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Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias steinschaden Rose Horowitz Yuanquan song Raymond G.perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNs)and the poor regenerative capacity of the central nervous system(CNs)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

First 150 years of catatonia:Looking back at its complicated history and forward to the road ahead

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World Journal of Psychiatry 2024年第5期14卷 600-606页

作者： Levente Csihi Gabor s Ungvari stanley N Caroff Gábor Gazdag Department of Psychiatry and Psychiatric Rehabilitation Jahn Ferenc South Pest HospitalBudapest 1204Hungary Division of Psychiatry School of MedicineUniversity of Western AustraliaCrawley 6009Western AustraliaAustralia section of Psychiatry University of Notre DameFremantle 6160Western AustraliaAustralia Behavioral Health service Corporal Michael J CresenczVeterans Affairs Medical CenterPhiladelphiaPA 19104United States Department of Psychiatry University of PennsylvaniaPerelman School of MedicinePhiladelphiaPA 19104United States Department of Psychiatry and Psychotherapy Faculty of MedicineSemmelweis UniversityBudapest 1083Hungary

Karl Ludwig Kahlbaum(1828-1899)was the first to conceptualize and describe the main clinical features of a novel psychiatric illness,which he termed catatonia in his groundbreaking monograph published 150 years *** Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course,a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical *** his classification system,Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox(schizophrenia)disease *** of the substantial influence of Kraepelin’s classification,catatonia was predominantly perceived as a component of schizophrenia for most of the 20th ***,with the advent of the psychopharmacotherapy era starting from the early 1950s,interest in catatonia in both clinical practice and research subsided until the early *** past two decades have witnessed a resurgence of interest in *** Diagnostic and statistical Manual of Mental Disorders Fifth Edition,marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical *** introduction of an independent diagnostic category termed“Catatonia Not Otherwise specified”significantly stimulated research in this *** authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.

关键词： Catatonia Historical overview Psychopharmacology Diagnostic and statistical Manual of Mental Disorders-5 Wernicke-Kleist-Leonhard school

Optical redox imaging of ANT1-de-cient muscles

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Journal of Innovative Optical Health sciences 2024年第1期17卷 135-140页

作者： He N.Xu Ryan M.Morrow Min Feng Huaqing Zhao Douglas Wallace Lin Z.Li Britton Chance Laboratory of Redox Imaging Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Center for Mitochondrial and Epigenomic medicine children's hospital of philadelphia Research Institute philadelphia PA 19104USA Center for Biostatistics and Epidemiology Lewis Katz school of medicine at Temple University philadelphia PA 19140USA

Adenine nucleotide translocator(ANT)is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner *** plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the *** isoform ANT1 predominately expresses in cardiac and skeletal *** or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular *** aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-de-cient *** and quadriceps resected from age-matched wild type(WT)and ANT1-de-cient mice were snap-frozen in liquid *** Chance redox scanner was utilized to perform 3D optical redox *** sample underwent scanning across 3–5 *** averaging analysis showed no signi-cant differences in the redox indices(NADH,flavin adenine dinucleotide containing-flavoproteins Fp,and the redox ratio Fp/(NADH+Fp)between WT and ANT1-de-cient ***,quadriceps had higher Fp than hearts in both groups(p¼0:0004 and 0.01,respectively).Furthermore,the quadriceps were also more oxidized(a higher redox ratio)than hearts in WT group(p¼0:004).NADH levels were similar in all *** data suggest that under non-stressful physical condition,the ANT1-de-cient muscle cells were in the same mitochondrial state as WT ones and that the signi-cant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-de-cient *** imaging of muscles under physical stress can be conducted in future.

关键词： ANT1 redox ratio flavoproteins

Lost in translation: Evaluating traditional Chinese medicine by western standards

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Pediatric Investigation 2022年第2期6卷 144-146页

作者： Cynara s.Leon Julian L.Allen the children’s hospital of philadelphia and the perelman school of medicine the University of PennsylvaniaPhiladelphiaPennsylvaniaUSA

In this issue of Pediatric Investigation,Xu et al.'reporl a study comparing two medications w ith immunomodulatory properties in the treatment of pediatric recurent respiratory tract infections(RRTI).Pidotimod is a synthetic dipeptide introduccd in the 1990s.2 while Yupingfeng(YPF)is a traditional Chinese medicine(TCM).TCM has roots as early as the 14th century *** the west,it certainly has its skepics.

关键词： roots modulator

Genomic information of children with malignant brain tumors for the prediction of length of hospitalization

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Cancer Communications 2023年第11期43卷 1271-1274页

作者： Yichuan Liu Hui-Qi Qu Xiao Chang Frank D Mentch Haijun Qiu Kenny Nguyen Xiang Wang Amir Hossein saeidian Deborah Watson Joseph Glessner Hakon Hakonarson Center for Applied Genomics (CAG) Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA Department of Pediatrics The Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA Division of Human Genetics Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA Division of Pulmonary medicine Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA Faculty of medicine University of IcelandReykjavikIceland

Dear Editor:Central nervous system tumors in the brain or spine are the most common solid tumors in children,which accounts for about 25%of cancers in children younger than 15 years of age,and are the most common cause of cancer deaths in children[1].The 5-year survival rate for central nervous system neoplasms has increased dramatically to 74%for patients under 18 years old(97%for benign/borderline malignant tumors)in 2022,compared to 20%in the 1970s[1].Without cure treatments and specific medications for many brain cancers,the dramatic increase of survival rate is largely due to improved hospital care and availability of clinical *** length of hospitalization of pediatric patients with brain cancer is an important indicator of prognosis as it reflects the required medical effort needed to care for these *** length of hospitalization is also critical for the healthcare system as hospital admission is a part of the care trajectory of the respective patients,related to the cost of medical care[2,3].

