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Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

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Acta Pharmaceutica Sinica B 2023年第1期13卷 213-226页

作者： Ahmed Haider Xiaoyun Deng Olivia Mastromihalis Stefanie K.Pfister Troels E.Jeppesen Zhiwei Xiao Vi Pham Shaofa Sun Jian rong Chunyu Zhao Jiahui Chen Yinlong Li theresa r.connors April T.Davenport James B.Daunais Vahid Hosseini Wenqing ran Arthur Christopoulos Lu Wang Celine Valant Steven H.Liang Department of radiology Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical SchoolBostonMA 02114USA Department of Nuclear Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Drug Discovery Biology Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia Neuromedicines Discovery Centre Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleVIC 3052Australia Hubei Collaborative Innovation Centre for Non-power Nuclear Technology College of Nuclear Technology&Chemistry and BiologyHubei University of Science and TechnologyXianning 437100China Department of Neurology Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Physiology and Pharmacology Wake Forest School of MedicineWinston SalemNC 27157USA Terasaki Institute for Biomedical Innovation(TIBI) Los AngelesCA 90024USA Center of Cyclotron and PET radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI Centerthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor4(M4)in schizophrenia and dementia with Lewy bodies,however,a clinically validated M4positron emission tomography(PET)radioligand is currently *** such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the ***-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12—a subtype-selective positive allosteric modulator(PAM).The radiofluorinated analogue,[18F]12,was synthesized in 28±10%radiochemical yield,>37 GBq/μmol and an excellent radiochemical purity>99%.Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of[18F]12 for the M4-rich ***,in the presence of carbachol,a significant increase in tracer binding was observed in the rat striatum,which was reduced by>60%under blocking conditions,thus indicating that orthosteric ligand interaction is required for efficient binding o f[18F]12 to the allosteric ***,however,the presence of carbachol was not required for high specific binding in the non-human primate(NHP)and human striatum,and did not further improve the specificity and selectivity of[18F]12 in higher *** results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP,where peak brain uptake of[18F]12 was found in the putamen and temporal *** conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising *** availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

关键词： Muscarinicacetylcholine receptor Positronemission tomography Neuroimaging Neuropharmacology Neurological disorders

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Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

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Neural regeneration research 2024年第8期19卷 1728-1733页

作者： Sanika M.Joshi theresa Currier Thomas Nafisa M.Jadavji College of Osteopathic Medicine Midwestern UniversityGlendaleCAUSA Department of Biomedical Sciences Midwestern UniversityGlendaleCAUSA Department of Child Health College of Medicine–PhoenixUniversity of ArizonaPhoenixAZUSA College of Veterinary Medicine Midwestern UniversityGlendaleCAUSA Department of Neuroscience Carleton UniversityOttawaCanada

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals ***-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic ***,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more *** aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain ***,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury *** search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and *** focus of each literature search was basic science *** year of publication in the literature searches was not *** analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to *** r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain *** details of supplementation post-traumatic brain injury need to be further ***,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model *** investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

关键词： folic acid nicotinamide one-carbon metabolism riboflavin traumatic brain injury vitamin B12 vitamin B2 vitamin B3

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Transjugular Intrahepatic Portosystemic Shunt Linked to Increased risk of Hepatocellular Carcinoma:A VA Matched Cohort Study

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 534-538页

作者： Shalini Bansal Tamar Taddei rebecca Wells Marina Serper theresa Bittermann Nadim Mahmud David E.Kaplan Sidney Kimmel Medical College at Thomas Jefferson University PhiladelphiaPAUSA Division of Gastroenterology and Hepatology Perelman School of Medicine University of PennsylvaniaPhiladelphiaPAUSA Corporal Michael J.Crescenz VA Medical Center PhiladelphiaPAUSA Division of Gastroenterology and Hepatology Yale University School of MedicineNew HavenCTUSA VA Connecticut Healthcare System West HavenCTUSA

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and often evolves from regenerating nodules in liver *** there have been significant advances in the treatment of HCC,the overall prognosis in patients with a large tumor burden,vascular invasion,or extrahepatic spread remains poor.1 The magnitude of liver stiffness in cirrhosis has been consistently associated with an increased risk of development of HCC.

