Human RNA Polymerase II Segregates from Genes and Nascent RNA and Transcribes in the Presence of DNA-Bound dCas9.

RNA polymerase II (Pol II) dysfunction is frequently implied in human disease. Understanding its functional mechanism is essential for designing innovative therapeutic strategies. To visualize its supra-molecular interactions with genes and nascent RNA, we generated a human cell line carrying ~335 consecutive copies of a recombinant β-globin gene.

Next-generation chemotherapy treatments based on black hole algorithms: From cancer remission to chronic disease management.

Problem: Therapeutic planning strategies have been developed to enhance the effectiveness of cancer drugs. Nevertheless, their performance is highly limited by the inefficient biological representativeness of predictive tumor growth models, which hinders their translation to clinical practice.

Objective: This study proposes a disruptive approach to oncology based on nature-inspired control using realistic Black Hole physical laws, in which tumor masses are trapped to experience attraction dynamics on their path to complete remission or to become a chronic disease.

Potentially inappropriate anticholinergic drug use among older adults in primary healthcare: prevalence and determinants.

Background: Considering the vulnerability of older adults to adverse drug reactions, medications with strong anticholinergic properties are considered potentially inappropriate for this population. This study aims to characterize older adults' profile of anticholinergics use and to identify the factors associated with their potentially inappropriate use.

Research Design And Methods: A retrospective study was conducted on 1200 older adults in primary health care centers of Portugal between April 2021 and August 2022.

Oncogenic and telomeric G-quadruplexes: Targets for porphyrin-triphenylphosphonium conjugates.

DNA chains with sequential guanine (G) repeats can lead to the formation of G-quadruplexes (G4), which are found in functional DNA and RNA regions like telomeres and oncogene promoters. The development of molecules with adequate structural features to selectively stabilize G4 structures can counteract cell immortality, highly described for cancer cells, and also downregulate transcription events underlying cell apoptosis and/or senescence processes. We describe here, the efficiency of four highly charged porphyrins-phosphonium conjugates to act as G4 stabilizing agents.

Development of a core outcome set for physiotherapy trials in adults with bronchiectasis (the COS-PHyBE study): A Delphi study and consensus meeting.

Background: Physiotherapy is recommended for bronchiectasis management, but there is disparity in evidence supporting its use. This is partly because of inconsistency and poor reporting of outcomes in available studies. A Core Outcome Set (COS) may improve trial consistency and decrease reporting bias.

Case report: Anti-ARHGAP26 autoantibodies in atypical dementia with Lewy bodies.

Background: Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia. Here, we report a case of dementia associated with anti-Rho-GTPase-activating protein 26 (ARHGAP26) autoantibodies, which have never been previously linked to DLB.

Methods: We describe the case of a 78-year-old man who underwent cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), F-fluorodesoxyglucose positron emission tomography (FDG-PET), and a detailed neuropsychological evaluation.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.

Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers.

Pressure ulcers/injuries prevention in emergency services: A scoping review.

Aim Of The Study: To map the available evidence on nursing care provided to prevent the development of pressure ulcers/injuries in emergency services.

Material And Methods: Scoping review that follows the Preferred Reporting Items for Systematic reviews and the Meta-Analyses extensions for Scoping Reviews and the Joanna Briggs Institute guidelines. The inclusion criteria were based on the PCC mnemonic.

Exploring the Real-Time Variability and Complexity of Sitting Patterns in Office Workers with Non-Specific Chronic Spinal Pain and Pain-Free Individuals.

Chronic spinal pain (CSP) is a prevalent condition, and prolonged sitting at work can contribute to it. Ergonomic factors like this can cause changes in motor variability. Variability analysis is a useful method to measure changes in motor performance over time.

Exploring the fate of phlorotannins from Laminaria digitata across the gastrointestinal tract: Insights into susceptibility and bioactivity prior and post gastrointestinal digestion.

Phlorotannins are phenolic compounds exclusive from brown macroalgae endowed with promising bioactive properties. However, considering that diet is their main route of entrance to our system, gastrointestinal digestion might affect such bioactive properties. Here, phlorotannin extracts obtained from Laminaria digitata were submitted to simulated gastrointestinal digestion to evaluate its impact on their antioxidant and anti-inflammatory properties.

A Proteogenomic Pipeline for the Analysis of Protein Biosynthesis Errors in the Human Pathogen Candida albicans.

Candida albicans is a diploid pathogen known for its ability to live as a commensal fungus in healthy individuals but causing both superficial infections and disseminated candidiasis in immunocompromised patients where it is associated with high morbidity and mortality. Its success in colonizing the human host is attributed to a wide range of virulence traits that modulate interactions between the host and the pathogen, such as optimal growth rate at 37 °C, the ability to switch between yeast and hyphal forms, and a remarkable genomic and phenotypic plasticity. A fascinating aspect of its biology is a prominent heterogeneous proteome that arises from frequent genomic rearrangements, high allelic variation, and high levels of amino acid misincorporations in proteins.

Sperm-borne miR-34c-5p and miR-191-3p as markers for sperm motility and embryo developmental competence.

