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Bone-targeted therapies to reduce skeletal morbidity in prostate cancer

Asian Journal of Andrology 2018年第3期20卷 215-220页

作者： Tanya B Dorff neeraj agarwal USC Keck School of Medicine USC Norris Comprehensive Cancer Center Genitourinary Oncology Los Angeles CA 90033 USA Hunts Man Cancer Institute Universityof Utah 2000 Circle of Hope Salt Lake City UT 84112 USA

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

关键词： bisphosphonate bone metastases prostate cancer radiopharmaceutical receptor activator of nuclear factor-kappa B-ligand

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Risk factors of COVID-19 infection among policemen: A case-control study

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Journal of Acute Disease 2020年第6期9卷 263-269页

作者： neeraj agarwal Bijit Biswas Department of Community and Family Medicine All India Institute of Medical SciencesPatnaBiharIndia

Objective:To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of ***:This case-control study was conducted in Bihar,located in the eastern part of *** total,6 confirmed COVID-19 cases(the case group)and 11 negative contacts of these cases(the control group)of Bihar Military Police participated in the ***:All subjects were male with a median age of 51(range:23-60)*** these 6 confirmed cases,5 cases were *** third(33.3%)of the case group and the majority(90.9%)of the control group reported maintenance of physical distance of at least 1 meter with others all the time,which was significantly different(P=0.028).There was no other statistically significant difference between the case group and the control ***:Physical distancing is the most effective public health measure to control contagious diseases like COVID-19,especially in the absence of an effective vaccine in police settings.

关键词： COVID-19 Police Epidemiology Risk factors Protective factors

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Dexamethasone treatment alters kinetics properties of liver mitochondrial F<sub>0</sub>.F<sub>1</sub>-ATPase and membrane lipid profiles in developing and adult rats

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Advances in Enzyme Research 2013年第1期1卷 1-15页

作者： Jignesh D. Pandya neeraj A. agarwal Hiren R. Modi Surendra S. Katyare Department of Biochemistry Faculty of Science The Maharaja Sayajirao University of Baroda Vadodara India

Dexamethasone—a potent synthetic glucocorticoid—has multiple diagnostic and therapeutic applications in wide range of age groups. However, the side-effects of dexamethasone (Dex) treatment including those on development are becoming increasingly apparent. Since the developmental processes are energy-dependent, we examined the effects of chronic Dex treatment on kinetics properties of liver mitochondrial F0.F1-ATPase and mitochondrial membrane lipid profiles in rats belonging to different developmental age groups (2, 3, 4 and 5 weeks) and in adults (~8 weeks). The animals were treated with a subcutaneous dose of 2 mg of Dex/kg body weight (or saline as vehicle) for three alternative days (at around 7.00 A.M.) prior to the day of sacrifice. Dex treatment resulted in significant reduction in F0.F1-ATPase activity in developmental age groups and in adults as compared to their age-matched vehicle-treated control group. The substrate kinetics analysis of F0.F1-ATPase resolved Km and Vmax values in 3 components in all the control age groups;whereas Dex treatment significantly altered the Km and Vmax values or abolished the entire components in age-specific manner. Dex treatment significantly lowered the energy of activation and altered phase transition temperature (TtoC) in all the developmental age groups and in adults. Dex treatment significantly increased the contents of total phospholipid (TPL), individual phospholipids classes and cholesterol (CHL) in all the developmental age groups whereas opposite pattern was observed in adults. The mitochondrial membrane became more fluidized in the developing age groups (2, 4 and 5 weeks);whereas no change was observed in 3-week and adult groups following Dex treatment. In present study, our data demonstrate comprehensive deleterious effects of chronic Dex treatment on liver mitochondrial membrane structure and F0.F1-ATPase functional properties with respect to energy metabolism. At the same time, our data also warns against exce

关键词： Dexamethasone Development Glucocorticoids Liver Mitochondria F0.F1-ATPase Substrate and Temperature Kinetics Lipid and Phospholipid Profiles

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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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Diagnosis and Detection of Alzheimer’s Disease Using Learning Algorithm

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Big Data Mining and Analytics 2023年第4期6卷 504-512页

作者： Gargi Pant Shukla Santosh Kumar Saroj Kumar Pandey Rohit agarwal neeraj Varshney Ankit Kumar the Department of Management Doon Business SchoolDehradun 248001India. Jaipuria Institute of Management Jaipur 302033India Department of Computer Engineering and Apllications GLA UniversityMathura 281406India.

In Computer-Aided Detection(CAD)brain disease classification is a vital ***’s Disease(AD)and brain tumors are the primary reasons of *** studies of these diseases are carried out by Magnetic Resonance Imaging(MRI),Positron Emission Tomography(PET),and Computed Tomography(CT)scans which require expertise to understand the *** disease is the most prevalent in the elderly and can be fatal in its later *** result can be determined by calculating the mini-mental state exam score,following which the MRI scan of the brain is *** from that,various classification algorithms,such as machine learning and deep learning,are useful for diagnosing MRI ***,they do have some limitations in terms of *** paper proposes some insightful pre-processing methods that significantly improve the classification performance of these MRI ***,it reduced the time it took to train the model of various pre-existing learning algorithms.A dataset was obtained from Alzheimer’s Disease Neurological Initiative(ADNI)and converted from a 4D format to a 2D *** clipping,grayscale image conversion,and histogram equalization techniques were used to pre-process the *** pre-processing,we proposed three learning algorithms for AD classification,that is random forest,XGBoost,and Convolution Neural Networks(CNN).Results are computed on dataset and show that it outperformed with exiting work in terms of accuracy is 97.57%and sensitivity is 97.60%.

