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Rakesh K. Jain

Bio: Rakesh K. Jain is an academic researcher from Harvard University. The author has contributed to research in topics: Angiogenesis & Vascular endothelial growth factor. The author has an hindex of 200, co-authored 1467 publications receiving 177727 citations. Previous affiliations of Rakesh K. Jain include Government Medical College, Thiruvananthapuram & University of Oslo.


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TL;DR: In this paper , the authors performed a large retrospective study of all patients treated with an ICI in a single academic network and found that concurrent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with better overall survival.
Abstract: Preclinical studies indicate that the concurrent use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) may improve outcomes in broad groups of patients with cancer. There are limited data on the association between the use of RAAS inhibitors and outcomes among patients treated with immune checkpoint inhibitors (ICIs).We performed a retrospective study of all patients treated with an ICI in a single academic network. Of 10,903 patients, 5910 were on any anti-hypertensive medication. Of those on anti-hypertensive therapy, 3426 were prescribed a RAAS inhibitor during ICI treatment, and 2484 were prescribed other anti-hypertensive medications. The primary outcome was overall survival in the entire cohort and in sub-groups by cancer types.Thoracic cancer (34%) and melanoma (16%) were the most common types of cancer. Those prescribed a RAAS inhibitor were older, more frequently male, and had more cardiovascular risk factors. In a Cox proportional hazard model, the concurrent use of RAAS inhibitors was associated with better overall survival (hazard ratio (HR):0.92, [95% Confidence Interval (CI):0.85-0.99], P = .032). Patients with gastrointestinal (HR:0.82, [95% CI: 0.67-1.01], P = .057) and genitourinary cancer (HR:0.81, [95% CI:0.64-1.01], P = .067) had a non-statistically significant better overall survival.In this large retrospective study, patients with hypertension who were concomitantly taking a RAAS inhibitor during ICI therapy had better overall survival. This benefit was primarily noted among patients with gastrointestinal and genitourinary cancers. Prospective randomized trials are warranted to further evaluate and specify the benefit of RAAS inhibitors in patients with cancer who receive ICI therapy.

16 citations

Journal ArticleDOI
TL;DR: The causal virus was characterized as a strain of Cowpea mild mottle virus (CPMMV) on the basis of mechanical inoculation, whitefly transmission, seed transmission and sequencing of the viral genome.
Abstract: Soybean crops showing systemic mottling, mosaic and leaf deformation were observed at high disease incidences (25.1–71.0%) in the kharif season of 2011 and 2012 in the experimental farm of the Indian Agricultural Research Institute (IARI), New Delhi. Symptomatic soybean leaves contained flexuous particles (650 × 12 nm), suggesting an infection by a Carlavirus. The causal virus was characterized as a strain of Cowpea mild mottle virus (CPMMV) on the basis of mechanical inoculation, whitefly transmission, seed transmission and sequencing of the viral genome. This is the first report of natural infection by a distinct strain of CPMMV in soybean in India.

16 citations

Journal ArticleDOI
TL;DR: Despite the broad range of treatment options currently available, nonadherence remains a significant problem in ADHD and evidence is currently lacking, the availability of new formulations may improve adherence.
Abstract: OBJECTIVE To review currently available formulations and emphasize unmet needs in the pharmacologic management of attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES Publications and clinical trials were identified through PubMed and ClinicalTrials.gov, respectively. A Web-based search identified prescribing information for approved agents for treating ADHD, along with relevant guidelines and diagnostic criteria. STUDY SELECTION The following search terms were used: (1) ADHD or attention-deficit/hyperactivity disorder or ADD or attention deficit hyperactivity disorder and/or (2) amphetamine or methylphenidate or atomoxetine or guanfacine or clonidine. Additional searches were performed using product brand names, and clinical trial was applied as a filter. Relevant studies were only included if published in English-language peer-reviewed journals and if involved agents were currently available (or pursuing approval) in the United States. Reviews of literature prior to 2005 and from 2005 to 2008 have been published previously; therefore, the present search focused on studies published from January 2009 through May 2016. In addition, reference lists of review articles and relevant studies were also examined to help identify additional studies. DATA EXTRACTION A total of 578 publications were identified from the PubMed search, from which 426 publications were initially excluded based on review of the title and abstract. Reasons for exclusion included a focus on comorbid disorders, specific subpopulations, endpoints unrelated to improving ADHD symptomatology (eg, executive function, cognition, substance use), or quality of life measures. A more thorough assessment of the remaining citations, including publications and prescribing information, produced the final 219. RESULTS Pharmacotherapy with stimulant and nonstimulant options is the most common approach for treating ADHD in adults and children. Stimulants are mostly formulated as either tablets or capsules; however, the newer generation includes transdermal patches, oral suspensions (liquids), chewable tablets, and orally disintegrating tablets. Nonstimulants are available in oral capsule (atomoxetine) and tablet (guanfacine and clonidine) formulations. CONCLUSIONS Despite the broad range of treatment options currently available, nonadherence remains a significant problem in ADHD. While evidence is currently lacking, the availability of new formulations may improve adherence.

16 citations

Journal ArticleDOI
TL;DR: A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F1female mice and it was found that a single generalized forcing function can be used to fit plasma concentration after s.c.p. injection for all doses.
Abstract: A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F 1 female mice at doses ranging from 3 mg/kg to 400 mg/kg. Using standard methods of parameter estimation as well as experimental determinations, an integrated approach was derived to account for the differences between the subcutaneous (s.c.) and intraperitoneal (i.p.) modes of injection. It was found that a single generalized forcing function can be used to fit plasma concentration after s.c. injection for all doses. Adequate fits (average error<20% while the standard deviation of experimental determinations was±22%) of L1210 cell data after s.c. injection were obtained. The best results were for a maximum facilitated influx constant Vmax of 0.424 Μg/min/ml, a Michaelis influx constant Km of 1,42 Μg/ml, and a first-order efflux constant α of 0.047 min−1.The model simulations were not sensitive to Vmax, Km,and αso long as the ratio Vmax/αwas approximately 9Μg/ml. The values of V max ,K m ,and α which were obtained from our analysis of the in vivodata can be explained on the basis of previously performed in vitroexperiments. The parameters obtained from modeling the s.c. data were then applied for i.p. injection data. The resulting fits were adequate (average error<20% while the standard deviation of experimental determinations was±22%). A single generalized forcing function for drug concentration in the peritoneal cavity after i.p. injection for all doses was derived. The application of these results enables the prediction of methotrexate concentration in neoplastic cells at other doses after either s.c. or i.p. injection.

16 citations

Journal ArticleDOI
TL;DR: New topical anti-infectives comprised of N,N-dichloro-beta,beta-disubstituted taurines have been examined for structure-stability relationships (SSR) based upon various alkyl, heteroalkyl and cycloalkyle beta-substitutions.

16 citations


Cited by
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04 Mar 2011-Cell
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

51,099 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations

Journal ArticleDOI
TL;DR: The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

10,161 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations