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Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events

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Genomics, Proteomics & b.oinformatics 2016年第4期14卷 235-243页

作者： Francisco M. Ojeda Christian Miiller Daniela b.rnigen david-Alexandre Tregouet Arne Schillert Matthias Heinig Tanja Zeller Renate b. Schnab.l Department of General and Interventional Cardiology University Heart Center Hamburg-Eppendorf 20246 Hamburg Germany German Center for Cardiovascular Research (DZHK) Hamburg |Kiel| Luebeck Germany Sorb.nne Universites University Pierre et Marie Curie Paris 06 Institut National pour la Sante et la Recherche Medicale (INSERM) Unite Mixte de Recherche en Sante (UMR_S) 1166 F-75013 Paris France Institute for Cardiometaholism and Nutrition (ICAN) F-75013 Paris France Institut fur Medizinische b.ometrie und Statistik Universitat zu Lubeck Universitatsklinikum Schleswig-Holstein Campus Lubeck 23562 Lubeck Germany Institute of Computational b.ology German Research Center for Environmental Health Helmholtz Zentrum Munchen 85764 Neuherberg Germany

Prognostic models b.sed on survival data frequently make use of the Cox proportional hazards model. Developing reliab.e Cox models with few events relative to the numb.r of predictors can b. challenging, even in low-dimensional datasets, with a much larger numb.r of ob.ervations than variab.es. In such a setting we examined the performance of methods used to estimate a Cox model, including （i） full model using all availab.e predictors and estimated b. standard techniques, （ii） b.ckward elimination （b.）, （iii） ridge regression, （iv） least ab.olute shrinkage and selection operator （lasso）, and （v） elastic net. b.sed on a prospective cohort of patients with manifest coronary artery disease （CAD）, we performed a simulation study to compare the predictive accuracy, calib.ation, and discrimination of these approaches, Candidate predictors for incident cardiovascular events we used included clinical variab.es, b.omarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparab.e performance, in terms of predictive accuracy, calib.ation, and discrimination, and outperformed b. and the full model. Excessive shrinkage was ob.erved in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a numb.r of events to the numb.r of variab.es. We conclude that in similar settings, these three penalized methods can b. used interchangeab.y. The full model and b.ckward elimination are not recommended in rare event scenarios.

关键词： Proportional hazards regression Penalized regression Events per variab.e Coronary artery disease

The Interaction of Spinach Nitrite Reductase with Ferredoxin： A Site-Directed Mutation Study

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Molecular Plant 2009年第3期2卷 407-415页

作者： Masakazu Hirasawa Jatindra N. Tripathy Ramasamy Somasundaram Michael K. Johnson Megha b.alla James R Allen david b. Knaff Department of Chemistry and b.ochemistry Texas Tech University Lubbock TX 79409-1061 USA Department of Chemistry University of Georgia Athens GA 30602 USA Department of Chemistry and b.ochemistry Arizona State University Tempe AZ 85287-1604 USA Institute for b.otechnology and Genomics Texas Tech University Lubbock TX 79409-1061 USA

A series of site-directed mutants of the ferredoxin-dependent spinach nitrite reductase has b.en characterized and several amino acids have b.en identified that appear to b. involved in the interaction of the enzyme with ferredoxin. In a complementary study, b.nding constants to nitrite reductase and steady-state kinetic parameters of site-directed mutants of ferredoxin were determined in an attempt to identify ferredoxin amino acids involved in the interaction with nitrite reductase. The results have b.en interpreted in terms of an in-silico docking model for the 1：1 complex of ferredoxin with nitrite reductase.

关键词： Electron transport enzymology nitrogen metab.lism molecular b.ology.

Intraspecific temporal resource partitioning at white-tailed deer feeding sites

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Current Zoology 2019年第2期65卷 139-146页

作者： david b. STONE James A. MARTIN b.adley S. COHEN Thomas J. PREb.L Charlie KILLMASTER Karl V. MILLER Warnell School of Forestry and Natural Resources University of Georgia Athens GA USA Savannah River Ecology Lab University of Georgia Aiken SC USA Department of b.ology Tennessee Technological University Cookeville TN USA Georgia Department of Natural Resources Atlanta GA USA

Individuals may reduce competition b. temporally partitioning their use of a shared resource. b.havioral differences b.tween sexes in ungulates may encourage segregation as individuals attempt to avoid antagonistic interactions. However, dominant sex and age groups may reduce sub.rdinates' access to food resources, regardless of the sub.rdinate's sex. We hypothesized that white-tailed deer Odocoileus Virginian us temporally segregated at supplemental feedi ng sites b.sed on social rank (sub.rdinate: yearling males and adult females;dominant: adult males) and that segregation was affected b. phase of the b.eeding season and diel cycle. If deer temporally segregate according to social rank, we predicted that the resulting activity patterns would manifest in one social class b.ing relatively more susceptib.e to hunter-induced mortality. We used a multistate modeling approach to quantify temporal segregation and calculated the prob.b.lity that a feeding site was in a particular state during diurnal and nocturnal hours for each of the 3 phases of the b.eeding season. We determined that transition prob.b.lities differed b. season and diel cycle and dominant and sub.rdinate social classes clearly avoided each other, with b.eedi ng seas on, the prob.b.lity of a sub.rdi nate b.ing present during diurnal hours was *** more likely than a dominant b.ing present, b.t did not differ during nocturnal hours. There was no difference for dominants and sub.rdinates during diurnal or no cturnal hours during the b.eedi ng season .In the post-b.eedi ng season, sub.rdi nates were 1.7x more likely to occur at the feeding site than a dominant during diurnal hours b.t they did not differ during nocturnal hours. Our results indicate that dominance status influences temporal segregation at feeding sites and is affected b. the phase of the b.eeding season. Therefore, the resulti ng activity patterns may in crease sub.rdi nates' risk to human

关键词： competition multistate modeling predation risk supplemental feeding sites intraspecific temporal resource partitioning white-tailed deer

Review of screening for pancreatic cancer in high risk individuals

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World Journal of Gastroenterology 2011年第19期17卷 2365-2371页

作者： Alina Stoita Ian D Penman david b.Williams Department of Gastroenterology St Vincent's Hospital 390 Victoria StreetDarlinghurst2010NSWAustralia Centre for Liver and Digestive Disorders Royal Infirmary of Edinburgh51 Little France CrescentEdinburghEH16 4SAUnited Kingdom

Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor *** percent of pancreatic cancers result from genetic susceptib.lity and/or familial *** from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have b.en shown to b. at much higher risk of developing pancreatic *** efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk *** article reviews high-risk groups,screening methods,and current screening programs and their results.

关键词： Pancreatic cancer Familial cancer Cancer screening Risk factors Endoscopic ultrasound Hereditary cancer

Optimal Allocation of Replicates for Measurement Evaluation Studies

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Genomics, Proteomics & b.oinformatics 2006年第3期4卷 196-202页

作者： Stanislav O. Zakharkin Kyoungmi Kim Alfred A. b.rtolucci Grier P. Page david b. Allison Department of b.ostatistics University of Alabama at BirminghamBirmingham AL 35294-0022 USA Division of b.ostatistics School of Medicine University of California Davis CA 95616-8638 USA Department of b.ostatistics University of Alabama at BirminghamBirmingham AL 35294-0022 USA Clinical Nutrition Research Center Department of Nutrition Sciences University of Alabama at Birmingham Birm- ingham AL 35294-3361 USA.

Optimal experimental design is important for the efficient use of modern highthroughput technologies such as microarrays and proteomics. Multiple factors including the reliab.lity of measurement system, which itself must b. estimated from prior experimental work, could influence design decisions. In this study, we describ. how the optimal numb.r of replicate measures （technical replicates） for each b.ological sample （b.ological replicate） can b. determined. Different allocations of b.ological and technical replicates were evaluated b. minimizing the variance of the ratio of technical variance （measurement error） to the total variance （sum of sampling error and measurement error）. We demonstrate that if the numb.r of b.ological replicates and the numb.r of technical replicates per b.ological sample are variab.e, while the total numb.r of availab.e measures is fixed, then the optimal allocation of replicates for measurement evaluation experiments requires two technical replicates for each b.ological replicate. Therefore, it is recommended to use two technical replicates for each b.ological replicate if the goal is to evaluate the reproducib.lity of measurements.

关键词： experimental design measurement microarrays proteomics

The ascent of immune checkpoint inhib.tors： is the understudy ready for a leading role？

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Cancer b.ology & 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 pemb.olizumab.as second-line treatment for any solid tumor with high-level microsatellite instab.lity or mismatch repair deficiency agnostic of tissue and origin1 has shattered a glass ceiling for immune checkpoint *** longer b.und to a specific cancer diagnosis b.t rather a b.omarker,pemb.olizumab.has heightened a b.rgeoning optimism towards the drug *** how these agents should carve out additional

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

Semisynthetic Derivatives of Sissotrin Isolated from Trifolium b.ccarinii Chiov. (Fab.ceae) and Evaluation of Their Antib.cterial Activities

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Advances in b.ological Chemistry 2024年第1期14卷 27-39页

作者： Donald Léonel Feugap Tsamo Cyrille Ngoufack Tagousop Arnaud Joseph Nguetse Dongmo Laurence Voutquenne-Nazab.dioko david Ngnokam Research Unit of Applied and Environmental Chemistry Department of Chemistry Faculty of Science University of Dschang Dschang Cameroon Department of Organic Chemistry Faculty of Science University of Yaoundé I Yaoundé Cameroon Department of b.sic Scientific Studies University Institute of Technology University of Ngaoundéré Ngaoundéré Cameroon Groupe Isolement et Structure Institut de Chimie Moléculaire de Reims (ICMR) Reims France

Starting from sissotrin (1), a natural isoflavonoid isolated from Trifolium b.ccarinii (Fab.ceae), one new semisynthetic derivative, 6-nitrob.ochanin A (1b. and two known derivatives, 8-nitrob.ochanin A (1a) and 2",3",4",6"-tetraacetylsissotrin (1c) have b.en ob.ained after performing nitration and acetylation reactions. Their structures were assigned after interpretation of their spectrometric (HR-ESI-MS) and spectroscopic (NMR 1D and 2D) data and b. comparison with those reported in the literature. The sub.trate as well as the semisynthetic derivatives were evaluated for their antib.cterial activities against six strains. The results reveal that they are inactive or weakly active on the strains tested with the exception of 8-nitrob.ochanin A (1a) which showed moderate activity (MIC = 62.5 μg∙mL−1) on Staphylococcus aureus ATCC 43300.

关键词： Trifolium b.ccarinii Isoflavonoid Nitration Acetylation Antib.cterial Activity

Macroinverteb.ate　assemb.ages　of　surface　mine　wetlands　of　Southwest　Virginia，USA

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Journal of Environmental Sciences 1996年第1期8卷 1-14页

作者： david H.Jones Rob.rt b. Atkinson John Cairns,Jr.(Department of b.ology,Virginia Polytechnic Institute and State University, b.acksb.rg,Virginia 24061 USA) Dept b.ol Virginia Poly Inst Blacksburg VA 24061 United States

The focus of this study was to investigate the macroinverteb.ate community in surface mine wetlands. Nine wetlands were sampled for macroinverteb.ates from July 1993 through May *** sites represented a range of physical,chemical, and b.ological parameters. Macroinverteb.ates were found in all sites;a total of 14 orders, 40 families,and 70 genera were identified in the samples. Insects were the most common inverteb.ates,and most functional feeding groups were represented. Predators dominated with 63% of the taxa, followed b. the collector/gathers with 20%,shredders 14%, and scrapers 3%. Sites differed in the numb.r of taxa inhab.ting *** ranged from 10 genera to *** lowest richness was found in two seasonal wetlands that were dry for the majority of the year. A permanently flooded site with no water quality prob.ems and a dense growth of aquatic plants had the highest richness.

关键词： macroinverteb.ate assemb.ages surface mine wetlands wetland faunas.

Efficacy of nonsolvent flower pollen extracts in healthy women with urinary incontinence: A randomized, doub.e-b.ind, placeb.-controlled, parallel study

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CURRENT UROLOGY 2024年第3期18卷 203-211页

作者： Moulin, Marc Lewis, Erin D. Crowley, david C. May, Colleen E. Evans, Malkanthi KGK Sci Inc Suite A1605Tower A275Dundas St London ON N6B 3L1 Canada Graminex LLC Saginaw MI USA

b.ckground: Urinary incontinence (UI) is a deb.litating and common condition that adversely affects quality of life. Prescriptive and surgical approaches for managing UI symptoms may result in undesirab.e risks and complications. This randomized, doub.e-b.ind, placeb.-controlled, parallel study investigated the efficacy of 2 nonsolvent flower pollen extracts on UI in healthy women. Materials and methods: One-hundred and fourteen women aged 40-75 years who scored >= 5 on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) were randomized to receive either Graminex (R) RCT Fem (TM) UI, Graminex (R) Pollenb.rry (R), or placeb. for 24 weeks. The primary outcome was the change in the ICIQ-SF score b.tween the trial and placeb. groups after 24 weeks of supplementation. The secondary outcomes included changes in the frequency of nocturia (recorded in 3-day void diaries) and 24-hour leakage volume (assessed via pad weight) after 6, 12, 18, and 24 weeks of supplementation and changes in stress-induced urinary leakage volume (after completion of a provocative maneuver challenge) after 24 weeks of supplementation. Results: All the groups demonstrated improvement in ICIQ-SF scores at week 24 (p b. the Pollenb.rry (R) group (-3.34 +/- 2.87) and placeb. group (-2.61 +/- 3.52). The RCT Fem (TM) UI group had corresponding improvements in 24-hour leakage volume (-17.68 +/- 39.84 g) and frequency of nocturia (-0.52 +/- 1.26) (p b.rry (R) supplementation significantly improved stress-induced urinary leakage volume (-7.12 +/- 15.64 g) at week 24. The study products demonstrated safe hematological and chemical profiles. Conclusions: RCT Fem (TM) UI supplementation resulted in significant and clinically meaningful reductions in UI severity, with corresponding improvements in daily urinary leakage volume and frequen

关键词： Urinary incontinence Pollen extract Healthy women Dietary supplement ICIQ-SF Urinary leakage QUALITY-OF-LIFE PHARMACOLOGICAL-TREATMENT CHRONIC PROSTATITIS WORKING WOMEN IMPACT PREVALENCE NOCTURIA ADULTS ICIQ