The rockefeller university

BackgroundHybrid effectiveness-implementation designs evaluate the effectiveness and implementation of interventions. We retrospectively evaluated the implementation of a stepped-wedge cluster randomized controlled trial of a facilitated telemedicine model (experimental) integrated into opioid treatment programs (OTPs) compared to offsite referral (control) for hepatitis C virus (HCV) treatment. The trial period was March 2017-October 2022. We compared organizational and implementation characteristics associated with an HCV cure and with high satisfaction with healthcare delivery.MethodsWe used the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to guide data collection and evaluation. We evaluated the clinical effectiveness outcome (HCV cure) and patient-centered outcomes (changes between in-person and telemedicine patient satisfaction questionnaire subscales: Time Spent With Doctor and General Satisfaction). We evaluated 7 organizational and 16 implementation variables. We used random forests to obtain a list of variables with total importance weight of at least 95%. We subsequently conducted a configurational comparative method of coincidence analysis (CNA) to identify the variable combinations that are associated with the best outcomes.ResultsThe effectiveness of reach was enhanced by site identification of HCV RNA positive individuals. We found that low patient load per provider or counselor, site liaison presence, and high case manager availability increased clinical effectiveness (i.e., HCV cure). Adoption and implementation, assessed by high healthcare delivery satisfaction among participants in both arms, was associated with site liaisons, frequent case manager onsite presence and consistency, and low provider patient volume. Among telemedicine participants, onsite notifications and provider involvement in recruitment were additional variables associated with high healthcare satisfaction. In referral, providing patient education, low counselor patient volume, case manager involvement in site activities, and high case manager education levels were additional variables associated with high healthcare delivery satisfaction. Intervention maintenance has occurred at 10 sites.ConclusionsCompared to referral, facilitated telemedicine requires fewer variables for high effectiveness and patient satisfaction. The frequent onsite presence and consistency of the case manager and low provider and counselor volumes improved outcomes among both approaches. Improved outcomes among referral participants required more publicity, patient education, higher case manager education, more involvement in site activities, and occurred in university-affiliated sites.Trial registrationClintrials.gov registration number NCT02933970; Comparison of Telemedicine to Usual Care for HCV Management for Methadone-maintained Individuals Full Text View ClinicalTrials.gov.

Zika virus (ZIKV) is an emerging arbovirus, and its infection is often asymptomatic or mild; however, it can lead to severe neurological disorders. Currently, there are no approved treatments or vaccines for ZIKV, highlighting the urgent need to explore potential therapeutic options. In this study, we evaluated the antiviral activity of a novel synthetic peptide (GA-peptide) against ZIKV in vitro. The GA-peptide exhibited dose-dependent inhibition of the virus, affecting multiple stages of the ZIKV replication cycle. It demonstrated virucidal activity and effectively protected Vero cells from ZIKV infection. Additionally, the GA-peptide disrupted viral entry by targeting both the attachment and internalization phases, as well as post-entry stages of the infection. In silico analyses identified potential viral targets that interact with the GA-peptide. These findings underscore the GApeptide's promising potential as a therapeutic agent against ZIKV and its relevance in the development of new antiviral drugs.

Measurements of the production yields of charm baryons (Lambda(+)(c)) and charm mesons (D-0) in proton-lead collisions at a nucleon-nucleon center-of-mass energy of 8.16 TeV are presented. The data were collected in 2016 with the CMS experiment and correspond to an integrated luminosity of 186 nb(-1). The Lambda(+)(c) baryon is reconstructed from the decay channel Lambda(+)(c) -> K(S)(0)p, while the D-0 meson is reconstructed via D-0 -> K- pi(+). The Lambda(+)(c) baryon and D-0 meson yields are extracted in several charged-particle multiplicity classes. No strong multiplicity dependence of the Lambda(+)(c) -to-D-0 yield ratio is observed, unlike the observed strange baryon to strange meson yield ratio of Lambda/(Lambda) over bar to K-S(0), which shows a strong multiplicity dependence. This observation indicates different mechanisms for the multiplicity evolution of hadronization processes for charm and strange quarks and provides new constraints to the understanding of heavy flavor production and collectivity in small collision systems.

Human monogenic traits can confer resistance to viral disease in infected individuals. Enhanced susceptibility can be driven directly by mutations in genes essential for control of the virus or indirectly via the production of autoantibodies against components of host defense. While the impact of viruses on individuals carrying these genotypes permitted their identification and has been amply studied, little is known about the impact of these human genotypes on the natural history of viruses, including not only persisting but also emerging viruses. We envisage several scenarios, including the possibility that genetically susceptible individuals serve as patient zeros, superspreaders, or mutation incubators, or that genetically resistant individuals even permit the selection of new viral mutants. Viruses are continually shared between individuals and even host species, where they can benefit from adaption to new environments. Current human viruses, as well as novel viruses from animal reservoirs, will continue to threaten the human population. Improvements in the scale of human genomic sequencing and analysis will permit testing hypotheses about the impact of human genetics on the origin and trajectory of viral infections, including future pandemics, which may ultimately help to prevent or curtail impending outbreaks.

Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate changes in protein skin levels of psoriasis patients after oral treatment with orismilast (a PDE4B/D inhibitor). The proteins were measured in extracts of tape-strip samples taken from the skin of patients with moderate-severe psoriasis participating in a 16-week Ph2b study (IASOS). The proteins were measured using the Olink technology or an ELISA assay. Our results show that protein levels of multiple proteins (32/71) were upregulated at baseline in the lesional skin compared to non-lesional skin, including three key biomarkers of the psoriasis disease pathology (IL-17A, CCL20 and TNF alpha). The protein levels of these three biomarkers were significantly reduced at Week 16, reaching a percent reduction of 52% and 51% for IL-17A, 66% and 60% for TNF alpha, and 41% and 54% for CCL20 for the two doses analysed (20 and 30 mg bid, respectively). In addition, we observed that the clinical response of a 75% reduction in PASI (PASI75) was associated with a 98% reduction in IL-17A protein levels in lesional skin, irrespective of the orismilast dose. In summary, a significant reduction of key proteins related to the TH17 axis and TH1 axis was observed in the skin of psoriasis patients after treatment with oral orismilast, supporting the observed clinical effect. Finally, this constitutes the first report where protein levels from the skin of psoriasis patients are quantified using tape strips as a minimally invasive skin sampling technology in combination with the Olink technology.Trial Registration: ClinicalTrials.gov identifier: NCT05190419

Motivation Large sequencing datasets are being produced and deposited into public archives at unprecedented rates. The availability of tools that can reliably and efficiently generate and store sequencing read summary statistics has become critical.Results As part of the effort by the Vertebrate Genomes Project (VGP) to generate high-quality reference genomes at scale, we sought to address the community's need for efficient sequence data evaluation by developing rdeval, a standalone tool to quickly compute and interactively display sequencing read metrics. Rdeval can either run on the fly or store key sequence data metrics in tiny read 'snapshot' files. Statistics can then be efficiently recalled from snapshots for additional processing. Rdeval can convert fa*[.gz] files to and from other popular formats including BAM and CRAM for better compression. Overall, while CRAM achieves the best compression, the gain compared to BAM is marginal, and BAM achieves the best compromise between data compression and access speed. Rdeval also generates a detailed visual report with multiple data analytics that can be exported in various formats. We showcase rdeval's functionalities using long-read data from different sequencing platforms and species, including human. For PacBio long-read sequencing, our analysis shows dramatic improvements in both read length and quality over time, as well as the benefit of increased coverage for genome assembly, though the magnitude varies by taxa.Availability and implementation Rdeval is implemented in C++ for data processing and in R for data visualization. Precompiled releases (Linux, MacOS, Windows) and commented source code for rdeval are available under MIT license at https://github.com/vgl-hub/rdeval. Documentation is available on ReadTheDocs (https://rdeval-documentation.readthedocs.io). Rdeval is also available in Bioconda and in Galaxy (https://usegalaxy.org). An automated test workflow ensures the consistency of software updates.

The transporter associated with antigen processing (TAP) delivers peptide antigens from the cytoplasm into the endoplasmic reticulum (ER) for loading onto major histocompatibility complex class I (MHC-I) molecules. To examine the mechanisms of peptide transport and release into the ER, we determined cryo-electron microscopy structures of the human TAP heterodimer in multiple functional states along the transport cycle. In the inward-facing conformation, when the peptide translocation cavity within the TAP heterodimer is exposed to the cytosol, ATP binding strengthened intradomain assembly. Transition to the outward-facing conformation, when the transporter opens to the ER lumen, led to a complete reconfiguration of the peptide-binding site, facilitating peptide release. ATP hydrolysis opened the catalytically active nucleotide-binding consensus site, and the subsequent separation of the nucleotide-binding domains reset the transport cycle. These findings establish a comprehensive structural framework for understanding unilateral peptide transport, vanadate trapping, and trans-inhibition-an internal feedback mechanism that prevents excessive peptide accumulation and activation of the ER stress response.

A goal of data visualization is to advance the understanding of multiparameter, large-scale datasets. In astrophysics, scientists map celestial objects to understand the hierarchical structure of the universe. In biology, genetic sequences and biological characteristics uncover evolutionary relationships and patterns (e.g., variation within species and ecological associations). Our highly interdisciplinary project entitled "A Cosmic View of Life on Earth" adapts an immersive astrophysics visualization platform called OpenSpace to contextualize diverse biological data. Dimensionality reduction techniques harmonize biological information to create spatial representations in which data are interactively explored on flat screens and planetarium domes. Visualizations are enriched with geographic metadata, 3-D scans of specimens, and species-specific sonifications (e.g., bird songs). The "Cosmic View" project eases the dissemination of stories related to biological domains (e.g., insects, birds, mammals, and human migrations) and facilitates scientific discovery.