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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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Neuronal and endothelial transglutaminase-2 expression in experimental autoimmune encephalomyelitis and multiple sclerosis

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Neural Regeneration Research 2022年第7期17卷 1471-1472页

作者： damien d.pearse Mousumi Ghosh Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA department of Neurological Surgery University of Miami Miller School of MedicineMiamiFLUSA Neuroscience Program Interdisciplinary Stem Cell InstituteUniversity of Miami Miller School of MedicineMiamiFLUSA department of Veterans Affairs Veterans Affairs Medical CenterMiamiFLUSA

Multiple sclerosis(MS)is a neurological condition characterized by the disruption of the blood-brain barrier,immune system activation,and infla mmation that is accompanied by glial reactivity,neuronal cell death,axon demyelination,and *** changes result in functional loss including paralysis,migraine,vision problems,spasticity,and neuropathic pain.

关键词： sclerosis paralysis autoimmune

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does being female provide a neuroprotective advantage following spinal cord injury?

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Neural Regeneration Research 2015年第10期10卷 1533-1536页

作者： Jeffrey P.datto Jackie Yang W.dalton dietrich damien d.pearse The Miami Project to Cure Paralysis University of Miami Miller School of Medicine The department of Neurological Surgery University of Miami Miller School of Medicine The department of Neurology University of Miami Miller School of Medicine The department of Cell Biology University of Miami Miller School of Medicine The Neuroscience Program University of Miami Miller School of Medicine The Interdisciplinary Stem Cell Institute University of Miami Miller School of Medicine

It has been controversial whether gender has any effect on recovery following spinal cord injury（SCI）. Past experimental and clinical research aimed at addressing this subject has led to constrasting findings on whether females hold any advantage in locomotor recovery. Additionally, for studies supporting the notion of a female gender related advantage, a definite cause has not been explained. In a recent study, using large sample sizes for comparative male and female spinal cord injury cohorts, we reported that a significant gender advantage favoring females existed in both tissue preservation and functional recovery after taking into consideration discrepancies in age and weight of the animals across sexes. Prior animal research frequently used sample sizes that were too small to determine significance with certainty and also did not account for two other factors that influence locomotor performance： age and weight. Our finding is important in light of controversy surrounding the effect of gender on outcome and the fact that SCI affects more than ten thousand new individuals annually, a population that is disproportionately male. By deepening our understanding of why a gender advantage exists, potential new therapeutics can be designed to improve recovery for the male population following the initial trauma or putatively augment the neuroprotective privilege in females for enhanced outcomes.

关键词： sex gender hormone neuroprotection estrogen progesterone apoptosis Schwann cell

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Primordial black hole mass functions as a probe of cosmic origin

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 164-171页

作者： Yi-Fu Cai Chengfeng Tang Geyu Mo Sheng-Feng Yan Chao Chen Xiao-Han Ma Bo Wang Wentao Luo damien A.Easson Antonino Marcianò deep Space Exploration Laboratory/School of Physical Sciences University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory for Researches in Galaxies and Cosmology/department of Astronomy School of Astronomy and Space ScienceUniversity of Science and Technology of ChinaHefei 230026China Istituto Nazionale di Fisica Nucleare(INFN) Sezione di MilanoMilano 20146Italy diSAT Universitàdegli Studi dell'InsubriaComo 22100Italy Jockey Club Institute for Advanced Study The Hong Kong University of Science and TechnologyHong KongChina department of Physics Arizona State UniversityTempe 85287-1504USA department of Physics&Center for Field Theory and Particle Physics Fudan UniversityShanghai 200433China Laboratori Nazionali di Frascati INFN Via Enrico Fermi 541 Frascati(Roma)00044Italy INFN sezione Roma Tor Vergata Rome I-00133Italy School of Physics University of Electronic Science and Technology of ChinaChengdu11731China

We discuss a novel window to probe the origin of our universe via the mass functions of primordial black holes(PBHs).The mass functions of PBHs are simply estimated using the conventional Press-Schechter formalism for two paradigms of cosmic origin,including inflationaryΛCdM and bounce *** standard inflationaryΛCdM model cannot generate an appreciable number of massive PBHs;however,non-trivial inflation models with blue-tilted power spectra at small scales and matter bounce cosmology provide formation mechanisms for heavy PBHs,which in turn,may seed the observed supermassive black holes(SMBHs).By fitting the SMBH mass functions at high redshift(z~6)derived from Sloan digital Sky Survey(SdSS)and Canada-France High-z Quasar Survey(CFHQS)quasars,for two paradigms of cosmic origin,we derive constraints on the PBH density fraction fPBHat z~6 and the characteristic mass M_(★),with the prior assumption that all SMBHs stem from *** demonstrate that this newly proposed procedure,relying on astronomical measurements that utilize deep-field surveys of SMBHs at high redshift,can be used to constrain models of cosmic ***,although not the main focus of this paper,we evolve the mass function from z~6 to z~0 through an assumption of 3×10^(8)-year Eddington’s accretion,and give a rough estimation of fPBHat z~0.

