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Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients

Translational Neurodegeneration 2021年第2期10卷 213-229页

作者： David Bayer Stefano Antonucci Hans-Peter Muller Rami Saad Luc Dupuis Volker Rasche Tobias M.Bockers albert c.ludolph Jan Kassubek Francesco Roselli Department of Neurology Ulm UniversityUlmGermany cEMMA(cellular and Molecular Mechanisms in Aging)Research Training Group UlmGermany University of Strasbourg StrasbourgFrance Department of Internal Medicine II Ulm University Medical CentreUlmGermany Institute of Anatomy and cell Biology Ulm UniversityUlmGermany German center for Neurodegenerative Diseases-DZNE UlmGermany

Background:Increased catabolism has recently been recognized as a clinical manifestation of amyotrophic lateral sclerosis(ALS).The hypothalamic systems have been shown to be involved in the metabolic dysfunction in ALS,but the exact extent of hypothalamic circuit alterations in ALS is yet to be *** we explored the integrity of large-scale cortico-hypothalamic circuits involved in energy homeostasis in murine models and in ALS ***:The rAAV2-based large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik software suites were used to identify and quantify projections from the forebrain to the lateral hypothalamus in the SOD1(G93A)ALS mouse model(hypermetabolic)and the FusΔNLS ALS mouse model(normo-metabolic).3 T diffusion tensor imaging(DTI)-magnetic resonance imaging(MRI)was performed on 83 ALS and 65 control cases to investigate cortical projections to the lateral hypothalamus(LHA)in ***:Symptomatic SOD1(G93A)mice displayed an expansion of projections from agranular insula,ventrolateral orbitofrontal and secondary motor cortex to the *** findings were reproduced in an independent cohort by using a different analytic *** contrast,in the FusΔNLS ALS mouse model hypothalamic inputs from insula and orbitofrontal cortex were maintained while the projections from motor cortex were *** DTI-MRI data confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS ***:This study provides converging murine and human data demonstrating the selective structural disruption of hypothalamic inputs in ALS as a promising factor contributing to the origin of the hypermetabolic phenotype.

关键词： rAAV2 Agranular insula Orbitofrontal cortex Lateral hypothalamus Hypermetabolism Amyotrophic lateral sclerosis

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Neuroflament light and heterogeneity of disease progression in amyotrophic lateral sclerosis:development and validation of a prediction model to improve interventional trials

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Translational Neurodegeneration 2021年第3期10卷 400-411页

作者： Simon Witzel Felix Frauhammer† Petra Steinacker David Devos Pierre‑François Pradat Vincent Meininger Stefen Halbgebauer Patrick Oeckl Joachim Schuster Simon Anders Johannes Dorst Markus Otto albert c.ludolph Department of Neurology University of UlmUlmGermany center for Molecular Biology Heidelberg UniversityHeidelbergGermany Depart‑ment of Medical Pharmacology Expert center for ParkinsonCHU‑LilleLille Neuroscience and CognitionInsermUMR‑S1172LICENDNS‑Park NetworkUniversity of LilleLilleFrance Laboratoire D’Imagerie Biomédicale Sorbonne UniversitéCNRSINSERMParisFrance APHP Département de NeurologieHôpital Pitié-SalpêtrièreParisFrance German centre for Neurodegenerative Diseases(DZNE)Site Ulm UlmGermany

Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical *** asked if blood neuroflament light chains(NfL)could be used to antici‑pate disease progression and increase trial ***:In 125 patients with ALS from three independent prospective studies-one observational study and two interventional trials-we developed and externally validated a multivariate linear model for predicting disease pro‑gression,measured by the monthly decrease of the ALS Functional Rating Scale Revised(ALSFRS-R)*** trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis:NfL levels,sex,age,site of onset,body mass index,disease duration,ALSFRS-R score,and monthly ALSFRS-R score decrease since disease *** then applied the resulting model in the other two study cohorts to assess the actual utility for interventional *** analyzed the impact on trial power in mixed-efects models and compared the performance of the NfL model with two currently used predictive approaches,which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period(lead-in)or since disease onset(ΔFRS).Results:Among the parameters provided,the NfL levels(Pction with site of onset(Pcontributed signifcantly to the prediction,forming a robust NfL prediction model(R=0.67).Model application in the trial cohorts confrmed its applicability and revealed superiority over lead-in andΔFRS-based *** NfL model improved statistical power by 61%and 22%(95%confdence intervals:54%-66%,7%-29%).conclusion:The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could signif‑cantly increase the trial ***00868166,registered March23,2009;NcT02306590,registered December 2,2014.

关键词： Neuroflament light Prediction model Disease progression Amyotrophic lateral sclerosis Interventional trials Statistical power

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Longitudinal diffusion tensor magnetic resonance imaging analysis at the cohort level reveals disturbed cortical and callosal microstructure with spared corticospinal tract in the TDP-43^(G298S) ALS mouse model

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Translational Neurodegeneration 2019年第1期8卷 333-345页

作者： Hans-Peter Müller David Brenner Francesco Roselli Diana Wiesner Alireza Abaei Martin Gorges Karin M.Danzer albert c.ludolph William Tsao Philip c.Wong Volker Rasche Jochen H.Weishaupt Jan Kassubek Department of Neurology University of UlmOberer Eselsberg 45RKUD-89081 UlmGermany German center for Neurodegenerative Diseases(DZNE) UlmGermany core Facility Small Animal MRI University of UlmUlmGermany Department of Pathology The Johns Hopkins University School of MedicineBaltimoreUSA

Background:In vivo diffusion tensor imaging(DTI)of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis(ALS).Methods:Ten mice with TDP-43^(G298S) overexpression under control of the Thy1.2 promoter and 10 wild type(wt)underwent longitudinal DTI scans at 11.7 T,including one baseline and one follow-up scan with an interval of about *** brain-based spatial statistics(WBSS)of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43^(G298S) mice compared to wt at the cohort *** were supplemented by tractwise fractional anisotropy statistics(TFAS)and histological evaluation of motor cortex for signs of neuronal ***:Alterations at the cohort level in TDP-43^(G298S) mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal *** loss in layer V of motor cortex was detected in TDP-43^(G298S) at the later(but not at the earlier)timepoint compared to ***:DTI mapping of TDP-43^(G298S) mice demonstrated progression in motor areas M1/*** and TFAS are useful techniques to localize TDP-43^(G298S) associated alterations over time in this ALS mouse model,as a biological marker.

关键词： Diffusion tensor imaging Amyotrophic lateral sclerosis Mutant TDP-43 Fiber tracking Mouse brain

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A natural history comparison check for updates of SOD1-mutant patients with amyotrophic lateral sclerosis between chinese and German populations

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Translational Neurodegeneration 2021年第4期10卷 551-553页

作者： Lu Tang Johannes Dorst Lu chen Xiaolu Liu Yan Ma Komelia Günther Sebastian Michels Kathrin Müller Axel Freischmidt Jochen H.Weishaupt Dongsheng Fan albert c.ludolph Department of Neurology Peking University Third HospitalBeijing 100191China Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases Peking University Third HospitalBeijing 100191China Department of Neurology Ulm University89081 UlmGermany German center for Neurodegenerative Diseases(DZNE) Ulm Site89081 UlmGermany

currently,there is no effective treatment for amyotrophic lateral sclerosis(ALS),despite the limited efficacy of riluzole[1]and edaravone[2].SOD1(coding for the cu/Zn superoxide dismutase)is the second most frequent genetic cause for ALS only after c9orf72 in patients with European ancestry while being the most frequent in Asian ALS populations[3],Multiple therapeutic approaches have targeted SOD1-related ALS,including the antisense oligonucleotide tofersen with promising results in a recent phase I/II trial[4].

关键词： SOD1 patients amyotrophic

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Highly efficient synthesis of β-amino esters via Mannich-type reaction under solvent-free conditions using Zncl_2 catalyst

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chinese chemical Letters 2009年第4期20卷 407-410页

作者： albert S.c.chan School of Pharmaceutical Science Sun Yat-Sen University

β-Amino esters were synthesized via Zncl2-catalyzed Mannich-type reaction of imines and malonate esters under solvent-free conditions in 6 min. The β-amino ester was converted into the corresponding aspartic acid de... 详细信息

关键词： β-Amino esters Aspartic acid derivativates Mannich-type reaction Solvent-free Krapcho decarboxylation reaction Zinc chloride

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Differential effect of ethanol intoxication on peripheral markers of cerebral injury in murine blunt traumatic brain injury

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Burns & Trauma 2021年第1期9卷 207-219页

作者： Zhenghui Li Jin Zhang Steffen Halbgebauer Akila chandrasekar Rida Rehman albert ludolph Tobias Boeckers Markus Huber-Lang Markus Otto Francesco Roselli Florian olde Heuvel Department of Neurology Ulm UniversityZBMF-Helmholtzstrasse 8/189081 UlmGermany Department of Neurosurgery Kaifeng Central HospitalKaifeng475000 Henan China German center for Neurodegenerative Diseases(DZNE) UlmGermany Institute of Anatomy and cell Biology Ulm UniversityUlmGermanyM24Albert-Einstein Allee 1189081 UlmGermany Institute of clinical and Experimental Trauma-Immunology University HospitalZBMF-Helmhotzstrasse 8/189081 UlmGermany Zoological Institute Braunschweig Cellular Neurobiology–BiozentrumSpielmannstrasse 738106 Braunschweig

Background:Blood-based biomarkers have proven to be a reliable measure of the severity and outcome of traumatic brain injury(TBI)in both murine models and *** particular,neuronspecific enolase(NSE),neurofilament light(NFL)and S100 beta(S100B)have been investigated in the clinical setting *** intoxication(EI)remains a significant comorbidity in TBI,with 30–40%of patients having a positive blood alcohol concentration *** effect of ethanol on blood-based biomarkers for the prognosis and diagnosis of TBI remains *** this study,we investigated the effect of EI on NSE,NFL and S100B and their correlation with blood–brain barrier integrity in a murine model of ***:We used ultra-sensitive single-molecule array technology and enzyme-linked immunosorbent assay methods to measure NFL,NSE,S100B and claudin-5 concentrations in plasma 3 hours ***:We showed that NFL,NSE and S100B were increased at 3 hours ***,ethanol blood concentrations showed an inverse correlation with NSE but not with NFL or ***-5 levels were increased post-injury but no difference was detected compared to ethanol *** increase in claudin-5 post-TBI was correlated with NFL but not with NSE or ***:Ethanol induces an effect on biomarker release in the bloodstream that is different from TBI not influenced by *** could be the basis of investigations into humans.

关键词： Traumatic brain injury Ethanol Biomarkers neurofilament light neuron-specific enolase S100B claudin-5

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Quality and readability of online information resources on insomnia

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Frontiers of Medicine 2017年第3期11卷 423-431页

作者： Yan Ma albert c. Yang Ying Duan Ming Dong albert S. Yeung Division of Interdisciplinary Medicine and Biotechnology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 USA Sleep Medicine center Airforee General Hospital Beijing 100142 China IBM Software Development Lab Littleton MA 01460 USA Depression clinical and Research Program Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA

The internet is a major source for health information. An increasing number of people, including patients with insomnia, search for remedies online; however, little is known about the quality of such information. This study aimed to evaluate the quality and readability of insomnia-related online information. Google was used as the search engine, and the top websites on insomnia that met the inclusion criteria were evaluated for quality and readability. The analyzed websites belonged to nonprofit, commercial, or academic organizations and institutions such as hospitals and universities. Insomnia-related websites typically included definitions （85%）, causes and risk factors （100%）, symptoms （95%）, and treatment options （90%）. cognitive behavioral therapy for insomnia （cBT-I） was the most commonly recommended approach for insomnia treatment, and sleep drugs are frequently mentioned. The overall quality of the websites on insomnia is moderate, but all the content exceeded the recommended reading ease levels. concerns that must be addressed to increase the quality and trustworthiness of online health information include sharing metadata, such as authorship, time of creation and last update, and conflicts of interest; providing evidence for reliability; and increasing the readability for a layman audience.

