Microsimulation Estimates of Decision Uncertainty and Value of Information Are Biased but Consistent.

Purpose: Individual-level state-transition microsimulations (iSTMs) have proliferated for economic evaluations in place of cohort state transition models (cSTMs). Probabilistic economic evaluations quantify decision uncertainty and value of information (VOI). Previous studies show that iSTMs provide unbiased estimates of expected incremental net monetary benefits (EINMB), but statistical properties of iSTM-produced estimates of decision uncertainty and VOI remain uncharacterized.

Is duchenne gene therapy a suitable treatment despite its immunogenic class effect?

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle weakness and eventual death due to cardiomyopathy or respiratory complications. Currently, there is no cure for DMD, with standard treatments primarily focusing on symptom management. Using immunosuppressive measures and optimized vector designs allow for gene therapies to better address the underlying genetic cause of the disease.

Establishing the Research Priorities of ADHD Professionals: An International Delphi Study.

Objectives: To determine ADHD research priorities from the perspective of ADHD professionals internationally.

Method: A two-stage modified Delphi design was used. In Stage 1 (qualitative), participants listed research questions relating to ADHD that they perceived to be most important ( = 132).

How Can One Metal Power Nucleic Acid Phosphodiester Bond Cleavage by a Nuclease? Multiscale Computational Studies Highlight a Diverse Mechanistic Landscape.

Despite the remarkable resistance of the nucleic acid phosphodiester backbone to degradation affording genetic stability, the P-O bond must be broken during DNA repair and RNA metabolism, among many other critical cellular processes. Nucleases are powerful enzymes that can enhance the uncatalyzed rate of phosphodiester bond cleavage by up to ∼10-fold. Despite the most well accepted hydrolysis mechanism involving two metals (M to activate a water nucleophile and M to stabilize the leaving group), experimental evidence suggests that some nucleases can use a single metal to facilitate the chemical step, a controversial concept in the literature.

Part II. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults.

Virtual reality-based preoperative planning for optimized trocar placement in thoracic surgery: A preliminary study.

Video-assisted thoracic surgery (VATS) is a minimally invasive approach for treating early-stage non-small-cell lung cancer. Optimal trocar placement during VATS ensures comprehensive access to the thoracic cavity, provides a panoramic endoscopic view, and prevents instrument crowding. While established principles such as the Baseball Diamond Principle (BDP) and Triangle Target Principle (TTP) exist, surgeons mainly rely on experience and patient-specific anatomy for trocar placement, potentially leading to sub-optimal surgical plans that increase operative time and fatigue.

Feasibility of video-based skill assessment for percutaneous nephrostomy training in Senegal.

Percutaneous nephrostomy can be an effective means of preventing irreparable renal damage from obstructive renal disease thereby providing patients with more time to access treatment to remove the source of the blockage. In sub-Saharan Africa, where there is limited access to treatments such as dialysis and transplantation, a nephrostomy can be life-saving. Training this procedure in simulation can allow trainees to develop their technical skills without risking patient safety, but still requires an ex-pert observer to provide performative feedback.

Deep learning model meets community-based surveillance of acute flaccid paralysis.

Acute flaccid paralysis (AFP) case surveillance is pivotal for the early detection of potential poliovirus, particularly in endemic countries such as Ethiopia. The community-based surveillance system implemented in Ethiopia has significantly improved AFP surveillance. However, challenges like delayed detection and disorganized communication persist.

PM and hospitalizations through the emergency department in people with disabilities: a nationwide case-crossover study in South Korea.

Background: Little is known about the impact of PM on people with disabilities. We aimed to explore the association between PM and hospitalization via the emergency department (ED admission) among people with disabilities, together with the attributable ED admission cases and costs.

Methods: We applied a time-stratified case-crossover design adjusting ozone, holiday, and temperature using seven years (2015-2021) of claim-based data on ED admissions from the Korean National Health Insurance Database.

Challenging perceptions about rural practice using narratives: a living library approach in medical education.

Introduction: The shortage of physicians in rural Canada is a continuing challenge. Canadian medical schools have adapted strategies to increase the supply of rural physicians. This study appraises the effectiveness of the living library (also called Human Library©) in medical education, as an avenue for medical and pre-medical students to engage in dialogue with rural health professionals.

Surgical interventions for spontaneous supratentorial intracerebral haemorrhage: a systematic review and network meta-analysis.

Background: Surgical interventions for spontaneous supratentorial intracerebral haemorrhage (ICH) include conventional craniotomy (CC), decompressive craniectomy (DC), and minimally invasive surgery (MIS), with the latter encompassing endoscopic surgery (ES) and minimally invasive puncture surgery (MIPS). However, the superiority of surgery over conservative medical treatment (CMT) and the comparative benefits of different surgical procedures remain unclear. We aimed to evaluate the efficacy and safety of various surgical interventions for treating ICH.

Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescents.

Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis.

Diversity and evolution of tyrosinase enzymes involved in the adhesive systems of mussels and tubeworms.

Mussels and tubeworms have evolved similar adhesive systems to cope with the hydrodynamics of intertidal environments. Both secrete adhesive proteins rich in DOPA, a post-translationally modified amino acid playing essential roles in their permanent adhesion. DOPA is produced by the hydroxylation of tyrosine residues by tyrosinase enzymes, which can also oxidize it further into dopaquinone.

Accumulation of alpha-synuclein pathology in the liver exhibits post-translational modifications associated with Parkinson's disease.

Accumulating evidence demonstrates that alpha-synuclein (α-syn) pathology associated with Parkinson's disease (PD) is not limited to the brain, as it also appears in a select number of peripheral tissues including the liver. In this study, we identified a number of PD-associated α-syn post-translational modifications in the livers of (Thy-1)-h[A30P] mice, a mouse model of familial PD expressing human α-syn harboring the A30P mutation driven by a neuron-specific promoter. , we also demonstrate that human hepatocytes induce post-translational modifications following α-syn fibrillar (PFF) treatment.

Single cell profiling of hematopoietic stem cell transplant recipients reveals TGF-β1 and IL-2 confer immunoregulatory functions to NK cells.

Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a CD56NK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor β1 (TGF-β1) in promoting a regulatory phenotype in NK cells.

Evaluation of the outcomes of equity-deserving individuals receiving services and support from integrated substance use health and mental health services: a pilot study protocol.

Background: Given the close relationship that can exist between substance use health and mental health (SUHMH) concerns, the need for more integrated services and support has been identified. However, research on the effective integration of SUHMH services and their impact on outcomes of individuals accessing them remains limited. In particular, the unique outcomes of individuals facing significant structural inequities in the health care system, i.

Violence risk prediction in mental health inpatient settings using the Dynamic Appraisal of Situational Aggression.

Introduction/background: Aggression and violence are common problems in healthcare settings and affects both patients and healthcare staff. The Dynamic Appraisal of Situational Aggression (DASA) is an assessment tool to guide assessment for short term risk in inpatient settings. There have been no large-scale studies examining the performance of the DASA across different clinical settings.

Influence of maternal nutrition and one-carbon metabolites supplementation on bovine antimicrobial peptides in fetal and maternal tissues.

Introduction: Maternal nutrition during pregnancy critically influences offspring development and immune function. One-carbon metabolites (OCM) are epigenetic modifiers that may modulate antimicrobial peptide (AMP) expression, which is vital for innate immunity. This study investigated the effects of maternal nutrient restriction and OCM supplementation on mRNA expression of AMP in fetal and maternal lung, mammary gland, and small intestine of beef cattle.

Non-coding RNAs and regulation of the PI3K signaling pathway in lung cancer: Recent insights and potential clinical applications.

Lung cancer (LC) is one of the most common causes of cancer-related death worldwide. It has been demonstrated that the prognosis of current drug treatments is affected by a variety of factors, including late stage, tumor recurrence, inaccessibility to appropriate treatments, and, most importantly, chemotherapy resistance. Non-coding RNAs (ncRNAs) contribute to tumor development, with some acting as tumor suppressors and others as oncogenes.

Emerging cancer therapies: targeting physiological networks and cellular bioelectrical differences with non-thermal systemic electromagnetic fields in the human body - a comprehensive review.

A steadily increasing number of publications support the concept of physiological networks, and how cellular bioelectrical properties drive cell proliferation and cell synchronization. All cells, especially cancer cells, are known to possess characteristic electrical properties critical for physiological behavior, with major differences between normal and cancer cell counterparts. This opportunity can be explored as a novel treatment modality in Oncology.

Internet-delivered cognitive behaviour therapy for university students: Preference trial for various course durations.

Background: Internet-delivered cognitive behaviour therapy (ICBT) is an accessible and effective treatment option for post-secondary students, but engagement and completion rates are less favourable than in non-student populations in routine care. Studies on students' treatment preferences suggest that a range of options should be offered. Examining students' engagement and outcomes associated with ICBT course options of varying durations can help inform how to optimally deliver ICBT to university students in routine care.

Pain is what you think: functional magnetic resonance imaging evidence toward a cognitive and affective approach for pain research.

The sensory/discriminative domain of pain is often given more consideration than the cognitive and affective influences that ultimately make pain what it is: a highly subjective experience that is based on an individual's life history and experiences. While many investigations of the underlying mechanisms of pain have focused on solely noxious stimuli, few have compared somatosensory stimuli that cross the boundary from innocuous to noxious. Of those that have, there is little consensus on the similarities and differences in neural signaling across these sensory domains.