关键词： origin cosmic massive

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BIERMER’s disease: About 4 Cases diagnosed at Regional University Hospital of Ouahigouya (Chur/Ohg) and Literature Review

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Open Journal of Gastroenterology 2024年第9期14卷 322-329页

作者： Zanga damien Ouattara Stève Léonce Zoungrana Saïdou Santi Emeline Agathe Carama Fabien dembele Bafima désiré diarra Alain Bougouma department of Gastroenteroly Ouahigouya Regional University Hospital Ouahigouya Burkina Faso department of Neurology Bogodogo University Hospital Ouagadougou Burkina Faso department of Gastroenterology Yalgado Oudraogo University Hospital Center Ouagadougou Burkina Faso

Megaloblastic pernicious anemia is an autoimmune disorder, considered rare in African context. The objective of this study was to report four clinical cases collected at the CHUR/OHG, and to review the literature. The study population consisted of two men and two women. The clinical manifestations were mainly neurological and hematological. The neurological signs were mainly paresthesia. One patient presented memory problems. On the biological level, macrocytic anemia and vitamin B12 deficiency were reported in two cases prior to treatment while the other two without serological assay of vitamin B12 were put on trial treatment. Anti-intrinsic factor antibodies were positive in three patients. The Schilling test was not used. Upper gastrointestinal endoscopy revealed atrophic fundic gastritis in all four patients who received treatment through intramuscular injection of hydroxocobalamin (vitamin B12). The evolution was favorable after one month of treatment in all cases. The literature review is dominated by clinical case reports, the largest cohorts of which are from the Maghreb.

关键词： Anemia Pernicious Megaloblastic Vitamin B12

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Highly toxic Aβ begets more Aβ

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Neural Regeneration Research 2024年第9期19卷 1871-1872页

作者： Merc M.Kemeh Noel d.Lazo Gustaf H.Carlson School of Chemistry and Biochemistry Clark UniversityWorcesterMAUSA

Alzheimer’s disease(Ad)is the most common form of dementia-the 7th leading cause of death *** the tissue level,Ad is characterized by the presence of extracellular amyloid plaques that are comprised primarily of the amyloid-βpeptide(Aβ),and by intraneuronal neurofibrillary tangles composed of *** genetics of early-onset Ad and longitudinal brain-imaging studies of late-onset Ad indicate that extracellular Aβdeposition,in general,precedes neurofibrillary tangle formation in neurons(Hampel et al.,2021;Young-pearse et al.,2023).

关键词： Aβ tau Alzheimer death

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Prevalence and Factors Associated with Sharing of Human Immunodeficiency Seropositivity Status among Serodiscordant Couples in the City of Parakou (Benin)

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Open Journal of Epidemiology 2024年第1期14卷 1-18页

作者： djossou Sègnon Eurydice Elvire damien Georgia Barikissou Meba Bio Mamatou Tokpanoude Ignace Ahanhanzo-Glele Rhonel Ataigba Iretinethania Elie Agossoukpe Benoit Kakpo-Zannou Rodrigue Kamoutchoni Corneille Aguemon Badirou Unité de santé publique de la Faculté des Sciences de la santé (FSS) Universitéd’Abomey-Calavi (UAC) Cotonou Bénin Association des Médecins Communautaires de Bénin (AMCB) Parakou Bénin Association Béninoise pour la Promotion de la Famille (ABPF) Parakou Bénin Centre d’Information de Prospective d’Ecoute et de Conseil sur les IST/VIH/Sida du Borgou et de l’Alibori (CIPEC/B-A) Parakou Bénin Institut de Formation enSoinsInfirmiers et Obstétricaux (IFSIO) Faculté de Médecine (FMP) Parakou Bénin Service de Psychiatrie Centre HospitalierUniversitaireDépartemental du BorgouAlibori (CHUD/B-A) Parakou Bénin Service de Médecine Interne H&#244pital Saint-Jean de Dieu de Boko N’Dali Bénin

Introduction: In serodiscordant couples, sharing serostatus is a crucial step in the HIV risk management process. The aim of this study was to determine the prevalence and factors associated with serostatus sharing among HIV serodiscordant couples in the city of Parakou. Setting and methods: This study was carried out in the city of Parakou, capital of northern Benin. It was a descriptive, analytical cross-sectional study with non-probability sampling for convenience. Socio-demographic data, as well as data on antecedents, behaviours, social and marital life, were collected using a questionnaire gave to the participants. Clinical and therapeutic data were collected from patients’ medical records and follow-up charts. data were analyzed and processed using R 4.3.1 software. The significance level was set at 5%, and logistic regression was used to identify potential predictors of shared serostatus among serodiscordant couples in the city of Parakou in 2022. Results: A total of 299 participants in long-term serodiscordant relationships were included in our study. The average age of the subjects was 37.55 ± 10.25 years. Women were the infected partner in 80.27% of cases. The most common level of education was secondary (33.45%). Most respondents (230 subjects, 76.92%) were married. The average duration of the couple’s relationship was 121.68 months ± 96.32. The most frequent screening circumstances were: Prevention of mother-to-child transmission (PMTCT) (50.84%) and hospital screening (26.09%). The infected partner shared his or her serostatus with his or her spouse in 47.83% of cases. Potential predictors of serostatus sharing within the couple were: marital status (p Conclusion: The sharing of serostatus within serodiscordant couples needs to be managed in a way that takes into account the social and marital characteristics of the couple.

