SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine.

Background: Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.

Objectives: To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation.

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

Discovering patient groups in sequential electronic healthcare data using unsupervised representation learning.

Introduction: Unsupervised feature learning methods inspired by natural language processing (NLP) models are capable of constructing patient-specific features from longitudinal Electronic Health Records (EHR).

Design: We applied document embedding algorithms to real-world paediatric intensive care (PICU) EHR data to extract patient-specific features from 1853 patients' PICU journeys using 647 unique lab tests and medication events. We evaluated the clinical utility of the patient features via a K-means clustering analysis.

Screening a 681-membered yeast collection for the secretion of proteins with antifungal activity.

Fungal pathogens pose a threat to human health and food security. Few antifungals are available and resistance to all has been reported. Novel strategies to control plant and human pathogens as well as food spoilers are urgently required.

The Global Prevalence of Reported Penicillin Allergy: A Systematic Review and Meta-Analysis.

Objectives: Patients labelled with penicillin allergy (PenA) often receive broader spectrum antibiotics, associated with antimicrobial resistance and poorer outcomes. However, ~95% of patients are likely mis-labelled. Whilst de-labelling programmes are gaining momentum, they have been restricted to a few countries.

Unveiling the trends: Growing cancer and venous thromboembolism mortality in older adults in the United States, 1999-2020.

Background: While cancer mortality rates in the United States (U.S.) have decreased due to advances in chemotherapy, older adults with cancer face an elevated risk of venous thromboembolism (VTE).

Accurate and efficient representation of intramolecular energy in ab initio generation of crystal structures. Part III: partitioning into torsional groups.

We present an approach to reduce this computational cost substantially, based on the partitioning of the molecule into geometrically separated torsional groups, with the dependence of the intramolecular energy and atomic point charges and dependent degrees of freedom on molecular conformation being computed as a linear combination of the contributions of these groups. This can lead to large savings in computational cost without a significant impact on accuracy, as demonstrated in the cases of N-acetyl-para-aminophenol (paracetamol) and methyl 4-hydroxybenzoate (methyl paraben). The approach is also applied successfully to two larger molecules, benzyl [4-(4-methyl-5-[(4-methylphenyl)sulfonyl]-1,3-thiazol-2-yl)phenyl]carbamate (molecule XX from the fifth CSP blind test) and (2S)-2-[4-(3-fluorobenzyloxy)benzylamino]propionamide (safinamide), for which we conduct the first reported CSP study.

Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Background: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.

Methods: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators.

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.

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.

Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier.

Unlabelled: Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings.

Cardiac organ chip: advances in construction and application.

Cardiovascular diseases are a leading cause of death worldwide, and effective treatment for cardiac disease has been a research focal point. Although the development of new drugs and strategies has never ceased, the existing drug development process relies primarily on rodent models such as mice, which have significant shortcomings in predicting human responses. Therefore, human-based in vitro cardiac tissue models are considered to simulate physiological and functional characteristics more effectively, advancing disease treatment and drug development.

Utilizing a Wireless Radar Framework in Combination With Deep Learning Approaches to Evaluate Obstructive Sleep Apnea Severity in Home-Setting Environments.

Objective: Common examinations for diagnosing obstructive sleep apnea (OSA) are polysomnography (PSG) and home sleep apnea testing (HSAT). However, both PSG and HSAT require that sensors be attached to a subject, which may disturb their sleep and affect the results. Hence, in this study, we aimed to verify a wireless radar framework combined with deep learning techniques to screen for the risk of OSA in home-based environments.

Addressing the overuse of hospital emergency departments in the Portuguese NHS: a new paradigm.

The escalating trend of inappropriate visits to Emergency Departments (ED) has led to significant concerns, including resource misallocation, compromised patient care, and an increased burden on healthcare workers. Portugal faces a notable challenge, reporting one of the highest ED visit rates, with an annual average of approximately 6 million ED visits from 2013 to 2023. In response, the "Call First, Save Lives" pilot project was launched by the Portuguese NHS Executive Board, in 2023, at the Local Health Unit (LHU) of Póvoa de Varzim/Vila do Conde.

Long-term colorectal cancer incidence in a post-endoscopic screening cohort, accounting for surveillance, by baseline polyp group, anatomic subsite, and sex.

Objectives: Colonoscopy surveillance is often performed in post-polypectomy cohorts, likely altering colorectal cancer (CRC) outcomes, but this is often not addressed in CRC incidence analyses. We examined CRC incidence post-endoscopic screening, accounting for surveillance.

Methods: We examined UK Flexible Sigmoidoscopy Screening Trial participants who had no, low-risk, or high-risk (≥10 mm, ≥3 adenomas, adenomas with villous features/high-grade dysplasia) distal polyps at screening.

Survival of Patients with Solid Tumours and Sepsis Admitted to Intensive Care in a Tertiary Oncology Centre: A Retrospective Analysis.

Introduction: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Patients with cancer are at risk of developing sepsis and requiring intensive care unit (ICU) admission. We aimed to assess survival of patients with a solid tumour admitted to ICU as an emergency with sepsis, and to identify predictors of 90-day survival at admission.

Synthesis and Polymerization of Thiophene-Bearing 2-Oxazolines and 2-Oxazines.

Intrinsically conductive polymers have garnered a great deal of attention for use in medical and bioelectronic applications. Despite this, challenges associated with the mechanical stability, processability, and fabrication of conducting polymers have limited their utility. To circumvent these limitations, thiophene substituted 2-oxazolines (2Ox) and 2-oxazines (2Ozi) are introduced, which can be polymerized to form a thermally stable and potentially melt-processable polymers as precursors for conductive polymers.

Characteristics of TSPO expression in marmoset EAE.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target.

New job, new habits? A multilevel interrupted time series analysis of changes in diet, physical activity and sleep among young adults starting work for the first time.

Background: The workplace is an important determinant of health that people are exposed to for the first-time during adolescence or early adulthood. This study investigates how diet, physical activity, and sleep change as people aged 16-30 years transition into work and whether this varies for different individuals and job types.

Methods: Multilevel linear regression models assessed changes in fruit and vegetable intake, sleep duration, and physical activity among 3,302 UK Household Longitudinal Study (UKHLS) participants aged 16-30 years, who started work for the first time between 2015 and 2023.

The multi-omics signatures of telomere length in childhood.

Background: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length.

Falls and balance impairment; what and how has this been measured in adults with joint hypermobility? A scoping review.

Background: People with joint hypermobility have excessive joint flexibility, which is more common in young women. The people with symptomatic hypermobility report poor balance and even falls. This scoping review aims to identify and map the available evidence related to balance and falling in adults with joint hypermobility to support research planning and ideas for treatment direction.