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Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina rita A Gomez julia r herrera Nancy L Martínez Brenda Hernández Yesenia García Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical Center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BACKGrOUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Pred statistically *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(Or):2.42(1.112–5.303,P=0.026);anti-IA2:Or:1.55(0.859–2.818,P=0.105);and anti-Zn8T:Or:7.32(2.039–26.279,P=0.002).CONCLUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural regeneration research 2025年第7期20卷 1944-1956页

作者： julia Castillo-González Elena González-rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

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Otolaryngology residency program factors associated with female resident representation

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 7-11页

作者： julia E.Canick James C.Campbell Charles r.Woodard Lars J.Grimm Alissa M.Collins Duke University School of Medicine DurhamNorth CarolinaUSA Department of Head and Neck Surgery&Communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Department of radiology Duke University School of MedicineDurhamNorth CarolinaUSA

Objective:Female representation in the field of otolaryngology is *** is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female *** study sought to identify program factors associated with greater female representation among resident ***:Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto rico were examined for a list of *** programs with a resident roster available,the genders of residents,faculty,program directors,and chairpersons were *** and city population for each program was also recorded,as was female resident *** were compared using Pearson Chi‐squared univariate ***:1,632 residents and 2,605 faculty were included in the analysis of 109 *** median female resident representation was 40%.Programs with larger faculty sizes,more female faculty,and urban location were associated with an above‐median female resident *** with a larger residency cohort approached significance regarding above‐median female resident *** female faculty representation,program director gender,chairperson gender,and US region were not associated with variation in female resident ***:Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total *** was also likely that a larger resident cohort size may affect female resident *** proportions of female faculty,program director,and chairperson gender,as well as the US region,were not associated with variation in female resident gender representation.

关键词： gender program director recruitment residency training

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Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel Michael Levy Anais r.Briant Etienne Javouhey Sophie Breinig julia Dina Marion Caseris Francois Angoulvant Stephane Leteurtre Morgan recher David W.Brossier Univ.Lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care Unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care Unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance UniversitéParis-Cite ParisFrance Biostatistics and Clinical research Unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare Unit Children's HospitalToulouseFrance Virology Department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance Department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance Department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care Unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHU Sainte Justine research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SArS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SArS-CoV-2 on the mortality rate associated with SArS-CoV-2-related illnesses in the pediatric intensive care unit(PICU).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SArS-CoV-2 polymerase chain reactions(PCrs)[acute corona virus disease 2019(COVID-19)or incidental SArS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICU registry(PICUre)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICU *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SArS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SArS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SArS-CoV-2 was considered certain in only one case(O.1%).Deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SArS-CoV-2 mortality in the French pediatric population was *** though the imputability of SArS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： Death Pediatric intensive care unit SArS-CoV-2

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DErDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;roux et al.,2006).

关键词： auditory hair

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Here comes the sun:How optimization of photosynthetic light reactions can boost crop yields

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Journal of Integrative Plant Biology 2022年第2期64卷 564-591页

作者： julia Walter Johannes Kromdijk Department of Plant Sciences University of CambridgeCambridgeCB23EA UK Carl r Woese Institute for Genomic Biology University of Illinois Urbana-ChampaignUrbanaIllinois61801 USA

Photosynthesis started to evolve some 3.5 billion years ago CO;is the substrate for photosynthesis and in the past 200-250 years,atmospheric levels have approximately doubled due to human industrial ***,this time span is not sufficient for adaptation mechanisms of photosynthesis to be evolutionarily *** increases in human population,shortage of arable land and food,and climate change call for actions,*** to substantial research efforts and advances in the last century,basic knowledge of photosynthetic and primary metabolic processes can now be translated into strategies to optimize photosynthesis to its full potential in order to improve crop yields and food supply for the *** different approaches have been proposed in recent years,some of which have already proven successful in different crop ***,we summarize recent advances on modifications of the complex network of photosynthetic light *** are the starting point of all biomass production and supply the energy equivalents necessary for downstream processes as well as the oxygen we breathe.

关键词： bioengineering crop improvement electron transfer light reactions photosynthesis photosystem stress tolerance

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Updates on the pathologic diagnosis and classification of mesothelioma

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 197-209页

作者： julia r.Farkas Mark Sharobim Jefree J.Schulte Department of Pathology and Laboratory Medicine University of WisconsinMadisonWI 53792USA

Mesothelioma is a rare malignant tumor of the serosal membranes that can be challenging to diagnose,especially on small biopsy *** are updated guidelines on the diagnosis and classification of mesothelioma,which incorporate advancements in understanding mesothelioma biology published in the literature over recent *** review will discuss marked developments and/or improvements that have been made,including:(1)to the histologic classifications of mesothelioma;(2)the use of such classifications and nuclear grading in prognosis;(3)the indispensability of ancillary studies in the diagnosis of mesothelioma;(4)the application of these pleural based classifications and diagnostic schemes in peritoneal mesothelioma;and(5)the potential for diagnosis of mesothelioma in situ.

