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Validation of an MRI-based prostate cancer prebiopsy Gleason score predictive nomogram

Current Urology 2022年第1期16卷 38-43页

作者： Adrianna jiaying Lee Amelia Wnorowski Nancy Ye Linhan Xu Michael Naslund bradford j.wood Maria j.Merino Baris Turkbey Peter L.Choyke Peter A.Pinto M.Minhaj Siddiqui University of Maryland BaltimoreMDUSA Baltimore VA Medical Center BaltimoreMDUSA Molecular Imaging Program National Cancer InstituteNational Institutes of HealthBethesdaMDUSA Center for Interventional Oncology National Cancer Institute&Clinical CenterNational Institutes of HealthBethesdaMDUSA Urologic Oncology Branch National Cancer InstituteNational Institutes of HealthBethesdaMDUSA

Background:Gleason score grading is a cornerstone of risk stratification and management of patients with prostate cancer(PCa).In this work,we derive and validate a nomogram that uses prostate multiparametric magnetic resonance imaging(MP-MRI)and clinical patient characteristics to predict biopsy Gleason scores(bGS).Materials and methods:A predictive nomogram was derived from 143 men who underwent MP-MRI prior to any prostate biopsy and then validated on an independent cohort of 235 men from a different institution who underwent MP-MRI for PCa *** positive lesions were defined as lesions positive on T2W and DWI sequences on *** specific antigen(PSA)density,number of screen positive lesions,and MRI suspicion were associated with PCa Gleason score on biopsy and were used to generate a predictive *** independent cohort was tested on the nomogram and the most likely bGS was ***:The mean PSA in the validation cohort was 9.25ng/mL versus 6.8ng/mL in the original cohort(p=0.001).The distribution of Gleason scores between the 2 cohorts were not significantly different(p=0.7).In the original cohort of men,the most probable nomogram generated Gleason score agreed with actual pathologic bGS findings in 61%of the *** the validation cohort,the most likely nomogram predicted bGS agreed with actual pathologic bGS 51%of the *** nomogram correctly identified any PCa versus non-PCa 63%of the time and clinically significant(Gleason score≥7)PCa 69%of the *** negative predictive value for clinically significant PCa using this prebiopsy nomogram was 74%in the validation ***:A preintervention nomogram based on PSA and MRI findings can help narrow down the likely pathologic finding on *** of the nomogram demonstrated a significant ability to correctly identify the most likely *** feasibility study demonstrates the potential of a prebiopsy prediction of bGS and based on the high negative predictive value,i

关键词： Multiparametric magnetic resonance imaging Nomogram Prostate cancer

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Global climate change is confounding species conservation strategies

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Integrative Zoology 2012年第2期7卷 158-164页

作者： Harold KOOPOWITZ bradford A.HAWKINS Department of Ecology and Evolutionary Biology University of CaliforniaIrvineCaliforniaUSA

Most organisms face similar problems with respect to their conservation in the face of global climate ***,we examine probable effects of climate change on the hyperdiverse plant family *** the 20th century,the major concerns for orchid conservation revolved around unsustainable harvest for the orchid trade and,more importantly,land conversion from natural ecosystems to those unable to support wild orchid pop*** conversion included logging,fire regimes and forest conversions to agricultural ***though those forms of degradation continue,an additional suite of threats has emerged,fueled by global climate *** climate change involves more than responses of orchid populations to increases in ambient *** temperature induces secondary effects that can be more significant than simple changes in *** these new threats are extended and prolonged fire seasons,rising sea levels,increases in cyclonic storms,seasonal climate shifts,changes in orthographic wind dew point and increased *** long-term outlook for orchid biodiversity in the wild is dismal,as it is for many animal groups,and we need to start rethinking strategies for conservation in a rapidly changing world.

关键词： biodiversity climate change conservation biology ex situ conservation orchids

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Predation of cassowary dispersed seeds:is the cassowary an effective disperser?

