Population-Level Sexual Mixing According to HIV Status and Preexposure Prophylaxis Use Among Men Who Have Sex With Men in Montreal, Canada: Implications for HIV Prevention.

Using cross-sectional survey data (Engage, 2017-2018) from 1,137 men who have sex with men, ≥16 years old, in Montreal, we compared observed human immunodeficiency virus (HIV) seroconcordance in previous-6-months' sexual partnerships with what would have been observed by chance if zero individuals serosorted. Of 5 recent partnerships where both individuals were HIV-negative, we compared observed concordance in preexposure prophylaxis (PrEP) use with the counterfactual if zero individuals selected partners based on PrEP use. We estimated the concordance by chance using a balancing-partnerships approach assuming proportionate mixing.

Behavioral Activation Augmented With Mobile Technology for Depression and Anxiety in Chronic Moderate-Severe Traumatic Brain Injury: Protocol for a Randomized Controlled Trial.

Objective: To describe and provide the rationale for a randomized controlled trial for depression or anxiety after moderate to severe traumatic brain injury (TBI), which will test 2 treatments based on behavioral activation (BA), a promising model to promote both positive mood and increased activity in this population.

Design: Randomized controlled trial with masked outcome assessment.

Setting: Outpatient catchment area of 1 TBI treatment center.

High-coverage genomes to elucidate the evolution of penguins.

Background: Penguins (Sphenisciformes) are a remarkable order of flightless wing-propelled diving seabirds distributed widely across the southern hemisphere. They share a volant common ancestor with Procellariiformes close to the Cretaceous-Paleogene boundary (66 million years ago) and subsequently lost the ability to fly but enhanced their diving capabilities. With ∼20 species among 6 genera, penguins range from the tropical Galápagos Islands to the oceanic temperate forests of New Zealand, the rocky coastlines of the sub-Antarctic islands, and the sea ice around Antarctica.

The Genome of the Endangered Dryas Monkey Provides New Insights into the Evolutionary History of the Vervets.

Genomic data can be a powerful tool for inferring ecology, behavior, and conservation needs of highly elusive species, particularly, when other sources of information are hard to come by. Here, we focus on the Dryas monkey (Cercopithecus dryas), an endangered primate endemic to the Congo Basin with cryptic behavior and possibly <250 remaining adult individuals. Using whole-genome sequencing data, we show that the Dryas monkey represents a sister lineage to the vervets (Chlorocebus sp.

A consensus set of genetic vulnerabilities to ATR inhibition.

The response to DNA replication stress in eukaryotes is under the control of the ataxia-telangiectasia and Rad3-related (ATR) kinase. ATR responds to single-stranded (ss) DNA to stabilize distressed DNA replication forks, modulate DNA replication firing and prevent cells with damaged DNA or incomplete DNA replication from entering into mitosis. Furthermore, inhibitors of ATR are currently in clinical development either as monotherapies or in combination with agents that perturb DNA replication.

Author Correction: Time-lapse imagery and volunteer classifications from the Zooniverse Penguin Watch project.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dyadic coping mediates the effects of attachment on quality of life among couples facing ovarian cancer.

Cancer is an interpersonal stressor affecting both patient and spouse. To examine the pathways that insecure adult attachment can impact health outcomes by way of dyadic processes, this cross-sectional study used the actor-partner interdependence mediation model to examine whether common dyadic coping (CDC) mediated the associations between attachment and quality of life (QOL). Couples (N = 106) facing ovarian cancer were recruited from a comprehensive cancer center and completed self-report questionnaires.

Identifying chemogenetic interactions from CRISPR screens with drugZ.

Background: Chemogenetic profiling enables the identification of gene mutations that enhance or suppress the activity of chemical compounds. This knowledge provides insights into drug mechanism of action, genetic vulnerabilities, and resistance mechanisms, all of which may help stratify patient populations and improve drug efficacy. CRISPR-based screening enables sensitive detection of drug-gene interactions directly in human cells, but until recently has primarily been used to screen only for resistance mechanisms.

Neurocognitive status and return to work after moderate to severe traumatic brain injury.

Purpose/objective: To examine the relationship of cognitive status to employment outcomes at 1-year post moderate-severe traumatic brain injury (TBI), using a brief telephone-administered instrument. Research Method/Design: Prospective longitudinal study in which 320 people with moderate-severe TBI, all employed at injury, were enrolled during inpatient rehabilitation and evaluated at 1-year postinjury. Follow-up measures included whether and when participants had returned to work (RTW), and cognitive status assessed with the Brief Test of Adult Cognition by Telephone (BTACT).

Patient-physician relationships, health self-efficacy, and gynecologic cancer screening among women with Lynch syndrome.

Background: Lynch syndrome, a hereditary cancer syndrome, predisposes women to colorectal, endometrial, and ovarian cancer. Current guidelines recommend that women with Lynch syndrome undergo risk-reducing gynecological surgery to reduce their chances of developing endometrial or ovarian cancer. Little is known about how women with Lynch syndrome perceive gynecological cancer screening, or the psychosocial factors associated with screening attitudes and behaviour.

Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.

