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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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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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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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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

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Protein & Cell 2024年第9期15卷 661-685页

作者： Sadaf Hasan Nabil Ghani Xiangli Zhao julia Good Amanda Huang Hailey Lynn Wrona Jody Liu Chuan-ju Liu Department of Orthopedic Surgery New York University Grossman School of MedicineNew YorkNY 10016United States Department of Medicine Division of Internal MedicineSaint Peter’s University HospitalRutgers UniversityNew BrunswickNJ 08901United States Cornell University IthacaNew YorkNYUnited States Department of Biomedical Engineering University of North Carolina Chapel HillChapel HillNC 27599United States New York University NY 14853United States Department of Cell Biology New York University Grossman School of MedicineNew YorkNY 10016United States Department of Orthopedics&rehabilitation Yale University School of MedicineNew HavenCT 06510United States

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as *** state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver *** is a glycolytic metabolite and a crucial node in various metabolic ***,its role and molecular mechanism in obesity and associated complications are *** this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic *** identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular ***,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent *** with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and ***,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its ***’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet.

关键词： metabolic disease pyruvate cytosolic phospholipase obesity

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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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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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Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

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Asian Journal of Andrology 2015年第5期17卷 716-719,I0005-I0006页

作者： julia r Dorin Formerly at MrC Human Genetics Unit IGMM University of Edinburgh now at MRC Centre for Inflammation Research University of Edinburgh Queen's MedicalResearch Institute 47 Little France Crescent Edinburgh EH16 4TJ Scotland UK

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitroand interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MrC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.

关键词： acrosome reaction antimicrobial capacitation epididymis sperm β-defensins

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Cold-temperature deformation of nano-sized tungsten and niobium as revealed by in-situ nano-mechanical experiments

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Science China(Technological Sciences) 2014年第4期57卷 652-662页

作者： LEE Seok-Woo CHENG YinTong rYU Ill GrEEr julia r. Division of Engineering and Applied Science California Institute of Technology School of Engineering Brown University

We constructed and developed an in-situ cryogenic nanomechanical system to study small-scale mechanical behavior of materials at low temperatures. Uniaxial compression of two body-centered-cubic （bcc） metals, Nb and W, with diameters between 400 and 1300 rim, was studied at room temperature and at 165 K. Experiments were conducted inside of a Scanning Electron Microscope （SEM） equipped with a nanomechanical module, with simultaneous cooling of sample and diamond tip. Stress-strain data at 165 K exhibited higher yield strengths and more extensive strain bursts on average, as compared to those at 298 K. We discuss these differences in the framework of nano-sized plasticity and intrinsic lattice resistance. Dislocation dynamics simulations with surface-controlled dislocation multiplication were used to gain insight into size and temperature effects on deformation of nano-sized bcc metals.

关键词： dislocation plasticity metal nanopillar cryogenics

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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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Perspective:Chemical Information Encoded in Electron Density

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物理化学学报 2018年第6期34卷 567-580页

作者： CONTrErAS-GArCíA julia YANG Weitao UPMC Univ Paris 06 CNRSUMR 7616Laboratoire de Chimie Théorique Department of Chemistry Duke University

In this perspective,we review the chemical information encoded in electron density and other ingredients used in semilocal *** information is usually looked at from the functional point of view:the exchange density or the enhancement factor are discussed in terms of the reduced density ***,what parts of a molecule do these 3D functions represent? We look atthese quantities in real space,aiming to understand the electronic structure information they encode and provide an insight from the quantum chemical topology(QCT).Generalized gradient approximations(GGAs) provide information about the presence of chemical interactions,whereas meta-GGAs can differentiate between the different bonding *** merging these two techniques,we show new insight into the failures of semilocal functionals owing to three main errors:fractional charges,fractional spins,and non-covalent *** build on simple *** also analyze the delocalization error in hydrogen chains,showing the ability of QCT to reveal the delocalization error introduced by semilocal ***,we show how the analysis of localization can help understand the fractional spin error in alkali atoms,and how it can be used to correct ***,we show that the poor description of GGAs of isodesmic reactions in alkanes is due to 1,3-interactions.

关键词： DFT Semi-local functional Electron density Quantum chemical topology

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