Clayton, Victoria,\nAustralia\nHandling Editors: Laura Bennet & Janna Morrison\nThe peer review history is available in the Supporting information section of this article\n(https://doi.org/10.1113/JP279501#support-information-section).\nSexual dimorphism in\nadipose tissue distribution\nWomen in the\nreproductive years\nShift in adipose tissue distribution\nGynoid\nAndroid\nPost-menopausal\nwomen\nMen\nGynoid body shape\nAndroid body shape\nAndroid body shape\nOestrogen\nPhysical activity\nAdaptive thermogenesis\nCardiometabolic\ndiseases\nOestrogen\nPhysical activity\nAdaptive thermogenesis\nCardiometabolic\ndiseases\nResting energy \nexpenditure\nCardiometabolic\ndiseases\nAbstract\nEnergy balance is determined by caloric intake and the rate at which energy\nis expended, with the latter comprising resting energy expenditure, physical activity and\nadaptive thermogenesis. The regulation of both energy intake and expenditure exhibits clear\nAnne Nicole De Jesus is a doctoral student under the supervision of Dr Belinda Henry. She received a\ndouble degree BA extended major in Psychology (2019) and BSc (Hons) major in Physiology (2020) at\nMonash University. Her current work explores the role of female sex hormones on brown fat activity and\nglucose metabolism in women across different stages of reproductive live. Belinda Henry is the Director\nof the Biomedicine Discovery Institute Graduate School and a Senior Lecturer within the Department of\nPhysiology at Monash University, Australia. She is the head of the Metabolic Neuroendocrinology Group.\nHer research centres on the discovery of novel means of altering energy expenditure through modulation"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 637
encoding: FLOAT32
metadata:
{"title": "The role of oestrogen in determining sexual dimorphism in energy balance", "chroma:document": "of the brain as a mechanism for prevention or treatment of obesity. Her work is particularly focused on\nthe process of thermogenesis and the mechanisms that underpin this process in brown adipose tissue and\nskeletal muscle. She has strong expertise in utilising large animal models for neuroendocrine research and she has recently established the Translational\nMetabolic and Exercise laboratory.\nThis review was presented at the Australian Physiological Society Diamond Jubilee Conference \u2018Sex differences in Physiology\u2019, which took place at\nGriffith University, Gold Coast QLD, Australia, 22 November 2021.\n\u00a9 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.\nDOI: 10.1113/JP279501\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution\nand reproduction in any medium, provided the original work is properly cited."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 638
encoding: FLOAT32
metadata:
{"title": "Australian Fertility Preservation Guidelines for People with Cancer 2022: Review and Recommendations", "chroma:document": "Perspectives\nMJA 217 (11) \u25aa 12 December 2022\n564\nAustralian fertility preservation guidelines \nfor people with cancer 2022: review and \nrecommendations\nBest practice in oncofertility care requires structured referral pathways, with access to \nfertility preservation counselling and technology\nF\nertility preservation is a rapidly advancing \nfield, and new strategies are continuously being \ndeveloped and refined.1 These strategies include \noocyte and embryo cryopreservation, ovarian tissue \ncryopreservation and subsequent autografting for \nfemales, and sperm cryopreservation and testicular \nbiopsy for males. Fertility preservation treatment is \noften urgent to prevent a delay in commencing cancer \ntreatments. It requires effective communication and \nreferral pathways between multidisciplinary teams, \nso that provision of fertility preservation care can be \ndelivered consistently.1\nIn Australia, cancer incidence and survival have \nboth increased.2 In 2022, it is projected that over \n8200 Australians under the age of 40 years will be \ndiagnosed with cancer, with an incidence of 60.7 cases \nper 100 000 population.2 This has nearly doubled from \n4277 cases diagnosed per year in 1982.2 The 5- year \nsurvival rate from all cancers has also improved in \nboth the paediatric and young adult populations aged \n0\u2013 19 years (75.5% survival in 1988 v 86.1% in 2017) and \nin the adult population aged 20\u2013 39 years (78.7% in 1988 \nv 88.6% in 2017).2\nCurrently, fertility preservation care is often \nunderimplemented.3 The barriers to overcome include \nlimited models of care and uneven access due to cost, \nlow health literacy, and patient education.3 As the use \nof fertility preservation increases, further reporting \non outcomes data is required.1 In order to improve \nthe quality of care, data collection by national and \ninternational registries is vital to identify the short \nand long term outcomes of fertility preservation \ninterventions.1\nAs the Clinical Oncology Society of Australia (COSA)"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 639
encoding: FLOAT32
metadata:
{"title": "Australian Fertility Preservation Guidelines for People with Cancer 2022: Review and Recommendations", "chroma:document": "Fertility Preservation Taskforce, we have developed \nthe 2022 guidelines,4 with updates in management \nincluding:\n\u2022 oocyte and embryo cryopreservation;\n\u2022 ovarian tissue cryopreservation and \ntransplantation;\n\u2022 testicular sperm extraction; and\n\u2022 testicular tissue cryopreservation in pre- pubertal \nboys.\nThe interdisciplinary working group designed \nclinically focused questions on important aspects of \nfertility for patients with cancer to inform guideline \ndevelopment. The draft guidelines were released for \npublic consultation by professional societies and other \ninterest groups in Australia from 2 to 28 June 2021, \ninvolving stakeholder input from the public. Using \nthe National Health and Medical Research Council \nLevels of Evidence and grades for recommendations,5 \nwe made 26 evidence- based recommendations, with \nsix consensus statements and two practice points.6 The \nfull COSA guidelines for fertility preservation for people \nwith cancer can be accessed at www.cancer.org.au/clini \ncal-guide lines/ cancer-ferti lity-prese rvation.\nImpact of cancer on fertility and discussing risk \nand referrals\nFuture fertility and the opportunity to have a \nfamily are among the most important concerns of \npeople with cancer.3 There is a wide variation in \nthe awareness of health care professionals of the \nneed for timely fertility discussion with people \ndiagnosed with cancer.3 The treatment of cancer \nin premenopausal women of childbearing age is \nassociated with both decreased pregnancy and \nlive birth rates7 (Box\u00a01). Women who receive cancer \ntreatment may be more likely to have reduced ovarian \nreserve than those who have not undergone cancer \ntreatment.8 Furthermore, sperm quality is reduced \nin men previously treated for cancer compared with \nthe general population.9 Azoospermia may occur \nafter cancer treatment including chemotherapy and \nradiation.\nThe lack of knowledge of current fertility preservation \noptions is a barrier to this discussion. Optimising \neducation and training of health care providers and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 640
encoding: FLOAT32
metadata:
{"title": "Australian Fertility Preservation Guidelines for People with Cancer 2022: Review and Recommendations", "chroma:document": "implementing a formal oncofertility service reduces \nthe risk of patient decisional conflict and regret \nregarding fertility preservation options.10 Referral \nof patients with cancer to a fertility preservation \nspecialist does not always occur, despite being \nacknowledged internationally as an important part of \nearly cancer management3 (Box\u00a02).\nThe provision of a fertility preservation program \nwithin a multidisciplinary team is associated \nwith improved referral pathways and timely \nfertility preservation discussion and treatment if \nrequired,3,10 with guidance available from both the \nAustralasian Oncofertility Consortium Charter11 \nand the International Oncofertility Competency \nFramework.12 Fertility counselling and the \nopportunity for fertility preservation are both \nassociated with increased quality of life, including \nbetter physical, social and psychological health, and \nlower decisional regret. Studies evaluating decision \naids have shown reduced decisional conflict and \nimproved education in people with cancer and \nparents of patients with cancer.13\n1 University of \nMelbourne,  \nMelbourne, VIC. \n2 Royal Women\u2019s \nHospital, Melbourne, VIC. \n3 Clinical Oncology \nSociety of, Australia, \nSydney, NSW. \n4 Queensland University \nof Technology,  \nBrisbane, QLD. \n5 Peter MacCallum \nCancer Centre, \nMelbourne, VIC. \n6 Royal Hospital for \nWomen, Sydney, NSW. \n7 University of New \nSouth, Wales,  \nSydney, NSW. \nViolet Kieu1,2\nCatharyn Stern1,2\nJessica Harris3\nYasmin Jayasinghe1,2\nNatalie Bradford4\nWanyuan Cui5\nRebecca Deans6,7\nTamara Hunter8\nCatherine Allingham9\nStefan C Kane1,2\nLei Shong Lau7\nShanna Logan7\nRobert McLachlan10\nKristen Neville4,7\nMichelle Peate1,2\nMarianne Phillips11\nCarla Saunders12\nMarianne Tome13\nRita Upreti10,14\nKate White15\nAntoinette \nAnazodo16,17\nRoger J Hart8,18"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 641
encoding: FLOAT32
metadata:
{"title": "Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study", "chroma:document": "Citation: Romney, C.E.; Arroyo, A.C.;\nRobles, T.F.; Zawadzki, M.J. Hugs\nand Cortisol Awakening Response\nthe Next Day: An Ecological\nMomentary Assessment Study. Int. J.\nEnviron. Res. Public Health 2023, 20,\n5340. https://doi.org/10.3390/\nijerph20075340\nAcademic Editor: Paul B. Tchounwou\nReceived: 1 February 2023\nRevised: 14 March 2023\nAccepted: 16 March 2023\nPublished: 30 March 2023\nCopyright:\n\u00a9 2023 by the authors.\nLicensee MDPI, Basel, Switzerland.\nThis article is an open access article\ndistributed\nunder\nthe\nterms\nand\nconditions of the Creative Commons\nAttribution (CC BY) license (https://\ncreativecommons.org/licenses/by/\n4.0/).\nInternational  Journal  of\nEnvironmental Research\nand Public Health\nArticle\nHugs and Cortisol Awakening Response the Next Day:\nAn Ecological Momentary Assessment Study\nChelsea E. Romney 1,*\n, Amber Carmen Arroyo 2, Theodore F. Robles 3 and Matthew J. Zawadzki 2\n1\nDepartment of Psychology, Brigham Young University, Provo, UT 84602, USA\n2\nDepartment of Psychological Sciences, University of California Merced, Merced, CA 95343, USA\n3\nDepartment of Psychology, University of California Los Angeles, Los Angeles, CA 90095, USA\n*\nCorrespondence: chelsea_romney@byu.edu; Tel.: +1-801-422-3280\nAbstract: Previous research suggests that affectionate touch such as hugs might downregulate stress\nsystems such as the hypothalamic pituitary adrenal (HPA) axis. However, the current literature lacks\nin generalizability beyond the laboratory setting and outside the context of romantic relationships.\nThe cortisol awakening response (CAR) is a measure of the HPA axis and is responsive to daily\n\ufb02uctuations in stress and social information. However, associations between affectionate touch and\nthe CAR have never been assessed. This study used ecological momentary assessment (EMA) to\nmeasure daily hugging behaviors in 104 \ufb01rst-year college students and salivary cortisol to assess\nthe CAR. Participants who reported more daily hugs in their social interactions had signi\ufb01cantly"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 642
encoding: FLOAT32
metadata:
{"title": "Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study", "chroma:document": "smaller CARs the next morning compared to days they reported fewer hugs. This study contributes\nto the literature on social interactions and stress responsive systems and emphasizes the importance\nof assessing affectionate touch behaviors such as hugs that can be exchanged outside the context of\nromantic relationships.\nKeywords: cortisol awakening response; affectionate touch; hugging; ecological momentary assessment\n1. Introduction\nAffectionate touch such as hugs can be used in social settings to communicate greetings,\nexcitement, support, and friendship. From Harry Harlow\u2019s (1965) seminal work with\nrhesus monkeys, we know that a lack of contact comfort may result in major issues with\npsychological and physical development [1]. In the recent context of social distancing in\nresponse to the COVID-19 pandemic, the study of in-person affectionate touch is timely,\nespecially as many of us are re-entering the social space and deciding whether it is safe to\nengage in affectionate touch behaviors.\nAffectionate touch is physical touch interactions that are intended to demonstrate\npositivity toward another person (e.g., love, care, fondness, and appreciation) [2]. Jakubiak\nand Feeney (2016) posit a model in which affectionate touch is processed through relational\u2013\ncognitive and neurobiological pathways to impact relational, psychological, and physical\nwell-being [3]. They assert that stress responses are in\ufb02uenced by affectionate touch receipt.\nLaboratory research suggests that affectionate touch may blunt the hypothalamic\u2013pituitary\u2013\nadrenal (HPA) axis response to stress that produces the hormone cortisol. In a study\nof couples in the laboratory, women who received affectionate touch through neck and\nshoulder massage before a stressor had signi\ufb01cantly lower cortisol and other physiological\nstress responses, such as heart rate, to the Trier Social Stress Test (TSST), compared to\nwomen who received verbal social support or no social interaction with their partner [4]."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 643
encoding: FLOAT32
metadata:
{"title": "Hugs and Cortisol Awakening Response the Next Day: An Ecological Momentary Assessment Study", "chroma:document": "In another TSST study in couples, both men and women had lower physiological stress\nresponse markers (i.e., lower cardiovascular reactivity) when they had a 10 min period\nof handholding and a 20 s hug before the stressor, compared to people who received no\npartner interaction [5].\nInt. J. Environ. Res. Public Health 2023, 20, 5340. https://doi.org/10.3390/ijerph20075340\nhttps://www.mdpi.com/journal/ijerph"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 644
encoding: FLOAT32
metadata:
{"title": "Cell Phone Radiation Exposure Limits and Engineering Solutions", "chroma:document": "Citation: H\u00e9roux, P.; Belyaev, I.;\nChamberlin, K.; Dasdag, S.; De Salles,\nA.A.A.; Rodriguez, C.E.F.; Hardell, L.;\nKelley, E.; Kesari, K.K.;\nMallery-Blythe, E.; et al. Cell Phone\nRadiation Exposure Limits and\nEngineering Solutions. Int. J. Environ.\nRes. Public Health 2023, 20, 5398.\nhttps://doi.org/10.3390/\nijerph20075398\nAcademic Editors: Daniela Varrica\nand Lingxin Chen\nReceived: 20 January 2023\nRevised: 17 March 2023\nAccepted: 31 March 2023\nPublished: 4 April 2023\nCopyright:\n\u00a9 2023 by the authors.\nLicensee MDPI, Basel, Switzerland.\nThis article is an open access article\ndistributed\nunder\nthe\nterms\nand\nconditions of the Creative Commons\nAttribution (CC BY) license (https://\ncreativecommons.org/licenses/by/\n4.0/).\nInternational  Journal  of\nEnvironmental Research\nand Public Health\nReview\nCell Phone Radiation Exposure Limits and Engineering Solutions\nPaul H\u00e9roux 1,*\n, Igor Belyaev 2\n, Kent Chamberlin 3, Suleyman Dasdag 4\n, Alvaro Augusto Almeida De Salles 5,\nClaudio Enrique Fernandez Rodriguez 6\n, Lennart Hardell 7,8\n, Elizabeth Kelley 9, Kavindra Kumar Kesari 10\n,\nErica Mallery-Blythe 11,12,13, Ronald L. Melnick 14,15, Anthony B. Miller 16, Joel M. Moskowitz 17\nand on behalf of\nthe International Commission on the Biological Effects of Electromagnetic Fields (ICBE-EMF) \u2020\n1\nDepartment of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University,\nMontreal, QC H3A 1G1, Canada\n2\nCancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences,\n814 38 Bratislava, Slovakia\n3\nDepartment of Electrical and Computer Engineering, University of New Hampshire, Durham, NH 03824, USA\n4\nBiophysics Department, Medical School, Istanbul Medeniyet University, Istanbul 34700, Turkey\n5\nGraduate Program on Electrical Engineering (PPGEE), Federal University of Rio Grande do Sul (UFRGS),\nPorto Alegre 90010-150, Brazil\n6\nDivision of Electrical and Electronics Engineering, Federal Institute of Rio Grande do Sul (IFRS),\nCanoas 92412-240, Brazil\n7"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 645
encoding: FLOAT32
metadata:
{"title": "Cell Phone Radiation Exposure Limits and Engineering Solutions", "chroma:document": "7\nDepartment of Oncology, Orebro University Hospital, 701 85 Orebro, Sweden (Retired)\n8\nThe Environment and Cancer Research Foundation, 702 17 Orebro, Sweden\n9\nICBE-EMF and International EMF Scientist Appeal, and Electromagnetic Safety Alliance, Tempe, AZ 85282, USA\n10\nDepartment of Applied Physics, School of Science, Aalto University, 02150 Espoo, Finland\n11\nPhysicians\u2019 Health Initiative for Radiation and Environment, East Sussex TN6, UK\n12\nBritish Society of Ecological Medicine, London W1W 6DB, UK\n13\nOceania Radiofrequency Scienti\ufb01c Advisory Association, Scarborough, QLD 4020, Australia\n14\nNational Toxicology Program (Retired), National Institute of Environmental Health Sciences,\nResearch Triangle Park, Durham, NC 27709, USA\n15\nRon Melnick Consulting LLC, North Logan, UT 84341, USA\n16\nDalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada\n17\nSchool of Public Health, University of California, Berkeley, CA 94704, USA\n*\nCorrespondence: paul.heroux@mcgill.ca; Tel.: +1-514-767-5556\n\u2020\nMembership of the Working Group is provided in the Acknowledgments.\nAbstract: In the 1990s, the Institute of Electrical and Electronics Engineers (IEEE) restricted its risk\nassessment for human exposure to radiofrequency radiation (RFR) in seven ways: (1) Inappropriate\nfocus on heat, ignoring sub-thermal effects. (2) Reliance on exposure experiments performed over\nvery short times. (3) Overlooking time/amplitude characteristics of RFR signals. (4) Ignoring\ncarcinogenicity, hypersensitivity, and other health conditions connected with RFR. (5) Measuring\ncellphone Speci\ufb01c Absorption Rates (SAR) at arbitrary distances from the head. (6) Averaging SAR\ndoses at volumetric/mass scales irrelevant to health. (7) Using unrealistic simulations for cell phone\nSAR estimations. Low-cost software and hardware modi\ufb01cations are proposed here for cellular phone\nRFR exposure mitigation: (1) inhibiting RFR emissions in contact with the body, (2) use of antenna"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 646
encoding: FLOAT32
metadata:
{"title": "Cell Phone Radiation Exposure Limits and Engineering Solutions", "chroma:document": "patterns reducing the Percent of Power absorbed in the Head (PPHead) and body and increasing the\nPercent of Power Radiated for communications (PPR), and (3) automated protocol-based reductions of\nthe number of RFR emissions, their duration, or integrated dose. These inexpensive measures do not\nfundamentally alter cell phone functions or communications quality. A health threat is scienti\ufb01cally\ndocumented at many levels and acknowledged by industries. Yet mitigation of RFR exposures to\nusers does not appear as a priority with most cell phone manufacturers.\nKeywords: cellular phone; SAR; cancer; electromagnetic hypersensitivity; radiofrequency radiation;\nantennas\nInt. J. Environ. Res. Public Health 2023, 20, 5398. https://doi.org/10.3390/ijerph20075398\nhttps://www.mdpi.com/journal/ijerph"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 647
encoding: FLOAT32
metadata:
{"title": "Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers", "chroma:document": "Systemic inflammation enhances stimulant-induced striatal \ndopamine elevation in tobacco smokers\nYasmin Zakiniaeiza,b,1,*, Jocelyn Hoyeb,c,1, Joseph Ryan Petrullib,c, Brittany LeVasseura, \nGelsina Stanleyb,c, Hong Gaob,c, Soheila Najafzadehb,c, Jim Ropchanb,c, Nabeel Nabulsib,c, \nYiyun Huangb,c, Ming-Kai Chenb,c, David Matuskeya,b,c, Daniel S. Barrona,d,e, Benjamin \nKelmendia, Robert K. Fulbrightc, Michelle Hampsona,c,f, Kelly P. Cosgrovea,b, Evan D. \nMorrisa,b,c,d\naDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA\nbYale Positron Emission Tomography (PET) Center, Yale School of Medicine, New Haven, CT, \nUSA\ncDepartment of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, \nUSA\ndDepartment of Psychiatry, Brigham & Women\u2019s Hospital, Boston, MA, USA\neDepartment of Anesthesiology, Perioperative, and Pain Medicine, Brigham & Women\u2019s Hospital, \nBoston, MA, USA\nfDepartment of Biomedical Engineering, Yale School of Medicine, New Haven, CT, USA\nAbstract\nImmune-brain interactions influence the pathophysiology of addiction. Lipopolysaccharide \n(LPS)-induced systemic inflammation produces effects on reward-related brain regions and the \ndopamine system. We previously showed that LPS amplifies dopamine elevation induced by \nmethylphenidate (MP), compared to placebo (PBO), in eight healthy controls. However, the effects \nof LPS on the dopamine system of tobacco smokers have not been explored. The goal of Study \n1 was to replicate previous findings in an independent cohort of tobacco smokers. The goal \nof Study 2 was to combine tobacco smokers with the aforementioned eight healthy controls to \nexamine the effect of LPS on dopamine elevation in a heterogenous sample for power and effect \nsize determination. Eight smokers were each scanned with [11C]raclopride positron emission \ntomography three times\u2014at baseline, after administration of LPS (0.8 ng/kg, intravenously) and \nMP (40 mg, orally), and after administration of PBO and MP, in a double-blind, randomized"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 648
encoding: FLOAT32
metadata:
{"title": "Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers", "chroma:document": "order. Dopamine elevation was quantified as change in [11C]raclopride binding potential (\u0394BPND) \nThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).\n*Corresponding author at: 40 Temple Street, Suite 7C, New Haven, CT 06511, USA. yasmin.zakiniaeiz@yale.edu (Y. Zakiniaeiz).\n1These authors contributed equally to this work.\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.bbi.2022.08.016.\nHHS Public Access\nAuthor manuscript\nBrain Behav Immun. Author manuscript; available in PMC 2023 April 12.\nPublished in final edited form as:\nBrain Behav Immun. 2022 November ; 106: 262\u2013269. doi:10.1016/j.bbi.2022.08.016.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 649
encoding: FLOAT32
metadata:
{"title": "Hemiataxia and crural hemiparesis following capsular infarct", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983 ;46:561-563\nShort report\nHemiataxia and crural hemiparesis following\ncapsular infarct\nE DE RENZI,* P NICHELLI,* G CRISIt\nFrom Clinica Neurologica* and Istituto di Radiologiat Universita di Modena, Modena, Italy\nSUMMARY Two patients presenting with hemiataxia and hemiparesis on the same side are\ndescribed. Both had cr scan evidence of an infarct located in the posterior limb of the con-\ntralateral internal capsule.\nThe association of cerebellar ataxia and pyramidal\nsigns involving the limbs of the same side was first\ndescribed by Fisher and Cole' in 1965, who tenta-\ntively located the lesion in the posterior limb of the\ninternal capsule. Subsequently ataxic hemiparesis\nhas been reported in six patients with lesion in the\nbasis pontis contralateral to the involved limb,25 in\na patient with a ventrolateral midbrain lesion6 and in\nthree patients showing CT scan evidence of an\ninfarct of the posterior limb of the internal cap-\nsule.7-9 We report two more cases of ataxia and\nhomolateral crural paresis. In both patients a lesion\nlocated in the posterior limb of the internal capsule\nwas identified on the CT scan.\nCase I\nA 45-year-old man was admitted to the wards after the\nsudden onset of a right hemiparesis. On neurological\nexamination he was alert and oriented. Speech and cranial\nnerves were normal. There was slight right-sided weakness\nof the peroneal muscles with minimal weakness of the\nextensor muscles of the right arm. Tendon reflexes on the\nright were slightly brisker than those on the left and the\nright plantar response was extensor. On standing with the\nfeet together the patient fell to the right. There was a\nsevere dysmetria on both finger-to-nose and heel-to-knee\ntests. Rapid alternating movements were slow and clumsy\non the right side. Sensory functions and visual fields were\nnormal. Weakness and ataxia increased in a step-wise fash-\nion in the next two days. Weakness was greater in the\nproximal muscles of the upper limb and in the distal mus-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 650
encoding: FLOAT32
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{"title": "Hemiataxia and crural hemiparesis following capsular infarct", "chroma:document": "cles of the lower limb. At the end of the fourth week of\nillness the right arm had completely recovered its strength,\nAddress\nfor\nreprint\nrequests:\nDr\nEnnio De\nRenzi,\nClinica\nNeurologica Via del Pozzo 71, 41100 Modena, Italy.\nReceived 21 October 1982 and in revised form 9 January 1983.\nAccepted 1 February 1983\nbut both upper and lower right extremities were still dys-\nmetric and the right lower limb was still moderately weak\nparticularly in the hamstrings and peroneal muscles. Four\nand a half months after the onset of disease, ataxia per-\nsisted with only minimal improvement, while weakness of\nthe left hamstrings had almost completely recovered.\nCT scan one day after admission revealed\na small\ndecreased density area in the left posterior limb of the\ninternal capsule with possible involvement of the adjacent\nthalamus. One month after the onset of illness CT scan\n(Fig la) showed a clear-cut hypodensity area in the two\nmiddle quarters of the posterior limb of the left internal\ncapsule. The lesion extended upward from a midthalamic\nto a high thalamic level, but spared the corona radiata and\nthat most superior part of internal capsule which\nis\nimmediately adjacent to corona radiata.\nCase 2\nA 55-year-old man, with a long history of hypertension\nand diabetes, suddenly noticed dragging of his left leg and\nloss of motor power and tingling of his left arm. On admis-\nsion the patient was alert and fully oriented. Visual fields\nwere intact. There was moderate left central facial weak-\nness and a gross left hemiparesis which in the upper limb,\nmainly affected the proximal muscles. Tendon reflexes\nwere slightly brisker on the left side. The left plantar\nresponse was extensor. Light touch and joint position sense\nwere slightly impaired on the left. At that time tests of\ncoordination could not be carried out, because of the\nsevere motor weakness. Computed tomography revealed a\nlow density area occupying a great part of the posterior\nlimb of the internal capsule with involvement of the most"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 651
encoding: FLOAT32
metadata:
{"title": "Hemiataxia and crural hemiparesis following capsular infarct", "chroma:document": "lateral part of the thalamus. The corona radiata also was\ninvolved (Fig lb). The patient's paralysis began to improve\nafter two weeks, and after a month the muscle power of\narm and forearm flexors and extensors had recovered to\nthe point of permitting finger-to-nose and finger-to-finger\ntesting. The latter manoeuvre was carried out holding the\nexaminer's thumb at the same horizontal level as the\npatient's hand, so that no movement of the shoulder mus-\ncles, which were still weak, was required. These tests dis-\n561"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 652
encoding: FLOAT32
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{"title": "Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status", "chroma:document": "https://doi.org/10.1093/brain/awac436\nBRAIN 2023: 146; 1243\u20131266 | 1243\nQuantitative myelin imaging with MRI \nand PET: an overview of techniques  \nand their validation status\nChris W. J. van der Weijden,1 \nEmma Biondetti,2 Ingomar W. Gutmann,3 \nHildebrand Dijkstra,4 Rory McKerchar,5 \nDaniele de Paula Faria,6 Erik F. J. de Vries,1 \nJan F. Meilof,7,8 Rudi A. J. O. Dierckx,1 Valentin H. Prevost9 and \nAlexander Rauscher5\nMyelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between the \nwraps. The measurement of damage to the myelin sheaths, the evaluation of the efficacy of therapies aiming to pro-\nmote remyelination and monitoring the degree of brain maturation in children all require non-invasive quantitative \nmyelin imaging methods. To date, various myelin imaging techniques have been developed. Five different MRI ap-\nproaches can be distinguished based on their biophysical principles: (i) imaging of the water between the lipid bi-\nlayers directly (e.g. myelin water imaging); (ii) imaging the non-aqueous protons of the phospholipid bilayer \ndirectly with ultra-short echo-time techniques; (iii) indirect imaging of the macromolecular content (e.g. magnetiza-\ntion transfer; inhomogeneous magnetization transfer); (iv) mapping of the effects of the myelin sheath\u2019s magnetic \nsusceptibility on the MRI signal (e.g. quantitative susceptibility mapping); and (v) mapping of the effects of the myelin \nsheath on water diffusion. Myelin imaging with PET uses radioactive molecules with high affinity to specific myelin \ncomponents, in particular myelin basic protein. This review aims to give an overview of the various myelin imaging \ntechniques, their biophysical principles, image acquisition, data analysis and their validation status.\n1\nDepartment of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center \nGroningen, 9713 GZ Groningen, The Netherlands\n2"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 653
encoding: FLOAT32
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{"title": "Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status", "chroma:document": "2\nDepartment of Neuroscience, Imaging, and Clinical Sciences, Institute for Advanced Biomedical Technologies, \u2018G. \nd\u2019Annunzio\u2019 University of Chieti-Pescara, 66100 Chieti, Italy\n3\nFaculty of Physics, University of Vienna, 1090 Vienna, Austria\n4\nDepartment of Radiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The \nNetherlands\n5\nDepartment of Pediatrics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada\n6\nDepartment of Radiology and Oncology, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo 05403- \n911, Brazil\n7\nDepartment of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center \nGroningen, 9713 GZ Groningen, The Netherlands\n8\nDepartment of Neurology, Martini Ziekenhuis, 9728 NT Groningen, The Netherlands\n9\nCT-MR Planning division department, Canon Medical Systems Corporation, Tochigi 324-8550, Japan\nCorrespondence to: Chris W. J. van der Weijden  \nDepartment of Nuclear Medicine and Molecular Imaging, UMCG  \nHanzeplein 1, 9713 GZ Groningen  \nThe Netherlands  \nE-mail: c.w.j.van.der.weijden@umcg.nl\nReceived June 10, 2022. Revised September 30, 2022. Accepted November 07, 2022. Advance access publication November 21, 2022\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by- \nnc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, \nplease contact journals.permissions@oup.com"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 654
encoding: FLOAT32
metadata:
{"title": "Correction: Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques", "chroma:document": "CORRECTION\nCorrection: Mitigation of endemic GI-tract\npathogen-mediated inflammation through\ndevelopment of multimodal treatment\nregimen and its impact on SIV acquisition in\nrhesus macaques\nRachele M. Bochart, Kathleen Busman-Sahay, Stephen Bondoc, David W. Morrow,\nAlexandra M. Ortiz, Christine M. Fennessey, Miranda B. Fischer, Oriene Shiel,\nTonya Swanson, Christine M. Shriver-Munsch, Hugh B. Crank, Kimberly M. Armantrout,\nAaron M. Barber-Axthelm, Charlotte Langner, Cassandra R. Moats, Caralyn S. Labriola,\nRhonda MacAllister, Michael K. Axthelm, Jason M. Brenchley, Brandon F. Keele, Jacob\nD. Estes, Scott G. Hansen, Jeremy V. Smedley\nThe published article [1] presents data from two separate animal studies. The first study con-\nducted at the National Cancer Institute (NCI) comprised an 18-rhesus macaque (RM) intrar-\nectal dose titration experiment to determine appropriate dosing of SIVmac239X for use in\nviral transmission/early necropsy studies. This notice addresses errors in the methodological\ndescription for the initial NCI study: in these animals, the authors did not assess gastrointesti-\nnal pathogens, microbiome, immunology, or mucosal barrier integrity, and the handling and\ntreatment of the animals differed from that employed in the subsequent study conducted at\nOregon National Primate Research Center (ONPRC). The originally published Materials and\nMethods section incorrectly reported some similarities between the animal handling and treat-\nment regimens used in the two studies. This Correction provides amended methodological\ninformation, including that the multimodal therapeutic regimen for the NCI study included\nonly metronidazole and fenbendazole, while the regimen for the ONPRC study included enro-\nfloxacin, paromomycin, fenbendazole, and azithromycin.\nInitial dose titration study at NCI\nThe terms \u201cproof of concept study\u201d and \u201cproof of concept animals\u201d are inaccurate and are\nreplaced in all instances with \u201cinitial dose titration study at NCI\u201d and \u201cinitial NCI dose titra-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 655
encoding: FLOAT32
metadata:
{"title": "Correction: Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques", "chroma:document": "tion study animals\u201d, respectively.\nIn the Materials and Methods section originally titled Proof of concept study assessing the\nimpact of the multimodal treatment regimen on acquisition of SIVmac239X, the correct text is\nas follows:\nInitial dose titration study at NCI assessing the impact of the multimodal treatment regi-\nmen on acquisition of SIVmac239X\nA total of 18 male Indian-origin rhesus macaques between 2.6 and 13.4 years of age were\nused in accordance with the policies of the Animal Care and Use Committee at the NCI, an\nAAALAC-accredited institution, which abides by the USDA Animal Welfare Regulations [38]\nand the Guide for the Care and Use of Laboratory Animals [37]. Animals were singly housed\nin accordance with the IACUC-approved protocol and facility practices for the NIH facilities\nwhere the work was conducted (NIH main campus, Bethesda, MD or NIH Animal Center,\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011343\nApril 19, 2023\n1 / 6\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Bochart RM, Busman-Sahay K, Bondoc S,\nMorrow DW, Ortiz AM, Fennessey CM, et al. (2023)\nCorrection: Mitigation of endemic GI-tract\npathogen-mediated inflammation through\ndevelopment of multimodal treatment regimen and\nits impact on SIV acquisition in rhesus macaques.\nPLoS Pathog 19(4): e1011343. https://doi.org/\n10.1371/journal.ppat.1011343\nPublished: April 19, 2023\nCopyright: \u00a9 2023 Bochart 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."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 656
encoding: FLOAT32
metadata:
{"title": "Research in brief", "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: 657
encoding: FLOAT32
metadata:
{"title": "Human monkeypox infection threat: A comprehensive overview", "chroma:document": "REVIEW\nHuman monkeypox infection threat: A\ncomprehensive overview\nYue Kang1, Yue Yu2, Silu XuID3*\n1 College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China, 2 School of\nPharmacy, Fujian Medical University, Fuzhou, Fujian China, 3 Department of Pharmacy, Jiangsu Cancer\nHospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical\nUniversity, Nanjing, Jiangsu, China\n* jsszlyy_xusilu@sina.com\nAbstract\nBackground\nAU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly:\nIn addition to the COVID-19 waves, the globe is recently facing global monkeypox (MPX)\noutbreak. As the daily confirmed cases of MPX infection across epidemic and nonepidemic\ncountries are increasing, taking measures to control global pandemic remains crucial.\nTherefore, this review aimed to provide fundamental knowledge for the prevention and con-\ntrol of future outbreaks of this emerging epidemic.\nMethods\nThe review was conducted using PubMed and Google Scholar databases; the search terms\nused were \u201cmonkeypox,\u201d \u201cMPX tropism,\u201d \u201creplication signaling of MPX,\u201d \u201cbiology and patho-\ngenicity of MPX,\u201d \u201cdiagnosis of MPX,\u201d \u201ctreatment of MPX,\u201d \u201cprevention of MPX,\u201d etc. The\nupdate epidemic data were collected from the websites of the World Health Organization\n(WHO), United States Centers for Disease Control and Prevention (CDC), and Africa Center\nfor Disease Control and Prevention (ADCC). High-quality research results published in\nauthoritative journals were summarized and preferred cited. Excluding all duplicates, non-\nEnglish published references, and irrelevant literature, totally 1,436 articles were assessed\nfor eligibility.\nResults\nIt is still difficult to diagnose the patient as MPX simply based on clinical manifestations;\ntherefore, under this situation, employing polymerase chain reaction (PCR) technology to\nprovide confirmed evidence for the diagnosis of MPX seems to be the preferred and indis-\npensable strategy. The treatment approach for MPX infection is mainly symptomatic and"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 658
encoding: FLOAT32
metadata:
{"title": "Human monkeypox infection threat: A comprehensive overview", "chroma:document": "supportive; anti-smallpox virus drugs including tecovirimat, cidofovir, and brincidofovir can\nbe employed in severe cases. Timely identification and isolation of confirmed cases, cutting\noff dissemination routes, and vaccination of close contacts are effective measures to control\nMPX. Also, smallpox vaccines (JYNNEOS, LC16m8, and ACAM2000) can be under consid-\neration due to their immunological cross-protection among Orthopoxvirus. NeverthelessAU : Pleasech\n,\ngiven the low quality and scarcity of relevant evidence of current antiviral drugs and\nPLOS NEGLECTED TROPICAL DISEASES\nPLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011246\nApril 20, 2023\n1 / 22\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Kang Y, Yu Y, Xu S (2023) Human\nmonkeypox infection threat: A comprehensive\noverview. PLoS Negl Trop Dis 17(4): e0011246.\nhttps://doi.org/10.1371/journal.pntd.0011246\nEditor: Zvi Bentwich, Ben-Gurion University of the\nNegev, ISRAEL\nPublished: April 20, 2023\nCopyright: \u00a9 2023 Kang 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.\nFunding: The author(s) received no specific\nfunding for this work.\nCompeting interests: The authors disclose no\nconflict of interest."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 659
encoding: FLOAT32
metadata:
