Are challenging walking environments linked to falls or risk of falling in children with cerebral palsy? A systematic review.

Background: Children with cerebral palsy (CP) regularly fall over and this has negative effects on their physical and psychosocial wellbeing (e.g., reduced activity participation).

The inter-trial and inter-session reliability of Theia3D-derived markerless gait analysis in tight versus loose clothing.

Background: Gait analysis is traditionally conducted using marker-based methods yet markerless motion capture is emerging as an alternative. Initial studies have begun to evaluate the reliability of markerless motion capture yet the evaluation of different clothing conditions across sessions and complete evaluation of the lower limb and pelvis reliability have yet to be considered. The aim of this study was to evaluate the inter-trial, inter-session and inter-session-clothing variation and root mean square differences between tight- or loose-fitting clothing during walking.

Status of surface electromyography assessment as part of clinical gait analysis in the management of patients with cerebral palsy - Outcomes of a Delphi process.

Background: The assessment of gait disorders in patients with neuromotor conditions, such as cerebral palsy (CP), has been a focus of clinical and research attention, with electromyography (EMG) offering a nuanced understanding of neurological and neuromuscular disorders. However, the interpretation of EMG data in the context of gait analysis remains challenging due to the complexity of neuromotor dynamics and variability in assessment methodologies.

Research Question: To which consensus can we get in a group of experts in the fields of neurological and neuromuscular disorders, biomechanics, and clinical gait analysis to establish standardized protocols and a common language for the measurement and analysis of EMG data in gait disorders, particularly in people living with CP?

Methods: A three-round Delphi process was conducted from February to September 2023 to gather opinions of 53 experts on the use of surface EMG data during gait in the context of CP.

Comparative evaluation of methods for the prediction of protein-ligand binding sites.

The accurate identification of protein-ligand binding sites is of critical importance in understanding and modulating protein function. Accordingly, ligand binding site prediction has remained a research focus for over three decades with over 50 methods developed and a change of paradigm from geometry-based to machine learning. In this work, we collate 13 ligand binding site predictors, spanning 30 years, focusing on the latest machine learning-based methods such as VN-EGNN, IF-SitePred, GrASP, PUResNet, and DeepPocket and compare them to the established P2Rank, PRANK and fpocket and earlier methods like PocketFinder, Ligsite and Surfnet.

The path ahead for understanding Toll-like receptor-driven systemic autoimmunity.

Five mammalian Toll-like receptors (TLR 3, 7, 8, 9, and 13) recognize nucleic acids (NA) and induce signals that control the function of multiple immune cell types and initiate both innate and adaptive immune responses. While these receptors enable recognition of diverse microbial threats, in some instances, they respond inappropriately to self-NA released from host cells and drive the development of autoimmune diseases. Specifically, activation of TLR7 and TLR8 by self-RNA and TLR9 by self-DNA has been linked to development of a collection of systemic autoimmune or autoinflammatory disorders, including systemic lupus erythematosus, systemic juvenile idiopathic arthritis, and macrophage activation syndrome.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Smaller Left Ventricular Size But Preserved Function in Adolescents and Adults Born Preterm.

Background: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise.

Evaluating the correspondence between the EQ-5D-5L and disease severity and quality of life in adults and adolescents with cystic fibrosis.

Background: The EQ-5D is the recommended measure to capture health-related quality of life (HRQoL), recognised for use in health technology appraisal bodies. In order to assess whether it is appropriate to use the EQ-5D for making decisions about the cost-utility of treatments in cystic fibrosis (CF), this study assesses the performance of the EQ-5D-5L in adults and adolescents with CF.

Method: This was a cross-sectional observational survey study of patients with CF attending a single large CF centre.

Robotic-assisted enucleation for renal masses: A comparison of on-clamp and off-clamp approach.

Introduction: In surgically excising renal masses, studies have demonstrated that tumor enucleation is an effective option. However, there is limited literature comparing off-clamp to on-clamp tumor enucleation.

Materials And Methods: We retrospectively reviewed the charts of 189 patients who underwent robotic-assisted laparoscopic partial nephrectomy via tumor enucleation by a single surgeon from March 2012 and April 2022.

Two sides of the same runner! The association between biomechanical and physiological markers of endurance performance in distance runners.

Background: The number of people who run to achieve competitive performance has increased, encouraging the scientific community to analyze the association of factors that can affect a runner performance.

Research Question: Is there association between running spatiotemporal and angular kinematics with the physiological markers of endurance performance during a cardiorespiratory exercise test?

Methods: This was an observational cross-sectional study with 40 distance runners simultaneously submitted to a running biomechanical analysis and cardiorespiratory exercise test on a treadmill. Mixed models were developed to verify the association between angular kinematic data obtained by the Movement Deviation Profile and the running spatiotemporal data with oxygen consumption and ventilatory thresholds.

Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma.

Objective: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).

Design: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.

Setting: UK secondary care.

Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.

Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen.

Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom.

Purpose: Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK.

A smoking cessation smartphone app that delivers real-time 'context aware' behavioural support: the Quit Sense feasibility RCT.

Background: During a quit attempt, cues from a smoker's environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides 'in the moment' support to help them manage these during a quit attempt.

Objective: To undertake a feasibility randomised controlled trial to estimate key parameters to inform a definitive randomised controlled trial of Quit Sense.

A unified analysis of evolutionary and population constraint in protein domains highlights structural features and pathogenic sites.

Protein evolution is constrained by structure and function, creating patterns in residue conservation that are routinely exploited to predict structure and other features. Similar constraints should affect variation across individuals, but it is only with the growth of human population sequencing that this has been tested at scale. Now, human population constraint has established applications in pathogenicity prediction, but it has not yet been explored for structural inference.

Control of adaptive immunity by pattern recognition receptors.

One of the most significant conceptual advances in immunology in recent history is the recognition that signals from the innate immune system are required for induction of adaptive immune responses. Two breakthroughs were critical in establishing this paradigm: the identification of dendritic cells (DCs) as the cellular link between innate and adaptive immunity and the discovery of pattern recognition receptors (PRRs) as a molecular link that controls innate immune activation as well as DC function. Here, we recount the key events leading to these discoveries and discuss our current understanding of how PRRs shape adaptive immune responses, both indirectly through control of DC function and directly through control of lymphocyte function.

The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care.

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited.

A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases.

Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma.

Classification of likely functional class for ligand binding sites identified from fragment screening.

Fragment screening is used to identify binding sites and leads in drug discovery, but it is often unclear which binding sites are functionally important. Here, data from 37 experiments, and 1309 protein structures binding to 1601 ligands were analysed. A method to group ligands by binding sites is introduced and sites clustered according to profiles of relative solvent accessibility.

Measuring the PULSE of Nursing: Development of a Dashboard to Evaluate and Monitor Nursing Care Models.

Background: Critical nursing shortages have required many health care organizations to restructure nursing care delivery models. At a tertiary health care center, 150 registered practical nurses were integrated into acute inpatient care settings.

Problem: A mechanism to continuously monitor the impact of this staffing change was not available.

Krüppel-like Factor (KLF) family members control expression of genes required for serous cavity and alveolar macrophage identities.

Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Kruppel-like Factor 2 (KLF2) in the development of embryonically derived Large Cavity Macrophages (LCM) in the serous cavities.