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Androgen deprivation therapy and side effects:are GnRH antagonists safer?

Asian journal of Andrology 2021年第1期23卷 3-10页

作者： stephen j freedland Per-Anders Abrahamsson Division of Urology Department of SurgeryCedars-Sinai Medical CenterLos AngelesCA 90048USA Section of Urology Durham VA Medical CenterDurhamNC 27705USA Department of Urology SkSne University HospitalLund UniversityMalmo 20502Sweden.

Androgen deprivation therapy(ADT)with gonadotropin-releasing hormone(GnRH)agonists and antagonists is the mainstay of advanced prostate cancer treatment.Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones(FSH),thereby lowering testosterone to castrate levels.This is associated with adverse events(AEs),including cardiovascular(CV)disorders,bone fractures,metabolic dysfunction,and impaired cognitive function.This literature review discusses these AEs,with a focus on CV and bone-related events.A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix.While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome,one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health,whereas antagonists do not.GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists,no differences in risk are predicted.Other common AEs with ADT include injection site reactions,which are much more common with degarelix than with GnRH agonists,which may reflect differing administration and injection techniques.Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists,especially in patients with pre-existing CV disease and other co-morbidities.Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.

关键词： androgen antagonists metabolic syndrome prostate cancer safety

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A REDUCED ORDER SCHWARZ METHOD FOR NONLINEAR MULTISCALE ELLIPTIC EQUATIONS BASED ON TWO-LAYER NEURAL NETWORKS

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journal of Computational Mathematics 2024年第2期42卷 570-596页

作者： Shi Chen Zhiyan Ding Qin Li stephen j.Wright Mathematics Department University of Wisconsin-MadisonMadisonWI 53706USA Department of Mathematics University of California-BerkeleyBerkeley CA 94720USA Mathematics Department and Discovery Institute University of Wisconsin-Madison MadisonWI 53706USA Computer Sciences Department University of WisconsinMadisonWI 53706USA

Neural networks are powerful tools for approximating high dimensional data that have been used in many contexts,including solution of partial differential equations(PDEs).We describe a solver for multiscale fully nonlinear elliptic equations that makes use of domain decomposition,an accelerated Schwarz framework,and two-layer neural networks to approximate the boundary-to-boundarymap for the subdomains,which is the key step in the Schwarz procedure.Conventionally,the boundary-to-boundary map requires solution of boundary-value elliptic problems on each subdomain.By leveraging the compressibility of multiscale problems,our approach trains the neural network offline to serve as a surrogate for the usual implementation of the boundary-to-boundary map.Our method is applied to a multiscale semilinear elliptic equation and a multiscale p-Laplace equation.In both cases we demonstrate significant improvement in efficiency as well as good accuracy and generalization performance.

关键词： Nonlinear homogenization Multiscale elliptic problem Neural networks Do-main decomposition

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The association between sexual function and prostate cancer risk in US veterans

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Asian journal of Andrology 2017年第2期19卷 191-195页

作者： Daniel F Zapata Lauren E Howard jennifer Frank Ross M Simon Cathrine Hoyo Delores j Grant stephen j freedland Adriana C Vidal Duke University Medical Center Division of Urology Department of Surgery Durham NC 27710 USA Durham Veterans Affairs Medical Center Urology Division Durham NC 27710 USA North Carolina State University Department of Biology Raleigh NC 27695 USA North Carolina Central University Department of Biology Durham NC 27707 USA Department of Surgery Division of Urology Samuel Oschin Comprehensive Cancer institute Cedars-Sinai Medical Center Los Angeles California 90048 USA

Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men. Among 448 men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, sexual function was ascertained from the Expanded Prostate Cancer Index Composite sexual assessment. We tested the link between sexual function and prostate cancer risk adjusting for multiple demographic and clinical characteristics using logistic regression. Multinomial logistic regression was used to test the associations with risk of low-grade （Gleason 〈6） and high-grade （Gleason 〉7 or 〉4 ＋ 3） disease versus no cancer. Of 448 men, 209 （47%） had a positive biopsy; these men were less likely to be white （43% vs 55%, P=0.013）, had higher prostate-specific antigen （PSA）（6.0 vs 5.4 ng ml-1, P 〈 0.001）, but with lower mean sexual function score （47 vs 54, P = 0.007）. There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. After adjusting for baseline differences, sexual function was linked with a decreased risk of overall prostate cancer risk （OR. 0.91 per lO-point change in sexual function, P= 0.004） and high-grade disease whether defined as Gleason ≥7 （OR： 0.86, P= 0.001） or 〉4 ＋ 3 （OR： 0.85, P= 0.009）. Sexual function was unrelated to low-grade prostate cancer （OR： 0.94, P = 0.13）. Thus, among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade prostate cancer. Confirmatory studies are needed.

