Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental ...approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery.
The Molecular Libraries Project began in 2005 to develop small-molecule tools to promote biological and biomedical discoveries. This Perspective highlights the last decade’s advances and looks at opportunities ahead for informed innovation in small-molecule drug discovery.
This is a research article whose main objective is to discuss the impact of the COVID-19 pandemic on the activities of research institutes in Poland. The sources of the paper are the results of ...surveys conducted twice in 2020, on a selected sample of research institutes associated with the Main Council of Research Institutes. For the purposes of the article, surveys of the literature and available sources were made, and the method of analysis and synthesis was applied. The article closes with a summary containing the most important conclusions.
The lack of race/ethnic and gender diversity in grants funded by the National Institutes of Health (NIH) is a persistent challenge related to career advancement and the quality and relevance of ...health research. We describe pilot programs at nine institutions supported by the NIH-sponsored Building Infrastructure Leading to Diversity (BUILD) program aimed at increasing diversity in biomedical research.
We collected data from the 2016-2017 Higher Education Research Institute survey of faculty and NIH progress reports for the first four years of the program (2015-2018). We then conducted descriptive analyses of data from the nine BUILD institutions that had collected data and evaluated which activities were associated with research productivity. We used Poisson regression and rate ratios of the numbers of BUILD pilots funded, students included, abstracts, presentations, publications, and submitted and funded grant proposals.
Teaching workshops were associated with more abstracts (RR 4.04, 95% CI 2.21-8.09). Workshops on grant writing were associated with more publications (RR 2.64, 95% CI 1.64-4.34) and marginally with marginally more presentations. Incentives to develop courses were associated with more abstracts published (RR 4.33, 95% CI 2.56-7.75). Workshops on research skills and other incentives were not associated with any positive effects.
Pilot interventions show promise in supporting diversity in NIH-level research. Longitudinal modeling that considers time lags in career development in moving from project development to grants submissions can provide more direction for future diversity pilot interventions.
Abstract
Pragmatic clinical trials (PCTs) are research investigations embedded in health care settings designed to increase the efficiency of research and its relevance to clinical practice. The ...Health Care Systems Research Collaboratory, initiated by the National Institutes of Health Common Fund in 2010, is a pioneering cooperative aimed at identifying and overcoming operational challenges to pragmatic research. Drawing from our experience, we present 4 broad categories of informatics-related challenges: (1) using clinical data for research, (2) integrating data from heterogeneous systems, (3) using electronic health records to support intervention delivery or health system change, and (4) assessing and improving data capture to define study populations and outcomes. These challenges impact the validity, reliability, and integrity of PCTs. Achieving the full potential of PCTs and a learning health system will require meaningful partnerships between health system leadership and operations, and federally driven standards and policies to ensure that future electronic health record systems have the flexibility to support research.
The prevalence of type 2 diabetes and obesity has risen dramatically for decades and is expected to rise further, secondary to the growing aging, sedentary population. The strain on global health ...care is projected to be colossal. This review explores the latest work and emerging ideas related to genetic and environmental factors influencing metabolism. Translational research and clinical applications, including the impact of the COVID-19 pandemic, are highlighted. Looking forward, strategies to personalize all aspects of prevention, management and care are necessary to improve health outcomes and reduce the impact of these metabolic diseases.
Successful efforts to stem the rise in obesity and type 2 diabetes will require a detailed understanding of the genetic and environmental factors affecting individuals as well as a broad consideration of societal challenges, including responses to COVID-19, faced by communities across the globe.
Petroleum refining operations such as hydroprocessing and fluid catalytic cracking (FCC) generate huge quantities of spent catalysts containing toxic and valuable metals (Ni, V, Mo, Co, W, Al, etc.), ...the management of which is a serious environmental issue. Besides environmental concerns, the different metals present in the spent catalysts are also a valuable commodity to modern industries. Therefore, these spent catalysts also provide an opportunity to use it as a source of value to the refiners. In recent years, a biotechnological based leaching process ‘bioleaching’ has emerged as a promising eco-friendly technique for the extraction of metals from these refinery spent catalysts. Among various bioleaching agents such as archean, bacterial, or fungi, the process mediated by the fungi (Aspergillus niger, Penicillium simplicissimum, and many others) is gaining attention owing to the high metal extraction ability of the various fungal produced metabolites (organic acids) under moderately acidic conditions. Furthermore, the ability of these fungi to withstand wide process conditions (pH, spent catalyst concentration, substrate types, etc.), high metal toxicity and use of low-cost organic substrate make them an ideal candidate for bioleaching. In this review article, we shed light on the role and mechanisms of fungi involved in extracting different metals from spent hydroprocessing and FCC catalysts. Key process parameters that affect the efficiency of fungal based bioleaching are discussed. The techno-economic challenges associated with the process are elaborated, and the needed future research directions to promote its commercial applications are highlighted. Based on our analysis, it can be argued that the fungi bioleaching has potential, however, some challenges (slower kinetics, and health and safety) should be addressed before the process can be scaled up for the commercial application.
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•Fungal bioleaching of petroleum refinery spent catalyst has been reviewed in detail.•The reaction mechanisms of each fungus are described.•Key techno-economic and environmental challenges are discussed.•Prospects for fungal bioleaching processes are discussed.
In early 2020, the unprecedented nature of COVID-19 prompted India, among many other countries, to put in place stark measures to stem the virus’ spread and the cost of human lives. We analyze data ...from phone-based surveys on disruptions to agricultural production and food security, administered with 1515 smallholder producers in the states of Haryana and Odisha. We find substantial heterogeneity in how the lockdown affected farmers in these two states, which is likely related to existing structural differences in market infrastructure and to differences in state-specific COVID-related policies. In Odisha, where mechanization is limited, farmers spent more on labor to harvest their crops, and distress selling was more prevalent due to the absence of a well-functioning procurement system for their crops. In Haryana, preexisting market infrastructure allowed the state to sustain procurement at stable prices, limiting impacts on smallholder production. As consumers, farmers in Haryana faced more disruptions than those in Odisha, due to reduced availability of foods in the markets, whereas farmers in Odisha benefited from more diverse cropping patterns and increased local supply of foods following transport restrictions.
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