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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,Pmanagement of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Assessing dominant factors affecting soil erosion using a portable rainfall simulator

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International Journal of Sediment research 2008年第4期23卷 376-386页

作者： J.VAHABI D.NIKKAMI Soil Conservation and Watershed management research institute

Investigating the causes of soil erosion is difficult in natural conditions owing to the presence of other factors. Without simplifying the experimental conditions, studying soil behavior with its numerous parameters while considering factors such as vegetation cover, topography, and rainfall is difficult and in most conditions impossible. The application of simulation approaches is therefore necessary to simplify the prototype. In this research, the effects of physical soil factors such as texture and antecedent soil moisture, along with land slope and vegetation cover were evaluated in the Taleghan watershed, Iran, using a rainfall simulator and soil erosion plots. For this purpose, a 89 × 120 cm rainfall simulator producing 24.5 and 32 mm/h rainfall intensities of 30 min duration, as a common condition of the study area, was used at 144 locations over soil erosion plots with dimensions of 95 × 125 cm. Plots had slope classes of 12–20 and 20–30 %, different soil textures, different antecedent soil moistures, and medium to poor vegetation cover conditions. It was found that for 24.5 and 32 mm/h rainfall intensities, the sediment yield had high correlations of –0.771 and –0.796 with vegetation cover and slight correlations of 0.045 and 0.029 with land slope respectively. Regression equations for predicting the sediment yield were also developed for different conditions.

关键词： Rainfall simulator Soil erosion Soil physical parameters Vegetation cover Taleghan watershed Iran

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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

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OPTIMAL AND INCENTIVE COMPATIBLE PRICING FOR HETEROGENEOUS PERIODS

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Journal of Systems Science and Systems Engineering 2008年第1期17卷 50-65页

作者： Jian CHEN Nan ZHANG Shuo HUANG research Center for Contemporary management Key Research Institute of Humanities and Social Sciences at Universities School of Economics and Management Tsinghua University Beijing 100084 China

This paper studies a service firm whose business time can be divided into several periods, each providing different value to customers. Heterogeneous service is a major reason resulting in imbalances between supply and demand. Since customers differ in their degree of impatience, firrns can use differential pricing mechanisms to optimize their objectives and match supply with demand in each period, by inducing customers to choose different periods. We study two types of firrns, an internal firm, the objective of which is to maximize the system＇s （including the f＇nan and all the customers） total net value, and a commercial firm, which aims to optimize its own profit. Though impatience factors are customers＇ private information, for each type of firm, we derive the optimal incentive compatible pricing policy, under which all the coming customers will follow the firm＇s assignment, that is, patient customers will buy the service in high-value periods, but their waiting time will be longer, while impatient customers will enter into the low-value periods, but they will be compensated by shorter waiting times. Furthermore, in the internal firm, we also prove that this mechanism enables the decentralization of decisions, while maintaining centralized system-wide optimality. Numerical analysis shows that when there is sufficient capacity, the internal firm does not always need to set lower prices than the commercial firm in every period.

关键词： Delay cost queuing differential pricing information asymmetry incentive compatibility

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Beyond statistical significance:Embracing minimal clinically important difference for better patient care

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World Journal of Methodology 2025年第1期15卷 33-41页

作者： Naveen Jeyaraman Madhan Jeyaraman Swaminathan Ramasubramanian Sangeetha Balaji Sathish Muthu Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia Department of research Methods Orthopaedic Research GroupCoimbatore 641045Tamil NaduIndia Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia Department of Biotechnology Faculty of EngineeringKarpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia Department of Orthopaedics Government Medical CollegeKarur 639004Tamil NaduIndia

The minimal clinically important difference(MCID)represents a pivotal metric in bridging the gap between statistical significance and clinical relevance,addressing the direct impact of medical interventions from the patient's *** comprehensive review analyzes the evolution,applications,and challenges of MCID across medical specialties,emphasizing its necessity in ensuring that clinical outcomes not only demonstrate statistical significance but also offer genuine clinical utility that aligns with patient expectations and *** discuss the evolution of MCID since its inception in the 1980s,its current applications across various medical specialties,and the methodologies used in its calculation,highlighting both anchor-based and distribution-based ***,the paper delves into the challenges associated with the application of MCID,such as methodological variability and the interpretation difficulties that arise in clinical *** for the future include standardizing MCID calculation methods,enhancing patient involvement in setting MCID thresholds,and extending research to incorporate diverse global *** steps are critical to refining the role of MCID in patient-centered healthcare,addressing existing gaps in methodology and interpretation,and ensuring that medical interventions lead to significant,patient-perceived improvements.

关键词： Minimal clinically important difference Patient-centered care Clinical relevance Global health

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CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

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Neural Regeneration research 2025年第8期20卷 2420-2432页

作者： Lin Yin Yalan Xu Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li Yin Wang Peifeng Li Hai Zhu Dong Wang Jing Li institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina College of Life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina Department of Urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang Song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Advances and challenges in diagnosing and managing adult autoimmune enteropathy

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World Journal of Gastroenterology 2025年第2期31卷 128-131页

作者： Grigorios Christodoulidis Sara E Agko Marina N Kouliou Konstantinos E Koumarelas Dimitris Zacharoulis Department of General Surgery University Hospital of LarissaLarissa 41110Greece Department of Intensive Care Unit Asklepios Paulinen Clinic WiesbadenWiesbaden 65197Germany Department of Emergency Medicine General Hospital of LarissaLarissa 41221Greece Department of Surgery University Hospital of LarissaLarissa 41334Greece

Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous *** has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac *** diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe *** criteria emphasize characteristic histological findings and exclusion of other causes of villous *** is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial *** primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional *** the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient *** research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.

关键词： Autoimmune enteropathy Diagnosis Prognosis Adult autoimmune enter-opathy and challenges Autoimmune enteropathy and treatment Autoimmune enteropathy and diagnostic criteria Pathophysiology of autoimmune enteropathy

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Effect of recombinant and native buffalo OVGP1 on sperm functions and in vitro embryo development: a comparative study

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Journal of Animal Science and Biotechnology 2018年第1期9卷 99-110页

作者： Suman Choudhary A.Kumaresan Manish Kumar Shivani Chhillar Hrudananda Malik Sudarshan Kumar Jai K.Kaushik Tirtha K.Datta Ashok K.Mohanty Animal Biotechnology Centre National Dairy Research Institute Livestock and Production management Section National Dairy Research Institute

Background： An oviduct-specific glycoprotein, OVGP1, is synthesized and secreted by non-ciliated epithelial cells of the mammalian oviduct which provides an essential milieu for reproductive functions. The present study reports the effects of recombinant buffalo OVGP1 that lacks post-translational modifications, and native Buffalo OVGP1 isolated from oviductal tissue, on frozen-thawed sperm functions and in vitro embryo ***： The proportion of viable sperms was greater（P 〈 0.05） in the recombinant OVGP1-treated group compared to the native OVGP1-treated group at 2 h, 3 h, and 4 h of incubation. The proportion of motile sperms at3 h and 4 h of incubation; and membrane-intact sperms at 4 h was greater（P 〈 0.05） in the native OVGP1-treated group compared to the control and recombinant OVGP1-treated groups. The proportion of capacitated and acrosome-reacted sperms was greater（P 〈 0.05） in the native OVGP1-treated group compared to the recombinant OVGP1 group at 4 h. The rates of cleavage of embryos and their development to the blastocyst stage were greater（P 〈 0.05） in the presence of either native or recombinant OVGP1 in comparison to control at 10 μg/mL concentration as compared to 5 or 20 μg/***： The study suggests that both native and recombinant OVGP1 impart a positive effect on various sperm features and in vitro embryo development. However, native OVGP1 was found to have a more pronounced effect in comparison to recombinant non-glycosylated OVGP1 on various sperm functions except viability. Hence,our current findings infer that glycosylation of OVGP1 might be essential in sustaining the sperm functions but not the in vitro embryo development.

关键词： Blastocyst Capacitation Fertilization Glycoprotein In vitro fertilization Oestrus Semen Sperm

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PROCESS CAPABILITY ANALYSIS AND ESTIMATION SCHEME FOR AUTOCORRELATED DATA

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Journal of Systems Science and Systems Engineering 2010年第1期19卷 105-127页

作者： Jing SUN Shengxian WANG Zhihui FU research Center for Contemporary management,Key research institute of Humanities and Social Sciences at Universities,School of Economics and management,Tsinghua University,Beijing 100084,P.R.China research Center for Contemporary management Key Research Institute of Humanities and Social Sciences at Universities School of Economics and Management Tsinghua University Beijing P.R. China

Autocorrelation is prevalent in continuous production processes, such as the processes in the chemical and pharmaceutical industries. With the development of measurement technology and data acquisition technology, sampling frequency is getting higher and the existence of autocorrelation cannot be ignored. This paper analyzes five estimation schemes of process capability for autocorrelated data. Comparisons among these schemes are discussed for small sample and large sample. In conclusion, this paper gives a procedure of process capability analysis for autocorrelated data.

关键词： Autocorrelation estimation process capability analysis statistical process control

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