关键词： erectile dysfunction prostate prostate cancer risk sexual function

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Re： Commentary on ＂The association between sexual function and prostate cancer risk in US veterans＂

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Asian journal of Andrology 2018年第1期20卷 100-100页

作者： Adriana C Vidal stephen j freedland Department of Surgery Cedars-Sinai Medical Center Samuel Oschin CancerInstitute Los Angeles CA 90048 USA

Dear Editor, Kai Wang and Linda B Cottler recently commented on our article entitled, ＂The association between sexual function and prostate cancer risk in US veterans＂ published in Asian journal ofAndrology.They made the good point that sexual function could be a clinical symptom of low serum testosterone, and that men with low testosterone may be using testosterone replacement therapy （TRT） which could be confounding the associations between sexual function and prostate cancer risk.

关键词： cancer risk replacement therapy

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Comparison of methods for deriving phenotypes from incomplete observation data with an application to age at puberty in dairy cattle

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journal of Animal Science and Biotechnology 2024年第2期15卷 535-545页

作者： Melissa A.stephen Chris R.Burke jennie E.Pryce Nicole M.Steele Peter R.Amer Susanne Meier Claire V.C.Phyn Dorian j.Garrick DairyNZ Ltd 605 Ruakura RoadHamilton 3240New Zealand AL Rae Centre for Genetics and Breeding-Massey University RuakuraHamilton 3214New Zealand Agriculture Victoria Research AgriBioCentre for AgriBioscienceBundooraVictoria 3083Australia School of Applied Systems Biology La Trobe UniversityBundooraVictoria 3083Australia AbacusBio DunedinNew Zealand

Background Many phenotypes in animal breeding are derived from incomplete measures,especially if they are challenging or expensive to measure precisely.Examples include time-dependent traits such as reproductive status,or lifespan.Incomplete measures for these traits result in phenotypes that are subject to left-,interval-and rightcensoring,where phenotypes are only known to fall below an upper bound,between a lower and upper bound,or above a lower bound respectively.Here we compare three methods for deriving phenotypes from incomplete data using age at first elevation(>1 ng/mL)in blood plasma progesterone(AGEP4),which generally coincides with onset of puberty,as an example trait.Methods We produced AGEP4 phenotypes from three blood samples collected at about 30-day intervals from approximately 5,000 Holstein–Friesian or Holstein–Friesian×jersey cross-bred dairy heifers managed in 54 seasonal-calving,pasture-based herds in New Zealand.We used these actual data to simulate 7 different visit scenarios,increasing the extent of censoring by disregarding data from one or two of the three visits.Three methods for deriving phenotypes from these data were explored:1)ordinal categorical variables which were analysed using categorical threshold analysis;2)continuous variables,with a penalty of 31 d assigned to right-censored phenotypes;and 3)continuous variables,sampled from within a lower and upper bound using a data augmentation approach.Results Credibility intervals for heritability estimations overlapped across all methods and visit scenarios,but estimated heritabilities tended to be higher when left censoring was reduced.For sires with at least 5 daughters,the correlations between estimated breeding values(EBVs)from our three-visit scenario and each reduced data scenario varied by method,ranging from 0.65 to 0.95.The estimated breed effects also varied by method,but breed differences were smaller as phenotype censoring increased.Conclusion Our results indicate that using some methods,phenotypes derived from one observ

关键词： Cattle Gibbs sampler Markov-chain Monte Carlo(MCMC) Puberty

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Harnessing the power of complex light propagation in multimode fibers for spatially resolved sensing

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Photonics Research 2024年第3期12卷 411-422页

作者： DARCY L.SMITH LINH V.NGUYEN MOHAMMAD I.REjA ERIK P.SCHARTNER HEIKE EBENDORFF-HEIDEPRIEM DAVID j.OTTAWAY stephen C.WARREN-SMITH Institute for Photonics and Advanced Sensing and School of Physics Chemistry and Earth SciencesThe University of AdelaideAdelaideSA 5005Australia Australian Research Council Centre of Excellence for Gravitational Wave Discovery(OzGrav) AdelaideSAAustralia Future Industries Institute University of South AustraliaMawson LakesSA 5095Australia Laser Physics and Photonics Devices Laboratory University of South AustraliaMawson LakesSA 5095Australia

The propagation of coherent light in multimode optical fibers results in a speckled output that is both complex and sensitive to environmental effects.These properties can be a powerful tool for sensing,as small perturbations lead to significant changes in the output of the fiber.However,the mechanism to encode spatially resolved sensing information into the speckle pattern and the ability to extract this information are thus far unclear.In this paper,we demonstrate that spatially dependent mode coupling is crucial to achieving spatially resolved measurements.We leverage machine learning to quantitatively extract the spatially resolved sensing information from three fiber types with dramatically different characteristics and demonstrate that the fiber with the highest degree of spatially dependent mode coupling provides the greatest accuracy.