Cancer-associated mutations in genes encoding RNA splicing factors (SFs) commonly occur in leukemias, as well as in a variety of solid tumors, and confer dependence on wild-type splicing. These observations have led to clinical efforts to directly inhibit the spliceosome in patients with refractory leukemias. Here, we identify that inhibiting symmetric or asymmetric dimethylation of arginine, mediated by PRMT5 and type I protein arginine methyltransferases (PRMTs), respectively, reduces splicing fidelity and results in preferential killing of SF-mutant leukemias over wild-type counterparts.

A robotic platform for flow synthesis of organic compounds informed by AI planning.

The synthesis of complex organic molecules requires several stages, from ideation to execution, that require time and effort investment from expert chemists. Here, we report a step toward a paradigm of chemical synthesis that relieves chemists from routine tasks, combining artificial intelligence-driven synthesis planning and a robotically controlled experimental platform. Synthetic routes are proposed through generalization of millions of published chemical reactions and validated in silico to maximize their likelihood of success.

Examining intrafamilial communication of colorectal cancer risk status to family members and kin responses to colonoscopy: a qualitative study.

Background: First-degree relatives (FDRs) of probands with colorectal cancer (CRC) may be at increased risk of CRC and require colonoscopy. Proband disclosure about this risk and need for colonoscopy is essential for FDRs to take appropriate action. Low colonoscopy rates are reported among FDRs and little is known about the proband disclosure process.

Antarctic Futures: An Assessment of Climate-Driven Changes in Ecosystem Structure, Function, and Service Provisioning in the Southern Ocean.

In this article, we analyze the impacts of climate change on Antarctic marine ecosystems. Observations demonstrate large-scale changes in the physical variables and circulation of the Southern Ocean driven by warming, stratospheric ozone depletion, and a positive Southern Annular Mode. Alterations in the physical environment are driving change through all levels of Antarctic marine food webs, which differ regionally.

Pooled library screening with multiplexed Cpf1 library.

Capitalizing on the inherent multiplexing capability of AsCpf1, we developed a multiplexed, high-throughput screening strategy that minimizes library size without sacrificing gene targeting efficiency. We demonstrated that AsCpf1 can be used for functional genomics screenings and that an AsCpf1-based multiplexed library performs similarly as compared to currently available monocistronic CRISPR/Cas9 libraries, with only one vector required for each gene. We construct the smallest whole-genome CRISPR knock-out library, Mini-human, for the human genome (n = 17,032 constructs targeting 16,977 protein-coding genes), which performs favorably compared to conventional Cas9 libraries.

There's no cure for brain injury: work-related stress in brain injury rehabilitation professionals.

: To explore the experience of work-related stress in brain injury professionals and to identify the contributing factors to work-related stress. : 17 brain injury professionals participated in one-time interviews conducted either in person or utilising video conferencing. The data were analysed utilising a Grounded Theory approach.

Should agility training for novice badminton players be physically or perceptually challenging?

Background: Despite its well-known importance in sports, agility is ambiguously defined and lack of research. Shuttle Run (SR) challenges physical quickness and is commonly used to improve the on-court agility of badminton players. In contrast, Reactive Initiation Training (RIT) challenges perceptual quickness, merely demanding rapid initiation of step toward the direction of shuttlecock.

Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss.

Type I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginines on proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting inhibition of type I PRMTs may offer a therapeutic approach for oncology. The current report describes GSK3368715 (EPZ019997), a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models.

Gay and bisexual men's views on reforming blood donation policy in Canada: a qualitative study.

Background: Researchers and activists have long called for changes to blood donation policies to end what is frequently framed as unjustified bans or deferral periods for men who have sex with men (MSM). Since 2016, in Canada, a man had to be abstinent from all sexual contact (anal or oral sex) with other men for at least 12 months in order to be an eligible blood donor. As of June 3, 2019, this deferral period was reduced to 3 months.

Using blackboard collaborate, a digital web conference tool, to support nursing students placement learning: A pilot study exploring its impact.

Ensuring student nurses, when in clinical placement areas, receive good quality Higher Education Institution (HEI) lecturer support is challenging. This is because conventional HEI placement support, is resource intensive and arguably infeasible with growing student numbers. Evidence suggests, however, that online collaborative learning solutions (e.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant-age LS aBMD data points.

Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.

Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth.

Application of an external fixator vascular compressor (EFVC) in the critically injured trauma patient: a novel damage control technique.

Methods of controlling hemorrhage in penetrating abdominal injuries are varied, ranging from electrocautery, ligation, laparotomy sponge packing, angiography, hemostatic agents, and direct manual pressure. Unfortunately, traditional methods are sometimes unsuccessful due to the location or nature of the hemorrhage, and manual pressure cannot be held indefinitely. We describe a novel damage control technique for hemorrhage control in these situations, followed by three cases where an external fixator vascular compressor (EFVC) was used to hold continual pressure.

A network of human functional gene interactions from knockout fitness screens in cancer cells.

Genetic interactions mediate the emergence of phenotype from genotype. The systematic survey of genetic interactions in yeast showed that genes operating in the same biological process have highly correlated genetic interaction profiles, and this observation has been exploited to infer gene function in model organisms. Such assays of digenic perturbations in human cells are also highly informative, but are not scalable, even with CRISPR-mediated methods.