Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.

ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.

The landscape of family medicine in India - A cross-sectional survey study.

Family medicine was recognized as a distinct specialty in India in the early 1980s, but it is at an early stage of implementation. There are few training programs, and little is known about family physicians' training, perceptions, and current practices. This paper describes the findings from the first national survey of family medicine in India.

Treatment outcomes among children and adolescents with extensively drug-resistant (XDR) and pre-XDR tuberculosis: Systematic review and meta-analysis.

Extensively drug-resistant (XDR) and pre-XDR- tuberculosis (TB) account for approximately a third of pediatric MDR-TB cases globally. Clinical management is challenging; recommendations are based on limited evidence. We assessed the clinical outcomes for children and adolescents treated for XDR-and pre-XDR-TB.

Brief social presence improves delayed memory for online lecture content.

During the COVID-19 pandemic, the use of videoconferencing platforms became ubiquitous in postsecondary education around the world, making it crucial to understand how to maximize the efficacy of synchronous online classes. Given that social information can act as a motivation and improve memory, the current study tested the hypothesis that brief social presence during an online class would act as a social reward that would increase delayed memory for lecture information. Undergraduate students attended a mock synchronous class during which they viewed a pre-recorded science lecture, and social presence was manipulated by having participants turn on their cameras before and after the lecture (high social presence) or having cameras remain off during the entire class (low social presence).

Specialty-specific Evaluation of Virtual care Outcomes: A retrospective QUality and safety analysis (S-EVOQUe).

The objective was to compare specialty-specific 7- and 30-day outcomes between virtual care visits and in-person visits which occurred during the SARS-CoV-2 pandemic. Using administrative data from provincial databases in Ontario, ambulatory care visits occurring virtually and in-person during specific timeframes within the pandemic were analyzed. Virtual care visits were matched with corresponding in-person visits based on multiple baseline patient characteristics.

The impact of Daylight Saving Time on dog activity.

While most studies on Daylight Saving Time (DST) focus on human sleep and well-being, there is a dearth of understanding of how this sudden, human-mitigated change affects the routines of companion animals. The objective of this study was to assess how DST influenced the morning activity pattern of dogs (Canis familiaris). We used accelerometers to record activity in 25 sled dogs and 29 caregiver-companion dog dyads located in or near Ontario, Canada during the Fall Back time shift.

From Equity, Diversity, and Inclusion to Justice: Calling in for Collective Learning and Action on Racism in Dietetics.

Equity, diversity, and inclusion (EDI) is the prevailing framework that has informed efforts in dietetics to redress racism. Although EDI has strengths, it has several weaknesses that ultimately hinder progress on racism in the profession. In this paper, we present racial justice as an alternative framework that, we assert, engenders more meaningful, purposive, and politically critical language, analysis, and action to redress racism and White supremacy.

Nurses and allied professionals' engagement in clinical research-in-practice: a statement of the Association of Cardiovascular Nursing & Allied Professions of the European Society of Cardiology.

Many nurses and allied professionals (NAPs) lack the skills, knowledge and confidence to engage in conducting and implementing research. This statement describes the importance of NAPs' involvement in clinical research within the context of cardiovascular care. The existing gaps, barriers and enablers to NAPs involvement in research as a potential response to workforce issues in these professions as well as to contribute to excellence in patient care delivery and associated outcomes are identified.

Simultaneous Unbinned Differential Cross-Section Measurement of Twenty-Four Z+jets Kinematic Observables with the ATLAS Detector.

Z boson events at the Large Hadron Collider can be selected with high purity and are sensitive to a diverse range of QCD phenomena. As a result, these events are often used to probe the nature of the strong force, improve Monte Carlo event generators, and search for deviations from standard model predictions. All previous measurements of Z boson production characterize the event properties using a small number of observables and present the results as differential cross sections in predetermined bins.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial.

Importance: Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial.

Objective: To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium.

Impact of cardiac position, morphology and operative technique on long-term fontan outcomes in heterotaxy.

Objectives: This study aimed to assess the outcomes of heterotaxy patients undergone the Fontan operation, focusing on morphological features and surgical techniques.

Methods: Eighty-two consecutive heterotaxy patients who underwent the Fontan operation from 1985 to 2021 were compared to 150 patients with tricuspid atresia (TA) and 144 patients with hypoplastic left heart syndrome (HLHS). The Kaplan-Meier method and Cox proportional hazard model were used to analyze transplant-free survival and predictor of outcomes.

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.