Explainable AI associates ECG aging effects with increased cardiovascular risk in a longitudinal population study.

Aging affects the 12-lead electrocardiogram (ECG) and correlates with cardiovascular disease (CVD). AI-ECG models estimate aging effects as a novel biomarker but have only been evaluated on single ECGs-without utilizing longitudinal data. We validated an AI-ECG model, originally trained on Brazilian data, using a German cohort with over 20 years of follow-up, demonstrating similar performance (r = 0.

Adherence to Oral Nutritional Supplements: A Review of Trends in Intervention Characteristics and Terminology Use Since the Year 2000.

Research on disease-related malnutrition and adherence to oral nutritional supplements (ONS) has increased in recent years. To guide future studies, it is important to identify trends in terminology use and intervention characteristics. This review aimed to map characteristics of research investigating adherence to ONS in patients with disease-related malnutrition and explore changes over time.

Is internet-based cognitive behavioral therapy for alcohol use disorder equally effective for men and women? Implications of a secondary analysis of a clinical trial.

Introduction: Excessive alcohol use is a major public health concern, for which internet interventions have shown to be effective. Group-average effects may however mask substantial inter-individual variations in changes; identifying predictors of this variation remains an important research question. Biological sex is associated with pharmacokinetic differences in alcohol tolerance, which is reflected in many national guidelines recommending sex-specific thresholds for excessive drinking.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on Clinical Outcomes in Allogeneic Hematopoietic Cell Transplantation: Does Speeding Up Neutrophil Engraftment Make a Difference?

Background: Despite decades of post-allogeneic hematopoietic cell transplantation (HCT) growth factor utilization, its role remains undefined, leading to ongoing debates and research. The theoretical impacts of growth factors have been challenged in numerous studies.

Methods: In this retrospective cohort study conducted at the Princess Margaret Cancer Centre, we analyzed the clinical outcomes of 509 patients who underwent allogeneic HCT between May 1, 2019, and May 31, 2022.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Meat intake in relation to composition and function of gut microbiota.

Objective: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors.

Design: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals.

Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

Choline Metabolites, Genetic Susceptibility, and Incident Heart Failure.

Background: Little is known about the associations between choline metabolites (total choline, phosphatidylcholine, and glycine) and the incidence of heart failure (HF).

Objectives: The purpose of this study was to assess the associations of choline metabolites with incident HF and examine the effect modification by genetic susceptibility.

Methods: This prospective cohort study followed 245,072 participants from the UK Biobank from baseline (2006-2010) until March 30, 2023.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Determinants of growth differentiation factor 15 plasma levels in outpatients with peripheral arterial disease.

Background: Growth differentiation factor 15 (GDF-15) is a robust prognostic biomarker in patients with cardiovascular (CV) disease, and a better understanding of its clinical determinants is desirable. We aimed to study the associations between GDF-15 levels and in outpatients with peripheral arterial disease (PAD).

Methods: An explorative cross-sectional study (Study of Atherosclerosis in Vastmanland, Västerås, Sweden) included 439 outpatients with carotid or lower extremity PAD.

Have People Treated With Antihypertensives Been Diagnosed With Hypertension? A Cross-Sectional Study in Stockholm, Sweden.

Purpose: Studies on antihypertensive treatment are important, as hypertension remains the major risk factor for cardiovascular morbidity and premature death. However, antihypertensive medicines are also used for other conditions, and the use of these medicines as a proxy for a diagnosis of hypertension might lead to misclassification in pharmacoepidemiological studies. This study aimed to investigate to what extent people dispensed antihypertensive medicines have been diagnosed with hypertension.

What are the important risk factors for excessive daytime sleepiness in a population-based cohort?

Excessive daytime sleepiness (EDS) is a common complaint in the general population and is associated with cardiovascular disease and increased mortality. We aimed to investigate whether sleep duration is related to excessive daytime sleepiness in the general population, both in itself and in combination with other factors. We performed a cross-sectional analysis in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort (n = 27,976; 14,436 females; aged 50-64 years) to assess how sleep-related factors along with anthropometric, lifestyle, socioeconomic factors as well as somatic disease and psychological distress, were related with EDS assessed by the Epworth sleepiness scale (ESS).

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

Myocardial Fibroblast Activation After Acute Myocardial Infarction: A Positron Emission Tomography and Magnetic Resonance Study.

Background: Myocardial fibrosis is a key healing response after myocardial infarction driven by activated fibroblasts. Gallium-68-labeled fibroblast activation protein inhibitor ([Ga]-FAPI) is a novel positron-emitting radiotracer that binds activated fibroblasts.

Objectives: The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction.

High percentage of immune Th1 and Tc1 cells infiltrating visceral adipose tissue in people with obesity.

Subcutaneous (SAT) and visceral (VAT) adipose tissue dysfunction during the obesity onset can lead to increased expression of inflammatory molecules, and consequently to immune cell infiltration. The aim was to deeply characterize the T cells, those infiltrating SAT and VAT, compared to peripheral blood (PB), in individuals undergoing bariatric surgery. Forty-two adult individuals were recruited, SAT and VAT samples were collected.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

The Stockholm early detection of cancer study (STEADY-CAN): rationale, design, data collection, and baseline characteristics for 2.7 million participants.

The Stockholm Early Detection of Cancer Study (STEADY-CAN) cohort was established to investigate strategies for early cancer detection in a population-based context within Stockholm County, the capital region of Sweden. Utilising real-world data to explore cancer-related healthcare patterns and outcomes, the cohort links extensive clinical and laboratory data from both inpatient and outpatient care in the region. The dataset includes demographic information, detailed diagnostic codes, laboratory results, prescribed medications, and healthcare utilisation data.

Patient's Perception of Primary Health Care Provision With Respect to Access, Continuity and Coordination-InCept: An International Qualitative Perspective.

Health care systems are confronted with an increasing burden of (multi-)morbidity and a shortfall of healthcare providers. Coordination and continuity of care in chronic and multi-morbid patient is especially important. As qualitative patient experience data within care processes is scarce, we aim to increase the understanding of chronically ill patient's perspectives by assessing patient experiences in different health systems while treated in primary care.

Efficacy and cost-effectiveness of an ACT and compassion-based intervention for women with breast cancer: study protocol of two randomised controlled trials {1}.

Background: Breast cancer is the most diagnosed cancer in women worldwide and carries a considerable psychosocial burden. Interventions based on Acceptance and Commitment Therapy (ACT) and compassion-based approaches show promise in improving adjustment and quality of life in people with cancer. The Mind programme is an integrative ACT and compassion-based intervention tailored for women with breast cancer, which aims to prepare women for survivorship by promoting psychological flexibility and self-compassion.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

Research Participants' Engagement and Retention in Digital Health Interventions Research: Protocol for Mixed Methods Systematic Review.

Background: Digital health interventions have become increasingly popular in recent years, expanding the possibilities for treatment for various patient groups. In clinical research, while the design of the intervention receives close attention, challenges with research participant engagement and retention persist. This may be partially due to the use of digital health platforms, which may lack adequacy for participants.

Treatment and treatment outcomes of snakebite envenoming in Uganda: a retrospective analysis.

Background: Snakebite envenoming is a neglected tropical disease that causes significant morbidity and mortality in rural sub-Saharan Africa. However, there is a notable lack of data concerning the management and treatment outcomes for those affected. This study addresses this gap by examining the management and treatment outcomes of snakebite victims in Uganda.