关键词： insomnia intemet readability information quality health literacy cognitive behavioral therapy treatment

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Manufacturing cost constrained topology optimization for additive manufacturing

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Frontiers of Mechanical Engineering 2019年第2期14卷 213-221页

作者： Jikai LIU Qian cHEN Xuan LIANG albert c.TO Department of Mechanical Engineering and Materials Science University of PittsburghPittsburghPA 15261USA

This paper presents a manufacturing cost constrained topology optimization algorithm considering the laser powder bed additive manufacturing *** optimization for additive manufacturing was recently extensively studied,and many related topics have been ***,metal additive manufacturing is an expensive process,and the high manufacturing cost severely hinders the widespread use of this ***,the proposed algorithm in this research would provide an opportunity to balance the manufheturing cost while pursuing the superior structural perfonnance through topology ***,the additive manufacturing cost model for laser powder bed-bascd process is established in this paper and real data is collected to support this ***,this cost model is transformed into a level set function-based expression,which is integrated into the level set topology optimization problem as a ***,by properly developing the sensitivity result,the metallic additive manufocturing part can be optimized with strictly constrained manufacturing *** of the proposed algorithm is proved by numerical design examples.

关键词： topology optimization manufacturing cost additive manufacturing powder bed

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Recognition of Human Actions through Speech or Voice Using Machine Learning Techniques

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computers, Materials & continua 2023年第11期77卷 1873-1891页

作者： Oscar Peña-cáceres Henry Silva-Marchan Manuela albert Miriam Gil Professional School of Systems Engineering Universidad César VallejoPiura20009Perú Escola Tècnica Superior d’Enginyeria Departament d’InformàticaUniversitat de ValènciaBurjassotValencia46100Spain Department of Mathematics Statistics and InformaticsUniversidad Nacional de TumbesTumbes24000Perú Valencian Research Institute for Artificial Intelligence Universitat Politècnica de ValènciaValencia46022Spain

The development of artificial intelligence(AI)and smart home technologies has driven the need for speech recognition-based *** demand stems from the quest for more intuitive and natural interaction between users and smart devices in their *** recognition allows users to control devices and perform everyday actions through spoken commands,eliminating the need for physical interfaces or touch screens and enabling specific tasks such as turning on or off the light,heating,or lowering the *** purpose of this study is to develop a speech-based classification model for recognizing human actions in the smart *** seeks to demonstrate the effectiveness and feasibility of using machine learning techniques in predicting categories,subcategories,and actions from sentences.A dataset labeled with relevant information about categories,subcategories,and actions related to human actions in the smart home is *** methodology uses machine learning techniques implemented in Python,extracting features using countVectorizer to convert sentences into numerical *** results show that the classification model is able to accurately predict categories,subcategories,and actions based on sentences,with 82.99%accuracy for category,76.19%accuracy for subcategory,and 90.28%accuracy for *** study concludes that using machine learning techniques is effective for recognizing and classifying human actions in the smart home,supporting its feasibility in various scenarios and opening new possibilities for advanced natural language processing systems in the field of AI and smart homes.

关键词： AI machine learning smart home human action recognition

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characterization of Fe_3O_4/P(St-MPEO) Amphiphilic Magnetic Polymer Microspheres

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chemical Research in chinese Universities 2002年第4期18卷 458-461页

作者： cHAN albert S. c. YIP c. W. Open Laboratory of chirotechnology and Department of Applied Biology and chemical Technology Open Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology Hong Kong Polytechnic University Hong Kong P. R. ChinaHong Kong Polytechnic University Hong Kong P. R. China

Amphiphilic magnetic microspheres consisting of styrene and poly(ethylene oxide) macromonomer(MPEO) were prepared by dispersion copolymerization in the presence of Fe_3O_4 magnetic fluid in an ethanol/water medium. The sizes of the magnetic microspheres and their distribution were characterized by means of scanning electron microscopy(SEM). The surface morphology and the average surface roughness of the microspheres were investigated by virtue of atomic force microscopy(AFM). It was found that the microspheres exhibit microscopic phase-separate and the mean square surface roughness of the microspheres increases with increasing MPEO used in the copolymerization. The amphiphilic magnetic microspheres containing 0 4-3 5 mg/g hydroxyl groups could be prepared from MPEO with different concentrations and styrene.

关键词： Amphiphilic magnetic polymer Microsphere copolymerization

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