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FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer’s Disease

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Advances in Molecular Imaging 2014年第2期4卷 15-26页

作者： John Murray Wai H. Tsui Yi Li Pauline McHugh Schantel Williams megan cummings Elizabeth Pirraglia Lilja Solnes Ricardo Osorio Lidia Glodzik Shankar Vallabhajosula Alexander Drzezga Satoshi Minoshima Mony J. de Leon Lisa Mosconi New York University School of Medicine New York USA University of Cologne Cologne Germany University of Washington Seattle USA Weill Cornell Medical College New York USA

Having a parent affected by late-onset Alzheimer’s disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid-β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. Methods: FDG- and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH-). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/-) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). Results: Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH- (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%;p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH- (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful. Conclusions: Automated analysis of FDG- and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH-subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger c

关键词： Alzheimer’s Disease Early Detection Positron Emission Tomography Amyloid Imaging Glucose Metabolism Normal Aging

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(p<0.05).Light activity was not associated with maxOXPHOS or 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

Prostaglandin E1 administration post liver transplantation and renal outcomes:A retrospective single center experience

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World Journal of Transplantation 2024年第4期14卷 101-109页

作者： Vinay Jahagirdar Mohamed Ahmed Ifrah Fatima Hassam Ali Laura Alba John H Helzberg Lee S cummings Matthew Wilkinson Jameson Forster Alisa Likhitsup Department of Internal Medicine Saint Luke’s Health System of Kansas City and the University of Missouri-Kansas CityKansas CityMO 64111United States Department of Gastroenterology and Hepatology East Carolina University Brody School of MedicineGreenvilleNC 27834United States Division of Internal Medicine Department of Gastroenterology and HepatologySaint Luke’s Health System of Kansas City and University of Missouri-Kansas CityKansas CityMO 64111United States Department of Surgery University of Missouri-Kansas City and Transplant SurgerySaint Luke’s Hospital of Kansas CityKansas CityMO 64111United States Department of Gastroenterology and Hepatology University of MichiganAnn ArborMI 48109United States

BACKGROUND Prostaglandin E1(PGE1),or alprostadil,is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation(LT).However,the benefits of PGE1 on renal function after LT have not yet been well *** To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney *** This retrospective study included all patients who underwent liver or liverkidney transplant at our institution from January,2011 to December,*** were classified based on whether they received ***1 was administered post-LT to those with transaminases>1000 U/L in the immediate postoperative ***,post-LT treatments and/or complications,renal function,and survival were *** logistic regression analysis was performed,and a two-tailed P value<0.05 was considered statistically *** A total of 145 patients underwent LT,with 44(30%)receiving *** patient characteristics were comparable,except the PGE1 group had significantly higher aspartate aminotransferase(AST)(1961.9 U/L±1862.3 U/L vs 878 U/L±741.4 U/L,P=0.000),alanine aminotransferase(1070.6 U/L±895 U/L vs 547.7 U/L±410 U/L,P=0.000),international normalized ratio on post-LT day 1(2±0.74 vs 1.8±0.4,P=0.03),a longer intensive care unit stay(8.1 days±11.8 days vs 3.8 days±4.6 days,P=0.003),more vasopressor use(55.53 hours±111 hours vs 16.33 hours±26.3 hours,P=0.002),and higher immediate postoperative complications(18.6%vs 4.9%,P=0.04).The PGE1 group also had a significantly higher 90-day readmission rate(29.6%vs 13.1%,P=0.02)and lower 1-year liver graft survival(87.5%vs 98.9%,P=0.005).However,30-day readmission(31.6%vs 27.4%,P=0.64),LT complications(hepatic artery thrombosis,biliary complications,rejection of liver graft,cardiomyopathy),1-year patient survival(96.9%vs 97.8%,P=0.77),overall liver graft survival,and overall patient survival were similar between t

