A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.

Chronic Health Conditions in the Workplace: Work Stressors and Supportive Supervision, Work Design, and Programs.

A large and growing number of workers are managing chronic physical and mental health conditions while working, necessitating attention from both researchers and leaders and practitioners in organizations. Much of the current discourse around research and practice in this area is focused on prevention of chronic disease and rehabilitation of disability to help workers return to work. Less commonly attended to are workplace factors that can support the quality of working life and the longevity of working life for workers with chronic health conditions.

Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.

Exome Sequencing in the Diagnostic Pathway for Suspected Rare Genetic Diseases: Does the Order of Testing Affect its Cost-Effectiveness?

Background: Patients with suspected rare diseases often experience lengthy and uncertain diagnostic pathways. This study aimed to estimate the cost-effectiveness of exome sequencing (ES) in different positions in the diagnostic pathway for patients suspected of having a rare genetic disease.

Methods: Data collected retrospectively from 305 patients suspected of having a rare genetic disease (RGD), who received clinical-grade ES and participated in the Canadian multicentre Care4Rare-SOLVE study, informed a discrete event simulation of the diagnostic pathway.

Embryotoxicity of statins and other prescribed drugs with reported off-target effects on cholesterol biosynthesis.

Cholesterol plays pivotal cellular functions ranging from maintaining membrane fluidity to regulating cell-cell signaling. High cholesterol causes cardiovascular diseases, low cholesterol is linked to neuropsychiatric disorders, and inborn errors of cholesterol synthesis cause multisystem malformation syndromes. Statins lower cholesterol levels by inhibiting the first, rate-limiting reaction of the cholesterol biosynthesis pathway catalyzed by hydroxymethyl-glutaryl-Coenzyme A reductase (HMGCR).

The noninvasive ventilation outcomes score in patients requiring NIV for COPD exacerbation without prior evidence of airflow obstruction.

Introduction: Exacerbation of COPD complicated by respiratory acidaemia is the commonest indication for noninvasive ventilation (NIV). The NIV outcomes (NIVO) score offers the best estimate of survival for those ventilated. Unfortunately, two-thirds of cases of COPD are unrecognised, and patients may present without COPD having been confirmed by spirometry.

A Modular Biosensor Design for Quantitative Measurement of Free Nedd8.

The objective of our study was to develop a genetically encoded biosensor for quantification of Nedd8, a post-translational modifier that regulates cellular signals through conjugation to other proteins. Perturbations in the balance of free (i.e.

A standardized approach to evaluate effectiveness of aerobic exercise training interventions in cardiovascular disease at the individual level.

Background: Reliable change indices can determine pre-post intervention changes at an individual level that are greater than chance or practice effect. We applied previously developed minimal meaningful change (MMC) scores for oxygen uptake (V̇O) values associated with estimated lactate threshold (θ), respiratory compensation point (RCP), and peak oxygen uptake (V̇O) to evaluate the effectiveness of exercise training in cardiovascular disease patients.

Methods: 303 patients (65 ± 11 yrs.

Changes in primary visual and auditory cortex of blind and sighted adults following 10 weeks of click-based echolocation training.

Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural "blueprints" may fundamentally constrain neuroplastic change, e.g.

BACK-to-MOVE: Machine learning and computer vision model automating clinical classification of non-specific low back pain for personalised management.

Background: Low back pain (LBP) is a major global disability contributor with profound health and socio-economic implications. The predominant form is non-specific LBP (NSLBP), lacking treatable pathology. Active physical interventions tailored to individual needs and capabilities are crucial for its management.

Designing, implementing and testing an intervention of affective intelligent agents in nursing virtual reality teaching simulations-a qualitative study.

Emotions play an important role in human-computer interaction, but there is limited research on affective and emotional virtual agent design in the area of teaching simulations for healthcare provision. The purpose of this work is twofold: firstly, to describe the process for designing affective intelligent agents that are engaged in automated communications such as person to computer conversations, and secondly to test a bespoke prototype digital intervention which implements such agents. The presented study tests two distinct virtual learning environments, one of which was enhanced with affective virtual patients, with nine 3rd year nursing students specialising in mental health, during their professional practice stage.

Artificial intelligence for ultrasound scanning in regional anaesthesia: a scoping review of the evidence from multiple disciplines.

Background: Artificial intelligence (AI) for ultrasound scanning in regional anaesthesia is a rapidly developing interdisciplinary field. There is a risk that work could be undertaken in parallel by different elements of the community but with a lack of knowledge transfer between disciplines, leading to repetition and diverging methodologies. This scoping review aimed to identify and map the available literature on the accuracy and utility of AI systems for ultrasound scanning in regional anaesthesia.

Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.

Objective: ACTN2, encoding alpha-actinin-2, is essential for cardiac and skeletal muscle sarcomeric function. ACTN2 variants are a known cause of cardiomyopathy without skeletal muscle involvement. Recently, specific dominant monoallelic variants were reported as a rare cause of core myopathy of variable clinical onset, although the pathomechanism remains to be elucidated.

Quantifying Improvement in V˙ o2peak and Exercise Thresholds in Cardiovascular Disease Using Reliable Change Indices.

Purpose: Improving aerobic fitness through exercise training is recommended for the treatment of cardiovascular disease (CVD). However, strong justifications for the criteria of assessing improvement in key parameters of aerobic function including estimated lactate threshold (θ LT ), respiratory compensation point (RCP), and peak oxygen uptake (V˙ o2peak ) at the individual level are not established. We applied reliable change index (RCI) statistics to determine minimal meaningful change (MMC RCI ) cutoffs of θ LT , RCP, and V˙ o2peak for individual patients with CVD.

The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.

Argininosuccinate lyase (ASL) is integral to the urea cycle detoxifying neurotoxic ammonia and the nitric oxide (NO) biosynthesis cycle. Inherited ASL deficiency causes argininosuccinic aciduria (ASA), a rare disease with hyperammonemia and NO deficiency. Patients present with developmental delay, epilepsy and movement disorder, associated with NO-mediated downregulation of central catecholamine biosynthesis.

Evaluation of the diagnostic accuracy of exome sequencing and its impact on diagnostic thinking for patients with rare disease in a publicly funded health care system: A prospective cohort study.

Purpose: To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases.

Methods: We prospectively enrolled 297 probands who met eligibility criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests.

Exome and genome sequencing for rare genetic disease diagnosis: A scoping review and critical appraisal of clinical guidance documents produced by genetics professional organizations.

Purpose: Exome and genome sequencing have rapidly transitioned from research methods to widely used clinical tests for diagnosing rare genetic diseases. We sought to synthesize the topics covered and appraise the development processes of clinical guidance documents generated by genetics professional organizations.

Methods: We conducted a scoping review of guidance documents published since 2010, systematically identified in peer-reviewed and gray literature, using established methods and reporting guidelines.

Do Clinical Exercise Tests Permit Exercise Threshold Identification in Patients Referred to Cardiac Rehabilitation?

Background: To evaluate the feasibility of "threshold-based" aerobic exercise prescription in cardiovascular disease, we aimed to quantify the proportion of patients whose clinical cardiopulmonary exercise test (CPET) permit identification of estimated lactate threshold (θ) and respiratory compensation point (RCP) and to characterize the variability at which these thresholds occur.

Methods: Breath-by-breath CPET data of 1102 patients (65 ± 12 years) referred to cardiac rehabilitation were analyzed to identify peak O uptake (V˙O; mL·min and mL·kg·min) and θ and RCP (reported as V˙O, %V˙O, and %peak heart rate [%HR]). Patients were grouped by the presence or absence of thresholds: group 0: neither θ nor RCP; group 1: θ only; and group 2: both θ and RCP.

Hereditary renal cancer patient and public involvement group: A collaborative, consensus decision process to develop a communication tool for patient use.

Patient and public involvement (PPI) must be more frequently embedded within clinical research to ensure translational outcomes are patient-led and meet patient needs. Active partnerships with patients and public groups are an important opportunity to hear patient voices, understand patient needs, and inform future research avenues. A hereditary renal cancer (HRC) PPI group was developed with the efforts of patient participants ( = 9), pooled from recruits within the early detection for HRC pilot study, working in collaboration with researchers and healthcare professionals ( = 8).

Novel Homozygous Variant in in Siblings With Hereditary Motor Neuropathy.

Background And Objectives: Coenzyme Q (CoQ) is an important electron carrier and antioxidant. The COQ7 enzyme catalyzes the hydroxylation of 5-demethoxyubiquinone-10 (DMQ), the second-to-last step in the CoQ biosynthesis pathway. We report a consanguineous family presenting with a hereditary motor neuropathy associated with a homozygous c.

The effect of physical exercise on anxiety in people with parkinson's disease: A systematic review of randomized control trials.

Background: Anxiety is a prominent disabling non-motor neuropsychiatric complication of Parkinson's disease (PD). Pharmacological treatments for PD and anxiety have drug interactions and negative side effects. Therefore, non-pharmacological interventions such as exercise has been proposed to reduce anxiety in people with PD (PwP).