关键词： Mesothelioma BrCA associated peptide 1(BAP1) methylthioadenosine phosphorylase(MTAP) nuclear grading mesothelioma in situ

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Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema

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慢性疾病与转化医学:英文版 2023年第3期9卷 258-262页

作者： julia Feige Fritz Klausner Johannes A.r.Pfaff Eugen Trinka Slaven Pikija Mahdi Safdarian Department of Neurology Neurocritical Care and NeurorehabilitationCentre of Cognitive NeuroscienceChristian Doppler University HospitalParacelsus Medical UniversitySalzburgMember of EpiCARESalzburgAustria Department of Neuroradiology Christian Doppler University HospitalParacelsus Medical UniversitySalzburgAustria Neuroscience Institute Christian‐Doppler University HospitalParacelsus Medical UniversityCentre for Cognitive NeuroscienceSalzburgAustria Institute of Public Health Medical Decision‐Making and HTAUMIT‐Private University for Health SciencesMedical Informatics and TechnologyHall in TyrolAustria

1|INTrODUCTION Capecitabine is an oral prodrug of 5-fluorouracil(5-FU),which is widely used for adjuvant and neoadjuvant chemotherapy of different solid tumors,particularly breast and colorectal cancers.1 Neurotoxicity of capecitabine has been consistently reported as capecitabine-induced toxic leukoencephalopathy,which includes bilateral lesions in the corpus callosum and corticospinal tract presenting as acute or delayed central nervous system toxicity.2 This side effect requires discontinuation of chemotherapy3;however,neurological symptoms due to capecitabine are reported to be usually reversible upon drug withdrawal.

关键词： capecitabine intramyelinic edema leukoencephalopathy stroke

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Dietary branched-chain amino acids modulate the dynamics of calcium absorption and reabsorption in proteinrestricted pigs

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Journal of Animal Science and Biotechnology 2022年第4期13卷 1083-1098页

作者： Mohammad Habibi Cedrick NShili julia Sutton Parniyan Goodarzi Adel Pezeshki Department of Animal and Food Sciences Oklahoma State University206C Animal Science BuildingStillwaterOK 74078USA

Background:Very low-protein(VLP)diets negatively impact calcium(Ca)metabolism and *** objective of this study was to investigate the effect of supplemental branched-chain amino acids(BCAA)and limiting amino acids(LAA)on Ca digestibility,absorption and reabsorption in pigs fed with VLP ***-eight piglets were assigned to six treatments:positive control(PC),negative control(NC),and NC containing LAA 25%,LAA 50%,LAA+BCAA 25%(LB25)and LAA+BCAA 50%(LB50)more than ***:relative to PC or NC,LB25 and LB50 had higher digestibility of Ca and plasma Ca and phosphorus(P),but lower plasma vitamin ***50 tended to increase vitamin D receptor transcript and protein in the gut,but decreased mrNA or protein abundance of parathyroid hormone 1 receptor(PTH1r),calbindin 1(CALB1),cytochrome P450 family 27 subfamily B member 1 and occludin in small ***50 increased the transcript of cytochrome P450 family 24 subfamily A member 1 and PTH1r but decreased the transcript of transient receptor potential cation channel subfamily V member 5,CALB1 and solute carrier family 17 member 4 in ***:Overall,BCAA increased Ca digestibility through regulating the transcellular and paracellular Ca absorption in the gut and reabsorption in kidney during protein restriction.

关键词： Branched-chain amino acids Calcium absorption and reabsorption Calcium digestibility Pig Very low protein diets

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SV2B defines a subpopulation of synaptic vesicles

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Journal of Molecular Cell Biology 2023年第9期15卷 1-13页

作者： Isabelle Paulussen Hannes Beckert Timothy FMusial Lena J.Gschossmann julia Wolf Mathieu Schmitt Jérôme Clasadonte Georges Mairet-Coello Christian Wolff Susanne Schoch Dirk Dietrich Synaptic Neuroscience Team Department of NeurosurgeryUniversity Hospital BonnBonn 53127Germany Synaptic Neuroscience Team Department of NeuropathologyUniversity Hospital BonnBonn 53127Germany Microscopy Core Facility Medical FacultyUniversity of BonnBonn 53127Germany UCB Pharma Braine l’Alleud 1420Belgium

Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein ***,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron ***2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active *** contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active ***2B and SV2A were found on the membrane in the peri-active zone,suggesting the recycling from both clusters of ***2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency *** data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial *** almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.

关键词： 3D electron microscopy synaptic vesicles synaptic vesicle proteins endocytosis trafficking spatial organization

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