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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes Jessica Rast Caichen Zhong Renee M Gardner Christina Dalman kristen Lyal cRAIG Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind Neil M Davies brian k lee Cecilia Magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden Medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community Medicine Region StockholmStockholmSweden k.G Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with epilepsy.Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy.We then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression.Finally,we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions.For example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric conditions.Conclusions Psychiatric comorbidities are common in patients with epilepsy.Genetic correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric conditions.These findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psychiatric comorbidities in epilepsy.

关键词： epilepsy Psychiat lifetime

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Areal Roughness of the Dorsal Nail Plate

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International Journal of Dermatology And Venereology 2024年第1期07卷 27-34页

作者： Beatty brian lee Li Edward Anaekwe Adaeze Anatomy Department NYIT College of Osteopathic Medicine Old Westbury NY 11568 USA Division of Paleobiology Friends Academy Locust Valley NY 11560

Objective: Beau lines, onychorrhexis, and psoriatic lesions of the dorsal nail plate may be missed by photographic methods, indicating a need for surface texture measurement methods that are more quantitative, sensitive, and repeatable than visual inspection or imaging. We conducted this study to evaluate the utility of surface texture measurements of cadaveric nails that can be associated with histopathological studies in the future.Methods: The nail plates of 4 cadaveric right pollices and halluces were cleaned and molded, cast in clear epoxy, and scanned with a Sensofar S Neox optical profilometer. A one-way analysis of variance was performed to determine statistical significance of findings.Results: Almost no differences were observed between the pollex and hallux scans and between the distal and proximal regions. The greatest differences were found between individuals. Although lower magnification (5×) is less sensitive than higher magnification (20×), the lower magnification represented and characterized more of the dorsal nail plate.Conclusion: The dorsal nail plate areal roughness has a measurable range of values that may serve as a starting point for evaluating pathological findings, particularly Beau lines and psoriatic lesions. The sensitivity of these techniques may be especially valuable in the recognition of less severe states of these diseases that may enable the diagnosis of earlier stages of growth disruptions (Beau lines) or psoriasis. Such applications could be especially useful in investigations of the health of wildlife populations or vulnerable human populations with incomplete treatment records.

关键词： nail plate surface metrology areal roughness

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CD200Rhigghh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells

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Cellular & Molecular Immunology 2024年第4期21卷 349-361页

作者： Ye Seon kim Yu Sun Jeong Geon Ho Bae Ji Hyeon kang Mingyu lee brian A.Zabel Yoe-Sik Bae Department of Biological Sciences Sungkyunkwan UniversitySuwon16419Republic of Korea Department of Health Science and Technology SAIHSTSungkyunkwan UniversitySeoul06351Republic of Korea Palo Alto Veterans Institute for Research Veterans Affairs HospitalPalo AltoCA94304USA

Distinct neutrophil populations arise during certain pathological conditions.The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear.In this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))cells.Compared to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-αproduction.Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) neutrophils.The administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased survival.Transcriptome analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection model.Taken together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.

关键词： Sepsis Neutrophils CD200R Autophagy IGF-1 Regulatory T cells

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Cardiovascular health awareness,risk perception,behavioural intention and INTERHEART risk stratification among middle-aged adults in Malaysia

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Asian Pacific Journal of Tropical Medicine 2024年第2期17卷 61-70页

作者： Siew-keah lee Ang-Lim Chua Clement Heng Yew Fong Ban Hao brian Cong Wen Ling Ng Jing Feng kong Yik-Ling Chew kai Bin Liew Yang Shao M.kandiah Faculty of Medicine and Health Sciences Universiti Tunku Abdul RahmanMalaysia Faculty of Medicine Universiti Teknologi MARAMalaysia Faculty of Pharmaceutical Sciences UCSI UniversityMalaysia Faculty of Pharmacy University of CyberjayaMalaysia The First Affiliated Hospital of Hainan Medical University China

Objective:To investigate the interrelationship between cardiovascular health awareness,risk perception,behavioural intention,and INTERHEART risk stratification in a middle-aged adult population in Malaysia.Methods:A cross-sectional survey with convenience sampling was conducted during November 2022 and January 2023.Participants completed validated questionnaires assessing cardiovascular health awareness,risk perception of cardiovascular diseases,behavioural intention towards adopting healthy habits,and INTERHEART risk stratification score(IHRS)based on established risk factors.A total of 602 respondents were included in the final analysis.Data were analysed with independent t-test/one-way ANOVA or Mann-Whitney/kruskal-Wallis to test the differences,Pearson correlation or linear regression test to analyze the association of independent and dependent variables.Results:There was a significant positive correlation between medical knowledge related to cardiovascular disease(CVD)and knowledge related to CVD risk prevention,risk perception,behavioural intention and IHRS(Pknowledge related to CVD and CVD risk prevention,risk perception,and behavioural intention.Males,laborers,active/former smokers,individuals with lower household income and educational levels,those involved in occupations not related to the healthcare sector,and those who did not receive the CVD health brochure or are unaware of health self-assessment tools are likely to have lower levels of knowledge,risk perception,and poorer behavioural intention regarding cardiovascular health(Pking status,awareness about CVD poster,self-assessment tools were repeatedly significantly associated with knowledge related to CVD and CVD risk prevention,risk perception,behavioral intention and/or IHRS(Pk perception

