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Antisense oligonucleotides provide optimism to the therapeutic landscape for tauopathies

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Neural Regeneration Research 2025年第3期20卷 803-804页

作者： Glenn A.harris Lauren R.Hirschfeld Rainwater Charitable Foundation Fort WorthTXUSA

Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.

关键词： tau metabolism diseases

The flattening of spacetime hierarchy of the N,N-dimethyltryptamine brain state is characterized by harmonic decomposition of spacetime(HADES) framework

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National Science Review 2024年第5期11卷 46-55页

作者： Jakub Vohryzek Joana Cabral Christopher Timmermann Selen Atasoy Leor Roseman David J.Nutt Robin L.Carhart-harris Gustavo Deco Morten L.Kringelbach Centre for Eudaimonia and Human Flourishing Linacre CollegeDepartment of Psychiatry University of Oxford Department of Psychiatry University of Oxford Center for Music in the Brain Aarhus University Center for Brain and Cognition Computational Neuroscience GroupDepartment of Information and Communication TechnologiesUniversitat Pompeu Fabra Life and Health Sciences Research Institute School of MedicineUniversity of Minho ICVS/3B's-PT Government Associate Laboratory Centre for Psychedelic Research Department of Brain Sciences Imperial College London Departments of Neurology and Psychiatry University of California San Francisco Institució Catalana de la Recerca i Estudis Avan?ats (ICREA) Department of Neuropsychology Max Planck Institute for Human Cognitive and Brain Sciences School of Psychological Sciences Monash University

The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. Here, we investigate healthy participants taking the serotonergic psychedelic N,N-dimethyltryptamine(DMT) with the Harmonic Decomposition of Spacetime(HADES) framework that can characterize how different harmonic modes defined in space are expressed over time. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition(DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni-to transmodal functional hierarchy of the brain,supporting the leading hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES'dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state.

关键词： spatio-temporal brain dynamics DMT harmonic modes

Dynamic knee valgus kinematics and their relationship to pain in women with patellofemoral pain compared to women with chronic hip joint pain

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Journal of Sport and Health Science 2019年第5期8卷 486-493页

作者： Eric Schmidt marcie.harris-haye. Gretchen B.Salsich Program in Physical Therapy Washington University School of MedicineSt.LouisMO 63108USA Program in Physical Therapy Department of Physical Therapy and Athletic TrainingSaint Louis UniversitySt.LouisMO 63104USA Department of Orthopaedic Surgery Washington University School of MedicineSt.LouisMO 63108USA

Background:Dynamic knee valgus(DKV)is an abnormal movement pattern visually characterized by excessive medial movement of the lower extremity during weight *** in hip and knee kinematic components of DKV may explain the emergence of different pain problems in people who exhibit the same observed movement *** a secondary analysis of exiting data sets,we sought to determine whether hip and knee frontal and transverse plane angles during a functional task differed between women with patellofemoral pain and women with chronic hip joint pain and the relationship between joint-specific kinematics and pain in these 2 pain ***:In the original studies,3-dimensional hip and knee kinematics during a single-limb squat were obtained in 20 women with patellofemoral pain and 14 women with chronic hip joint pain who demonstrated visually classified *** intensity during the squat was assessed in both *** the secondary analysis,kinematic data were compared between pain groups using their respective control groups as a *** each pain group,correlation coefficients were used to determine the relationship between kinematics and pain during the ***:Hip adduction and contralateral pelvic drop were greater in those with chronic hip joint pain compared to those with patellofemoral pain(effect sizes ≥0.40).Greater knee external rotation(r= 0.47,p= 0.04)was correlated with greater knee pain in those with patellofemoral pain,while greater hip adduction(r = 0.53,p = 0.05)and greater hip internal rotation(r = 0.55,p = 0.04)were correlated with greater hip pain in those with chronic hip joint ***:Hip frontal plane motion was greater in those with chronic hip joint pain compared to those with patellofemoral *** both groups,greater abnormal movement at the respective joint(e.g.,knee external rotation in the patellofemoral pain group and hip adduction and internal rotation in the chronic hip joint pain gro