{"title": "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions", "chroma:document": "REVIEW ARTICLE\nOPEN\nSignaling pathways in vascular function and hypertension:\nmolecular mechanisms and therapeutic interventions\nJun Ma\n1, Yanan Li1, Xiangyu Yang1, Kai Liu1, Xin Zhang1, Xianghao Zuo1, Runyu Ye1, Ziqiong Wang1, Rufeng Shi1,\nQingtao Meng1\u2709 and Xiaoping Chen1\u2709\nHypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of\nresearch, hypertension remains dif\ufb01cult to cure due to its complex mechanisms involving multiple interactive factors and our\nlimited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that\naffects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of\nblood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators re\ufb02ecting vascular function. Blood vessels are\ncomposed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main\nperformers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying\nvascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways\ninvolved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway,\nvarious vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system,\noxidative stress-related signaling pathway, immunity/in\ufb02ammation pathway, etc. Meanwhile, we will also summarize the treatment\nmethods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being\napplied to clinical work.\nSignal Transduction and Targeted Therapy  (2023) 8:168 \n; https://doi.org/10.1038/s41392-023-01430-7\nINTRODUCTION\nHypertension represents a signi\ufb01cant risk factor for cardiovascular"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 660
encoding: FLOAT32
metadata:
{"title": "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions", "chroma:document": "and cerebrovascular diseases (CVDs) and remains the primary\ncause of premature mortality on a global scale.1 The estimated\nnumber\nof\npeople\naged\n30\u201379-year-old\nwith\nhypertension\ndoubled from 648 million in 1990 to 1.27 billion in 2019.2 The\nprevention and control of hypertension represent a crucial global\npublic health strategy in the effort to reduce premature mortality\nfrom CVDs.3\nBlood pressure (BP) is de\ufb01ned as the lateral pressure exerted on\nthe walls of blood vessels per unit area during the \ufb02ow of blood.\nHypertension is characterized by an increase in systolic BP and/or\ndiastolic BP. There are two primary factors that directly affect BP:\nthe volume of intravascular \ufb02uid and the capacity for vasodilation.\nThe amount of \ufb02uid in the blood vessels is mainly related to the\neveryday intake and output volume. Vasodilatation is the basic\nfunction of blood vessels.4 The capacity for vasodilation is\nin\ufb02uenced by vascular elasticity, caliber, and reactivity. Poorer\nthe vasodilatation capacity, higher the BP. The disturbance of\nvascular contraction and/or relaxation function exerts a great\nin\ufb02uence on the onset and progression of hypertension. As\nvasodilatation capacity plays a crucial role in regulating BP, it has\ngarnered signi\ufb01cant attention in the \ufb01eld of vascular biology\nresearch.5\nChanges in signaling pathways in vascular endothelial cells\n(ECs) and vascular smooth muscle cells (VSMCs) are key molecular\nmechanisms which trigger vascular dysfunction and promote the\ndevelopment of hypertension. Here, we reviewed all key signaling\npathways in vascular function and hypertension, as well as their\ntreatment application value in clinical settings.\nVASCULAR STRUCTURE AND FUNCTIONS OF EACH LAYER\nBlood vessels are composed of three distinct layers, including\nintima, media, and adventitia (Fig. 1). The intima is mainly\ncomposed of ECs, which organize themselves into a continuous\nmonolayer, allowing blood perfusion. On their surface, ECs form a\nsurrounding extracellular matrix (ECM) known as the glycocalyx,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 661
encoding: FLOAT32
metadata:
{"title": "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions", "chroma:document": "which extends beyond the cell surface into the vascular lumen.\nThis structure plays a crucial role in providing a barrier function for\nECs, preventing the transmural migration of leukocytes and\nplatelet adhesion.6,7 Intima is the \u201csensor\u201d of vessels, as it can\nsense various stimuli (such as \ufb02uid shear force, cytokines, etc.) in\nthe blood and actively control the degree of vascular relaxation\nand contraction. This active regulation is mainly achieved through\nthe secretion of various mediators from ECs.8 ECs serve not only as\na barrier-forming cell population, acting as a responsive interface,\nbut also actively regulate their microenvironment, serving as\ngatekeepers of organ development, homeostasis, and tissue\nregeneration.9 ECs dysfunction has been regarded as a pivotal\nmechanism in early pathogenesis of hypertension.10 Generalized\nde\ufb01nition of ECs function or endothelial function involves barrier,\nReceived: 9 November 2022 Revised: 3 March 2023 Accepted: 31 March 2023\n1Department of Cardiology, West China Hospital, Sichuan University, No. 37, Guo Xue District, Chengdu, Sichuan 610041, People\u2019s Republic of China\nCorrespondence: Qingtao Meng (mengqingtao9@163.com) or Xiaoping Chen (xiaopingchen23@163.com)\nThese authors contributed equally: Jun Ma, Yanan Li, Xiangyu Yang\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: 662
encoding: FLOAT32
metadata:
{"title": "PET imaging of animal models with depressive-like phenotypes", "chroma:document": "https://doi.org/10.1007/s00259-022-06073-4\nREVIEW ARTICLE\nPET imaging of\u00a0animal models with\u00a0depressive\u2011like phenotypes\nDaniel\u00a0Aaron\u00a0Vazquez\u2011Matias \u00a0\u00b7 Erik\u00a0F.\u00a0J.\u00a0de\u00a0Vries \u00a0\u00b7 Rudi\u00a0A.\u00a0J.\u00a0O.\u00a0Dierckx \u00a0\u00b7 Janine\u00a0Doorduin\n1\n1\n1\n1 \nReceived: 8 July 2022 / Accepted: 3 December 2022 \n\u00a9 The Author(s) 2023\nAbstract\nMajor depressive disorder is a growing and poorly understood pathology. Due to technical and ethical limitations, a significant \nproportion of the research on depressive disorders cannot be performed on patients, but needs to be investigated in animal \nparadigms. Over the years, animal studies have provided new insight in the mechanisms underlying depression. Several of \nthese studies have used PET imaging for the non-invasive and longitudinal investigation of the brain physiology. This review \nsummarises the findings of preclinical PET imaging in different experimental paradigms of depression and compares these \nfindings with observations from human studies. Preclinical PET studies in animal models of depression can be divided into \nthree main different approaches: (a) investigation of glucose metabolism as a biomarker for regional and network involve-\nment, (b) evaluation of the availability of different neuroreceptor populations associated with depressive phenotypes, and \n(c) monitoring of the inflammatory response in phenotypes of depression. This review also assesses the relevance of the use \nof PET imaging techniques in animal paradigms for the understanding of specific aspects of the depressive-like phenotypes, \nin particular whether it might contribute to achieve a more detailed characterisation of the clinical depressive phenotypes \nfor the development of new therapies for depression.\nKeywords Major depressive disorder\u00a0\u00b7 Depressive-like behaviour\u00a0\u00b7 Preclinical imaging\u00a0\u00b7 Neuroreceptor\u00a0\u00b7 PET\u00a0\u00b7 Animal \nmodels\nIntroduction\nMajor depressive disorder (MDD) is one of the most prev-\nalent psychiatric disorders worldwide [1]. It presents a \nclinical course characterised by a broad and heterogenous"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 663
encoding: FLOAT32
metadata:
{"title": "PET imaging of animal models with depressive-like phenotypes", "chroma:document": "constellation of symptoms, which may lead to harmful con-\nsequences, such as prolonged periods of disability, or even \nsuicidal behaviour. According to data from the World Health \nOrganisation (WHO), around 300 million people worldwide \nare affected by depression and it is predicted that this dis-\norder will become the first cause of incapacity in terms of \ndisability-adjusted life years (DALYs) by 2030 [1]. This lack \nof understanding entails a major challenge to both clinicians \nand fundamental researchers, and may hamper the selec-\ntion of effective therapeutic schemes, and slow down the \ndevelopment of new therapies. One of the most notorious \nexamples of these knowledge-gaps is the lack of reliable \ndiagnostic auxiliary tools to stage severity and monitor the \nclinical course of MDD in the managing protocols [2].\nCurrently, there are no reliable diagnostic biomarkers avail-\nable to stage patients with MDD or predict the outcome of \ntreatment [3]. Present MDD management protocols are largely \nbased on antidepressant drugs. The use of these antidepres-\nsants began as a serendipitous finding after these drugs were \nprescribed to patients with different illnesses, and improve-\nments in the affective state were found as a side effect [4, 5]. \nMMD standard treatment includes drugs like selective and \nnon-selective serotonin and norepinephrine reuptake inhibi-\ntors, which are used as first line of treatment. However, about \n50\u201370% of MDD patients experience incomplete remission of \nsymptoms after receiving standard antidepressant treatment \n[6\u20138]. In view of the high rates of treatment failure with stand-\nard antidepressant therapy, and the limited understanding of \nthe pathophysiology, it is necessary to fill the knowledge gaps \nregarding MDD in order to develop and prescribe more effec-\ntive treatments. New insights could be obtained from clinical \nstudies, but these studies are expensive, time-consuming and \nThis article is part of the Topical Collection on Preclinical Imaging.\n * Janine Doorduin"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 664
encoding: FLOAT32
metadata:
{"title": "PET imaging of animal models with depressive-like phenotypes", "chroma:document": "j.doorduin@umcg.nl\n1 \nDepartment of\u00a0Nuclear Medicine and\u00a0Molecular Imaging, \nUniversity Medical Centre Groningen, University \nof\u00a0Groningen, Groningen, the\u00a0Netherlands\nEuropean Journal of Nuclear Medicine and Molecular Imaging (2023) 50:1564\u20131584\n/ Published online: 16 January 2023\n1 3"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 665
encoding: FLOAT32
metadata:
{"title": "Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations", "chroma:document": "Vol:.(1234567890)\nNeurotherapeutics (2023) 20:140\u2013153\nhttps://doi.org/10.1007/s13311-023-01348-6\n1 3\nREVIEW\nPreclinical Interventions in\u00a0Mouse Models of\u00a0Frontotemporal \nDementia Due to\u00a0Progranulin Mutations\nShreya\u00a0N.\u00a0Kashyap1\u00a0\u00b7 Nicholas\u00a0R.\u00a0Boyle1\u00a0\u00b7 Erik\u00a0D.\u00a0Roberson1 \nAccepted: 20 January 2023 / Published online: 13 February 2023 \n\u00a9 The Author(s) 2023\nAbstract\nHeterozygous loss-of-function mutations in progranulin (GRN) cause frontotemporal dementia (FTD), a leading cause \nof early-onset dementia characterized clinically by behavioral, social, and language deficits. There are currently no FDA-\napproved therapeutics for FTD-GRN, but this has been an active area of investigation, and several approaches are now in \nclinical trials. Here, we review preclinical development of therapies for FTD-GRN with a focus on testing in mouse models. \nSince most FTD-GRN-associated mutations cause progranulin haploinsufficiency, these approaches focus on raising pro-\ngranulin levels. We begin by considering the disorders associated with altered progranulin levels, and then review the basics \nof progranulin biology including its lysosomal, neurotrophic, and immunomodulatory functions. We discuss mouse models \nof progranulin insufficiency and how they have been used in preclinical studies on a variety of therapeutic approaches. These \ninclude approaches to raise progranulin expression from the normal allele or facilitate progranulin production by the mutant \nallele, as well as approaches to directly increase progranulin levels by delivery across the blood\u2013brain barrier or by gene \ntherapy. Several of these approaches have entered clinical trials, providing hope that new therapies for FTD-GRN may be \nthe next frontier in the treatment of neurodegenerative disease.\nKeywords Frontotemporal dementia\u00a0\u00b7 Neurodegeneration\u00a0\u00b7 Progranulin\u00a0\u00b7 Haploinsufficiency\u00a0\u00b7 Lysosome\u00a0\u00b7 Gene therapy\nThe approval of the first amyloid immunotherapies by the \nUS Food and Drug Administration for patients with Alzhei-"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 666
encoding: FLOAT32
metadata:
{"title": "Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations", "chroma:document": "mer\u2019s disease, although not without controversy, marks the \nbeginning of a new era in the treatment of neurodegenera-\ntive dementias. Therapeutics targeting one of the primary \ndisease-associated molecules are now approved, and a neu-\nropathological hallmark of neurodegenerative dementia can \nbe substantially eliminated from the brains of those affected. \nFollowing aducanumab, lecanemab, and other amyloid \nimmunotherapies likely to follow, treatments targeting pro-\ngranulin for frontotemporal dementia (FTD) may be among \nthe next round of disease-modifying neurodegenerative dis-\nease therapeutics.\nOne advantage in the pursuit of progranulin-targeted \ntherapeutics is that, unlike amyloid-beta, tau, and other \nproteins associated with neurodegenerative diseases that \nhave gain-of-function effects, the mechanism of progran-\nulin-related disease is clearly loss-of-function. Thus, \nthe approach to progranulin therapeutics can focus on \nboosting levels of progranulin, which, while not trivial, \nis likely more straightforward than identifying specific \ndownstream gain-of-function effects along with strategies \nto selectively block them. Indeed, several progranulin-\ntargeting therapies have already entered clinical trials. \nSuch progress, of course, comes on the heels of rigorous \npreclinical studies, many of which have utilized mouse \nmodels.\nOur goal here is to review data from preclinical testing of \npotential treatments for progranulin-related FTD in mouse \nmodels. Before considering studies on specific therapeutic \napproaches, we begin with a review of the neurologic disor-\nders caused by progranulin insufficiency and other diseases \nassociated with progranulin, key features of progranulin \nbiology, and the currently available mouse models and out-\ncome measures used in preclinical studies on progranulin \ntherapeutics.\nShreya N. Kashyap and Nicholas R. Boyle are equal contributors.\n * Erik D. Roberson \n \neroberson@uabmc.edu\n1 \nCenter for\u00a0Neurodegeneration and\u00a0Experimental"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 667
encoding: FLOAT32
metadata:
{"title": "Preclinical Interventions in Mouse Models of Frontotemporal Dementia Due to Progranulin Mutations", "chroma:document": "Therapeutics, Alzheimer\u2019s Disease Center, Medical Scientist \nTraining Program, Department of\u00a0Neurology, University \nof\u00a0Alabama at\u00a0Birmingham, Birmingham, AL\u00a035294, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 668
encoding: FLOAT32
metadata:
{"title": "Animal Models of Childhood Exposure to Lead or Manganese: Evidence for Impaired Attention, Impulse Control, and Affect Regulation and Assessment of Potential Therapies", "chroma:document": "Vol.:(0123456789)\n1 3\nNeurotherapeutics (2023) 20:3\u201321 \nhttps://doi.org/10.1007/s13311-023-01345-9\nREVIEW\nAnimal Models of\u00a0Childhood Exposure to\u00a0Lead or\u00a0Manganese: \nEvidence for\u00a0Impaired Attention, Impulse Control, and\u00a0Affect \nRegulation and\u00a0Assessment of\u00a0Potential Therapies\nDonald R.\u00a0Smith1 \u00a0\u00b7 Barbara\u00a0J.\u00a0Strupp2\nAccepted: 18 January 2023 / Published online: 28 February 2023 \n\u00a9 The Author(s) 2023\nAbstract\nBehavioral disorders involving attention and impulse control dysfunction, such as ADHD, are among the most prevalent \ndisorders in children and adolescents, with significant impact on their lives. The etiology of these disorders is not well \nunderstood, but is recognized to be multifactorial, with studies reporting associations with polygenic and environmental \nrisk factors, including toxicant exposure. Environmental epidemiological studies, while good at establishing associations \nwith a variety of environmental and genetic risk factors, cannot establish causality. Animal models of behavioral disorders, \nwhen properly designed, can play an essential role in establishing causal relationships between environmental risk factors \nand a disorder, as well as provide model systems for elucidating underlying neural mechanisms and testing therapies. Here, \nwe review how animal model studies of developmental lead or manganese exposure have been pivotal in (1) establishing a \ncausal relationship between developmental exposure and lasting dysfunction in the\u00a0domains of attention, impulse control, \nand affect regulation, and (2) testing the efficacy of specific therapeutic approaches for alleviating the lasting deficits. The \nlead and manganese case studies illustrate how animal models can advance knowledge in ways that are not possible in human \nstudies. For example, in contrast to the Treatment of Lead Poisoned Children (TLC) human clinical trial evaluating succimer \nchelation efficacy to improve cognitive functioning in lead-exposed children, our developmental lead exposure animal model"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 669
encoding: FLOAT32
metadata:
{"title": "Animal Models of Childhood Exposure to Lead or Manganese: Evidence for Impaired Attention, Impulse Control, and Affect Regulation and Assessment of Potential Therapies", "chroma:document": "showed that succimer chelation can produce lasting cognitive benefits if chelation sufficiently reduces brain lead levels. In \naddition, this study revealed that succimer treatment in the absence of lead exposure produces lasting cognitive dysfunction, \nhighlighting potential risks of chelation in off-label uses, such as the treatment of autistic children without a history of lead \nexposure. Our animal model of developmental manganese exposure has demonstrated that manganese can cause lasting \nattentional and sensorimotor deficits, akin to an ADHD-inattentive behavioral phenotype, thereby providing insights into \nthe role of environmental exposures as contributors to ADHD. These studies have also shown that oral methylphenidate \n(Ritalin) can fully alleviate the deficits produced by early developmental Mn exposure. Future work should continue to focus \non the development and use of animal models that appropriately recapitulate the complex behavioral phenotypes of behav-\nioral disorders, in order to determine the mechanistic basis for the behavioral deficits caused by developmental exposure to \nenvironmental toxicants, and the efficacy of existing and emerging therapies.\nKeywords Attention deficit\u00a0\u00b7 ADHD\u00a0\u00b7 Neurotoxicity\u00a0\u00b7 Lead\u00a0\u00b7 Manganese\u00a0\u00b7 Animal model\nIntroduction\nBehavioral disorders, particularly those involving learn-\ning, attention, and impulse control, are among the most \nprevalent disorders in children [1]. While the etiologies of \nbehavioral disorders are often poorly understood, they are \ngenerally recognized to be multifactorial in nature, with \nepidemiological studies providing evidence for both genetic \nand environmental risk factors. For example, substantial evi-\ndence has emerged over the past several decades supporting \n * Donald R. Smith \n \ndrsmith@ucsc.edu\n1 \nDepartment of\u00a0Microbiology and\u00a0Environmental Toxicology, \nUniversity of\u00a0California, Santa\u00a0Cruz, CA\u00a095060, USA\n2 \nDivision of\u00a0Nutritional Sciences and\u00a0Department \nof\u00a0Psychology, Cornell University, Ithaca, NY\u00a014853, USA"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 670
encoding: FLOAT32
metadata:
{"title": "Efficacy of the modified vaccinia Ankara virus vaccine and the replication-competent vaccine ACAM2000 in monkeypox prevention", "chroma:document": "Elsevier has created a Monkeypox Information Center in response to the \ndeclared public health emergency of international concern, with free \ninformation in English on the monkeypox virus. The Monkeypox Information \nCenter is hosted on Elsevier Connect, the company's public news and \ninformation website.  \n  \nElsevier hereby grants permission to make all its monkeypox related \nresearch that is available on the Monkeypox Information Center - including \nthis research content - immediately available in publicly funded \nrepositories, with rights for unrestricted research re-use and analyses in \nany form or by any means with acknowledgement of the original source. \nThese permissions are granted for free by Elsevier for as long as the \nMonkeypox Information Center remains active."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 671
encoding: FLOAT32
metadata:
{"title": "Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy", "chroma:document": "RESEARCH ARTICLE\nTreatment with benznidazole and\npentoxifylline regulates microRNA\ntranscriptomic profile in a murine model of\nChagas chronic cardiomyopathy\nPriscila Silva Grijo\u00b4 Farani1,2, Beatriz Iandra da Silva Ferreira1, Khodeza Begum3,\nGlaucia Vilar-Pereira2, Isabela Resende Pereira2, Edith A. Ferna\u00b4ndez-Figueroa4, Roberto\nAlejandro Cardenas-Ovando4, Igor C. Almeida3, Sourav Roy3, Joseli Lannes-Vieira2,\nOtacilio Cruz MoreiraID1*\n1 Real-Time PCR Platform RPT09A, Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz\nInstitute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, 2 Laboratory of Biology of the Interactions,\nOswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, 3 Border Biomedical Research\nCenter, Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, United States of\nAmerica, 4 Computational and Integrative Genomics, Instituto Nacional de Medicina Geno\u00b4mica, Arenal\nTepepan, Mexico City, Mexico\n* otacilio@ioc.fiocruz.br\nAbstract\nChronic Chagas cardiomyopathy (CCC) is one of the leading causes of morbidity and mor-\ntality due to cardiovascular disorders in endemic areas of Chagas disease (CD), a neglected\ntropical illness caused by the protozoan parasite Trypanosoma cruzi. CCC is characterized\nby parasite persistence and inflammatory response in the heart tissue, which occur parallel\nto microRNA (miRNA) alterations. Here, we investigated the miRNA transcriptome profiling\nin the cardiac tissue of chronically T. cruzi-infected mice treated with a suboptimal dose of\nbenznidazole (Bz), the immunomodulator pentoxifylline alone (PTX), or the combination of\nboth (Bz+PTX), following the CCC onset. At 150 days post-infection, Bz, PTX, and Bz+PTX\ntreatment regimens improved electrocardiographic alterations, reducing the percentage of\nmice afflicted by sinus arrhythmia and second-degree atrioventricular block (AVB2) when\ncompared with the vehicle-treated animals. miRNA Transcriptome profiling revealed consid-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 672
encoding: FLOAT32
metadata:
{"title": "Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy", "chroma:document": "erable changes in the differential expression of miRNAs in the Bz and Bz+PTX treatment\ngroups compared with the control (infected, vehicle-treated) group. The latter showed path-\nways related to organismal abnormalities, cellular development, skeletal muscle develop-\nment, cardiac enlargement, and fibrosis, likely associated with CCC. Bz-Treated mice\nexhibited 68 differentially expressed miRNAs related to signaling pathways like cell cycle,\ncell death and survival, tissue morphology, and connective tissue function. Finally, the Bz\n+PTX-treated group revealed 58 differentially expressed miRNAs associated with key sig-\nnaling pathways related to cellular growth and proliferation, tissue development, cardiac\nfibrosis, damage, and necrosis/cell death. The T. cruzi-induced upregulation of miR-146b-\n5p, previously shown in acutely infected mice and in vitro T. cruzi-infected cardiomyocytes,\nwas reversed upon Bz and Bz+PTX treatment regimens when further experimentally vali-\ndated. Our results further our understanding of molecular pathways related to CCC\nPLOS NEGLECTED TROPICAL DISEASES\nPLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0011223\nMarch 27, 2023\n1 / 29\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Silva Grijo\u00b4 Farani P, Iandra da Silva\nFerreira B, Begum K, Vilar-Pereira G, Pereira IR,\nFerna\u00b4ndez-Figueroa EA, et al. (2023) Treatment\nwith benznidazole and pentoxifylline regulates\nmicroRNA transcriptomic profile in a murine model\nof Chagas chronic cardiomyopathy. PLoS Negl\nTrop Dis 17(3): e0011223. https://doi.org/10.1371/\njournal.pntd.0011223\nEditor: Armando Jardim, McGill university,\nCANADA\nReceived: September 27, 2022\nAccepted: March 7, 2023\nPublished: March 27, 2023\nCopyright: \u00a9 2023 Silva Grijo\u00b4 Farani et al. This is an\nopen access article distributed under the terms of\nthe Creative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 673
encoding: FLOAT32
metadata:
{"title": "Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy", "chroma:document": "Data Availability Statement: All relevant data are\nwithin the paper and its Supporting Information\nfiles.\nFunding: This work received financial support from\nCoordenac\u00b8\u00e3o de Aperfeic\u00b8oamento de Pessoal de\nN\u0131\u00b4vel Superior Brasil (CAPES - Finance Code 001 to\nPSGF and BIFS), Conselho Nacional de\nDesenvolvimento Cient\u0131\u00b4fico e Tecnolo\u00b4gico (CNPq -\nOCM is a researcher fellow of CNPq 1D (311539/"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 674
encoding: FLOAT32
metadata:
{"title": "Summary of the joint National Institutes of Health and the Food and Drug Administration workshop titled \\215exploring the science s\\\rurrounding the safe use of bioactive ingredients in infant formula: Considerations for an assessment framework\\216", "chroma:document": "Summary of the joint National Institutes of Health and the Food \nand Drug Administration workshop titled \u201cexploring the science \nsurrounding the safe use of bioactive ingredients in infant \nformula: Considerations for an assessment framework\u201d\nSharon M. Donovan, PhD1, Steven A. Abrams, MD2, Meghan B. Azad, PhD3,4, Mandy B. \nBelfort, MD, MPH5, Lars Bode, PhD6, Susan E. Carlson, PhD7, David C. Dallas, PhD8, \nKasper Hettinga, PhD9, Kirsi J\u00e4rvinen, MD, PhD10, Jae H. Kim, MD, PhD11, Carlito B. \nLebrilla, PhD12, Michelle K. McGuire, PhD13, David A. Sela, PhD14, Josef Neu, MD15\n1Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL;\n2Department of Pediatrics Dell Medical School, The University of Texas at Austin, Austin, TX;\n3Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada;\n4Manitoba Interdisciplinary Lactation Centre (MILC), Children\u2019s Hospital Research Institute of \nManitoba, Winnipeg, Canada;\n5Department of Pediatric Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard \nMedical School, Boston, MA;\n6Department of Pediatrics and Mother-Milk-Infant Center of Research Excellence (MOMI CORE), \nUniversity of California, San Diego, La Jolla, CA;\n7Department of Dietetics and Nutrition, Kansas University Medical Center and The University of \nKansas, Kansas City, KS;\n8Department of Nutrition, Oregon State University, Corvallis, OR;\n9Department of Food Sciences and Agrotechnology, Wageningen University, Wageningen, \nNetherlands;\n10Department of Pediatrics, Golisano Children\u2019s Hospital and University of Rochester School of \nMedicine and Dentistry, Rochester, NY;\n11Perinatal Institute, Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center and \nUniversity of Cincinnati College of Medicine, Cincinnati, OH;\n12Department of Chemistry, University of California, Davis, Davis, CA;\n13School of Family and Consumer Sciences, University of Idaho, Moscow, ID;\n14Department of Food Science, University of Massachusetts, Amherst, Amherst, MA;"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 675
encoding: FLOAT32
metadata:
{"title": "Summary of the joint National Institutes of Health and the Food and Drug Administration workshop titled \\215exploring the science s\\\rurrounding the safe use of bioactive ingredients in infant formula: Considerations for an assessment framework\\216", "chroma:document": "Reprint requests: Josef Neu, MD, University of Florida. neuj@peds.ufl.edu. \nAffiliations: 1Eunice Kennedy Shrive National Institute of Child Health and Human Development, Bethesda, MD; 2Center for Food \nSafety and Applied Nutrition, College Park, MD; 3Office of Dietary Supplements, National Institutes of Health, Bethesda, MD.\nHHS Public Access\nAuthor manuscript\nJ Pediatr. Author manuscript; available in PMC 2023 April 22.\nPublished in final edited form as:\nJ Pediatr. 2023 April ; 255: 30\u201341.e1. doi:10.1016/j.jpeds.2022.11.027.\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: 676
encoding: FLOAT32
metadata:
{"title": "TrkC Intracellular Signalling in the Brain Fear Network During the Formation of a Contextual Fear Memory", "chroma:document": "Vol.:(0123456789)\n1 3\nhttps://doi.org/10.1007/s12035-023-03292-0\nTrkC Intracellular Signalling in\u00a0the\u00a0Brain Fear Network During \nthe\u00a0Formation of\u00a0a\u00a0Contextual Fear Memory\nFrancisca\u00a0Silva1,2\u00a0\u00b7 Gianluca\u00a0Masella1,2\u00a0\u00b7 Maria\u00a0Francisca\u00a0Madeira1\u00a0\u00b7 Carlos\u00a0B.\u00a0Duarte1,3\u00a0\u00b7 M\u00f3nica\u00a0Santos1,2 \nReceived: 10 October 2022 / Accepted: 21 February 2023 \n\u00a9 The Author(s) 2023\nAbstract\nLearned fear is orchestrated by a brain fear network that comprises the amygdala, hippocampus and the medial prefrontal \ncortex. Synaptic plasticity within this network is critical for the formation of proper fear memories. Known for their role \nin the promotion of synaptic plasticity, neurotrophins position as obvious candidates in the regulation of fear processes. \nIndeed, recent evidence from our laboratory and others associates dysregulated signalling through neurotrophin-3 and its \nreceptor TrkC with the pathophysiology of anxiety and fear-related disorders. Here, we put wild-type C57Bl/6J mice through \na contextual fear conditioning paradigm in order to characterize TrkC activation and expression in the main brain regions \ninvolved in (learned) fear \u2013 amygdala, hippocampus, and prefrontal cortex \u2013 during the formation of a fear memory. We \nreport an overall decreased activation of TrkC in the fear network during fear consolidation and reconsolidation. During \nreconsolidation, hippocampal TrkC downregulation was accompanied by a decrease in the expression and activation of Erk, \na critical signalling pathway in fear conditioning. Moreover, we did not find evidence that the observed decrease of TrkC \nactivation was caused by altered expression of dominant negative form of TrkC, neurotrophin-3, or the PTP1B\u00a0phosphatase. \nOur results indicate hippocampal TrkC inactivation through Erk signalling as a potential mechanism in the regulation of \ncontextual fear memory formation.\nKeywords Fear conditioning\u00a0\u00b7 Neurotrophin 3\u00a0\u00b7 Erk\u00a0\u00b7 Akt\u00a0\u00b7 PLC\nIntroduction\nExcessive (learned) fear is a shared feature of anxiety disor-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 677
encoding: FLOAT32
metadata:
{"title": "TrkC Intracellular Signalling in the Brain Fear Network During the Formation of a Contextual Fear Memory", "chroma:document": "ders [1], the most prevalent group of mental disorders world-\nwide with more than 300 million people affected by one of \nthese conditions [2\u20134]. Importantly, most patients are still \nresistant or relapse to currently available pharmacological \nand/or cognitive behavioural therapies [5, 6].\nPavlovian fear conditioning is a translationally relevant \nmodel, key in both understanding the physiology of fear and \nthe pathophysiology of anxiety disorders. Fear condition-\ning is an associative learning process in which a neutral \nstimulus, such as a tone or a specific context (conditioned \nstimulus, CS), is presented together with an aversive stimu-\nlus, usually a foot shock (unconditioned stimulus, US), to \ngenerate a conditioned fear response [7]. The fear acquisition \nphase is followed by a consolidation phase, lasting hours to \ndays, during which memories are formed [8]. Subsequent \nexposure to the CS, in absence of the US, is sufficient to \nevoke freezing behaviour, demonstrating the effective for-\nmation of a conditioned fear memory. Re-exposure to the \nCS after the stabilization of fear memories causes them \nto become labile and susceptible to disruption [9]. In this \nstate, depending on the characteristics of the CS exposure, \nmemories can progress to extinction, or they can undergo \nreconsolidation. Reconsolidation is the process through \nwhich memories re-stabilize after having been destabilized \nby exposure to the CS. It is thought to allow the integration \nof new information into the memory trace, and shares most, \nbut not all, molecular mechanisms with fear consolidation \n[10, 11].\nFear conditioning is mediated by the brain fear circuit, \na complex ensemble of brain areas with highly specialized \n * M\u00f3nica Santos \n \nmjpsantos@cnc.uc.pt; monicapsantos@hotmail.com\n1 \nCNC \u2013 Center for\u00a0Neuroscience and\u00a0Cell Biology, University \nof\u00a0Coimbra, Coimbra, Portugal\n2 \nInstitute of\u00a0Interdisciplinary Research, University of\u00a0Coimbra \n(iiiUC), Coimbra, Portugal\n3 \nDepartment of\u00a0Life Sciences, University of\u00a0Coimbra,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 678
encoding: FLOAT32
metadata:
{"title": "TrkC Intracellular Signalling in the Brain Fear Network During the Formation of a Contextual Fear Memory", "chroma:document": "Coimbra, Portugal\n/ Published online: 8 March 2023\nMolecular Neurobiology (2023) 60:3507\u20133521"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 679
encoding: FLOAT32
metadata:
{"title": "A Circular RNA Expressed from the", "chroma:document": "Vol.:(0123456789)\n1 3\nhttps://doi.org/10.1007/s12035-023-03253-7\nA Circular RNA Expressed from\u00a0the\u00a0FAT3 Locus Regulates Neural \nDevelopment\nSabine\u00a0Seeler1,2\u00a0\u00b7 Maria\u00a0Schertz\u00a0Andersen1\u00a0\u00b7 Tamas\u00a0Sztanka\u2011Toth3\u00a0\u00b7 Mateja\u00a0Rybiczka\u2011Te\u0161ulov4\u00a0\u00b7 \nMarleen\u00a0H.\u00a0van\u00a0den\u00a0Munkhof4\u00a0\u00b7 Chi\u2011Chih\u00a0Chang1\u00a0\u00b7 Muyesier\u00a0Maimaitili2,5\u00a0\u00b7 Morten\u00a0Trillingsgaard\u00a0Ven\u00f81,6\u00a0\u00b7 \nThomas\u00a0Birkballe\u00a0Hansen1\u00a0\u00b7 R.\u00a0Jeroen\u00a0Pasterkamp4\u00a0\u00b7 Agnieszka\u00a0Rybak\u2011Wolf3\u00a0\u00b7 Mark\u00a0Denham2,5\u00a0\u00b7 Nikolaus\u00a0Rajewsky3\u00a0\u00b7 \nLasse\u00a0Sommer\u00a0Kristensen1,2\u00a0\u00b7 J\u00f8rgen\u00a0Kjems1 \nReceived: 27 July 2022 / Accepted: 28 January 2023 \n\u00a9 The Author(s) 2023\nAbstract\nCircular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative \nregulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is \nlimited. Here, using RNA-sequencing, we show that circRNA levels increased substantially over the course of differentiation \nof human embryonic stem cells into rostral and caudal neural progenitor cells (NPCs), including three of the most abundant \ncircRNAs, ciRS-7, circRMST, and circFAT3. Knockdown of circFAT3 during early neural differentiation resulted in minor \ntranscriptional alterations in bulk RNA analysis. However, single-cell transcriptomics of 30 and 90\u00a0days differentiated cerebral \norganoids deficient in circFAT3 showed a loss of telencephalic radial glial cells and mature cortical neurons, respectively. \nFurthermore, non-telencephalic NPCs in cerebral organoids showed changes in the expression of genes involved in neural \ndifferentiation and migration, including FAT4, ERBB4, UNC5C, and DCC. In\u00a0vivo depletion of circFat3 in mouse prefrontal \ncortex using in utero electroporation led to alterations in the positioning of the electroporated cells within the neocortex. \nOverall, these findings suggest a conserved role for circFAT3 in neural development involving the formation of anterior cell \ntypes, neuronal differentiation, or migration."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 680
encoding: FLOAT32
metadata:
{"title": "A Circular RNA Expressed from the", "chroma:document": "Keywords ncRNAs\u00a0\u00b7 circRNAs\u00a0\u00b7 Cerebral organoids\u00a0\u00b7 scRNA-seq\u00a0\u00b7 Neural development\u00a0\u00b7 circFAT3\nIntroduction\nThe mammalian nervous system develops through a suc-\ncession of tightly orchestrated processes including neural \ninduction, neural tube patterning along the anterior\u2013pos-\nterior and dorsal\u2013ventral axes, progenitor cell expansion, \nneural differentiation, and neuronal migration [1, 2]. Several \ntypes of non-coding RNAs (ncRNAs), including microR-\nNAs (miRNAs) [3] and long ncRNAs (lncRNAs) [4, 5], \nSabine Seeler and Maria Schertz Andersen contributed equally to \nthis work.\nLasse Sommer Kristensen and J\u00f8rgen Kjems contributed equally to \nthis work.\n * Lasse Sommer Kristensen \n \nlasse@biomed.au.dk\n * J\u00f8rgen Kjems \n \njk@mbg.au.dk\n1 \nInterdisciplinary Nanoscience Center, Department \nof\u00a0Molecular Biology and\u00a0Genetics, Aarhus University, 8000 \nAarhus C, Aarhus, Denmark\n2 \nDepartment of\u00a0Biomedicine, The Skou Building, Aarhus \nUniversity, 8000 Aarhus C, Aarhus, Denmark\n3 \nBerlin Institute for\u00a0Medical Systems Biology (BIMSB), \nMDC Berlin-Mitte, 10115\u00a0Berlin, Germany\n4 \nDepartment of\u00a0Translational Neuroscience, University \nMedical Center Utrecht Brain Center, 3584 CG, Utrecht, \nNetherlands\n5 \nDanish Research Institute of\u00a0Translational Neuroscience, \nNordic EMBL Partnership for\u00a0Molecular Medicine, Aarhus \nUniversity, 8000 Aarhus C, Aarhus, Denmark\n6 \nOmiics ApS, 8200 Aarhus N, Aarhus, Denmark\n/ Published online: 25 February 2023\nMolecular Neurobiology (2023) 60:3239\u20133260"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 681
encoding: FLOAT32
metadata:
{"title": "Super-resolution in brain positron emission tomography using a real-time motion capture system", "chroma:document": "Super-resolution in brain positron emission tomography using a \nreal-time motion capture system\nYanis Chemlia,d, Marc-Andr\u00e9 T\u00e9traultb, Thibault Marina, Marc D. Normandina, Isabelle \nBlochc,d, Georges El Fakhria, Jinsong Ouyanga,1,*, Yoann Petibona,1\naGordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital, \nHarvard Medical School, Boston, MA, United States\nbDepartment of Computer Engineering, Universt\u00e9 de Sherbrooke, Sherbrooke, QC, Canada\ncSorbonne Universit\u00e9, CNRS, LIP6, Paris, France\ndLTCI, T\u00e9l\u00e9com Paris, Institut Polytechnique de Paris, France\nAbstract\nSuper-resolution (SR) is a methodology that seeks to improve image resolution by exploiting the \nincreased spatial sampling information obtained from multiple acquisitions of the same target with \naccurately known sub-resolution shifts. This work aims to develop and evaluate an SR estimation \nframework for brain positron emission tomography (PET), taking advantage of a high-resolution \ninfra-red tracking camera to measure shifts precisely and continuously. Moving phantoms and \nnon-human primate (NHP) experiments were performed on a GE Discovery MI PET/CT scanner \n(GE Healthcare) using an NDI Polaris Vega (Northern Digital Inc), an external optical motion \ntracking device. To enable SR, a robust temporal and spatial calibration of the two devices was \ndeveloped as well as a list-mode Ordered Subset Expectation Maximization PET reconstruction \nalgorithm, incorporating the high-resolution tracking data from the Polaris Vega to correct motion \nfor measured line of responses on an event-by-event basis. For both phantoms and NHP studies, \nthe SR reconstruction method yielded PET images with visibly increased spatial resolution \ncompared to standard static acquisitions, allowing improved visualization of small structures. \nQuantitative analysis in terms of SSIM, CNR and line profiles were conducted and validated our \nobservations. The results demonstrate that SR can be achieved in brain PET by measuring target"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 682