关键词： Cardiovascular risk knowledge Risk perception Behavioural intention INTERHEART Middle-aged Lifestyle Physical activity Psychosocial stress

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Changes in Lipoprotein Lipase in the Heart Following Diabetes Onset

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Engineering 2023年第1期20卷 19-25页

作者： Chae Syng lee Yajie Zhai brian Rodrigues Faculty of Pharmaceutical Sciences University of British ColumbiaVancouverBC V6T 1Z3Canada

Due to its constant pumping and contraction, the heart requires a substantial amount of energy, with fatty acids (FAs) providing a major part of its adenosine triphosphate (ATP). However, the heart is incapable of making this substrate and attains its FAs from multiple sources, including the action of lipoprotein lipase (LPL). LPL is produced in cardiomyocytes and subsequently secreted to its heparan sulfate proteoglycan (HSPG) binding sites on the plasma membrane. To then move LPL to the endothelial cell (EC) lumen, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) attaches to interstitial LPL and transfers it to the vascular lumen, where the LPL is ready to perform its function of breaking down circulating triglycerides (TG) into FAs. The endo-β-glucuronidase heparanase (Hpa) is unique in that it is the only known mammalian enzyme to cleave heparan sulfate (HS), thereby promoting the abovementioned release of LPL from the cardiomyocyte HSPG. In diabetes, it has been suggested that changes in how the heart generates energy are responsible for the development of diabetic cardiomyopathy (DCM). Following moderate diabetes, with the reduction in glucose utilization, the heart increases its LPL activity at the vascular lumen due to an increase in Hpa action. Although this adaptation might be beneficial to compensate for the underutilization of glucose by the heart, it is toxic over the long term, as harmful lipid metabolite accumulation, along with augmented FA oxidation and thus oxidative stress, leads to cell death. This coincides with the loss of a cardioprotective growth factor—namely, vascular endothelial growth factor B (VEGFB). This review discusses interconnections between Hpa, LPL, and VEGFB and their potential implications in DCM. Given that mechanism-based therapeutic care for DCM is unavailable, understanding the pathology of this cardiomyopathy, along with the contribution of LPL, will help us advance its clinical management.

关键词： Cardiac metabolism Lipopr otein lipase Heparanase Vascular endothelial growth factor Diabetic car diomyopathy

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Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs

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Bioactive Materials 2023年第5期23卷 551-562页

作者： Jeffrey Luo Anjani Darai Thanapat Pongkulapa brian Conley Letao Yang Inbo Han ki-Bum lee Department of Chemistry and Chemical Biology RutgersThe State University of New JerseyPiscatawayNJ08854USA Department of Neurosurgery CHA University School of MedicineCHA Bundang Medical Center59 Yaptap-roBundang-guSeongnam-siGyeonggi-do13496Republic of Korea

Intervertebral disc(IVD)degeneration is a leading cause of back pain and precursor to more severe conditions,including disc herniation and spinal stenosis.While traditional growth factor therapies(e.g.,TGFβ)are effective at transiently reversing degenerated disc by stimulation of matrix synthesis,it is increasingly accepted that bioscaffolds are required for sustained,complete IVD regeneration.Current scaffolds(e.g.,metal/polymer composites,non-mammalian biopolymers)can be improved in one or more IVD regeneration demands:biodegradability,noninvasive injection,recapitulated healthy IVD biomechanics,predictable crosslinking,and matrix repair induction.To meet these demands,tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel(BIOGEL).The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min,allowing a human operator to easily inject the therapeutic constructs into degenerated IVD.Moreover,BIOGEL encapsulation of TGFβpotentiated histological repair(e.g.,tissue architecture and matrix synthesis)and functional recovery(e.g.,high water retention by promoting the matrix synthesis and reduced pain)in an in vivo rat IVD degeneration/nucleotomy model.This BIOGEL procedure readily integrates into existing nucleotomy procedures,indicating that clinical adoption should proceed with minimal difficulty.Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules,our developed material platform can be extended to other payloads and degenerative injuries.

