Examining the Biophysical Properties of the Inner Membrane of Gram-Negative ESKAPE Pathogens.

The World Health Organization has identified multidrug-resistant bacteria as a serious global health threat. Gram-negative bacteria are particularly prone to antibiotic resistance, and their high rate of antibiotic resistance has been suggested to be related to the complex structure of their cell membrane. The outer membrane of Gram-negative bacteria contains lipopolysaccharides that protect the bacteria against threats such as antibiotics, while the inner membrane houses 20-30% of the bacterial cellular proteins.

The Public Mental Health Framework: thinking about law as preventive medicine.

Health, mental health, and well-being are not 'natural' but are shaped by social and environmental factors. This article aims to reorient the development of all laws and policies to do more to prevent mental ill-health and promote well-being as a core function of the contemporary state. It introduces a new conceptual and empirical model, the Public Mental Health Framework, based on three areas of research: (i) the social determinants of health and mental health, which include social structures and daily living conditions (such as poverty, inequality, education, employment, discrimination, adverse childhood experiences, and crime); (ii) health and human rights; and (iii) the intermediate social model of disability.

MITIGATING OVER-SATURATED FLUORESCENCE IMAGES THROUGH A SEMI-SUPERVISED GENERATIVE ADVERSARIAL NETWORK.

Multiplex immunofluorescence (MxIF) imaging is a critical tool in biomedical research, offering detailed insights into cell composition and spatial context. As an example, DAPI staining identifies cell nuclei, while CD20 staining helps segment cell membranes in MxIF. However, a persistent challenge in MxIF is saturation artifacts, which hinder single-cell level analysis in areas with over-saturated pixels.

Bimetallic Nickel-Palladium Nanoparticles Supported on Multiwalled Carbon Nanotubes for Suzuki Cross-Coupling Reactions in Continuous Flow.

An efficient Suzuki cross-coupling reaction under continuous flow conditions was developed utilizing an immobilized solid supported catalyst consisting of bimetallic nickel-palladium nanoparticles (Ni-Pd/MWCNTs). In this process, the reactants can be continuously pumped into a catalyst bed at a high flow rate of 0.6 mL/min and the temperature of 130 °C while the Suzuki products are recovered in high steady-state yields for prolonged continuous processing.

Exploratory study of patients' and carers' preferences for postdischarge surgical wound monitoring using survey and interviews.

Objectives: To explore patients' and carers' preferences for postdischarge surgical wound monitoring.

Design: Explanatory mixed methods study with an online survey followed by online interviews.

Setting: The online survey was distributed via the Cardiothoracic Interdisciplinary Research Network and cardiac surgery patient and public involvement groups in London and Leicester, UK.

Effects of Quercetin and Citrulline on Nitric Oxide Metabolites and Antioxidant Biomarkers in Trained Cyclists.

Background: Quercetin (QCT) and citrulline (CIT) have been independently associated with improved antioxidant capacity and nitric oxide (NO) production, potentially enhancing cardiovascular function and exercise performance. This study aimed to evaluate the combined and independent effects of QCT and CIT supplementation on NO metabolites and antioxidant biomarkers in 50 trained cyclists undergoing a 20 km cycling time trial (TT).

Methods: In a randomized, double-blind, placebo-controlled design, forty-two male and eight female trained cyclists were assigned to QCT + CIT, QCT, CIT, or placebo (PL) groups.

Exertional Compartment Syndrome Strategies for Evaluation and Management.

Objective: The exertional compartment syndrome (ECS) is often a delayed diagnosis. Compartment pressure measurements (CPM) confirm the diagnosis. Herein we present our algorithm for the evaluation and management (E&M) of ECS.

Exploring the experiences of minoritised groups at life sciences conferences in the UK: new perspectives and actions to improve inclusivity in the sector.

Attending and participating in scientific research meetings and conferences is a key mechanism for researchers to share information and knowledge, build networks, and establish relationships and collaborations to support career development. In the UK, researchers from minoritised or underrepresented groups, may have a different experience at a conference than their peers. As a high profile provider of genomics-focussed life science conferences, Wellcome Connecting Science is committed to ensuring that our events are as inclusive as possible.

Clinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias.

Introduction: NUP98 rearrangements are rare in acute leukemias and portend a poor prognosis.

Methods: This study explored clinicopathologic and molecular features of five patients with NUP98 rearranged (NUP98-r) acute leukemias, including three females and two males with a median age of 34 years.

Results: NUP98 fusion partners were associated with distinctive leukemia characteristics and biology.

Adaptive clinical trial of AZD7442 and SARS-CoV-2 vaccination in immunosuppressed patients highly vulnerable to infection with SARS-CoV-2 virus (RAPID-PROTECTION): protocol for a multicentre, interventional open-label, randomised controlled trial.

Introduction: Despite repeated vaccinations against SARS-CoV-2 virus, patients who are immunocompromised remain at very high risk of catching SARS-CoV-2 virus and becoming unwell. AZD7442 (Evusheld) is a long-acting monoclonal antibody treatment that has been shown in clinical trials to prevent SARS-CoV-2 infection for up to a year after a single dose. Vaccines require a healthy immune system to generate protective immunity.

A non-randomised open-label exploratory 'window of opportunity' study of TG02 treatment in patients with locally advanced primary and recurrent mutant colorectal cancer.

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with -mutant colorectal cancer.

Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF.

Unraveling the Meaning of Effective Uptake Coefficients in Multiphase and Aerosol Chemistry.