Background: Sperm-borne microRNAs play a pivotal role in influencing essential cellular processes during fertilization, impacting the quality of embryo development. Dysregulated microRNA profiles have been associated with compromised embryonic development and increased incidences of pregnancy loss.

Objective: This study aimed to investigate the potential associations between the abundance of miR-34c-5p and miR-191-3p in human spermatozoa with sperm quality, as well as with embryo quality and metabolic performance during in vitro development.

Effect of Arm-Ergometry Versus Treadmill Supervised Exercise on Cardiorespiratory Fitness and Walking Distances in Patients With Peripheral Artery Disease: The ARMEX Randomized Clinical Trial.

Purpose: To compare arm-ergometry and treadmill supervised exercise training on cardiorespiratory fitness and walking distances in patients with peripheral artery disease (PAD).

Methods: ARMEX was a single-center, single-blinded, parallel group, non-inferiority trial enrolling symptomatic patients with PAD. Patients were randomized (1:1 ratio) to a 12-wk arm-ergometry (AEx) or standard treadmill (TEx) supervised exercise training protocol.

Enhancing Dental Pulp Stem Cell Proliferation and Odontogenic Differentiation with Protein Phosphatase 1-Disrupting Peptide: An In Vitro Study.

The reparative and regenerative capabilities of dental pulp stem cells (DPSCs) are crucial for responding to pulp injuries, with protein phosphatase 1 (PP1) playing a significant role in regulating cellular functions pertinent to tissue healing. Accordingly, this study aimed to explore the effects of a novel cell-penetrating peptide Modified Sperm Stop 1-MSS1, that disrupts PP1, on the proliferation and odontogenic differentiation of DPSCs. Employing MSS1 as a bioportide, DPSCs were cultured and characterized for metabolic activity, cell proliferation, and cell morphology alongside the odontogenic differentiation through gene expression and alkaline phosphatase (ALP) activity analysis.

Assessment of communicative competence in adult patients with minimum response in intensive care units: A scoping review.

Background: Few formal instruments exist to assess the communicative competence of patients hospitalized in intensive care units (ICUs). This can limit interventions by health professionals.

Aims: To map the categories and instruments for assessing the communicative competence of adult patients with minimal response in ICUs.

Unmasking vaccine hesitancy and refusal: a deep dive into Anti-vaxxer perspectives on COVID-19 in Spain.

Background: At the time of the emergence of COVID-19, denialist and anti-vaccine groups have also emerged and are shaking public confidence in vaccination.

Methods: A qualitative study was conducted using online focus groups. Participants had not received any doses of vaccination against the disease.

Functional capacity using sit-to-stand tests in people with chronic obstructive pulmonary disease and its relationship with disease severity-a cross-sectional study with matched controls.

Background: Functional capacity impairment is a crucial consequence of chronic obstructive pulmonary disease (COPD). Although it can be identified with simple tests, such as the sit-to-stand tests, its prevalence, relation with disease severity, and the characteristics of people presenting this impairment remain unknown.

Objective: To explore the functional capacity of people with COPD.

Senescent cell-derived vaccines: a new concept towards an immune response against cancer and aging?

Two recent seminal works have untangled the intricate role of tumor-associated senescent cells in cancer progression, or regression, by guiding our immune system against cancer cells. The characterization of these unique, yet diverse cell populations, should be considered, particularly when contemplating the use of senolytics, which are drugs that selectively eliminate senescent cells, in a cancer framework. Here, we will describe the current knowledge in this field.

Modeling 3D Tumor Invasiveness to Modulate Macrophage Phenotype in a Human-Based Hydrogel Platform.

The immune system is a pivotal player in determining tumor fate, contributing to the immunosuppressive microenvironment that supports tumor progression. Considering the emergence of biomaterials as promising platforms to mimic the tumor microenvironment, human platelet lysate (PLMA)-based hydrogel beads are proposed as 3D platforms to recapitulate the tumor milieu and recreate the synergistic tumor-macrophage communication. Having characterized the biomaterial-mediated pro-regenerative macrophage phenotype, an osteosarcoma spheroid encapsulated into a PLMA hydrogel bead is explored to study macrophage immunomodulation through paracrine signaling.

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

Introduction: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.

Methods: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

Unravelling the complex interplay of factors behind exercise limitations and physical inactivity in COPD.

Exercise limitation and physical inactivity are known treatable traits for people with COPD. Maximising exercise capacity and keeping people physically active improves health status and survival rates among people with COPD. However, managing these two treatable traits can be extremely challenging for clinicians due to the complex intersectionality of factors influencing an individual's capacity, opportunity and motivation to engage in physical activity.

Fluid biomarkers unveil signatures of pathological aging.

Aging is a multifaceted and highly varied process in the brain. Identifying aging biomarkers is one means of distinguishing pathological from physiological aging. The aim of this narrative review is to focus on two new developments in the field of fluid biomarkers and draw attention to this excellent tool for the early detection of potential brain pathologies that delay, alter, or enable physiological aging to become pathological.