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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao Department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Pediatric Intensive care Unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： Mitochondrial dysfunction Mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

Prevention of ventilator-associated pneumonia with inhaled antibiotics

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World Journal of Emergency Medicine 2024年第3期15卷 165-168页

作者： Stephan Ehrmann Jie Li Intensive care Medicine INSERM CIC 1415CRICS-TriggerSep FCRIN research networkUniversity Hospital Center in ToursTours 37044France Respiratory Pathology research Center National Institute of Health and Medical ResearchTours 37000France Department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicago 60612USA

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable *** interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated *** high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

关键词： pneumonia ventilator respiratory

Consilience and unity in ocular anterior segment research

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1173-1183页

作者： Houmam Araj Department of health and Human Services National Eye Institute/National Institutes of Health(NEI/NIH)BethesdaMaryland 20892USA

In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the *** defines consilience as“literally a‘jumping together’of knowledge with a linking of facts…to create a common groundwork of explanation”.It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques–unifying available knowledge is just as *** involves the necessity to resolve contradictory findings,reduce silos,and acknowledge *** take the cornea and the lens as case studies of our ***,in this perspective,we discuss the conflicting and fragmented information on protein aggregation,oxidative damage,and *** are fields of study that are integrally tied to anterior segment *** goal is to highlight the vital need for Wilson’s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility,and most importantly,to greater understanding and not simply knowing.

关键词： anterior segment ocular surface cornea lens cataract posterior capsular opacification protein aggregation oxidative damage antioxidants fibrosis wound healing consilience

Mapping the clinical practice of traditional,complementary and integrative medicine in oncology in Western countries:A multinational cross-sectional survey

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Journal of Integrative Medicine 2024年第1期22卷 64-71页

作者： Matthias Huemer Sandro Graca Sarah Bitsche Guenter Hofmann Mike Armour Martin Pichler Palliative care Unit Division of OncologyDepartment of Internal MedicineMedical University of Graz8036 GrazAustria Northern College of Acupuncture York YO16LJUnited Kingdom School of health and Society Faculty of EducationHealth and WellbeingUniversity of WolverhamptonWolverhampton WV11LYUnited Kingdom national institute of Complementary Medicine health research institute Western Sydney UniversityPenrith NSW 2751Australia Translational health research institute Western Sydney UniversityPenrith NSW 2751Australia Medical research institute of New Zealand Wellington 6021New Zealand Translational Oncology University Hospital of Augsburg86156 AugsburgGermany

Background Many cancer patients seek adjunctive therapies to biomedical cancer treatments at some point of their disease *** acupuncture is increasingly recommended by leading oncological associations,limited evidence exists concerning the evidence-informed practice and adherence to current guidelines of traditional complementary and integrative medicine(TCIM)practitioners treating cancer *** An international online-survey assessed the demographical data,clinical practice,and sources of information used by TCIM practitioners in Austria,Germany,United States of America,Australia,and New *** In total,404 respondents completed the survey,of which 254(62.9%)treated cancer *** practitioners were acupuncturists and herbalists(57.1%),had(16.8±9.9)years of clinical experience and see a median of 2(1,4)cancer patients per *** cancer(61.8%)is the most common cancer type seen in TCIM *** TCIM treatments are frequently concurrent with the patient’s cancer specific treatment(39.9%),which is also reflected by the main goal of a TCIM treatment to alleviate side effects(52.4%).However,only 28.0%of the respondents are in contact with the treating *** to the respondents,pain is most effectively treated using acupuncture,while herbal medicine is best for cancer-related *** practitioners mostly use certified courses(33.1%)or online databases(28.3%)but often believe that experts are more reliable to inform their practice(37.0%)than research publications(32.7%).Conclusion Acupuncturists and herbalists commonly treat cancer *** practitioners use TCIM as an adjunct to biomedicine as supportive care and use it largely in accordance with current oncological guidelines.