关键词： Carcinoma invasion cirrhosis

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Clinical studies in COVID-related olfactory disorders:review of an institutional experience

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 129-136页

作者： theresa Tharakan Dorina Kallogjeri Jay F.Piccirillo Department of Otolaryngology-Head and Neck Surgery Clinical Outcomes Research OfficeSchool of MedicineWashington University in St LouisSt LouisMissouriUSA

Objective:To share a single institutional experience with clinical research on COVID-related olfactory dysfunction(OD).Data Source/Method:Narrative review of published original data and ongoing clinical trials on COVID-related OD at Washington University from 2020 to ***:There were three new diagnostic-/patient-reported outcome measures developed and *** report five clinical trials of interventions for COVID-related olfactory disorders:combined Visual-Olfactory Training(VOLT)with patient-preferred scents versus standard olfactory training(VOLT trial),oral gabapentin versus placebo(Gabapentin for the relief of Acquired Chemosensory Experience trial),nasal theophylline irrigations versus placebo(Smell Changes and Efficacy of Nasal Theophylline trial),stellate ganglion block(single-arm),and mindfulness-based stress reduction(MBSr)versus lifestyle intervention(MBSr trial).Conclusions:Initial intervention trials for COVID-related OD have shown potential for improving subjective and objective olfactory ***,there remains no gold standard treatment that definitively outperforms placebo in controlled ***,continued investigation of novel therapeutic strategies for COVID-related OD is necessary to maximize olfactory outcomes for affected patients.

关键词： chemosensory disorders COVID olfactory dysfunction

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Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena Huber Hartmann raifer Torsten Frech Svenja Nolte theresa Dombrowski Franz Cemic Natascha Sommer robert ringseis Klaus Eder Karsten Krüger Christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(Or)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly regulatory T cells Subclinical atherosclerosis

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Study of Factors Associated with the Practice of Vaccination against COVID-19 among Medical Science Students in Dakar (Senegal)

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Open Journal of Epidemiology 2024年第2期14卷 199-220页

作者： Chafika Ibrahim Zanguina theresa Stella Esperance Fouckou Moko Jean Augustin Diegane Tine Department of Medicine El Hadji Ibrahima Niasse University of Dakar Dakar Senegal Department of Preventive Medicine and Public Health Faculty of Medicine Pharmacy and Odontology Cheikh Anta Diop University Dakar Senegal

Introduction: Almost a year after the start of the COVID-19 pandemic, Senegal embarked on a vaccination campaign to protect its population. The objective of this study was to identify the factors influencing the COVID-19 vaccination practices within a health training university in Dakar. Methodology: This was a cross-sectional, descriptive and analytical study carried out from October 21 2021 to February 21 2022 among students at the Elhadj Ibrahima Niass private University in Dakar, Senegal. A 28-question online questionnaire was sent to all students enrolled at the university during this period. results: Of the 576 students who responded, the average age was 22.60 years, with females predominating (57.81%). Medical students accounted for 66.14% of participants, pharmacy 22.40% and dental surgery 11.46%. Of these, 42.01% were bachelor’s students, 29.51% master’s students and 28.47% doctoral students. Vaccination coverage was 50.35%. Students who considered COVID-19 to be very dangerous were more likely to be vaccinated (Or = 5.05 [2.24-11.9]). Those with poor knowledge of vaccines were less likely to be vaccinated (Or = 0.07 [0.03-0.18]), as were those with poor knowledge of contraindications to vaccination (Or = 0.49 [0.28-0.86]). No association was found between vaccination status and socio-demographic or educational characteristics. Conclusion: In view of the importance of knowledge about COVID-19 vaccination, our results suggest that it is important to involve health students in the Ministry of Health’s awareness-raising strategies, because their support is necessary for better public awareness.

关键词： COVID-19 Vaccination Health Students Senegal

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科学新闻 2024年第1期 63-64页

作者： theresa Mercer 倪伟波克兰菲尔德大学

“我很抱歉。”我含泪对首席研究员（PI）解释道，我不能按原计划休完产假回来了。在成为母亲之前，我曾天真地认为孩子会适合我的学业计划。但现在，随着假期即将结束，我意识到自己不能像以前那样简单地生活下去。一方面，我搬到了这...

“我很抱歉。”我含泪对首席研究员（PI）解释道，我不能按原计划休完产假回来了。在成为母亲之前，我曾天真地认为孩子会适合我的学业计划。但现在，随着假期即将结束，我意识到自己不能像以前那样简单地生活下去。一方面，我搬到了这个国家的另一边和丈夫一起，他拥有终身教职。我原本以为我们可以建立一个与通勤相适应的日常生活，但现在发现这既不现实，也不可持续。另一方面，我想要一些时间来学习做一个妈妈。我不想永远离开科学，但我担心这个决定可能意味着学术生涯的结束——可我别无选择。

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Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

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Journal of Sport and Health Science 2024年第5期13卷 621-630页

