Aging with HIV and HIV-associated neurocognitive impairment.

Antiretroviral therapy (ART) is the most effective therapeutic intervention for HIV infection. With improved survival, comorbidities, including neuropsychiatric and HIV-associated neurocognitive impairment (NCI) are of increasing concern to aging people with HIV (PWH). The clinical features and the inter-individual variability of the aging process confound the elucidation of the diagnosis and underlying mechanisms of cognitive dysfunction in aging PWH.

Tranexamic dosing for major joint arthroplasty in adult patients with chronic kidney disease: A pharmacokinetic study and new dosing regimen.

Background: Tranexamic acid is an anti-fibrinolytic agent routinely used during hip and knee joint replacement surgery to minimize bleeding. Chronic kidney disease is a common chronic health problem seen among adults requiring major arthroplasty surgery. Tranexamic acid is renally cleared and may accumulate in chronic kidney disease.

Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.

Unlabelled: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species.

Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering.

Protein engineering has emerged as a powerful approach toward the development of novel therapeutics targeting the MYC/MAX/E-box network, an active driver of >70% of cancers. The MYC/MAX heterodimer regulates numerous genes in our cells by binding the Enhancer box (E-box) DNA site and activating the transcription of downstream genes. Traditional small molecules that inhibit MYC face significant limitations that include toxic effects, drug delivery challenges, and resistance.

Comparative Improvement in Health-Related Quality of Life with Advanced Therapies for Moderate-to-Severe Crohn's Disease: A Network Meta-Analysis.

Background And Aims: The comparative efficacy of advanced therapies to improve health-related quality of life (HR-QoL) in Crohn's disease (CD) is unknown. We aimed to compare the impact of approved advanced therapies for moderate-to-severe CD on HR-QoL.

Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL from inception to December 2023.

Prognostic significance and accuracy of oncologists' estimates of survival time in recurrent ovarian cancer.

Objective: We evaluated the accuracy of oncologists' estimates of expected survival time in recurrent ovarian cancer.

Methods: Oncologists estimated expected survival time at baseline for each patient, who were then followed up for survival time. We hypothesized that oncologists' estimates of expected survival time would be independently significant predictors of survival, unbiased (approximately equal proportions [50%] living longer versus shorter than their expected survival time), or imprecise (<30% within 0.

Can we learn from failures? A systematic review of phase III trials in platinum-resistant ovarian cancer.

Objective: This systematic review analyzed phase III trials in platinum-resistant ovarian cancer to understand their poor outcomes and guide future trials.

Methods: A systematic review adhering to PRISMA guidelines was conducted. PubMed/Medline, Cochrane Library CENTRAL, and EMBASE were searched for randomized phase III trials (2010-January 2024) involving patients with platinum-resistant ovarian cancer.

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial.

Objective: The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy.

Methods: Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival.

Nutrient intakes of Canadian children and adolescents at school by meal occasion and location of food preparation.

Canadian children consume a significant proportion of daily foods at school, do not benefit from any federal school food program, and have historically inadequate diets. Assessment of dietary intakes at school can inform policy discussions for the design, funding, and delivery of school-based nutrition interventions. The objectives were to examine the most recent nationally representative dietary intake data of Canadian children at school by (i) location of food preparation, (ii) meal occasion, and (iii) as a proportion of total daily intakes.

Biologic Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Despite limited breakthroughs in COPD pharmacotherapy, recent trials have shown promising results for biologics in COPD patients. However, robust evidence synthesis in this area is currently lacking.

Methods: We conducted a systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL from inception to July 17, 2024, to identify randomized trials of biologic medications in patients with COPD.

Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.

Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites.

CTU Hornet 65 Niner: A network dataset of geographically distributed low-interaction honeypots.

This data article introduces a new network dataset created to help understand how geographical location impacts the quality, type, and amount of incoming network attacks received by honeypots. The dataset consists of 12.4 million network flows collected from nine low-interaction honeypots in nine cities across the world for 65 days, from April 29th to July 1st, 2024.

Epidemiology of Epstein-Barr Virus Chronic High Viral Load in Kidney Transplant Recipients.

Background: Epstein-Barr virus (EBV) chronic high viral load (CHVL) may be defined by >16 000 copies/mL whole blood or >200 copies/10 peripheral blood mononuclear cells in >50% samples exceeding 6 mo. EBV CHVL has only been characterized in a few small pediatric studies, with heterogeneous results and unclear clinical significance.

Methods: This single-center observational study evaluated adult and pediatric kidney transplant recipients transplanted between 2010 and 2021 on tacrolimus/mycophenolate-based/prednisone immunosuppression.

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

Hepatitis C Virus Seroprevalence, Incidence, and Screening Patterns in Ontario Preexposure Prophylaxis Users.

Background: Hepatitis C virus (HCV) has emerged as a sexually transmitted infection in gay, bisexual, and other men who have sex with men (GBM). We estimated the seroprevalence and incidence of HCV infection and examined patterns of HCV testing among GBM using human immunodeficiency virus preexposure prophylaxis (PrEP) in Ontario, Canada.

Methods: We analyzed data from the Ontario PrEP Cohort Study (ON-PrEP), a prospective cohort of PrEP users from 10 Ontario clinics.

Impact of Policy Changes Expanding Access to Direct-Acting Antivirals on Hepatitis C Virus-Related Hospitalizations in People With HIV: A Population-Based Study.

Background: The burden of hepatitis C virus (HCV)-related hospitalizations is substantial, particularly among people with HIV and HCV. In Ontario, Canada, use of direct-acting antivirals (DAAs) increased following policies removing fibrosis-stage restrictions and approving of pangenotypic agents in 2017 and 2018, respectively. We examined the impact of expanded DAA access on HCV-related hospitalizations in people with HIV.

Evidence update on the cancer risk of vaping e-cigarettes: A systematic review.

Introduction: There is substantial interest in the association of vaping e-cigarettes with the risk of cancer. We analyzed this risk in different populations by updating the Kings College London (KCL) review to include the period between July 2021 and December 2023.

Methods: We searched six databases and included peer-reviewed human, animal, and cell/ original studies examining the association between e-cigarettes and cancer risk, but we excluded qualitative studies.

Clustering Sequence Data with Mixture Markov Chains with Covariates Using Multiple Simplex Constrained Optimization Routine (MSiCOR).

Mixture Markov Model (MMM) is a widely used tool to cluster sequences of events coming from a finite state-space. However, the MMM likelihood being multi-modal, the challenge remains in its maximization. Although Expectation-Maximization (EM) algorithm remains one of the most popular ways to estimate the MMM parameters, however, convergence of EM algorithm is not always guaranteed.

Functional principal component analysis with informative observation times.

Functional principal component analysis has been shown to be invaluable for revealing variation modes of longitudinal outcomes, which serve as important building blocks for forecasting and model building. Decades of research have advanced methods for functional principal component analysis, often assuming independence between the observation times and longitudinal outcomes. Yet such assumptions are fragile in real-world settings where observation times may be driven by outcome-related processes.

"When you're in the office, it means you managed to get somewhere": An interpretive descriptive study of the perceptions of adolescents accessing primary care for mental health services.

Objective: Primary care offers an entry point into the health care system for adolescents experiencing mental illnesses. This study explored the perceptions of adolescents with an anxiety or mood disorder accessing primary care for mental health services.

Methods: Qualitative interpretive descriptive design was employed.

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.