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Mechanism of PARP inhibitor resistance and potential overcoming strategies

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Genes & Diseases 2024年第1期11卷 306-320页

作者： Xiaoyu Fu Ping Li Qi Zhou Ruyuan He Guannan Wang Shiya Zhu Amir Bagheri gary Kupfer Huadong Pei Juanjuan Li Department of Oncology Georgetown Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC 20057USA Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Cancer Center Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Thoracic Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China

PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)*** is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair *** the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the *** this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.

关键词： Drug resistance Homologous recombination PARP PARP inhibitor Poly(ADP-ribose)polymerase

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis:A systematic review and meta-analysis

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Cancer Innovation 2024年第3期3卷 22-32页

作者： Wenhua Song Nan Zhang Tonglian Lv Yang Zhao Guangping Li gary Tse Tong Liu Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina Department of Radiology Second Hospital of Tianjin Medical UniversityTianjinChina School of Nursing and Health Studies Hong Kong Metropolitan UniversityHong KongChina Cardiac Electrophysiology Unit Cardiovascular Analytics GroupPowerHealth LimitedHong KongChina

Background:The role of surgery in metastatic breast cancer(MBC)is currently *** novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual ***:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery ***:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference *** models were trained to make individualized treatment *** who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the *** probability weighting(IPW)was used to minimize *** effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal ***:In total,5269 female patients with MBC were *** was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving *** debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also ***:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery *** method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

关键词： breast surgery causal inference deep learning metastatic breast cancer

Comparison of Block Design Nonparametric Subset Selection Rules Based on Alternative Scoring Rules

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Applied Mathematics 2024年第5期15卷 355-389页

作者： gary C. McDonald Sajidah Alsaeed Department of Mathematics and Statistics Oakland University Rochester MI USA

This article compares the size of selected subsets using nonparametric subset selection rules with two different scoring rules for the observations. The scoring rules are based on the expected values of order statistics of the uniform distribution (yielding rank values) and of the normal distribution (yielding normal score values). The comparison is made using state motor vehicle traffic fatality rates, published in a 2016 article, with fifty-one states (including DC as a state) and over a nineteen-year period (1994 through 2012). The earlier study considered four block design selection rules—two for choosing a subset to contain the “best” population (i.e., state with lowest mean fatality rate) and two for the “worst” population (i.e., highest mean rate) with a probability of correct selection chosen to be 0.90. Two selection rules based on normal scores resulted in selected subset sizes substantially smaller than corresponding rules based on ranks (7 vs. 16 and 3 vs. 12). For two other selection rules, the subsets chosen were very close in size (within one). A comparison is also made using state homicide rates, published in a 2022 article, with fifty states and covering eight years. The results are qualitatively the same as those obtained with the motor vehicle traffic fatality rates.

关键词： Order Statistics Rank Scoring Methods Probability of a Correct Selection Subset Size Motor Vehicle Traffic Fatality Rates Homicide Rates Asymptotic Distributions

On Performance Characteristics of a Nonparametric Subset Selection Procedure with a Small Randomized Block Experimental Design

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Applied Mathematics 2024年第9期15卷 630-650页

作者： gary C. McDonald Sajidah Alsaeed Department of Mathematics and Statistics Oakland University Rochester MI USA

This article addresses the issue of computing the constant required to implement a specific nonparametric subset selection procedure based on ranks of data arising in a statistical randomized block experimental design. A model of three populations and two blocks is used to compute the probability distribution of the relevant statistic, the maximum of the population rank sums minus the rank sum of the “best” population. Calculations are done for populations following a normal distribution, and for populations following a bi-uniform distribution. The least favorable configuration in these cases is shown to arise when all three populations follow identical distributions. The bi-uniform distribution leads to an asymptotic counterexample to the conjecture that the least favorable configuration, i.e., that configuration minimizing the probability of a correct selection, occurs when all populations are identically distributed. These results are consistent with other large-scale simulation studies. All relevant computational R-codes are provided in appendices.