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Integrative Zoology 2011年第3期6卷 168-177页

作者： Matt G.bradford David A.WESTCOTT CSIRO-Sustainable Ecosystems Tropical Forest Research CentreAthertonQueenslandAustralia

Post-dispersal predation is a potentially significant modifier of the distribution of recruiting plants and an often unmeasured determinant of the effectiveness of a frugivore’s dispersal *** the wet tropical forests of Austra-lia and New Guinea,the cassowary provides a large volume,long distance dispersal service incorporating benefi-cial gut processing;however,the resultant clumped deposition might expose seeds to elevated *** exam-ined the contribution of post-dispersal seed predation to cassowary dispersal effectiveness by monitoring the fate of 11 species in southern cassowary(Casuarius casuarius johnsonii Linnaeus)droppings over a period of 1 *** all species,the rate of predation and removal was relatively *** 1 month,70%of seeds remained intact and outwardly viable,while the number fell to 38%after 1 *** proportion of seeds remaining intact in droppings varied considerably between species:soft-seeded and large-seeded species were more likely to escape removal and ***,across all species,seeds in droppings were no more likely to be predated than those left undispersed under the parent *** speculate that seed predating and scatter-hoarding rodents are responsible for the vast majority of predation and removal from droppings and that the few seeds which undergo secondary dispersal survive to *** findings reinforce the conclusion that the cassowary is an impor-tant seed disperser;however,dispersal effectiveness for particular plant species can be reduced by massive post-dispersal seed mortality.

关键词： Australia Casuarius casuarius disperser effectiveness secondary dispersal seed shadow

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Effects of TNF receptor blockade on in vitro cell survival and response to negative energy balance in dairy cattle

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journal of Animal Science and Biotechnology 2018年第2期9卷 430-438页

作者： C.A.Martel L.K.Mamedova j.E.Minton M.Garcia C.Legallet B.j.bradford Department of Animal Sciences and Industry Kansas State University

Background: Associative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor(TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide(TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed ***: Capability of TRLP to inhibit TNFα signaling was confirmed on primary bovine hepatocytes treated with recombinant bovine TNFα and 4 doses of TRLP(0, 1, 10, 50 μmol/L) over 24 h. Next, 4 lactating Holstein cows(parity 1.4 ± 0.5, 433 ± 131 d in milk) in an incomplete Latin rectangle design(3 × 2) were subcutaneously administered with different TRLP doses(0, 1.5, 3.0 mg/kg BW) every 4 h for 24 h, followed by an intravenous injection of TNFα(5 μg/kg BW). Before and for 2 h after TNFα injection, TRLP decreased plasma non-esterified fatty acid(NEFA)concentration(P ≤ 0.05), suggesting an altered metabolic response to inflammation. Finally, 10 non-pregnant, nonlactating Holstein cows(3.9 ± 1.1 yr of age) were randomly assigned to treatments: control(carrier: 57% DMSO in PBS)or TRLP(1.75 mg TRLP/kg BW per day). Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed-restricted cows fed 30% of maintenance energy requirements. Daily blood samples were analyzed for glucose,insulin, β-hydroxybutyrate, NEFA, and haptoglobin concentrations, with no treatment effects detected. On d 7, cows completed a glucose tolerance test(GTT) by i.v. administration of a dextrose bolus(300 mg glucose/kg BW). Glucose,insulin, and NEFA responses failed to demonstrate any significant effect of treatment during the GTT. However, plasma and liver analyses were not indicative of dramatic lipolysis or hepatic lipidosis, suggesting that the feed restriction protoc

关键词： Dairy cows Fatty liver Glucose tolerance test Tumor necrosis factorα

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Restricted nutrient intake does not alter serum-mediated measures of implant response in cell culture

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journal of Animal Science and Biotechnology 2014年第1期5卷 80-87页

作者： Christopher D Reinhardt Tiffany L Lee Daniel U Thomson Laman K Mamedova Barry j bradford Department of Animal Sciences and Industry 232 Weber Hall Kansas State University Department of Clinical Sciences A-111 Mosier Hall Kansas State University

Background： During nutritional stress, reduced intake may reduce the efficacy of anabolic implants. This study was conducted to evaluate basic cellular responses to a growth promotant implant at two intake levels. Methods： Sixteen crossbred steers （293 ± 19.3 kg） were used to evaluate the impact of anabolic implants in either an adequate or a restricted nutritional state. Steers were trained to individual Calan gates, and then randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted off presence or absence of an anabolic growth implant （Revalor-XS, 200 mg TBA and 40 mg estradiol; IMPLANT or CONTROL） and a moderate energy, pelleted, starting cattle diet fed at either 2.0 × or 1.0 × maintenance energy （NEM） requirements （HIGH or LOW）. Serum （d O, 14, and 28） was used for application to bovine muscle satellite cells. After treatment with the serum （20% of total media） from the trial cattle, the satellite cells were incubated for 72 h. Protein abundance of myosin heavy chain （MHC）, phosphorylated extracellular signal-related kinase （phospho-ERK）, and phosphorylated mammalian target of rapamycin （phospho-mTOR） were analyzed to determine the effects of implant, intake, and their interaction （applied via the serum）. Results： Intake had no effect on MHC （P = 0.85） but IMPLANT increased （P 〈 0.01） MHC abundance vs. CONTROL. Implant status, intake status, and the interaction had no effect on the abundance of phospho-ERK （P〉0.23）. Implanting increased phospho-mTOR （P 〈 0.01） but there was no effect （P 〉 0.51） of intake or intake x implant. Conclusions： The nearly complete lack of interaction between implant and nutritional status indicates that the signaling molecules measured herein respond to implants and nutritional status independently. Furthermore, results suggest that the muscle hypertrophic effects of anabolic implants may not be mediated by circulating IGF-1.

关键词： Beef cattle Implant Muscle Myosin heavy chain Nutrient restriction Satellite cells

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Degree One Loading by Pressure Variations at the CMB

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journal of Earth Science 2013年第5期24卷 736-749页

作者： Ming Fang bradford H Hager Weijia Kuang Department of Earth Atmospheric & Planetary Sciences Massachusetts Institute of Technology Planetary Geodynamics Laboratory NASA Goddard Space Flight Center

Hemispherical asymmetry in core dynamics induces degree-1 pressure variations at the core mantle boundary （CMB）, which in turn deforms the overlaying elastic mantle, at the same time keeps center of mass of the whole Earth stationary in space. We develop a systematic procedure to deal with the degree-1 CMB pressure loading. We find by direct calculation a surprisingly negative load Love number h1=-1.425 for vertical displacement. Further analysis indicates that the negative hi corre- sponds to thickening above the positive load that defies intuition that pressure inflation pushes over- laying material up and thins the enveloping shell. We also redefine the pressure load Love numbers in general to enable comparison between the surface mass load and the CMB pressure load for the whole spectrum of harmonic degrees. We find that the gravitational perturbations from the two kinds of loads at degrees n〉l are very similar in amplitude but opposite in sign. In particular, if the CMB pressure variation at degree 2 is at the level of -1 hpa/yr （1 cm water height per year）, it would perturb the variation of Earth＇s oblateness, known as the j2, at the observed level.

关键词： Degree One Loading by Pressure Variations at the CMB MRSP

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Development of an in vitro macrophage screening system on the immunomodulating effects of feed components

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journal of Animal Science and Biotechnology 2021年第2期12卷 639-648页

作者： S.E.Sivinski L.K.Mamedova R.A.Rusk C.C.Elrod T.H.Swartz j.M.McGill B.j.bradford Department of Animal Sciences and Industry Kansas State UniversityManhattan 66506USA Department of Diagnostic Medicine/Pathobiology Kansas State UniversityManhattan 66506USA Natural Biologics NewfieldNY 14867USA 2265K Anthony Hall 474 S.Shaw LaneEast LansingMI 48824USA

