Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease.

TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders.

Does Sleep Moderate the Effects of Exercise Training or Complex Mental and Social Activities on Cognitive Function in Adults With Chronic Stroke? Secondary Analysis of a Randomized Trial.

Background: Exercise (EX) or cognitive and social enrichment (ENRICH) are 2 strategies for promoting cognition poststroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown.

Methods: A 3-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (ie, ≥12 months since stroke).

Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial- The ABC-Sepsis Trial.

Objectives: International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital.

Trade-offs between overall survival and side effects in the treatment of metastatic breast cancer: eliciting preferences of patients with primary and metastatic breast cancer using a discrete choice experiment.

Objectives: There has been a recent proliferation in treatment options for patients with metastatic breast cancer. Such treatments often involve trade-offs between overall survival and side effects. Our study aims to estimate the trade-offs that could be used to inform decision-making at the individual and policy level.

Early prehabilitation reduces admissions and time in hospital in patients with newly diagnosed lung cancer.

Objectives: Lung cancer is the leading cause of cancer death in the UK. Prehabilitation aims to maximise patient fitness and minimise the negative impact of anticancer treatment. What constitutes prehabilitation before non-surgical anticancer treatment is not well established.

Mistranslating the genetic code with leucine in yeast and mammalian cells.

Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do not recognize the anticodon bases. Single nucleotide anticodon variants in their cognate tRNAs can lead to mistranslation.

New quality outcome indicators for bone metastases: expert consensus analysis of patients, their families and specialist healthcare professionals.

Objectives: As workload increases, surgical care for patients with bone metastases is increasingly decentralised, with a shift in management away from primary bone tumour units to local centres. We must ensure that patients have similar outcomes regardless of where they receive their treatment. The aim was to develop and validate a set of quality outcome indicators (QOIs) to evaluate treatment success for patients undergoing surgery for bone metastases.

Automated radiosynthesis of [F]DPA-714 on a commercially available IBA Synthera®.

The goal of this work was to develop a reliable method to produce the well-validated microglial activation PET tracer, [F]DPA-714, routinely for clinical and preclinical research using an IBA Synthera®. Optimization of literature methods included reduced precursor mass and use of TBA HCO as the phase transfer agent in place of Kryptofix® 222 in a 65-min synthesis with an average activity yield of 24.6 ± 3.

rTMS for post-covid-19 condition: A sham-controlled case series involving iTBS-300 and iTBS-600.

Post-Covid-19 Condition (PCC) is a syndrome comprised of symptoms persisting 3 months or more beyond SARS-CoV-2 primary infection. It is typically characterized by fatigue, cognitive problems and psychiatric symptoms, as well as cardiac symptoms that contribute to exercise intolerance in many. Despite the high prevalence of PCC among those with a prior SARS-CoV-2 infection, there is currently no widely accepted rehabilitation strategy, and many conventional modalities are movement-based.

Cross-sectional and longitudinal neural predictors of physical activity and sedentary behaviour from a 6-month randomized controlled trial.

A sedentary lifestyle offers immediate gratification, but at the expense of long-term health. It is thus critical to understand how the brain evaluates immediate rewards and long-term health effects in the context of deciding whether to engage in moderate-to-vigorous physical activity (MVPA) or sedentary behaviour (SB). In this secondary analysis of a 6-month randomized controlled trial to increase MVPA and reduce SB among community-dwelling adults, we explored how neural activity during an executive control task was associated with MVPA and SB levels.

Diabetes status and cognitive function in middle-aged and older adults in the Canadian longitudinal study on aging.

Objectives: Diabetes is recognized as a significant risk factor for cognitive impairment. However, this association has not been thoroughly examined using large-scale population-based datasets in the Canadian context. The objective of this study was to investigate the potential association between cognitive function and diabetes in a large population-based sample of middle-aged and older Canadians.

Economic Evaluation of Exercise or Cognitive and Social Enrichment Activities for Improved Cognition After Stroke.

Importance: Cognitive impairment is prevalent in survivors of stroke, affecting approximately 30% of individuals. Physical exercise and cognitive and social enrichment activities can enhance cognitive function in patients with chronic stroke, but their cost-effectiveness compared with a balance and tone program is uncertain.

Objective: To conduct a cost-effectiveness and cost-utility analysis of multicomponent exercise or cognitive and social enrichment activities compared with a balance and tone program.

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.

Introduction: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo.

Painterly Style Transfer With Learned Brush Strokes.

Real-world paintings are made, by artists, using brush strokes as the rendering primitive to depict semantic content. The bulk of the Neural Style Transfer (NST) is known transferring style using texture patches, not strokes. The output looks like the content image, but some are traced over using the style texture: it does not look painterly.

Next-generation cognitive assessment: Combining functional brain imaging, system perturbations and novel equipment interfaces.

Conventional cognitive assessment is widely used in clinical and research settings, in educational institutions, and in the corporate world for personnel selection. Such approaches involve having a client, a patient, or a research participant complete a series of standardized cognitive tasks in order to challenge specific and global cognitive abilities, and then quantify performance for the desired end purpose. The latter may include a diagnostic confirmation of a disease, description of a state or ability, or matching cognitive characteristics to a particular occupational role requirement.

Evaluation of the association of area-level socioeconomic deprivation and breast cancer recurrence by oestrogen receptor subtypes in Scotland.

Background: Women from socioeconomically deprived areas have lower breast cancer (BC) incidence rates for screen-detected oestrogen receptor (ER) + tumours and higher mortality for select tumour subtypes. We aimed to determine if ipsilateral breast cancer recurrence (IBR) differs by Scottish Index of Multiple Deprivation (SIMD) quintile and tumour subtype in Scotland.

Methods: Patient data for primary invasive BC diagnosed in 2007-2008 in Scotland was analysed.

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

Background: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.

Methods: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment.

Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol.

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified-release morphine in chronic breathlessness.

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

Introduction: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.

Methods And Analysis: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery.