Exome sequencing of UK birth cohorts.

Birth cohort studies involve repeated surveys of large numbers of individuals from birth and throughout their lives. They collect information useful for a wide range of life course research domains, and biological samples which can be used to derive data from an increasing collection of omic technologies. This rich source of longitudinal data, when combined with genomic data, offers the scientific community valuable insights ranging from population genetics to applications across the social sciences.

A Novel Model Using ML Techniques for Clinical Trial Design and Expedited Patient Onboarding Process.

Introduction: Clinical trials are critical for drug development and patient care; however, they often need more efficient trial design and patient enrolment processes. This research explores integrating machine learning (ML) techniques to address these challenges. Specifically, the study investigates ML models for two critical aspects: (1) streamlining clinical trial design parameters (like the site of drug action, type of Interventional/Observational model, etc) and (2) optimizing patient/volunteer enrolment for trials through efficient classification techniques.

Isolated Alkaline Phosphatase Elevation in Severe Osteoporosis Treatment: Implications of Teriparatide.

In severe osteoporosis, anabolic agents such as teriparatide (Forteo) are more commonly used. As a PTH analog, teripararide has a limited side effect profile with potential for mild hypercalcemia and dyspepsia. In this report we highlight another less common side effect, asymptomatic elevation in alkaline phosphatase.

Variation in the commissioning of specialist weight management services and bariatric surgery across England: Results of a freedom of information-based mapping exercise across the 42 integrated Care Systems of England.

Specialist weight management services including bariatric surgery are commissioned within regions of England called Integrated Care Systems (ICSs) with eligibility and treatment guidelines determined as part of the National Institute for Health and Care Excellence (NICE) guidance. Reported variation in commissioning and bariatric surgery eligibility criteria has not been previously mapped. Freedom of Information (FOI) requests provide a tool, supported by legislation, to ask questions of public authorities including ICSs such that they must respond accurately.

Impact of pedicle screw accuracy on clinical outcomes after 1- or 2-level minimally invasive transforaminal lumbar interbody fusion.

Objective: When creating minimally invasive spine fusion constructs, accurate pedicle screw fixation is essential for biomechanical strength and avoiding complications arising from delicate surrounding structures. As research continues to analyze how to improve accuracy, long-term patient outcomes based on screw accuracy remain understudied. The objective of this study was to analyze long-term patient outcomes based on screw accuracy.

Transforming Medicine: Cutting-Edge Applications of Nanoscale Materials in Drug Delivery.

Since their inception in the early 1960s, the development and use of nanoscale materials have progressed tremendously, and their roles in diverse fields ranging from human health to energy and electronics are undeniable. The application of nanotechnology inventions has revolutionized many aspects of everyday life including various medical applications and specifically drug delivery systems, maximizing the therapeutic efficacy of the contained drugs by means of bioavailability enhancement or minimization of adverse effects. In this review, we utilize the CAS Content Collection, a vast repository of scientific information extracted from journal and patent publications, to analyze trends in nanoscience research relevant to drug delivery in an effort to provide a comprehensive and detailed picture of the use of nanotechnology in this field.

Effectiveness and Safety of Vildagliptin Sustained Release in the Management of Type 2 Diabetes Mellitus: Real-World Evidence in Indian Patients [NOVELTY Study].

Background And Objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.

Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.

Early Versus Late Atrial Fibrillation Recurrence After Pulsed Field Ablation: Insights From the admIRE Trial.

Background And Aims: Studies have shown correlations between early recurrence (ER) and late recurrence (LR) of atrial arrhythmia after ablation with thermal technologies. This admIRE trial (NCT05293639) subanalysis aims to analyze ER versus LR in patients with paroxysmal atrial fibrillation (PAF) undergoing pulsed field ablation (PFA).

Methods: Patients with symptomatic paroxysmal atrial fibrillation and ≥1 transtelephonic monitoring transmission during the blanking period were included (n=169).

Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.

High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function.

Secure artificial intelligence at the edge.

Sensors for the perception of multimodal stimuli-ranging from the five senses humans possess and beyond-have reached an unprecedented level of sophistication and miniaturization, raising the prospect of making man-made large-scale complex systems that can rival nature a reality. Artificial intelligence (AI) at the edge aims to integrate such sensors with real-time cognitive abilities enabled by recent advances in AI. Such AI progress has only been achieved by using massive computing power which, however, would not be available in most distributed systems of interest.

micro-RNA 451-a as a Circulating Biomarker for Neuroblastoma.

Introduction: Micro ribonucleic acids (miRNAs) are small non-coding RNAs that modulate the expression of various genes. They have an important role in cancer pathogenesis. Differential expression of multiple miRNAs have been used as potential diagnostic and prognostic markers.

A Mobile App-Based Gratitude Intervention's Effect on Mental Well-Being in University Students: Randomized Controlled Trial.

Background: Gratitude interventions are used to cultivate a sense of gratitude for life and others. There have been mixed results of the efficacy of gratitude interventions' effect on psychological well-being with a variety of populations and methodologies.

Objectives: The objective of our study was to test the effectiveness of a gratitude intervention smartphone app on university students' psychological well-being.

Molecular dynamics-guided reaction discovery reveals endoperoxide-to-alkoxy radical isomerization as key branching point in α-pinene ozonolysis.

Secondary organic aerosols (SOAs) significantly impact Earth's climate and human health. Although the oxidation of volatile organic compounds (VOCs) has been recognized as the major contributor to the atmospheric SOA budget, the mechanisms by which this process produces SOA-forming highly oxygenated organic molecules (HOMs) remain unclear. A major challenge is navigating the complex chemical landscape of these transformations, which traditional hypothesis-driven methods fail to thoroughly investigate.

A multi-model study to inform the United States' 2035 NDC.

In 2025, countries are expected to submit a third round of nationally determined contributions (NDCs) that outline emission reduction goals for 2035. These new NDCs will be important for global alignment with the Paris Agreement's long-term goals. Setting an ambitious and plausible 2035 NDC in the United States (US) could be crucial in motivating high levels of ambition globally.

Absorption cross section of gas phase isoprene in the infrared-visible range.

We have recorded the gas phase spectrum of isoprene at room temperature from the mid-infrared range and into the visible range (600 cm to 17050 cm). Absorption spectra were obtained by Fourier transform infrared, conventional dispersion ultraviolet-visible-near-infrared and cavity ring-down spectroscopy to cover the entire range with a resolution comparable to that of the instruments on the James Webb Space Telescope. We have assigned the CH-stretching fundamental and overtone bands corresponding to the Δv=1-6 transitions based on anharmonic vibrational calculations using normal mode and local mode models, for the lower- and higher-energy regions, respectively.

Sensitivity of future regional and global energy markets and macroeconomic activity to a hypothetical global energy market disruption.

In this paper we contribute to a long history of research studying interactions between energy systems, international energy trade, and macroeconomic activity. We develop and employ methods to quantify transmission pathways for energy markets to affect the macroeconomy and CO emissions. We track the long-term consequences of a hypothetical permanent disruption to global energy markets, cession of Russian fossil fuel exports, for energy markets, regional and global economic activity (gross domestic product [GDP]), labor and capital markets, and CO emissions against two dramatically different reference scenarios.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

A nucleotide code governs Lis1's ability to relieve dynein autoinhibition.

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.

Prevalence of Trismus in Head and Neck Cancer Patients in Kerala, South India.

Introduction: Trismus is a common complication of head and neck cancer (HNC) treatment. Understanding its prevalence and its risk factors is vital for enhancing clinical outcomes and the overall quality of life of these patients.

Objective: The study aimed to assess the prevalence and the factors associated with trismus among HNC patients.