关键词： Liver transplantation Alprostadil Protective agents Transplant Prostaglandin E1

Debris Fan Produced by Failure of Canyon-Blocking Pyroclastic Flows

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Disease modification and Neuroprotection in neurodegenerative disorders

Journal of Water Resource and Protection（水资源与保护） 2024年第5期 328页

作者： Michael L. cummings

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Translational Neurodegeneration 2017年第1期6卷 232-238页

作者： Jeffrey cummings Cleveland Clinic Lou Ruvo Center for Brain Health 888 W Bonneville AveLas VegasNV 89106USA

Background:Disease modifying therapies(DMTs)are urgently needed for neurodegenerative diseases(NDD)such as Alzheimer’s disease(AD)and many other disorders characterized by protein aggregation and *** advances in understanding the neurobiology of NDD,there are no approved ***:Defining disease-modification is critical to drug-development programs.A DMT is an intervention that produces an enduring change in the trajectory of clinical decline of an NDD by impacting the disease processes leading to nerve cell death.A DMT is neuroprotective,and neuroprotection will result in disease *** modification can be demonstrated in clinical trials by a drug-placebo difference in clinical outcomes supported by a drug-placebo difference on biomarkers reflective of the fundamental pathophysiology of the ***,disease modification can be supported by findings on a staggered start or delayed withdrawal clinical trial *** multiple biomarkers is necessary to support a comprehensive view of disease ***:Disease modification is established by demonstrating an enduring change in the clinical trajectory of an NDD based on intervention in the fundamental pathophysiology of the disease leading to nerve cell *** data are collected in clinical *** defining a DMT will assist in NDD drug development programs.

关键词： Alzheimer’s disease Frontotemporal dementia Progressive supranuclear palsy Corticobasal degeneration Amyotropic lateral sclerosis Multiple system atrophy Disease modification Disease modifying therapy

The endogenous progenitor response following traumatic brain injury:a target for cell therapy paradigms

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Neural Regeneration Research 2022年第11期17卷 2351-2354页

作者： Anna Badner Brian J.cummings Department of Psychiatry and Behavioral Sciences Stanford UniversityPalo AltoCAUSA Sue and Bill Gross Stem Cell Center University of California-IrvineIrvineCAUSA Institute for Memory Impairments and Neurological Disorders University of California-IrvineIrvineCAUSA Physical Medicine and Rehabilitation University of California-IrvineIrvineCAUSA Department of Anatomy and Neurobiology University of California-IrvineIrvineCAUSA

Although there is ample evidence that central nervous system progenitor pools respond to traumatic brain injury,the reported effects are variable and likely contribute to both recovery as well as *** a better understanding of the diverse progenitor populations in the adult brain and their niche-specific reactions to traumatic insult,treatments can be tailo red to enhance the benefits and dampen the deleterious effects of this *** review provides an overview of endogenous precursors,the associated effects on cognitive recovery,and the potential of exogenous cell therapeutics to modulate these endogenous repair *** the hippocampal dentate gyrus and subventricular zone of the lateral ventricles,more recently identified sites of adult neurogenesis,the meninges,as well as circumventricular organs,are also discussed as targets for endogenous ***,this review highlights that progenitor prolife ration alone is no longer a meaningful outcome and studies must strive to better chara cterize precursor spatial localization,transcriptional profile,morphology,and functional synaptic *** improved insight and a more targeted approach,the stimulation of endogenous neurogenesis remains a promising strategy for recovery following traumatic brain injury.

关键词： cell therapy endogenous repair neurogenic niche progenitors traumatic brain injury

25 Years of sensory drive： the evidence and its watery bias

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Current Zoology 2018年第4期64卷 471-484页

作者： Molly E. cummings John A. ENDLER Department of Integrative Biology University of Texas Austin TX 78712 USA School of Life and Environmental Sciences Deakin University Waurn Ponds VIC 3216 Australia

It has been 25years since the formalization of the Sensory Drive hypothesis was published in the American Naturalist （1992）. Since then, there has been an explosion of research identifying its utility in contributing to our understanding of inter- and intra-specific variation in sensory systems and signaling properties. The main tenet of Sensory Drive is that environmental characteristics will influence the evolutionary trajectory of both sensory （detecting capabilities） and signaling （detectable features and behaviors） traits in predictable directions. We review the accumulating evidence in 154 studies addressing these questions and categorized their approach in terms of testing for environmental influence on sensory tuning, signal characteristics, or both. For the subset of studies that examined sensory tuning, there was greater support for Sensory Drive processes shaping visual than auditory tuning, and it was more prevalent in aquatic than terrestrial habitats. Terrestrial habitats and visual traits were the prevalent habitat and sensory modality in the 104 studies showing support for environmental influence on signaling properties. An additional 19 studies that found no supporting evidence for environmental influence on signaling traits were all based in terrestrial ecosystems and almost exclusively involved auditory signals. Only 29 studies examined the complete coevolutionary process between sensory and signaling traits and were dominated by fish visual communication. We discuss biophysical factors that may contribute to the visual and aquatic bias for Sensory Drive evidence, as well as biotic factors that may contribute to the lack of Sensory Drive processes in terrestrial acoustic signaling systems.

关键词： animal communication sensory drive sensory ecology sexual selection

The ascent of immune checkpoint inhibitors： is the understudy ready for a leading role？

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Cancer Biology & Medicine 2017年第4期14卷 341-347页

作者： Amy L. cummings Edward B. Garon Department of Hematology and Oncology David Geffen School of Medicine at the University of California Los Angeles 90095 USA

The recent approval of pembrolizumab as second-line treatment for any solid tumor with high-level microsatellite instability or mismatch repair deficiency agnostic of tissue and origin1 has shattered a glass ceiling for immune checkpoint *** longer bound to a specific cancer diagnosis but rather a biomarker,pembrolizumab has heightened a burgeoning optimism towards the drug *** how these agents should carve out additional

关键词： PD The ascent of immune checkpoint inhibitors:is the understudy ready for a leading role PFS OS ORR IHC

Molecular simulation study of dynamical properties of room temperature ionic liquids with carbon pieces

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Science China Chemistry 2016年第5期59卷 594-600页

作者： Guang Feng Wei Zhao Peter T.cummings Song Li State Key Laboratory of Coal Combustion School of Energy and Power Engineering Huazhong University of Science and Technology Department of Chemical and Biomolecular Engineering Vanderbilt University

Room temperature ionic liquids(RTILs) with dispersed carbon pieces exhibit distinctive physiochemical properties. To explore the molecular mechanism, RTILs/carbon pieces mixture was investigated by molecular dynamics(MD) simulation in this work. Rigid and flexible carbon pieces in the form of graphene with different thicknesses and carbon nanotubes in different sizes were dispersed in a representative RTIL 1-butyl-3-methyl-imidazolium dicyanamide([Bmim][DCA]). This study demonstrated that the diffusion coefficients of RTILs in the presence of flexible carbons are similar to those of bulk RTILs at varying temperatures, which is in contrast to the decreased diffusion of RTILs in the presence of rigid carbons. In addition, interfacial ion number density at rigid carbon surfaces was higher than that at flexible ones, which is correlated with the accessible external surface area of carbon pieces. The life time of cation-anion pair in the presence of carbon pieces also exhibited a dependence on carbon flexibility. RTILs with dispersed rigid carbon pieces showed longer ion pair life time than those with flexible ones, in consistence with the observation in diffusion coefficients. This work highlights the necessity of including the carbon flexibility when performing MD simulation of RTILs in the presence of dispersed carbon pieces in order to obtain the reliable dynamical and interfacial structural properties.

关键词： room temperature ionic liquids carbon pieces flexibility dynamical property ion pair stability interfacial structure