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BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

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Neural Regeneration research 2024年第2期19卷 447-457页

作者： Michael W.Weible II Michael D.Lovelace Hamish D.Mundell Tsz Wai Rosita Pang Tailoi Chan-Ling Bosch Institute Discipline of Anatomy and Histology(F13)University of SydneySydneyNSWAustralia School of Environment and Science Griffith UniversityNathanQLDAustralia Discipline of Medicine Nepean Clinical SchoolFaculty of Medicine and HealthUniversity of SydneyKingswoodNSWAustralia New South Wales Brain Tissue Resource Centre School of Medical SciencesFaculty of Medicine and HealthUniversity of SydneyCharles Perkins Centre(D17)SydneyNSWAustralia

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well ***-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is *** was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory *** and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/*** immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,*** neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent *** cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage ***-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in *** is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal *** data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterize

关键词： BMPRⅡ bone morphogenetic protein histotypic human spinal cord development leukemia inhibitory factor neurosphere organotypic reaggregate sensory columns

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Intermittent fasting-a double edged sword for atherosclerosis

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Life Metabolism 2024年第3期3卷 9-11页

作者： Jacques Togo Hoon-Ki Sung Translational Medicine Program The Hospital for Sick ChildrenTorontoOntario M5G 0A4Canada Department of Laboratory Medicine and Pathobiology University of TorontoTorontoOntario M5S 1A8Canada

The impact of alternate-day fasting(ADF)on atherosclerosis remains poorly understood,particularly in high-risk popula*** a recent paper published in Life Metabolism,Deng et *** that ADF exacerbated both early and advanced atherosclerotic lesion development in Apoe^(-/-)mice through suppression of hepatic activating transcription factor 3(ATF3)and consequent dysregulation of cholesterol metabolism.

关键词： fasting atherosclerosis

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Performance of generative pre-trained transformers (GPTs) in Certification Examination of the College of Family Physicians of Canada

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Family Medicine and Community health 2024年第S1期12卷 12-19页

作者： Mehdi Mousavi Shabnam Shafiee Jason M Harley Jackie Chi Kit Cheung Samira Abbasgholizadeh Rahimi Department of Family Medicine Faculty of MedicineUniversity of SaskatchewanNipawinSaskatchewanCanada Department of Family Medicine Saskatchewan Health AuthorityRiverside Health ComplexTurtlefordSaskatchewanCanada Department of Surgery Faculty of Medicine and Health SciencesMcGill UniversityMontrealQuebecCanada research Institute of the McGill University health Centre MontrealQuebecCanada Institute for health Sciences Education Faculty of Medicine and Health SciencesMcGill UniversityMontrealQuebecCanada McGill University School of Computer Science MontrealQuebecCanada CIFAR AI Chair Mila-Quebec AI InstituteMontrealQuebecCanada Department of Family Medicine McGill UniversityMontrealQuebecCanada Mila Quebec AI-Institute MontrealQuebecCanada Faculty of Dentistry Medicine and Oral health Sciences McGill UniversityMontrealQuebecCanada Lady Davis Institute for Medical research Jewish General HospitalMontrealQuebecCanada

Introduction The application of large language models such as generative pre-trained transformers(GPTs)has been promising in medical education,and its performance has been tested for different medical *** study aims to assess the performance of GPTs in responding to a set of sample questions of short-answer management problems(SAMPs)from the certification exam of the College of Family Physicians of Canada(CFPC).Method Between August 8th and 25th,2023,we used GPT-3.5 and GPT-4 in five rounds to answer a sample of 77 SAMPs questions from the CFPC *** independent certified family physician reviewers scored AI-generated responses twice:first,according to the CFPC answer key(ie,CFPC score),and second,based on their knowledge and other references(ie,Reviews’score).An ordinal logistic generalised estimating equations(GEE)model was applied to analyse repeated measures across the five *** According to the CFPC answer key,607(73.6%)lines of answers by GPT-3.5 and 691(81%)by GPT-4 were deemed ***’s scoring suggested that about 84%of the lines of answers provided by GPT-3.5 and 93%of GPT-4 were *** GEE analysis confirmed that over five rounds,the likelihood of achieving a higher CFPC Score Percentage for GPT-4 was 2.31 times more than GPT-3.5(OR:2.31;95%CI:1.53 to 3.47;p<0.001).Similarly,the Reviewers’Score percentage for responses provided by GPT-4 over 5 rounds were 2.23 times more likely to exceed those of GPT-3.5(OR:2.23;95%CI:1.22 to 4.06;p=0.009).Running the GPTs after a one week interval,regeneration of the prompt or using or not using the prompt did not significantly change the CFPC score *** In our study,we used GPT-3.5 and GPT-4 to answer complex,open-ended sample questions of the CFPC exam and showed that more than 70%of the answers were accurate,and GPT-4 outperformed GPT-3.5 in responding to the *** language models such as GPTs seem promising for assisting candidates of the CFPC exam by pr

