Project description:GigaScience is now 5 years old, having been launched at the 2012 Intelligent Systems for Molecular Biology conference. Anyone who has attended what is the largest computational biology conference since then has had the opportunity to join us for each birthday celebration-and receive 1 of our fun T-shirts as a party prize. Since launching, we have pushed our agenda of openness, transparency, reproducibility, and reusability. Here, we look back at our first 5 years and what we have done to forward our open science goals in scientific publishing. Our mainstay has been to create a process that allows the availability and publication of as many "research objects" as possible to create a more complete way of communicating how the research process is done.
Project description:Over the past 20 years, there has been tremendous progress in retinal gene therapy. The safety and efficacy results in one early-onset severe blinding disease may lead to the first gene therapy drug approval in the United States. Here, we review how far the field has come over the past two decades and speculate on the directions that the field will take in the future.
Project description:BackgroundAvailable evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed.ObjectivesWe investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ? 2.5 ?m (PM2.5; fine particles), ? 10 ?m, and 2.5-10 ?m, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters.MethodsThis study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000-2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations.ResultsWe found positive associations for most of our evaluated outcome-exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance.ConclusionWe observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic.
Project description:Lipid nanoparticles (LNPs) have shown remarkable success in delivering genetic materials like COVID-19 LNP vaccines, such as mRNA-1273/SpikeVax by Moderna and BNT162b2/Comirnaty by BioNTech/Pfizer, as well as siRNA for rare inherited diseases, such as Onpattro from Alnylam Pharmaceuticals. These LNPs are advantageous since they minimize side effects, target specific cells, and regulate payload delivery. There has been a surge of interest in these particles due to their success stories; however, we still do not know much about how they work. This perspective will recapitulate the evolution of lipid-based gene delivery, starting with Felgner's pioneering 1987 PNAS paper, which introduced the initial DNA-transfection method utilizing a synthetic cationic lipid. Our journey takes us to the early 2020s, a time when advancements in bionano interactions enabled us to create biomimetic lipoplexes characterized by a remarkable ability to evade capture by immune cells in vivo. Through this overview, we propose leveraging previous achievements to assist us in formulating improved research goals when optimizing LNPs for medical conditions such as infectious diseases, cancer, and heritable disorders.
Project description:Implications In this commentary, we describe the evidence-based approach used to identify the primary cause of EVALI and to curb the 2019 outbreak. We also discuss future research opportunities and public health practice considerations to prevent a resurgence of EVALI.
Project description:Covid Act Now (CAN) developed an epidemiological model that takes various non-pharmaceutical interventions (NPIs) into account and predicts viral spread and subsequent health outcomes. In this study, the projections of the model developed by CAN were back-tested against real-world data, and it was found that the model consistently overestimated hospitalizations and deaths by 25%-100% and 70%-170%, respectively, due in part to an underestimation of the efficacy of NPIs. Other COVID models were also back-tested against historical data, and it was found that all models generally captured the potential magnitude and directionality of the pandemic in the short term. There are limitations to epidemiological models, but understanding these limitations enables these models to be utilized as tools for data-driven decision-making in viral outbreaks. Further, it can be valuable to have multiple, independently developed models to mitigate the inaccuracies of or to correct for the incorrect assumptions made by a particular model.
Project description:The field of Alzheimer disease (AD) prevention has been a culmination of basic science, clinical, and translational research. In the past three years since the new 2011 AD diagnostic guidelines, large-scale collaborative efforts have embarked on new clinical trials with the hope of someday preventing AD. This review will shed light on the historical and scientific contexts in which these trials were based on, as well as discuss potential challenges these trials may face in the coming years. Primary preventive measures, such as lifestyle, multidomain, medication, and supplemental interventions, will be analyzed. Secondary prevention as represented by disease-modifying interventions, such as antiamyloid therapy and pioglitazone, will also be reviewed. Finally, hypotheses on future directions for AD prevention trials will be proposed.
Project description:In commemoration of the centennial of the 1918 influenza pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. We also highlight persisting mysteries in the origins and severity of the 1918 pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations.
Project description:Over the past two decades, population researchers have engaged in a far-reaching and productive program of research on demographic responses to changes in the natural environment. This essay "looks back" to the origins of these developments, identifying pivotal agenda-setting moments in the 1990s and tracing the impact on contemporary research. The essay also "looks forward" to identify critical gaps and challenges that remain to be addressed and to set an agenda for future research on population responses to environmental change. It recommends that the multidimensionality of environmental contexts and change be fully embraced, long run as well as short term effects be investigated, variability in the effects of environmental change in relation to social institutions, policy implementation, and environmental context be examined, movement between contexts as well as change in situ as sources of environmental change be considered, and interconnections among demographic processes in response to environmental change be explored. Taking these steps will position demographers to contribute significantly to a larger and deeper understanding of environmental change and its consequences, locally, regionally, and globally.
Project description:Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases.