Notes

CLIMB-COVID: constant intergrated , helping decentralised sequencing pertaining to SARS-CoV-2 genomic monitoring.
We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.Virulent non-tuberculous Mycobacteria (NTMs) successfully reside and multiply within the phagosomes of phagocytic cells such as monocytes and macrophages. Macrophages play a very important role in the innate clearance of intracellular pathogens including NTMs. Attenuated Mycobacterium avium subsp. hominissuis 100 enters macrophages but is incapable of escaping these cells via canonical mycobacteria escape mechanisms. Alternatively, virulent Mycobacterium avium subsp. hominissuis 104 and Mycobacterium abscessus subsp. abscessus are able to modify macrophages to suit their growth, survival and ultimately escape from macrophages, while non-virulent Mycobacterium smegmatis is readily killed by macrophages. In this study we focused on early infection of macrophages with NTMs to determine the phenotypic response of macrophages, M1 or M2 differentiation, and phosphorylation alterations that can affect cellular response to invading bacteria. Our findings indicate that infection of the macrophage with MAH 100 and M. stidine, significantly impaired the survival of MAH 104 in macrophages. Our findings suggest that the virulent MAH 104 and M. abscessus enhance its survival in the macrophage possibly through interference with the epigenome responses.Drug resistance mutations of hepatitis C virus (HCV) negatively impact viral replicative fitness. RNA viruses are known to change their replication behaviour when subjected to suboptimal selection pressure. Here, we assess whether mutation supply in HCV is sufficiently large to allow the selection of its variants during dual or triple direct-acting antiviral (DAA) treatment associated with augmented virus fitness or impairment. We engineered randomly mutagenized full-genome libraries to create a highly diverse population of replication-competent HCV variants in cell culture. These variants exhibited escape when treated with NS5A/NS5B inhibitors (daclatasvir/sofosbuvir), and relapse on treatment with a combination of NS3/NS5A/NS5B inhibitors (simeprevir or paritaprevir/daclatasvir/sofosbuvir). Analysis of the relationship between virus fitness and drug resistance of JFH1-derived NS5A-5B variants showed a significant positive correlation (P=0.003). At the earliest time points, intracellular RNA levels remain unchanged in both the subgenomic replicon and infection assays, whereas extracellular RNA levels increased upto ten-fold compared to wild-type JFH1. Beneficial substitutions hyperstimulated phosphatidylinositol 4-phosphate during DAA treatment, and showed decreased dependence on cyclophilins during cyclosporine A treatment, indicating an interplay of virus-host molecular mechanisms in beneficial substitution selection that may necessitate infectious virus production. This comprehensive study demonstrates a possible role for HCV fitness of overcoming drug-mediated selection pressure.HIV remains a principal inequity for queer men across the United States. Biomedical practices all but dominate interventions, and HIV-related stress persists among queer men. Regarding HIV as discourse is not well represented in prevention and care. This study is a response, then, to this need that seeks to build an HIV-informed model of praxis, entitled HIV Stress Exchange. A Queer Discourse Study was conducted with 20 queer men across two generations, pre-AIDS and post-AIDS. The data included in-depth interviews and material resources participants brought to the conversation. In all, this data speaks to the ways in which HIV is given life in discourse and what meaning it holds in embodied lives. Resultantly, five themes materialized, inclusive of all ages and sero-statuses HIV provided meaning as in-/validated, un-/voiced, un-/intelligible, holding intimacy/-ies, and being PrEP/-ared. Based on the findings, the conceptual model for HIV Stress Exchange is presented along with an HIV-informed model of practice.In this study, the researchers investigated the factors that affect women's breast cancer prevention behaviors. The sample of this cross-sectional and descriptive study consisted of 406 participants aged 20 and older. The study was conducted in February-March 2021 within the administrative borders of a province located in the Southeastern Anatolia Region of Turkey. The data were collected via an online platform using Personal Information Form and the Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors. The mean Scale of Factors Affecting Women's Breast Cancer Prevention Behaviors score of the participants was moderate as 107.20 ± 17.86. The frequency of breast cancer prevention behaviors was found to be lower in the participants with low literacy, those who were unemployed, those with low income, those living in villages and those who did not perform breast self-examination (p  less then  0.05). It is recommended to plan educational studies on breast cancer screening behaviors by considering regional differences.Professionalism is defined and described in a variety of ways that differ considerably in details and quantity. While professionalism has become increasingly important, educators' opinions regarding the types of professionalism vary. The objective of this qualitative study was to evaluate faculty and preceptors' perspectives regarding veterinary medical students' professionalism during their clinical rotations. A thematic content analysis was performed to classify 2,014 comments. Five main themes emerged (a) work ethic and attitude; (b) effective interactions with clients and delivering patient care; (c) effective interactions with health care professionals; (d) punctuality, task completion, and organization; and (e) commitment to improving competency in self and others. The importance of professionalism was stressed by both groups of faculty and preceptors through written comments; however, the magnitude of each theme differed. The results indicate that without understanding