Cytoplasmic Regulation of the Poly(A) Tail Length as a Potential Therapeutic Target.

Virtually all mRNAs acquire a poly(A) tail co-transcriptionally, but its length is dynamically regulated in the cytoplasm in a transcript-specific manner. The length of the poly(A) tail plays a crucial role in determining mRNA translation, stability, and localization. This dynamic regulation of poly(A) tail length is widely used to create post-transcriptional gene expression programs, allowing for precise temporal and spatial control.

Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma.

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

The main sources of molecular organization in the cell. Atlas of self-organized and self-regulated dynamic biostructures.

One of the most important goals of contemporary biology is to understand the principles of the molecular order underlying the complex dynamic architecture of cells. Here, we present an overview of the main driving forces involved in the cellular molecular complexity and in the emergent functional dynamic structures, spanning from the most basic molecular organization levels to the complex emergent integrative systemic behaviors. First, we address the molecular information processing which is essential in many complex fundamental mechanisms such as the epigenetic memory, alternative splicing, regulation of transcriptional system, and the adequate self-regulatory adaptation to the extracellular environment.

Acetamiprid retention in agricultural acid soils: Experimental data and prediction.

The overuse of pesticides in agriculture has led to widespread pollution of soils and water resources, becoming a problem of great concern. Nowadays, special attention is given to neonicotinoids, particularly acetamiprid, the only neonicotinoid insecticide allowed for outdoor use in the European Union. Once acetamiprid reaches the soil, adsorption/desorption is the main process determining its bioavailability and environmental fate.

Albendazole-ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial.

Background: Treatments for soil-transmitted helminthiases face challenges, especially in addressing Trichuris trichiura. Combination regimens, particularly of ivermectin and albendazole, are promising. We aimed to assess the safety, efficacy, and palatability of a combination tablet for the treatment of T trichiura, hookworm, and Strongyloides stercoralis infections among school-aged children in Ethiopia, Kenya, and Mozambique.

Assessment of pandemic-related pregnancy stress from seven western countries using Rasch analyses.

Introduction: This study examined psychometric properties of the Pandemic-Related Pregnancy Stress Scale (PREPS) using a Rasch Model (RM) in a large sample of pregnant women from Germany, Israel, Italy, Poland, Spain, Switzerland and the United States of America (USA).

Material And Methods: Rasch analyses were used to analyze a sample of 7185 pregnant women who completed the PREPS during the COVID-19 pandemic onset from April to August 2020. Psychological, sociodemographic, and obstetric factors were also collected and analyzed.

Wild bees show local spatial and temporal dynamics in southeastern US blueberry farmscapes.

Wild bee communities are the target of various conservation and ecological restoration programs. Strategic conservation can influence bee communities visiting fields and help mitigate pollinator limitations in fruit production. However, planning compatible conservation strategies and gauging their effectiveness requires understanding how local communities vary across space and time in crops and adjacent semi-natural areas.

Clinical and Structural Parameters in Autosomal Dominant Optic Atrophy Patients: A Cross-Sectional Study Using Optical Coherence Tomography.

Background: Autosomal Dominant Optic Atrophy (ADOA) is a hereditary optic neuropathy characterized by retinal ganglion cell degeneration and optic nerve fiber loss. This study examined the correlation between clinical and structural parameters in patients with ADOA using optical coherence tomography (OCT) and explored potential clinical biomarkers.

Methods: A cross-sectional, case-control observational study included 27 patients with ADOA and 27 age- and sex-matched healthy controls.

Supervised Exercise for Patients With Metastatic Breast Cancer: A Cost-Utility Analysis Alongside the PREFERABLE-EFFECT Randomized Controlled Trial.

Purpose: To evaluate the cost utility of a 9-month supervised exercise program for patients with metastatic breast cancer (mBC), compared with control (usual care, supplemented with general activity advice and an activity tracker). Evidence on the cost-effectiveness of exercise for patients with mBC is essential for implementation in clinical practice and is currently lacking.

Methods: A cost-utility analysis was performed alongside the multinational PREFERABLE-EFFECT randomized controlled trial, conducted in 8 centers across Europe and Australia.

The model of fear of movement/(re)injury runs clockwise from catastrophizing: evidence from a sample of outpatients with chronic non-specific low back pain.

Objective: To provide evidence that catastrophizing is the primer of the cognitive-behavioural model of fear of movement/(re)injury (FAM).

Design: A cross-sectional analysis of 180 outpatients with chronic non-specific low back pain who completed the Pain Catastrophizing Scale (PCS), the Tampa Scale of Kinesiophobia (TSK), the Roland-Morris Disability Questionnaire (RMDQ), the Hospital Anxiety and Depression Scale - Depression (HADS-D), and a pain intensity numerical rating scale (NRS). The intercorrelations of the outcome measures were estimated using Pearson's correlation coefficient (r), and regression analyses were used to examine their predictive values by following the left side of the FAM clockwise from the PCS (p = 0.

