Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Readiness assessment for cervical cancer elimination and prevention of human papillomavirus (HPV)-related cancers in Europe - are we winning the RACE?

Introduction: To address the cervical cancer burden globally, the World Health Organization and European Union released strategies to facilitate HPV-related cancers prevention, including cervical cancer elimination. This research assessed European country level readiness to achieve cervical cancer elimination by adhering to such strategies.

Areas Covered: Readiness for cervical cancer elimination was assessed across a range of guiding questions relevant to three defined key domains: vaccination, screening, and treatment, each with two sub-domains focusing on decision making and implementation efforts.

Assessment of Prenatal Transportation Stress and Sex on Gene Expression Within the Amygdala of Brahman Calves.

As the amygdala is associated with fear and anxiety, it is important to determine the potential effects of gestational stressors on behavior and stress responses in offspring. The objective of this study was to investigate the effects of prenatal transportation stress on amygdala gene expression in 25-day-old Brahman calves, focusing on sex-specific differences. Amygdala tissue samples from prenatally stressed (PNS) and control bull and heifer calves were analyzed using RNA sequencing.

The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes.

Aim: A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone.

Materials And Methods: Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time-to-event analysis.

Exploring code portability solutions for HEP with a particle tracking test code.

Traditionally, high energy physics (HEP) experiments have relied on x86 CPUs for the majority of their significant computing needs. As the field looks ahead to the next generation of experiments such as DUNE and the High-Luminosity LHC, the computing demands are expected to increase dramatically. To cope with this increase, it will be necessary to take advantage of all available computing resources, including GPUs from different vendors.

The role of silicon in drug discovery: a review.

This review aims to highlight the role of silicon in drug discovery. Silicon and carbon are often regarded as being similar with silicon located directly beneath carbon in the same group in the periodic table. That being noted, in many instances a clear dichotomy also exists between silicon and carbon, and these differences often lead to vastly different physiochemical and biological properties.

Regional changes of maximum dose insecticide responses in diamondback moth (Lepidoptera: Plutellidae) populations from Georgia and Florida, USA.

Maximum dose bioassays were conducted to assess the efficacy of multiple registered active ingredients for diamondback moth (DBM), Plutella xylostella (L.), control in Georgia and Florida from 2021 to 2023 as a follow-up to an earlier study. Low efficacy (<40% mortality) was recorded for the highest labeled rate of Bacillus thuringiensis var.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study.

Introduction: Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes.

Pet Owners' Preferences for Quality of Life Improvements and Costs Related to Innovative Therapies in Feline Pain Associated with Osteoarthritis-A Quantitative Survey.

This research aimed to explore UK cat owners' preferences for treatments for feline osteoarthritis (OA) by exploring preferences around quality of life (QoL) improvements, safety considerations, and costs associated with hypothetical innovative pain therapies. Aspects identified in an existing conceptual framework were extracted for inclusion in exploratory interviews with cat owners ( = 3) to identify key domains that contribute to the QoL of cats. QoL descriptions for cats with OA and hypothetical product attributes were developed and validated through interviews with veterinarians ( = 3).

Exciton diffusion in organic semiconductors: precision and pitfalls.

Nanometer exciton diffusion is a fundamental process important in virtually all applications of organic semiconductors. Many measurement techniques have been developed to measure exciton diffusion length () at the nanometer scale; however, these techniques have common challenges that the community has worked for decades to overcome. In this perspective, we lay out the principal challenges researchers need to overcome to obtain an accurate measurement of .

Profiling Dynamic Patterns of Single-Cell Motility.

Cell motility plays an essential role in many biological processes as cells move and interact within their local microenvironments. Current methods for quantifying cell motility typically involve tracking individual cells over time, but the results are often presented as averaged values across cell populations. While informative, these ensemble approaches have limitations in assessing cellular heterogeneity and identifying generalizable patterns of single-cell behaviors, at baseline and in response to perturbations.

Herbal extract dietary supplementation effect on growth performance and meat quality in broiler raised under two stocking densities.

The number of birds or their total live weight in relation to a given area is known as stocking density; higher stocking densities will cause more stress to the birds, which may have an impact on their physiological state, productivity, carcass quality, growth performance, immunity, metabolism, and meat quality. The present study aimed to investigate the potential impact of 2 different stocking densities on growth performance, carcass characteristics, meat quality, serum, and expression of Insulin like growth factor-1 (IGF-1), muscle regulatory genes expression and serum biochemical indicators of broilers supplemented with essential oils (EO). In total, 784-day-old chicks of Ross 308 were randomly assigned into 4 different groups with 7 replicates for each: Normal feed (no essential oils [EO] added) and normal stocking as 9 bird/m, (NSD).

The synergistic impact of type 2 diabetes and MASLD on cardiovascular, liver, diabetes-related and cancer outcomes.

Background And Aims: We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.

Methods: Using TriNetX, a global federated research network (n = 114 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared MASLD with T2D to MASLD alone; analysis 2 compared T2D with MASLD to T2D alone.

IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy that exploits transcriptional networks driven by IRF4. We employ a multi-omics approach to discover IRF4 vulnerabilities, integrating functional genomics screening, spatial proteomics, and global chromatin mapping. ARID1A, a member of the SWI/SNF chromatin remodeling complex, is required for IRF4 expression and functionally associates with IRF4 protein on chromatin.

Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.

Aim: To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis.

Methods: A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort.

Targeting aberrant fatty acid synthesis and storage in endocrine resistant breast cancer cells.

Background: Lipid metabolic reprogramming is an emerging characteristic of endocrine therapy (ET) resistance in estrogen receptor-positive (ER+) breast cancer. We explored changes in lipid metabolism in ER+ breast cancer cell lines following acquired resistance to common endocrine treatments and tested efficacy of an inhibitor in current clinical trials.

Methods: We derived ER+ breast cancer cell lines resistant to Tamoxifen (TamR), Fulvestrant (FulvR), and long-term estrogen withdrawal (EWD).