关键词： fiber spatially resolved

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SARS-CoV-2 triggers Dickkopf-1(Dkk-1)modulation of T helper cells and lung pathology in mice

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Genes & Diseases 2024年第4期11卷 9-12页

作者： Yifan Wu Freedom M.Green stephen A.Shaw Lauren j.Bonilla Shannon E.Ronca Maria Elena Bottazzi Farrah Kheradmand jill E.Weatherhead Department of Pathology&Immunology One Baylor PlazaHoustonTX 77030USA Department of Pediatrics One Baylor PlazaHoustonTX 77030USA Department of Medicine One Baylor PlazaHoustonTX 77030USA National School of Tropical Medicine One Baylor PlazaHoustonTX 77030USA Molecular Virology&Microbiology One Baylor PlazaHoustonTX77030USA Biologyof Inflammation Center Baylor College of MedicineOne BaylorPlazaHoustonTX77030USA Michael E.DeBakey VA Center for Translational Research on Inflammatory Diseases HoustonTX 77030USA

Severe acute respiratory syndrome coronavirus 2(SARSCov-2)is the etiologic agent of the coronavirus disease 19(COVID-19)pandemic.In viral infections like SARS-CoV-2,a robust anti-viral type 1 immune response,including upregulation of type 1 CD4+T helper cells(Th1),is required for effective viral clearance while minimizing end-organ pathology and collateral tissue damage.

关键词： pathology acute respiratory

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Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

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journal of Sport and Health Science 2024年第1期13卷 13-17,F0003页

作者： Erik A.Willis stephen D.Herrmann Mary Hastert Chelsea L.Kracht Tiago V.Barreira john M.Schuna jr. Zhenghua Cai Minghui Quan Scott A.Conger Wendy j.Brown Barbara E.Ainsworth Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA Kansas Center for Metabolism and Obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA Division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Clinical Science Division Pennington Biomedical Research CenterBaton RougeLA 70808USA Exercise Science Department Syracuse UniversitySyracuseNY 13244USA School of Exercise&Sport Science Oregon State UniversityCorvallisOR 97331USA School of Exercise and Health Shanghai University of SportShanghai 200438China Department of Kinesiology Boise State UniversityBoiseID 83725USA School of Human Movement and Nutrition Sciences The University of QueenslandSt.LuciaQLD 4072Australia Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4229Australia College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older adults.MET values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older adults.Results:We identified 68 articles and extracted energy expenditure data on 427 PAs.From these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older adults.We developed a website to present the OA Compendium MET_(60+)values:https://pacompendium.com.Conclusion:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older adults.It is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

关键词： Energy expenditure Exercise MET Older adults

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Error field penetration in j-TEXT tokamak based on two-fluid drift-MHD model

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Chinese Physics B 2024年第4期33卷 545-551页

作者：王文徐涛张仪 the j-TEXT team State Key Laboratory of Advanced Electromagnetic Technology International Joint Research Laboratory of Magnetic Confinement Fusion and Plasma PhysicsSchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074China

An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant surfaces.We have studied the plasma responses using Fitzpatrick's improved two-fluid model and program LAYER.We calculated the error field penetration threshold for j-TEXT.In addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration value.However,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the penetration.By scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency decreases.Finally,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.

关键词： plasma responses drift-MHD model error field penetration

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A Modified Lagrange Method for Solving Convex Quadratic Optimization Problems

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Open journal of Optimization 2024年第1期13卷 1-20页

作者： Twum B. stephen Avoka john Christian j. Etwire School of Mathematical Science C. K. Tedam University of Technology and Applied Sciences Navrongo Ghana Department of Mathematics University for Development Studies Tamale Ghana

In this paper, a modified version of the Classical Lagrange Multiplier method is developed for convex quadratic optimization problems. The method, which is evolved from the first order derivative test for optimality of the Lagrangian function with respect to the primary variables of the problem, decomposes the solution process into two independent ones, in which the primary variables are solved for independently, and then the secondary variables, which are the Lagrange multipliers, are solved for, afterward. This is an innovation that leads to solving independently two simpler systems of equations involving the primary variables only, on one hand, and the secondary ones on the other. Solutions obtained for small sized problems (as preliminary test of the method) demonstrate that the new method is generally effective in producing the required solutions.

关键词： Quadratic Programming Lagrangian Function Lagrange Multipliers Optimality Conditions Subsidiary Equations Modified Lagrange Method

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