关键词： Canada prompt education

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Implications of conscious AI in primary healthcare

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Family Medicine and Community health 2024年第S1期12卷 1-5页

作者： Dorsai Ranjbari Samira Abbasgholizadeh Rahimi McGill University Faculty of Medicine and health Sciences MontrealQuebecCanada Family Medicine Faculty of Medicine and Health Sciences and Faculty of Dental Medicine and Oral Health SciencesMcGill UniversityMontrealQuebecCanada Mila-Quebec AI Institute MontrealQuebecCanada Lady Davis Institute for Medical research Jewish General HospitalMontrealQuebecCanada

The conversation about consciousness of artificial intelligence(AI)is an ongoing topic since *** the numerous applications of AI identified in healthcare and primary healthcare,little is known about how a conscious AI would reshape its use in this *** there is a wide range of ideas as to whether AI can or cannot possess consciousness,a prevailing theme in all arguments is *** this uncertainty and the high stakes associated with the use of AI in primary healthcare,it is imperative to be prepared for all scenarios including conscious AI systems being used for medical diagnosis,shared decision-making and resource management in the *** commentary serves as an overview of some of the pertinent evidence supporting the use of AI in primary healthcare and proposes ideas as to how consciousnesses of AI can support or further complicate these *** the scarcity of evidence on the association between consciousness of AI and its current state of use in primary healthcare,our commentary identifies some directions for future research in this area including assessing patients’,healthcare workers’and policy-makers’attitudes towards consciousness of AI systems in primary healthcare settings.

关键词： consciousness prevailing conscious

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Inferring community transmission of SARS-CoV-2 in the United Kingdom using the ONS COVID-19 Infection Survey

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Infectious Disease Modelling 2024年第2期9卷 299-313页

作者： Ruth McCabe Gabriel Danelian Jasmina Panovska-Griffiths Christl A.Donnelly Department of Statistics University of OxfordUK National Institute for health and Care research health Protection research Unit in Emerging and Zoonotic Infections UK United Kingdom health Security Agency UK The Queen's College University of OxfordUK The Pandemic Sciences Institute University of OxfordUK MRC Centre for Global Infectious Disease Analysis Imperial College LondonUK

Key epidemiological parameters,including the effective reproduction number,,and the instantaneous growth rate,,generated from an ensemble of models,have been informing public health policy throughout the COVID-19 pandemic in the four nations of the United Kingdom of Great Britain and Northern Ireland(UK).However,estimation of these quantities became challenging with the scaling down of surveillance systems as part of the transition from the“emergency”to“endemic”phase of the *** Office for National Statistics(ONS)COVID-19 Infection Survey(CIS)provided an opportunity to continue estimating these parameters in the absence of other data *** used a penalised spline model fitted to the publicly-available ONS CIS test positivity estimates to produce a smoothed estimate of the prevalence of SARS-CoV-2 positivity over *** resulting fitted curve was used to estimate the“ONS-based”and across the four nations of the *** produced under this model are compared to government-published estimates with particular consideration given to the contribution that this single data stream can offer in the estimation of these *** on the nation and parameter,we found that up to 77%of the variance in the government-published estimates can be explained by the ONS-based estimates,demonstrating the value of this singular data stream to track the epidemic in each of the four *** additionally find that the ONS-based estimates uncover epidemic trends earlier than the corresponding government-published *** work shows that the ONS CIS can be used to generate key COVID-19 epidemiological parameters across the four UK nations,further underlining the enormous value of such population-level studies of *** is not intended as an alternative to ensemble modelling,rather it is intended as a potential solution to the aforementioned challenge faced by public health officials in the UK in early 2022.

关键词： Effective reproduction number Instantaneous growth rate SARS-CoV-2 COVID-19 ONS COVID-19 Infection Survey Surveillance

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BET inhibition prevents aberrant RUNX1 and ERG transcription in STAG2 mutant leukaemia cells

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Journal of Molecular Cell Biology 2020年第5期12卷 397-399页

作者： Jisha Antony Gregory Gimenez Terry Taylor Umaima Khatoon Robert Day Ian MMorison Julia AHorsfield Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9016New Zealand Maurice Wilkins Centre for Molecular Biodiscovery The University of AucklandPrivate Bag 92019AucklandNew Zealand Southern Community Laboratories Dunedin 9016New Zealand Department of Biochemistry University of OtagoDunedin 9054New Zealand

Cohesin is a multiprotein complex that not only is essential for cell division but also has key roles in genome organization that underpin its gene regulatory *** mutations of genes encoding cohesin subunits occur in myeloid malignancies at 10%–12%(Kon et al.,2013),and the frequency of cohesin mutation in Down syndrome-associated megakaryoblastic leukaemia is even higher(~50%)(Yoshida et al.,2013).Cohesin insufficiency reinforces stem cell programmes and impairs differentiation in haematopoietic stem cells(Mazumdar et al.,2015;Mullenders et al.,2015;Viny et al.,2015).The STAG2 subunit of cohesin is the most frequently mutated in myeloid malignancies(Kon et al.,2013).In contrast to other cohesin subunits,complete loss of STAG2 is tolerated due to partial compensation by ***2 and STAG1 have redundant roles in cell division(Benedetti et al.,2017;van der Lelij et al.,2017).However,cohesin-STAG1 and cohesin-STAG2 have non-redundant roles in facilitating 3D genome organization to delineate tissue-specific gene expression(Kojic et al.,2018).

关键词： function. redundant

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Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all *** physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic *** few or too many blood vessels are associated with the onset and progression of many *** response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases

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Intersection of autophagy with pathways of antigen presentation

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Protein & Cell 2012年第12期3卷 911-920页

作者： Natalie L.Patterson Justine D.Mintern Department of Biochemistry and Molecular Biology The University of MelbourneParkvilleVictoria 3010Australia

Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell *** ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of ***,autophagy can also directly intersect with,and impact,other major pathways of cellular ***,we will review the contribution of autophagy to pathways of antigen *** autophagy machinery acts to modulate both MHCⅠ and MHCⅡ antigen *** such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

关键词： autophagy antigen presentation antigen presenting cells dendritic cells MHCⅠ MHCⅡ

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Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphé nuclei

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Neural Regeneration research 2020年第3期15卷 457-463页

作者： Hanna E.Reinebrant Julie A.Wixey Kathryn M.Buller UQ Centre for Clinical research Faculty of Medicine The University of Queensland

Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate. The main objective of this study was to determine how serotonergic neurons, remaining in the dorsal raphé nuclei after neonatal HI, respond to an external stimulus(restraint stress). On postnatal day 3(P3), male rat pups were randomly allocated to one of the following groups:(i) control + no restraint(n = 5),(ii) control + restraint(n = 6),(iii) P3 HI + no restraint(n = 5) or(iv) P3 HI + restraint(n = 7). In the two HI groups, rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6% O2 for 30 minutes. Six weeks after P3 HI, on P45, rats were subjected to restraint stress for 30 minutes. Using dual immunolabeling for Fos protein, a marker for neuronal activity, and serotonin(5-hydroxytrypamine; 5-HT), numbers of Fos-positive 5-HT neurons were determined in five dorsal raphé nuclei. We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphé nuclei compared to control animals. However, following P3 HI, the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphé ventrolateral, interfascicular and ventral nuclei compared with control animals exposed to restraint stress. In contrast, numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphé dorsal and caudal nuclei were not affected by P3 HI. These data indicate that not only are dorsal raphé serotonergic neurons lost after neonatal HI, but also remaining dorsal raphé serotonergic neurons have reduced differential functional viability in response to an external stimulus. Procedures were approved by the University of Queensland Animal Ethics Committee(

关键词： dorsal raphé nuclei Fos hypoxia-ischemia neonate newborn brain injury preterm restraint stress serotonin

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Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo

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Protein & Cell 2011年第4期2卷 333-346页

作者： Sharyn Bayne He Li Margaret E.E.Jones Alex R.Pinto Michelle van Sinderen Ann Drummond Evan R.Simpson Jun-Ping Liu Department of Immunology Central Eastern Clinical SchoolMonash UniversityVictoria 3800Australia Prince Henry’s Institute of Medical research Clayton VIC 3168Australia Current address:research Services M459The University of Western Australia35 Stirling HighwayCRAWLEY WA 6009Australia Current address:Murdoch Children’s research Institute Royal Children’s HospitalParkvilleVic 3052Australia

Estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues;however the mechanisms underlying the mitogenic actions of estrogen are not fully *** we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a signi-ficant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue-specific *** inhibition entails a significant shortening of telomeres and compromised proliferation in the follicular granulosa cell compartment of *** expression analysis showed decreased levels of proto-oncogene c-Myc and the telomerase catalytic subunit,telomerase reverse transcriptase(TERT),in response to estrogen *** replacement therapy led to increases in TERT gene expression,telomerase activity,telomere length and ovarian tissue growth,thereby reinstating ovary development to normal in four *** data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation by upregulating the genes of c-Myc and TERT in *** deficiency or over-activity may cause ovarian tissue aging or tumorigenesis,respectively,through estrogen regulation of telomere remodeling.

关键词： estrogen telomerase reverse transcriptase(TERT) telomeres ovary mice

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