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Apalutamide for metastatic castration-sensitive prostate cancer:final analysis of the Asian subpopulation in the TITAN trial

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Asian Journal of Andrology 2023年第6期25卷 653-661页

作者： Byung Ha Chung Jian Huang Hiroji Uemura Young deuk Choi Zhang-Qun Ye Hiroyoshi Suzuki Taek Won Kang da-Lin He Jae Young Joung sabine d brookman-may Sharon McCarthy Amitabha Bhaumik Anildeep Singh Suneel Mundle Simon Chowdhury Neeraj Agarwal ding-Wei Ye Kim N Chi Hirotsugu Uemura Gangnam Severance Hospital Yonsei University College of MedicineSeoul 06273South Korea Sun Yat-Sen Memorial Hospital Sun Yat-Sen UniversityGuangzhou 510123China Yokohama City University Medical Center Minami-kuYokohamaKanagwa 232-0024Japan Severance Hospital Yonsei University College of MedicineSeoul 03722South Korea Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Toho University Sakura Medical Center Chiba 285-0841Japan Chonnam National University Hospital and Medical School Gwangju 61469South Korea department of Urology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Prostate Cancer Center National Cancer CenterGoyang 10408South Korea Janssen Research and development Spring HousePA 19002USA Ludwig Maximilians University Munich 80539Germany Janssen Research and development RaritanNJ 08869USA Janssen Medical Affairs Asia PacificSingapore 118222Singapore Guy’s and St Thomas’NHS Foundation Trust London SE14YBUK University of Utah Huntsman Cancer Institute Salt Lake CityUT 84112USA Fudan University Shanghai Cancer Center Shanghai 200032China Vancouver Prostate Centre University of British ColumbiaVancouverBritish Columbia V6H 3Z6Canada Kindai University Faculty of MedicineOsaka-Sayama 589-8511Japan

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(AdT)versus AdT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian ***-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or *** endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for *** Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus *** a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to *** outcomes were comparable between subgroups with low-and high-volume disease at *** new safety issues were *** provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.

关键词： apalutamide Asia event-driven analysis metastatic castration-sensitive prostate cancer overall survival

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data-driven analysis of chemicals,proteins and pathways associated with peanut allergy:from molecular networking to biological interpretation

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Food Science and Human Wellness 2024年第3期13卷 1322-1335页

作者： Emmanuel Kemmler Julian Braun Florent Fauchère sabine dölle-Bierke Kirsten Beyer Robert Preissner Margitta Worm Priyanka Banerjee Institute for Physiology Charité-University Medicine BerlinBerlin 10115Germany Member of the KFO339 FOOD@Berlin 10115Germany Si-M/“der Simulierte Mensch”a science framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin Berlin 10115Germany Charité-Universitätsmedizin Berlin corporate member of Freie Universität BerlinHumboldt-Universität zu Berlinand Berlin Institute of HealthBerlin 10115Germany division of Allergy and Immunology Department of DermatologyVenerology and AllergyCharité-Universitätsmedizin Berlincorporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinBerlin 10115Germany Pediatrics Campus VirchowCharité-University Medicine BerlinBerlin 10115Germany

Peanut allergy is majorly related to severe food induced allergic *** food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food ***,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and ***,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and *** the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic *** results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.

关键词： Allergy informatics Knowledge-graph data analysis Food allergy Peroxisome proliferator-activated receptors Fatty acids

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碰撞激活诱导的双势阱势能面可以实现9-甲基-8-氧鸟嘌呤-9-甲基腺嘌呤碱基对阳离子自由基的质子转移

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Chinese Journal of Chemical Physics 2024年第2期37卷 330-340,I0022-I0039,I0104页

作者： may Myat Moe 刘剑波美国纽约城市大学皇后学院化学与生物化学系纽约11367 美国纽约城市大学研究生院纽约10016

8-氧鸟嘌呤(OG)是最常见的核碱基氧化损伤,它在复制过程中可以用Hoogsteen的模式与腺嘌呤(A)错误配对.0G.A碱基对不仅可以诱发G·C→T·A的颠换突变,而且由于OG的电离势和氧化电位低于天然dNA碱基更容易受到电离辐射和单电子氧化的影响... 详细信息

8-氧鸟嘌呤(OG)是最常见的核碱基氧化损伤,它在复制过程中可以用Hoogsteen的模式与腺嘌呤(A)错误配对.0G.A碱基对不仅可以诱发G·C→T·A的颠换突变,而且由于OG的电离势和氧化电位低于天然dNA碱基更容易受到电离辐射和单电子氧化的影响,本文报道了[9MOG·9MA]^(·+)碱華对阳离子自由基的形成.和碰撞诱导解离,该碱基对利用9-甲基8-氧鸟嘌呤(9MOG)和9-甲基腺嘌呤(9MA)模拟相对应的核苷酸.实验通过电喷雾产生Cu(Ⅱ)碱基复合物继之以氧化分离产生[9MOG·9MA]^(·+),并使用导向离子束串级质谱仪检测[9MOG·9MA]^(·+)的碰撞诱导解离、通过测量在不同碰撞能量下的解离产物和反应截面,可以得出[9MOG-H]+[9MA+H]^(+)(主要解离通道)和9MOG^(·+)+9MA(次要通道)的0 K解离阈能分别为1.8和1.65 eV.使用密度泛函理论对[9MOG·9MA]^(·+)的结构计算发现其所有重要构象都发生了质子转移生成[9MOG-H]^(·)·[9MA+H]^(+).另一方面,9MOG^(·+)+9MA的解离通道却需要9MOG^(·+)9MA作为中间体.看似矛盾的结果可以用碰撞活化后反应势能面上出现的双重势阱和由此触发的激发态质子转移平衡([9MOG-H]^(·)·[9MA+H]^(+))^(*)→←(9MOG6(·+)·9MA)^(*)来解释.本文实验和理论研究揭示了这种生物学上重要的非规范碱基对如何在氧化和电离损伤时发生解离.

关键词：碱基对阳离子自由基碰撞诱导解离碱基对内质子转移反应势能面电喷雾电离质谱导向离子束散射

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Vlale circumcision is not associated with an ncreased prevalence of erectile dysfunction

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Asian Journal of Andrology 2014年第4期16卷 652-653页

作者： Ingmar Wolff Matthias may Bernd Hoschke sabine brookman-may department of Urology CarI-Thiem-Hospital Cottbus Cottbus department of Urology St. Elisabeth-Hospital Straubing Straubing department of Urology University Hospital Ludwig Maximilian University Munich Germany.

dear Editor, The impact of circumcision on erectile function and sexual satisfaction is currently controversially discussed. Recently, Bronselaer et al.1 reported on a studybased on an online survey including 1059 （77.4%） uncircumcised and 310 （22.6%） circumcised men. They found a significantly higher sexual pleasure at all aspects of the glans penis and higher orgasm intensity at the lateral and dorsal sides of the glans in uncircumcised men. There was also a trend for higher orgasm intensity at the ventral side of the glans penis although statistical significance was not reached. Bronselaer et al？

关键词： SEXUAL SATISFACTION

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Process engineering of demineralisation of moderate to high ash Indian coals through NaOH‑HCl leaching and HF leaching

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International Journal of Coal Science & Technology 2024年第2期11卷 111-122页

作者： Heena dhawan d.K.Sharma ANRF Ministry of ScienceNew DelhiIndia department of Energy Science and Engineering Indian Institute of Technology DelhiNew Delhi 110016India

Chemical leaching of coals would be required to produce cleaner coals for some special applications where physical benefi-ciation may not be effective *** would also help in recovering Li and rare earth metals besides in the sequestration of CO_(2).About 20 Indian coals having complexly distributed moderate to high ash contents were sequentially treated with various alkali–acid such as NaOH-HCl,HF,HCl,HCl-HF,and NaOH-HCl-HF *** aimed to establish and design the best stepwise sequential process for the highest degree of demineralisation through a chemical leaching *** and process intensification studies were carried *** than 80%demineralisation of Madhaipur and Neemcha coals was observed using the best sequential treatment designed *** repeated stepwise treatment of the alkali and the acid was also studied,which was found to significantly enhance the degree of demineralisation of *** integrated process of alkali–acid leaching followed by solvent extraction(Organo-refining)and vice versa of the treated coal was also studied for producing cleaner coals.

关键词： Alkali–acid leaching demineralisation Integrated process Rare earth elements

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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn d.Roseborough Wenxuan Wang Jeng-liang d.Wu Shawn N.Whitehead department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and dentistry Western UniversityLondonONCanada deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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designing a medical ethics curriculum in ophthalmology

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Annals of Eye Science 2024年第1期9卷 4-9页

作者： Matthew d.Gearinger Flaum Eye Institute University of Rochester Medical CenterRochesterNYUSA

Ethical principles form a bedrock to medical practice in any specialty,guiding physicians to appropriate attitudes and behaviors.A formal ethics curriculum can be difficult to generate de novo in an ophthalmology training program.A number of barriers exist in most ophthalmology departments:trainees may think ethics is of secondary importance compared to core basic and clinical science topics;most ophthalmology faculty have no formal degree in medical ethics;there is limited didactic time with competing academic,clinical,and surgical priorities;work-hours regulations may limit the time available to deliver“para-professional”lectures;and there is a belief that the medical ethics lectures during medical school is a sufficient amount of coursework to last through a physician’s career with no need for continuing professional *** four pillars of medical ethics are beneficence,non-maleficence,autonomy,and *** addition,morals,ethics,and professionalism are important aspects of sound medical practice.A curriculum specific to medical ethics in ophthalmology can be developed in any of our sub-specialties and include lectures,curated readings,case rounds,and clinic wrap-up *** considerations are part of everyday clinical practice,and a structured ethics curriculum can be incorporated into ophthalmology training *** concept of backward design can be used to structure the curriculum,starting with the expected outcome,then designing authentic assessments,and finally putting together a learning plan that has students actively involved in ethical *** paper will provide a guide to developing an ethics curriculum for an ophthalmology training program utilizing the concept of backwards design and guide the reader through the process of developing expected learning outcomes,authentic assessments,and a unified learning plan.

