Barrel expansion of outer membrane protein G nanopore through β-hairpin duplication.

Outer membrane β-barrel proteins (OMPs) are channels found in the outer membranes of Gram-negative bacteria characterized by a stable and diverse barrel architecture, which has made them attractive for nanopore sensing applications. Here, we systematically investigated the feasibility of expanding outer membrane protein G (OmpG) from its native 14-stranded β-barrel to an enhanced conductance variant by independently duplicating each of its seven hairpin units and inserting them downstream of their endogenous positions. Most combinations did not increase pore diameter, but duplication of the terminal seventh hairpin exhibited a rare population of pores with enhanced conductance, suggesting barrel enlargement.

Hypercubes to identify geomarkers of rapid cystic fibrosis lung disease progression.

Background: Prior research has shown that place-based environmental exposures and community characteristics, known as geomarkers, are associated with accelerated lung function decline and increased mortality in individuals with cystic fibrosis (CF). Although geomarkers have been linked to pulmonary outcomes in other respiratory diseases, it is unknown which have the greatest predictive power for rapid lung function decline in CF.

Methods: We adapted an existing statistical procedure, which arranges candidate variables in a k-dimensional hypercube, where the hypercube forms a set of variables for a multi-stage selection process involving complex longitudinal data.

Can contaminated musculoskeletal autografts and allografts Be safely and effectively used in Patients? A systematic review.

Background: Musculoskeletal autografts and allografts are used frequently in orthopaedics, and contamination of the grafts can occur. When intraoperative contamination is recognized, the graft can be salvaged for use and postoperative complications minimized with effective decontamination. The purpose of this systematic review was to critically evaluate safety and efficacy of decontamination protocols for tendon, meniscus, and osteochondral grafts in order to provide evidence-based guidelines for graft salvage.

Advancing Real-World Evidence Through a Federated Health Data Network (EHDEN): Descriptive Study.

Background: Real-world data (RWD) are increasingly used in health research and regulatory decision-making to assess the effectiveness, safety, and value of interventions in routine care. However, the heterogeneity of European health care systems, data capture methods, coding standards, and governance structures poses challenges for generating robust and reproducible real-world evidence. The European Health Data & Evidence Network (EHDEN) was established to address these challenges by building a large-scale federated data infrastructure that harmonizes RWD across Europe.

Assessing Covariate Balance With Small Sample Sizes.

Propensity score adjustment addresses confounding by balancing covariates in subject treatment groups through matching, stratification, or weighting. Diagnostics test the success of adjustment. For example, if the standardized mean difference (SMD) for a relevant covariate exceeds a threshold like 0.

CLEAR: A vision to support clinical evidence lifecycle with continuous learning.

Human knowledge of diseases, treatments, and prevention techniques is constantly evolving. The generation of clinical evidence using randomized controlled trials on human subjects occurs notably slowly and inefficiently. The Learning Health System (LHS) has been proposed to facilitate the continuous improvement of individual and population health through a cycle of knowledge, practice, and data.

Evaluation of the impact of defining observable time in real-world data on outcome incidence.

Objective: In real-world data (RWD), defining the observation period-the time during which a patient is considered observable-is critical for estimating incidence rates (IRs) and other outcomes. Yet, in the absence of explicit enrollment information, this period must often be inferred, introducing potential bias.

Materials And Methods: This study evaluates methods for defining observation periods and their impact on IR estimates across multiple database types.

Flipping a simulation before instruction can improve students' learning, interest and perceived competence.

Background: Using simulations in science instruction can help make abstract topics more concrete and boost students' understanding.

Aims: The current research examined whether using a simulation as an exploratory learning activity before an accompanying lecture has additional learning and motivational benefits compared to a more common lecture-then-simulation approach.

Samples: Participants (Experiment 1, N = 168; Experiment 2, N = 357) were undergraduate students in several sections of a first-year chemistry course.

Residing in a low-income-low-food-access neighbourhood and asthma in early and middle childhood in the Environmental influences on Child Health Outcomes (ECHO) program: a multisite cohort study.

Importance: Access to healthy and affordable foods may play a role in reducing inflammation and in healthy pulmonary immune system development.

Objective: To investigate the association between residing in a low-income and low-food-access (LILA) neighbourhood and risk of childhood asthma. A positive association was hypothesised.

Disparities in the association of ambient air pollution with childhood asthma incidence in the ECHO consortium: A US-wide multi-cohort study.

Background: Characterization of US sociodemographic disparities in air pollution respiratory effects has often been limited by lack of participant diversity, geography, exposure characterization, and small sample size.

Methods: We included 34 sites comprising 23,234 children (born 1981-2021) from the Environmental influences on Child Health Outcomes (ECHO) Program with data on asthma diagnosis until age 10 (182,008 person-years). Predicted annual exposure to fine particulate matter (1988-2021), nitrogen dioxide (2000-2016), and ground ozone (2000-2016) were assigned based on residential histories.

Outdoor air pollution and psychiatric symptoms in adolescents: a study of peripheral inflammatory marker associations.

Introduction: Fine particulate matter (PM) air pollution is associated with increased internalizing symptoms (e.g. depressive and anxiety symptoms), particularly during adolescence-a critical period for the emergence of anxiety disorders and vulnerability to neurotoxicants.

Large-scale Empirical Identification of Candidate Comparators for Pharmacoepidemiological Studies.

Background And Objective: The new user cohort design has emerged as a best practice for the estimation of drug effects from observational data. However, despite its advantages, this design requires the selection and evaluation of comparators for appropriateness, a process that can be challenging. The objective of this work was to introduce an empirical approach to rank candidate comparators in terms of their similarity to a target drug in high-dimensional covariate space.

Prenatal ambient air pollution associations with DNA methylation in asthma- and allergy-relevant genes: findings from ECHO.

Prenatal exposure to air pollution is an important risk factor for child health outcomes, including asthma. Identification of DNA methylation changes associated with air pollutant exposure can provide new intervention targets to improve children's health. The aim of this study is to test the association between prenatal air pollutant exposure and DNA methylation in developmental and asthma-/allergy-relevant biospecimens (placenta, buccal, cord blood, nasal mucosa, and lavage).

Variation in Phenotype Definitions in Observational Clinical Research: A Review of Three Conditions.

Our study examined the heterogeneity of phenotype algorithms (PA) in literature on Alzheimer's disease (AD), major depressive disorder (MDD), and pulmonary arterial hypertension (PAI), focusing on the impact of PA differences on patient overlap and incidence rate variability across conditions in six observational databases. We reviewed 49 replicated PAs (13 for AD, 23 for MDD, and 13 for PAI) and found significant heterogeneity. These varied PAs identified distinct patient cohorts, resulting in significant incidence rate heterogeneity.

Comparative Safety of Second-Line Antihyperglycemic Agents in Older Adults with Type 2 Diabetes: A Multinational Real-World Evidence From LEGEND-T2DM.

Background: As prescribing of newer antihyperglycemic agents expands, there remains limited comparative safety data for older adults-a population particularly vulnerable to adverse drug events and underrepresented in clinical trials. We aimed to evaluate the real-world safety of second-line antihyperglycemic agents among older adults with type 2 diabetes.

Methods: We conducted a multinational cohort study using nine harmonized electronic health record and claims databases from the U.

senescence and senolytic functional assays.

A detailed understanding of aging biology and the development of anti-aging therapeutic strategies remain imperative yet inherently challenging due to the protracted nature of aging. Cellular senescence arises naturally through replicative exhaustion and is accelerated by clinical treatments or environmental stressors. The accumulation of senescent cells-defined by a loss of mitogenic potential, resistance to apoptosis, and acquisition of a pro-inflammatory secretory phenotype-has been implicated as a key driver of chronic disease, tissue degeneration, and organismal aging.

Can we develop real-world prognostic models using observational healthcare data? Large-scale experiment to investigate model sensitivity to database and phenotypes.