关键词： alzheimer’s disease deep learning random forest XGBoost

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Feasibility and efficacy of gentamicin for treating neonatal sepsis in community-based settings:a systematic review

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世界儿科杂志:英文版 2016年第4期12卷 408-414页

作者： Nishant Jaiswal Meenu Singh Ritika Kondel Navjot Kaur Kiran K.Thumburu Ajay Kumar Harpreet Kaur Neelima Chadha neeraj Gupta Amit agarwal Samir Malhotra Nusrat Shafiq ICMR Advanced Centre for Evidence Based Child Health Postgraduate Institute of Medical Education and ResearchChandigarhIndia Department of Pharmacology Postgraduate Institute of Medical Education and ResearchChandigarh160012India Department of Pediatrics Postgraduate Institute of Medical Education and ResearchChandigarhIndia Dr.Tulsi Das Library Postgraduate Institute of Medical Education and ResearchChandigarhIndia Department of Library University Business SchoolPunjab UniversityChandigarhIndia Department of Pediatrics AIIMSJodhpurRajasthanIndia

Background:Neonatal sepsis is a leading cause of neonatal deaths in developing *** current recommended in-hospital treatment is parenteral ampicillin(or penicillin)and gentamicin in young infants for 10-14 days;however,very few could access and *** current review is to evaluate the feasibility of gentamicin in community based ***:Both observational and randomized controlled trials were ***,Embase,Cochrane Central Register of Controlled Trials and Central Trial Register of India were searched until September *** assessed the risk of bias by Cochrane Collaboration’s"risk of bias"***:Two observational studies indicated feasibility ensuring coverage of population,decrease in case fatality rate in the group treated by community health *** an RCT,no significant difference was observed in the treatment failure rates[odds ratio(OR)=0.88],and the mortality in the first and second week(OR=1.53;OR=2.24)between gentamicin and ceftriaxone *** the gentamicin group,the combination of penicillin and gentamicin showed a lower rate of treatment failure(OR=0.44)and mortality at second week of life(OR=0.17)as compared to the combination of gentamicin and oral ***:Gentamicin for the treatment of neonatal sepsis is both feasible and effective in community-based settings and can be used as an alternative to the hospitalbased care in resource compromised *** there was less evidence in the management of neonatal sepsis in hospitals as was seen in this review in which we included only one RCT and three observational studies.

关键词： gentamicin neonatal sepsis neonates

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Erythropoietin therapy after out-of-hospital cardiac arrest:A systematic review and meta-analysis

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World Journal of Cardiology 2017年第12期9卷 830-837页

作者： Rahul Chaudhary Jalaj Garg Parasuram Krishnamoorthy Kevin Bliden neeraj Shah Nayan agarwal Rahul Gupta Abhishek Sharma Karl B Kern Nainesh C Patel Paul Gurbel Department of Medicine Sinai Hospital of BaltimoreBaltimoreMD 21215United States Division of Cardiology Lehigh Valley Health NetworkAllentownPA 18103United States Department of Medicine Division of CardiologyEinstein Healthcare NetworkPhiladelphiaPA 19141United States Inova Heart and Vascular Institute Inova Medical CenterFairfaxVA 22042United States Division of Cardiovascular Medicine University of FloridaGainesvilleFL 32611United States Queens Cardiac Care QueensNY 11428United States Division of Cardiovascular Medicine State University of New YorkBrooklynNY 12246United States Division of Cardiology University of Arizona College of MedicineTucsonAZ 85721United States

AIM To assess safety and efficacy of early erythropoietin(Epo) administration in patients with out-of-hospital cardiac arrest(OHCA).METHODS A systematic literature search was performed using PubM ed,MEDLINE,EMBASE,EBSCO,CINAHL,Web of Science and Cochrane databases,of all studies published from the inception through October 10,*** criteria included:(1) Adult humans with OHCA and successful sustained return of spontaneous circulation;and(2) studies including mortality/brain death,acute thrombotic events as their end *** efficacyoutcome was "brain death or Cerebral Performance Category(CPC) score of 5".Secondary outcomes were "CPC score 1,and 2-4","overall thrombotic events" and "acute coronary stent thrombosis".RESULTS We analyzed a total of 606 participants(n = 276 received Epo and n = 330 with standard of care alone) who experienced OHCA enrolled in 3 clinical *** significant difference was observed between the Epo and no Epo group in brain death or CPC score 5(OR = 0.77;95%CI:0.42-1.39),CPC score 1(OR = 1.16,95%CI:0.82-1.64),and CPC score 2-4(OR = 0.77,95%CI:0.44-1.36).Epo group was associated with increased thrombotic complications(OR = 2.41,95%CI:1.26-4.62) and acute coronary stent thrombosis(OR = 8.16,95%CI:1.39-47.99).No publication bias was *** Our study demonstrates no improvement in neurological outcomes and increased incidence of thrombotic events and acute coronary stent thrombosis in OHCA patients who were treated with Epo in addition to standard therapy.

关键词： Erythropoietin Thrombosis Cardiac arrest Cardiopulmonary resuscitation

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