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Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in lrp5

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骨研究:英文版 2023年第3期11卷 595-606页

作者： Cassandra R.Diegel Ina Kramer Charles Moes Gabrielle E.Foxa Mitchell J.McDonald Zachary B.Madaj Sabine Guth Jun liu jennifer l.harris Michaela Kneissel Bart O.Williams Department of Cell Biology Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Diseases of Aging and Regenerative Medicine Novartis Institutes for Biomedical ResearchCH-4002 BaselSwitzerland Bioinformatics and Biostatistics Core Van Andel Institute333 Bostwick Ave.NEGrand RapidsMI 49503USA Oncology Novartis Institutes for Biomedical ResearchSan DiegoCA 92121USA

Proper regulation of Wnt signaling is critical for normal bone development and *** in several Wnt signaling components,which increase the activity of the pathway in the skeleton,cause high bone mass in human subjects and mouse *** bone mass is often accompanied by severe headaches from increased intracranial pressure,which can lead to fatality and loss of vision or hearing due to the entrapment of cranial *** addition,progressive forehead bossing and mandibular overgrowth occur in almost all *** that would provide symptomatic relief in these subjects are ***-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled *** inhibition of porcupine is a highly selective method of Wnt signaling *** treated three different mouse models of high bone mass caused by aberrant Wnt signaling,including homozygosity for loss-of-function in Sost,which models sclerosteosis,and two strains of mice carrying different point mutations in lrp5(equivalent to human G171V and A214V),at 3 months of age with porcupine inhibitors for 5–6 *** significantly reduced both trabecular and cortical bone mass in all three *** demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.

关键词： homeostasis function mass

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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05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

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Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

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World Journal of Diabetes 2024年第4期15卷 598-605页

作者： Vasileios K Mavroeidis jennifer Knapton Francesca Saffioti Daniel l Morganstein Department of HPB Surgery Bristol Royal InfirmaryUniversity Hospitals Bristol and Weston NHS Foundation TrustBristol BS28HWUnited Kingdom Department of Gastrointestinal Surgery Southmead HospitalNorth Bristol NHS TrustBristol BS105NBUnited Kingdom Department of Academic Surgery Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom Department of Gastroenterology and Hepatology Oxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom UCl Institute for liver and Digestive Health University College LondonLondon NW32PFUnited Kingdom Department of Endocrinology Chelsea and Westminster Hospital NHS Foundation TrustLondon SW109NHUnited Kingdom Department of Gastrointestinal Unit Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom

Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic *** centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved *** this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic *** 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and *** preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative *** incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe *** involvement of a specialist diabetes team is essential to ensure a holistic *** the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve *** various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required *** need for perioperative support of diabetic

关键词： Pancreatectomy Pancreatoduodenectomy Whipple’s Pancreatitis Diabetes specialist Type 3c pancreatogenic diabetes mellitus

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Primary care providers practice patterns regarding female pelvic floor disorders

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Family Medicine and Community Health 2024年第1期12卷 9-15页

作者： Anna Weimer jennifer l Hallock Chi Chiung Grace Chen Magee-Women's Hospital of UPMC PittsburghPennsylvaniaUSA Kaiser Permanente Northern California SacramentoCaliforniaUSA Johns Hopkins Medical Institutions Campus BaltimoreMarylandUSA

Introduction Pelvic floor disorders(PFDs)pose substantial physical and psychological burdens for a growing number of *** the ubiquity of these conditions and known patient reluctance to seek care,primary care providers(PCPs)have a unique opportunity to increase treatment and provide appropriate referrals for these *** An online survey was administered to PCPs to assess provider practices,knowledge,comfort managing and ease of referral for *** regression was used to assess the association between demographic/practice characteristics of PCPs and two primary outcomes of interest:discomfort with management and difficulty with referral of *** Of the 153 respondents to the survey,more felt comfortable managing stress urinary incontinence(SUI)and overactive bladder(OAB),compared with pelvic organ prolapse(POP)and faecal incontinence(FI)and were less likely to refer patients with urinary *** providers elicited symptoms for POP and FI as compared with SUI and *** variables that were significantly associated with discomfort with management varied by PFD,but tended to correlate with less exposure to PFDs(eg,those with fewer years of practice,and internal medicine and family physicians as compared with geriatricians);whereas the factors that were significantly associated with difficulty in referral,again varied by PFD,but were related to practice characteristics(eg,specialist network,type of practice,practice setting and quantity of patients).Conclusion These findings highlight the need to increase PCPs awareness of PFDs and develop effective standardised screening protocols,as well as collaboration with pelvic floor specialists to improve screening,treatment and referral for patients with PFDs.

