Factors associated with willingness to use daily antibiotics as STI prophylaxis among HIV-PrEP-experienced gay and bisexual men in Australia.

Background Gay and bisexual men (GBM) who use HIV preexposure prophylaxis (HIV-PrEP) have high rates of bacterial sexually transmitted infections (STIs). The use of daily antibiotics as STI preexposure prophylaxis (STI-PrEP) may be appealing to GBM who are using or have previously used HIV-PrEP (HIV-PrEP-experienced) for the prevention of bacterial STIs. Methods We examined willingness to use daily STI-PrEP among a cross-sectional sample of HIV-PrEP-experienced GBM in Australia who participated in an observational online cohort study from August 2018 to March 2020. Factors associated with willingness to use daily STI-PrEP were determined using bivariate and multivariate logistic regression. Results Of the 1347 participants, half (54.3%) were willing to use daily STI-PrEP. Factors independently associated with greater willingness to use daily STI-PrEP included having >10 sexual partners in the last 6 months, using methamphetamine in the last 6 months, being more conscious about avoiding STIs, having a greater number of STIs since commencing HIV-PrEP, being willing to take HIV-PrEP for as long as they were at risk of acquiring HIV, and only using condoms when a sexual partner requested them. Conversely, factors associated with less willingness to use daily STI-PrEP included being university educated, using nondaily dosing regimens of HIV-PrEP, preferring event-driven HIV-PrEP, and being concerned about long-term HIV-PrEP adverse effects. Conclusions Sexually transmitted infection PrEP is likely to be appealing to many HIV-PrEP-experienced GBM, especially those who engage in activities associated with a higher risk of STI transmission. However, they are less likely to be willing to use STI-PrEP unless it aligns with their HIV-PrEP dosing regimen, suggesting that research into the safety and efficacy of alternative STI prophylaxis dosing options should be prioritized

Attitudes Towards Treatment as Prevention Among PrEP-Experienced Gay and Bisexual Men in Australia

The introduction of HIV pre-exposure prophylaxis (PrEP) has the potential to impact the attitudes gay and bisexual men (GBM) who consequently choose to take PrEP have towards treatment as prevention (TasP), and the extent to which they are willing to have condomless anal intercourse (CLAI) with an HIV-positive sexual partner who has an undetectable viral load (UVL). Using a cross-sectional sample from an observational cohort study conducted from August 2018 to March 2020, we examined the extent to which PrEP-experienced GBM are willing to have CLAI with a partner who has a UVL. Simple and multiple logistic regression models were used to identify associated variables. Of the 1386 participants included in the analyses, 79.0% believed in the effectiveness of TasP, and 55.3% were willing to have CLAI with a partner who has a UVL. Wiling participants were less worried about getting HIV when taking PrEP and more likely to believe in TasP. Further research is needed to better understand the gap between belief in TasP and willingness to have CLAI with a partner who has a UVL among PrEP-experienced GBM

Scholarly insight Spring 2017: A Data Wrangler Perspective

We are pleased to offer you our Scholarly insight Spring 2017: a Data wrangler perspective. The OU is going through several fundamental changes, whereby strategic, pedagogical informed research and insight what drives student learning and academic performance is essential. One of the strategic priorities of Students First (Open University UK, 2017b) and big shifts in OU Redesign (Open University UK, 2017a) is to “simplify and clarify choice for students based upon recommend learning and/or appropriate directed pathways”. Making sense of Big Data in particular can be a challenge, especially students are following different pathways and qualification routes across the OU. Demand for actionable insights to help students make the best out of their OU experience and qualification in particular is currently strong (Open University UK, 2017a, 2017b), especially a desire for evidence of impact of “what works” (Ferguson & Clow, 2017). Furthermore, insights from big data and learning analytics in particular are now increasingly taken into consideration at the OU when designing, writing and revising modules, and in the evaluation of specific teaching approaches and technologies (Herodotou, Heiser, & Rienties, 2017; Herodotou, Rienties, et al., 2017; Rienties, Boroowa, et al., 2016). With the new ways of working with Data Wrangling, first we have provided our basic statistical analyses in form of our Key Metrics report. Based upon three well-attended workshops to further improve our working with the Faculties in January/February 2017, for which we are forever grateful, we have further fine-tuned our ways of working, and Key Metrics report in particular (e.g., adding nations data). Second, the Datawrangler team has worked extensively with the Faculties on “bespoke requests” from Faculties, and where possible shared the insights across all Schools and Faculties. Some of this work is reflected in this report, while other insights will be shared in the next Autumn report. Third, the focus groups indicated that overall the Scholarly insight report was well received, but was rather lengthy and lacked specific input and recommendations for each Faculty. Therefore, we have worked with key stakeholders to identify the top 10 big data and pedagogical “concerns and problems” in each Faculty, which we afterwards narrowed down to a top 5, and subsequently a top 3. Working organically in various Faculty sub-group meetings and in a google doc with various key stakeholders in the Faculties , we hope that our Scholarly Insights can help to inform and help first and foremost our students, but also spark some ideas how to further improve our module designs and qualification pathways. Some of the topics in this top 10 will be addressed in the next Autumn report, and we are of course keen to hear what other topics require Big Data and Scholarly insight

National and Regional Implications of Targeting the Conservation Reserve

Within the Conservation Reserve (CR) program, a change in program criteria could reduce the amount of erosion material entering our nation\u27s waterways. The inclusion of land adjacent to water bodies, flowing streams, and river waterways may reduce erosion from these lands and improve water quality. These buffer strip areas, removed from production and placed in the reserve with a vegetative cover, would limit sedimentation and act to prevent upland erosion materials from reaching waterway channels, thus enhancing the programs\u27 environmental benefits. This paper analyzes the economic benefits of including buffer strups as eligible CR land, and it reviews the problems of identifying such areas

Mitochondrial DNA deletions in muscle satellite cells: implications for therapies.

Progressive myopathy is a major clinical feature of patients with mitochondrial DNA (mtDNA) disease. There is limited treatment available for these patients although exercise and other approaches to activate muscle stem cells (satellite cells) have been proposed. The majority of mtDNA defects are heteroplasmic (a mixture of mutated and wild-type mtDNA present within the muscle) with high levels of mutated mtDNA and low levels of wild-type mtDNA associated with more severe disease. The culture of satellite cell-derived myoblasts often reveals no evidence of the original mtDNA mutation although it is not known if this is lost by selection or simply not present in these cells. We have explored if the mtDNA mutation is present in the satellite cells in one of the commonest genotypes associated with mitochondrial myopathies (patients with single, large-scale mtDNA deletions). Analysis of satellite cells from eight patients showed that the level of mtDNA mutation in the satellite cells is the same as in the mature muscle but is most often subsequently lost during culture. We show that there are two periods of selection against the mutated form, one early on possibly during satellite cell activation and the other during the rapid replication phase of myoblast culture. Our data suggest that the mutations are also lost during rapid replication in vivo, implying that strategies to activate satellite cells remain a viable treatment for mitochondrial myopathies in specific patient groups

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified