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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural regeneration research 2025年第4期20卷 1207-1216页

作者： Pascal J.goldschmidt-Clermont Aisha Khan george Jimsheleishvili Patricia graham Adriana Brooks risset Silvera Alexander J.P.goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi James d.guest miller School of medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional rating Scale-revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Brain-penetrating neurotrophic factor mimetics: HEr-096 as a disease-modifying therapy for Parkinson’s disease

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Neural regeneration research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira m.Holmström Henri J.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

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getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of methodology 2025年第1期15卷 20-25页

作者： Nadeesha r Samarasinghe Taniya S Nagpal michele L Barbeau Charys m martin division of general Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(mSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving mSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of mSK concepts(90.0%)and activity levels(97.7%).many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement mSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： medical education musculoskeletal Anatomy Exercise Online learning

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Landslide inventory validation and susceptibility mapping in the gerecse Hills, Hungary

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geo-Spatial Information Science 2021年第3期24卷 498-508页

作者： dávid gerzsenyi gáspár Albert department of Cartography and geoinformatics Eötvös Loránd UniversityBudapestHungary

Landslides pose a threat to property both in the populated and cultivated areas of the gerecse Hills (Hungary). The currently available landslide inventory database holds the records from many sites in the area, but the database is out-of-date. Here we address the problem of revising the National Landslides Cadastre landslide inventory database by creating a landslide suscept-ibility map with a multivariate model based on likelihood ratio functions. The model is applied to the TandEm-X dEm (0.4″ res.), the current landslide inventory of the area, and data acquired from geological maps. By comparing the distributions of four variables in the landslide and non-landslide area with grid computation methods, the model yields landslide susceptibility estimates for the study area. The estimations show to what extent a certain area is similar to the sample areas, therefore, its likelihood to be affected by landslides in the future. The accuracy of the model predictions was checked in the field and compared to the results of our previous study using the SrTm-1 dEm for a similar analysis. The model gave accurate estimates when certain correction measures were applied to the input datasets. The limitations of the model, the input datasets, and the suggested correction measures are also discussed.

关键词： Landslide susceptibility landslide inventory TandEm-X gerecse Hills landslides geomorphometry

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machine Learning Techniques in Predicting Hot deformation Behavior of metallic materials

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Computer modeling in Engineering & Sciences 2025年第1期142卷 713-732页

作者： Petr Opela Josef Walek Jaromír Kopecek department of metallurgical Technologies Faculty of Materials Science and TechnologyVSB–Technical University of OstravaOstrava70800Czech Republic FZU—Institute of Physics of the Czech Academy of Sciences Prague18200Czech Republic

In engineering practice,it is often necessary to determine functional relationships between dependent and independent *** relationships can be highly nonlinear,and classical regression approaches cannot always provide sufficiently reliable ***,machine Learning(mL)techniques,which offer advanced regression tools to address complicated engineering issues,have been developed and widely *** study investigates the selected mL techniques to evaluate their suitability for application in the hot deformation behavior of metallic *** mL-based regression methods of Artificial Neural Networks(ANNs),Support Vector machine(SVm),decision Tree regression(dTr),and gaussian Process regression(gPr)are applied to mathematically describe hot flow stress curve datasets acquired experimentally for a medium-carbon *** the gPr method has not been used for such a regression task before,the results showed that its performance is the most favorable and practically unrivaled;neither the ANN method nor the other studied mL techniques provide such precise results of the solved regression analysis.

关键词： machine learning gaussian process regression artificial neural networks support vector machine hot deformation behavior

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The value of prognostic markers for pediatric trauma patients

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World Journal of Emergency medicine 2023年第6期14卷 448-453页

作者： Cansu durak Ebru guney Sahin Yasar Yusuf Can alican Sarisaltik Kubra Boydag guvenc department of Pediatric Intensive Care Sancaktepe Sehit Prof.Dr.IlhanVarank Training and Research HospitalHealth Science UniversityIstanbul 34785Turkiye republic of Turkiye ministry of Health Cayirova District Health DirectorateKocaeli 41420Turkiye

BACKgrOUNd: despite the rapid development of pediatric intensive care medicine, there are still limited data in the literature regarding the follow-up of pediatric trauma patients in pediatric intensive care units(PICUs). In this study, we aim to evaluate our experience with children admitted and followed up with the diagnosis of trauma at our ***: We evaluated the retrospective data of 77 pediatric trauma patients who were admitted to the PICU at Sancaktepe Sehit Prof. dr. IlhanVarank Training and research Hospital from August 2020 to december 2022. The demographic data, clinical parameters and laboratory results were recorded. The primary outcome was the mortality in PICU. The performances of markers in predicting mortality were evaluated with receiver operating characteristic(rOC) ***: The median age of the patients was 70(33–157) months, and the median duration of hospitalization in the PICU was 6(2–11) d. Of the 77 patients, 9 died due to trauma(11,1%). Among the clinical parameters, Pediatric risk of mortality III(PrISm III) Score, inotrope requirement, extracorporeal treatment requirement, and mechanical ventilator requirement were significantly higher in non-survivors than in survivors. Among the laboratory parameters, procalcitonin(PCT), lactate/albumin ratio(LAr), neutrophil/lymphocyte ratio(NLr), and transfusion requirement were significantly higher in non-survivors than in ***: In pediatric trauma patients, baseline PCT, LAr, and NLr values can be used to identify patients at risk for mortality.

关键词： Critical care Pediatric Lactate Procalcitonin Trauma

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Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis

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Neural regeneration research 2025年第11期20卷 3229-3230页

作者： Savina Apolloni Nadia d’Ambrosi department of Biology University of Rome Tor VergataRomeItaly

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and *** the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 *** is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.

关键词： STAT3 dissection sclerosis

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Projective Hilbert modules and sequential approximations

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Science China mathematics 2025年第1期 137-168页

作者： Lawrence g.Brown Huaxin Lin department of mathematics Purdue University department of mathematics East China Normal University department of mathematics University of Oregon Shanghai Institute for mathematics and Interdisciplinary Sciences

We show that when A is a separable C*-algebra,every countably generated Hilbert A-module is projective（with bounded module maps as morphisms）.We also study the approximate extensions of bounded module *** the case where A is a σ-unital simple C*-algebra with strict comparison,and every strictly positive lower semicontinuous affine function on quasitraces can be realized as the rank of an element in the Cuntz semigroup,we show that the Cuntz semigroup is equivalent to unitarily equivalent classes of countably generated Hilbert A-modules if and only if A has stable rank one.

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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural regeneration research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle m.Koss department of Surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;m1 and m2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

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SBL-JP-0004: A promising dual inhibitor of JAK2 and PI3KCd against gastric cancer

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Oncology research 2025年第1期33卷 235-243页

作者： Hassan m Otifi department of Pathology College of Medicine King Khalid University Abha 62521 Saudi Arabia.

Background:gastric cancer (gC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in gC progression, making them attractive targets for therapeutic interventions.methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCd kinases. KATOIII and SNU-5 gC cells were used for evaluation.results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCd kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBL-JP-0004 displayed an half-maximal inhibitory concentration (IC) value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCd enzymes. SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with half-maximal growth inhibitory concentration (gI) values of 250.8 and 516.3 nm, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOIII cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOIII cells and 10.05% in SNU-5 cells) were observed with SBL-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCd kinases for treating gC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： dual inhibition gastric cancer (gC) JAK2 molecular docking molecular dynamics simulation PI3KCd SBL-JP-0004

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