关键词： Anterior knee pain syndrome Femoroacetabular impingement Hip joint Kinematics Knee joint Single-limb squat

Post-operative protein supplementation following orthopaedic surgery: A systematic review

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Sports Medicine and Health Science 2024年第1期6卷 16-24页

作者： Andrew George Brendan M.Holderread Bradley S.Lambert Joshua D.harris Patrick C.McCulloch Houston Methodist Orthopedics and Sports Medicine 6445 Main Street Suite 2300HoustonTX77030USA Houston Methodist Orthopedic Biomechanics Research Laboratory 6670 Bertner AveHoustonTX77030USA

Decreased mechanical loading after orthopaedic surgery predisposes patients to develop muscle *** purpose of this review was to assess whether the evidence supports oral protein supplementation can help decrease postoperative muscle atrophy and/or improve patient outcomes following orthopaedic surgery.A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis(PRISMA).PubMed(MEDLINE),Embase,Scopus,and Web of Science were searched for randomized controlled trials that assessed protein or amino acid supplementation in patients undergoing orthopaedic *** investigators independently conducted the search using relevant Boolean *** outcomes included functional or physiologic measures of muscle atrophy or *** studies including 611 patients(224 males,387 females)were *** studies evaluated protein supplementation after ACL reconstruction(ACLR),3 after total hip arthroplasty(THA),5 after total knee arthroplasty(TKA),and 3 after surgical treatment of hip *** supplementation showed beneficial effects across all types of *** primary benefit was a decrease in muscle atrophy compared to placebo as measured by muscle cross sectional *** authors also demonstrated improved functional measures and quicker achievement of rehabilitation *** supplementation has beneficial effects on mitigating muscle atrophy in the postoperative period following ACLR,THA,TKA,and surgical treatment of hip *** effects often correlate with improved functional measures and quicker achievement of rehabilitation *** research is needed to evaluate long-term effects of protein supplementation and to establish standardized population-specific regimens that maximize treatment efficacy in the postoperative period.

关键词： Orthopaedic surgery Protein supplementation Systematic review Muscle atrophy

From source to emplacement:The origin of leucogranites from the Sikkim-Darjeeling Himalayas,India

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Geoscience Frontiers 2024年第1期15卷 384-401页

作者： Tanya Srivastava Nigel harris Catherine Mottram Kumar Batuk Joshi Nishchal Wanjari Department of Geology Sikkim UniversityGangtokIndia School of Environment Earth&Ecosystem SciencesOpen UniversityMiltonKeynesUK School of the Environment Geography and GeosciencesUniversity of PortsmouthUK National Centre for Earth Science Studies ThiruvananthapuramKeralaIndia

Himalayan leucogranites are important for understanding the tectonic evolution of collision zones in general and the causes of crustal melting in the Himalayan orogen in *** paper aims to understand the melt source and emplacement age of the leucogranites from Sikkim in order to decipher the deep geodynamic processes of the eastern *** U-Pb analysis of the Higher Himalayan Sequence(HHS)metamorphic core reveals a prolonged period of crustal melting between>33 Ma and ca.14 *** and trace element abundances are presented for 27 leucogranites from North Sikkim that are classified into two-mica and tourmaline leucogranite *** are peraluminous in composition,characterized by high SiO2(70.91-74.9 wt.%),Al2O3(13.69-15.82 wt.%),and low MgO(0.13-0.74 wt.%).Elemental abundances suggest that Sikkim Himalayan leucogranites are derived from crustal *** two-mica leucogranites are derived from a metagreywacke source,whereas the tourmaline leucogranites are sourced from metapelitic sources,with inherited zircons indicating an HHS origin for both types.U-Pb zircon geochronology of the two mica leucogranites indicates ages of ca.19-15 Ma,consistent with crustal melting recorded in HHS gneisses from *** from both the two-mica and tourmaline leucogranites yield a crystallization age of ca.15-14 Ma,coeval with movement on the Main Central Thrust and South Tibetan Detachment System which further provides constraints on the timing and mechanism of petrogenesis of leucogranites in the Sikkim Himalayas.