encoding: FLOAT32
metadata:
{"title": "Super-resolution in brain positron emission tomography using a real-time motion capture system", "chroma:document": "motion in real-time using a high-resolution infrared tracking camera.\nThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)\n*Corresponding author at: 125 Nashua St. Suite 660, Boston, MA 02114-1101. ouyang.jinsong@mgh.harvard.edu (J. Ouyang).\n1Co-senior authors\nDeclaration of Competing Interest\nNone.\nCredit authorship contribution statement\nYanis Chemli: Methodology, Software, Investigation, Formal analysis, Validation, Writing \u2013 original draft, Writing \u2013 review & \nediting. Marc-Andr\u00e9 T\u00e9trault: Investigation. Thibault Marin: Software, Writing \u2013 review & editing. Marc D. Normandin: \nInvestigation, Resources. Isabelle Bloch: Supervision, Writing \u2013 review & editing. Georges El Fakhri: Supervision, Resources, \nFunding acquisition. Jinsong Ouyang: Conceptualization, Methodology, Investigation, Supervision, Writing \u2013 review & editing, \nProject administration. Yoann Petibon: Conceptualization, Methodology, Investigation, Supervision, Writing \u2013 review & editing, \nProject administration.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 May 15.\nPublished in final edited form as:\nNeuroimage. 2023 May 15; 272: 120056. doi:10.1016/j.neuroimage.2023.120056.\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: 683
encoding: FLOAT32
metadata:
{"title": "Sequencing of Circulating Cell-free DNA during\\nPregnancy", "chroma:document": "Sequencing of Circulating Cell-free DNA during Pregnancy\nDiana W. Bianchi, M.D.,\nPrenatal Genomics and Fetal Therapy Section, Medical Genetics Branch, National Human \nGenome Research Institute, National Institutes of Health, Bethesda\nRossa W.K. Chiu, M.B., B.S., Ph.D.\nLi Ka Shing Institute of Health Sciences and the Department of Chemical Pathology, Chinese \nUniversity of Hong Kong, Shatin, Hong Kong\nAbstract\nSequence analysis of cell-free DNA (cfDNA) fragments that circulate in the blood of pregnant \nwomen, along with the translation of this method into screening for fetal chromosome \nabnormalities, is a success story of modern genomic medicine. In less than a decade, prenatal \ncfDNA testing has gone from small, proof-of-principle studies to a global transformation of \nprenatal care. As of late 2017, a total of 4 million to 6 million pregnant women had had DNA \nfrom their plasma analyzed to screen for fetal aneuploidy.1 The exponential growth of the test has \nbeen a function of the role of the biotechnology industry in its development and marketing. Here \nwe review what has been learned from the wide-scale implementation of this testing, how it has \nchanged prenatal clinical care, and what ethical concerns have arisen, and we speculate about what \nlies ahead.\nPATH TO CLINICAL IMPLEMENTATION\nTwenty years ago, cfDNA was identified as a plasma analyte when Y chromosomal \n\u201cfetal\u201d DNA was extracted and amplified from the blood of pregnant women carrying \nmale fetuses.2 During pregnancy, DNA fragments are released from the placenta into the \nmaternal circulation as cytotrophoblast and syncytiotrophoblast cells undergo physiologic \ncycles of fusion and apoptosis (see video).3 In contrast to the isolation of intact fetal cells \nfrom maternal blood, analysis of circulating DNA fragments is performed on a plasma \nsample that contains both maternal and placental cfDNA. The ratio of placental to total \n(consisting of maternal and placental) cfDNA is known as the fetal fraction, which increases"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 684
encoding: FLOAT32
metadata:
{"title": "Sequencing of Circulating Cell-free DNA during\\nPregnancy", "chroma:document": "as pregnancy advances.4,5 Testing of cfDNA is generally performed from the 10th week of \ngestation onward, since this is when the fetal fraction in the maternal circulation reaches \nthe minimum amount needed for an informative test result. The fetal fraction is only one \nof several variables that affect the sensitivity of the test. Other variables include the number \nof cfDNA molecules sequenced, the proportion of guanine and cytosine bases in a specific \nchromosome, and the presence of maternal and fetal copy-number variants.6\nDisclosure forms provided by the authors are available with the full text of this article at NEJM.org.\nHHS Public Access\nAuthor manuscript\nN Engl J Med. Author manuscript; available in PMC 2023 April 24.\nPublished in final edited form as:\nN Engl J Med. 2018 August 02; 379(5): 464\u2013473. doi:10.1056/NEJMra1705345.\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: 685
encoding: FLOAT32
metadata:
{"title": "Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2", "chroma:document": "ARTICLE\nOPEN\nPreventive and therapeutic bene\ufb01ts of nel\ufb01navir in rhesus\nmacaques and human beings infected with SARS-CoV-2\nZhijian Xu\n1,2,3, Danrong Shi4, Jian-Bao Han5, Yun Ling6, Xiangrui Jiang1,3, Xiangyun Lu4, Chuan Li1,3, Likun Gong1,3,7, Guangbo Ge8,\nYani Zhang8, Yi Zang1,3, Tian-Zhang Song5,9, Xiao-Li Feng5, Ren-Rong Tian5,9, Jia Ji4, Miaojin Zhu4, Nanping Wu4, Chunhui Wu1,3,\nZhen Wang1,3, Yechun Xu1,2,3, Cheng Peng1,2,3, Min Zheng\n4, Junling Yang1,3, Feifei Du1,3, Junliang Wu1,3,7, Peipei Wang1,3,\nJingshan Shen\n1,3\u2709, Jianliang Zhang6\u2709, Yong-Tang Zheng\n5,9\u2709, Hangping Yao\n4,10\u2709 and Weiliang Zhu\n1,2,3\u2709\nEffective drugs with broad spectrum safety pro\ufb01le to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.\nHere we report that nel\ufb01navir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-\n19. Preincubation of nel\ufb01navir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 \u03bcM), while its antiviral\nactivity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 \u03bcM (EC50). In comparison with vehicle-\ntreated animals, rhesus macaque prophylactically treated with nel\ufb01navir had signi\ufb01cantly lower temperature and signi\ufb01cantly\nreduced virus loads in the nasal and anal swabs of the animals. At necropsy, nel\ufb01navir-treated animals had a signi\ufb01cant reduction of\nthe viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive\npatients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nel\ufb01navir and control groups, showed that the\nnel\ufb01navir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever\ntime by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral ef\ufb01ciency and clinical bene\ufb01ts in\nrhesus macaque model and in COVID-19 patients, together with its well-established good safety pro\ufb01le in almost all ages and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 686
encoding: FLOAT32
metadata:
{"title": "Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2", "chroma:document": "during pregnancy, indicated that nel\ufb01navir is a highly promising medication with the potential of preventative effect for the\ntreatment of COVID-19.\nSignal Transduction and Targeted Therapy  (2023) 8:169 \n; https://doi.org/10.1038/s41392-023-01429-0\nINTRODUCTION\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a\nhighly infectious positive-strand RNA virus causing COVID-19\n(coronavirus disease 2019), has evolved through Alpha, Beta,\nGamma, Delta, and Omicron mutant strains, resulting in an\nunabated global pandemic trend. Although quite a few COVID-19\nvaccines have been used worldwide since 2021, which could\nsigni\ufb01cantly protect people from getting severely ill or dying, as\nmany as hundreds of thousands of infection cases are currently\nreported each day.1 Therefore, effective drugs with good safety\npro\ufb01les are highly expected to protect the SARS-CoV-2 infected\npeople by stopping the virus replication in the body to prevent\nthe people from becoming severe or dying. There are two well\nknown drug targets for SARS-CoV-2, one is RNA-dependent RNA\npolymerase (RdRp) and the other is main protease (Mpro).\nReplication of RNA from an RNA template is catalyzed by RdRp,\nleading to its vital role in SARS-CoV-2 replication and transcription.\nMpro, also known as 3C-like protease (chymotrypsin-like protease),\ncleaving at least 11 sites of SARS-CoV-2 polyprotein, is highly\nconservable among coronaviruses. Sequence alignment revealed\nthat the Mpro of SARS-CoV-2 shares 96% similarity with that of\nSARS-CoV-1. In addition, Mpro has no human homolog, making\nMpro the most attractive drug target to treat COVID-19.\nSmall\nmolecule\nantivirals\nhave\nthe\nadvantages\nof\neasy\nmanufacture, low cost and good accessibility.2\u20134 There are several\nsmall molecule drugs shown bene\ufb01cial effects in preclinical and\nclinical trials. For example, in the Evaluation of Protease Inhibition\nfor Covid-19 in High-Risk Patients (EPIC-HR) double-blind con-\ntrolled trial with a total of 2246 unvaccinated patients from July 16"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 687
encoding: FLOAT32
metadata:
{"title": "Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2", "chroma:document": "to December 9, 2021 when the Delta mutant dominated,\nReceived: 24 September 2022 Revised: 8 March 2023 Accepted: 4 April 2023\n1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 2Drug Discovery and Design Center,\nShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 3School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049,\nChina; 4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Af\ufb01liated Hospital, Zhejiang\nUniversity School of Medicine, Hangzhou 310003, China; 5Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science,\nKunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China; 6Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan\nUniversity, Shanghai 201508, China; 7Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203,\nChina; 8Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese\nMedicine, Shanghai 201203, China; 9Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of\nBioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China and 10Jinan\nMicroecological Biomedicine Shandong Laboratory, Jinan 250117, China\nCorrespondence:\nJingshan\nShen\n(shenjingshan@simm.ac.cn)\nor\nJianliang\nZhang\n(zhangjianliang@shphc.org.cn)\nor\nYong-Tang\nZheng\n(zhengyt@mail.kiz.ac.cn)\nor\nHangping Yao (yaohangping@zju.edu.cn) or Weiliang Zhu (wlzhu@simm.ac.cn)\nThese authors contributed equally: Zhijian Xu, Danrong Shi, Jian-Bao Han, Yun Ling, Xiangrui Jiang, Xiangyun Lu"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 688
encoding: FLOAT32
metadata:
{"title": "Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2", "chroma:document": "www.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: 689
encoding: FLOAT32
metadata:
{"title": "The unique properties of IgG4 and its roles in health and disease", "chroma:document": "Nature Reviews Immunology\nnature reviews immunology\nhttps://doi.org/10.1038/s41577-023-00871-z\nReview article\n Check for updates\nThe unique properties of IgG4  \nand its roles in health and disease\nTheo Rispens1 & Maartje G. Huijbers\u2009\n \u20092,3 \nAbstract\nIgG4 is the least abundant subclass of IgG in human serum and has \nunique functional features. IgG4 is largely unable to activate antibody-\ndependent immune effector responses and, furthermore, undergoes \nFab (fragment antigen binding)-arm exchange, rendering it bispecific \nfor antigen binding and functionally monovalent. These properties \nof IgG4 have a blocking effect, either on the immune response or \non the target protein of IgG4. In this Review, we discuss the unique \nstructural characteristics of IgG4 and how these contribute to its \nroles in health and disease. We highlight how, depending on the \nsetting, IgG4 responses can be beneficial (for example, in responses \nto allergens or parasites) or detrimental (for example, in autoimmune \ndiseases, in antitumour responses and in anti-biologic responses). \nThe development of novel models for studying IgG4 (patho)physiology \nand understanding how IgG4 responses are regulated could offer \ninsights into novel treatment strategies for these IgG4-associated \ndisease settings.\nSections\nIntroduction\nDevelopment of an IgG4 \nresponse\nStructure and function of IgG4\nPhysiological roles of IgG4\nIgG4-dependent pathology\nIgG4-related diseases\nFuture directions\n1Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands. \n2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. 3Department of \nNeurology, Leiden University Medical Center, Leiden, The Netherlands. \n\u2009e-mail: M.G.M.Huijbers@lumc.nl"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 690
encoding: FLOAT32
metadata:
{"title": "In vitro effects of cannabidiol and its main metabolites in mouse and human Sertoli cells", "chroma:document": "In vitro effects of cannabidiol and its main metabolites in mouse \nand human Sertoli cells\nYuxi Li1, Qiangen Wu1, Xilin Li2, Linda S. Von Tungeln1, Frederick A. Beland1, Dayton \nPetibone2, Lei Guo1, Patrick Cournoyer3, Supratim Choudhuri3, Si Chen1,*\n1Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and \nDrug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA\n2Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. \nFood and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA\n3Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, U.S. Food and Drug \nAdministration, College Park, MD 20740, USA.\nAbstract\nCannabidiol (CBD) is a major cannabinoid present in extracts of the plant Cannabis sativa \n(marijuana). While the therapeutic effects of CBD on epilepsy have been demonstrated, less is \nunderstood regarding its potential adverse effects. Recent studies revealed that CBD induced \ntoxicity in the male reproductive system of animal models. In this study, we used TM4, an \nimmortalized mouse Sertoli cell line, and primary human Sertoli cells to evaluate the toxicities of \nCBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD. CBD induced concentration- \nand time-dependent cytotoxicity in mouse and human Sertoli cells, which mainly resulted from \nthe inhibition of the G1/S-phase cell cycle transition. CBD also inhibited DNA synthesis and \ndownregulated key cell cycle proteins. Moreover, CBD reduced the mRNA and protein levels \nof a functional marker, Wilms\u2019 tumor 1. Similar to CBD, 7-carboxy-CBD and 7-hydroxy-CBD \ninhibited cellular proliferation and decreased DNA synthesis. 7-Carboxy-CBD was less cytotoxic \nthan CBD, while 7-hydroxy-CBD showed comparable cytotoxicity to CBD in both mouse and \nhuman Sertoli cells. Compared to mouse Sertoli cells, CBD, 7-hydroxy-CBD, and 7-carboxy-CBD \nwere more cytotoxic in human Sertoli cells. Our results indicate that CBD and its main metabolites"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 691
encoding: FLOAT32
metadata:
{"title": "In vitro effects of cannabidiol and its main metabolites in mouse and human Sertoli cells", "chroma:document": "can inhibit cell proliferation in mouse and human Sertoli cells.\nKeywords\nCannabidiol; 7-Carboxy-CBD; 7-Hydroxy-CBD; Male reproductive toxicity; Sertoli cells; Cell \ncycle arrest; DNA synthesis; Wilms\u2019 tumor 1\n*Corresponding author. Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, \nJefferson, AR 72079, USA. Si.Chen@fda.hhs.gov. \nConflict of interest: The authors declare no conflict of interest.\nCompliance with ethical standards\nDisclaimer: This article reflects the views of the authors and does not necessarily reflect those of the U.S. Food and Drug \nAdministration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or \nrecommendation.\nHHS Public Access\nAuthor manuscript\nFood Chem Toxicol. Author manuscript; available in PMC 2023 April 24.\nPublished in final edited form as:\nFood Chem Toxicol. 2022 January ; 159: 112722. doi:10.1016/j.fct.2021.112722.\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: 692
encoding: FLOAT32
metadata:
{"title": "Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases", "chroma:document": "Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic \nstrategy for neurodegenerative diseases\nChu Chen\nDepartment of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe \nR. and Teresa Lozano Long School of Medicine, University of Texas Health San Antonio, San \nAntonio, Texas, 78229, USA\nAbstract\nEndocannabinoids are endogenous lipid signaling mediators that participate in a variety of \nphysiological and pathological processes. 2-Arachidonoylglycerol (2-AG) is the most abundant \nendocannabinoid and is a full agonist of G-protein-coupled cannabinoid receptors (CB1R \nand CB2R), which are targets of \u03949-tetrahydrocannabinol (\u03949-THC), the main psychoactive \ningredient in cannabis. While 2-AG has been well recognized as a retrograde messenger \nmodulating synaptic transmission and plasticity at both inhibitory GABAergic and excitatory \nglutamatergic synapses in the brain, growing evidence suggests that 2-AG also functions as an \nendogenous terminator of neuroinflammation in response to harmful insults, thus maintaining \nbrain homeostasis. Monoacylglycerol lipase (MAGL) is the key enzyme that degrades 2-AG \nin the brain. The immediate metabolite of 2-AG is arachidonic acid (AA), a precursor of \nprostaglandins (PGs) and leukotrienes. Several lines of evidence indicate that pharmacological \nor genetic inactivation of MAGL, which boosts 2-AG levels and reduces its hydrolytic metabolites, \nresolves neuroinflammation, mitigates neuropathology, and improves synaptic and cognitive \nfunctions in animal models of neurodegenerative diseases, including Alzheimer\u2019s disease (AD), \nmultiple sclerosis (MS), Parkinson\u2019s disease (PD), and traumatic brain injury (TBI)-induced \nneurodegenerative disease. Thus, it has been proposed that MAGL is a potential therapeutic \ntarget for treatment of neurodegenerative diseases. As the main enzyme hydrolyzing 2-AG, \nseveral MAGL inhibitors have been identified and developed. However, our understanding"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 693
encoding: FLOAT32
metadata:
{"title": "Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases", "chroma:document": "of the mechanisms by which inactivation of MAGL produces neuroprotective effects in \nneurodegenerative diseases remains limited. A recent finding that inhibition of 2-AG metabolism \nin astrocytes, but not in neurons, protects the brain from TBI-induced neuropathology might shed \nsome light on this unsolved issue. This review provides an overview of MAGL as a potential \ntherapeutic target for neurodegenerative diseases and discusses possible mechanisms underlying \nthe neuroprotective effects of restraining degradation of 2-AG in the brain.\nCorrespondence should be addressed to: Chu Chen, PhD, Department of Cellular and Integrative Physiology, School of Medicine, \nUniversity of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA, Tel: (210) 450-5376, Fax: (210) \n567-4410, chenc7@uthscsa.edu or chen502@gmail.com. \nConflict of interest statement\nThe authors declare that there are no conflicts of interest.\nHHS Public Access\nAuthor manuscript\nPharmacol Ther. Author manuscript; available in PMC 2023 April 24.\nPublished in final edited form as:\nPharmacol Ther. 2023 April ; 244: 108394. doi:10.1016/j.pharmthera.2023.108394.\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: 694
encoding: FLOAT32
metadata:
{"title": "Bridging to Allotransplantation\\204Is Pig Liver Xenotransplantation the Best Option?", "chroma:document": "Bridging to Allotransplantation\u2014Is Pig Liver \nXenotransplantation the Best Option?\nVladimir Lamm, MD1, Burcin Ekser, MD, PhD2, Parsia A. Vagefi, MD3, David K.C. Cooper, \nMD, PhD, FRCS4\n1Division of Gastroenterology, Department of Medicine, Washington University School of \nMedicine, St. Louis, MO.\n2Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, \nIndianapolis, IN.\n3Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern \nMedical Center, Dallas, TX.\n4Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, \nBirmingham, AL.\nAbstract\nIn the past 20 y, the number of patients in the United States who died while waiting for a \nhuman donor liver totaled >52 000. The median national wait time for patients with acute liver \nfailure and the most urgent liver transplant listing was 7 d in 2018. The need for a clinical \n\u201cbridge\u201d to allotransplantation is clear. Current options for supporting patients with acute liver \nfailure include artificial liver support devices, extracorporeal liver perfusion, and hepatocyte \ntransplantation, all of which have shown mixed results with regard to survival benefit and are \nlargely experimental. Progress in the transplantation of genetically engineered pig liver grafts in \nnonhuman primates has grown steadily, with survival of the pig graft extended to almost 1 mo \nin 2017. Further advances may justify consideration of a pig liver transplant as a clinical bridge \nto allotransplantation. We provide a brief history of pig liver xenotransplantation, summarize \nthe most recent progress in pig-to-nonhuman primate liver transplantation models, and suggest \ncriteria that may be considered for patient selection for a clinical trial of bridging by genetically \nengineered pig liver xenotransplantation to liver allotransplantation.\nCorrespondence: Vladimir Lamm, MD, Division of Gastroenterology Department of Medicine, Washington University School of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 695
encoding: FLOAT32
metadata:
{"title": "Bridging to Allotransplantation\\204Is Pig Liver Xenotransplantation the Best Option?", "chroma:document": "Medicine, 660 S. Euclid Ave, Campus Box 8124, St. Louis, MO 63110. (lamm@wustl.edu). Correspondence: David K.C. Cooper, \nMD, PhD, FRCS, Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, LHRB 752, 701 19th \nSt S, Birmingham, AL 35294. (dkcooper@uabmc.edu).\nAll listed authors participated in the writing of this review article. V.L. and D.K.C.C. drafted the article, revised it critically for \nimportant intellectual content, approved the final version of the work to be published, and agreed to be accountable for all aspects of \nthe work. B.E. and P.A.V. revised the article critically for important intellectual content; approved the final version of the work to be \npublished; and agreed to be accountable for all aspects of the work.\nThe authors declare no conflicts of interest.\nHHS Public Access\nAuthor manuscript\nTransplantation. Author manuscript; available in PMC 2023 April 24.\nPublished in final edited form as:\nTransplantation. 2022 January 01; 106(1): 26\u201336. doi:10.1097/TP.0000000000003722.\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: 696
encoding: FLOAT32
metadata:
{"title": "Suggested Patient Selection Criteria for Initial Clinical Trials of Pig Kidney Xenotransplantation in the USA", "chroma:document": "Suggested Patient Selection Criteria for Initial Clinical Trials of \nPig Kidney Xenotransplantation in the USA\nAbhijit Jagdale, MD1, Vineeta Kumar, MD2, Douglas J. Anderson, MD1,3, Jayme E. Locke, \nMD, MPH1,3, Michael J. Hanaway, MD3, Devin E. Eckhoff, MD1,3, Hayato Iwase, MD, PhD1, \nDavid K.C. Cooper, MD, PhD, FRCS1\n1.Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of \nAlabama at Birmingham, Birmingham, AL, USA\n2.Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, \nBirmingham, AL, USA\n3.Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, \nBirmingham, AL, USA\nLay summary\nThere is a critical shortage of kidneys for transplantation into patients with kidney failure. \nGenetically-engineered pigs could provide an additional source. Increasing success is being \nreported of the transplantation of pig kidneys in nonhuman primates. Consideration is now being \ngiven to the selection of patients for the first clinical trial of pig kidney transplantation. In some \nUS states, patients aged 55\u201365, particularly if of blood group O, may wait >5 years for a donor \norgan, by which time >50% are likely to have died or removed from the wait-list because they \nare no longer acceptable for transplantation. We suggest these patients, if otherwise healthy, might \naccept the opportunity of early pig kidney transplantation.\nIntroduction\nMore than 80 000 patients with end-stage renal disease (ESRD) are on the wait-list for \nkidney transplantation in the USA,1 most of whom are receiving chronic hemodialysis. \nThe 5-year mortality of wait-listed patients is approximately 40%,2\u20135 whereas the median \nwaiting time to receive a deceased human donor kidney is 4 years.6 Many patients will not \nlive long enough to undergo kidney allotransplantation.\nChronic dialysis is associated with a relatively high mortality and increased comorbidities \nthat may render the patient unsuitable for renal transplantation. Furthermore, the quality of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 697
encoding: FLOAT32
metadata:
{"title": "Suggested Patient Selection Criteria for Initial Clinical Trials of Pig Kidney Xenotransplantation in the USA", "chroma:document": "Correspondence: David K.C. Cooper, MD, PhD, FRCS, Xenotransplantation Program, Department of Surgery, University of Alabama \nat Birmingham (UAB), Birmingham, AL 35294-0007, USA., Tel: 412-443-4294, dkcooper@uabmc.edu.\nAuthor contribution:\nDKCC, AJ: Conceived and/or designed the study. AJ: acquired data, played an important role in interpreting the results, drafted the \nmanuscript. DKCC, VK, DA, JL, MH, DE, HI: revised the manuscript and approved the final version.\nDKCC confirm that he has had full access to the data in the study and final responsibility.\nConflict of interest\nNo author has a conflict of interest\nHHS Public Access\nAuthor manuscript\nTransplantation. Author manuscript; available in PMC 2023 April 24.\nPublished in final edited form as:\nTransplantation. 2021 September 01; 105(9): 1904\u20131908. doi:10.1097/TP.0000000000003632.\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: 698
encoding: FLOAT32
metadata:
{"title": "Sleeping Beauty transposon system for GDNF overexpression of entrapped stem cells in fibrin hydrogel in a rat model of Parkinson\u0090s disease", "chroma:document": "Vol.:(0123456789)\n1 3\nhttps://doi.org/10.1007/s13346-023-01289-9\nSleeping Beauty transposon system for\u00a0GDNF overexpression \nof\u00a0entrapped stem cells in\u00a0fibrin hydrogel in\u00a0a\u00a0rat model of\u00a0Parkinson\u2019s \ndisease\nLaura\u00a0Stahn1 \u00a0\u00b7 Justyna\u00a0Rasi\u0144ska1\u00a0\u00b7 Tilo\u00a0Dehne2\u00a0\u00b7 Stefanie\u00a0Schreyer1\u00a0\u00b7 Aileen\u00a0Hakus1\u00a0\u00b7 Manfred\u00a0Gossen3,4\u00a0\u00b7 \nBarbara\u00a0Steiner1\u00a0\u00b7 Shabnam\u00a0Hemmati\u2011Sadeghi1,2\nAccepted: 30 December 2022 \n\u00a9 The Author(s) 2023\nAbstract\nThere is currently no causal treatment available for Parkinson\u2019s disease (PD). However, the use of glial cell line\u2013derived neurotrophic \nfactor (GDNF) to provide regenerative effects for neurons is promising. Such approaches require translational delivery systems that \nare functional in diseased tissue. To do so, we used a non-viral Sleeping Beauty (SB) transposon system to overexpress GDNF in \nadipose tissue\u2013derived mesenchymal stromal cells (adMSCs). Entrapment of cells in fibrin hydrogel was used to boost potential \nneurorestorative effects. Functional GDNF-adMSCs were able to secrete 1066.8 \u00b1 169.4\u00a0ng GDNF/120,000 cells in\u00a0vitro. The \nGDNF-adMSCs were detectable for up to 1\u00a0month after transplantation in a mild 6-hydroxydopamine (6-OHDA) hemiparkinson \nmale rat model. Entrapment of GDNF-adMSCs enabled GDNF secretion in surrounding tissue in a more concentrated manner, also \ntending to prolong GDNF secretion relatively. GDNF-adMSCs entrapped in hydrogel also led to positive immunomodulatory effects \nvia an 83% reduction of regional IL-1\u03b2 levels compared to the non-entrapped GDNF-adMSC group after 1\u00a0month. Furthermore, \nGDNF-adMSC-treated groups showed higher recovery of tyrosine hydroxylase (TH)-expressing cells, indicating a neuroprotec-\ntive function, although this was not strong enough to show significant improvement in motor performance. Our findings establish a \npromising GDNF treatment system in a PD model. Entrapment of GDNF-adMSCs mediated positive immunomodulatory effects."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 699
encoding: FLOAT32
metadata:
{"title": "Sleeping Beauty transposon system for GDNF overexpression of entrapped stem cells in fibrin hydrogel in a rat model of Parkinson\u0090s disease", "chroma:document": "Although the durability of the hydrogel needs to be extended to unlock its full potential for motor improvements, the neuroprotec-\ntive effects of GDNF were evident and safe. Further motor behavioral tests and other disease models are necessary to evaluate this \ntreatment option adequately.\nKeywords Neurodegeneration\u00a0\u00b7 Adipose tissue\u2013derived mesenchymal stromal cells (adMSCs)\u00a0\u00b7 Neurotrophic factors\u00a0\u00b7 \nFibrin hydrogel\u00a0\u00b7 Transplantation\u00a0\u00b7 Tissue engineering\nAbbreviations\n6-OHDA \n 6-Hydroxydopamine\nadMSCs \n Adipose tissue\u2013derived mesenchymal stromal \ncells\nAAV \n Adeno-associated virus\nBSA \n Bovine serum albumin\nCPu \n Caudoputamen\nDAPI \n 4\u2032,6-Diamidino-2-phenylindole\neGFP \n Enhanced green fluorescent protein\nELISA \n Enzyme-linked immunosorbent assay\nFDA \n \u00a0Fluorescein diacetate\nGDNF \n Glial cell-derived neurotrophic factor\nIFN-\u03b3 \n Interferon-\u03b3\nIL \n Interleukin\nIQR \n Interquartile range\nKC/GRO  Keratinocyte chemoattractant/growth-regu-\nlated oncogene\nmin \n minutes\nMRI \n Magnetic resonance imaging\nNuMa \n Nuclear mitotic apparatus protein 1\nPBS \n Phosphate buffered saline\nPD \n Parkinson\u2019s disease\nPI \n Propidium iodide\nSB \n Sleeping Beauty\nSN \n Substantia nigra\nSNpc \n Substantia nigra pars compacta\nTH \n Tyrosine hydroxylase\nBarbara Steiner and Shabnam Hemmati-Sadeghi contributed equally.\n * Laura Stahn \n \nlaura.stahn@charite.de\nExtended author information available on the last page of the article\n/ Published online: 28 February 2023\nDrug Delivery and Translational Research (2023) 13:1745\u20131765"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 700
encoding: FLOAT32
metadata:
{"title": "Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial", "chroma:document": "Copyright \u00a9 2023  Korean Stroke Society\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which \npermits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\npISSN: 2287-6391 \u2022 eISSN: 2287-6405\n242 \nhttps://j-stroke.org\nOriginal Article\nJournal of Stroke 2023;25(2):242-250\nhttps://doi.org/10.5853/jos.2022.02957\nModerate-Intensity Rosuvastatin Plus Ezetimibe Versus \nHigh-Intensity Rosuvastatin for Target Low-Density \nLipoprotein Cholesterol Goal Achievement in Patients \nWith Recent Ischemic Stroke: A Randomized \nControlled Trial\nKeun-Sik Hong,\n1 Oh Young Bang,\n2 Jong-Ho Park,\n3 Jin-Man Jung,\n4 Sang-Hun Lee,\n4 Tae-Jin Song,\n5  \nHyo Suk Nam,\n6 Hee-Kwon Park,\n7 Keun-Hwa Jung,\n8 Sung Hyuk Heo,\n9 Jaseong Koo,\n10 Kyung-Ho Yu,\n11  \nKwang-Yeol Park,\n12 Chi Kyung Kim,\n13 Hong-Kyun Park,\n1 Jiyoon Lee,\n14 Juneyoung Lee,\n14 Woo-Keun Seo\n2\n1Department of Neurology, Ilsan Paik Hospital, Inje University, Goyang, Korea\n2Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea\n3Department of Neurology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea \n4Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea\n5Department of Neurology, Seoul Hospital, Ewha Women\u2019s University College of Medicine, Seoul, Korea\n6Department of Neurology, Yonsei University College of Medicine, Seoul, Korea\n7Department of Neurology, Inha University Hospital, Incheon, Korea\n8Department of Neurology, Seoul National University College of Medicine, Seoul, Korea\n9Department of Neurology, Kyung Hee University Medical Center, Seoul, Korea\n10Department of Neurology, Seoul St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul, Korea\n11Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Korea"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 701
encoding: FLOAT32
metadata:
{"title": "Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial", "chroma:document": "12Department of Neurology, Chung-Ang University Hospital, Seoul, Korea\n13Department of Neurology, Korea University Guro Hospital, Seoul, Korea\n14Department of Biostatistics, Korea University College of Medicine, Seoul, Korea\nBackground and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin \nalone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with \nrecent ischemic stroke. \nMethods This randomized, open-label, controlled trial assigned patients with recent ischemic \nstroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin \n20 mg once daily (ROS20). The primary endpoint was LDL-C reduction \u226550% from baseline at 90 \ndays. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and \ncomposite of major vascular events. \nResults Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The \nbaseline LDL-C level was 130.2\u00b134.7 mg/dL in the ROS10/EZT10 group and 131.0\u00b133.9 mg/dL in the \nROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group \nand 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352\u20132.795]; P= \n0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 \ngroups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 \nand ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group \nand 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. \nCorrespondence: Keun-Sik Hong\nDepartment of Neurology, Inje University \nIlsan Paik Hospital, 170 Juhwa-ro, \nIlsanseo-gu, Goyang 10380, Korea\nTel: +82-31-910-7680\nEmail: nrhks455@gmail.com\nhttps://orcid.org/0000-0002-4684-6111\nReceived: September 15, 2022\nRevised: January 17, 2023\nAccepted: February 14, 2023"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 702
encoding: FLOAT32
metadata:
{"title": "Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy", "chroma:document": "The Journal of Clinical Investigation   \nR E S E A R C H  A R T I C L E\n1\nIntroduction\nEfforts to clear HIV infection require a careful assessment of all \nthe tissue reservoirs in which the virus persists despite durable \nantiretroviral therapy (ART). The CNS is a site with unique biolog-\nical, immunological, and pharmacological features (1). However, \nrigorous evidence of viral persistence in the CNS cells of humans \non durable suppressive ART is incomplete (2\u20135). Circulating T cells \nhave been well characterized as the major HIV reservoir in the \nperipheral blood and may circulate into the CNS, contributing to \nHIV persistence in the brain (6). Myeloid cells are another major \ncellular component of the immune system infected by SIV and HIV, \nand infection may persist in brain myeloid cells (BrMCs) (7\u201313). \nViral rebound in the CNS was reported upon interruption of therapy \nin the humanized myeloid-only mouse model of HIV latency (11). \nReplication-competent SIV has also been reported in brain macro-\nphages of ART-suppressed, SIV-infected rhesus macaques (14\u201316).\nGiven the obvious challenges in accessing human brain tis-\nsue, the HIV reservoir in BrMCs, including long-lived and self- \nrenewing microglia (MG), has not been rigorously studied in \npeople with HIV (PWH) on long-term ART. The lack of physio-\nlogically relevant cellular model systems that faithfully replicate \npersistent HIV infection in BrMCs or MG poses another challenge \nto the study of these CNS cell types. Immortalized MG cell lines, \nsuch as HMC3 and C20, have been used as HIV infection models \nbut have transcriptional profiles distinct from that of primary MG \n(17), making them less relevant to the study of the biology of HIV \npersistence in the CNS. Human studies of HIV persistence in the \nCNS have been limited to the examination of archived postmor-\ntem brain tissues. Most studies of HIV reservoirs in brain tissue \nhave lacked confirmation of ART adherence and viral suppres-\nsion prior to death and may have utilized brain tissues that had"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 703
encoding: FLOAT32
metadata:
{"title": "Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy", "chroma:document": "begun to degrade prior to collection. Thus, it remains unclear \nwhether human BrMCs, and especially long-lived MG, are latent-\nly infected, and if they encode replication-competent HIV despite \ndurable, successful ART.\nTo address these challenges, we first developed protocols to \nisolate highly pure populations of BrMCs and MG from the tissues \nof nonhuman primates (NHPs). We then adapted these protocols \nto the study of human brain tissues containing large numbers of \nBrain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following \ncessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we \nisolated brain myeloid cells (BrMCs) from nonhuman primates and rapid autopsy of people with HIV (PWH) on ART and \nsought evidence of persistent viral infection. BrMCs predominantly displayed microglial markers, in which up to 99.9% \nof the BrMCs were TMEM119+ MG. Total and integrated SIV or HIV DNA was detectable in the MG, with low levels of cell-\nassociated viral RNA. Provirus in MG was highly sensitive to epigenetic inhibition. Outgrowth virus from parietal cortex \nMG in an individual with HIV productively infected both MG and PBMCs. This inducible, replication-competent virus and \nvirus from basal ganglia proviral DNA were closely related but highly divergent from variants in peripheral compartments. \nPhenotyping studies characterized brain-derived virus as macrophage tropic based on the ability of the virus to infect cells \nexpressing low levels of CD4. The lack of genetic diversity in virus from the brain suggests that this macrophage-tropic \nlineage quickly colonized brain regions. These data demonstrate that MG harbor replication-competent HIV and serve as  \na persistent reservoir in the brain.\nBrain microglia serve as a persistent HIV reservoir \ndespite durable antiretroviral therapy"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 704
encoding: FLOAT32
metadata:
{"title": "Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy", "chroma:document": "Yuyang Tang,1,2 Antoine Chaillon,3 Sara Gianella,3 Lilly M. Wong,1 Dajiang Li,1 Theresa L. Simermeyer,1 Magali Porrachia,3  \nCaroline Ignacio,3 Brendon Woodworth,3 Daniel Zhong,1 Jiayi Du,1 Eduardo de la Parra Polina,1 Jennifer Kirchherr,1 Brigitte Allard,1 \nMatthew L. Clohosey,1 Matt Moeser,4 Amy L. Sondgeroth,4 Gregory D. Whitehill,5 Vidisha Singh,6 Amir Dashti,6 Davey M. Smith,3 \nJoseph J. Eron,2,7 Katherine J. Bar,5 Ann Chahroudi,6,8 Sarah B. Joseph,1,4,9 Nancie M. Archin,1,2 David M. Margolis,1,2,7,9 and Guochun Jiang1,2,10\n1University of North Carolina (UNC) HIV Cure Center, and 2Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 3Department \nof Medicine, UCSD, La Jolla, California, USA. 4UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, North Carolina, USA. 5Department of Medicine, \nUniversity of Pennsylvania, Philadelphia, Pennsylvania, USA. 6Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. 7Department of Epidemiology, Gillings School of Global \nPublic Health, University of North Carolina at Chapel Hill, North Carolina, USA. 8Center for Childhood Infections and Vaccines of Children\u2019s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA. \n9Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 10Department of Epidemiology, Gillings School of Global \nPublic Health, University of North Carolina at Chapel Hill, North Carolina, USA.\nConflict of interest: The authors have declared that no conflict of interest exists.\nCopyright: \u00a9 2023, Tang et al. This is an open access article published under the \nterms of the Creative Commons Attribution 4.0 International License.\nSubmitted: November 23, 2022; Accepted: April 25, 2023; Published: June 15, 2023.\nReference information: J Clin Invest. 2023;133(12):e167417."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 705
encoding: FLOAT32
metadata:
{"title": "Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy", "chroma:document": "https://doi.org/10.1172/JCI167417."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 706
encoding: FLOAT32
metadata:
{"title": "Crossed optic ataxia: possible role of the dorsal splenium", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:533-539\nCrossed optic ataxia: possible role of the dorsal\nsplenium\nJOSE M FERRO,* JM BRAVO-MARQUES,* A CASTRO-CALDAS,* LOBO ANTUNESt\nFrom the Language Research Laboratory* and the Neuropathology Laboratory, t Centro de Estudos Egas\nMoniz (INIC), Department ofNeurology, Hospital de Santa Maria, Lisbon, Portugal\nSUMMARY An unusual combination of disconnective syndromes is reported: transcortical motor\naphasia,\nleft arm apraxia and optic ataxia. Neuropathological examination showed\na\nleft\nparieto-occipital and a subcortical frontal infarct and a lesion of the dorsal part of the posterior\ntwo-fifths of the callosum. The frontal lesion caused the transcortical motor aphasia and pro-\nduced the left arm apraxia. Visuomotor incoordination in the right hemispace was due to the left\nparieto-occipital infarct, while the crossed optic ataxia in the left hemispace was attributed to the\ncallosal lesion. It is proposed that the pathway that serves crossed visual reaching passes through\nthe dorsal part of the posterior callosum. This case reinforces the growing evidence that fibres in\nthe corpus callosum are arranged in ventro-dorsal functional lamination.\nOptic ataxia or visuomotor ataxia' consists of a dis-\nturbance in reaching under visual control that may\naffect one or both hands, and be present either in\nthe whole or in part of the visual fields. A probable\nexplanation for this defect is a disconnection be-\ntween the visual and motor areas, in such a way that\nvisual perception, naming, and reading are possible,\nalthough visual information cannot gain access to\nthe hand motor areas in order to steer manual reach-\ning. This explanation was supported by the experi-\nmental study of Haaxma and Kuypers2 who could\ndisturb visual guided hand movements by means of a\nparietal leucotomy in the split-brain monkey. The\nreports by Castaigne and associates3 4 of visual\nataxia following surgical section of the parieto-\noccipital junction, which severed association fibres"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 707
encoding: FLOAT32
metadata:
{"title": "Crossed optic ataxia: possible role of the dorsal splenium", "chroma:document": "between the occipital and frontal lobes, are also in\nkeeping with this view. It is suggested from these\nstudies that the pathway subserving visuomotor\nbehaviour connects the occipital with the frontal\nlobe and crosses through the posterior parietal lobe.\nThe pathway connecting the visual areas of one\nhemisphere with the contralateral motor and pre-\nmotor areas (in which a lesion, according to Rondot,\nAddress for reprint requests: Jos6 M Ferro, MD, Neurobehavioral\nUnit, Centro de Estudos Egas Moniz, Hospital Santa Maria, 1600\nLisboa, Portugal.\nReceived 14 May 1982 and in revised form 23 January 1983.\nAccepted 7 February 1983\nRecondo and Dumas',\ninduces\na crossed\noptic\nataxia, that is, inability to reach in one hemifield\nwith the hand of the opposite side) is, according to\nmost animal studies, via the callosum.5-9 Further, it\nappears that adequate interhemispheric transmis-\nsion for the visual control of the ipsilateral hand and\nfingers is effected by the splenium.'0 Evidence from\nclinical studies is scanty because the majority of\ncases of optic ataxia which underwent anatomical\nstudy\nhad\nbilateral\noptic\nataxia\nand\nbilateral\nparieto-occipital lesions.' Stenvers\" stated that for\ncrossed visuomotor reaching,\nvisual information\ncould travel from the occipital to the ipsilateral fron-\ntal lobe and then to the contralateral one, crossing\nthe anterior callosum (case 34) or be transferred\nfrom one occipital lobe to the opposite, via the post-\nerior callosum, and then, ipsilaterally, to the frontal\nlobe. Indeed, crossed visuomotor ataxia in Boller S12\ncase is explained by lesions severing both pathways.\nIn the present clinico-pathological study we propose\nthat the pathway that serves crossed visuomotor\ncontrol travels through the dorsal part of the post-\nerior callosum.\nCase report\nA 73-year-old right-handed woman had speech and visual\ndisturbances and slight right-sided weakness of sudden\nonset. Blood pressure was 100/70 mmHg, the pulse was\nirregular with premature beats, and a systolic blowing"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 708
encoding: FLOAT32
metadata:
{"title": "Crossed optic ataxia: possible role of the dorsal splenium", "chroma:document": "murmur was heard in the aortic area. There was a slight\n533"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 709
encoding: FLOAT32
metadata:
{"title": "Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia", "chroma:document": "Vol:.(1234567890)\nJournal of Neurology (2023) 270:2360\u20132369\nhttps://doi.org/10.1007/s00415-023-11637-x\n1 3\nORIGINAL COMMUNICATION\nReduced cerebello\u2011cerebral functional connectivity correlates \nwith\u00a0disease severity and\u00a0impaired white matter integrity in\u00a0Friedreich \nataxia\nRebecca\u00a0Kerestes1\u00a0\u00b7 Hannah\u00a0Cummins1\u00a0\u00b7 Nellie\u00a0Georgiou\u2011Karistianis2\u00a0\u00b7 Louisa\u00a0P.\u00a0Selvadurai1\u00a0\u00b7 Louise\u00a0A.\u00a0Corben3\u00a0\u00b7 \nMartin\u00a0B.\u00a0Delatycki3\u00a0\u00b7 Gary\u00a0F.\u00a0Egan2,4\u00a0\u00b7 Ian\u00a0H.\u00a0Harding1,4 \nReceived: 17 November 2022 / Revised: 7 February 2023 / Accepted: 19 February 2023 / Published online: 1 March 2023 \n\u00a9 The Author(s) 2023\nAbstract\nFriedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease characterised in most cases by progressive and \ndebilitating motor dysfunction. Degeneration of cerebellar white matter pathways have been previously reported, alongside \nindications of cerebello-cerebral functional alterations. In this work, we examine resting-state functional connectivity changes \nwithin cerebello-cerebral circuits, and their associations with disease severity (Scale for the Assessment and Rating of Ataxia \n[SARA]), psychomotor function (speeded and paced finger tapping), and white matter integrity (diffusion tensor imaging) \nin 35 adults with FRDA and 45 age and sex-matched controls. Voxel-wise seed-based functional connectivity was assessed \nfor three cerebellar cortical regions (anterior lobe, lobules I-V; superior posterior lobe, lobules VI-VIIB; inferior posterior \nlobe, lobules VIIIA-IX) and two dentate nucleus seeds (dorsal and ventral). Compared to controls, people with FRDA \nshowed significantly reduced connectivity between the anterior cerebellum and bilateral pre/postcentral gyri, and between \nthe superior posterior cerebellum and left dorsolateral PFC. Greater disease severity correlated with lower connectivity in \nthese circuits. Lower anterior cerebellum-motor cortex functional connectivity also correlated with slower speeded finger"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 710
encoding: FLOAT32
metadata:
{"title": "Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia", "chroma:document": "tapping and less fractional anisotropy in the superior cerebellar peduncles, internal capsule, and precentral white matter in \nthe FRDA cohort. There were no significant between-group differences in inferior posterior cerebellar or dentate nucleus \nconnectivity. This study indicates that altered cerebello-cerebral functional connectivity is associated with functional status \nand white matter damage in cerebellar efferent pathways in people with FRDA, particularly in motor circuits.\nKeywords Friedreich ataxia\u00a0\u00b7 Cerebellum\u00a0\u00b7 Resting state\u00a0\u00b7 Anterior\u00a0\u00b7 Superior\u00a0\u00b7 Dentate\nIntroduction\nFriedreich ataxia (FRDA) is a recessively inherited neuro-\ndegenerative disorder principally characterised by progres-\nsive motor incoordination [1] that manifests secondary to \ndegeneration in the spinal cord, cerebellum, and cerebello-\ncerebral connections [2].\u00a0Quantitative structural magnetic \nresonance imaging (MRI) studies have been key to defining \nthe pattern and evolution of anatomical brain changes in \npeople with FRDA. MRI studies indicate early, robust, and \nprogressive volume loss in the dentate nuclei [3, 4], which \nare the primary sites of pathology in the brain [5]. Atro-\nphy of the cerebellar cortex is more subtle and considered a \nlate feature of the disease. This volume loss is particularly \nweighted to the anterior lobe and adjacent areas of the pos-\nterior lobe (i.e., lobules I-VI) [2, 6]], which connect to motor \nand premotor areas of the cerebral cortex. Loss of volume \nRebecca Kerestes and Hannah Cummins equally contributed.\n * Ian H. Harding \n \nian.harding@monash.edu\n1 \nDepartment of\u00a0Neuroscience, Central Clinical School, \nMonash University, Melbourne, Australia\n2 \nTurner Institute for\u00a0Brain and\u00a0Mental Health, School \nof\u00a0Psychological Sciences, Monash University, Melbourne, \nAustralia\n3 \nBruce Lefroy Centre for\u00a0Genetic Health Research, Murdoch \nChildren\u2019s Research Institute, Melbourne, Australia\n4 \nMonash Biomedical Imaging, Monash University, \nMelbourne, VIC\u00a03800, Australia"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 711
encoding: FLOAT32
metadata:
{"title": "Quantitative immunopeptidomics reveals a tumor stroma\\205specific target for T cell therapy", "chroma:document": "Quantitative immunopeptidomics reveals a tumor stroma\u2013\nspecific target for T cell therapy\nGloria B. Kim1,\u2020, Jens Fritsche2,\u2020, Sebastian Bunk2,\u2020, Andrea Mahr2, Felix Unverdorben2, \nKevin Tosh1, Hong Kong1, Colby R. Maldini1, Chui Lau1, Sriram Srivatsa1, Shuguang \nJiang1, Joshua Glover1, Derek Dopkin1, Carolyn X. Zhang1, Heiko Schuster2, Daniel \nJ. Kowalewski2, Valentina Goldfinger2, Martina Ott2, David Fuhrmann2, Maike Baues2, \nHans Boesmueller3, Christoph Schraeder2, Gisela Schimmack2, Colette Song2, Franziska \nHoffgaard2, Michael Roemer2, Chih-Chiang Tsou4, Martin Hofmann2, Thomas Treiber2, \nMeike Hutt2, Leonie Alten2, Maike Jaworski2, Amir Alpert4, Sarah Missel2, Carsten \nReinhardt2, Harpreet Singh2,4, Oliver Schoor2, Steffen Walter4, Claudia Wagner2, Dominik \nMaurer2,\u2021, Toni Weinschenk2,4,*,\u2021, James L. Riley1,*,\u2021\nexclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works\n*Corresponding author. toni.weinschenk@immatics.com (T.W.); rileyj@upenn. edu (J.L.R.).\n\u2020These authors contributed equally to this work.\n\u2021These authors contributed equally to this work.\nAuthor contributions: G.B.K., K.T., H. Singh, C.R., S.W., T.W., and J.L.R. designed the study. G.B.K., H. Singh, S.W., T.W., and \nJ.L.R. provided funding. D.M., T.W., S.M., O.S., and J.L.R. supervised the project. The original draft was written by G.B.K., S.B., \nJ.F., D.M., T.W., and J.L.R. Editing and review were supported by all authors. Sample procurement and analysis was performed and \nsupervised by M.O. MS was performed and supervised by D.J.K. and T.W. RNA sequencing was analyzed by F.H. Data processing, \ndatabase development, bioinformatics, and statistical analyses were performed by F.H., M.R., C.-C.T., and J.F. Target discovery was \nperformed by A.M., C. Song, and J.F. Absolute peptide copy number determination was performed by V.G., C. Schraeder, and H. \nSchuster. ISH was performed by D.F., M.B., and M.O. Pathology review was performed by H.B. Selection of similar peptides and cell"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 712
encoding: FLOAT32
metadata:
{"title": "Quantitative immunopeptidomics reveals a tumor stroma\\205specific target for T cell therapy", "chroma:document": "lines for off-target toxicity studies was performed by G.S., S.B., and H. Schuster. TCR discovery and characterization of wild-type \nTCR variants were performed by G.B.K., K.T., C.L., L.A., A.A., and S.B. Affinity enhancement of F9 TCR and selection of maturated \nvariants were performed by F.U., M. Hutt, M. Hofmann, T.T., and S.B. In vitro characterization of antitumor efficacy and safety \nprofiling of affinity-enhanced F9 TCR variants were performed by G.B.K., C.X.Z., S.S., M.J., A.A., and C.W. In vivo studies were \nperformed by G.B.K., K.T., H.K., C.R.M., S.J., J.G., D.D., and C.X.Z.\nSUPPLEMENTARY MATERIALS\nwww.science.org/doi/10.1126/scitranslmed.abo6135 \nFigs. S1 to S8\nTables S1 to S4\nMDAR Reproducibility Checklist \nView/request a protocol for this paper from Bio-protocol.\nCompeting interests: J.F., S.B., A.M., F.U., H. Schuster, D.J.K., V.G., M.O., D.F., M.B., C. Song, G.S., C. Schraeder, F.H., M.R., \nC.-C.T., M. Hofmann, T.T., M. Hutt, L.A., M.J., A.A., S.M., O.S., H. Singh, C.R., S.W., C.W., D.M., and T.W. were employees \nof Immatics in the course of this work and may have securities from Immatics. J.L.R. is a cofounder and holds an equity interest \nin Tmunity Therapeutics. C.R., H. Singh, S.W., and T.W. are management board members of Immatics. All other authors have no \ncompeting interests. The following patent applications relate to subject matter in this paper: PCT/EP2011/053863 (entitled \u201cNovel \nImmunotherapy against several tumors including gastrointestinal and gastric cancer\u201d), disclosing subject matter coinvented by J.F., \nH. Singh, S.W., and T.W.; PCT/EP2017/066630 (entitled \u201cT cell receptors and immune therapy using the same\u201d), disclosing subject \nmatter coinvented by S.B., S.W., D.M., and L.A.; PCT/EP2018/080176 (entitled \u201cNovel engineered T cell receptors and immune \ntherapy using the same\u201d), disclosing subject matter coinvented by S.B., F.U., M. Hofmann, M. Hutt, C.W., D.M., and L.A.; PCT/"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 713
encoding: FLOAT32
metadata:
{"title": "Quantitative immunopeptidomics reveals a tumor stroma\\205specific target for T cell therapy", "chroma:document": "EP2014/066755 (entitled \u201cNovel immunotherapy against several tumors, such as lung cancer, including NSCLC\u201d), disclosing subject \nmatter coinvented by J.F., C. Song, H. Singh, S.W., and T.W.; PCT/EP2016/055817 (entitled \u201cNovel peptides and combination \nof peptides for use in immunotherapy against pancreatic cancer and other cancers\u201d), disclosing subject matter coinvented by J.F., \nA.M., M.O., H. Singh, O.S., C.W., and T.W.; PCT/EP2016/059053 (entitled \u201cNovel peptides and combination of peptides for use \nin immunotherapy against lung cancer, including NSCLC and other cancers\u201d), disclosing subject matter coinvented by J.F., A.M., \nC. Song, H. Singh, O.S., C.W., and T.W.; PCT/EP2016/060007 [entitled \u201cNovel peptides and combination of peptides and scaffolds \nthereof for use in immunotherapy against colorectal carcinoma (CRC) and other cancers\u201d], disclosing subject matter coinvented \nby J.F., A.M., H. Singh, O.S., and T.W.; and PCT/EP2016/079059 (entitled \u201cPeptides and combination of peptides for use in \nimmunotherapy against breast cancer and other cancers\u201d), disclosing subject matter coinvented by J.F., A.M., H. Singh, O.S., and T.W.\nHHS Public Access\nAuthor manuscript\nSci Transl Med. Author manuscript; available in PMC 2023 April 26.\nPublished in final edited form as:\nSci Transl Med. 2022 August 31; 14(660): eabo6135. doi:10.1126/scitranslmed.abo6135.\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: 714
encoding: FLOAT32
metadata:
{"title": "Biopsy and findings in patient receiving cerebellar stimulation for epilepsy", "chroma:document": "Journal of Neurology, Neurosurgery, and Psychiatry 1983 ;46: 266-273\nBiopsy and post-mortem findings in a patient\nreceiving cerebellar stimulation for epilepsy\nGDS WRIGHT, RO WELLER\nFrom the Wessex Neurological Centre and Department ofNeuropathology, Southampton General Hospital,\nSouthampton, UK\nSUMMARY\nCerebellar stimulating equipment was implanted in a 24-year-old male with severe\nepilepsy. He received continuous alternating stimulation for at least two months, intermittent\nbilateral stimulation on demand for at least two months and numerous short bursts of stimulation\nduring preliminary testing and calibration of the apparatus. The patient died during a prolonged\ngrand mal seizure 16 months after implantation and this paper reports the findings at necropsy. A\nspecial study was made of the degree of tissue damage in the cerebellar hemispheres resulting\nfrom implantation of the electrodes and subsequent cerebellar stimulation. There was deep\ngrooving of the upper aspect of the cerebellum under the electrodes but only a minor degree of\nneuronal loss and gliosis was observed in the underlying cortex. Purkinje cell populations in the\ncerebellum at necropsy were similar to those in a biopsy specimen taken 16 months previously\nduring implantation. The electrodes were covered with a thick layer of fibrous tissue but they\nwere not adherent to the cerebellar surface. Thus, the main significant findings in the present case\nwere the very slight structural damage to the cerebellum in contact with the electrodes and the\nintense fibrosis around the electrodes themselves. These features are discussed in relation to the\nefficacy of long-term cerebellar stimulation.\nCerebellar stimulation has been recommended as a\nuseful treatment in severe epilepsy and in a variety\nof motor disorders.' 2 There is, however, still consid-\nerable uncertainty about the degree of tissue dam-\nage caused by implantation of the electrodes and by\nchronic electrical stimulation of the cerebellum.3\nAlthough the study of a number of human and ani-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 715
encoding: FLOAT32
metadata:
{"title": "Biopsy and findings in patient receiving cerebellar stimulation for epilepsy", "chroma:document": "mal brains has shown that pathological changes\ncan occur with cerebellar stimulation, firm criteria\nhave not yet been determined to enable optimal\nparameters for cerebellar stimulation to be defined.3\nThere are only a few reports of post-mortem\nstudies in patients who have received cerebellar\nstimulation.249 The present paper is a post-mortem\nstudy of a 24-year-old male with severe epilepsy\nwho died 16 months after the implantation of cere-\nbellar electrodes. Electrode access resistance was\nmeasured\nat\nimplantation\nand\nthe\nstimulating\nAddress for reprint requests: Dr GDS Wright, Department of\nNeurology, St James's University Hospital, Beckett Street, Leeds\nLS9 7TF, UK.\nReceived 16 July 1982\nAccepted 4 October 1982\n266\nequipment was accurately calibrated. The function-\ning of the stimulating equipment was regularly\nreviewed and reasonable estimates of the charge\ndensity at the cerebellar surface and the total charge\ndelivered to the cerebellum are therefore available.\nCase history\nThe patient, (SB, born 8/1/55), was 24 years old at the time\nof his admission to the Southampton cerebellar stimulation\ntrial. His epilepsy began at the age of seven years and there\nwere no predisposing factors. He suffered from grand mal\nepilepsy, complex partial epilepsy and petit mal epilepsy.\nThe grand mal attacks occurred rarely, but could be severe\nand prolonged. Complex partial attacks occuffed up to five\ntimes a day and the petit mal attacks up to forty or more in\na day. Medication consisted of phenytoin 200 mg twice\ndaily and carbamazepine 200 mg four times a day and he\nhad been on this combination for over six months before\nadmission. It was considered the best combination and the\noptimal\ndosage\nand\ngave serum\nlevels\nof phenytoin\n1-3 mg/100 ml and carbamazepine 0-7 mg/100 ml. Previ-\nously he had, at different times, been treated with these\ndrugs in different dosages and with primidone.\nAt operation on 20 March 1979 under general anaes-\nthesia, two eight-button electrode pads with an electrode"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 716
encoding: FLOAT32
metadata:
{"title": "Biopsy and findings in patient receiving cerebellar stimulation for epilepsy", "chroma:document": "surface area 32 mm2 (Avery Laboratories Inc) were placed"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 717
encoding: FLOAT32
metadata:
{"title": "Safety and preservation of cardiac function following therapeutic vaccination against Trypanosoma cruzi in rhesus macaques", "chroma:document": "Safety and preservation of cardiac function following therapeutic \nvaccination against Trypanosoma cruzi in rhesus macaques\nEric Dumonteila,*, Claudia Herreraa, Preston A. Marxa,b\naDepartment of Tropical Medicine, School of Public Health and Tropical Medicine, Vector-Borne \nand Infectious Disease Research Center, Tulane University, New Orleans, LA, USA\nbDivision of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, \nLA, USA\nAbstract\nBackground:\u00a0Chronic Chagasic cardiomyopathy is responsible for a large disease burden in \nthe Americas, and a therapeutic vaccine would be highly desirable. We tested the safety and \nefficacy of a therapeutic DNA vaccine encoding antigens TSA-1 and Tc24 for preventing cardiac \nalterations in experimentally infected macaques. A secondary objective was to evaluate the \nfeasibility of detecting changes in cardiac alterations in these animals.\nMethods:\u00a0Na\u00efve rhesus macaques were infected with Trypanosoma cruzi and treated with three \ndoses of DNA vaccines.\nResults:\u00a0Blood cell counts and chemistry indicated that therapeutic vaccination was safe, as \nhepatic and renal function appeared unaffected by the vaccination and/or infection with T. cruzi. \nElectrocardiographic (ECG) recordings indicated that no marked arrhythmias developed up to 7 \nmonths post-infection. Univariate analysis of ECG parameters found no significant differences in \nany of these parameters between vaccinated and control macaques. However, linear discriminant \nanalysis revealed that control macaques presented clear alterations in their ECG patterns at 7 \nmonths post-infection, indicative of the onset of conduction defects and cardiac alterations, and \nthese changes were prevented in vaccine treated macaques.\nConclusions:\u00a0This is the first evidence that therapeutic vaccination against T. cruzi can prevent \ncardiac alterations in non-human primates, strengthening the rationale for developing a human \nvaccine against Chagas disease.\nKeywords"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 718
encoding: FLOAT32
metadata:
{"title": "Safety and preservation of cardiac function following therapeutic vaccination against Trypanosoma cruzi in rhesus macaques", "chroma:document": "Keywords\nChagas disease; DNA vaccine; Cardiomyopathy; Non-human primates; Electrocardiograph\nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).\n*Corresponding author. Department of Tropical Medicine, Vector-Borne and Infectious Disease Research Center, School of Public \nHealth and Tropical Medicine, Tulane University, 1440 Canal St., New Orleans, LA, 70112, USA. edumonte@tulane.edu (E. \nDumonteil). \nDeclaration of competing interest\nThe authors have no conflict of interest.\nHHS Public Access\nAuthor manuscript\nJ Microbiol Immunol Infect. Author manuscript; available in PMC 2023 April 26.\nPublished in final edited form as:\nJ Microbiol Immunol Infect. 2023 April ; 56(2): 400\u2013407. doi:10.1016/j.jmii.2022.09.003.\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: 719
encoding: FLOAT32
metadata:
{"title": "DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice", "chroma:document": "The Journal of Clinical Investigation   \nR E S E A R C H  A R T I C L E\n1\nIntroduction\nAtherosclerosis, the buildup of plaque and hardening of the arter-\nies over time, is a widespread and debilitating disease in older \npopulations. Many risk factors contribute to the development of \natherosclerosis, including unhealthy diets, smoking, genetics, \ndiabetes, aging, and obesity. Among them, aging is one of the \nmost important factors, increasing the prevalence, incidence, and \nmortality associated with atherosclerosis (1, 2). The most serious \ncomplication and leading cause of death associated with athero-\nsclerosis is the thrombotic occlusion of the arteries following ero-\nsion or rupture of an atherosclerotic plaque. The cap of the plaque \nconsists of a layer of vascular smooth muscle cells (VSMCs) that \nhave dedifferentiated into synthetic, noncontractile cells that \ntypically proliferate and migrate, but also a small population of \nsenescent, inflammatory VSMCs (3).\nPrevious research has shown that cellular senescence is \nassociated with the development and progression of atheroscle-\nrosis (4). Cellular senescence, a hallmark phenotype of cells in \naging tissues, is characterized by increased production of cyclin- \ndependent kinase inhibitors and tumor suppressors such as p16 \n(CDKN2A), p21 (CDKN1A), and p53 (TP53) as well as many fac-\ntors of the senescence-associated secretory phenotype (SASP), \nincluding cytokines (e.g., IL-6, IL-8), chemokines (e.g., CCL2), \nadhesion molecules (e.g., ICAM1), matrix remodeling enzymes \n(e.g., MMPs), and angiogenic factors (e.g., VEGF). Senescent cells \nalso display a senescence-associated \u03b2-galactosidase (SA\u2013\u03b2-gal) \nactivity (5, 6). Although senescent cells possess the ability to be \nboth beneficial and harmful depending on the biological situa-\ntion, there is little doubt that the accrual of senescent cells in older \nhuman tissues is detrimental and contributes to pathologies asso-\nciated with aging (7\u20139). As a result of their widespread detrimen-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 720
encoding: FLOAT32
metadata:
{"title": "DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice", "chroma:document": "tal effects in many diseases, interest is escalating in developing \ntherapies directed against senescent cells (senotherapies) and in \ndiscovering senescence-associated cell-surface proteins. Impor-\ntantly, VSMCs cultured from atherosclerotic plaques display a \nmyriad of these senescence traits; thus, further research on senes-\ncent VSMCs in atherosclerosis is crucial to our understanding of \nthe progression and treatment of this age-associated disease (10).\nThe development of age-related multifactorial diseases such \nas atherosclerosis is associated with persistent systemic inflam-\nmation. However, the dynamic interplay among aging, inflamma-\ntion, and VSMC senescence is not well understood. A recent study \nfound that dipeptidyl peptidase 4 (DPP4) is highly expressed on \nthe surface of senescent cells (11). While the effect of DPP4 on \nVSMCs is not characterized, DPP4 inhibitors, known as gliptins, \nare clinically used to treat diabetes (12). In animal models, gliptins \nhave the ability to reduce atherosclerosis and inflammation inde-\npendently of the canonical role of DPP4 in glucose metabolism \n(13\u201317). Thus, we set out to investigate the ability of DPP4 inhib-\nSenescent vascular smooth muscle cells (VSMCs) accumulate in the vasculature with age and tissue damage and secrete \nfactors that promote atherosclerotic plaque vulnerability and disease. Here, we report increased levels and activity of \ndipeptidyl peptidase 4 (DPP4), a serine protease, in senescent VSMCs. Analysis of the conditioned media from senescent \nVSMCs revealed a unique senescence-associated secretory phenotype (SASP) signature comprising many complement and \ncoagulation factors; silencing or inhibiting DPP4 reduced these factors and increased cell death. Serum samples from persons \nwith high risk for cardiovascular disease contained high levels of DPP4-regulated complement and coagulation factors. \nImportantly, DPP4 inhibition reduced senescent cell burden and coagulation and improved plaque stability, while single-cell"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 721
encoding: FLOAT32
metadata:
{"title": "DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice", "chroma:document": "resolution of senescent VSMCs reflected the senomorphic and senolytic effects of DPP4 inhibition in murine atherosclerosis. \nWe propose that DPP4-regulated factors could be exploited therapeutically to reduce senescent cell function, reverse \nsenohemostasis, and improve vascular disease.\nDPP4 inhibition impairs senohemostasis to improve \nplaque stability in atherosclerotic mice\nAllison B. Herman,1 Dimitrios Tsitsipatis,1 Carlos Anerillas,1 Krystyna Mazan-Mamczarz,1 Angelica E. Carr,1 Jordan M. Gregg,1 \nMingyi Wang,2 Jing Zhang,2 Marc Michel,1 Charnae\u2019 A. Henry-Smith,1 Sophia C. Harris,2 Rachel Munk,1 Jennifer L. Martindale,1 \nYulan Piao,1 Jinshui Fan,1 Julie A. Mattison,3 Supriyo De,1 Kotb Abdelmohsen,1 Robert W. Maul,4 Toshiko Tanaka,3  \nAnn Zenobia Moore,3 Megan E. DeMouth,5 Simone Sidoli,6 Luigi Ferrucci,3 Yie Liu,1 Rafael de Cabo,3  \nEdward G. Lakatta,2 and Myriam Gorospe1\n1Laboratory of Genetics and Genomics, 2Laboratory of Cardiovascular Sciences, 3Translational Gerontology Branch, and 4Laboratory of Molecular Biology and Immunology, National Institute on Aging (NIA) \nIntramural Research Program (IRP), NIH, Baltimore, Maryland, USA. 5Department of Microbiology and Immunology and 6Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.\nConflict of interest: The authors have declared that no conflict of interest exists.\nCopyright: \u00a9 2023, Herman et al. This is an open access article published under the \nterms of the Creative Commons Attribution 4.0 International License.\nSubmitted: October 3, 2022; Accepted: April 19, 2023; Published: June 15, 2023.\nReference information: J Clin Invest. 2023;133(12):e165933. \nhttps://doi.org/10.1172/JCI165933."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 722
encoding: FLOAT32
metadata:
{"title": "Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases", "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: 723
encoding: FLOAT32
metadata:
{"title": "Development of \\215hunger neurons\\216 and the unanticipated relationship between energy metabolism and mother-infant interactions", "chroma:document": "Development of \u201chunger neurons\u201d and the unanticipated \nrelationship between energy metabolism and mother-infant \ninteractions\nOnur Iyilikci1,#, Marcelo R. Zimmer1,#, Marcelo O. Dietrich1,2,3,*\n1Laboratory of Physiology of Behavior, Department of Comparative Medicine, Yale School of \nMedicine, New Haven, CT, USA.\n2Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.\n3Yale Center for Molecular and Systems Metabolism, Yale School of Medicine, New Haven, CT, \nUSA.\nAbstract\nOver the course of a lifetime, the perinatal period plays an outsized role in the function of \nphysiological systems. Here, we discuss how neurons that regulate energy metabolism contribute \nto the infant\u2019s relationship with the mother. We focus our discussion on Agrp neurons, which \nare located in the arcuate nucleus of the hypothalamus. These neurons heavily regulate energy \nmetabolism. Because offspring transition from a period of dependence on the caregiver to \nindependence, we discuss the importance of the caregiver-offspring relationship for the function \nof Agrp neurons. We present evidence that, in the adult, Agrp neurons motivate the animal to \neat, while, in the neonate, they motivate the offspring to seek the proximity of the caregiver. \nWe specifically highlight the peculiarities in the development of Agrp neurons and how they \nrelate to the regulation of metabolism and behavior over the course of a lifetime. In sum, this \nreview considers the unique insights that ontogenetic studies can offer toward our understanding \nof complex biological systems, such as the regulation of energy metabolism and mother-infant \nattachment.\nKeywords\nHypothalamus; obesity; diabetes; development; melanocortin system; mother-infant relationship; \nenergy balance; metabolism\nLife as an infant\nCompared to adults, infants deal with distinct physiological disturbances, and, thus, they \nneed regulatory processes that are specific to each stage of development. For example, due"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 724
encoding: FLOAT32
metadata:
{"title": "Development of \\215hunger neurons\\216 and the unanticipated relationship between energy metabolism and mother-infant interactions", "chroma:document": "to their small body size, limited fat resources, and greater surface area to volume ratio\u2014\nwhich increases heat loss\u2014neonates are particularly vulnerable to cold exposure. As an \n*Correspondence to: marcelo.dietrich@yale.edu.\n#These authors contributed equally.\nHHS Public Access\nAuthor manuscript\nBiol Psychiatry. Author manuscript; available in PMC 2023 May 15.\nPublished in final edited form as:\nBiol Psychiatry. 2022 May 15; 91(10): 907\u2013914. doi:10.1016/j.biopsych.2022.02.962.\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: 725
encoding: FLOAT32
metadata:
{"title": "Bone Marrow Mesenchymal Stem Cells Reversed Ovarian Aging-related m6A RNA Methylation Modification Profile in Aged Granulosa Cells", "chroma:document": "Vol.:(0123456789)\n1 3\nhttps://doi.org/10.1007/s12015-022-10485-y\nBone Marrow Mesenchymal Stem Cells Reversed Ovarian \nAging\u2011related m6A RNA Methylation Modification Profile in\u00a0Aged \nGranulosa Cells\nChuan\u00a0Tian1\u00a0\u00b7 Yuanyuan\u00a0An2\u00a0\u00b7 Jing\u00a0Zhao1\u00a0\u00b7 Xiangqing\u00a0Zhu1\u00a0\u00b7 Wei\u00a0Wei1\u00a0\u00b7 Guangping\u00a0Ruan1\u00a0\u00b7 Ye\u00a0Li1\u00a0\u00b7 Xinghua\u00a0Pan1 \nAccepted: 1 December 2022 \n\u00a9 The Author(s) 2022\nAbstract\nBackground Ovarian ageing causes endocrine disturbances and the degeneration of systemic tissue and organ functions \nto seriously affect women's physical and mental health, and effective treatment methods are urgently needed. Based on our \nprevious studies using juvenile rhesus monkey bone marrow mesenchymal stem cells (BMMSCs) to treat ovarian ageing \nin rhesus monkey, we found that BMMSCs improved ovarian structure and function. This study continues to explore the \nmechanism by which BMMSCs reversed granulosa cell (GC) ageing.\nMethods A GC ageing model and coculture system of BMMSCs were established, changes in the level of the N6-methyl-\nadenosine (m6A) methylation modification were detected, m6A-modified RNA immunoprecipitation sequencing (MeRIP-\nseq) were performed, correlations between m6A peaks and mRNA expression were determined, and the expression of hub \ngenes was identified using Q-PCR, immunofluorescence staining, and western blot.\nResults Our results showed that  H2O2 successfully induced GC ageing and that BMMSCs reversed measures of GC ageing. \nBMMSCs increased the expression of the FTO protein and reduced the overall level of m6A. We identified 797 m6A peaks \n(348 hypomethylated and 449 hypermethylated peaks) and 817 differentially expressed genes (DEGs) (412 upregulated and \n405 downregulated) after aged GCs were cocultured with BMMSCs, which significantly associated with ovarian function \nand epigenetic modification. The epigenetic repressive mark and important cell cycle regulator lysine demethylase 8 (KDM8) \nwas downregulated at both the mRNA and protein levels, histone H3 was upregulated in aged GCs after BMMSC coculture,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 726
encoding: FLOAT32
metadata:
{"title": "Bone Marrow Mesenchymal Stem Cells Reversed Ovarian Aging-related m6A RNA Methylation Modification Profile in Aged Granulosa Cells", "chroma:document": "and KDM8 was upregulated after FTO was inhibited through FB23.\nConclusions Our study revealed an essential role for m6A in BMMSCs in reversing GC ageing, and FTO regulated KDM8 \nmediates histone H3 changes may as a novel regulatory mechanism in BMMSCs to reverse GC ageing.\nKeywords BMMSCs\u00a0\u00b7 Ovarian ageing\u00a0\u00b7 m6A\u00a0\u00b7 Lysine demethylase 8 (KDM8)\nAbbreviations\nBMMSCs \n Bone marrow mesenchymal stem cells\nhGC \n Human granulosa cell\nMeRIP-seq  M6A-modified RNA immunoprecipitation \nsequencing\nKDM8 \n Lysine demethylase 8\nm6A \n N6-methyladenosine\nDEGs \n Differentially expressed genes\nIntroduction\nThe world's population is ageing rapidly, and the number \nof elderly individuals has increased significantly, which \nhas placed great pressure on society and become one of \nthe major economic challenges facing contemporary soci-\nety [1\u20133]. The ovary is a dynamic reproductive endocrine \norgan that enacts female reproductive function through \novulation and the secretion of sex hormones and affects \ntissues and organs throughout the body [4, 5], it is also \none of the most sensitive organs to ageing. A variety of \n * Xinghua Pan \n \nxinghuapankm@163.com\n1 \nThe Basic Medical Laboratory of\u00a0the\u00a0920Th Hospital \nof\u00a0Joint Logistics Support Force of\u00a0PLA, The Transfer \nMedicine Key Laboratory of\u00a0Cell Therapy Technology \nof\u00a0Yunan Province, The Integrated Engineering Laboratory \nof\u00a0Cell Biological Medicine of\u00a0State and\u00a0Regions, \nKunming\u00a0650032, Yunnan\u00a0Province, China\n2 \nThe Affiliated Stomatology of\u00a0Kunming Medical University, \nKunming\u00a0650106, Yunnan\u00a0Province, China\n/ Published online: 7 January 2023\nStem Cell Reviews and Reports (2023) 19:953\u2013967"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 727
encoding: FLOAT32
metadata:
{"title": "Dichotomous Regulation of Striatal Plasticity by Dynorphin", "chroma:document": "Dichotomous Regulation of Striatal Plasticity by Dynorphin\nRenzhi Yang1,*, Rupa R. Lalchandani Tuan2,3,*, Fuu-Jiun Hwang2, Daniel W. Bloodgood2, \nDong Kong4, Jun B. Ding2,5,6,\u2020\n1Biology Graduate Program, Stanford University, Stanford, CA 94305, USA\n2Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA\n3Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, CA 94158, USA\n4Division of Endocrinology, Department of Pediatrics, F.M. Kirby Neurobiology Center, Boston \nChildren\u2019s Hospital and Harvard Medical School, Boston MA 02115, USA\n5Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, \nUSA\n6Stanford Bio-X, Stanford University, Stanford, CA 94305, USA\nAbstract\nModulation of corticostriatal plasticity alters the information flow throughout basal ganglia \ncircuits and represents a fundamental mechanism for motor learning, action selection, and reward. \nSynaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and \niSPNs) is regulated by two distinct networks of GPCR signaling cascades. While it is well-known \nthat dopamine D2 and adenosine A2a receptors bi-directionally regulate iSPN plasticity, it remains \nunclear how D1 signaling modulation of synaptic plasticity is counteracted by dSPN-specific Gi \nsignaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation \n(LTP) through Kappa Opioid Receptor (KOR) signaling in dSPNs. Both KOR antagonism and \nconditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels \nof D1 receptor activation. Behaviorally, mice lacking dynorphin in D1 neurons show comparable \nmotor behavior and reward-based learning, but enhanced flexibility during reversal learning. These \nfindings support a model in which D1R and KOR signaling bidirectionally modulate synaptic \nplasticity and behavior in the direct pathway.\n\u2020 Correspondence: J.B.D. (dingjun@stanford.edu).\n*Equal contribution\nAUTHOR CONTRIBUTIONS"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 728
