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In vivo radiometric analysis of glucose uptake and distribution in mouse bone

Bone Research 2016年第1期4卷 31-38页

作者： Meredith L Zoch Diane S Abou Thomas L clemens Daniel LJ Thorek ryan c riddle Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Baltimore USA Division of Nuclear Medicine an Molecular Imaging Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore USA Baltimore Veterans Administration Medical center Baltimore USA Department of Oncology Cancer Molecular and Functional Imaging Program Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore USA

Bone formation and remodeling occurs throughout life and requires the sustained activity of osteoblasts and osteoclasts, particularly during periods of rapid bone growth. Despite increasing evidence linking bone cell activity to global energy homeostasis, little is known about the relative energy requirements or substrate utilization of bone cells. In these studies, we measured the uptake and distribution of glucose in the skeleton in vivo using positron-emitting 18F-fluorodeoxyglucose （[lSF]-FDG） and non-invasive, high-resolution positron emission tomography/computed tomography （PE~/cT） imaging and ex vivo autoradiography. Assessment of [~SF]-FDG uptake demonstrated that relative to other tissues bone accumulated a significant fraction of the total dose of the glucose analog..Skeletal accumulation was greatest in young mice undergoing the rapid bone formation that characterizes early development. PET/cT imaging revealed that [lSF]-FDG uptake was greatest in the epiphyseal and metaphyseal regions of long bones, which accords with the increased osteoblast numbers and activity at this skeletal site. Insulin administration significantly increased skeletal accumulation of [lSF]-FDG, while uptake was reduced in mice lacking the insulin receptor specifically in osteoblasts or fed a high-fat diet. Our results indicated that the skeleton is a site of significant glucose uptake and that its consumption by bone cells is subject to regulation by insulin and disturbances in whole-body metabolism.

关键词： bone FDG

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Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

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Bone Research 2014年第1期2卷 33-42页

作者： Julie L Frey David P Stonko Marie-claude Faugere ryan c riddle Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Division of Nephrology Bone & Mineral Metabolism University of Kentucky Veterans Administration Medical center

The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

关键词： PTH Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone Figure

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Are school uniforms associated with gender inequalities in physical activity? A pooled analysis of population-level data from 135 countries/regions

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Journal of Sport and Health Science 2024年第4期13卷 590-598页

作者： Mairead ryan Luiza I.c.Ricardo Nicole Nathan Riikka Hofmann Esther van Sluijs Medical Research council Epidemiology Unit University of CambridgeCambridge CB20QQUK Faculty of Education University of CambridgeCambridge CB28PQUK Hunter New England Population Health WallsendNSW 2287Australia School of Medicine and Public Health College of HealthMedicine and WellbeingUniversity of NewcastleCallaghanNSW 2308Australia Hunter Medical Research Institute New Lambton HeightsNSW 2305Australia National centre of Implementation Science University of NewcastleCallaghanNSW 2308Australia

Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment ***:An ecological study design was *** collected data about global uniform practices using an online *** searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance *** selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were *** calculated absolute and relative gender inequalities in physical activity for each *** regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured ***:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%cI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%cI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%cI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary *** initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compli

关键词： School policy clothing child Adolescent Accelerometer

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Towards global coverage of gridded parameterization for cLImate GENerator(cLIGEN)

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Big Earth Data 2024年第1期8卷 142-165页

作者： Andrew T.Fullhart Guillermo E.Ponce-campos Menberu B.Meles ryan P.McGehee Haiyan Wei Gerardo Armendariz Shea Burns David c.Goodrich Southwest Watershed Research center USDA-ARS TucsonAZUSA School of Natural Resources and the Environment University of ArizonaTucsonAZUSA Sustainable Agricultural Water Systems Unit USDA-ARS DavisCAUSA Agricultural and Biosystems Engineering Iowa State UniversityAmesIAUSA

Stochastic weather generators create time series that reproduce key weather dynamics present in long-term *** dataset detailed herein is a large-scale gridded parameterization for cLImate GENerator(cLIGEN)that fills spatial gaps in the coverage of existing regional cLIGEN parameterizations,thereby obtaining near-global availability of combined *** dataset primarily covers countries north of 40°latitude with 0.25°spatial *** cLIGEN parameters were estimated based on 20-year records from four popular global climate *** parameters were statistically downscaled to estimate point-scale values,while point-scale temperature and solar radiation parameters were approximated by direct calculation from high-resolution *** parameter values were used in some cases,such as with wind ***-validation was done to assess the downscaling approach for six precipitation parameters using known point-scale values from ground-based cLIGEN *** parameter values were derived from daily accumulation records at 7,281 stations and high temporal resolution records at 609 *** sensitive parameters,monthly average storm accumulation and maximum 30-minute intensity,were shown have RMSE values of 1.48 mm and 4.67 mm hr^(−1),*** precipitation and the annual number of days with precipitation occurrence were both within 5%of ground-based parameterizations,effectively improving climate data availability.

