Plos One
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After claiming nearly five hundred thousand lives globally, the COVID-19 pandemic is showing no signs of slowing down. While the UK, USA, Brazil and parts of Asia are bracing themselves for the second wave-or the extension of the first wave-it is imperative to identify the primary social, economic, environmental, demographic, ethnic, cultural and health factors contributing towards COVID-19 infection and mortality numbers to facilitate mitigation and control measures. ⋯ States forming the early hotspots are regions with high airport or road traffic resulting in human interaction. US states with high population density and testing tend to exhibit consistently high infected and death numbers. Mortality rate seems to be driven by individual physiology, preexisting condition, age etc., rather than gender, healthcare facility or ethnic predisposition. Finally, policymaking on the timing of lockdowns should primarily consider the pre-lockdown infected numbers along with population density and airport traffic.
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Allowing members of the crowd to propose novel microtasks for one another is an effective way to combine the efficiencies of traditional microtask work with the inventiveness and hypothesis generation potential of human workers. However, microtask proposal leads to a growing set of tasks that may overwhelm limited crowdsourcer resources. Crowdsourcers can employ methods to utilize their resources efficiently, but algorithmic approaches to efficient crowdsourcing generally require a fixed task set of known size. ⋯ Cost forecasting allows the crowdsourcer to decide between eliciting new tasks from the crowd or receiving responses to existing tasks based on whether or not new tasks will cost less to complete than existing tasks, efficiently balancing resources as crowdsourcing occurs. Experiments with real and synthetic crowdsourcing data show that cost forecasting leads to improved accuracy. Accuracy and efficiency gains for crowd-generated microtasks hold the promise to further leverage the creativity and wisdom of the crowd, with applications such as generating more informative and diverse training data for machine learning applications and improving the performance of user-generated content and question-answering platforms.
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Alterations in fibroblast growth factor receptor (FGFR) genes have been identified as potential driver oncogenes. Pharmacological targeting of FGFRs may therefore provide therapeutic benefit to selected cancer patients, and proof-of-concept has been established in early clinical trials of FGFR inhibitors. Here, we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials. ⋯ The preclinical pharmacokinetic profile suggests target inhibition is achievable by INCB054828 in vivo with low oral doses. INCB054828 suppressed the growth of xenografted tumor models with FGFR1, 2, or 3 alterations as monotherapy, and the combination of INCB054828 with cisplatin provided significant benefit over either single agent, with an acceptable tolerability. The preclinical data presented for INCB054828, together with preliminary clinical observations, support continued investigation in patients with FGFR alterations, such as fusions and activating mutations.
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The novel coronavirus 2019 (COVID-19) global pandemic has drastically affected the world economy, raised public anxiety, and placed a substantial psychological burden on the governments and healthcare professionals by affecting over 4.7 million people worldwide. As a preventive measure to minimise the risk of community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in India, a nationwide lockdown was imposed initially for 21 days to limit the movement of 1.3 billion people. These restrictions continue in most areas, with a conditional relaxation occurring in a few Indian states. ⋯ Additionally, we identified 18 mutations in the SARS-CoV-2 spike glycoprotein and a few selected mutations showed to increase stability, binding affinity, and molecular flexibility in the overall tertiary structure of the protein that may facilitate interaction between the receptor binding domain (RBD) of spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. The study provides a pragmatic view of haplotype-dependent spread of SARS-CoV-2 in India which could be important in tailoring the pharmacologic treatments to be more effective for those infected with the most common haplotypes. The findings based on the time-lapse sentinel surveillance of SARS-CoV-2 will aid in the development of a real-time practical framework to tackle the ongoing, fast-evolving epidemic challenges in the country.
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Chest CT findings related to mortality of patients with COVID-19: A retrospective case-series study.
As the current outbreak of COVID-2019 disease has spread to the other more than 150 countries besides China around the world and the death number constantly increased, the clinical data and radiological findings of death cases need to be explored so that more physicians, radiologists and researchers can gain important information to save more lives. ⋯ Chest CT findings and laboratory test results were worsening in patients who died of COVID-19, with moderate positive correlations between CT severity scores and inflammation-related factors of leucocytes, neutrophils, and IL-2R. Chest CT imaging may play an more important role in monitoring disease progression and predicting prognosis.