encoding: FLOAT32
metadata:
{"title": "Dichotomous Regulation of Striatal Plasticity by Dynorphin", "chroma:document": "R.Y., R.R.L., and J.B.D. conceived this project. R.Y. performed electrophysiology recording and operant chamber behavior \nexperiments. R.R.L. characterized lox-pDyn mice, and performed immunostaining and behavioral experiments. F.J.H. performed \nthe spine imaging. D.K. and J.B.D. designed and generated lox-pDyn mice. R.Y. and R.R.L. analyzed the data. R.Y., R.R.L., D.W.B. \nand J.B.D. wrote the manuscript with input from all authors.\nCONFLICT OF INTEREST\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nMol Psychiatry. Author manuscript; available in PMC 2023 May 17.\nPublished in final edited form as:\nMol Psychiatry. 2023 January ; 28(1): 434\u2013447. doi:10.1038/s41380-022-01885-0.\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: 729
encoding: FLOAT32
metadata:
{"title": "New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine", "chroma:document": "REVIEW ARTICLE\nOPEN\nNew genetic and epigenetic insights into the chemokine\nsystem: the latest discoveries aiding progression toward\nprecision medicine\nHanli Xu\n1,4, Shuye Lin2,4, Ziyun Zhou1, Duoduo Li1, Xiting Zhang1, Muhan Yu1, Ruoyi Zhao1, Yiheng Wang1, Junru Qian1, Xinyi Li1,\nBohan Li1, Chuhan Wei1, Keqiang Chen3, Teizo Yoshimura3, Ji Ming Wang3 and Jiaqiang Huang1,2,3\u2709\n\u00a9 The Author(s) 2023\nOver the past thirty years, the importance of chemokines and their seven-transmembrane G protein-coupled receptors (GPCRs) has been\nincreasingly recognized. Chemokine interactions with receptors trigger signaling pathway activity to form a network fundamental to\ndiverse immune processes, including host homeostasis and responses to disease. Genetic and nongenetic regulation of both the\nexpression and structure of chemokines and receptors conveys chemokine functional heterogeneity. Imbalances and defects in the system\ncontribute to the pathogenesis of a variety of diseases, including cancer, immune and in\ufb02ammatory diseases, and metabolic and\nneurological disorders, which render the system a focus of studies aiming to discover therapies and important biomarkers. The integrated\nview of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states,\nincluding, among others, coronavirus disease 2019 (COVID-19). In this review, by reporting the latest advances in chemokine biology and\nresults from analyses of a plethora of sequencing-based datasets, we outline recent advances in the understanding of the genetic variations\nand nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological\nnetwork, focusing on chemokine-mediated in\ufb02ammation and cancer. Clari\ufb01cation of the molecular basis of dynamic chemokine-receptor\ninteractions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 730
encoding: FLOAT32
metadata:
{"title": "New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine", "chroma:document": "Keywords: Chemokine; Chemokine receptor; Migration; Homeostasis; Genetics; Epigenetics\nCellular & Molecular Immunology (2023) 20:739\u2013776; https://doi.org/10.1038/s41423-023-01032-x\nLeukocyte migration is a central component of physiological and\npathological responses [1\u20139]. Chemokines are the largest family of\ncytokines and have chemotactic activity that is essential for host\nresponses in homeostasis and diseases. Chemokines activate cell-\nsurface G-protein-coupled\nreceptors\n(GPCRs) to generate\na\nregulatory\nnetwork\nand\nplay\nindispensable\nroles\nin\nmany\nprocesses in immunobiology [10\u201317]. Imbalances and defects in\nthis system alter host susceptibility to diseases, including diverse\nin\ufb02ammatory disorders, infections and malignancies [17\u201320]. In\nthis article, we highlight the most recent \ufb01ndings related to\nchemokines and receptors regarding their genetic variations and\nnongenetic heterogeneity. Our review provides molecular insights\nfor chemokine biology to realize precision medicine.\nBACKGROUND\nHistory\nSince the discovery of the human chemokine CXCL8 or IL-8\n(CXCL8/IL-8) in the last century [21\u201323], chemokines have been\nrecognized to exist in a complicated mega system [10\u201312, 14\u201317].\nThe rather short but rich history in the \ufb01eld includes two waves of\nchemokine identi\ufb01cation [11, 23\u201326]: the \ufb01rst discovery of\nin\ufb02ammatory chemokines and receptors that mainly attract\nneutrophils and macrophages (M\u03c6s) in the early 1990s and the\nsecond round of chemokines and receptor discovery after the\nmid-1990s, which identi\ufb01ed those chemokines and receptors\nrelated to homeostasis and the traf\ufb01cking of lymphocytes and\ndendritic cells (DCs). However, chemokine research was really\ninitiated in 1977 after the discovery of platelet factor 4 (PF4), also\ncalled CXCL4, which was the \ufb01rst identi\ufb01ed peptide containing a\nprototypical chemokine structure with uncharacterized chemoat-\ntractant activity [24, 26\u201328]. The discovery that CXCL8 and CCL2\n(originally called MCP-1) [21, 22] have chemotactic activity was"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 731
encoding: FLOAT32
metadata:
{"title": "New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine", "chroma:document": "nevertheless a landmark \ufb01nding in immunology [23, 24].\nRecently,\nrapid advances in technologies,\nsuch as next-\ngeneration sequencing (NGS), mass spectrometry and nuclear\nmagnetic resonance (NMR), have created abundant datasets\nallowing integrative multiomics analysis of chemokines even at\nReceived: 11 October 2022 Accepted: 14 April 2023\nPublished online: 17 May 2023\n1College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University, 3 ShangyuanCun, Haidian District, 100044 Beijing, P.R.\nChina. 2Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, 101149 Beijing, China. 3Laboratory of Cancer\nInnovation, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. 4These authors contributed equally: Hanli Xu, Shuye Lin.\n\u2709email: jqhuang@bjtu.edu.cn\nwww.nature.com/cmi\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 732
encoding: FLOAT32
metadata:
{"title": "Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates", "chroma:document": "Frequency Variation and Dose Modi\ufb01cation of Benznidazole\nAdministration for the Treatment of Trypanosoma cruzi\nInfection in Mice, Dogs, and Nonhuman Primates\nJuan M. Bustamante,a Brooke E. White,a Gregory K. Wilkerson,b* Carolyn L. Hodo,c\u00a7 Lisa D. Auckland,c Wei Wang,a^\nStephanie McCain,d\nSarah A. Hamer,c Ashley B. Saunders,e\nRick L. Tarletona,f\naCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA\nbMD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, Bastrop, Texas, USA\ncDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Research, Texas A&M University, College Station, Texas, USA\ndBirmingham Zoo, Birmingham, Alabama, USA\neDepartment of Small Animal Clinical Sciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA\nfDepartment of Cellular Biology, University of Georgia, Athens, Georgia, USA\nABSTRACT\nTrypanosoma cruzi naturally infects a broad range of mammalian species\nand frequently results in the pathology that has been most extensively characterized\nin human Chagas disease. Currently employed treatment regimens fail to achieve parasi-\ntological cure of T. cruzi infection in the majority of cases. In this study, we have extended\nour previous investigations of more effective, higher dose, intermittent administration pro-\ntocols using the FDA-approved drug benznidazole (BNZ), in experimentally infected mice\nand in naturally infected dogs and nonhuman primates (NHP). Collectively, these studies\ndemonstrate that twice-weekly administration of BNZ for more than 4 months at doses\nthat are ;2.5-fold that of previously used daily dosing protocols, provided the best\nchance to obtain parasitological cure. Dosing less frequently or for shorter time periods\nwas less dependable in all species. Prior treatment using an ineffective dosing regimen\nin NHPs did not prevent the attainment of parasitological cure with an intensi\ufb01ed BNZ"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 733
encoding: FLOAT32
metadata:
{"title": "Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates", "chroma:document": "dosing protocol. Furthermore, parasites isolated after a failed BNZ treatment showed\nnearly identical susceptibility to BNZ as those obtained prior to treatment, con\ufb01rming the\nlow risk of induction of drug resistance with BNZ and the ability to adjust the treatment\nprotocol when an initial regimen fails. These results provide guidance for the use of BNZ\nas an effective treatment for T. cruzi infection and encourage its wider use, minimally\nin high value dogs and at-risk NHP, but also potentially in humans, until better options are\navailable.\nKEYWORDS Trypanosoma cruzi, Chagas disease, benznidazole, cure, dogs, nonhuman\nprimates\nC\nhagas disease is a vector-borne parasitic disease caused by the hemo\ufb02agellate proto-\nzoan Trypanosoma cruzi and is one of the major worldwide causes of infection-induced\nmyocardial disease. T. cruzi is widely distributed and transmitted to a broad range of mam-\nmals, from the southern United States to the far south of Chile and Argentina. Managing\nChagas disease is particularly challenging; human infections are not routinely diagnosed\nbefore health-impacting tissue damage is substantial and without treatment, the infection\ngenerally persists for life. Systematic vector control can limit new human infections but can\nbe expensive and labor-intensive and may have less impact on the rate of new infections in\nanimals in some settings (1\u20133). The current treatment for human T. cruzi infection depends\non two nitroheterocyclic compounds, benznidazole (BNZ) and nifurtimox (NFX), that are\ngiven in an intensive treatment regimen (usually 30 to 60 twice-daily doses for BNZ and\nCopyright \u00a9 2023 American Society for\nMicrobiology. All Rights Reserved.\nAddress correspondence to Rick L. Tarleton,\ntarleton@uga.edu.\n*Present address: Gregory K. Wilkerson,\nDepartment of Clinical Sciences, North Carolina\nState University College of Veterinary Medicine,\nRaleigh, North Carolina, USA.\n\u00a7Present address: Carolyn L. Hodo, MD\nAnderson Cancer Center, Michale E. Keeling\nCenter for Comparative Medicine and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 734
encoding: FLOAT32
metadata:
{"title": "Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates", "chroma:document": "Research, Bastrop, Texas, USA.\n^Present address: Wei Wang, General\nDynamics Information Technology, Inc., Falls\nChurch, Virginia, USA.\nThe authors declare no con\ufb02ict of interest.\nReceived 30 January 2023\nReturned for modi\ufb01cation 22 February 2023\nAccepted 22 March 2023\nPublished 11 April 2023\nMay 2023\nVolume 67 Issue 5\n10.1128/aac.00132-23\n1\nEXPERIMENTAL THERAPEUTICS"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 735
encoding: FLOAT32
metadata:
{"title": "The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration", "chroma:document": "The G118R plus R263K Combination of Integrase Mutations\nAssociated with Dolutegravir-Based Treatment Failure Reduces\nHIV-1 Replicative Capacity and Integration\nMeng A. Xiao,a,b Jenna Cleyle,a,b Sunbin Yoo,a,b Mekayla Forrest,a,b\nZo\u00eb Krullaars,c Hanh Thi Pham,a,b\nThibault Mespl\u00e8dea,b,*\naMcGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montr\u00e9al, Quebec, Canada\nbDepartment of Microbiology and Immunology, Faculty of Medicine, McGill University, Montr\u00e9al, Quebec, Canada\ncViroscience Department, Erasmus Medical Center, Rotterdam, Zuid-Holland, The Netherlands\nABSTRACT\nHuman immunode\ufb01ciency virus (HIV) treatment with antiretroviral regi-\nmens containing integrase strand transfer inhibitors such as dolutegravir (DTG) and\nbictegravir (BIC) offers high levels of protection against the development of drug re-\nsistance mutations. Despite this, resistance to DTG and BIC can occur through the\ndevelopment of the R263K integrase substitution. Failure with DTG has also been\nassociated with the emergence of the G118R substitution. G118R and R263K are usu-\nally found separately but have been reported together in highly treatment-experi-\nenced persons who experienced treatment failure with DTG. We used cell-free strand\ntransfer and DNA binding assays and cell-based infectivity, replicative capacity, and\nresistance assays to characterize the G118R plus R263K combination of integrase\nmutations. R263K reduced DTG and BIC susceptibility ;2-fold, in agreement with\nour previous work. Single-cycle infectivity assays showed that G118R and G118R plus\nR263K conferred ;10-fold resistance to DTG. G118R alone conferred low levels of re-\nsistance to BIC (3.9-fold). However, the G118R plus R263K combination conferred\nhigh levels of resistance to BIC (33.7-fold), likely precluding the use of BIC after DTG\nfailure with the G118R plus R263K combination. DNA binding, viral infectivity, and\nreplicative capacity of the double mutant were further impaired, compared to single"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 736
encoding: FLOAT32
metadata:
{"title": "The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration", "chroma:document": "mutants. We propose that impaired \ufb01tness helps to explain the scarcity of the\nG118R plus R263K combination of integrase substitutions in clinical settings and that\nimmunode\ufb01ciency likely contributes to its development.\nKEYWORDS HIV drug resistance, dolutegravir, bictegravir, integrase inhibitors,\nintegrase, R263K, G118R\nC\nurrent treatment for human immunode\ufb01ciency virus (HIV) infection consists of combi-\nnations of two or three antiretroviral drugs that can be taken orally daily or intramuscu-\nlarly every 2 months (1). In addition, every-6-month subcutaneous injections of lenacapavir\nwere approved recently in combination with other antiretroviral drugs for the treatment of\nhighly treatment-experienced individuals with limited therapeutic options (2). Regardless of\ntheir form of administration, for all regimens, treatment failure occurs in some cases when vi-\nral suppression cannot be achieved or maintained, and drug resistance mutations can\nemerge (3). The ability of an antiretroviral treatment regimen, or of a particular drug, to pro-\ntect against the development of HIV resistance mutations upon treatment failure is called its\nbarrier to resistance. Although antiretroviral drugs with a low barrier to resistance can be\ncombined to form regimens suf\ufb01cient to maintain virological suppression in the context\nof optimal treatment adherence, drugs with high barriers to resistance may improve clin-\nical outcomes on population and individual levels. Advantages associated with a high\nbarrier to resistance include cost-effectiveness associated with reduced genotyping and\nCopyright \u00a9 2023 American Society for\nMicrobiology. All Rights Reserved.\nAddress correspondence to Thibault Mespl\u00e8de,\nt.mesplede@erasmusmc.nl.\n*Present address: Thibault Mespl\u00e8de,\nViroscience Department, Erasmus Medical\nCenter, Rotterdam, Zuid-Holland,\nThe Netherlands.\nThe authors declare no con\ufb02ict of interest.\nReceived 13 October 2022\nReturned for modi\ufb01cation 2 November 2022\nAccepted 16 March 2023\nPublished 18 April 2023\nMay 2023\nVolume 67 Issue 5"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 737
encoding: FLOAT32
metadata:
{"title": "The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration", "chroma:document": "10.1128/aac.01386-22\n1\nANTIVIRAL AGENTS"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 738
encoding: FLOAT32
metadata:
{"title": "Targeting strategies for bone diseases: signaling pathways and clinical studies", "chroma:document": "REVIEW ARTICLE\nOPEN\nTargeting strategies for bone diseases: signaling pathways and\nclinical studies\nHao Xu1, Wentao Wang1, Xin Liu1, Wei Huang2, Chen Zhu2, Yaozeng Xu1, Huilin Yang1,3\u2709, Jiaxiang Bai1,3\u2709 and Dechun Geng\n1,3\u2709\nSince the proposal of Paul Ehrlich\u2019s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted\ntherapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise\ntherapeutic ef\ufb01cacy is realized in speci\ufb01c pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened\nblood \ufb02ow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for\nskeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic\napproach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established\nbone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we\nprovide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting\nstrategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of\nthe classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key\nmembrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug\ndelivery, different delivery strategies targeting bone matrix, bone marrow, and speci\ufb01c bone cells are summarized with a\ncomparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of\nbone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and\nfuture trends in this area."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 739
encoding: FLOAT32
metadata:
{"title": "Targeting strategies for bone diseases: signaling pathways and clinical studies", "chroma:document": "Signal Transduction and Targeted Therapy  (2023) 8:202 \n; https://doi.org/10.1038/s41392-023-01467-8\nINTRODUCTION\nBone is a solid structure undergoing perpetual renewal with\ncrucial functions such as kinematic support, visceral protection,\nand regulation of hematopoiesis and mineral balance.1 Main-\ntenance of these functions depends on normal bone mass and\nstrength, which are achieved through bone remodeling. Skeletal\ndiseases, such as osteoporosis, are usually accompanied by\nabnormal bone remodeling, in which osteoclast-mediated bone\nresorption preponderates over osteoblast-mediated bone forma-\ntion, leading to decreased bone mass, deteriorated microstructure,\nand increased fragile fracture risk.2 In light of the perplexing\npathological\nmechanism\nunderlying\nabnormal\nremodeling,\nsymptom-relief therapy by anti-resorption and pro-formation is\nthe main choice, in addition to the elemental calcium and vitamin\nD supplements.\nSince the proposal of Paul Ehrlich\u2019s \u201cmagic bullet\u201d concept over\n100 years ago, great advances have occurred in drugs that target\nintended cellular structures.3 In bone-targeted pharmacological\ntherapy, anti-resorption agents, such as bisphosphonates, selec-\ntive estrogen receptor modulators (SERMs), receptor activator of\nnuclear factor-kB (RANK) ligand (RANKL) inhibitors, and anabolic\nmedications, such as type 1 parathyroid hormone receptor\n(PTH1R)\nligands,\nsclerostin\ninhibitors,\nhave\nemerged\nwith\ndemonstrated ef\ufb01cacy in treating diseases characterized by\nabnormal bone remodeling.4,5 Nevertheless, the improvement in\nbone parameters by these agents does not simply imply a regain\nof normal bone remodeling, as is observed by the attendant\nsuppression of anti-resorption agents to the bone formation or a\nslight increase in bone resorption by anabolic agents.6,7 Further-\nmore, side effects such as osteonecrosis,8 rebound fractures,9\ncardiovascular events,10 and osteosarcoma genesis,11 impede\neffective long-term management of bone diseases, which under-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 740
encoding: FLOAT32
metadata:
{"title": "Targeting strategies for bone diseases: signaling pathways and clinical studies", "chroma:document": "scores a need to improve these established targets for more\nprecise therapy.\nFortunately, with the deepening knowledge of bone biology,\nthe mechanism underlying some side effects has been recognized\nwith a prominent decrease by preclinical improvements of these\ndrugs. In addition, recent insights have revealed that bone\nremodeling is a coordinated process spatiotemporally mediated\nby all bone cells instead of single activities by the basic\nmulticellular units consisting of osteoblasts (OBs) and osteoclasts\n(OCs).12 Osteocytes, immune cells, vessel endothelial cells, and\nbone marrow cells were shown to possess multiple in\ufb02uences\nduring the remodeling process,13\u201315 and some emerging ther-\napeutic strategies targeting these bone cells, especially the\ncrosstalk between them, have shown promise in promoting bone\nReceived: 1 January 2023 Revised: 2 April 2023 Accepted: 19 April 2023\n1Department of Orthopedics, The First Af\ufb01liated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P. R. China; 2Department of Orthopedics, The First\nAf\ufb01liated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031 Anhui, China and 3Orthopaedic Institute, Medical\nCollege, Soochow University, Suzhou 215006 Jiangsu, China\nCorrespondence: Huilin Yang (suzhouspine@163.com) or Jiaxiang Bai (jxbai1995@163.com) or Dechun Geng (szgengdc@suda.edu.cn)\nThese authors contributed equally: Hao Xu, Wentao Wang, Xin Liu\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: 741
encoding: FLOAT32
metadata:
{"title": "Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China", "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: 742
encoding: FLOAT32
metadata:
{"title": "Harringtonine: A more effective antagonist for Omicron variant", "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: 743
encoding: FLOAT32
metadata:
{"title": "Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure", "chroma:document": "Abatacept GVHD prophylaxis in unrelated hematopoietic cell\ntransplantation for pediatric bone marrow failure\nElizabeth O. Stenger,1 Benjamin Watkins,1 Kelsey Rogowski,1 Kuang-Yueh Chiang,2 Ann Haight,1 Kathryn Leung,1 Muna Qayed,1\nSharmila Raghunandan,1 Yvonne Suessmuth,1 Leslie Kean,3 and John Horan1,3\n1Division of Pediatric Hematology/Oncology, A\ufb02ac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; 2Division of Pediatric\nHematology/Oncology, University of Toronto/The Hospital for Sick Children, Toronto, Canada; and 3Division of Pediatric Hematology/Oncology, Dana-Farber/Boston\nChildren\u2019s Hospital, Boston, MA\nKey Points\n\u2022 Four doses of Aba can\nbe safely added to\nstandard 2-drug GVHD\nprophylaxis in URD\nHCT for pediatric bone\nmarrow failure.\n\u2022 No severe acute or\nchronic GVHD was\nseen in pediatric\npatients with bone\nmarrow failure with\nAba-containing\nprophylaxis after URD\nHCT.\nHematopoietic cell transplantation (HCT) is the only readily available cure for many life-\nthreatening pediatric nonmalignant diseases (NMD), but most patients lack a matched\nrelated donor and are at higher risk for graft-versus-host disease (GVHD). Use of abatacept\n(Aba) to target donor T-cell activation has been safe and effective in preventing GVHD after\nunrelated donor (URD) HCT for malignant diseases (Aba2 trial). Our primary objective\nwas to evaluate the tolerability of Aba added to standard GVHD prophylaxis (cyclosporine\nand mycophenolate mofetil) in pediatric patients with NMD undergoing URD HCT. In this\nsingle-arm, single-center phase 1 trial, 10 patients receiving reduced intensity or\nnonmyeloablative conditioning underwent URD HCT. Immune reconstitution was assessed\nlongitudinally via \ufb02ow cytometry and compared to pediatric patients on Aba2. Nine\npatients successfully engrafted, with 1 primary graft rejection in the setting of inadequate\ncell dose; secondary graft rejection occurred in 1 patient with concurrent cytomegalovirus"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 744
encoding: FLOAT32
metadata:
{"title": "Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure", "chroma:document": "viremia. Two deaths occurred, both unrelated to Aba. One patient developed probable\nposttransplant lymphoproliferative disease, responsive to rituximab and immune\nsuppression withdrawal. No patients developed severe acute or chronic GVHD, and 8\npatients were off systemic immunosuppression at 1 year. Immune reconstitution did not\nappear to be impacted by Aba, and preservation of na\u00efve relative to effector memory CD4+ T\ncells was seen akin to Aba2. Thus, 4 doses of Aba were deemed tolerable in pediatric\npatients with NMD following URD HCT, with encouraging preliminary ef\ufb01cacy and\nsupportive immune correlatives in this NMD cohort.\nIntroduction\nAllogeneic hematopoietic cell transplantation (HCT) is the only standard-of-care curative therapy for\nmany severe nonmalignant diseases (NMDs) which affect children.1-4 While a diverse group of dis-\neases, including highly prevalent hemoglobinopathies and less prevalent diseases such as severe\naplastic anemia (SAA) and Fanconi anemia (FA), they universally lead to signi\ufb01cant morbidity and early\nmortality. These diseases can be cured with a HCT, without which patients face a myriad of\nSubmitted 11 July 2022; accepted 28 November 2022; prepublished online on Blood\nAdvances\nFirst\nEdition\n1\nFebruary\n2023.\nhttps://doi.org/10.1182/\nbloodadvances.2022008545.\nDeidenti\ufb01ed individual participant data from this clinical trial will be made available,\nupon request, 3 months after publication and for a period of up to 5 years.\nData are available on request from the corresponding author, Elizabeth O. Stenger\n(estenge@emory.edu).\nThe study protocol is included as a data supplement available with the online version\nof this article.\nThe full-text version of this article contains a data supplement.\n\u00a9 2023 by The American Society of Hematology. Licensed under Creative Commons\nAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0),\npermitting only noncommercial, nonderivative use with attribution. All other rights\nreserved.\nREGULAR ARTICLE\n2196"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 745
encoding: FLOAT32
metadata:
{"title": "Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure", "chroma:document": "2196\n23 MAY 2023 \u2022 VOLUME 7, NUMBER 10"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 746
encoding: FLOAT32
metadata:
{"title": "Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor", "chroma:document": "Lateral cerebellothalamic tract activation underlies DBS therapy \nfor Essential Tremor\nAnneMarie Brindaa,1, Julia P. Slopsemaa,1, Rebecca D. Butlera, Salman Ikramuddinc, \nThomas Bealla, William Guoa, Cong Chua, Remi Patriatb, Henry Braunb, Mojgan Goftaria, \nTara Palnitkarb, Joshua Amanc, Lauren Schrockc, Scott E. Cooperc, Joseph Matsumotoc, \nJerrold L. Vitekc, Noam Harelb, Matthew D. Johnsona,d,*\naDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA\nbDepartment of Radiology, CMRR, University of Minnesota, Minneapolis, MN, 55455, USA\ncDepartment of Neurology, University of Minnesota, Minneapolis, MN, 55455, USA\ndInstitute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA\nAbstract\nBackground:\u00a0While deep brain stimulation (DBS) therapy can be effective at suppressing tremor \nin individuals with medication-refractory Essential Tremor, patient outcome variability remains a \nsignificant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract \n(CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to \nThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).\n*Corresponding author. Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church \nStreet SE, Minneapolis, MN, 55455, USA. john5101@umn.edu (M.D. Johnson).\n1These authors contributed equally to this work.\nDeclaration of competing interest\nThe authors declare the following financial interests/personal relationships which may be considered as potential competing interests: \nTara Palnitkar: consultant for Surgical Information Sciences; Remi Patriat: consultant for Surgical Information Sciences; Jerrold Vitek: \nconsultant for Medtronic, Boston Scientific, Abbott, and Surgical Information Sciences; Noam Harel: consultant and a shareholder for \nSurgical Information Sciences; all other authors declare no conflict of interest."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 747
encoding: FLOAT32
metadata:
{"title": "Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor", "chroma:document": "CRediT authorship contribution statement\nAnneMarie Brinda: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing \u2013 original draft, \nWriting \u2013 review & editing, Visualization. Julia P. Slopsema: Conceptualization, Methodology, Software, Validation, Formal \nanalysis, Investigation, Writing \u2013 original draft, Writing \u2013 review & editing, Visualization. Rebecca D. Butler: Conceptualization, \nMethodology, Software, Validation, Formal analysis, Investigation, Writing \u2013 review & editing, Visualization. Salman Ikramuddin: \nInvestigation, Formal analysis, Writing \u2013 review & editing. Thomas Beall: Methodology, Software, Writing \u2013 review & editing. \nWilliam Guo: Methodology, Software, Writing \u2013 review & editing. Cong Chu: Methodology, Software, Writing \u2013 review & \nediting. Remi Patriat: Methodology, Software, Validation, Investigation, Writing \u2013 review & editing, Visualization. Henry Braun: \nMethodology, Software, Validation, Investigation, Writing \u2013 review & editing. Mojgan Goftari: Methodology, Software, Validation, \nWriting \u2013 review & editing. Tara Palnitkar: Methodology, Software, Validation, Investigation, Writing \u2013 review & editing, \nVisualization. Joshua Aman: Investigation, Writing \u2013 review & editing. Lauren Schrock: Investigation, Writing \u2013 review & editing. \nScott E. Cooper: Conceptualization, Investigation, Writing \u2013 review & editing. Joseph Matsumoto: Conceptualization, Investigation, \nWriting \u2013 review & editing. Jerrold L. Vitek: Conceptualization, Investigation, Writing \u2013 review & editing. Noam Harel: \nConceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Writing \u2013 review & editing, Supervision, \nProject administration, Funding acquisition. Matthew D. Johnson: Conceptualization, Methodology, Software, Validation, Formal \nanalysis, Investigation, Writing \u2013 original draft, Writing \u2013 review & editing, Visualization, Supervision, Project administration, \nFunding acquisition.\nAppendix A. Supplementary data"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 748
encoding: FLOAT32
metadata:
{"title": "Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor", "chroma:document": "Supplementary data to this article can be found online at https://doi.org/10.1016/j.brs.2023.02.002.\nHHS Public Access\nAuthor manuscript\nBrain Stimul. Author manuscript; available in PMC 2023 May 21.\nPublished in final edited form as:\nBrain Stimul. 2023 ; 16(2): 445\u2013455. doi:10.1016/j.brs.2023.02.002.\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: 749
encoding: FLOAT32
metadata:
{"title": "A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm", "chroma:document": "Clinical Infectious Diseases                                          \nS U P P L E M E N T  A R T I C L E\nA Holistic Review of the Preclinical Landscape for \nLong-Acting Anti-infective Drugs Using HIV as a Paradigm\nMegan Neary, Andrew Owen, and Adeniyi Olagunju\nDepartment of Pharmacology and Therapeutics, Centre of Excellence for Long-acting Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, \nMerseyside, United Kingdom\nLack of predictive preclinical models is a key contributor to the steep attrition rate in drug development. Successful clinical \ntranslation may be higher for new chemical entities or existing approved drugs reformulated for long-acting (LA) \nadministration if preclinical studies designed to identify any new uncertainties are predictive of human exposure and response. \nIn this review, we present an overview of standard preclinical assessments deployed for LA formulations and delivery systems, \nusing human immunodeficiency virus LA therapeutics preclinical development as a paradigm. Key progress in the preclinical \ndevelopment of novel LA antiretrovirals formulations and delivery systems are summarized, including bispecific broadly \nneutralizing monoclonal antibody and small molecule technologies for codelivery of multiple drugs with disparate solubility \nproperties. There are new opportunities to take advantage of recent developments in tissue engineering and 3-dimensional in \nvitro modeling to advance preclinical modeling of anti-infective activity, developmental and reproductive toxicity assessment, \nand to apply quantitative modeling and simulation strategies. These developments are likely to drive the progression of more \nLA anti-infective drugs and multipurpose technologies into clinical development in the coming years.\nKeywords. long-acting; antiretroviral; preclinical; in vitro models.\nCorrespondence: A. Olagunju, Centre of Excellence for Long-acting Therapeutics, Institute of"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 750
encoding: FLOAT32
metadata:
{"title": "A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm", "chroma:document": "Systems, Molecular and Integrative Biology, Biosciences Building, Crown Street, Liverpool L69 \n7BE, UK (olagunju@liverpool.ac.uk).\nClinical Infectious Diseases\u00ae\n2022;75(S4):S490\u20137 \n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. All rights reserved. For permissions, please e-mail: journals.permissions \n@oup.com\nhttps://doi.org/10.1093/cid/ciac685\nDecisions about progressing new drug candidates to clinical de-\nvelopment are guided by evidence from preclinical studies. \nThese are the cornerstone of new drug development and clin-\nical translation, providing the critical data that inform \nfirst-in-human trials (see Figure 1). The landscape for long- \nacting (LA) anti-infective development over the past 12 months \nwas marked by some significant developments, particularly for \nhuman immunodeficiency virus (HIV), which will be used as a \nparadigm to discuss the preclinical development of LA anti- \ninfective drugs. LA therapeutics offer a transformational ap-\nproach to HIV treatment and preexposure prophylaxis, largely \ncircumventing established issues around treatment fatigue and \nassociated nonadherence by offering regimens with extended \ndosing intervals.\nMultiple LA candidates for treatment of HIV are in develop-\nment and are at different points in the drug development pipe-\nline. Multicountry approval of LA-injectable cabotegravir plus \nrilpivirine administered intramuscularly every two months \nwas a major milestone for LA HIV treatment, despite virological \nfailure in patients with baseline nonnucleoside reverse \ntranscriptase inhibitor or integrase strand transfer inhibitor re-\nsistance [1\u20133]. The US Food and Drug Administration (FDA) \nissued a Complete Response Letter with easily resolvable con-\ncerns about incompatibility with borosilicate glass vials in re-\nsponse to a New Drug Application for the LA lenacapavir \n(capsid inhibitor) administered every 6 months for treatment \nin heavily treatment-experienced patients with multidrug resis-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 751
encoding: FLOAT32
metadata:
{"title": "A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm", "chroma:document": "tant HIV-1 infection [4]. The clinical hold has since been lifted \nby the FDA for injectable lenacapavir [5]. Investigational New \nDrug Applications for LA islatravir (nucleoside reverse tran-\nscriptase translocation inhibitor) monthly oral formulation \nand annual implant formulation have been placed on clinical \nhold due to observations of reductions in total lymphocyte \nand CD4+ T-cell count.\nFrom the 12% of novel drug candidates that pass preclinical \ntesting, only 11% successfully make it to the market, mostly \nbecause of failures resulting from unanticipated toxicity \n(about 50%) or suboptimal efficacy. About 50% of postap-\nproval withdrawals are also from toxicity. Lack of predictive \npreclinical models is a key driver of this steep attrition rate, \nand it has been suggested that clinical trial success rate can \nbe theoretically increased to > 55% with better preclinical \nmodels [6]. If preclinical studies designed to identify any \nnew uncertainties are predictive of human exposure and re-\nsponse, translation of LA medicines should have a much high-\ner success rate. However, additional considerations are \nevident for LA medicines and key knowledge gaps relating \nto drug absorption remain.\nS490 \u2022 CID 2022:75 (Suppl 4) \u2022 Neary et al"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 752
encoding: FLOAT32
metadata:
{"title": "Macrophages in immunoregulation and therapeutics", "chroma:document": "REVIEW ARTICLE\nOPEN\nMacrophages in immunoregulation and therapeutics\nShanze Chen1, Abdullah F.U.H. Saeed2, Quan Liu3, Qiong Jiang1, Haizhao Xu1,4, Gary Guishan Xiao5\u2709, Lang Rao\n6\u2709 and\nYanhong Duo7\u2709\nMacrophages exist in various tissues, several body cavities, and around mucosal surfaces and are a vital part of the innate immune\nsystem for host defense against many pathogens and cancers. Macrophages possess binary M1/M2 macrophage polarization\nsettings, which perform a central role in an array of immune tasks via intrinsic signal cascades and, therefore, must be precisely\nregulated. Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered. In addition, the\nclinical importance of tumor-associated macrophages is becoming more widely recognized as signi\ufb01cant progress has been made\nin understanding their biology. Moreover, they are an integral part of the tumor microenvironment, playing a part in the regulation\nof a wide variety of processes including angiogenesis, extracellular matrix transformation, cancer cell proliferation, metastasis,\nimmunosuppression, and resistance to chemotherapeutic and checkpoint blockade immunotherapies. Herein, we discuss immune\nregulation in macrophage polarization and signaling, mechanical stresses and modulation, metabolic signaling pathways,\nmitochondrial and transcriptional, and epigenetic regulation. Furthermore, we have broadly extended the understanding of\nmacrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions. Moreover,\nwe discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis. Lastly,\nwe discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.\nSignal Transduction and Targeted Therapy  (2023) 8:207 \n; https://doi.org/10.1038/s41392-023-01452-1\nINTRODUCTION\nThe primary formation of host resistance, contrary to infectious"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 753
encoding: FLOAT32
metadata:
{"title": "Macrophages in immunoregulation and therapeutics", "chroma:document": "pathogens in disease, is the innate immune framework mainly\nmade of innate immune cellular entities and cells originating from\nmyeloid, comprising macrophages, monocytes, granulocytes, and\ndendritic cells (DCs).1,2 When disease ensues, pathogen-associated\nmolecular patterns (PAMPs) and damage-associated molecular\npatterns (DAMPs) are recognized via the cell surface or intracellular\npattern recognition receptors (PPRs) from innate immune cells, for\nexample,\nToll-like\nreceptors\n(TLRs),\nadvanced\nglycation\nend\nproducts (RAGE) and Nod-like receptors (NLRs).2 Successively, the\ninteraction of PAMPs or DAMPs through particular receptors\ntriggers\nsignaling\ncascades\nfollowing\nassociation\nat\nreactive\noxygenic and nitrogen-related species, chemokines, proin\ufb02amma-\ntory cytokines, and antimicrobial-associated peptides, including\naugmented phagocytosis and the ef\ufb01cient elimination of microbial\ninfection.2,3 In addition, instigating the innate immune system leads\nto the follow-up with the trigger of more speci\ufb01c adaptive\nimmunity. However, given the advantages of the innate immune\nsystem, this tends to remain a double-edged sword employing\nin\ufb02ammation that will damage the host.2 Hence, it is signi\ufb01cant to\ncomprehend the immune regulatory strategies that govern the\nin\ufb02ammatory progression\u2019s commencement, extent, and goals.\nMacrophages are innate immune cells \ufb01rst identi\ufb01ed by Elia\nMetchnikoff in star\ufb01sh hatchlings in 1882 when tangerine tree\nthistles were used, then in Daphnia magna or essential water \ufb02ea\ninfested with fungal spores as the cells responsible for the cycle of\nphagocytosis of foreign materials. For this accomplishment, the\nNobel Prize (Physiology and Medicine) was presented to Elia\nMetchnikoff in 1908. In this way, macrophages are the primary\ninnate immune cells identi\ufb01ed 130 years ago.4\nMacrophages are crucial in innate immunity by regulating\nseveral homeostatic and evolutionary host defense immune\nresponses. Besides, macrophages partake in many other biological"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 754
encoding: FLOAT32
metadata:
{"title": "Macrophages in immunoregulation and therapeutics", "chroma:document": "events, including modulating reactive oxygen species (ROS)\nendogenous intensities, iron homeostasis, tissue injury repair,\nand numerous other metabolic functions.5,6 In addition, macro-\nphages have three essential functions, i.e., immunomodulation,\nphagocytosis, and antigen presentation. They are vital for\nperforming normal immune reactions under various pathophy-\nsiological conditions.7\nAs the relationship between TAMs and malignant tumors\nexpands into more apparent, TAMs are suggested as possible\nbiomarkers for diagnosing and prognosis tumors and therapeutic\ntargets in various cancers. Inhibiting monocyte recruitment,\ntargeting\nTAM\nactivation,\nconverting\nTAMs\nto\nanticancer\nReceived: 5 September 2022 Revised: 6 March 2023 Accepted: 26 April 2023\n1Department of Respiratory Diseases and Critic Care Unit, Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People\u2019s Hospital\n(The Second Clinical Medical College, Jinan University; The First Af\ufb01liated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; 2Department of\nCancer Biology, Beckman Research Institute of City of Hope National Medical Center, Los Angeles, CA 91010, USA; 3Department of Laboratory Medicine, Huazhong University of\nScience and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen University, Shenzhen 518052, China; 4Department of Respiratory, The First Af\ufb01liated Hospital,\nSchool of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; 5State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences,\nSchool of Chemical Engineering, Dalian University of Technology, Dalian, China; 6Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen\n518132, China and 7Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden\nCorrespondence: Gary Guishan Xiao (gxiao@dlut.edu.cn) or Lang Rao (lrao@szbl.ac.cn) or Yanhong Duo (duoduo7753@126.com)"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 755
encoding: FLOAT32
metadata:
{"title": "Macrophages in immunoregulation and therapeutics", "chroma:document": "These authors contributed equally: Shanze Chen, Abdullah F.U.H. Saeed, Quan Liu\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: 756
encoding: FLOAT32
metadata:
{"title": "Maternal outcomes of placental abruption with intrauterine fetal death and delivery routes: A nationwide observational study", "chroma:document": "708\u2003|\u2003  \n \nActa Obstet Gynecol Scand. 2023;102:708\u2013715.\nwileyonlinelibrary.com/journal/aogs\nReceived: 20 October 2022\u2003|\u2003Revised: 14 February 2023\u2003|\u2003Accepted: 21 March 2023\nDOI: 10.1111/aogs.14569  \nO R I G I N A L  R E S E A R C H  A R T I C L E\nMaternal outcomes of placental abruption with intrauterine \nfetal death and delivery routes: A nationwide observational \nstudy\nYoshimitsu Wada1\n\u2003|   Hironori Takahashi1\u2003|   Yusuke Sasabuchi2\u2003|   Rie Usui1\n\u2003|   \nManabu Ogoyama1\n\u2003|   Hirotada Suzuki1\u2003|   Akihide Ohkuchi1\u2003|   Hiroyuki Fujiwara1\nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction \nin any medium, provided the original work is properly cited and is not used for commercial purposes.\n\u00a9 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of \nObstetrics and Gynecology (NFOG).\nAbbreviations: CD, cesarean delivery; CI, confidence interval; DIC, disseminated intravascular coagulation; IPTW, inversed probability weighting; IQR, interquartile range; IUFD, \nintrauterine fetal death; OR, odds ratio; PA, placental abruption; VD, vaginal delivery.\n1Department of Obstetrics and \nGynecology, Jichi Medical University, \nTochigi, Japan\n2Data Science Center, Jichi Medical \nUniversity, Tochigi, Japan\nCorrespondence\nHironori Takahashi, Jichi Medical \nUniversity, 3311- 1 Yakushiji, Shimotsuke, \nTochigi 329- 0498, Japan.\nEmail: hironori@jichi.ac.jp\nAbstract\nIntroduction: Placental abruption is a serious complication, especially when accom-\npanied by intrauterine fetal death. The optimal delivery route for placental abruption \nwith intrauterine fetal death for reducing maternal complications is still unclear. In \nthis study we aimed to compare the maternal outcomes between cesarean delivery \nand vaginal delivery in women with placental abruption with intrauterine fetal death."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 757
encoding: FLOAT32
metadata:
{"title": "Maternal outcomes of placental abruption with intrauterine fetal death and delivery routes: A nationwide observational study", "chroma:document": "Material and methods: Using the Japan Society of Obstetrics and Gynecology na-\ntionwide perinatal registry database, we identified pregnant women with placental \n abruption with intrauterine fetal death between 2013 and 2019. The following women \nwere excluded: those with multiple pregnancies, placenta previa, placenta accreta \nspectrum, amniotic fluid embolism, or whose delivery route was missing data. The \nassociation between delivery routes (cesarean delivery and vaginal delivery) and the \nmaternal outcome was examined using a linear regression model with inverse prob-\nability weighting. The primary outcome was the amount of bleeding during delivery. \nMissing data were imputed using multiple imputation.\nResults: The number of women with placental abruption with intrauterine fetal death \nwas 1218/1601932 (0.076%). Of 1134 women analyzed, 608 (53.6%) underwent ce-\nsarean delivery. Bleeding during delivery (median [interquartile range]) was 1650.00 \n(950.00\u2013 2450.00) (mL) and 1171.00 (500.00\u2013 2196.50) (mL) in cesarean and vaginal \ndelivery, respectively. Bleeding during delivery (mL) was significantly greater in cesar-\nean delivery than in vaginal delivery (regression coefficient, 1086.39; 95% confidence \ninterval, 130.96\u2013 2041.81; p\u2009=\u20090.026). Maternal death and uterine rupture occurred in \nfour (0.4%) and five (0.4%) women, respectively. The four maternal deaths were noted \nin the vaginal delivery group.\nConclusions: Bleeding during delivery was significantly greater in cesarean delivery than \nthat in vaginal delivery in women with placental abruption with intrauterine fetal death."}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 758
encoding: FLOAT32
metadata:
{"title": "Similar somatotopy for active and passive digit representation in primary somatosensory cortex", "chroma:document": "R E S E A R C H A R T I C L E\nSimilar somatotopy for active and passive digit representation\nin primary somatosensory cortex\nZeena-Britt Sanders1\n|\nHarriet Dempsey-Jones2,3\n|\nDaan B. Wesselink1,2\n|\nLaura R. Edmondson4\n|\nAlexander M. Puckett3,5\n|\nHannes P. Saal5\n|\nTamar R. Makin1,2,6\n1Wellcome Centre of Integrative\nNeuroimaging, FMRIB, John Radcliffe Hospital,\nOxford, UK\n2Institute of Cognitive Neuroscience,\nUniversity College London, London, UK\n3School of Psychology, The University of\nQueensland, Brisbane, Australia\n4Department of Psychology, University of\nSheffield, Sheffield, UK\n5Queensland Brain Institute, The University of\nQueensland, Brisbane, Australia\n6MRC Cognition and Brain Sciences Unit,\nUniversity of Cambridge, Cambridge, UK\nCorrespondence\nHarriet Dempsey-Jones, School of Psychology,\nThe University of Queensland, St. Lucia,\nBrisbane 4067, Australia.\nEmail: h.dempseyjones@uq.edu.au\nFunding information\nH2020 European Research Council,\nGrant/Award Number: 715022; Leverhulme\nTrust Research Project Grant, Grant/Award\nNumber: RPG-2022-031; Wellcome Trust,\nGrant/Award Number: 215575/Z/19/Z;\nMedical Research Council, Grant/Award\nNumber: MC_UU_00030/10\nAbstract\nScientists traditionally use passive stimulation to examine the organisation of primary\nsomatosensory cortex (SI). However, given the close, bidirectional relationship\nbetween the somatosensory and motor systems, active paradigms involving free\nmovement may uncover alternative SI representational motifs. Here, we used 7 Tesla\nfunctional magnetic resonance imaging to compare hallmark features of SI digit rep-\nresentation between active and passive tasks which were unmatched on task or stim-\nulus properties. The spatial location of digit maps, somatotopic organisation, and\ninter-digit representational structure were largely consistent between tasks, indicat-\ning representational consistency. We also observed some task differences. The active\ntask produced higher univariate activity and multivariate representational information"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 759
encoding: FLOAT32
metadata:
{"title": "Similar somatotopy for active and passive digit representation in primary somatosensory cortex", "chroma:document": "content (inter-digit distances). The passive task showed a trend towards greater\nselectivity for digits versus their neighbours. Our findings highlight that, while the\ngross features of SI functional organisation are task invariant, it is important to also\nconsider motor contributions to digit representation.\nK E Y W O R D S\nfinger representations, fMRI, hand map, motor, representational similarity analysis,\nsomatosensation, topography\n1\n|\nINTRODUCTION\nTraditionally, the organisation of the somatosensory system has been\nstudied using passive tactile stimulation protocols, that is, contacting\nstationary digit(s) with tactile stimuli (examples in humans: (Besle\net al., 2014; Sanchez-Panchuelo et al., 2010) and in primates: (Michael\nM. Merzenich et al., 1978; Sur et al., 1980)). While providing a highly\ncontrolled means to study the primary somatosensory cortex (SI),\nactive touch tasks (Kikkert et al., 2016; Schellekens et al., 2018),\ninvolving movement of the digits, may provide somatosensory inputs\nmore like those that occur habitually. In daily life, the majority of hand\ninputs to SI occur from deliberate action (i.e., driven by motor control),\nor are directly relevant for supporting motor control (Scott, 2004).\nAccordingly, somatosensory hand representation reflects habitual pat-\nterns of coordinated action between digits (Ejaz et al., 2015; Ingram\net al., 2008). These usage effects manifest in greater overlap between\nZeena-Britt Sanders and Harriet Dempsey-Jones contributed equally to this work.\nLead author: Tamar R. Makin, MRC Cognition and Brain Sciences Unit, University of\nCambridge, Cambridge CB2 7EF, UK.\nReceived: 20 July 2022\nRevised: 11 December 2022\nAccepted: 13 March 2023\nDOI: 10.1002/hbm.26298\nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,\nprovided the original work is properly cited.\n\u00a9 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.\n3568"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 760
encoding: FLOAT32
metadata:
{"title": "Similar somatotopy for active and passive digit representation in primary somatosensory cortex", "chroma:document": "3568\nHum Brain Mapp. 2023;44:3568\u20133585.\nwileyonlinelibrary.com/journal/hbm"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 761
encoding: FLOAT32
metadata:
{"title": "Long-Lasting effects of Subthalamic Nucleus Coordinated Reset Deep Brain Stimulation in the Non-Human Primate Model of Parkinson\\\rism: A case report", "chroma:document": "Long-Lasting effects of Subthalamic Nucleus Coordinated Reset \nDeep Brain Stimulation in the Non-Human Primate Model of \nParkinsonism: A case report\nJoyce Chelangat Borea, Brett A. Campbella,b, Hanbin Choa, Francesco Puccic,d, Raghavan \nGopalakrishnanc, Andre G. Machadoa,c,d, Kenneth B. Baker, PhDa,c\naDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, \n44106, United States.\nbDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, \n44106\ncCenter for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, \n44106, United States.\ndDepartment of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, 44106, \nUnited States.\nDear Editor,\nContinuous, high-frequency isochronal (i.e., \u201ctraditional\u201d) deep brain stimulation (tDBS), \nis a standard treatment option for advanced-stage Parkinson\u2019s disease (PD). However, \ntDBS is limited by side effects [1] and its chronic nature can necessitate frequent \nbattery replacement. To address these issues, a novel stimulation method, coordinated reset \n(CR)-DBS, was developed through computational modeling [2\u20133]. To date, however, data \naddressing its underlying electrophysiological effects are limited [3]. The goal of this study \nwas to characterize the sub-acute and carryover motor and electrophysiological effects of \nCR-DBS in terms of both local field potential (LFP) power changes and brain connectivity \nin the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) non-human primate (NHP) \nmodel of parkinsonism.\nAnimal care complied with the National Institutes of Health Guide for the Care and Use \nof Laboratory Animals and a protocol approved by the Cleveland Clinic Institutional \nAnimal Care and Use Committee (IACUC). A 14-year-old adult female NHP (Macaca \nmulatta) was instrumented with a DBS lead in the subthalamic nucleus (STN) and a pair of \ntwelve-contact electrocorticography (ECoG) arrays spanning from medial somatosensory to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 762
encoding: FLOAT32
metadata:
{"title": "Long-Lasting effects of Subthalamic Nucleus Coordinated Reset Deep Brain Stimulation in the Non-Human Primate Model of Parkinson\\\rism: A case report", "chroma:document": "prefrontal cortex (Figure 1A) as described previously [4\u20135]. The M1 region was identified \nas the contacts showing the lowest threshold for corticospinal activation, with localization \nconfirmed by 3D reconstruction of the co-registered preoperative MRI and postoperative CT \n(Figure 1B) [6].\nCorresponding author: Kenneth B. Baker, PhD, Department of Neurosciences, Lerner Research Institute (NC-30), Cleveland Clinic, \nCleveland, OH, USA. Tel: (216) 445-2244 Fax: (216) 444-7927, bakerk6@ccf.org. \nHHS Public Access\nAuthor manuscript\nBrain Stimul. Author manuscript; available in PMC 2023 May 23.\nPublished in final edited form as:\nBrain Stimul. 2022 ; 15(3): 598\u2013600. doi:10.1016/j.brs.2022.04.005.\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: 763
encoding: FLOAT32
metadata:
{"title": "Innate immune regulations and various siRNA modalities", "chroma:document": "Vol.:(0123456789)\n1 3\nDrug Delivery and Translational Research \nhttps://doi.org/10.1007/s13346-023-01361-4\nREVIEW ARTICLE\nInnate immune regulations and\u00a0various siRNA modalities\nAnju\u00a0Kaushal1 \nAccepted: 29 April 2023 \n\u00a9 Controlled Release Society 2023\nAbstract\nRNAi therapeutics are designed to produce the precise silencing effects against the gene-linked diseases which were known \nto be untreatable in the past. The highly immunostimulatory nature of siRNA enhances the off-target effects and easily get \nattacked by nucleases; hence, their modulation is essentially required for accurate alterations to be made in the structures to \nintensify the pharmacological attributes. The phosphonate modifications act as shield against undue phosphorylation effects, \nand the molecular changes in ribose sugar lowers the level of immunogenicity and increases the binding efficacy. When \nbases are substituted with virtual/or pseudo bases, they eventually reduce the off-target effects. These changes modulate the \nnucleic acid sensors and control the hyper-activation of innate immune response. Various modification designs based on \nSTC (universal pattern), ESC, ESC + (advanced patterns) and disubstrate have been explored to silence the gene expression \nof various diseases e.g., hepatitis, HIV, influenza, RSV, CNV and acute kidney injury. This review describes the various \ninnovative siRNA therapeutics and their implications on the developed immune regulations to silence the disease effects.\nKeywords RNAi\u00a0\u00b7 siRNA modification\u00a0\u00b7 Innate immune immune response\u00a0\u00b7 Gene silencing\nIntroduction\nInterfering RNA (RNAi) technology is being employed to \ntarget the disease-associated gene to knockdown/or silence \nits debilitating effect by halting the activity of associated \nmRNA, therefore, repressing the translation process. Fire \nand Mello, in 1998, have demonstrated the RNAi concept \nfor the first time, using dsRNA in Caenorhabditis elegans \nto observe the silencing effects. These discoveries on the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 764
encoding: FLOAT32
metadata:
{"title": "Innate immune regulations and various siRNA modalities", "chroma:document": "RNA-mediated process of gene regulations have advanced \nour knowledge in this field [1]. Later on, the work has been \nextended to watch the effects of siRNA molecular machines \nin plants. The final effects demonstrated the guide sequence-\ndependent endo-nucleolytic cleavage was linked to inhibit the \ntranslation by mRNA [2]. By 2001, microRNA (miRNA) has \nalso been explored and classified in small RNA regulators \n[3]. In the past, siRNA therapeutics development has faced \nmany challenges regarding stability and specificity along \nwith accurate drug delivery to the target tissues. But, the \nmost recent advancements in the arena of chemistry, genetics \nand biotechnology have revolutionized the field of nucleic \nacid developments to the next level.\nIn the past decade, incredible efforts have been made \nto study many chemical modification geometries and \nto analyse and evaluate their efficacy and biosafety in \nmodified-siRNA drugs. siRNA/or mRNA used in higher \nconcentration, without modification-treatments, can \nenhance the immunostimulatory effects of nucleic acid \nsensors initiating the strong innate immune response, by \nsecreting excessive IFN-\u03b1. The nucleoside modifications \nare an effective tool to increase stability and reduce the \nimmunogenicity of nucleic-acid therapeutics [6]. Various \nsiRNA modification chemistries are being used to control  \nthe innate immune stimulations in context with increasing  \npotency and decreasing the involved toxicities. Off-target \neffects mediated by siRNAs, however, is one more param-\neter which considerably affect the precision and accu-\nracy in the drug effectiveness. Chemical modifications \nof nucleotides can be placed at the phosphate backbone, \nribose moiety and base. Phosphothioate (PS)-modified oli-\ngonucleotides are hydrophobic and more stable with an \nincreased half-life of oligonucleotides and enhance their \naffinity to specific proteins. The protein binding capacity \nof oligonucleotides is advantageous to penetrate into the"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 765
encoding: FLOAT32
metadata:
{"title": "Innate immune regulations and various siRNA modalities", "chroma:document": "cells, but excessive bindings could lead the in-vivo toxic-\nity with a consequence of eliminating of drug metabo-\nlites from the body. siRNA joined with PS will not make \nany changes in-vivo biodistribution and can accumulate \n * Anju Kaushal \n \nanjukaushal186@hotmail.com; anjukaushal186@gmail.com\n1 \nNew Zealand Organization for\u00a0Quality-Member, Auckland, \nNew\u00a0Zealand"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 766
encoding: FLOAT32
metadata:
{"title": "Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model", "chroma:document": "J Antimicrob Chemother 2022; 77: 2964\u20132971 \nhttps://doi.org/10.1093/jac/dkac252 Advance Access publication 1 August 2022                 \nSafety and efficacy of a biodegradable implant releasing \ntenofovir alafenamide for vaginal protection in a macaque model\nI. Massud1, A. Krovi2, K. Nishiura1, S. Ruone1, L. Li2, A. Holder1, J. Gary3\u2020, P. Mills4\u2021, J. Mitchell1, G. Khalil1, Y. Pan1, \nE. Luecke2, G. Gatto2, W. Heneine1, J. G. Garc\u1f77a-Lerma1, L. Johnson2, A. van der Straten5 and C. Dobard\n1*\n1Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and \nPrevention, Atlanta, GA, USA; 2RTI International, Research Triangle Park, NC, USA; 3Infectious Diseases Pathology Branch, Division of High- \nConsequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infection Diseases, Centers for Disease Control and \nPrevention, Atlanta, GA, USA; 4Comparative Medicine Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic \nInfection Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA; 5Center for AIDS Prevention Studies (CAPS), Department \nof Medicine, University of California San Francisco, San Francisco, CA and ASTRA Consulting, Kensington, CA, USA\n*Corresponding author. E-mail: gok5@cdc.gov\n\u2020Present address: Neuropathology, StageBio, Frederick, MD, USA.\n\u2021Present address: Department of Comparative Medicine, Tulane University, New Orleans, LA, USA.\nReceived 9 March 2022; accepted 24 June 2022\nObjectives: To advance the initiative of ending the global epidemic, long-lasting HIV protection is needed \nthrough sustained release of antiretroviral drugs for months to years. We investigated in macaques the safety \nand efficacy of biodegradable polycaprolactone implants releasing tenofovir alafenamide for HIV pre-exposure \nprophylaxis (PrEP). \nMethods: Implants were administered subcutaneously in the arm using a contraceptive trocar. Efficacy against"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 767
encoding: FLOAT32
metadata:
{"title": "Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model", "chroma:document": "vaginal simian-HIV (SHIV) infection was investigated in six pigtailed macaques that received two tenofovir ala-\nfenamide implants (0.35 mg/day), one in each arm, for a total release rate of tenofovir alafenamide at 0.7 mg/ \nday. Macaques were exposed to SHIV twice weekly for 6 weeks. Statistical analyses were used to compare out-\ncome with eight untreated controls. Histological assessments were performed on skin biopsies collected near \nimplantation sites. \nResults: Median (range) tenofovir diphosphate level in PBMCs was 1519 (1068\u20131898) fmol/106 cells. All maca-\nques with tenofovir alafenamide implants were protected against vaginal SHIV infection. In contrast, 7/8 con-\ntrols were infected after a median of 4 SHIV exposures (P = 0.0047). Histological assessment of tissues near \ntenofovir alafenamide implant sites showed inflammation and necrosis in 5/6 animals, which were not evident \nby visual inspection. \nConclusions: We demonstrated complete protection against vaginal SHIV infection with two implants releasing \na total of 0.7 mg of tenofovir alafenamide per day. We also identified tenofovir diphosphate concentrations in \nPBMCs associated with complete vaginal protection. Consistent with previous findings, we observed adverse lo-\ncal toxicity and necrosis near the tenofovir alafenamide implant site. Improved tenofovir alafenamide implants \nthat are safe and maintain high efficacy have the potential to provide long-lasting protection against vaginal \nHIV infection.\nPublished by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy 2022. \nThis work is written by (a) US Government employee(s) and is in the public domain in the US.\nIntroduction\nThe HIV epidemic remains one of the highest global public health \npriorities.1 Although new HIV infections have steadily declined \nsince the peak in 1997, an estimated 1.5 million became newly \ninfected in 2020.2 Daily oral pre-exposure prophylaxis (PrEP) \nwith the combination of emtricitabine and tenofovir disoproxil"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 768
encoding: FLOAT32
metadata:
{"title": "Safety and efficacy of a biodegradable implant releasing tenofovir alafenamide for vaginal protection in a macaque model", "chroma:document": "fumarate or tenofovir alafenamide has been highly effective in \npreventing HIV acquisition when taken as prescribed.3,4\nHowever, inadequate adherence to the daily oral regimen re-\nduces effectiveness and public health impact. As efforts to scale \nup PrEP worldwide accelerate, it is a high priority to identify novel \nPrEP modalities that accommodate the different needs among \nusers. To this end, the pipeline for HIV prevention options is \n2964"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 769
encoding: FLOAT32
metadata:
{"title": "Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models", "chroma:document": "The Journal of Infectious Diseases                                \nM A J O R  A R T I C L E\nSecond-Generation Human Immunodeficiency Virus \nIntegrase Inhibitors Induce Differentiation Dysregulation \nand Exert Toxic Effects in Human Embryonic Stem Cell \nand Mouse Models\nMarie-Soleil R. Smith,1,2 Haneesha Mohan,3 Abhinav Ajaykumar,1,2,a Anthony Y. Y. Hsieh,1,2 Lou Martineau,1 Ronil Patel,1 Izabella Gadawska,1,2\nChristopher Sherwood,4 Lena Serghides,3,5,6, James M. Piret,4,7,8 and H\u00e9l\u00e8ne C. F. C\u00f4t\u00e91,2,9\n1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; 2Centre for Blood Research, University of British Columbia, Vancouver, Canada; 3Toronto \nGeneral Hospital Research Institute, University Health Network, Toronto, Canada; 4Michael Smith Laboratories, University of British Columbia, Vancouver, Canada; 5Department of Immunology and \nInstitute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; 6Women\u2019s College Research Institute, Toronto, Canada; 7Department of Chemical and Biological Engineering, \nUniversity of British Columbia, Vancouver, Canada; 8School of Biomedical Engineering, The University of British Columbia, Vancouver, Canada; and 9Women\u2019s Health Research Institute, Vancouver, \nCanada\nBackground. Each year, approximately 1.1 million children are exposed in utero to human immunodeficiency virus \nantiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube \ndefect signal in infants exposed to the integrase strand transfer inhibitor (InSTI) dolutegravir from conception, suggesting that \nexposure during early fetal development may be detrimental\nMethods. The effects of InSTIs on 2 human embryonic stem cell (hESC) lines were characterized with respect to markers of \npluripotency, early differentiation, and cellular health. In addition, fetal resorptions after exposure to InSTIs from conception \nwere analyzed in pregnant mice."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 770
encoding: FLOAT32
metadata:
{"title": "Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models", "chroma:document": "Results. At subtherapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased \nhESC counts and pluripotency and induced dysregulation of genes involved in early differentiation. At therapeutic \nconcentrations, bictegravir induced substantial hESC death and fetal resorptions. It is notable that first-generation InSTI \nraltegravir did not induce any hESC toxicity or differentiation, at any concentration tested.\nConclusions. Exposure to some InSTIs, even at subtherapeutic concentrations, can induce adverse effects in hESCs and pregnant \nmice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to \nfurther elucidate the effect of InSTIs on embryonic development, as well as their long-term safety after in utero exposure.\nKeywords. antiretroviral; hESC; HIV; integrase inhibitor; pregnancy.\nReceived 19 July 2022; editorial decision 14 September 2022; accepted 16 September 2022; \npublished online 19 September 2022\naPresent affiliation: Scientist at AbCellera Biologics, Vancouver, BC, Canada.\nPresented in part: 17th European AIDS Conference (EACS), November 2019. Basel, \nSwitzerland; 27th Conference on Retroviruses and Opportunistic Infections (CROI), March \n2020, Boston (Virtual), MA, USA; 29th Annual Canadian Conference on HIV/AIDS Research \n(CAHR), May 2020, Quebec (Virutal), Canada; 28th CROI, February 2022, Denver (Virtual), CO, \nUSA; 30th CAHR, April 2022, London (Virtual), Canada.\nCorrespondence: H\u00e9l\u00e8ne C. F. C\u00f4t\u00e9, PhD, Department of Pathology and Laboratory Medicine, \nUniversity of British Columbia, G227-2211 Wesbrook Mall, Vancouver, B.C. Canada, V6T 2B5 \n(helene.cote@ubc.ca).\nThe Journal of Infectious Diseases\u00ae\n2022;226:1992\u20132001 \n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases \nSociety of America. All rights reserved. For permissions, please e-mail: journals.permissions \n@oup.com\nhttps://doi.org/10.1093/infdis/jiac386"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 771
encoding: FLOAT32
metadata:
{"title": "Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models", "chroma:document": "More than half of the estimated 36 million adults with human \nimmunodeficiency virus (HIV) are women [1]. With increasing \naccess to combination antiretroviral therapy (cART), 85% of \npregnant women with HIV worldwide now receive cART dur-\ning pregnancy. This has successfully reduced vertical transmis-\nsion rates to <2% globally [1]. Although most antiretrovirals \n(ARVs) can cross the placenta [2], the short- and long-term \nsafety of exposure in the context of conception and pregnancy \nhave not been fully characterized. Given how common in utero \nARV exposure is, this represents an important knowledge gap \nidentified by many researchers and care providers [2\u20134].\nRecommended first-line cART for pregnant women typically \ninclude a nucleoside reverse-transcriptase inhibitor backbone \nwith a base drug consisting of either the nonnucleoside reverse- \ntranscriptase inhibitor efavirenz (EFV), the protease inhibitors \nritonavir-boosted darunavir (DRVr), or ritonavir-boosted ataza-\nnavir (ATVr), or one of the integrase strand transfer inhibitors \n(InSTIs) dolutegravir (DTG), or raltegravir (RAL) [5, 6]. Owing \nto their efficacy and generally favorable tolerability, InSTIs have \ngained popularity and mass use [5]. Both DTG and RAL effective-\nly suppress HIV viremia during pregnancy [7, 8], but the use of \nfirst-generation InSTI RAL is much less common than DTG, ow-\ning in part to its requirement for twice-daily administration and \nlack of a fixed-dose combination. Regarding other InSTIs, stan-\ndard dosing of cobicistat-boosted elvitegravir (EVGc) during \npregnancy results in lessened drug exposure due to reduced \n1992 \u2022 JID 2022:226 (1 December) \u2022 Smith et al"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 772
encoding: FLOAT32
metadata:
{"title": "A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues", "chroma:document": "J Antimicrob Chemother 2022; 77: 3180\u20133186 \nhttps://doi.org/10.1093/jac/dkac300 Advance Access publication 14 September 2022         \nA post-mortem analysis of tenofovir, lamivudine, efavirenz and \nfluconazole penetration in female genital tissues\nFan Wang1, Olivie C. Namuju2, Katelyn A. Pastick\n3,4, Kizito Abdusalaamu2, Usha Mishra1, Lindsey Collins1, \nDavid R. Boulware\n3, Robert Lukande5, David B. Meya3,5 and Melanie R. Nicol\n1*\n1Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA; 2Infectious Disease Institute, \nKampala, Uganda; 3Department of Medicine, University of Minnesota, Minneapolis, MN, USA; 4Massachusetts General Hospital, Boston, \nMA, USA; 5Makerere University, Kampala, Uganda\n*Corresponding author. E-mail: mrnicol@umn.edu\nReceived 11 April 2022; accepted 11 August 2022\nBackground: Optimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treat-\nment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, \nvagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus). \nMethods: Autopsies were performed and post-mortem tissues were collected within 24 h of death for female \nparticipants with advanced HIV in Uganda (n = 27). Tenofovir, lamivudine, efavirenz and fluconazole concentra-\ntions were measured using LC-MS/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration \nwas calculated as tissue-to-plasma concentration ratios (TPRs). \nResults: TPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and \n0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a ref-\nerence compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in \nuterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 773
encoding: FLOAT32
metadata:
{"title": "A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues", "chroma:document": "samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater \nthan 1 for both efavirenz and fluconazole. \nConclusions: Penetration of anti-infectives was not homogeneous among the FGT compartments. \nApproximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the pre-\nvention of local HIV replication and transmission in the FGT.\n\u00a9 The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. \nFor permissions, please e-mail: journals.permissions@oup.com\nIntroduction\nThe female genital tract (FGT) is a significant anatomical site of \npathogen persistence and sexual transmission of infectious dis-\neases. Optimal drug exposure in the FGT is paramount for preven-\ntion and treatment of FGT-involved infectious diseases, such as \nHIV and vaginal candidiasis. Although much of the focus on mu-\ncosal HIV transmission in women has been the lower FGT, HIV in-\nfection can occur throughout the entire FGT, as demonstrated in \nthe rhesus macaque vaginal transmission model of simian im-\nmunodeficiency virus.1 Candidiasis, while more often defined as \nvulvovaginal compared with other FGT sites, can, in rare cases, \noccur in the upper FGT as well.2 Despite this, our knowledge of \nFGT tissue exposure to antiretrovirals and antifungals has pre-\ndominantly been obtained through sampling of the lower FGT, \nmostly via cervicovaginal tissue and cervicovaginal fluid.3\u20139\nStudies related to FGT drug exposure in upper tissue tracts (i.e. \novarian and uterine tissue) in non-pregnant women are scarce \ndue to lack of easiness of sampling.\nIn order to fill the knowledge gap surrounding exposure of \nanti-infectives in solid tissues of the upper and lower FGT, we ex-\nplored tissue penetration of two commonly prescribed NRTIs, te-\nnofovir and lamivudine, and an NNRTI, efavirenz, in addition to an \nantifungal, fluconazole, in post-mortem FGT tissues (i.e. ovarian,"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 774
encoding: FLOAT32
metadata:
{"title": "A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues", "chroma:document": "uterine, cervical and vaginal) from a population of Ugandan wo-\nmen living with HIV/AIDs prior to the time of death.\nMethods\nStudy participants and sample collection\nAll study participants were hospitalized patients living with HIV/AIDs who \npassed away at Mulago National Referral Hospital in Kampala, Uganda \nfrom 2017 to 2020. Written informed consent was obtained from the \nnext of kin. ART history, including recent medication adherence, was ex-\ntracted from medical charts and from interviews with caretakers. \n3180"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 775
encoding: FLOAT32
metadata:
{"title": "Inside-out assembly of viral antigens for the enhanced vaccination", "chroma:document": "ARTICLE\nOPEN\nInside-out assembly of viral antigens for the enhanced\nvaccination\nFengqiang Cao1,2,3, Sha Peng1,2,3, Yaling An4,5, Kun Xu4,6, Tianyi Zheng4,7, Lianpan Dai\n4, Kenji Ogino2,3\u2709, To Ngai\n8,\nYufei Xia1,9,10\u2709 and Guanghui Ma\n1,3,9,10\u2709\nCurrent attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect\nthat pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural\ndissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance.\nHere, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In\nthis manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP\nwas absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging\nstrategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-\npotentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes.\nIn both H1N1 in\ufb02uenza and SARS-CoV-2 vaccines, rMASE signi\ufb01cantly increased antigen-speci\ufb01c antibody secretion, memory T cell\nengagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the\ndelivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced\nvaccinations against the enveloped RNA virus.\nSignal Transduction and Targeted Therapy  (2023) 8:189 \n; https://doi.org/10.1038/s41392-023-01414-7\nINTRODUCTION\nA major challenge in vaccine design is stimulating the potency\nand duration of the immune responses.1,2 The immune responses\nto infection or vaccination are temporal sequences of events,\nwhich depend on the ordered exposure of antigenic components"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 776
encoding: FLOAT32
metadata:
{"title": "Inside-out assembly of viral antigens for the enhanced vaccination", "chroma:document": "to the immune system,3,4 as well as the coordinated actions of the\nlymph\nnodes,\nimmunocytes,\ncytokines,\netc.5,6\nThus,\npotent\nvaccines are expected to harness spatial and temporal control\nover sequential immune activation.7\nTo address\nthis,\nnano- and micro-delivery\nsystems\nwith\ncontrollable physicochemical properties and multi-level nanos-\ntructures are engineered to deliver multiple vaccine compo-\nnents.8,9 Additionally, since pathogens are the perfect vehicles of\nnatural selection, there is a trend to mimic their structures or\nphysiochemical properties.10,11 Increased lymph node accumula-\ntion of antigen, antigen uptake, and antigen cross-presentation\nhave been witnessed in previous attempts to replicate live\npathogens\u2019 sizes, shapes, charges, and softness.12,13 As for the\ndelivery kinetics, it is thought to replicate the natural dissemina-\ntion of multiple antigenic components, which may dictate the\nexposure sequence for subsequent immune activation in a\nbiomimetic manner.14\nNonetheless, pathogens usually evolve to escape the immune\nsystem rather than to provoke it.15\u201317 In the case of enveloped\nRNA viruses, genome replication results in the accumulation of\npathogen-associated molecular patterns, which can lead to a\nstrong host anti-viral response.18,19 To circumvent this, immuno-\ngenic components, such as viral genes and proteins (e.g.,\nnucleocapsid\nprotein,\nNP),\nare\ntightly\nbound\nand\nhidden\ninside.20,21 Subsequently, the embedded NP is delayed in its\nexposure to immune surveillance, leading to suppressed type I\ninterferon (IFN-I) expression, as well as impeded anti-viral effects.22\nAccordingly, the exact replicas of natural dissemination may not\nbe an optimal solution. As a preliminary test, we treated bone\nmarrow-derived dendritic cells (BMDCs) with the surface antigen\nand NP of H1N1 in\ufb02uenza virus (A/Puerto Rico/8/1934)23 and\nSARS-CoV-2 (hCoV-19/China/CAS-B001/2020),24 respectively. In\nthe presence of the surface antigen, higher doses of NP resulted"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 777