关键词： Rank Statistics Least Favorable Configuration Probability of Correct Selection Slippage Configuration Equal Spaced Configuration Counterexample Configuration

Electronic properties of 2D materials and their junctions

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Nano Materials Science 2024年第1期6卷 1-23页

作者： Taposhree Dutta Neha Yadav Yongling Wu gary J.Cheng Xiu Liang Seeram Ramakrishna Aoussaj Sbai Rajeev Gupta Aniruddha Mondal Zheng Hongyu Ashish Yadav Department of Chemistry Indian Institute of Engineering Science and TechnologyShibpurWest Bengal711103India Center for Advanced Laser Manufacturing(CALM) Shandong University of TechnologyZibo255000PR China School of Industrial Engineering Purdue University315 N.Grant St.West LafayetteIN47907United States Birck Nanotechnology Center Purdue University1205 W State St.West LafayetteIN47907United States Advanced Materials Institute Qilu University of TechnologyShandong Academy of SciencesJinan250014PR China Nanoscience and Nanotechnology Initiative National University of Singapore10 Kent Ridge Crescent119260Singapore Faculty of Applied Phsyics and Mathematics Gdansk University of Technology Narutowicza 11/1280233GdanskPoland Department of Physics School of EngineeringUniversity of Petroleum&Energy StudiesDehradun248007UttarakhandIndia Department of Physics National Institute of Technology DurgapurDurgapur713209West BengalIndia

With an extensive range of distinctive features at nano meter-scale thicknesses,two-dimensional(2D)materials drawn the attention of the scientific *** tremendous advancements in exploratory research on 2D materials,knowledge of 2D electrical transport and carrier dynamics still in its ***,here we highlighted the electrical characteristics of 2D materials with electronic band structure,electronic transport,dielectric constant,carriers *** atomic thinness of 2D materials makes substantially scaled field-effect transistors(FETs)with reduced short-channel effects conceivable,even though strong carrier mobility required for high performance,low-voltage device *** also discussed here about factors affecting 2D materials which easily enhanced the activity of those materials for various ***,Those 2D materials used in state-of-the-art electrical and optoelectronic devices because of the extensive nature of their electronic band structure.2D materials offer unprecedented freedom for the design of novel p-n junction device topologies in contrast to conventional bulk *** also,describe the numerous 2D p-n junctions,such as homo junction and hetero junction including mixed dimensional ***,we talked about the problems and potential for the future.

关键词： 2D materials Electrical properties p-n junctions Mixed hereto junctions Homo junctions Electrical transport

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu gary M.K.Tse Wei Kang Ka Fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

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World Journal of Diabetes 2024年第5期15卷 867-875页

作者： Ying Liu Cun-Yu Lu Yi Zheng Yu-Min Zhang Ling-Ling Qian Ku-Lin Li gary Tse Ru-Xing Wang Tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjin 300211China Department of Cardiology Xuzhou No.1 Peoples HospitalXuzhou 221005Jiangsu ProvinceChina Department of Cardiology Wuxi 9^(th)People’s Hospital Affiliated to Soochow UniversityWuxi 214062Jiangsu ProvinceChina Department of Cardiology Wuxi People’s Hospital Affiliated to Nanjing Medical UniversityWuxi 214023Jiangsu ProvinceChina School of Nursing and Health Studies Metropolitan UniversityHong Kong 999077China Kent and Medway Medical School Kent CT27NTCanterburyUnited Kingdom

Diabetes mellitus is a prevalent disorder with multi-system manifestations,causing a significant burden in terms of disability and deaths ***-tensin receptor-neprilysin inhibitor(ARNI)belongs to a class of medications for treating heart failure,with the benefits of reducing hospitalization rates and *** review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications,discussing possible physiological and molecular mechanisms,with insights for future applications.

关键词： Angiotensin receptor-neprilysin inhibitor Diabetic mellitus Complication

Launch of the transdisciplinary health science journal hLife

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Biosafety and Health 2024年第1期6卷 1-2页

作者： Qun Yan Kieran gary Thow Editorial office of hLife Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China The University of Chinese Academy of Sciences Beijing 101408China

The launch ceremony of the health science journal hLife was held at the Institute of Microbiology,Chinese Academy of Sciences(CAS)on 15 November *** 100 guests attended the event,including the editors-in-chief of hLife and editorial board members,representatives from sister journals,regulatory agency leaders,and leaders of the Institute of Microbiology,CAs,and other related departments(Fig.1).