关键词： Serodiscordance Sharing of Serostatus HIV Partner Benin

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Multiple origin of the lichenicolous life habit in Helotiales,based on nuclear ribosomal sequences

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Fungal diversity 2015年第1期70卷 55-72页

作者： Ave Suija damien Ertz James d.Lawrey Paul diederich Institute of Ecology and Earth Sciences University of Tartu40 Lai st.EE-51005 TartuEstonia département Bryophytes et Thallophytes Jardin botanique national de BelgiqueDomaine de BouchoutB-1860 MeiseBelgium department of Environmental Science and Policy George Mason UniversityMSN 5G810900 University BoulevardManassasVA 20110-2203USA Musée national d’historie naturelle 25 rue MunsterL-2160 LuxembourgLuxembourg

The Helotiales are an ecologically and morphologically highly diverse group of ascomycetes that also includes lichen-inhabiting(lichenicolous)*** generated sequence data of three rdNA regions(nuSSU,nuLSU,5.8S of ITS)from 28 lichenicolous specimens representing nine genera in order to determine their phylogenetic *** on the most complete dataset of helotialean fungi to date,the analyses were performed using Maximum Likelihood(ML)and Bayesian *** results suggest that 1)the lichen-inhabiting life-style in Helotiales was subjected to gains or losses at least three times;2)Thamnogalla,previously tentatively included in Ostropales,is shown to belong to Helotiales;3)ascomata found intermixed with pycnidia of the asexual diplolaeviopsis ranula and possessing the same pigments are tentatively considered as the sexual morph of this taxon,and are shown to belong to Helotiales;4)the lichenicolous species of ***,Llimoniella,Rhymbocarpus,Skyttea,Thamnogalla and Unguiculariopsis form a well-supported clade together with non-lichenicolous encoelioid fungi from the genera Ionomidotis,Cordierites and Encoelia;5)Geltingia associata forms a highly supported clade with the fungicolous asexual fungus Eleutheromyces subulatus,whereas Pezizella epithallina clusters with an aquatic asexual fungus Tetracladium sp.;6)Phaeopyxis punctum belongs to Ostropomycetidae(Lecanoromycetes),but its deep relationships to other groups remain unresolved based on rdNA sequences.

关键词： Convergence Helotiales rdNA Taxonomy diplolaeviopsis Geltingia Llimoniella Pezizella Phaeopyxis Rhymbocarpus Skyttea Thamnogalla Unguiculariopsis

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Carbamylated lipoproteins in diabetes

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World Journal of diabetes 2023年第3期14卷 159-169页

作者： damien denimal department of Biochemistry University Hospital of DijonDijon 21079France INSERM LNC UMR1231 University of BurgundyDijon 21078France

diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in *** addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in *** with type 2 diabetes(T2d)exhibit higher levels of carbamylated low-density lipoproteins(cLdL)and high-density lipoproteins(cHdL).Accumulating evidence suggests that cLdL plays a role in atherosclerosis in *** levels have been shown to predict cardiovascular events and all-cause *** facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair ***,cLdL induces thrombus formation and platelet *** the other hand,recent data have demonstrated that cHdL serum level is independently associated with all-cause and cardiovascular-related mortality in T2d *** relationship may be causative since the atheroprotective properties of HdL are altered after ***,cHdL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit *** together,it seems very likely that the abnormalities in the biological functions of LdL and HdL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

关键词： Carbamylation Lipoprotein diabetes Low-density lipoprotein High-density lipoprotein Myeloperoxidase

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Gym-ANM: Reinforcement learning environments for active network management tasks in electricity distribution systems

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能源与人工智能(英文) 2021年第3期5卷 171-193页

作者： Robin Henry damien Ernst School of Engineering Sanderson BuildingThe University of EdinburghEdinburgh EH93FBUK department of Electrical Engineering and Computer Science Montefiore InstituteUniversity of LiegeLiege B-4000Belgium

Active network management(ANM)of electricity distribution networks include many complex stochastic sequential optimization *** problems need to be solved for integrating renewable energies and distributed storage into future electrical *** this work,we introduce Gym-ANM,a framework for designing reinforcement learning(RL)environments that model ANM tasks in electricity distribution *** environments provide new playgrounds for RL research in the management of electricity networks that do not require an extensive knowledge of the underlying dynamics of such *** with this work,we are releasing an implementation of an introductory toy-environment,ANM6-Easy,designed to emphasize common challenges in *** also show that state-of-the-art RL algorithms can already achieve good performance on ANM6-Easy when compared against a model predictive control(MPC)***,we provide guidelines to create new Gym-ANM environments differing in terms of(a)the distribution network topology and param-eters,(b)the observation space,(c)the modeling of the stochastic processes present in the system,and(d)a set of hyperparameters influencing the reward ***-ANM can be downloaded at https://***/robinhenr y/gym-anm.

关键词： Gym-ANM Reinforcement learning Active network management distribution networks Renewable energy

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