ConspectusReactions of gas phase molecules with surfaces play key roles in atmospheric and environmental chemistry. Reactive uptake coefficients (γ), the fraction of gas-surface collisions that yield a reaction, are used to quantify the kinetics in these heterogeneous and multiphase systems. Unlike rate coefficients for homogeneous gas- or liquid-phase reactions, uptake coefficients are system- and observation-dependent quantities that depend upon a multitude of underlying elementary steps.

Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease.

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohn's disease (CD) model (Tnf), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host's immune susceptibility to drive region-specific disease. We identified an intracellular bacterium and murine counterpart to the human sexually transmitted , as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD.

Discovery of FHD-286, a First-in-Class, Orally Bioavailable, Allosteric Dual Inhibitor of the Brahma Homologue (BRM) and Brahma-Related Gene 1 (BRG1) ATPase Activity for the Treatment of SWItch/Sucrose Non-Fermentable (SWI/SNF) Dependent Cancers.

BRM (SMARCA2) and BRG1 (SMARCA4) are mutually exclusive ATPase subunits of the mSWI/SNF (BAF) chromatin remodeling complex. BAF is an attractive therapeutic target because of its role in transcription, and mutations in the subunits of BAF are common in cancer and neurological disorders. Herein, we report the discovery of compound () as a potent allosteric inhibitor of the dual ATPase subunits from a high-throughput screening hit with a BRM IC of ∼27 μM.

A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.

SARS-CoV-2 infections led to a worldwide pandemic in 2020. As of 2024, therapeutics against SARS-CoV-2 have continued to be desirable. NSP14 is a dual-function methyltransferase (MTase) and exonuclease (ExoN) with key roles in SARS-CoV-2 genome propagation and host immune system evasion.

Treatment of e-cigarette use among hospitalised adolescents and young adults: a protocol for intervention development and evaluation of preliminary efficacy and implementation outcomes in a randomised controlled trial.

Introduction: Hospitalisation represents an opportunity to identify and treat e-cigarette use among adolescents and young adults (AYAs). Knowledge on how to provide this care is lacking. We aim to fill this gap by developing an e-cigarette use intervention and evaluating preliminary efficacy and implementation outcomes among hospitalised AYAs.

Low Prevalence of SARS-CoV-2 in Farmed and Free-Ranging White-Tailed Deer in Florida.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in multiple animal species, including white-tailed deer (WTD), raising concerns about zoonotic transmission, particularly in environments with frequent human interactions. To understand how human exposure influences SARS-CoV-2 infection in WTD, we compared infection and exposure prevalence between farmed and free-ranging deer populations in Florida. We also examined the timing and viral variants in WTD relative to those in Florida's human population.

Lignocellulose biosorbents: Unlocking the potential for sustainable environmental cleanup.

Climate change, the overconsumption of fossil fuels, and rapid population and economic growth have collectively driven a growing emphasis on environmental sustainability and the need for effective resource management. Chemicals or materials not currently regulated are known as contaminants of emergent concern (CECs). Nevertheless, wastewater is thought to be its main source, and worries about its probable presence in the environment are growing due to its potential damage to human and environmental health.

Search for Fractionally Charged Particles with CUORE.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5  cm×5  cm×5  cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter.

Conceptualizing the Social Determinants of Mental Health Within an International Human Rights Framework: A Focus on Housing and Employment.

The social determinants of health and international human rights law share many overlapping concerns and goals in promoting human well-being. However, so far they have been developing largely in silos, resulting in calls for greater interdisciplinary collaboration. The purpose of this paper is to explore how the social determinants of health-specifically mental health-can fit within international human rights law conceptually and practically.

Regulation of Paneth cell-specific genes in COVID-19 patients and SARS-CoV-2-infected mice by quantification of mRNA from exfoliated cells in stool samples.

The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we could observe Paneth cell-specific gene regulation from exfoliated cells in infectious conditions, we obtained stool samples from patients with COVID-19 and uninfected controls.

Dermal CIC-Rearranged Sarcoma With Neuroendocrine Differentiation Mimicking Merkel Cell Carcinoma.

Capicua transcriptional repressor (CIC)-rearranged sarcoma (CRS) is a rare and recently described tumor that most commonly affects patients between 15 and 30 years of age. It is an undifferentiated round cell malignancy, with a disease defining CIC fusion, with double homeobox 4 (DUX4) being the most common partner. Here, we report a 77-year-old woman who presented with a cutaneous thigh mass with a clinical morphology suggesting Merkel cell carcinoma.

PTEN loss in glioma cell lines leads to increased extracellular vesicle biogenesis and PD-L1 cargo in a PI3K-dependent manner.

Phosphatase and Tensin Homolog (PTEN) is one of the most frequently lost tumor suppressors in cancer and the predominant negative regulator of the PI3K-AKT signaling axis. A growing body of evidence has highlighted the loss of PTEN with immuno-modulatory functions including the upregulation of the programmed death ligand-1 (PD-L1), an altered tumor-derived secretome that drives an immunosuppressive tumor immune microenvironment and resistance to certain immunotherapies. Given their roles in immunosuppression and tumor growth, we examined whether the loss of PTEN would impact the biogenesis, cargo, and function of extracellular vesicles (EVs) in the context of the anti-tumor associated cytokine interferon-γ.

Eighty-Nine Cases of Primary Prostatic Signet Ring Cell Carcinoma-Systematic Review.

Signet ring cell adenocarcinoma is a rare subtype of mucinous adenocarcinoma that affects the gastrointestinal tract and the prostate. Prostatic signet ring cell carcinoma comprises 0.02% of all cases of prostate cancer and 0.