Background:While feed components capable of modulating the immune system are highly sought after and marketed,often little evidence is available to support functional immune response ***,a high-throughput in vitro cell screening system was developed to test these compounds for innate immune signaling effects,using Saccharomyces cerevisiae and its cell wall components in addition to lauric acid and its esters as models in two separate *** screening system utilized RAW 264.7 murine macrophages to assess live *** cells and ***-derived cell wall componentsβ-glucan,mannan,and zymosan(a crude cell wall preparation containing bothβ-glucan and mannan).D-mannose was also evaluated as the monomer of *** also examined the effect of a saturated fatty acid(C12:0,lauric acid)and its esters(methyl laurate and glycerol monolaurate)on innate immune cell activation and cellular *** cells were transfected with a vector that drives expression of alkaline phosphatase upon promoter activation of nuclear factorκ-light-chain-enhancer of activated B cells(NFκB),a major inflammatory/immune transcription *** cells were incubated with 0.01,0.1 or 1 mg/mL of yeast compounds alone or RAW cells were challenged with LPS and then incubated with yeast *** a separate experiment,RAW cells were incubated with 0,0.5,2.5,12.5,62.5,and 312.5μmol/L of lauric acid,methyl laurate,or glycerol monolaurate alone,or RAW cells were challenged with LPS and then incubated with fatty acid ***:Treatment with zymosan orβ-glucan alone induced NFκB activation in a dose-dependent manner,whereas treatment with D-mannose,mannan,or live *** cells did ***-treatment with mannan after an LPS challenge decreased NFκB activation,suggesting that this treatment may ameliorate LPS-induced *** increases in NFκB activation were found when fatty acid treatments were applied in the absence of LPS,yet substantial reductio

关键词： Inflammation In vitro screening system NFκB

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Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation

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Neural Regeneration Research 2015年第12期10卷 2072-2080页

作者： Yi Xu Qing-hua Hou Shawn D.Russell bradford C.Bennett Andrew j.Sellers Qiang Lin Dong-feng Huang Department of Rehabilitation Medicine the First Affiliated Hospital of Sun Yat-sen University Guangdong Provincial Engineering Technology Research Center for Rehabilitation Medicine and Clinical Translation Motion Analysis and Motor Performance Laboratory Department of Orthopedics and Mechanical EngineeringUniversity of Virginia Department of Neurology Guangdong No.2 Provincial People’s Hospital H.C Sweere Center for Clinical Biomechanics and Applied Ergonomics Northwestern Health Science University Department of Radiology Naval Medical Center Portsmouth

Gait disorders drastically affect the quality of life of stroke survivors,making post-stroke rehabilitation an important research *** brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait ***,a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly *** first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery,and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait *** post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity,it evolves over time,is idiosyncratic,and may develop maladaptive ***,noninvasive brain stimulation has limited reach capability and is facilitative-only in ***,we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation ***,when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors,stimulation montages should be customized according to the specific types of neuroplasticity found in each *** could be done using multiple mapping techniques.

关键词： nerve regeneration stroke cerebrovascular disorders transcranial magnetic stimulation neuroplasticity transcranial direct current stimulation electrical stimulation therapy gait walking gait disorders rehabilitation neural regeneration

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全球地表热流的产生与分布

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地球物理学报 2001年第2期44卷 171-179页

作者：叶正仁 bradford H.Hager 中国科学院地质与地球物理研究所北京100101 DepartmentofEarth

全球地表热流是反映地球内部热与动力学过程的一种主要能流 .本文在三维球坐标框架下 ,就几个不同的粘度模型分别研究地幔内部密度异常 (基于全球地震层析结果 )以及板块运动激发的地幔流动的热效应及其对于观测地表热流产生和分布特征... 详细信息

全球地表热流是反映地球内部热与动力学过程的一种主要能流 .本文在三维球坐标框架下 ,就几个不同的粘度模型分别研究地幔内部密度异常 (基于全球地震层析结果 )以及板块运动激发的地幔流动的热效应及其对于观测地表热流产生和分布特征的贡献 .由于地幔动力系统具有较高的Pe数 ,可以期望由板块运动激发的地幔流动将强烈地扰动地幔内部初始传导状态下的温度场以及地表热的热流分布 .结果表明 ,与地幔内部密度异常产生的热效应相比 ,运动的板块及其激发的地幔流动在全球地表观测热流的产生和分布特征上起着更为重要的作用 .观测到的大洋中脊处的高热流在很大程度上可以归因于板块激发的地幔流动的热效应 .计算的平均温度剖面较好地揭示了岩石圈和D″层的温度特征 ,即温度随深度的剧烈变化 ,这与我们目前通过其他手段对岩石圈和D″层的温度结构了解是一致的 .一个下地幔粘度比上地幔高出 30倍的粘度结构 (文中使用的粘度模型 2 )较之其余模型的拟合程度似乎更好 .

关键词：地表热流地幔流动 Peclet数板块运动粘度模型密度热效应

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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry j.bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A Ketosis

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