关键词： journal editorial sister

青藏高原及其周边三叠纪综合地层、生物群与古地理演化

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中国科学：地球科学 2024年第4期54卷 1171-1210页

作者：武桂春纪占胜 gary GLASH 曾庆高姚建新中国地质科学院地质研究所自然资源部地层与古生物重点实验室北京100037 中国地质科学院自然资源部深地科学与探测技术实验室北京100094 Department of Geology and Environmental Sciences State University of New York-FredoniaFredoniaNY 14063USA 西藏自治区地质矿产勘察开发局拉萨850010

青藏高原三叠纪古生物化石丰富,目前已建立了以菊石、牙形类、双壳类、腕足类和放射虫化石为主的海相生物序列以及以孢粉类化石为主的陆相生物序列,为青藏高原三叠纪年代地层划分对比提供了生物标尺.青藏高原在三叠纪整体处于海洋沉积区... 详细信息

青藏高原三叠纪古生物化石丰富,目前已建立了以菊石、牙形类、双壳类、腕足类和放射虫化石为主的海相生物序列以及以孢粉类化石为主的陆相生物序列,为青藏高原三叠纪年代地层划分对比提供了生物标尺.青藏高原在三叠纪整体处于海洋沉积区,海相三叠系发育,主要沉积类型有滨浅海相碎屑岩、浅海台地相碳酸盐岩、半深海斜坡-深海相碎屑岩、硅质岩、海陆过渡相含煤碎屑岩、滨浅海或陆相火山碎屑岩.青藏高原各个地层区的沉积地层序列在垂向上明显分为4个阶段:(1)早三叠世初期广泛接受海侵,发育台地相碳酸盐岩和滨浅海相碎屑岩沉积;(2)中三叠世拉丁期至晚三叠世卡尼期海侵规模最大,与早三叠世相比,沉积相整体变深,发育半深海斜坡-深海相薄层碳酸盐岩、细碎屑岩、硅质岩沉积,部分地区岩浆活动强烈;(3)晚三叠世诺利期海退,沉积相整体变浅,大面积发育台地相碳酸盐岩沉积和滨浅海碎屑岩沉积,在秦-祁-昆一带多表现为陆相地层沉积或陆相剥蚀区;(4)瑞替期持续海退,发育滨浅海碎屑岩或海陆过渡相含煤碎屑岩沉积.根据沉积地层的横向展布和垂向变化,本文对青藏高原三叠纪的沉积古地理按早三叠世、中三叠世-晚三叠世卡尼期、晚三叠世诺利期和晚三叠世瑞替期4个时期进行了描述.整体上,青藏高原在三叠纪是以印度河-雅鲁藏布江缝合带为拉张中心,沉积相向南、北两侧由深变浅,形成了南部冈瓦纳古陆被动边缘沉积体系和北部欧亚古陆被动大陆边缘沉积体系.班公湖-怒江缝合带与南侧的冈底斯地块(或拉萨地块)和北侧的南羌塘地块在沉积特征上比较一致,不是裂解拉张中心.古生物区系研究同样显示印度河-雅鲁藏布江缝合带在三叠纪时期是一个重要的古生物地理区系分界线,班公湖-怒江缝合带在该时期则不具有古生物地理区系分隔的意义.三叠纪时期是潘吉亚超大陆(Pangea)裂解的高峰期,该事件在青藏高原的主要响应是早、中三叠世沿印度河-雅鲁藏布江缝合带发生伸展裂解.印支运动在青藏高原主要表现为晚三叠世地壳抬升引起的沉积相变,在秦-祁-昆一带表现为海相沉积变为陆相沉积或陆相剥蚀区,而在冈底斯至南羌塘的广大地区,表现为台地相碳酸盐岩变为滨浅海相碎屑岩或海陆过渡相含煤碎屑岩.

关键词：青藏高原三叠系生物地层岩石地层古生物区系沉积古地理