关键词： Bioorthogonal chemistry Growth factor Injectable hydrogel Intervertebral disc degeneration Tissue engineering

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Mapping microstructure to shock-induced temperature fields using deep learning

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npj Computational Materials 2023年第1期9卷 516-523页

作者： Chunyu Li Juan Carlos Verduzco brian H.lee Robert J.Appleton Alejandro Strachan School of Materials Engineering Purdue UniversityWest LafayetteIN 47907USA

The response of materials to shock loading is important to planetary science,aerospace engineering,and energetic materials.Thermally activated processes,including chemical reactions and phase transitions,are significantly accelerated by energy localization into hotspots.These result from the interaction of the shockwave with the materials’microstructure and are governed by complex,coupled processes,including the collapse of porosity,interfacial friction,and localized plastic deformation.These mechanisms are not fully understood and the lack of models limits our ability to predict shock to detonation transition from chemistry and microstructure alone.We demonstrate that deep learning can be used to predict the resulting shock-induced temperature fields in composite materials obtained from large-scale molecular dynamics simulations with the initial microstructure as the only input.The accuracy of the Microstructure-Informed Shock-induced Temperature net(MISTnet)model is higher than the current state of the art and its evaluation requires a fraction of the computation cost.

关键词： microstructure Microstructure friction

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Cholecystectomy for asymptomatic gallstones:Markov decision tree analysis

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World Journal of Clinical Cases 2022年第29期10卷 10399-10412页

作者： brian Juin Hsien lee Qai Ven Yap Jee keem Low Yiong Huak Chan Vishal G Shelat lee kong Chian School of Medicine Nanyang Technological UniversitySingapore S308232Singapore Biostatistics Unit Yong Loo Lin School of MedicineNational University of SingaporeSingapore S117597Singapore Department of General Surgery Tan Tock Seng HospitalSingapore S308433Singapore

Gallstones are a common public health problem,especially in developed countries.There are an increasing number of patients who are diagnosed with gallstones due to increasing awareness and liberal use of imaging,with 22.6%-80% of gallstone patients being asymptomatic at the time of diagnosis.Despite being asymptomatic,this group of patients are still at life-long risk of developing symptoms and complications such as acute cholangitis and acute biliary pancreatitis.Hence,while early prophylactic cholecystectomy may have some benefits in selected groups of patients,the current standard practice is to recommend cholecystectomy only after symptoms or complications occur.After reviewing the current evidence about the natural course of asymptomatic gallstones,complications of cholecystectomy,quality of life outcomes,and economic outcomes,we recommend that the option of cholecystectomy should be discussed with all asymptomatic gallstone patients.Disclosure of material information is essential for patients to make an informed choice for prophylactic cholecystectomy.It is for the patient to decide on watchful waiting or prophylactic cholecystectomy,and not for the medical community to make a blanket policy of watchful waiting for asymptomatic gallstone patients.For patients with high-risk profiles,it is clinically justifiable to advocate cholecystectomy to minimize the likelihood of morbidity due to complications.

关键词： Asymptomatic Cholecystectomy Cholelithiasis Gallbladder Gallstone

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RANkL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

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Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae kibyeong kim keunsoo kang Haemin kim Minjoon lee brian Oh kaichi kaneko Sungkook Ma Jae Hoon Choi Hojoong kwak Eun Young lee Sung Ho Park kyung-Hyun Park-Min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA Department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA Department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea Department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea Department of Microbiology Dankook UniversityCheonan3116Republic of Korea Department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANkL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANkL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANkL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANkL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANkL-responsive SEs. The depletion of BATF1/3 inhibited RANkL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANkL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANkL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeuti

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

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Experimental and modeling study of de novo formation of PCDD/PCDF on MSW fly ash

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Journal of Environmental Sciences 2007年第1期19卷 117-122页

作者： LI Xiao-dong ZHANG Ji YAN Jian-hua CEN ke-fa RYAN Shawn P GULLETT brian k lee Chunwai State key Laboratory of Clean Energy Utilization Institute for Thermal Power Engineering Zhefiang University Hangzhou 310027 China U.S. Environmental Protection Agency Office of Research and Development National Risk Management Research Laboratory E305-01 Research Triangle Park North Carolina 27711 USA

The effect of sulfur dioxide （SO2） on the formation of polychlorinated dibenzo-p-dioxins （PCDDs） and polychlorinated dibenzofurans （PCDFs） has been studied in an entrained-flow reactor （EFR） under simulated waste combustion conditions. A chlorination model based on conditional probability was employed to evaluate the homologue patterns of PCDDs and PCDFs. Results revealed that the presence of SO2 did not alter the formation pathway although SO2 suppressed PCDD/F formation. The prediction model of PCDF showed good agreement with the experimental data （R--0.95）, whereas the prediction for PCDDs did not correlate well with the experimental data. This may be explained because potential chlorination pathways play a significant role in PCDF formation, whereas PCDDs are mainly formed through condensation reactions. Furthermore, the result indicated that the steric hindrance during formation has more effects on PCDD than on PCDF due to the symmetric molecular structures of PCDDs.

关键词： PCDDs PCDFs de novo synthesis formation chlorination model sulfur dioxide air pollution waste combustion

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