encoding: FLOAT32
metadata:
{"title": "Inside-out assembly of viral antigens for the enhanced vaccination", "chroma:document": "in the up-regulated expression of IFN-\u03b1, suggesting a robust anti-\nviral effect (Supplementary Fig. 1).\nReceived: 12 July 2022 Revised: 13 January 2023 Accepted: 8 March 2023\n1State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; 2Graduate School of Bio-Applications\nand Systems Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan; 3Institute of Global Innovation Research, Tokyo\nUniversity of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan; 4CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of\nMicrobiology, Chinese Academy of Sciences, Beijing 100101, PR China; 5Savaid Medical School, University of Chinese Academy of Sciences, Beijing, PR China; 6Key Laboratory of\nTropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Af\ufb01liated Hospital, Hainan Medical University, Hainan\n571199, PR China; 7Zhejiang University School of Medicine, Hangzhou 310058, PR China; 8Department of Chemistry, The Chinese University of Hong Kong, Shatin, N. T., Hong\nKong 999077, PR China; 9University of Chinese Academy of Sciences, Beijing 100049, PR China and 10Innovation Academy for Green Manufacture Chinese Academy of Sciences,\nBeijing 100190, PR China\nCorrespondence: Kenji Ogino (kogino@cc.tuat.ac.jp) or Yufei Xia (yfxia@ipe.ac.cn) or Guanghui Ma (ghma@ipe.ac.cn)\nThese authors contributed equally: Fengqiang Cao, Sha Peng, Yaling An\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: 778
encoding: FLOAT32
metadata:
{"title": "Thematic Issues 2020-2022-CN", "chroma:document": "Current Neuropharmacology\n\u0002\u0003\u0003\u0004\u0005\u0006\u0007\b\t\n\u000b\u0007\b\f\r\n\u000e\u0002\u0003\u0003\u0004\u0005\u0006\u0007\u000f\t\b\u000b\u0010\u0007\f\n\u0002\u0003\u0004\u0005\u0006\u0003\u0005\n\u0007\u0005\u0006\b\t\n\u000b\n\u0004\f\r\u000e\u000f\u0010\n\u0011\u000e\u000f\u0010\u0012\u0013\u0014\n\u0015\u0016\u0015\u0017\nSend Orders for Reprints to reprints@benthamscience.net \n560\n \nCurrent Neuropharmacology, 2023, 21, 560-577 \n \nREVIEW ARTICLE \nTherapeutic Approaches to Non-Motor Symptoms of Parkinson's Disease: \nA Current Update on Preclinical Evidence \n \nPoornima D.E. Weerasinghe-Mudiyanselage1,#, Sohi Kang1,#, Joong-Sun Kim1 and Changjong Moon1,* \n1Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, \nChonnam National University, Gwangju 61186, South Korea \n \nAbstract: Despite being classified as a movement disorder, Parkinson\u2019s disease (PD) is characterized \nby a wide range of non-motor symptoms that significantly affect the patients' quality of life. However, \nclear evidence-based therapy recommendations for non-motor symptoms of PD are uncommon. Ani-\nmal models of PD have previously been shown to be useful for advancing the knowledge and treat-\nment of motor symptoms. However, these models may provide insight into and assess therapies for \nnon-motor symptoms in PD. This paper highlights non-motor symptoms in preclinical models of PD \nand the current position regarding preclinical therapeutic approaches for these non-motor symptoms. \nThis information may be relevant for designing future preclinical investigations of therapies for non-\nmotor symptoms in PD. \n \nA R T I C L E  H I S T O R Y \n \n \nReceived: June 19, 2022 \nRevised: August 30, 2022 \nAccepted: September 02, 2022 \n \nDOI:  \n10.2174/1570159X20666221005090126 \n \n \nKeywords: Non-motor symptoms, Parkinson\u2019s disease, patients' quality of life, preclinical models, therapeutics, rapid eye move-\nment (REM). \n1. INTRODUCTION \n \nParkinson\u2019s disease (PD) is one of the most prevalent \nneurodegenerative disorders owing to the main impairment \nof the nigrostriatal system with dopamine (DA) deficiency, \nwhich is characterized by a combination of motor and non-\nmotor symptoms [1, 2]. Furthermore, PD is a chronic, pro-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 779
encoding: FLOAT32
metadata:
{"title": "Thematic Issues 2020-2022-CN", "chroma:document": "gressive disease that requires continued treatment to prevent \nthe deterioration of quality of life [3]. Although various clin-\nical trials have been conducted for the most current sympto-\nmatic therapies [4, 5], therapies for PD are still not complete-\nly satisfactory. Moreover, continuous preclinical investiga-\ntions are essential to clarify the efficacy of existing therapies \nin different animal models that mimic specific pathological \naspects of PD.  \n \nIn patients, PD is defined not only by motor symptoms \nbut also by a complex range of non-motor symptoms present \nthroughout disease progression [6]. The prodromal period of \nPD is characterized by a variety of non-motor symptoms, \nsuch as hyposmia, rapid eye movement (REM), constipation, \nfatigue, erectile dysfunction, pain, depression, and cognitive \nimpairment [6, 7]. Alternatively, these and other non-motor \nsymptoms may arise later in the disease course [6, 8]. For \nexample, cognitive deficits may become more severe as the \ndisease progresses [8]. Mild cognitive impairment is an \n \n*Address correspondence to this author at the Department of Veterinary \nAnatomy and Animal Behavior, College of Veterinary Medicine and BK21 \nFOUR Program, Chonnam National University, 77 Yongbong-ro, Buk-gu, \nGwangju 61186, South Korea, Tel: +82-62-530-2838;  \nE-mail: moonc@chonnam.ac.kr  \n#These first two authors contributed equally to this work. \nintermediate stage on the gradient between normal cognitive \nfunction and dementia and is linked with an increased risk of \ndementia [9]. Thus, mild cognitive impairment has been \nsuggested as an important predictor of the progression to PD \ndementia [10, 11]. Some non-motor symptoms remain undis-\nclosed because patients are embarrassed or unaware that the \nsymptoms are linked to PD [12]. Consequently, the non-\nmotor symptoms of PD are poorly recognized and treated \n[6]. However, non-motor symptoms can be equally debilitat-\ning in patients [13, 14], and the majority of non-motor symp-"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 780
encoding: FLOAT32
metadata:
{"title": "Thematic Issues 2020-2022-CN", "chroma:document": "toms do not respond to treatments targeting motor symptoms \n[15, 16].  \n \nNon-motor symptoms of PD most likely involve different \nmechanisms, such as DAergic, non-DAergic, genetic, or \ndrug-induced pathways [6]. For instance, DAergic and nora-\ndrenergic denervation of the limbic system are noted in pa-\ntients with PD and depression [17, 18]. The appearance of \nnon-motor symptoms in PD patients with Parkin [19], SNCA \n[20], LRRK2 [21] or GBA [22] mutations implies a genetic \nbasis for non-motor symptoms. Long-term use of DA re-\nplacement therapies can lead to non-motor side effects, such \nas diarrhea, nausea, hallucination, blurred vision, and hypo-\ntension [2, 23-26]. The heterogeneous nature and differential \nresponses to DAergic and non-DAergic treatments make the \nmanagement of non-motor symptoms challenging in clinical \npractice. Some non-motor symptoms, such as apathy, anxie-\nty, and primary pain, are responsive to DA replacement ther-\napy [2]. However, PD-associated dementia is responsive to \nnon-DAergic therapies such as cholinesterase inhibitors and \nN-methyl-d-aspartate receptor (NMDAR) antagonists [27].  \n1875-6190/23 $65.00+.00\n\u00a9 2023 Bentham Science Publishers"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 781
encoding: FLOAT32
metadata:
{"title": "Oligodendrocyte death initiates synchronous remyelination to restore cortical myelin patterns in mice", "chroma:document": "Oligodendrocyte death initiates synchronous remyelination to \nrestore cortical myelin patterns in mice\nTimothy W. Chapman1, Genaro E. Olveda1, Xhoela Bame1, Elizabeth Pereira1, Robert A. \nHill1,#\n1Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA\nAbstract\nMyelin degeneration occurs in neurodegenerative diseases and aging. In these conditions, \nresident oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes that carry \nout myelin repair. To investigate the cellular dynamics underlying these events, we developed a \nnoninflammatory demyelination model that combines intravital two-photon imaging with a single-\ncell ablation technique called two-photon apoptotic targeted ablation (2Phatal). Oligodendrocyte \n2Phatal in both sexes results in a myelin degeneration cascade that triggers rapid forms of \nsynchronous remyelination on defined axons. This remyelination is driven by oligodendrocytes \ndifferentiated from a subset of morphologically distinct, highly branched OPCs. Moreover, \nremyelination efficiency depends on the initial myelin patterns, as well as the age of the organism. \nIn summary, using 2Phatal, we show a form of rapid synchronous remyelination, mediated by a \ndistinct subset of OPCs, capable of restoring the original myelin patterning in adulthood but not \naging.\nINTRODUCTION\nMyelination increases neural circuit processing speed and efficiency1,2. Many \nneurodegenerative conditions result from myelin dysfunction and myelin is one of the \nearliest structures to degenerate in aging3-5. The cellular mechanisms that allow for the \ncontinued refinement and myelin plasticity observed in adulthood6-8 are thought to be \nco-opted for myelin repair. Yet, it is not fully known how these cycles of degeneration and \nrepair occur at the cellular level, in vivo.\nRemyelination is primarily carried out by resident, self-renewing oligodendrocyte precursor \ncells (OPCs), which can differentiate into oligodendrocytes throughout life9,10. OPCs are"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 782
encoding: FLOAT32
metadata:
{"title": "Oligodendrocyte death initiates synchronous remyelination to restore cortical myelin patterns in mice", "chroma:document": "dynamic, engaging in tissue surveillance, response to damage, and remyelination11-14. \nThere is some evidence that functional heterogeneity within the OPC population exists15-20. \n#corresponding author: robert.hill@dartmouth.edu.\nAUTHOR CONTRIBUTIONS\nT.W.C and R.A.H conceived of, designed, and performed all experiments and most of the data analysis and quantification. \nG.E.O. performed OPC morphological and migration analyses and contributed to quantification associated with sheath and node \nremyelination. Xh.B. contributed to data analysis and quantification. E.P. contributed to OPC fate analysis and imaging data collation. \nT.W.C and R.A.H. wrote the paper and R.A.H. directed the study.\nCOMPETING INTERESTS\nThe authors declare no competing interests.\nHHS Public Access\nAuthor manuscript\nNat Neurosci. Author manuscript; available in PMC 2023 October 01.\nPublished in final edited form as:\nNat Neurosci. 2023 April ; 26(4): 555\u2013569. doi:10.1038/s41593-023-01271-1.\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript\nAuthor Manuscript"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 783
encoding: FLOAT32
metadata:
{"title": "Frequency dependent emotion differentiation and directional coupling in amygdala, orbitofrontal and medial prefrontal cortex network with intracranial recordings", "chroma:document": "ARTICLE\nOPEN\nFrequency dependent emotion differentiation and directional\ncoupling in amygdala, orbitofrontal and medial prefrontal\ncortex network with intracranial recordings\nSaurabh Sonkusare\n1,2,3, Ding Qiong1,4, Yijie Zhao\n3,4, Wei Liu1, Ruoqi Yang1, Alekhya Mandali\n2,5,6, Luis Manssuer1,2,3,\nChencheng Zhang\n1, Chunyan Cao1, Bomin Sun\n1, Shikun Zhan\n1\u2709 and Valerie Voon\n2,3\u2709\n\u00a9 The Author(s) 2022\nThe amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit, yet their\nemotion induced responses and interactions have been poorly investigated with direct intracranial recordings. Such high-\ufb01delity\nsignals can uncover precise spectral dynamics and frequency differences in valence processing allowing novel insights on\nneuromodulation. Here, leveraging the unique spatio-temporal advantages of intracranial electroencephalography (iEEG) from a\ncohort of 35 patients with intractable epilepsy (with 71 contacts in amygdala, 31 in OFC and 43 in mPFC), we assessed the spectral\ndynamics and interactions between the amygdala, OFC and mPFC during an emotional picture viewing task. Task induced activity\nshowed greater broadband gamma activity in the negative condition compared to positive condition in all the three regions.\nSimilarly, beta activity was increased in the negative condition in the amygdala and OFC while decreased in mPFC. Furthermore,\nbeta activity of amygdala showed signi\ufb01cant negative association with valence ratings. Critically, model-based computational\nanalyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-\namygdala and OFC-mPFC. Our \ufb01ndings provide direct neurophysiological evidence for a much-posited model of top-down\nin\ufb02uence of mPFC over amygdala and a bidirectional in\ufb02uence between OFC and the amygdala. Altogether, in a relatively large\nsample size with human intracranial neuronal recordings, we highlight valence-dependent spectral dynamics and dyadic coupling"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 784
encoding: FLOAT32
metadata:
{"title": "Frequency dependent emotion differentiation and directional coupling in amygdala, orbitofrontal and medial prefrontal cortex network with intracranial recordings", "chroma:document": "within the amygdala-mPFC-OFC network with implications for potential targeted neuromodulation in emotion processing.\nMolecular Psychiatry (2023) 28:1636\u20131646; https://doi.org/10.1038/s41380-022-01883-2\nINTRODUCTION\nThe amygdala, orbitofrontal cortex (OFC) and medial prefrontal\ncortex (mPFC) are critical to emotional processing and regulation\n[1]. Human neuroimaging studies with functional magnetic\nresonance imaging (fMRI) provide substantial evidence for their\ninvolvement in emotion perception and evaluation [2, 3]. How-\never, fMRI is dependent on the sluggish haemodynamic response\n(>3 s) and which remains an indirect measure of neuronal activity\n[4]. In contrast, intracranial electroencephalography (iEEG) records\ndirect neuronal\npopulation\nlevel\nactivity\nat\nhigh\ntemporal\nresolution enabling insights into precise spectral dynamics. Thus,\niEEG can potentially uncover speci\ufb01c frequency and timing\ndifferences underlying various emotions which may inform\nstimulation and targets for neuromodulation. Although a few\nstudies have investigated emotional processing in the amygdala\nusing iEEG, they have focussed predominantly on event related\npotentials (ERPs) [5, 6] with limited reporting of precise time-\nresolved spectral dynamics [7, 8]. Furthermore, only one iEEG\nstudy has examined OFC and mPFC activity in emotion processing\n[9] to the best of our knowledge and crucially none have\ninvestigated the interactions amongst this key emotion circuit\nwith direct recordings. Consequently, direct evidence of valence-\ndependent coupling between the amygdala, the OFC, and mPFC\nremains poorly investigated in humans despite it being strongly\nimplicated in affect and psychopathology [10].\nThe prefrontal cortex is believed to play a role in top-down\nmodulation of amygdala activity providing contextualisation and\nevaluation of stimuli while the amygdala drives bottom-up\nsalience processing [11]. However, the prefrontal cortex is a\nrelatively large heterogenous structure with various distinct"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 785
encoding: FLOAT32
metadata:
{"title": "Frequency dependent emotion differentiation and directional coupling in amygdala, orbitofrontal and medial prefrontal cortex network with intracranial recordings", "chroma:document": "anatomical and functional divisions including the OFC and mPFC\n[12, 13]. Structurally, the amygdala is highly interconnected with\nboth the OFC [14] and mPFC [15]. Tract tracing studies from non-\nhuman primate brains reveal afferent \ufb01bres from the OFC and\nmPFC terminating in the amygdala [15]. In turn, efferent \ufb01bres\nfrom the amygdala project to the OFC and mPFC [16]. Such\nstructural connectivity constrains functional interactions between\nbrain regions for fast and ef\ufb01cient transfer of information [17]\nhighlighting the integrated coupling within this amygdala-OFC-\nmPFC network.\nReceived: 8 March 2022 Revised: 4 November 2022 Accepted: 10 November 2022\nPublished online: 2 December 2022\n1Department of Neurosurgery, Centre for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2Department of\nPsychiatry, University of Cambridge, Cambridge, UK. 3Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China. 4Key Laboratory of\nComputational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China. 5Nuf\ufb01eld Department of Clinical Neurosciences, University\nof Oxford, Oxford, UK. 6MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK. \u2709email: shikun_zhan@hotmail.com; voonval@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: 786
encoding: FLOAT32
metadata:
{"title": "Acute psilocybin enhances cognitive flexibility in rats", "chroma:document": "ARTICLE\nOPEN\nAcute psilocybin enhances cognitive \ufb02exibility in rats\nAlejandro Torrado Pacheco\n1\u2709, Randall J. Olson1, Gabriela Garza\n1,2 and Bita Moghaddam1\u2709\n\u00a9 The Author(s) 2023\nPsilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-\nguided interventions. To understand the neural basis for this pattern of clinical ef\ufb01cacy, experimental and conceptual approaches\nthat are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that\nacute psilocybin improves cognitive \ufb02exibility, which then enhances the impact of clinician-assisted interventions. Consistent with\nthis idea, we \ufb01nd that acute psilocybin robustly improves cognitive \ufb02exibility in male and female rats using a task where animals\nswitched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not in\ufb02uence\nPavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned\nbehavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin\u2019s effect on set-shifting, while a\n5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship\nbetween psilocybin\u2019s pharmacology and its impact on \ufb02exibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine\n(DOI) impaired cognitive \ufb02exibility in the same task, suggesting that this effect of psilocybin does not generalize to all other\nserotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive \ufb02exibility provides a useful behavioral\nmodel to investigate its neuronal effects relevant to its positive clinical outcome.\nNeuropsychopharmacology (2023) 48:1011\u20131020; https://doi.org/10.1038/s41386-023-01545-z\nINTRODUCTION\nRecent clinical trials indicate that psilocybin is an effective\ntreatment for symptoms of several psychiatric disorders, including"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 787
encoding: FLOAT32
metadata:
{"title": "Acute psilocybin enhances cognitive flexibility in rats", "chroma:document": "anxiety and depression [1\u20135]. A unique aspect of these studies is\nthat sustained therapeutic ef\ufb01cacy is observed when one or a few\ndoses of psilocybin are administered during clinician-guided\nfacilitation or intervention [6\u201311]. To date, clinical data showing\nthat psilocybin has therapeutic ef\ufb01cacy as a stand-alone treatment\nis lacking, suggesting that its effects may be, at least in part, due\nto the combination of therapeutic intervention and exposure to\nacute psilocybin. Accordingly, multiple ongoing clinical trials are\nassessing the ef\ufb01cacy of joining psychotherapy or cognitive\nbehavioral therapy with psilocybin treatment (e.g., NCT05227612).\nWhile the pharmacology of psilocybin is relatively well character-\nized, how this translates to its clinical effects remains unclear.\nWhat are the mechanisms that underlie psilocybin\u2019s clinical\nef\ufb01cacy when combined with psychotherapy or other clinician-\nguided interventions? Though several ideas have been proposed\n[12], we focused on the hypothesis that acutely psilocybin creates\na cognitive state that improves therapeutic intervention by\nrelaxing prior beliefs, promoting \ufb02exible thinking, and increasing\ncognitive \ufb02exibility [1, 13, 14].\nCognitive \ufb02exibility is the ability to switch between mental\nprocesses in order to appropriately adapt behavior to changes in\nthe environment. Impairments in cognitive \ufb02exibility are a\nprominent feature of many psychiatric disorders, including major\ndepression (MDD) and substance use disorders [15\u201319], which\nhave shown a positive response to psilocybin-assisted treatment.\nThus, the capacity to improve cognitive \ufb02exibility in order to\nfacilitate breaking out of rigid behavioral patterns and beliefs is a\nplausible mechanism by which psilocybin may exert its therapeu-\ntic bene\ufb01ts [1, 14, 20].\nPreclinical studies are critical for advancing our mechanistic\nunderstanding of the therapeutic ef\ufb01cacy of psilocybin. There is a\ngrowing appreciation that traditional behavioral tests used to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 788
encoding: FLOAT32
metadata:
{"title": "Acute psilocybin enhances cognitive flexibility in rats", "chroma:document": "study antidepressant effects do not reliably translate to effects in\nhuman populations [21]. While several traditional preclinical\napproaches to study depression-like behaviors in rodents have\nbeen used in conjunction with psilocybin [22, 23], little is known\nabout the acute effect of this drug on cognitive \ufb02exibility and\nrelated constructs. Other work has examined the acute effects of\npsychedelics on cognitive \ufb02exibility, but none of these studies\nused psilocybin [24, 25]. We hypothesize that the acute effects of\npsilocybin may be inducing a state of increased cognitive\n\ufb02exibility\nthat\nenhances\nthe\ntherapeutic\nresponse\nduring\nclinician-assisted sessions.\nTo assess cognitive \ufb02exibility, we used a set-shifting task, which\ntests an animal\u2019s ability to modify behavior, among competing\nand previously learned strategies, in response to changes in\nenvironmental contingencies. We \ufb01nd that acute psilocybin\ntreatment improves set-shifting behavior without in\ufb02uencing\nappetitive or aversive learning. Psilocybin\u2019s effect on cognitive\n\ufb02exibility was diminished by a 5HT2A but not by a 5HT2C\nserotonin receptor antagonist. Consistent with other studies\nshowing impaired cognitive \ufb02exibility with psychedelics other\nthan\npsilocybin\n[24,\n25],\nwe\n\ufb01nd\nthat\n2,5-Dimethoxy-4-\nReceived: 20 October 2022 Revised: 27 January 2023 Accepted: 30 January 2023\nPublished online: 20 February 2023\n1Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA. 2Present address: Department of Biomedical Engineering, University of\nMichigan, Ann Arbor, MI 48109, USA. \u2709email: pachecoa@ohsu.edu; bita@ohsu.edu\nwww.nature.com/npp\n1234567890();,:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 789
encoding: FLOAT32
metadata:
{"title": "Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox", "chroma:document": "Elsevier has created a Monkeypox Information Center in response to the \ndeclared public health emergency of international concern, with free \ninformation in English on the monkeypox virus. The Monkeypox Information \nCenter is hosted on Elsevier Connect, the company's public news and \ninformation website.  \n  \nElsevier hereby grants permission to make all its monkeypox related \nresearch that is available on the Monkeypox Information Center - including \nthis research content - immediately available in publicly funded \nrepositories, with rights for unrestricted research re-use and analyses in \nany form or by any means with acknowledgement of the original source. \nThese permissions are granted for free by Elsevier for as long as the \nMonkeypox Information Center remains active."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 790
encoding: FLOAT32
metadata:
{"title": "Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors", "chroma:document": "RESEARCH ARTICLES\nOpen camera or QR reader and\nscan code to access this article\nand other resources online.\nAssessment of Pre-Clinical Liver Models Based on Their Ability\nto Predict the Liver-Tropism of Adeno-Associated Virus Vectors\nAdrian Westhaus,1,2,{ Marti Cabanes-Creus,1,{ Kimberley L. Dilworth,1 Erhua Zhu,3 David Salas Go\u00b4 mez,4\nRenina G. Navarro,1 Anais K. Amaya,3 Suzanne Scott,1,3,5 Magdalena Kwiatek,6 Alexandra L. McCorkindale,7\nTara E. Hayman,7 Silke Frahm,8 Dany P. Perocheau,9\u201311 Bang Manh Tran,12 Elizabeth Vincan,12\u201314\nSharon L. Wong,15,16 Shafagh A. Waters,15\u201317 Georgina E. Riddiough,12,18 Marcos V. Perini,18\nLaurence O.W. Wilson,5,19 Julien Baruteau,9\u201311 Sebastian Diecke,8 Gloria Gonza\u00b4lez-Aseguinolaza,4\nGiorgia Santilli,2 Adrian J. Thrasher,2 Ian E. Alexander,3,20 and Leszek Lisowski1,21,22,*\n1Translational Vectorology Research Unit, Children\u2019s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia; 2Great\nOrmond Street Institute of Child Health, University College London, London, United Kingdom; 3Gene Therapy Research Unit, Children\u2019s Medical Research Institute and\nSydney Children\u2019s Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia; 4Gene Therapy and Regulation of Gene Expression\nDepartment, IdiSNA,InstitutodeInvestigacio\u00b4n SanitariadeNavarra,Universidad deNavarra, CIMA, Pamplona,Spain; 5Australian e-HealthResearch Centre,Commonwealth\nScienti\ufb01c and Industrial Research Organisation, Sydney, Australia; 6Military Institute of Hygiene and Epidemiology, The Biological Threats Identi\ufb01cation and Countermeasure\nCentre,Pu\u0142awy,Poland; 7Inventia Life SciencePty Ltd.,Sydney,Australia; 8StemCellTechnology Platform,Max Delbru\u00a8ckCentrumforMolecular Medicine, Berlin,Germany;\n9Genetics and Genomic Medicine Department, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom; 10Metabolic Medicine"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 791
encoding: FLOAT32
metadata:
{"title": "Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors", "chroma:document": "Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 11National Institute of Health Research Great Ormond Street\nHospital Biomedical Research Centre, London, United Kingdom; 12Department of Infectious Diseases, Melbourne Medical School, The University of Melbourne at the Peter\nDoherty Institute for Infection and Immunity, Melbourne, Australia; 13Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty\nInstitute for Infection and Immunity, Melbourne, Australia; 14Curtin Medical School, Curtin University, Perth, Australia; 15Molecular and Integrative Cystic Fibrosis (miCF)\nResearch Centre, University of New South Wales and Sydney Children\u2019s Hospital, Sydney, Australia; 16School of Biomedical Sciences, Faculty of Medicine, University of\nNew South Wales, Sydney, Australia; 17Department of Respiratory Medicine, Sydney Children\u2019s Hospital, Faculty of Medicine, University of New South Wales, Sydney,\nAustralia; 18Department of Surgery, Austin Health Precinct, The University of Melbourne, Austin Health, Heidelberg, Australia; 19Applied BioSciences, Faculty of Science and\nEngineering, Macquarie University, Sydney, Australia; 20Discipline of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney,\nAustralia; 21Vector and Genome Engineering Facility, Children\u2019s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia;\n22Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, Warszawa, Poland.\n{These authors\u2019 contributed equally to this work.\nAn earlier draft of this article was posted as a preprint at bioRxiv (doi: content/10.1101/2022.09.28.510021v1).\nThe liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors. Multiple clinical trials\nhave been undertaken for this target in the past 15 years; however, we are still to see market approval of the \ufb01rst liver-targeted"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 792
encoding: FLOAT32
metadata:
{"title": "Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors", "chroma:document": "adeno-associated virus (AAV)\u2013based gene therapy. Inef\ufb01cient expression of the therapeutic transgene, vector-induced liver\ntoxicity andcapsid, and/or transgene-mediated immune responsesreportedathigh vectordosesare the main challengestodate.\nOne of the contributing factors to the insuf\ufb01cient clinical outcomes, despite highly encouraging preclinical data, is the lack of\nrobust, biologically and clinically predictive preclinical models. To this end, this study reports \ufb01ndings of a functional\nevaluation of6 AAV vectors in 12 preclinical models of the human liver, withthe aim to uncover which combinationof models\nis the most relevant for the identi\ufb01cation of AAV capsid variant for safe and ef\ufb01cient transgene delivery to primary human\nhepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepa-\ntocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses\nof each system. This should allow the development of novel gene therapies targeting the human liver.\n*Correspondence: Dr. Leszek Lisowski, Vector and Genome Engineering Facility, Children\u2019s Medical Research Institute, Faculty of Medicine and Health, The University of\nSydney, 214 Hawkesbury Road, Westmead, NSW 2145, Australia. E-mail: llisowski@cmri.org.au\n\u00aa Adrian Westhaus et al. 2023; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License [CC-BY]\n(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nIn the April 2023 issue of Human Gene Therapy (vol. 34, no. 7\u20138; 273\u2013288), the article entitled \u2018\u2018Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict\nthe Liver-Tropism of Adeno-Associated Virus Vectors\u2019\u2019 has been updated on May 2, 2023 after \ufb01rst online publication of April 17,2023 to re\ufb02ect Open Access, with copyright"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 793
encoding: FLOAT32
metadata:
{"title": "Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors", "chroma:document": "transferring to the author(s), and a Creative Commons License (CC-BY) added (http://creativecommons.org/licenses/by/4.0).\nHUMAN GENE THERAPY, VOLUME 34, NUMBERS 7 and 8\nDOI: 10.1089/hum.2022.188 j 273\nMary Ann Liebert, Inc."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 794
encoding: FLOAT32
metadata:
{"title": "Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents", "chroma:document": "Vol.:(0123456789)\n1 3\nBrain Structure and Function (2023) 228:1153\u20131176 \nhttps://doi.org/10.1007/s00429-023-02619-w\nMETHODOLOGY\nMapping the\u00a0primate thalamus: systematic approach to\u00a0analyze \nthe\u00a0distribution of\u00a0subcortical neuromodulatory afferents\nIsabel\u00a0P\u00e9rez\u2011Santos1,2 \u00a0\u00b7 Miguel\u00a0\u00c1ngel\u00a0Garc\u00eda\u2011Cabezas1,2,3 \u00a0\u00b7 Carmen\u00a0Cavada1,2 \nReceived: 12 September 2022 / Accepted: 9 February 2023 / Published online: 8 March 2023 \n\u00a9 The Author(s) 2023\nAbstract\nNeuromodulatory afferents to thalamic nuclei are key for information transmission and thus play critical roles in sensory, \nmotor, and limbic processes. Over the course of the last decades, diverse attempts have been made to map and describe \nsubcortical neuromodulatory afferents to the primate thalamus, including axons using acetylcholine, serotonin, dopamine, \nnoradrenaline, adrenaline, and histamine. Our group has been actively involved in this endeavor. The published descriptions \non neuromodulatory afferents to the primate thalamus have been made in different laboratories and are not fully comparable \ndue to methodological divergences (for example, fixation procedures, planes of cutting, techniques used to detect the afferents, \ndifferent criteria for identification of thalamic nuclei\u2026). Such variation affects the results obtained. Therefore, systematic \nmethodological and analytical approaches are much needed. The present article proposes reproducible methodological and \nterminological frameworks for primate thalamic mapping. We suggest the use of standard stereotaxic planes to produce \nand present maps of the primate thalamus, as well as the use of the Anglo-American school terminology (vs. the German \nschool terminology) for identification of thalamic nuclei. Finally, a public repository of the data collected under agreed-on \nframeworks would be a useful tool for looking up and comparing data on the structure and connections of primate thalamic \nnuclei. Important and agreed-on efforts are required to create, manage, and fund a unified and homogeneous resource of"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 795
encoding: FLOAT32
metadata:
{"title": "Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents", "chroma:document": "data on the primate thalamus. Likewise, a firm commitment of the institutions to preserve experimental brain material is \nmuch needed because neuroscience work with non-human primates is becoming increasingly rare, making earlier material \nstill more valuable.\nKeywords Thalamus\u00a0\u00b7 Thalamic nuclei\u00a0\u00b7 Acetylcholine\u00a0\u00b7 Dopamine\u00a0\u00b7 Adrenaline\u00a0\u00b7 Noradrenaline\u00a0\u00b7 Serotonin\u00a0\u00b7 Histamine\nIntroduction\nThe thalamus is a nuclear complex in the diencephalon, \nwhose neurons participate in sensory, motor, and limbic \nfunctions. These functions are supported by bidirectional \nconnections with the cerebral cortex and a variety of subcor-\ntical afferents from sensory pathways, globus pallidus, cer-\nebellum, amygdala, and the hypothalamus. The information \ncarried by the subcortical afferents, as well as from cortical \nlayers V and VI, is processed, modulated, integrated, and \ntransmitted to the cerebral cortex by thalamocortical projec-\ntion neurons (Jones 2007).\nThe thalamus receives cortical afferents, which are \nglutamatergic, and subcortical afferents, which are either \nglutamatergic (for example, from the cerebellum or the \nsomatosensory gracile and cuneate nuclei), GABAergic \n(for example, from the internal globus pallidus or the sub-\nstantia nigra reticulata), as well as cholinergic, adrenergic, \nnoradrenergic, dopaminergic, serotoninergic, histaminergic, \nand peptidergic. This review focuses on the cholinergic and \naminergic afferents, which are functionally modulatory; \nthey shall be referred to as \u201cneuromodulatory afferents\u201d \nthroughout the text, to distinguish them from glutamatergic \nIsabel P\u00e9rez-Santos and Miguel \u00c1ngel Garc\u00eda-Cabezas have equally \ncontributed.\n * Carmen Cavada \n \ncarmen.cavada@uam.es\n1 \nDepartment of\u00a0Anatomy, Histology and\u00a0Neuroscience, \nSchool of\u00a0Medicine, Facultad de Medicina, Universidad \nAut\u00f3noma de Madrid, Calle Arzobispo Morcillo 4, \n28029\u00a0Madrid, Spain\n2 \nPhD Program in\u00a0Neuroscience, Universidad Aut\u00f3noma de \nMadrid-Cajal, Madrid, Spain\n3 \nNeural Systems Laboratory, Department of\u00a0Health Sciences,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 796
encoding: FLOAT32
metadata:
{"title": "Mapping the primate thalamus: systematic approach to analyze the distribution of subcortical neuromodulatory afferents", "chroma:document": "Boston University, Boston, MA, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 797
encoding: FLOAT32
metadata:
{"title": "Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala", "chroma:document": "Vol.:(0123456789)\n1 3\nBrain Structure and Function (2023) 228:1201\u20131257 \nhttps://doi.org/10.1007/s00429-023-02644-9\nREVIEW\nEmotion, motivation, decision\u2011making, the\u00a0orbitofrontal cortex, \nanterior cingulate cortex, and\u00a0the\u00a0amygdala\nEdmund\u00a0T.\u00a0Rolls1,2 \nReceived: 27 January 2023 / Accepted: 12 April 2023 / Published online: 13 May 2023 \n\u00a9 Springer-Verlag GmbH Germany, part of Springer Nature 2023\nAbstract\nThe orbitofrontal cortex and amygdala are involved in emotion and in motivation, but the relationship between these functions \nperformed by these brain structures is not clear. To address this, a unified theory of emotion and motivation is described in \nwhich motivational states are states in which instrumental goal-directed actions are performed to obtain rewards or avoid \npunishers, and emotional states are states that are elicited when the reward or punisher is or is not received. This greatly \nsimplifies our understanding of emotion and motivation, for the same set of genes and associated brain systems can define \nthe primary or unlearned rewards and punishers such as sweet taste or pain. Recent evidence on the connectivity of human \nbrain systems involved in emotion and motivation indicates that the orbitofrontal cortex is involved in reward value and \nexperienced emotion with outputs to cortical regions including those involved in language, and is a key brain region involved \nin depression and the associated changes in motivation. The amygdala has weak effective connectivity back to the cortex in \nhumans, and is implicated in brainstem-mediated responses to stimuli such as freezing and autonomic activity, rather than in \ndeclarative emotion. The anterior cingulate cortex is involved in learning actions to obtain rewards, and with the orbitofrontal \ncortex and ventromedial prefrontal cortex in providing the goals for navigation and in reward-related effects on memory \nconsolidation mediated partly via the cholinergic system."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 798
encoding: FLOAT32
metadata:
{"title": "Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala", "chroma:document": "Keywords Emotion\u00a0\u00b7 Motivation\u00a0\u00b7 Reward\u00a0\u00b7 Human orbitofrontal cortex\u00a0\u00b7 Cingulate cortex\u00a0\u00b7 Amygdala\u00a0\u00b7 Ventromedial \nprefrontal cortex\u00a0\u00b7 Memory\u00a0\u00b7 Depression\u00a0\u00b7 Consciousness\u00a0\u00b7 Mind-brain problem\u00a0\u00b7 Welfare\nIntroduction and\u00a0aims\nThere have been considerable advances recently in under-\nstanding the connectivity and connections of the human \norbitofrontal cortex and amygdala, and how they relate \nto emotion (Rolls et\u00a0al. 2023a, d), but how these systems \nand processes are related to motivation has been much less \nexplored. This paper shows how the brain systems involved \nin motivation are similar to those involved in emotion, and \nprovides a framework for understanding how emotion and \nmotivation are related to each other, and how similar brain \nsystems are involved in both. This paper aims to make key \nadvances in our understanding of how the orbitofrontal \ncortex and amygdala structure (anatomy and connectivity) \nis related to the two key functions performed by these brain \nregions, emotion and motivation.\nTo understand the neuroscience of both emotion and \nmotivation, it is important to have a framework for under-\nstanding the relation between emotion and motivation. This \npaper first sets out a theory of emotion, and a framework for \nunderstanding the relation between emotion and motivation, \nand then considers how brain regions involved in emotion \nand motivation, the orbitofrontal cortex, anterior cingulate \ncortex, and amygdala, are involved in emotion and moti-\nvation. Special reference is made to these brain regions in \nprimates including humans, to ensure that what is described \nin relevant to understanding brain systems involved in emo-\ntion and motivation in humans, and their disorders. Recent \nevidence about the connectivity of these systems in humans \nmakes this paper very timely (Rolls et\u00a0al. 2023a, d). A sec-\nond aim is to show how emotion and its brain systems are \nhighly adaptive from an evolutionary and gene specification \nperspective. The third aim is to consider where and how \n * Edmund T. Rolls"}


