Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement.

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientific community. Data from the first phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools-including CellxGene, Minerva, and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC's approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.

Observational study of organisational responses of 17 US hospitals over the first year of the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has required significant modifications of hospital care. The objective of this study was to examine the operational approaches taken by US hospitals over time in response to the COVID-19 pandemic. DESIGN, SETTING AND PARTICIPANTS: This was a prospective observational study of 17 geographically diverse US hospitals from February 2020 to February 2021. OUTCOMES AND ANALYSIS: We identified 42 potential pandemic-related strategies and obtained week-to-week data about their use. We calculated descriptive statistics for use of each strategy and plotted percent uptake and weeks used. We assessed the relationship between strategy use and hospital type, geographic region and phase of the pandemic using generalised estimating equations (GEEs), adjusting for weekly county case counts. RESULTS: We found heterogeneity in strategy uptake over time, some of which was associated with geographic region and phase of pandemic. We identified a body of strategies that were both commonly used and sustained over time, for example, limiting staff in COVID-19 rooms and increasing telehealth capacity, as well as those that were rarely used and/or not sustained, for example, increasing hospital bed capacity. CONCLUSIONS: Hospital strategies during the COVID-19 pandemic varied in resource intensity, uptake and duration of use. Such information may be valuable to health systems during the ongoing pandemic and future ones.

An international survey of healthcare workers use of personal protective equipment during the early stages of the COVID-19 pandemic.

OBJECTIVE: Little is known regarding the specific ways personal protective equipment (PPE) has been used and reused during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate the patterns of PPE use and the impact of PPE availability on the attitudes and well-being of an international population of healthcare workers. METHODS: This was an online, cross-sectional survey of healthcare workers. The survey was disseminated internationally using social media, specialty society list-serves, and email augmented by snowball sampling to healthcare workers who provided direct care to patients with suspected or confirmed COVID-19. The survey was conducted between April 13 and May 1, 2020. The primary outcome was self-reported PPE use during aerosol-generating medical procedures. Other outcomes included PPE use during care for respiratory patients in general, PPE reuse, PPE decontamination, and healthcare worker impressions related to their work and the pandemic. RESULTS: A total of 2227 healthcare workers from 23 countries completed the survey. The N95 was the most common respirator among the 1451 respondents who performed aerosol-generating procedures (n = 1050, 72.3%). Overall, 1783 (80.1%) of providers reported general reuse of PPE, which was similar across US regions but less common in Canada, Italy, and Spain. The most commonly reused item of PPE was the N95 respirator, with the majority of respondents who reused PPE reporting N95 reuse (n = 1157, 64.9%). Of the 1050 individuals who wore an N95 mask while performing an aerosol-generating medical procedure, 756 (72%) reported re-using an N95, and 344 (45.5%) reported reuse for >3 days. Qualitative results identified several common themes, including (1) lack of availability of PPE, (2) fear and anxiety as a result of inadequate PPE, (3) potential exposure to family members, and (4) concerns regarding workload and pay. CONCLUSIONS: This international survey of healthcare workers found that N95 respirators were commonly used to care for patients with respiratory symptoms with and without aerosol-generating medical procedures. Healthcare workers reported an unprecedented need to reuse PPE that was designed for single-use, specifically the N95 respirator. The reuse of PPE increased the perceived risk for COVID-19 infection and harmed mental health.

Chronic Chemogenetic Stimulation of the Nucleus Accumbens Produces Lasting Reductions in Binge Drinking and Ameliorates Alcohol-Related Morphological and Transcriptional Changes.

Binge drinking is a dangerous pattern of behavior. We tested whether chronically manipulating nucleus accumbens (NAc) activity (via clozapine-N-oxide (CNO) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD)) could produce lasting effects on ethanol binge-like drinking in mice selectively bred to drink to intoxication. We found chronically increasing NAc activity (4 weeks, via CNO and the excitatory DREADD, hM3Dq) decreased binge-like drinking, but did not observe CNO-induced changes in drinking with the inhibitory DREADD, hM4Di. The CNO/hM3Dq-induced reduction in ethanol drinking persisted for at least one week, suggesting adaptive neuroplasticity via transcriptional and epigenetic mechanisms. Therefore, we defined this plasticity at the morphological and transcriptomic levels. We found that chronic binge drinking (6 weeks) altered neuronal morphology in the NAc, an effect that was ameliorated with CNO/hM3Dq. Moreover, we detected significant changes in expression of several plasticity-related genes with binge drinking that were ameliorated with CNO treatment (e.g., Hdac4). Lastly, we found that LMK235, an HDAC4/5 inhibitor, reduced binge-like drinking. Thus, we were able to target specific molecular pathways using pharmacology to mimic the behavioral effects of DREADDs.