关键词： Agriculture climate hydrology soil erosion stochastic weather generator

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Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： ryan A.Dornbier chirag P.Doshi Shalin c.Desai Petar Bajic Michelle Van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler Thomas M.T.Turk Alan J.Wolfe Kristin G.Baldea Loyola University Medical center Department of UrologyMaywoodILUSA Loyola University chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains *** evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis ***:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without *** sample types were subjected to expanded quantitative urine culture(EQUc)and 16 S ribosomal RNA gene ***:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS *** controls had uric acid stone *** EQUc,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to *** validate our EQUc results,we performed 16 S ribosomal RNA gene *** 12/16(75.0%)sequence-positive stones,EQUc reliably isolated at least one species of the sequenced *** were detected in both“infectious”and“non-infectious”stone ***:Bacteria are more common and more abundant in MetS stones than control *** findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

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Exploring a targeted approach for public health capacity restrictions during cOVID-19 using a new computational model

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Infectious Disease Modelling 2024年第1期9卷 234-244页

作者： Ashley N.Micuda Mark R.Anderson Irina Babayan Erin Bolger Logan cantin Gillian Groth Ry Pressman-cyna charlotte Z.Reed Noah J.Rowe Mehdi Shafiee Benjamin Tam Marie c.Vidal Tianai Ye ryan D.Martin Department of Physics Engineering Physics&AstronomyQueen's UniversityKingstonONCanada Department of Medical Biophysics Western UniversityLondonONCanada Department of Mathematics and Statistics Queen's UniversityKingstonONCanada Department of Biology Queen's UniversityKingstonONCanada Department of Electrical and computer Engineering Nazarbayev UniversityNur-SultanKazakhstan Energetic cosmos Laboratory Nazarbayev UniversityNur-SultanKazakhstan School of computing Queen's UniversityKingstonONCanada Department of Biomedical and Molecular Sciences Queen's UniversityKingstonONCanada Department of Physics University of OxfordOxfordUnited Kingdom Department of Physics Stanford UniversityStanfordCAUnited States

This work introduces the Queen's University Agent-Based Outbreak Outcome Model(QUABOOM).This tool is an agent-based Monte carlo simulation for modelling epidemics and informing public health *** illustrate the use of the model by examining capacity restrictions during a *** find that public health measures should focus on the few locations where many people interact,such as grocery stores,rather than the many locations where few people interact,such as small *** also discuss a case where the results of the simulation can be scaled to larger population sizes,thereby improving computational efficiency.

关键词： Monte-carlo Agent-based epidemic modelling cOVID-19 Small business capacity restrictions Public health Basic reproductive number

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Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

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World Journal of Diabetes 2024年第3期15卷 455-462页

作者： Ahmed Eldib Shilton Dhaver Karim Kibaa Astrid Atakov-castillo Tareq Salah Marwa Al-Badri Abdelrahman Khater ryan Mccarragher Omnia Elenani Elena Toschi Osama Hamdy Department of clinical Behavioral&Outcomes ResearchJoslin Diabetes CenterBostonMA 02215United States Department of Medicine Harvard Medical SchoolBostonMA 02115United States

BAcKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HcL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HcL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical *** this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HcL in real-world clinical *** To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with *** We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1c:7.6%±0.8%)who were treated with HcL at Joslin clinic from 2017 to *** measured A1c and percent of glucose time-in-range(%TIR)at baseline and 12 *** measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes *** At 12 mo,A1c decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1c,%TIR or ***,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(Pcemia fear survey/worry scale decreased significantly by 24.9%(Pced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of clarke questionnaire showed no increase in awareness of hypoglycemic ***-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HcL ***,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration o

关键词： Artificial pancreas continuous blood glucose monitor Type 1 diabetes Hybrid closed-loop insulin delivery Quality of life

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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi calkins Sebastian Rudden camille Jones Jessie Doan Bora Jang Elisa Schrader Echeverri ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip J.Santangelo James E.Dahlman George c.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.coulter Department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(cNS).However,delivery to the cNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the cNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the cNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

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Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： cecilie Skarstad Norevik Aleksi M.Huuha Ragnhild N.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv ryan Belma Skender Jose Bianco N.Moreira Asgeir Kobro-Flatmoen Menno P.Witter Nathan Scrimgeour Atefe R.Tari cardiac Exercise Research Group(cERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of Neurology and clinical Neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil centre of Molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems Neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(pcised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： cytokines High-intensity interval training Inflammation Neurons Plasma transfusion

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Inter-signal interaction and uncertain information in anuran multimodal signals

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current Zoology 2011年第2期57卷 153-161页

作者： ryan c. TAYLOR Barrett A. KLEIN Michael J. ryan Department of Biological Sciences Salisbury University Salisbury MD 21801 USA Section of Integrative Biology University of Texas at Austin Austin TX 78712 USA Smithsonian Tropical Research Institute P.O. Box 0843-03092 Balboa Ancon Republic of Panama

Disentangling the influence of multiple signal components on receivers and elucidating general processes influencing complex signal evolution are difficult tasks. In this study we test mate preferences of female squirrel treefrogs Hyla squirella and female tungara frogs Physalaemus pustulosus for similar combinations of acoustic and visual components of their multimodal courtship signals. In a two-choice playback experiment with squirrel treefrogs, the visual stimulus of a male model significantly increased the attractivness of a relatively unattractive slow call rate. A previous study demonstrated that faster call rates are more attractive to female squirrel treefrogs, and all else being equal, models of male frogs with large body stripes are more attractive. In a similar experiment with female tungara frogs, the visual stimulus of a robotic frog failed to increase the attractiveness of a relatively unattractive call. Females also showed no preference for the distinct stripe on the robot that males commonly bear on their throat. Thus, features of conspicuous signal components such as body stripes are not universally important and signal function is likely to differ even among species with similar ecologies and communication systems. Finally, we discuss the putative information content of anuran signals and suggest that the categorization of redundant versus multiple messages may not be sufficient as a general explanation for the evolution of multimodal signaling. Instead of relying on untested assumptions concerning the information content of signals, we discuss the value of initially collecting comparative empirical data sets related to receiver responses.

关键词： Inter-signal interaction Multimodal signaling Signal detection Signal weighting Squirrel treefrog Hyla squirella Tfingara frog Physalaemus pustulosus Vocal sac

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