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topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 799
encoding: FLOAT32
metadata:
{"title": "Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala", "chroma:document": "Edmund.Rolls@oxcns.org\n \nhttps://www.oxcns.org\n1 \nOxford Centre for\u00a0Computational Neuroscience, Oxford, UK\n2 \nDepartment of\u00a0Computer Science, University of\u00a0Warwick, \nCoventry, UK"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 800
encoding: FLOAT32
metadata:
{"title": "Changes in brain rhythms and connectivity tracking fear acquisition and reversal", "chroma:document": "Vol.:(0123456789)\n1 3\nBrain Structure and Function (2023) 228:1259\u20131281 \nhttps://doi.org/10.1007/s00429-023-02646-7\nORIGINAL ARTICLE\nChanges in\u00a0brain rhythms and\u00a0connectivity tracking fear acquisition \nand\u00a0reversal\nGabriele\u00a0Pirazzini1\u00a0\u00b7 Francesca\u00a0Starita2\u00a0\u00b7 Giulia\u00a0Ricci1\u00a0\u00b7 Sara\u00a0Garofalo2\u00a0\u00b7 Giuseppe\u00a0di\u00a0Pellegrino2\u00a0\u00b7 Elisa\u00a0Magosso1\u00a0\u00b7 \nMauro\u00a0Ursino1\nReceived: 21 November 2022 / Accepted: 17 April 2023 / Published online: 2 May 2023 \n\u00a9 The Author(s) 2023\nAbstract\nFear conditioning is used to investigate the neural bases of threat and anxiety, and to understand their flexible modifications \nwhen the environment changes. This study aims to examine the temporal evolution of brain rhythms using electroencephalo-\ngraphic signals recorded in healthy volunteers during a protocol of Pavlovian fear conditioning and reversal. Power changes \nand Granger connectivity in theta, alpha, and gamma bands are investigated from neuroelectrical activity reconstructed \non the cortex. Results show a significant increase in theta power in the left (contralateral to electrical shock) portion of \nthe midcingulate cortex during fear acquisition, and a significant decrease in alpha power in a broad network over the left \nposterior-frontal and parietal cortex. These changes occur since the initial trials for theta power, but require more trials (3/4) \nto develop for alpha, and are also present during reversal, despite being less pronounced. In both bands, relevant changes in \nconnectivity are mainly evident in the last block of reversal, just when power differences attenuate. No significant changes in \nthe gamma band were detected. We conclude that the increased theta rhythm in the cingulate cortex subserves fear acquisi-\ntion and is transmitted to other cortical regions via increased functional connectivity allowing a fast theta synchronization, \nwhereas the decrease in alpha power can represent a partial activation of motor and somatosensory areas contralateral to"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 801
encoding: FLOAT32
metadata:
{"title": "Changes in brain rhythms and connectivity tracking fear acquisition and reversal", "chroma:document": "the shock side in the presence of a dangerous stimulus. In addition, connectivity\u00a0changes at the end of reversal may reflect \nlong-term alterations in synapses necessary to reverse the previously acquired contingencies.\nKeywords Fear conditioning\u00a0\u00b7 Reversal\u00a0\u00b7 Granger connectivity\u00a0\u00b7 Theta rhythm\u00a0\u00b7 Alpha rhythm\nIntroduction\nFear conditioning is a paradigm used in neuroscience to \nstudy the neurobiological bases of threat and anxiety (Duits \net\u00a0al. 2015; Starita et\u00a0al. 2016, 2019a). In this experimental \nprotocol, a neutral stimulus (conditioned stimulus, CS +) is \npaired with an aversive stimulus (unconditioned stimulus, \nUS) to trigger neural adjustments at the basis of fear acqui-\nsition, finally resulting in the expression of a fear response \nin the presence of the CS + alone. In some experiments, a \nsecond conditioned stimulus (CS-) is unpaired with the US \nto serve as a control condition.\nResults in rodents, primates, and humans provide a \nprecise scenario showing the amygdala, hippocampus, \nand medial prefrontal cortex (mPFC) involvement in fear \nacquisition (Bechara et\u00a0al. 1995, 1999; LaBar et\u00a0al. 1995, \n1998; Knight et\u00a0al. 2005; Cheng et\u00a0al. 2006; Fullana et\u00a0al. \n2016; Bertini et\u00a0al. 2020; Battaglia et\u00a0al. 2020). Further-\nmore, brain oscillations in the theta range (4\u20138\u00a0Hz) play a \npivotal role in this process (Sperl et\u00a0al. 2019). In rodents \nenhanced theta synchrony between the amygdala and \nmPFC has been observed, which differentiated between \nthreat and safety (Likhtik et\u00a0al. 2014). In rats, behavioral \nfear expression, like freezing, coincides with internally \ngenerated theta oscillations in prefrontal-amygdala cir-\ncuits (Karalis et\u00a0al. 2016). In primates, theta power and \ncoherence in the amygdala and anterior cingulate cortex \nincrease during fear learning, but progressively decline \n * Gabriele Pirazzini \n \ngabriele.pirazzini3@unibo.it\n1 \nDepartment of\u00a0Electrical, Electronic, and\u00a0Information \nEngineering \u201cGuglielmo Marconi\u201d, University of\u00a0Bologna, \nArea di Campus Cesena, Via Dell\u2019Universit\u00e0 50,"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 802
encoding: FLOAT32
metadata:
{"title": "Changes in brain rhythms and connectivity tracking fear acquisition and reversal", "chroma:document": "47521\u00a0Cesena, Italy\n2 \nCenter for\u00a0Studies and\u00a0Research in\u00a0Cognitive Neuroscience, \nDepartment of\u00a0Psychology \u201cRenzo Canestrari\u201d, University \nof\u00a0Bologna, 40126\u00a0Bologna, Italy"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 803
encoding: FLOAT32
metadata:
{"title": "Mapping the primate thalamus: historical perspective and modern approaches for defining nuclei", "chroma:document": "Vol.:(0123456789)\n1 3\nBrain Structure and Function (2023) 228:1125\u20131151 \nhttps://doi.org/10.1007/s00429-022-02598-4\nREVIEW\nMapping the\u00a0primate thalamus: historical perspective and\u00a0modern \napproaches for\u00a0defining nuclei\nMiguel\u00a0\u00c1ngel\u00a0Garc\u00eda\u2011Cabezas1,2,3 \u00a0\u00b7 Isabel\u00a0P\u00e9rez\u2011Santos1,2 \u00a0\u00b7 Carmen\u00a0Cavada1,2 \nReceived: 9 May 2022 / Accepted: 14 November 2022 / Published online: 9 January 2023 \n\u00a9 The Author(s) 2023\nAbstract\nThe primate thalamus has been subdivided into multiple nuclei and nuclear groups based on cytoarchitectonic, myeloarchi-\ntectonic, connectional, histochemical, and genoarchitectonic differences. Regarding parcellation and terminology, two main \nschools prevailed in the twentieth century: the German and the Anglo-American Schools, which proposed rather different \nschemes. The German parcellation and terminology has been mostly used for the human thalamus in neurosurgery atlases; \nthe Anglo-American parcellation and terminology is the most used in experimental research on the primate thalamus. In \nthis article, we review the historical development of terminological and parcellation schemes for the primate thalamus over \nthe last 200\u00a0years. We trace the technological innovations and conceptual advances in thalamic research that underlie each \nparcellation, from the use of magnifying lenses to contemporary genoarchitectonic stains during ontogeny. We also discuss \nthe advantages, disadvantages, and practical use of each parcellation.\nKeywords Thalamic nucleus\u00a0\u00b7 Nuclear parcellation\u00a0\u00b7 Cytoarchitecture\u00a0\u00b7 Myeloarchitecture\u00a0\u00b7 Genoarchitecture\u00a0\u00b7 New \nNeuromorphology\nIntroduction\nThe thalamus is a mass of subcortical gray matter on the \nlateral walls of the third ventricle. Some thalamic neurons \nrelay sensory information from the periphery to the cerebral \ncortex and others participate in cognitive and emotional pro-\ncessing through strong reciprocal connections with the cer-\nebral cortex and connections with the amygdala, striatum, \nand hypothalamus (Jones 2007)."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 804
encoding: FLOAT32
metadata:
{"title": "Mapping the primate thalamus: historical perspective and modern approaches for defining nuclei", "chroma:document": "The structure of the thalamus is not homogeneous. Tha-\nlamic neurons are diverse and, together with glial cells, are \ndistributed unevenly across multiple nuclei that can be iden-\ntified and delineated by microscopic examination of brain \nsections stained with different techniques. Neuroanatomists \nof the last 200\u00a0years identified multiple nuclei and nuclear \ngroups in the primate thalamus based on cytoarchitectonic, \nmyeloarchitectonic, connectional, and histochemical differ-\nences that prompted different theoretical paradigms. Regard-\ning terminology, two main schools, the German and the \nAnglo-American Schools, prevailed in the twentieth century \nand proposed rather different schemes for primate thalamic \nnuclei. The German terminology is mostly used in atlases of \nhuman neurosurgery (e.g., Schaltenbrand and Bailey 1959; \nAndrew and Watkins 1968; Van Buren and Borke 1972; \nTasker 1990). In contrast, the Anglo-American terminol-\nogy is mostly used in experimental research on primates, \nincluding humans (Hirai and Jones 1989) and non-human \nprimates (e.g., Olszewski 1952; Goldman-Rakic and Porrino \n1985; S\u00e1nchez-Gonz\u00e1lez et\u00a0al. 2005). More recently, geno-\narchitectonic studies using in\u00a0situ hybridization in vertebrate \nembryos to detect the spatial and temporal expression of \nmorphogenetic genes across the neural plate and neural tube \nhave opened the path for a New Neuromorphology (Nieu-\nwenhuys and Puelles 2016), which is based on the origin of \nbrain structures in ontogeny and phylogeny, and will likely \nimpact future parcellations and terminologies for thalamic \nnuclei in human and non-human primates.\n * Carmen Cavada \n \ncarmen.cavada@uam.es\n1 \nDepartment of\u00a0Anatomy, Histology and\u00a0Neuroscience, \nSchool of\u00a0Medicine, Universidad Aut\u00f3noma de Madrid, \nCalle Arzobispo Morcillo 4, 28029\u00a0Madrid, Spain\n2 \nPhD Program in\u00a0Neuroscience, Universidad Aut\u00f3noma de \nMadrid-Cajal, Madrid, Spain\n3 \nNeural Systems Laboratory, Department of\u00a0Health Sciences, \nBoston University, Boston, MA, USA"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 805
encoding: FLOAT32
metadata:
{"title": "Phenotypic and functional analysis of CD1a+ dendritic cells from cats chronically infected with feline immunodeficiency virus", "chroma:document": "Phenotypic and functional analysis of CD1a+ dendritic cells from \ncats chronically infected with feline immunodeficiency virus\nLin Zhang1, Stacie Reckling2, Gregg A. Dean1\nGregg A. Dean: gregg.dean@colostate.edu\n1Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine, \nColorado State University, Fort Collins, CO 80523, USA, Telephone: 970-491-6144, FAX: \n970-491-0603\n2Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina \nState University, Raleigh, NC 27606, USA\nAbstract\nNumerous studies suggest dendritic cell (DC) dysfunction is central to the dysregulated immune \nresponse during HIV infection; however, in vivo studies are lacking. In the present study we \nused feline immunodeficiency virus (FIV) infection of cats as a model for HIV-1 infection to \nassess the maturation and function of dendritic cells, in vivo and in vitro. We compared CD1a+ \nDC migration, surface phenotype, endocytosis, mixed leukocyte reaction (MLR) and regulatory T \ncell (Treg) phenotype induction by CD1a+ cells isolated from lymph nodes of FIV-infected and \ncontrol cats. Results showed that resident CD1a+ DC in lymph nodes of chronically FIV-infected \ncats are phenotypically mature, can stimulate normal primary T cell proliferation, override Treg \nsuppression and do not skew toward Treg induction. In contrast, FIV infection had deleterious \neffects on antigen presentation and migratory capacity of CD1a+ cells in tissues.\nKeywords\nFeline immunodeficiency virus; dendritic cells; CD1a; regulatory T cells\n1. Introduction\nFeline immunodeficiency virus (FIV) is a naturally occurring pathogenic lentivirus that \ninfects domestic and non-domestic cats causing an immunodeficiency syndrome similar \nto HIV infection of people [1]. In addition to well-studied deficiencies in the adaptive \nimmune response, innate immune defects caused by FIV have also been described [1, 2]. \nWe have previously shown that FIV-infected cats have a delayed and impaired response"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 806
encoding: FLOAT32
metadata:
{"title": "Phenotypic and functional analysis of CD1a+ dendritic cells from cats chronically infected with feline immunodeficiency virus", "chroma:document": "Correspondence to: Gregg A. Dean, gregg.dean@colostate.edu.\nConflict of interest statement: The authors declare no conflicts of interest.\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 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\nComp Immunol Microbiol Infect Dis. Author manuscript; available in PMC 2023 June 09.\nPublished in final edited form as:\nComp Immunol Microbiol Infect Dis. 2015 October ; 42: 53\u201359. doi:10.1016/j.cimid.2015.07.003.\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: 807
encoding: FLOAT32
metadata:
{"title": "Antibody-dependent cellular cytotoxicity, infected cell binding and neutralization by antibodies to the SIV envelope glycoprotein", "chroma:document": "RESEARCH ARTICLE\nAntibody-dependent cellular cytotoxicity,\ninfected cell binding and neutralization by\nantibodies to the SIV envelope glycoprotein\nMichael W. Grunst1\u00a4, Ruby A. Ladd2, Natasha M. Clark1, Hwi Min Gil2, Vadim A. Klenchin1,\nRosemarie Mason3, Genoveffa Franchini4, Mario Roederer3, David T. EvansID1,2*\n1 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin,\nUnited States of America, 2 Wisconsin National Primate Research Center, University of Wisconsin-Madison,\nMadison, Wisconsin, United States of America, 3 Vaccine Research Center, National Institute of Allergy and\nInfectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of\nAmerica, 4 Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland,\nUnited States of America\n\u00a4 Current address: Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut, United\nStates of America\n* dtevans2@wisc.edu\nAbstract\nAntibodies specific for diverse epitopes of the simian immunodeficiency virus envelope gly-\ncoprotein (SIV Env) have been isolated from rhesus macaques to provide physiologically\nrelevant reagents for investigating antibody-mediated protection in this species as a nonhu-\nman primate model for HIV/AIDS. With increasing interest in the contribution of Fc-mediated\neffector functions to protective immunity, we selected thirty antibodies representing different\nclasses of SIV Env epitopes for a comparison of antibody-dependent cellular cytotoxicity\n(ADCC), binding to Env on the surface of infected cells and neutralization of viral infectivity.\nThese activities were measured against cells infected with neutralization-sensitive (SIV-\nmac316 and SIVsmE660-FL14) and neutralization-resistant (SIVmac239 and SIVsmE543-3)\nviruses representing genetically distinct isolates. Antibodies to the CD4-binding site and\nCD4-inducible epitopes were identified with especially potent ADCC against all four viruses."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 808
encoding: FLOAT32
metadata:
{"title": "Antibody-dependent cellular cytotoxicity, infected cell binding and neutralization by antibodies to the SIV envelope glycoprotein", "chroma:document": "ADCC correlated well with antibody binding to virus-infected cells. ADCC also correlated\nwith neutralization. However, several instances of ADCC without detectable neutralization\nor neutralization without detectable ADCC were observed. The incomplete correspondence\nbetween ADCC and neutralization shows that some antibody-Env interactions can uncouple\nthese antiviral activities. Nevertheless, the overall correlation between neutralization and\nADCC implies that most antibodies that are capable of binding to Env on the surface of viri-\nons to block infectivity are also capable of binding to Env on the surface of virus-infected\ncells to direct their elimination by ADCC.\nAuthor summary\nAntibodies to the envelope glycoprotein (Env) of simian immunodeficiency virus (SIV)\nhave been isolated to investigate mechanisms of antibody-mediated protection in rhesus\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011407\nMay 30, 2023\n1 / 26\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Grunst MW, Ladd RA, Clark NM, Gil HM,\nKlenchin VA, Mason R, et al. (2023) Antibody-\ndependent cellular cytotoxicity, infected cell binding\nand neutralization by antibodies to the SIV\nenvelope glycoprotein. PLoS Pathog 19(5):\ne1011407. https://doi.org/10.1371/journal.\nppat.1011407\nEditor: Guido Silvestri, Emory University, UNITED\nSTATES\nReceived: November 17, 2022\nAccepted: May 8, 2023\nPublished: May 30, 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\navailable within the manuscript and Supporting\ninformation files.\nFunding: Research reported in this publication was\nsupported by National Institutes of Heath grants\nAI121135, AI095098, AI148379, AI161816,\nAI167732 and AI098485 to DTE. This work was"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 809
encoding: FLOAT32
metadata:
{"title": "Antibody-dependent cellular cytotoxicity, infected cell binding and neutralization by antibodies to the SIV envelope glycoprotein", "chroma:document": "also supported in part by the Office of the Director,\nNational Institutes of Health award number\nP51OD011106 to the Wisconsin National Primate"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 810
encoding: FLOAT32
metadata:
{"title": "HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men", "chroma:document": "RESEARCH ARTICLE\nHIV, asymptomatic STI, and the rectal mucosal\nimmune environment among young men who\nhave sex with men\nVanessa E. Van DorenID1*, S. Abigail Smith1, Yi-Juan Hu2, Gregory Tharp3,\nSteven Bosinger3,4, Cassie G. Ackerley1, Phillip M. Murray1, Rama R. Amara3,4, Praveen\nK. Amancha1, Robert A. Arthur5, H. Richard Johnston5, Colleen F. Kelley1,6\n1 The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine,\nEmory University School of Medicine, Atlanta, Georgia, United States of America, 2 Department of\nBiostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, United\nStates of America, 3 Emory National Primate Research Center, Emory University, Atlanta, Georgia, United\nStates of America, 4 Department of Microbiology and Immunology, Emory University, Atlanta, Georgia,\nUnited States of America, 5 Emory Integrated Computational Core, Emory University, Atlanta, Georgia,\nUnited States of America, 6 Grady Health System, Atlanta, Georgia, United States of America\n* vvandor@emory.edu\nAbstract\nYoung men who have sex with men (YMSM) are disproportionately affected by HIV and bac-\nterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet\nresearch into the immunologic effects of these infections is typically pursued in siloes. Here,\nwe employed a syndemic approach to understand potential interactions of these infections on\nthe rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18\u201329\nyears with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal\nsecretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral ther-\napy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive\nimmune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the\nrectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 811
encoding: FLOAT32
metadata:
{"title": "HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men", "chroma:document": "STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV\nand HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV,\nbut not asymptomatic STI, was associated with profound alterations in the cellular composi-\ntion of the rectal mucosa. We did not detect a difference in the microbiome composition asso-\nciated with HIV, but asymptomatic bacterial STI was associated with a higher probability of\npresence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome,\nthere was evidence of statistical interaction; asymptomatic bacterial STI was associated with\nupregulation of numerous inflammatory genes and enrichment for immune response path-\nways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was\nnot associated with differences in tissue HIV RNA viral loads or in HIV replication in explant\nchallenge experiments. Our results suggest that asymptomatic bacterial STI may contribute\nto inflammation particularly among YMSM with HIV, and that future research should examine\npotential harms and interventions to reduce the health impact of these syndemic infections.\nPLOS PATHOGENS\nPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1011219\nMay 30, 2023\n1 / 23\na1111111111\na1111111111\na1111111111\na1111111111\na1111111111\nOPEN ACCESS\nCitation: Van Doren VE, Smith SA, Hu Y-J, Tharp\nG, Bosinger S, Ackerley CG, et al. (2023) HIV,\nasymptomatic STI, and the rectal mucosal immune\nenvironment among young men who have sex with\nmen. PLoS Pathog 19(5): e1011219. https://doi.\norg/10.1371/journal.ppat.1011219\nEditor: Daniel C. Douek, Vaccine Research Center,\nUNITED STATES\nReceived: February 17, 2023\nAccepted: May 10, 2023\nPublished: May 30, 2023\nPeer Review History: PLOS recognizes the\nbenefits of transparency in the peer review\nprocess; therefore, we enable the publication of\nall of the content of peer review and author\nresponses alongside final, published articles. The\neditorial history of this article is available here:"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 812
encoding: FLOAT32
metadata:
{"title": "HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men", "chroma:document": "https://doi.org/10.1371/journal.ppat.1011219\nCopyright: \u00a9 2023 Van Doren et al. This is an open\naccess article distributed under the terms of the\nCreative Commons Attribution License, which\npermits unrestricted use, distribution, and\nreproduction in any medium, provided the original\nauthor and source are credited.\nData Availability Statement: All relevant data are\nwithin the paper and its Supporting information\nfiles."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 813
encoding: FLOAT32
metadata:
{"title": "Hydroxychloroquine Causes Early Inner Retinal Toxicity and Affects Autophagosome\\205Lysosomal Pathway and Sphingolipid Metabolism i\\\rn the Retina", "chroma:document": "Hydroxychloroquine Causes Early Inner Retinal Toxicity and \nAffects Autophagosome\u2013Lysosomal Pathway and Sphingolipid \nMetabolism in the Retina\nKoushik Mondal1, Hunter Porter2, Jerome Cole II1, Hemang K. Pandya2, Sandip K. \nBasu1, Sufiya Khanam1, Chi-Yang Chiu3, Vinay Shah2, Daniel J. Stephenson4, Charles E. \nChalfant4,5,6, Nawajes Mandal1,2,7,8,9\n1Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health \nScience Center, Memphis, TN 38163, USA\n2Department of Ophthalmology, Dean McGee Eye Institute, The University of Oklahoma Health \nSciences Center, Oklahoma City OK-73104, USA\n3Division of Biostatistics, Department of Preventive Medicine, University of Tennessee Health \nScience Center, Memphis, TN 38163, USA\n4Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, \nTampa, FL 33620, USA\n5The Moffitt Cancer Center, Tampa, FL 33620, USA\n6Research Service, James A. Haley Veterans Hospital, Tampa, FL 33612, USA\n7Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, \nMemphis, TN 38163, USA\n\u2709Nawajes Mandal, nmandal@uthsc.edu.\nKoushik Mondal, Hunter Porter, Jerome Cole II, Hemang K. Pandya and Sandip K. Basu are equally contributing authors.\nAuthor Contribution Koushik Mondal performed experiment, analyzed data, prepared illustrations and wrote the manuscript; \nHunter Porter performed experiment, analyzed data, prepared illustrations, and wrote and edited the manuscript; Jerome Cole II \nperformed experiment; Hemang K. Pandya recruited patients, retrieved patient and clinical data, and analyzed data; Sandip K. Basu \nanalyzed data, and wrote and edited the manuscript; Vinay Shah recruited patients and retrieved patient and clinical data; Daniel \nJ Stephenson performed experiment and analyzed data; Charles E Chalfant provided facility and analyzed data; Nawajes Mandal \ndesigned experiment, obtained IRB and IACUC approvals, provided facility, analyzed data, and wrote and edited manuscript.\nConflict of Interests None."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 814
encoding: FLOAT32
metadata:
{"title": "Hydroxychloroquine Causes Early Inner Retinal Toxicity and Affects Autophagosome\\205Lysosomal Pathway and Sphingolipid Metabolism i\\\rn the Retina", "chroma:document": "Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/\ns12035-022-02825-3.\nEthics Approval and Consent to Participate Human study was approved by University of Oklahoma Institutional Review Board for \nthe Protection of Human Subjects; IRB#: 5218; Approval Date: 02/27/2015\nStudy Title: Sphingolipids, Autoimmune Diseases and Retinopathies.\nConsent for Publication Human study and consent to publish was approved by University of Oklahoma; Institutional Review Board \nfor the Protection of Human Subjects; IRB#: 5218; Approval Date: 02/27/2015.\nAuthor Consent All the authors have seen the manuscript and approved for publication.\nResearch involving Human Participants Human study was approved by University of Oklahoma; Institutional Review Board for \nthe Protection of Human Subjects; IRB#: 5218; Approval Date: 02/27/2015; Study Title: Sphingolipids, Autoimmune Diseases and \nRetinopathies.\nAnimals: Animal studies approved by UTHSC IACUC committee. Approval # 19-0104.\nInformed Consent Obtained for all participants according to the approved IRB#: 5218; protocol at the University of Oklahoma. \nApproval Date: 02/27/2015.\nStudy Title: Sphingolipids, Autoimmune Diseases and Retinopathies.\nHHS Public Access\nAuthor manuscript\nMol Neurobiol. Author manuscript; available in PMC 2023 June 12.\nPublished in final edited form as:\nMol Neurobiol. 2022 June ; 59(6): 3873\u20133887. doi:10.1007/s12035-022-02825-3.\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: 815
encoding: FLOAT32
metadata:
{"title": "Food insecurity is associated with higher respiratory quotient and lower glucagon-like peptide-1", "chroma:document": "Food insecurity is associated with higher respiratory quotient \nand lower glucagon-like peptide-1\nJetaun M. Booker, BS,\nDouglas C. Chang, MD,\nEmma J. Stinson, MPH,\nCassie M. Mitchell, PhD, RD,\nSusanne B. Votruba, PhD, RD,\nJonathan Krakoff, MD,\nMarci E. Gluck, PhD,\nTom\u00e1s Cabeza de Baca, PhD**\nObesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research \nBranch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of \nHealth, Department of Health and Human Services, Phoenix, AZ, USA\nAbstract\nObjective:\u00a0Food insecurity is known to be associated with obesity but its association with \nphysiological measures is unclear. Therefore, we hypothesized that compared to food secure, \nindividuals with food insecurity would have higher 24-h energy expenditure (EE[kcal/d]) and a \n24-h respiratory quotient (RQ[ratio]). Subsequently, we explored hormones involved in appetite \nregulation, substrate oxidation, and EE.\nMethods:\u00a0One hundred-thirteen non-diabetic healthy participants (75M; Age 40\u00b112 [years]; BMI \n30\u00b18 [kg/m2]) were included in this analysis. Participants completed the Food Security Short \nForm, a DXA scan, and spent 24 hours in a human respiratory chamber following a weight \nmaintaining diet.\nResults:\u00a0Compared to individuals with food security, participants with food insecurity had no \ndifference in 24-h EE. However, they had higher carbohydrate oxidation rates (p = 0.03), and \nlower lipid oxidation rates (p = 0.02), resulting in higher 24-h RQ (p<0.01). They also had lower \nfasting glucagon-like peptide 1 (GLP-1 [p = 0.03]) concentrations.\nConclusions:\u00a0Food insecurity is associated with higher 24-h RQ and lower fasting GLP-1 \nconcentrations, metabolic and hormonal differences previously shown to drive greater calorie \n**Contact Info: Tom\u00e1s Cabeza de Baca, PhD, Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 816
encoding: FLOAT32
metadata:
{"title": "Food insecurity is associated with higher respiratory quotient and lower glucagon-like peptide-1", "chroma:document": "Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 North 16th \nStreet, Phoenix, Arizona, 85016, USA, tommy.cabezadebaca@nih.gov, 602-200-5300. \nDisclosure: The authors declare no conflict of interest.\nCompeting Interests Statement\nThe authors declare no competing financial interests.\nClinical Trial Registration: clinicaltrials.gov: NCT00342732\nHHS Public Access\nAuthor manuscript\nObesity (Silver Spring). Author manuscript; available in PMC 2023 June 13.\nPublished in final edited form as:\nObesity (Silver Spring). 2022 June ; 30(6): 1248\u20131256. doi:10.1002/oby.23437.\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: 817
encoding: FLOAT32
metadata:
{"title": "Identification of antigenic epitopes recognized by tumor infiltrating lymphocytes in high grade serous ovarian cancer by multi-omics profiling of the auto-antigen repertoire", "chroma:document": "Vol.:(0123456789)\n1 3\nCancer Immunology, Immunotherapy (2023) 72:2375\u20132392 \nhttps://doi.org/10.1007/s00262-023-03413-7\nRESEARCH\nIdentification of\u00a0antigenic epitopes recognized by\u00a0tumor infiltrating \nlymphocytes in\u00a0high grade serous ovarian cancer by\u00a0multi\u2011omics \nprofiling of\u00a0the\u00a0auto\u2011antigen repertoire\nDouglas\u00a0G.\u00a0Millar1\u00a0\u00b7 S.\u00a0Y.\u00a0Cindy\u00a0Yang1\u00a0\u00b7 Azin\u00a0Sayad1\u00a0\u00b7 Qingchuan\u00a0Zhao2\u00a0\u00b7 Linh\u00a0T.\u00a0Nguyen1\u00a0\u00b7 Kathrin\u00a0Warner1\u00a0\u00b7 \nAmi\u00a0G.\u00a0Sangster1\u00a0\u00b7 Munehide\u00a0Nakatsugawa1\u00a0\u00b7 Kenji\u00a0Murata1\u00a0\u00b7 Ben\u00a0X.\u00a0Wang1\u00a0\u00b7 Patricia\u00a0Shaw1\u00a0\u00b7 Blaise\u00a0Clarke1\u00a0\u00b7 \nMarcus\u00a0Q.\u00a0Bernardini3\u00a0\u00b7 Trevor\u00a0Pugh1\u00a0\u00b7 Pierre\u00a0Thibault2\u00a0\u00b7 Naoto\u00a0Hirano1,4\u00a0\u00b7 Claude\u00a0Perreault2\u00a0\u00b7 Pamela\u00a0S.\u00a0Ohashi1,4\nReceived: 2 November 2022 / Accepted: 16 February 2023 / Published online: 21 March 2023 \n\u00a9 The Author(s) 2023\nAbstract\nImmunotherapeutic strategies aimed at enhancing tumor cell killing by tumor-specific T cells hold great potential for reduc-\ning tumor burden and prolonging survival of cancer patients. Although many potential tumor antigens have been described, \nidentifying relevant targets when designing anti-cancer vaccines or targeted cell therapies remains a challenge. To identify \nnovel, potentially immunogenic candidate tumor antigens, we performed integrated tumor transcriptomic, seromic, and \nproteomic analyses of high grade serous ovarian cancer (HGSC) patient tumor samples. We identified tumor neo-antigens \nand over-expressed antigens using whole exome and RNA sequencing and examined these in relation to patient-matched \nauto-antibody repertoires. Focusing on MHC class I epitopes recognized by  CD8+ T cells, HLA-binding epitopes were \nidentified or predicted from the highly expressed, mutated, or auto-antibody target antigen, or MHC-associated peptides \n(MAPs). Recognition of candidate antigenic peptides was assessed within the tumor-infiltrating T lymphocyte (TIL) popula-\ntion expanded from each patient. Known tumor-associated antigens (TAA) and cancer/testis antigens (CTA) were commonly"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 818
encoding: FLOAT32
metadata:
{"title": "Identification of antigenic epitopes recognized by tumor infiltrating lymphocytes in high grade serous ovarian cancer by multi-omics profiling of the auto-antigen repertoire", "chroma:document": "found in the auto-antibody and MAP repertoires and  CD8+ TILs recognizing epitopes from these antigens were detected, \nalthough neither expression level nor the presence of auto-antibodies correlated with TIL recognition. Auto-antibodies \nagainst tumor-mutated antigens were found in most patients, however, no TIL recognition of the highest predicted affinity \nneo-epitopes was detected. Using high expression level, auto-antibody recognition, and epitope prediction algorithms, we \nidentified epitopes in 5 novel antigens (MOB1A, SOCS3, TUBB, PRKAR1A, CCDC6) recognized by HGSC patient TILs. \nFurthermore, selection of epitopes from the MAP repertoire identified 5 additional targets commonly recognized by multi-\nple patient TILs. We find that the repertoire of TIL specificities includes recognition of highly expressed and immunogenic \nself-antigens that are processed and presented by tumors. These results indicate an ongoing autoimmune response against a \nrange of self-antigens targeted by HGSC TILs.\nKeywords Auto-antibodies\u00a0\u00b7 Seromics\u00a0\u00b7 Transcriptomics\u00a0\u00b7 Epitope prediction\u00a0\u00b7 Tumor-associated antigens\u00a0\u00b7 Cancer vaccine\nIntroduction\nTherapeutic vaccination against tumor-expressed antigens \ncan promote tumor-specific T cell-mediated killing of can-\ncer cells and represents a promising form of immunother-\napy for cancer. Tumor target antigens fall broadly into two \nclasses: tumor-associated antigens (TAAs), including tis-\nsue differentiation antigens, tumor over-expressed antigens, \nand cancer/testis antigens (CTA); and tumor-specific anti-\ngens (TSA) including mutated neo-antigens and aberrantly \nexpressed translation products from non-canonical reading \nframes [1\u20133]. Neo-antigens arise from somatic mutations \n * Pamela S. Ohashi \n \npohashi@uhnresearch.ca\n1 \nTumor Immunotherapy Program, Princess Margaret Cancer \nCentre, 610 University Avenue, Toronto, ON\u00a0M5G\u00a02M9, \nCanada\n2 \nInstitute for\u00a0Research in\u00a0Immunology and\u00a0Cancer, Universit\u00e9 \nde Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada\n3"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 819
encoding: FLOAT32
metadata:
{"title": "Identification of antigenic epitopes recognized by tumor infiltrating lymphocytes in high grade serous ovarian cancer by multi-omics profiling of the auto-antigen repertoire", "chroma:document": "3 \nDivision of\u00a0Gynecologic Oncology, Cancer Clinical Research \nUnit (CCRU), Princess Margaret Cancer Centre, Toronto, \nON, Canada\n4 \nDepartment of\u00a0Immunology, University of\u00a0Toronto, Toronto, \nON, Canada"}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 820
encoding: FLOAT32
metadata:
{"title": "An atlas of white matter anatomy, its variability, and reproducibility based on constrained spherical deconvolution of diffusion\\\r MRI", "chroma:document": "An atlas of white matter anatomy, its variability, and \nreproducibility based on constrained spherical deconvolution of \ndiffusion MRI\nAhmed M. Radwana,b,\u2217, Stefan Sunaerta,b,c, Kurt Schillingd, Maxime Descoteauxe, Bennett \nA. Landmanf, Mathieu Vandenbulckeb,g,h, Tom Theysb,i,j, Patrick Dupontb,k, Louise \nEmsella,b,g,h\naKU Leuven, Department of Imaging and pathology, Translational MRI, Leuven, Belgium\nbKU Leuven, Leuven Brain Institute (LBI), Department of Neurosciences, Leuven, Belgium\ncUZ Leuven, Department of Radiology, Leuven, Belgium\ndVanderbilt University Medical Center, Department of Radiology and Radiological Sciences, \nNashville, TN, USA\neSCIL, Universit\u00e9 de Sherbrooke, Quebec, Canada\nfVanderbilt University, Department of Electrical Engineering and Computer Engineering, Nashville, \nTN, USA\ngKU Leuven, Department of Neurosciences, Neuropsychiatry, Leuven, Belgium\nhKU Leuven, Department of Geriatric Psychiatry, University Psychiatric Center (UPC), Leuven, \nBelgium\niKU Leuven, Department of Neurosciences, Research Group Experimental Neurosurgery and \nNeuroanatomy, Leuven, Belgium\nThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)\n\u2217Corresponding author at: Department of Imaging and pathology, Translational MRI, KU Leuven, Leuven, Belgium. \nahmed.radwan@kuleuven.be, radwanphd@gmail.com (A.M. Radwan). \nData and code sharing statement\nAll data used in this work can be recovered from their respective online sources mentioned above. The accompanying supplementary \ninformation document contains more detail on the datasets used in this work, further explanation of the FWT method, and additional \nsimilarity analysis results. The FWT workflows can be downloaded from (https://github.com/KUL-Radneuron/KUL_FWT.git). \nFinally, the Open Science Framework repository (https://osf.io/snq2d/) contains additional screenshots of single subject bundles, \nbundle heatmaps, original and symmetric versions of the HCP-template atlas bundles, and additional tractograms."}


created_at: 2024-01-19 12:53:35
topic: persistent://default/default/e46a62c8-f631-4b0d-b6c6-0d8d30ab5865
id: 821
encoding: FLOAT32
metadata:
{"title": "An atlas of white matter anatomy, its variability, and reproducibility based on constrained spherical deconvolution of diffusion\\\r MRI", "chroma:document": "Declaration of Competing Interest\nMaxime Descoteaux is a founder and co-owner of Imeka Solutions Inc. No conflicts related to the current work.\nCredit authorship contribution statement\nAhmed M. Radwan: Conceptualization, Methodology, Data curation, Software, Writing \u2013 original draft, Visualization, Investigation, \nFormal analysis. Stefan Sunaert: Software, Resources, Supervision, Visualization, Investigation, Formal analysis, Writing \u2013 \noriginal draft, Writing \u2013 review & editing. Kurt Schilling: Conceptualization, Methodology, Writing \u2013 review & editing. Maxime \nDescoteaux: Supervision, Writing \u2013 review & editing. Bennett A. Landman: Supervision, Writing \u2013 review & editing. Mathieu \nVandenbulcke: Supervision, Writing \u2013 review & editing. Tom Theys: Supervision, Writing \u2013 review & editing. Patrick Dupont: \nSupervision, Investigation, Writing \u2013 review & editing. Louise Emsell: Conceptualization, Supervision, Methodology, Visualization, \nInvestigation, Formal analysis, Writing \u2013 original draft, Writing \u2013 review & editing.\nSupplementary materials\nSupplementary material associated with this article can be found, in the online version, at doi:10.1016/j.neuroimage.2022.119029.\nHHS Public Access\nAuthor manuscript\nNeuroimage. Author manuscript; available in PMC 2023 June 14.\nPublished in final edited form as:\nNeuroimage. 2022 July 01; 254: 119029. doi:10.1016/j.neuroimage.2022.119029.\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: 822
encoding: FLOAT32
metadata:
{"title": "Neutralizing antibodies targeting a novel epitope on envelope protein exhibited broad protection against flavivirus without risk of disease enhancement", "chroma:document": "Yen\u00a0et\u00a0al. \nJournal of Biomedical Science           (2023) 30:41  \nhttps://doi.org/10.1186/s12929-023-00938-y\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.\nNeutralizing antibodies targeting a\u00a0novel \nepitope on\u00a0envelope protein exhibited broad \nprotection against\u00a0flavivirus without\u00a0risk \nof\u00a0disease enhancement\nLi\u2011Chen Yen1, Hsin\u2011Wei Chen2, Chia\u2011Lo Ho3, Chang\u2011Chi Lin1,4, Yi\u2011Ling Lin1,5, Qiao\u2011Wen Yang1, Kuo\u2011Chou Chiu6,7, \nShu\u2011Pei Lien2, Ren\u2011Jye Lin8 and Ching\u2011Len Liao1,2,8*   \nAbstract \nBackground Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has \nrestrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus \nvaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E \nprotein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the"}