关键词： malignant neoplasms younger

Deciphering “the language of nature”: A transformer-based language model for deleterious mutations in proteins

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The Innovation 2023年第5期4卷 47-58页

作者： Theodore T.Jiang Li Fang Kai Wang Raymond G.perelman Center for Cellular and Molecular Therapeutics Children's Hospital of PhiladelphiaPhiladelphiaPA 19104USA Palisades Charter High school Pacific PalisadesCA 90272USA Massachusetts Institute of Technology CambridgeMA 02139USA Department of Genetics and Biomedical Informatics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Department of Pathology and Laboratory medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Various machine-learning models,including deep neural network models,have already been developed to predict deleteriousness of missense(non-synonymous)*** improvements to the current state of the art,however,may still benefit from a fresh look at the biological problem using more sophisticated self-adaptive machine-learning *** advances in the field of natural language processing show that transformer models—a type of deep neural network—to be particularly powerful at modeling sequence information with context *** this study,we introduce MutFormer,a transformer-based model for the prediction of deleterious missense mutations,which uses reference and mutated protein sequences from the human genome as the primary *** takes advantage of a combination of self-attention layers and convolutional layers to learn both long-range and short-range dependencies between amino acid mutations in a protein *** first pre-trained MutFormer on reference protein sequences and mutated protein sequences resulting from common genetic variants observed in human *** next examined different fine-tuning methods to successfully apply the model to deleteriousness prediction of missense ***,we evaluated MutFormer’s performance on multiple testing datasets.

关键词： delete prediction apply

Non-canonical role of the ATR pathway in axon regeneration as a mechanosensitive brake

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Neural Regeneration Research 2022年第11期17卷 2423-2424页

作者： Feng Li Yuanquan song Institute for Translational Brain Research Fudan UniversityShanghaiChina Raymond G.perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of Philadelphiaand Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA

DNA damage has been linked to *** DNA damage response(DDR)pathways help preserve DNA integrity in the nervous system during both the developmental and mature *** of factors in various signaling pathways responsive to different types of DNA damage have been associated with developmental syndromes with neurological symptoms(McKinnon,2009;Araújo and Kuraoka,2019;Khokhlova et al.,2020).

关键词： damage ATR DDR

Integrated analysis on transcriptome and behaviors defines HTT repeat-dependent network modules in Huntington's disease

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Genes & Diseases 2022年第2期9卷 479-493页

作者： Lulin Huang Li Fang Qian Liu Abolfazl Doostparast Torshizi Kai Wang The Key Laboratory for Human Disease Gene study of sichuan Province Department of Clinical LaboratorySichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan 610054PR China Raymond G.perelman Center for Cellular and Molecular Therapeutics Children's Hospital of PhiladelphiaPhiladelphiaPA 19104USA

Huntington's disease(HD)is caused by a CAG repeat expansion in the huntingtin(HTT)***-in mice carrying a CAG repeat-expanded Htt will develop HD *** studies suggested dysregulated molecular networks in a CAG length genotype-and the age-dependent manner in brain tissues from knock-in mice carrying expanded Htt CAG ***,a large-scale phenome analysis defined a behavioral signature for HD genotype in knock-in mice carrying expanded Htt CAG ***,an integrated analysis correlating phenotype features with genotypes(CAG repeat expansions)was not conducted *** this study,we revealed the landscape of the behavioral features and gene expression correlations based on 445 mRNA samples and 445 microRNA samples,together with behavioral features(396 PhenoCube behaviors and 111 NeuroCube behaviors)in Htt CAG-knock-in *** identified 37 behavioral features that were significantly associated with CAG repeat length including the number of steps and hind limb stand *** behavioral features were associated with several gene coexpression groups involved in neuronal dysfunctions,which were also supported by the single-cell RNA sequencing data in the striatum and the spatial gene expression in the *** also identified 15 chemicals with significant responses for genes with enriched behavioral features,most of them are agonist or antagonist for dopamine receptors and serotonin receptors used for neurology/*** study provides further evidence that abnormal neuronal signal transduction in the striatum plays an important role in causing HD-related phenotypic behaviors and provided rich information for the further pharmacotherapeutic intervention possibility for HD.

关键词： Behaviors CAG repeat Huntington’s disease Mice single-cell RNA sequencing small chemicals striatum Transcriptome

Artificial Intelligence in Omics

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 811-813页

作者： Feng Gao Kun Huang Yi Xing Department of Physics School of ScienceTianjin UniversityTianjin 300072China Frontiers science Center for synthetic Biology and Key Laboratory of systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin 300072China Department of Biostatistics and Health Data science Indiana University School of MedicineIndianapolisIN 46202USA IUPUI Fairbanks school of Public Health IndianapolisIN 46202USA Regenstrief Institute IndianapolisIN 46202USA Center for Computational and Genomic medicine The Children’s Hospital of PhiladelphiaPhiladelphiaPA 19104USA Department of Biomedical and Health Informatics The Children’s Hospital of PhiladelphiaPhiladelphiaPA 19104USA Department of Pathology and Laboratory medicine Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Artificial intelligence(AI)is a powerful approach for solving complex problems in the processing,analysis,and interpretation of omics data,as well as the integration of multi-omics and clinical *** recent years,AI has enabled remarkable breakthroughs across diverse biomedical fields,such as genomic variant interpretation,protein structure prediction,disease diagnosis,and drug *** to provide a forum for advances in the development and application of AI-based tools in omics,we have organized a special issue“Artificial Intelligence in Omics”for the journal Genomics,Proteomics&Bioinformatics(GPB).

关键词： diagnosis breakthrough journal