Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial.

Aims: This study tested the efficacy and safety of a 12-week course of lisdexamfetamine in reducing methamphetamine use, an outcome which is associated with improvements in health and wellbeing, in people dependent on methamphetamine.

Design, Setting And Participants: This study was a randomised double-blind placebo-controlled trial conducted in six specialist outpatient clinics in Adelaide, Melbourne, Newcastle and Sydney, Australia (2018-2021). Participants were164 adults with methamphetamine dependence, reporting at least 14 use days out of the previous 28 days (62% male, 38% female, < 1% other; mean age 39 years).

Design of pseudosymmetric protein hetero-oligomers.

Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers.

Assessing the impact of physical, mental and cognitive impairments on health-related quality of life in sepsis survivors following intensive care admission in New Zealand.

Aim: To assess the impact of physical, mental and cognitive impairments on health-related quality-of-life (QoL) of individuals who have survived sepsis after admission to an Intensive Care Unit (ICU) in New Zealand.

Methods: Survivors from a trial investigating vitamin C as an adjunctive therapy in patients with sepsis in Christchurch Hospital ICU were invited to enrol in a longitudinal QoL follow-up study. Patients were interviewed at hospital discharge, 30, 90 and 180 days, using validated physical and mental health assessment questionnaires (Short-Form-36, EuroQol-5-Dimension).

AI: A transformative opportunity in cell biology.

The success of artificial intelligence (AI) algorithms in predicting protein structure and more recently, protein interactions, demonstrates the power and potential of machine learning and AI for advancing and accelerating biomedical research. As cells are the fundamental unit of life, applying these tools to understand and predict cellular function represents the next great challenge. However, given the complexity of cellular structure and function, the diversity of cell types and the dynamic plasticity of cell states, the task will not be easy.

CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data.

Hundreds of millions of single cells have been analyzed using high-throughput transcriptomic methods. The cumulative knowledge within these datasets provides an exciting opportunity for unlocking insights into health and disease at the level of single cells. Meta-analyses that span diverse datasets building on recent advances in large language models and other machine-learning approaches pose exciting new directions to model and extract insight from single-cell data.

Neurological complications of immune checkpoint inhibitors: a practical guide.

Immune checkpoint inhibition unleashes the power of the immune system against tumour cells. Immune checkpoint inhibitors (ICIs) block the inhibitory effects of cytotoxic T-lymphocyte associated protein 4, programmed death protein 1, programmed death ligand 1 and lymphocyte activation gene 3 molecules on T-cells, and so enhance physiological cytotoxic effects. ICIs can significantly improve survival from cancers, including those previously associated with poor treatment response, such as metastatic melanoma.

Health equity engineering: Optimizing hope for a new generation of healthcare.

Medical researchers are increasingly prioritizing the inclusion of underserved communities in clinical studies. However, mere inclusion is not enough. People from underserved communities frequently experience chronic stress that may lead to accelerated biological aging and early morbidity and mortality.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests.

Purpose: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers.

Methods: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

The healthy habits questionnaire (HHQ): Validation of a measure designed to assess problematic influential behaviours amongst families of children living with obesity or a risk of developing obesity.

The 48-item Healthy Habits Questionnaire (HHQ-48) was developed to (1) monitor positive changes in family lifestyles following engagement in the Parents Plus Healthy Families (PP-HF) parent training programme and (2) be utilised as a standalone measure in clinical settings to identify and track problematic influential behaviours amongst families of children in weight-management services. This study aimed to develop and validate a brief version of the HHQ-48. The scale was administered to a cross-sectional community sample ( = 480), and on two occasions to a control sample ( = 50) and an experimental sample ( = 40) from a randomised controlled trial (RCT) of the PP-HF programme to assess test-retest reliability and sensitivity to change respectively.

Assisting the Learning of Clinical Reasoning by Veterinary Medical Learners with a Case Example.

Effective clinical reasoning is essential for veterinary medical education, particularly in managing complex cases. This review explores strategies for learning clinical reasoning by veterinary medical learners, using a case example of mastitis to illustrate key concepts. Clinical reasoning encompasses cognitive, metacognitive, social, and situational activities, yet the literature on practical applications in veterinary education remains limited.

