A Digital Tool (Technology-Assisted Problem Management Plus) for Lay Health Workers to Address Common Mental Health Disorders: Co-production and Usability Study in Pakistan.

Background: Mental health remains among the top 10 leading causes of disease burden globally, and there is a significant treatment gap due to limited resources, stigma, limited accessibility, and low perceived need for treatment. Problem Management Plus, a World Health Organization-endorsed brief psychological intervention for mental health disorders, has been shown to be effective and cost-effective in various countries globally but faces implementation challenges, such as quality control in training, supervision, and delivery. While digital technologies to foster mental health care have the potential to close treatment gaps and address the issues of quality control, their development requires context-specific, interdisciplinary, and participatory approaches to enhance impact and acceptance.

Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Evaluating and Comparing the Content Coverage of Quality Measure Sets from Israel, the United States, and the United Kingdom.

Background: Quality of care can be measured in several dimensions: different clinical disciplines, structures/processes/outcomes of care (SPO), and also different domains of quality (effectiveness, safety, care coordination, patient-centeredness, efficiency, timeliness, and community/population health). To our knowledge, no previous study has compared different sets of performance measures in terms of how well they cover these different aspects of quality.

Objective: Compare the content coverage of major quality measure sets from Israel, the US, and the UK.

Investigating the longitudinal bi-directional relationship between self-reported restrictive eating behaviours and sleep in UK adolescents within the Millennium Cohort Study.

Objective: This study aimed to investigate the longitudinal bi-directional relationship between self-reported restrictive eating behaviours and sleep characteristics within a sample of UK adolescents from the Millennium Cohort Study (MCS).

Method: Using a Structural Equation Modelling approach, the present study investigated the prospective associations between individual sleep behaviours (e.g.

Estimating hypothetical estimands with causal inference and missing data estimators in a diabetes trial case study.

The ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here, we report analyses of a clinical trial in type 2 diabetes, targeting the effects of randomized treatment, handling rescue treatment and discontinuation of randomized treatment using the so-called hypothetical strategy. We show how this can be estimated using mixed models for repeated measures, multiple imputation, inverse probability of treatment weighting, G-formula, and G-estimation.

Carboxy-Amidated AamAP1-Lys has Superior Conformational Flexibility and Accelerated Killing of Gram-Negative Bacteria.

C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility.

Use of AI in Cardiac CT and MRI: A Scientific Statement from the ESCR, EuSoMII, NASCI, SCCT, SCMR, SIIM, and RSNA.

Artificial intelligence (AI) offers promising solutions for many steps of the cardiac imaging workflow, from patient and test selection through image acquisition, reconstruction, and interpretation, extending to prognostication and reporting. Despite the development of many cardiac imaging AI algorithms, AI tools are at various stages of development and face challenges for clinical implementation. This scientific statement, endorsed by several societies in the field, provides an overview of the current landscape and challenges of AI applications in cardiac CT and MRI.

Deep Learning Superresolution for Simultaneous Multislice Parallel Imaging-Accelerated Knee MRI Using Arthroscopy Validation.

Background Deep learning (DL) methods can improve accelerated MRI but require validation against an independent reference standard to ensure robustness and accuracy. Purpose To validate the diagnostic performance of twofold-simultaneous-multislice (SMSx2) twofold-parallel-imaging (PIx2)-accelerated DL superresolution MRI in the knee against conventional SMSx2-PIx2-accelerated MRI using arthroscopy as the reference standard. Materials and Methods Adults with painful knee conditions were prospectively enrolled from December 2021 to October 2022.

Global Impact of Mass Vaccination Campaigns on Circulating Type 2 Vaccine-Derived Poliovirus Outbreaks: An Interrupted Time-Series Analysis.

Background: Between 2016 and 2023, 3248 cases of circulating vaccine-derived type 2 poliomyelitis (cVDPV2) were reported globally and supplementary immunization activities (SIAs) with monovalent type 2 oral poliovirus vaccine (mOPV2) and novel type 2 oral poliovirus vaccine (nOPV2) targeted an estimated 356 and 525 million children, respectively. This analysis estimates the community-level impact of nOPV2 relative to mOPV2 SIAs.

Methods: We fitted interrupted time-series regressions to surveillance data between January 2016 and November 2023 to estimate the impact of nOPV2 and mOPV2 SIAs on cVDPV2 poliomyelitis incidence and prevalence in environmental surveillance across 37 countries, directly comparing the impact of SIAs in 13 countries where both vaccines were used.

Comparison of different microbiome analysis pipelines to validate their reproducibility of gastric mucosal microbiome composition.

Microbiome analysis has become a crucial tool for basic and translational research due to its potential for translation into clinical practice. However, there is ongoing controversy regarding the comparability of different bioinformatic analysis platforms and a lack of recognized standards, which might have an impact on the translational potential of results. This study investigates how the performance of different microbiome analysis platforms impacts the final results of mucosal microbiome signatures.

Analyzing free fatty acids in seminal plasma from asthenozoospermia patients undergoing antioxidant therapy.

Objective: Different aspects of the functions of free fatty acid (FFA) in seminal plasma and their implications on male fertility are known. However, the profile of FFA in seminal plasma in asthenozoospermic patients following antioxidant therapy has not been studied.

Methods: In this case-control study, the total antioxidant capacity (TAC) and FFA profile of the seminal plasma were determined in 80 patients (29 normozoospermic volunteers and 51 asthenozoospermic men) who were treated with antioxidants for three months.

Context as politicised psycho-geographies: The psychological relationship between individual, politics, and country.

This paper sheds light on how spaces become contested sites for identity construction and negotiation to take place. Applying the Social Representations Approach, a qualitative study of 10 focus group discussions (n = 39), was conducted in Singapore, Malaysia and the UK to explore how, and why racialised identity construction changed in each socio-political context. The study challenged two underlying assumptions in social psychology: (1) that the meaning of the racialised category holds constant across time and space, and (2) there exists a pan-racial identification among Asian identities, for example, which at times allows for racialised categories to be manipulated as variables.

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Background And Aims: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

Methods: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan.

How well do empirical molecular mechanics force fields model the cholesterol condensing effect?

Membrane properties are determined in part by lipid composition, and cholesterol plays a large role in determining these properties. Cellular membranes show a diverse range of cholesterol compositions, the effects of which include alterations to cellular biomechanics, lipid raft formation, membrane fusion, signaling pathways, metabolism, pharmaceutical therapeutic efficacy, and disease onset. In addition, cholesterol plays an important role in non-cellular membranes, with its concentration in the skin lipid matrix being implicated in several skin diseases.

Improving the generalization of protein expression models with mechanistic sequence information.

The growing demand for biological products drives many efforts to maximize expression of heterologous proteins. Advances in high-throughput sequencing can produce data suitable for building sequence-to-expression models with machine learning. The most accurate models have been trained on one-hot encodings, a mechanism-agnostic representation of nucleotide sequences.

Exploring child and youth understanding of loneliness through qualitative insights and evaluating loneliness measures considering those lived experiences.

The overall goal of this paper is to enhance the understanding and measurement of loneliness by identifying key experiential characteristics of loneliness in children and adolescents, and determine whether there is a need for refined assessment tools that accurately capture that experience. In Study 1, we synthesized the qualitative research on the child and youth experience of loneliness and found shared characteristics of loneliness, with some differences related to developmental changes (e.g.

Identification of a TNIK-CDK9 axis as a targetable strategy for platinum-resistant ovarian cancer.

Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.

Mpox (monkeypox): a comprehensive updated of current epidemic evidence.

Mpox, formerly referred to as monkeypox, is a viral disease endemic to central Africa, resulting from the monkeypox virus (MPXV). This study provides a current overview of the Mpox epidemic as of 2024, emphasizing significant developments and epidemiological trends. The World Health Organization (WHO) initially designated a clade Ⅱb outbreak as a global health emergency in May 2022, which was subsequently managed through vaccination and public health interventions by May 2023.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

Advancements in liver retraction techniques for laparoscopic gastrectomy.

Traditionally, liver retraction for laparoscopic gastrectomy is done manual methods, such as the placement of retractors through the accessory ports and using a Nathanson retractor. However, these techniques often posed issues including extra abdominal incisions, risk of liver injury or ischaemia, and the potential for compromised visualization. Over the years, the development of innovative liver retraction techniques has significantly improved the safety and efficacy of laparoscopic gastrectomy and similar other hiatal procedures.

Unusual presentation of medication-induced atrial fibrillation: A case report.

This case highlights that atrial fibrillation can occur as an adverse effect of tamsulosin even in younger patients at lower doses, challenging the conventional understanding that this complication primarily affects older individuals on higher doses. Clinicians should remain vigilant for this potential side effect across all patient demographics to ensure prompt identification and management.

Management of Patients with Myocardial Injury After Noncardiac Surgery: A Retrospective Chart Review.

Background: Myocardial injury after noncardiac surgery (MINS) is associated with an increased incidence of cardiac morbidity and mortality. Little is known about how these patients are managed.

Methods: We performed a single-centre retrospective chart review of patients referred to a postoperative clinic with the diagnosis of MINS.

A Hybrid Rehabilitation Program for Adults with Peripheral Artery Disease (HY-PAD): A Pre-Post Intervention Study to Assess Its Feasibility.

Background: Supervised exercise programs improve walking impairment and quality of life (QoL) in patients with peripheral artery disease (PAD). However, such programs are underutilized, due to their limited accessibility. A feasible and effective exercise program is needed.

Pharmaco-Invasive Strategy Vs Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction in Latin America: A Meta-Analysis.

Background: Primary percutaneous coronary intervention (PCI) is the established treatment for ST-segment elevation myocardial infarction (STEMI), but often it is not readily available in low-resource settings. We assessed the safety and efficacy of the pharmaco-invasive strategy compared to primary PCI for STEMI in Latin America.

Methods: MEDLINE, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS) were searched for the period from their inception to September 2023, for studies that compared a pharmaco-invasive strategy vs primary PCI in Latin America.