关键词： bladder floor difficulty

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Floor dust erosion during early stages of coal dust explosion development

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International Journal of Mining Science and Technology 2019年第6期29卷 825-830页

作者： Marcia l.harris Michael J.Sapko Center for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) Pittsburgh Mining Research Division (PMRD)

An ignition of methane and air can generate enough air flow to raise mixtures of combustible coal and rock *** expanding high temperature combustion products ignite the suspended dust mixture and will continue to propagate following the available combustible fuel *** the concentration of the dispersed rock dust is sufficient,the flame will stop ***-scale explosion tests were conducted within the National Institute for Occupational Safety and Health(NIOSH)lake lynn Experimental Mine(llEM)to measure the dynamic pressure history and the post-explosion dust scour *** aim of this effort is to provide quantitative data on depth of dust removal during the early stages of explosion development and its relationship to the depth of floor dust collected for assessing the incombustible content most likely to participate in the combustion *** experimental work on dust removal on is not only important for coal mine safety but also for industrial dust explosions.

关键词： Underground Coal dust Explosion Dust sampling

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Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

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Global Health Journal 2024年第1期8卷 11-15页

作者： Max J.Goodman jennifer livschitz Ji Won Kim Megan l.Schultz Medical College of Wisconsin MilwaukeeWI 53226USA Department of Pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for *** medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such *** is important that medical students have nuanced global medical perspectives and can contribute to the global medical ***:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health ***:In 2021,a novel medical student PPC was established that began between an American and Japanese medical *** a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online *** total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income *** primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their *** February 2022,American PPC members were emailed a qualitative survey to assess the PPC's ***:The survey was completed by 42%of American PPC members,95%of which were 22-26 *** were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural *** a global communication platform for students during medical school education may be an additional way to train aspiring global l

关键词： Pen-pals Medical student Global health Cultural competency

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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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A predictive model for ethylene-mediated auxin and cytokinin patterning in the Arabidopsis root

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Plant Communications 2024年第7期5卷 120-137页

作者： Simon Moore George Jervis jennifer F.Topping Chunli Chen Junli liu Keith lindsey Department of Biosciences Durham UniversitySouth RoadDurham DH13LEUK Hubei Hongshan laboratory College of Life Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China National Key laboratory for Germplasm Innovation and Utilization for Fruit and Vegetable Horticultural Crops Huazhong Agricultural UniversityWuhanHubei 430070China

The interaction between auxin and cytokinin is important in many aspects of plant *** measurements of both auxin and cytokinin concentration and reporter gene expression clearly show the coexistence of auxin and cytokinin concentration patterning in Arabidopsis root ***,in the context of crosstalk among auxin,cytokinin,and ethylene,little is known about how auxin and cytokinin concentration patterns simultaneously emerge and how they regulate each other in the Arabidopsis *** work utilizes a wide range of experimental observations to propose a mechanism for simultaneous patterning of auxin and cytokinin *** addition to revealing the regulatory relationships between auxin and cytokinin,this mechanism shows that ethylene signaling is an important factor in achieving simultaneous auxin and cytokinin patterning,while also predicting other experimental *** the mechanism with a realistic in silico root model reproduces experimental observations of both auxin and cytokinin *** made by the mechanism can be compared with a variety of experimental observations,including those obtained by our group and other independent experiments reported by other *** of these predictions include patterning of auxin biosynthesis rate,changes in PIN1 and PIN2 patterns in pin3,4,7 mutants,changes in cytokinin patterning in the pls mutant,PlS patterning,and various trends in different *** research reveals a plausible mechanism for simultaneous patterning of auxin and cytokinin concentrations in Arabidopsis root development and suggests a key role for ethylene pattern integration.

关键词： Arabidopsis root auxin patterning cytokinin patterning ethylene signaling in silico digital root spatiotemporal modeling

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CSPP1 stabilizes microtubules by capping both plus and minus ends

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Journal of Molecular Cell Biology 2024年第2期16卷 36-46页

作者： Zhikai Wang Wenwen Wang Shuaiyu liu Fengrui Yang Xu liu Shasha Hua lĳuan Zhu Aoqing Xu Donald lHill Dongmei Wang Kai Jiang jennifer lippincott-Schwartz Xing liu Xuebiao Yao MOE Key laboratory for Membraneless Organelles and Cellular Dynamics Center for Advanced Interdisciplinary Science and Biomedicine of IHMUniversity of Science and Technology of China School of Life SciencesHefei 230027China Anhui Key laboratory for Cellular Dynamics and Chemical Biology Hefei National Research Center for Interdisciplinary Sciences at the MicroscaleHefei 230027China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430071China Comprehensive Cancer Center University of AlabamaBirminghamAL 35233USA Janelia Research Campus Howard Hughes Medical InstituteAshburnVA 20147USA

Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular ***,how these free MT tips are stabilized remains poorly ***,we report that centrosome and spindle pole protein 1(CSPP1)caps and stabilizes both plus and minus ends of static ***-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends,whose dynamic instability was concomitantly ***,MT ends in CSPP1-overexpressing cells were hyper-stabilized,while those in CSPP1-depleted cells were much more *** CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting ***,CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated *** findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.

关键词： CSPP1 microtubule plus end minus end capping

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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 ll 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 lyses determined minimal differences in predicti

关键词： Correlations Echo intensity Elderly Intramuscular fat Strength

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