Background: Large observational healthcare databases are frequently used to develop models to be implemented in real-world clinical practice populations. For example, these databases were used to develop COVID severity models that guided interventions such as who to prioritize vaccinating during the pandemic. However, the clinical setting and observational databases often differ in the types of patients (case mix), and it is a nontrivial process to identify patients with medical conditions (phenotyping) in these databases.

Integrating geospatial data with birth cohorts to explore social determinants of health and asthma.

Place-based measures of environmental exposures, climate, neighborhood characteristics, housing, and other social determinants of health are powerful predictors of health outcomes, including asthma. In addition, social determinants of health are likely causes of the persistent racial and ethnic disparities in asthma prevalence and morbidity. The objectives of this commentary are to (1) provide an overview of geospatial data and resources available to researchers to incorporate into studies of asthma-related outcomes, (2) provide a general approach to consider geospatial data in birth cohorts, (3) demonstrate the use of geospatial data in asthma-related research, and (4) highlight challenges and future opportunities for the use of geospatial data in asthma-related research and birth cohort studies.

Origami with small molecules: exploiting the C-F bond as a conformational tool.

When present within an organic molecule, the C-F bond tends to align in predictable ways with neighbouring functional groups, due to stereoelectronic effects such as hyperconjugation and electrostatic attraction/repulsion. These fluorine-derived conformational effects have been exploited to control the shapes, and thereby enhance the properties, of a wide variety of functional molecules including pharmaceutical agents, liquid crystals, fragrance chemicals, organocatalysts, and peptides. This comprehensive review summarises developments in this field during the period 2010-2024.

Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life.

Background: Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development.

Objective: We sought to determine how early-life wheeze trajectories impact later life asthma gene expression.

Methods: The Children's Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing.

A rapid cycle analytics framework for vaccine safety surveillance within a real-world data network: Experience with enhanced surveillance of the Janssen COVID-19 vaccine.

Objective: To complement and support routine pharmacovigilance, Janssen conducted rapid real-world data analyses for near real-time safety monitoring of the Janssen COVID-19 vaccine and to contextualize potential safety signals.

Methods: Analyses were performed in four U.S.

AI-Assisted Label-Free Monitoring Bone Mineral Metabolism on Demineralized Bone Paper.

Effective drug development for bone-related diseases, such as osteoporosis and metastasis, is hindered by the lack of physiologically relevant in vitro models. Traditional platforms, including standard tissue culture plastic, fail to replicate the structural and functional complexity of the natural bone extracellular matrix. Recently, osteoid-mimicking demineralized bone paper (DBP), which preserves the intrinsic collagen structure of mature bone and exhibits semitransparency, has demonstrated the ability to reproduce in-vivo-relevant osteogenic processes and mineral metabolism.

Editorial Commentary: Upper-Extremity Limb Asymmetry May Complicate Objective Evaluation of Criteria on the Basis of Return to Sport Evaluation After Arthroscopic Bankart Repair.

Although there are many reported postoperative rehabilitation protocols after arthroscopic Bankart repair, significant variability exists within each protocol, leaving a lack of consensus or standardized evaluation of return to play. As such, criteria-based return to sport protocols have been established in an attempt to normalize the rehabilitation while reducing the recurrence rate after this procedure. This type of protocol has been published with promising results, but validation of the protocol has been difficult.

Effects of dietary supplementation of creatine on fetal development in gilts at d 60 and d 90 of gestation.

Background: The creatine-creatine kinase-phosphocreatine (Cr-CK-PCr) system maintains intracellular ratios of ATP/ADP for support of cellular functions and has been characterized at the placental-uterine interface of rodents, primates, swine and sheep, and thus may support fetal development. This study determined effects of dietary supplementation of creatine (Cr) to gestating gilts on fetal development, the number and ratio of primary and secondary muscle fibers, and on protein expression in endometrium and fetal biceps-femoris muscle, respectively in fetal pigs on d 60 and d 90 of gestation.

Methods: Reproductively mature gilts were synchronized to estrus using Matrix, observed for estrus (d 0), and artificially inseminated 12 h and 36 h later.