Covalent Template-Directed Synthesis: A Powerful Tool for the Construction of Complex Molecules.

Template-directed synthesis has become a powerful methodology to access complex molecules. Noncovalent templating has been widely used in the last few decades, but less attention has been paid to covalent template-directed synthesis, despite the fact that this methodology was used for the first reported synthesis of a catenane. This review highlights the evolution of covalent templating over the last 60 years, thereby providing a toolbox for the design of efficient covalent templating processes.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Benchmarking residue-resolution protein coarse-grained models for simulations of biomolecular condensates.

Intracellular liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components and perform essential biological functions. Molecular simulations play a crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In this study, we systematically compare six state-of-the-art sequence-dependent residue-resolution models to evaluate their performance in reproducing the phase behaviour and material properties of condensates formed by seven variants of the low-complexity domain (LCD) of the hnRNPA1 protein (A1-LCD)-a protein implicated in the pathological liquid-to-solid transition of stress granules.

Ambivalent partnership of the Drosophila posterior class Hox protein Abdominal-B with Extradenticle and Homothorax.

Hox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through interactions with Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) proteins. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action.

Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.

Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.

Sex Differences in Aortic Valve Inflammation and Remodeling in Chronic Severe Aortic Regurgitation.

Aortic regurgitation (AR) is more prevalent in male, although cellular and molecular mechanisms underlying the sex differences in prevalence and pathophysiology are unknown. This study evaluates the impact of sex on aortic valve (AV) inflammation and remodeling as well as the cellular differences in valvular interstitial cells (VICs) and valvular endothelial cells (VECs) in patients with AR. A total of 144 patients (27.

Improved Description of Environment and Vibronic Effects with Electrostatically Embedded ML Potentials.

Incorporation of environment and vibronic effects in simulations of optical spectra and excited state dynamics is commonly done by combining molecular dynamics with excited state calculations, which allows to estimate the spectral density describing the frequency-dependent system-bath coupling strength. The need for efficient sampling, however, usually leads to the adoption of classical force fields despite well-known inaccuracies due to the mismatch with the excited state method. Here, we present a multiscale strategy that overcomes this limitation by combining EMLE simulations based on electrostatically embedded ML potentials with the QM/MMPol polarizable embedding model to compute the excited states and spectral density of 3-methyl-indole, the chromophoric moiety of tryptophan that mediates a variety of important biological functions, in the gas phase, in water solution, and in the human serum albumin protein.

Effectiveness of oral platelet lysate gel to treat oral mucosal manifestations associated with chronic graft versus host disease.

Background: Chronic graft-vs-host disease (cGvHD) is a severe immune-mediated complication that affects patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Oral manifestations of cGvHD, such as ulcers and mucosal inflammation, significantly impair quality of life and often require long-term treatment. Existing therapies provide limited relief, prompting the exploration of new approaches, including the use of autologous platelet lysate (PL) gel for its regenerative properties.

An Infrequent Guest in Orthopedic Infections.

is a species of anaerobic gram-positive coccus considered part of human microbiota. It has been described as a cause of skin and soft tissue infections, but it is not a common cause of operation-related infections. Describe the characteristics, treatment, and results of musculoskeletal infection by treated in our center.

Genome-Wide Association Study and Genomic Predictions for Hydroxycinnamate Concentrations in Maize Stover.

Hydroxycinnamates, like ferulate (FA) and -coumarate (CA), are important components of maize cell walls, which influence pest resistance, ruminal digestibility, and biofuel production. Increasing their concentration has been linked to increased pest resistance, but also may lead to a decrease in nutritional value or bioethanol production efficiency. Therefore, improving forage quality or biofuel production without compromising plant resistance and a thorough understanding of the biosynthesis and deposition of these compounds is necessary, especially in stover, which is the feedstock for second-generation biofuel production and determines animal forage quality.

Identification of Antigens Recognized by Murine Intestinal IgAs by a Gel-Independent Immunoproteomic Approach.

As part of the intestinal microbiota, can elicit a humoral response in the gastrointestinal tract (GIT) that is mainly directed toward hyphal antigens. This response has been implicated in controlling the invasive form of the fungus and maintaining the yeast as an innocuous commensal. However, the specific targets of this response are still unknown.

Acute Pancreatitis: An Update of Evidence-Based Management and Recent Trends in Treatment Strategies.

Acute pancreatitis is a common gastrointestinal disease leading to hospitalisation. Recent advancements in its management have primarily focussed on the development of early phase medical interventions targeting inflammatory pathways, optimisation of supportive treatment (including fluid resuscitation, pain management and nutritional management), appropriate use of antibiotics, implementation of minimally invasive interventions for infected necrosis, and the necessity of follow-up for long-term complications. These advancements have significantly improved personalised management and overall outcomes of acute pancreatitis.