Core charge of imidazolium annulated triphenylene derivatives induces discotic columnar mesomorphism.

Thermotropic ionic liquid crystals have remained a relatively little studied group of materials despite their many potential applications as anisotropic ionic liquids and charge (ion and electron/hole) transporting materials. Particularly rare are core charged discotic liquid crystals because their synthesis is usually more involved, and their molecular design is less established. Presented here is a straightforward and versatile synthetic approach to imidazolium annulated triphenylene derivatives.

Sex-dependent responses to acute sodium bicarbonate different dose treatment: A randomized double-blind crossover study.

Objectives: This study quantified blood bicarbonate (HCO) kinetics and gastrointestinal upset to determine the gender-related ergogenic potential of sodium bicarbonate (0.15-, 0.25- and 0.

Understanding the additional impact of prediabetes and type 2 diabetes mellitus on vitamin C requirements in people living with obesity.

Obesity and diabetes are known to negatively affect vitamin C status. However, whether the presence of diabetes, in addition to obesity, contributes an additional impact on vitamin C status is currently uncertain. In a cohort of 152 adults living with obesity, we assessed metabolic and nutrient parameters in participants without diabetes (n = 92), and with prediabetes (n = 22) and type 2 diabetes mellitus (T2DM; n = 35).

Influence of acute heat mitigation strategies on core temperature, heart rate and aerobic performance in females: A systematic literature review.

This review examined the effect of acute heat mitigation strategies on physiological strain and exercise performance in females exercising in the heat. Three databases were searched for original research with an acute heat mitigation (intervention) and control strategy in active females and reporting core temperature, heart rate and/or aerobic exercise performance/capacity with ≥ 24°C wet bulb globe temperature. Hedges' effect sizes were calculated to evaluate outcomes.

Enhancing clinical genomic accuracy with panelGC: a novel metric and tool for quantifying and monitoring GC biases in hybridization capture panel sequencing.

Accurate assessment of fragment abundance within a genome is crucial in clinical genomics applications such as the analysis of copy number variation (CNV). However, this task is often hindered by biased coverage in regions with varying guanine-cytosine (GC) content. These biases are particularly exacerbated in hybridization capture sequencing due to GC effects on probe hybridization and polymerase chain reaction (PCR) amplification efficiency.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR.

Analytical and clinical validation of direct detection of antimicrobial resistance markers by plasma microbial cell-free DNA sequencing.

Unlabelled: Sequencing of plasma microbial cell-free DNA (mcfDNA) has gained increased acceptance as a valuable adjunct to standard-of-care testing for diagnosis of infections throughout the body. Here, we report the analytical and clinical validation of a novel application of mcfDNA sequencing, the non-invasive detection of seven common antimicrobial resistance (AMR) genetic markers in 18 important pathogens. The AMR markers include SCC, , , , and .

Stiff person syndrome.

Stiff Person syndrome (SPS) is a rare autoimmune disorder of the central nervous system characterized by stiffness and spasms in the lumbar and proximal lower limb muscles. Nonmotor symptoms include phobias, anxiety, and depression. SPS exists on a spectrum ranging from a focal disease known as the stiff limb syndrome to progressive encephalomyelitis with rigidity and myoclonus.

TBK1 and IKKε protect target cells from IFNγ-mediated T cell killing via an inflammatory apoptotic mechanism.

Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether T cell-derived IFNγ directly kills infected and tumor target cells, and how this may be regulated. Here, we report that target cell expression of the kinases TBK1 and IKKε regulate IFNγ cytotoxicity by suppressing the ability of T cell-derived IFNγ to kill target cells.

Creating sustainable capacity for river science in the Congo basin through the CRuHM project.

In this article, we examine the scientific and sustainable research capacity outcomes of the 'Congo River: user Hydraulics and Morphology' or CRuHM project, a six-year effort supported by the Royal Society's Africa Capacity Building Initiative. This project brought together a consortium of African and UK universities to undertake the first large-scale scientific expeditions to the Congo basin of the modern era in order to better understand the hydraulics and geomorphology of this understudied but globally important river. The river is essential for navigation, irrigation, drinking water and hydroelectric power generation for the 10 basin countries and is critically important for biodiversity and global nutrient, carbon and climatological cycles.