关键词： Integrative medicine Acupuncture Oncology Evidence-informed practice International survey

Assembly of functional carboxymethyl cellulose/polyethylene oxide/anatase TiO_(2) nanocomposites and tuning the dielectric relaxation, optical, and photoluminescence performances

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Journal of Semiconductors 2024年第7期45卷 26-38页

作者： Asmaa M.Ismail Abeer A.Reffaee Fawzy G.El Desouky Spectroscopy Department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt Microwave Physics and Dielectrics Department National Research CentreDokkiCairoEgypt Solid State Physics Department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt

Nanocomposite films consisting of carboxymethyl cellulose,polyethylene oxide(CMC/PEO),and anatase titanium diox-ide(TO)were produced by the use of sol-gel and solution casting ***2 nanocrystals were effectively incorporated into CMC/PEO polymers,as shown by X-ray diffraction(XRD)and attenuated total reflectance fourier transform infrared(ATR-FTIR)*** roughness growth is at high levels of TO nanocrystals(TO NCs),which means increasing active sites and defects in CMC/*** differential scanning calorimetry(DSC)thermograms,the change in glass transition temperature(Tg)val-ues verifies that the polymer blend interacts with TO *** increment proportions of TO NCs have a notable impact on the dielectric performances of the nanocomposites,as *** electrical properties of the CMC/PEO/TO nanocomposite undergo significant *** nanocomposite films exhibit a red alteration in the absorption edge as the concentration of TO NCs increases in the polymer *** decline in the energy gap is readily apparent as the weight percentage of TO NCs *** photoluminescence(PL)emission spectra indicate that the sites of the luminescence peak maximums show slight variation;peaks get wider,while their intensities decrease dramatically as the concentration of TO *** nanocomposite materials show potential for multifunctional applications including optoelectronics,antireflection coatings,pho-tocatalysis,light emitting diodes,and solid polymer electrolytes.

关键词： anatase TiO_(2) CMC/PEO nanocomposites optical photoluminescent electrical optoelectronics

Accuracy and precision of dried urine spot method for the detection of Schistosoma mansoni circulating cathodic antigens in resource-limited settings

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Infectious Diseases of Poverty 2024年第1期13卷 103-104页

作者： Abdallah Zacharia Clemence Kinabo Twilumba Makene Huda Omary George Ogweno Faraja Lyamuya Billy Ngasala Muhimbili University of health and Allied Sciences Dar es Salaam Tanzania national institute for Medical research Mwanza Tanzania Neglected Tropical Diseases Control Program Ministry of Health Dodoma Tanzania

Background The World health Organization recommends the use of Schisto point-of-care circulating cathodic anti-gens(Schisto POC-CCA)for screening of Schistosoma mansoni as it offers better sensitivity than ***,there are limitation facing the use of this method including timely availability of the test *** aim of this study was to determine the reliability of dried urine spot(DUS)method for collection of urine and detection of *** using Schisto POC-CCA cassettes in a resource-limited *** A cross-sectional study was conducted between October and November 2022 among 250 primary school children in Sengerema District,northwestern *** CCA was detected in filter paper-based DUSs,liquid urine using DUS Schisto POC-CCA(index),and direct urine Schisto POC-CCA(comparator)methods *** eggs in stool were detected using duplicate Kato-Katz(KK)*** measures of accuracy were com-puted and compared between the index and comparator *** strength of agreement between inter-raters precisions was tested using Cohen's kappa(k).Results This study revealed *** prevalence rates of 28.8%,54.0%and 50.8%by duplicate KK,direct urine Schisto POC-CCA and DUS Schisto POC-CCA methods *** mean intensity of infection among infected participants Was 86.3 eggs per gram of stool(EPG)ranging from 12.0 EPG to 824.0 *** sensitivity of DUS Schisto POC-CCA and direct urine Schisto POC-CCA Was 94.44%(95%CI:89.15-99.74%)and 97.22%(95%CI:93.43-100.00%)*** DUS Schisto POC-CCA method had slightly higher specificity(66.85%)than direct urine Schisto POC-CCA method(63.48%).The accuracy of the DUS Schisto POC-CCA Was found to be slightly high(74.80%,95%CI:68.94-79.06%)compared to that of direct urine Schisto POC-CCA(73.20%,95%CI:67.25-78.59%).There was good agreement between two laboratory technologists who performed the DUS Schisto POC-CCA method on similar samples(k=0.80,95%CI:0.59-0.95).Con

关键词： Accuracy Point-of-care circulating cathodic antigen Dried urine spot Schistosoma mansoni Sensiti Specificity

Long non-coding RNAs with essential roles in neurodegenerative disorders

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Neural Regeneration research 2024年第6期19卷 1212-1220页

作者： Wandi Xiong Lin Lu Jiali Li Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology the Chinese Academy of Sciences Tsinghua-Peking Center for Life Sciences national institute on Drug Dependence Peking University PKU/McGovern institute for Brain research Peking University institute of Mental health National Clinical Research Center for Mental Disorders Key Laboratory of Mental Health and Peking University Sixth Hospital Peking University

Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number of long non-coding RNAs(lncRNAs) have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns, across different neurodegenerative diseases. However, the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood. This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles, regulatory mechanisms, and research status of lncRNAs in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Finally, this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases, hoping to provide broader implications for developing effective treatments.

关键词： Alzheimer's disease amyotrophic lateral sclerosis biomarker Huntington's disease long non-coding RNAs neurodegenerative diseases Parkinson's disease therapy transcriptional regulation translational regulation

Global,regional and national burdens of bipolar disorders in adolescents and young adults:a trend analysis from 1990 to 2019

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General Psychiatry 2024年第1期37卷 122-132页

作者： Yunxi Zhong Yifan Chen Xiaoying Su Meiqi Wang Qixiu Li Ziming Shao Long Sun Centre for health Management and Policy research School of Public HealthCheeloo College of MedicineShandong UniversityJinanShandongChina national health Commission of China(NHC)Key Laboratory of health Economics and Policy research Shandong UniversityJinanShandongChina nstitute of health and Elderly care Shandong UniversityJinanShandongChina

Background Bipolar disorder is identified as a cause of severe damage to the physical,psychological and social functioning of adolescents and young *** The aim of this study is to ascertain the trends in the burden of bipolar disorder among individuals aged 10-24 years at global,regional and national levels from 1990 to *** The data analysed in this study were from the Global Burden of Diseases *** numbers,rates per 100000 population,average annual percentage changes(AAPCs)of incidence,prevalence and years lived with disability(YLDs)of bipolar disorder are reported at the global,regional and national levels among individuals aged 10-24 *** trends by age,sex and Social Development Index(SDI)were further *** Globally,the incidence of bipolar disorder among adolescents and young adults increased from 79.21 per 100000 population(95%uncertainty interval(Ul):58.13 to 105.15)in 1990 to 84.97 per 100000 population(95%Ul:61.73 to 113.46)in 2019,AAPC 0.24(95%confidence interval(Cl):0.22 to 0.26).In the past three decades,there has been an increase in incidence,prevalence and YLDs in both males and *** largest increase in incidence between 1990 and 2019 was observed in those aged 20-24 years old from 51.76 per 100000 population(95%Ul:26.81 to 87.20)in 1990 to 58.37 per 100000 population(95%UI:30.39 to 98.55)in 2019;AAPC 0.42(95%Cl:0.38 to 0.47).By the SDI quintile,the largest increase in incidence was observed in the middle SDl;however,the high SDI countries had the highest ***,the largest increase in incidence was observed in southern Latin *** the national level,the most pronounced increase in the incidence was in *** The global increase in incidence among adolescents and young adults between 1990 and 2019 indicates that strategies to improve their mental health still need to be emphasised.

关键词： adolescent bipolar young