关键词： Leucogranites Gneiss U-Pb geochronology Zircon Monazite Sikkim-Darjeeling Himalayas

Below-Moho Earthquakes of Tibet, Himalaya, the Indian Foreland, and Worldwide: How, Where and Why?

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Acta Geologica Sinica(English Edition) 2024年第S1期 27-29页

作者： Simon L.KLEMPERE WANG Shiqi SONG Xiaohan Jackie R.harris Hitank KASAUNDHAN LIANG Xiaofeng Department of Geophysics Stanford University Department of Geology Carleton College Research School of Earth Sciences Australian National University Institute of Geology and Geophysics Chinese Academy of Sciences

We seek to understand lithospheric rheology by mapping continental earthquake depths relative to Moho depth, across the entire India/Asia convergent orogen, and eventually worldwide. Such mapping has particular value in geothermometry, and potentially in identifying regions of delamination. How: We are extending our Sn/Lg method beyond amplitude ratios of regional seismic phases measured on arrays(array Sn/Lg method, Wang and Klemperer, 2021) to include frequency proxies for earthquake depth relative to Moho(Wang & Klemperer, 2024a, b; harris et al., 2024).

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Exploring the associations between skeletal muscle echogenicity and physical function in aging adults:A systematic review with meta-analyses

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Journal of Sport and Health Science 2024年第6期13卷 820-840页

作者： Dustin J.Oranchuk Stephan G.Bodkin Katie L.Boncella Michael O.harris-Love Muscle Morphology Mechanicsand Performance LaboratoryDepartment of Physical Medicine and RehabilitationUniversity of Colorado Anschutz Medical CampusAuroraCO 80045USA Department of Physical Therapy

Background:Assessment and quantification of skeletal muscle within the aging population is vital for diagnosis,treatment,and injury/disease *** clinical availability of assessing muscle quality through diagnostic ultrasound presents an opportunity to be utilized as a screening tool for function-limiting ***,relationships between muscle echogenicity and clinical functional assessments require authoritative ***,we aimed to(a) synthesize the literature to assess the relationships between skeletal muscle echogenicity and physical function in older adults(≥60 years),(b) perform pooled analyses of relationships between skeletal muscle echogenicity and physical function,and(c) perform sub-analyses to determine between-muscle ***:CINAHL,Embase,MEDLINE,PubMed,and Web of Science databases were systematically searched to identify articles relating skeletal muscle echogenicity to physical function in older ***-of-bias assessments were conducted along with funnel plot ***-analyses with and without sub-analyses for individual muscles were performed utilizing Fisher's Z transformation for the most common measures of physical ***'s Z was back-transformed to Pearson's r for ***:Fifty-one articles(n=5095,female=~2759,male=~2301,72.5± 5.8 years,mean±SD(1 study did not provide sex descriptors))were extracted for review,with previously unpublished data obtained from the authors of 13 *** rectus femoris(n=34) and isometric knee extension strength(n=22) were the most accessed muscle and physical qualities,*** relationship between quadriceps echogenicity and knee extensor strength was moderate(n=2924,r=-0.36(95% confidence interval:-0.38 to-0.32),p <0.001),with all other meta-analyses(grip strength,walking speed,sit-to-stand,timed up-and-go) resulting in slightly weaker correlations(r:-0.34 to-0.23,all p <0.001).Sub-analyses determined minimal differences in predicti

关键词： Correlations Echo intensity Elderly Intramuscular fat Strength

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与镜质体反射率有关的砂岩孔隙度演化

国外地质（成都） 1993年第1期 29-35页

作者： haye.,JB 叶素娟

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变压器安全负荷的预测

电力技术简讯 1991年第1期 16-18页

作者： haye.,WC 王钟麟