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.

Immediate Versus Delayed Mobilization After Cubital Tunnel Release Surgery: A Systematic Review and Meta-analysis.

It is unknown whether early mobilization after cubital tunnel decompression improves functional outcomes without increasing complication risks. This systematic review aims to evaluate the effectiveness of early mobilization compared to delayed mobilization of the elbow after ulnar nerve decompression. Randomized controlled trials (RCTs) and observational studies comparing adults who received early mobilization or late mobilization were included.

Exploring Skin Tone Diversity in a Plastic Surgery Resident Education Curriculum.

Gaps remain in surgical education regarding the representation of skin tone diversity. To improve equity and prevent misdiagnosis leading to worsened health outcomes, efforts must be made to ensure educational photographs are representative of the diverse patient populations plastic surgery residents will be treated in their future practices. Four study investigators examined 96 h of recorded lecture seminars from a Canadian plastic surgery resident education curriculum from May 2020 to December 2021.

Spaced Transcranial Direct Current Stimulation for Major Depression.

Objective: This study investigated spaced transcranial direct current stimulation for major depressive disorder, focusing on feasibility.

Methods: In a prospective open-label study, 30 participants with major depressive disorder were enrolled to receive a 50-session transcranial direct current stimulation (tDCS) treatment over 2 weeks. The feasibility, safety, tolerability, and preliminary therapeutic effects of this tDCS protocol were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and 1-week and 4-week follow-ups, as well as with the 6-item HAM-D (HAM-D-6) daily during treatment.

Language Mapping With rTMS in Healthy Pediatric Patients.

Purpose: Repetitive transcranial magnetic stimulation (rTMS) is a potentially effective, noninvasive tool for language mapping. However, there is a paucity of data in pediatric patients. In this study, we aimed to map language sites in healthy pediatric participants with navigated rTMS.

Estimating greenhouse gas emissions from the health sector in Canada: Mind the gap.

Healthcare is a surprisingly large contributor to climate change, responsible for a significant quantity of global Greenhouse Gas (GHG) emissions. Global commitments to achieve "net zero" health systems, including by the federal government in Canada, suggest a growing need to understand and mobilize capacity for GHG emissions estimation across Canada's health sector. Our analysis highlights efforts by public sector healthcare organizations in Canada to estimate an increasingly broad scope of GHG emissions, building on longstanding efforts to report or reduce energy-related emissions from facilities.

Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.

Knowledge translation initiatives at the Transitional Pain Service: insights from healthcare provider outreach and patient education.

Evidence-based treatment of chronic pain requires a multidisciplinary approach grounded in the biopsychosocial model. Implementing this approach within health systems relies on its acceptance by both healthcare providers and patients. While pioneering multidisciplinary pain clinics can serve as a model for implementation, a systematic effort is needed to share knowledge effectively and broadly.

Identification of patient demographic, clinical, and SARS-CoV-2 genomic factors associated with severe COVID-19 using supervised machine learning: a retrospective multicenter study.

Background: Drivers of COVID-19 severity are multifactorial and include multidimensional and potentially interacting factors encompassing viral determinants and host-related factors (i.e., demographics, pre-existing conditions and/or genetics), thus complicating the prediction of clinical outcomes for different severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants.

Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.

Objective: Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs.

Exploring when to exploit: the cognitive underpinnings of foraging-type decisions in relation to psychopathy.

Impairments in reinforcement learning (RL) might underlie the tendency of individuals with elevated psychopathic traits to behave exploitatively, as they fail to learn from their mistakes. Most studies on the topic have focused on binary choices, while everyday functioning requires us to learn the value of multiple options. In this study, we evaluated the cognitive correlates of naturalistic foraging-type decision-making and their electrophysiological signatures in a community sample (n = 108) with varying degrees of psychopathic traits.

Enantioselective Borylcupration/Cyclization of Alkene-Tethered Oxime Esters.

A copper-catalyzed enantioselective synthesis of borylated 1-pyrrolines from γ,δ-unsaturated oxime esters is reported. Twenty-four novel 1-pyrroline derivatives are reported in yields ranging from 26% to 96% and enantioselectivities from 74.5:25.