作者： Yujia(Susanna)Qiao Terri L.Blackwell Peggy M.Cawthon Paul M.Coen Steven r.Cummings Giovanna Distefano Samaneh Farsijani Daniel E.Forman Bret H.Goodpaster Stephen B.Kritchevsky theresa Mau Frederico G.S.Toledo Anne B.Newman Nancy W.Glynn Department of Epidemiology School of Public HealthUniversity of PittsburghPittsburghPA 15261USA San Francisco Coordinating Center California Pacific Medical Center Research InstituteSan FranciscoCA 94143USA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCA 94143USA Translational research Institute AdventHealthOrlandoFL 32804USA Department of Medicine(Geriatrics and Cardiology) University of Pittsburghand GeriatricsResearchEducationand Clinical Center(GRECC)VA Pittsburgh Healthcare SystemPittsburghPA 15261USA Department of Internal Medicine Section on Gerontology and Geriatric MedicineWake Forest School of MedicineWinston-SalemNC 27109USA Division of Endocrinology and Metabolism Department of MedicineUniversity of PittsburghPittsburghPA 15261USA

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older ***,many studies reporting these effects were based on self-reported PA or structured exercise ***,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle ***:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 ***-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)*** regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary *** a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle ***:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(pr ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.

关键词： Aging Exercise Mitochondria

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Evaluation of Ear and Facial Indices of Ibibio and Efik Female Children of Akwa Ibom and Cross river States, Nigeria

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Journal of Biosciences and Medicines 2024年第7期12卷 1-8页

作者： Nsikak Michael Umoh Kelechi Chinkata Uruakpa Eru Eru Mba Michael Effiong Oku theresa Isamoh Nnenna Williams Eric Agim Agaba Samson Omini Paulinus John Emah Gabriel Udo-Affah Department of Anatomical Sciences Faculty of Basic Medical Sciences College of Medical Sciences University of Calabar Calabar Nigeria

Background: The ear and face are indispensable and distinctive features for hearing and identification. Objectives: This study was designed to generate anthropometric data of the ear and facial indices of females of Efik and Ibibio children in Cross river and Akwa Ibom States, show morphological and aesthetic differences and ethnicity. Methods: A total of 600 female children (300 Efiks and 300 Ibibios) aged 2 to 10 years that met the inclusion criteria were chosen from selected primary schools in Calabar Municipality, Calabar South of Cross river State and from Uyo, Itu of Akwa Ibom State, Nigeria. Standardized measurements of face length, face width, ear length, and ear width were taken with a spreading caliper;the facial (proscopic) and ear (auricular) indices were determined. results: Efik subjects presented a mean face length of 8.36 ± 0.06 cm, face width of 11.04 ± 0.04 cm, ear length of 4.92 ± 0.02 cm, and ear width of 3.06 ± 0.01 cm. Ibibio subjects had mean values for face length, face width, ear length, and ear width as 8.17 ± 0.05 cm, 10.75 ± 0.05 cm, 4.77 ± 0.03 cm, and 2.94 ± 0.02 cm respectively. The mean facial index and ear index for Efik subjects were 75.68 ± 0.31 and 62.16 ± 0.27 respectively;while the mean facial and ear indices for Ibibio subjects were 74.79 ± 0.36 and 61.80 ± 0.34 respectively. Statistical analysis demonstrated significant differences in face length, ear length, ear width and facial index, with the Efik subjects having higher values than Ibibio subjects (p Conclusion: The results showed hypereuryproscopic face as the prevalent face type among females of both ethnic groups, therefore can be of importance in sex, ethnic, and racial differentiation, and in clinical practice, aesthetics and forensic medicine.

关键词： Anthropometry Ear Facial Indices Identification Nigeria

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Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

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World Journal of Gastroenterology 2009年第3期15卷 270-279页

作者： theresa A Mikhailov Sylvia E Furner Department of Pediatrics Division of Critical CareMedical College of Wisconsin9000 W.Wisconsin AvenueMS# 681MilwaukeeWI 53226United States School of Public Health Division of Epidemiology and BiostatisticsUniversity of Illinois Chicago 1603 W.Taylor St.M/C 923ChicagoIL 60612United States

Inflammatory bowel disease is a chronic,debilitating disorder of the gastrointestinal *** etiology of inflammatory bowel disease has not been elucidated,but is thought to be multifactorial with both environmental and genetic influences.A large body of research has been conducted to elucidate the etiology of inflammatory bowel *** article reviews this literature,emphasizing the studies of breastfeeding and the studies of genetic factors,particularly NOD2 polymorphisms.

关键词： Inflammatory bowel disease Crohn'sdisease Ulcerative colitis Etiology risk factors Protective factors NOD2/CArD15 Single nucleotidepolymorphisms

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