professionalism elements, the lack of conceptual clarity and consensus related to expected behaviors and attitudes would make it challenging to assess professionalism appropriately. The themes identified can be used to begin a discussion about expected behavior among faculty, preceptors, and students, therefore prompting a reasonable assessment of professionalism, as well as avoiding unprofessional behavior.We examine the psychological symptoms and suicide attempts and/or self-injury behaviors of survivors of childhood sexual abuse (CSA) according to individual and familial characteristics. The participants of this study included 80 adolescents aged 14-17 years. We show that high psychological symptom scores may indicate that the perpetrator was a family member and that penetration occurred. In addition, most of the participating survivors have experienced numerous problems, largely related to psychological symptoms. Considering the results regarding survivors who had previously attempted suicide, we demonstrate that the perpetrators in these cases were mostly reliable/loved people, while these survivors generally hid the events and were exposed to penetration more often. We conclude that survivors exposed to CSA by a reliable/loved person, blaming themselves, having low social support, and displaying certain symptoms should be followed closely and necessary psychosocial interventions for suicide should be applied.Despite recent advances in transgenic animal models and display technologies, humanization of mouse sequences remains one of the main routes for therapeutic antibody development. Traditionally, humanization is manual, laborious, and requires expert knowledge. Although automation efforts are advancing, existing methods are either demonstrated on a small scale or are entirely proprietary. To predict the immunogenicity risk, the human-likeness of sequences can be evaluated using existing humanness scores, but these lack diversity, granularity or interpretability. Meanwhile, immune repertoire sequencing has generated rich antibody libraries such as the Observed Antibody Space (OAS) that offer augmented diversity not yet exploited for antibody engineering. Here we present BioPhi, an open-source platform featuring novel methods for humanization (Sapiens) and humanness evaluation (OASis). Sapiens is a deep learning humanization method trained on the OAS using language modeling. Based on an in silico humanization benchmark of 177 antibodies, Sapiens produced sequences at scale while achieving results comparable to that of human experts. D-Luciferin chemical structure OASis is a granular, interpretable and diverse humanness score based on 9-mer peptide search in the OAS. OASis separated human and non-human sequences with high accuracy, and correlated with clinical immunogenicity. BioPhi thus offers an antibody design interface with automated methods that capture the richness of natural antibody repertoires to produce therapeutics with desired properties and accelerate antibody discovery campaigns. The BioPhi platform is accessible at https//biophi.dichlab.org and https//github.com/Merck/BioPhi.RB1CC1/FIP200 is a subunit of the ULK1 complex in more complex eukaryotes. This large polypeptide was proposed to be a functional homolog of the Atg17 and Atg11 scaffolding proteins in yeast. Previous studies showed that RB1CC1 can bind to various proteins of the macroautophagy/autophagy machinery, where the RB1CC1 Claw domain directly interacts with a short linear segment of its interactors. A mechanistic insight into how the small globular RB1CC1 Claw domain can interact with such an array of structurally variable proteins has been elusive. The recent study by Zhou et al., discussed here, yields structural data that not only provide a unifying mechanistic explanation of these interactions, but also reveals previously unknown RB1CC1 interactors and opens a new field for exploration of autophagy regulation.Abbreviations FIR FIP200-interacting region; LIR LC3-interacting region; pS/p-S phosphorylated serine.In this article we focus on interpreting multidimensional scaling (MDS) configurations using facet theory. The facet theory approach is attempting to partition a representational space, facet by facet, into regions with certain simplifying constraints on the regions' boundaries (e.g., concentric circular sub-spaces). A long-standing problem has been the lack of computational methods for optimal facet-based partitioning. We propose using support vector machines (SVM) to perform this task. SVM is highly attractive for this purpose as they allow for linear as well as nonlinear classification boundaries in any dimensionality. Using various classical examples from the facet theory literature we elaborate on the combined use of MDS and SVM for facet-based partitioning. Different types of MDS are discussed, and options for SVM kernel specification, tuning, and performance evaluation are illustrated.Low health literacy (HL) is associated with adverse health behaviors and poor health, and brief, high-quality instruments for measuring HL in children are scarce. The Health Literacy for School-Aged Children (HLSAC) instrument is a 10-item theory-based and internationally validated tool for measuring HL. The purpose of this study was to translate and validate the HLSAC instrument among Danish school-aged children. The instrument was translated into Danish by a standardized forward-backward translation process, and then pre-tested for face validity with 61 pupils from four schools. Thereafter, the instrument was tested among 805 pupils in grades 6 to 7 (age 11-14 years) from 15 schools. When HL was modeled as one latent factor with all 10 items loading on this factor, the confirmative factor analysis showed standardized factor loadings from 0.52 to 0.75 (p less then .001) and an excellent model fit. The association between HL and food intake as a health behavior example (p less then .001, r2 = .027) indicates the predictive validity of the instrument.
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