关键词： Medical ethics curriculum design medical education

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design of Resilient Sensor Networks Balancing Resilience and Efficiency

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International Journal of disaster Risk Science 2024年第1期15卷 107-115页

作者： Sergey N.Vecherin Kiril d.Ratmanski Luke Hogewood Igor Linkov Cold Regions Research and Engineering Laboratory Engineering Research and Development CenterHanoverNH 03755USA Environmental Laboratory Engineering Research and Development CenterVicksburgMS 39180USA

In recent years,the notion of resilience has been developed and applied in many technical areas,becoming exceptionally pertinent to disaster risk *** a disaster situation,accurate sensing information is the key to efficient recovery *** general,resilience aims to minimize the impact of disruptions to systems through the fast recovery of critical functionality,but resilient design may require redundancy and could increase *** this article,we describe a method based on binary linear programming for sensor network design balancing efficiency with *** application of the developed framework is demonstrated for the case of interior building surveillance utilizing infrared sensors in both twoand three-dimensional *** method provides optimal sensor placement,taking into account critical functionality and a desired level of resilience and considering sensor type and *** problem formulation,resilience requirements,and application of the optimization algorithm are described in *** of sensor locations with and without resilience requirements shows that resilient configuration requires redundancy in number of sensors and their intelligent *** tasks are successfully solved by the described method,which can be applied to strengthen the resilience of sensor networks by *** proposed methodology is suitable for large-scale optimization problems with many sensors and extensive coverage areas.

关键词： Binary linear programming Optimal sensor placement Redundant networks Resilience and efciency Resilient sensor networks

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Natural parasites in conjunction with behavioral and color traits explain male agonistic behaviors in a lizard

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Current Zoology 2024年第1期70卷 59-69页

作者： Rodrigo Megia-Palma dhanashree Paranjpe Robert d.Cooper Pauline Blaimont Barry Sinervo department of Biomedicine and Biotechnology Parasitology UnitUniversidad de Alcala(UAH)E-28805Alcala de HenaresSpain CIBio Centro de Investigagao em Biodiversidade e Recursos GeneticosInBIO Laboratorio AssociadoCampus de VairaoUniversidade do PortoP-4485-661 VairaoPortugal BIOPOLIS Program in Genomics Biodiversity and Land PlanningCIBIOCampus de VairaoP-4485-661 VairaoPortugal Rupa Rahul Bajaj Center for Environment and Art Empress Botanical GardensKavade MalaPuneIndia department of Ecology and Evolutionary Biology University of CaliforniaLos AngelesCA 90095USA department of Biology University of Houston Downtown1Main St.HoustonTX 77002USA department of Ecology and Evolutionary Biology University of CaliforniaSanta CruzCA 95064USA

Male competition conforms to a cost-benefit model,because while aggression may increase reproductive prospects,it can also increase the risk of *** hypothesize that an additional cost in aggressive males would be an increase in parasite load associated with a high energy investment into sexual *** of these infections,in turn,may downmodulate the level of host aggression via energetic *** staged dyadic male contests in the lab to investigate the relationships of multiple parasites with the agonistic behavior of lizard hosts,Sceloporus *** also included both color and behavioral traits from opponents in the analyses because(1)color patches of lizards may serve as intraspecific signals used by conspecifics to assess the quality of opponents,and(2)contests between male lizards fit classical models of escalated aggression,where lizards increase aggression displays in response to an opponent's *** results conform to our hypothesis because male lizards displayed more pushups when they had more ***,some parasites may modulate the levels of aggression because lizards infected by hematic coccidians performed fewer ***,lizards also displayed fewer pushups when both the chroma and size of the opponent's blue patch were *** results thus also supported the role of the blue patch of *** as a sexual armament,because it contributed to the deterrence of aggression from opponent *** revealed that natural parasitic infections in lizard hosts can contribute to their agonistic *** encourage future studies to account for parasites in behavioral testswithlizards.

关键词： Ixodes pacificus Lankesterella sexual selection social interactions ticks

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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

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International Journal of Extreme Manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath Mitra Sushant Ciliveri Jose d Avila William dernell Stuart B Goodman Susmita Bose W.M.Keck Biomedical Materials Research Laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America Veterinary Clinical Sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. Mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3d printing antibacterial performance

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