Small molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.

Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.

Combinatorial phenotypic landscape enables bacterial resistance to phage infection.

Success of phage therapies is limited by bacterial defenses against phages. While a large variety of anti-phage defense mechanisms has been characterized, how expression of these systems is distributed across individual cells and how their combined activities translate into protection from phages has not been studied. Using bacterial single-cell RNA sequencing, we profiled the transcriptomes of ~50,000 cells from cultures of a human pathobiont, , infected with a lytic bacteriophage.

Clinical Care Pathways for Second and Third Trimester Termination of Pregnancy for Medical Reasons in Canada.

Objective: Termination of pregnancy in the 2/3 trimester for fetal or maternal complications (i.e., for medical reasons) is an essential health service.

Translational research in Australian mental health policy: a scoping review.

ObjectivesThe role of translational research in improving mental health care has been highlighted in federal policy; however, an examination of how and to what extent it has been articulated at this level has not been undertaken. The aim of this scoping review was to characterise translational research concepts in federal mental health policy.MethodsAustralian Government websites were searched for federal policy documents that made recommendations for mental health services in primary care and/or community settings.

In Situ Self-Assembled Naringin/ZIF-8 Nanoparticle-Embedded Bacterial Cellulose Sponges for Infected Diabetic Wound Healing.

The treatment of diabetic foot ulcers (DFUs) represents a significant challenge due to the complexity of the wound microenvironment. Several factors, including infection, inflammation, and impaired angiogenesis, can complicate the healing process and reduce the effectiveness of current clinical treatments. To address these challenges, this work develops a multifunctional sponge containing a zeolitic imidazolate framework-8/bacterial cellulose (ZIF-8/BC) matrix loaded with the antioxidant naringin (Nar).

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Bayesian Effect Size Ranking to Prioritise Genetic Risk Variants in Common Diseases for Follow-Up Studies.

Biological datasets often consist of thousands or millions of variables, e.g. genetic variants or biomarkers, and when sample sizes are large it is common to find many associated with an outcome of interest, for example, disease risk in a GWAS, at high levels of statistical significance, but with very small effects.

The dynamics of capillary flow in an open-channel system featuring trigger valves.

Trigger valves are fundamental features in capillary-driven microfluidic systems that stop fluid at an abrupt geometric expansion and release fluid when there is flow in an orthogonal channel connected to the valve. The concept was originally demonstrated in closed-channel capillary circuits. We show here that trigger valves can be successfully implemented in open channels.

Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.

Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. We found that Delta-like1 (Dll1) Notch ligands in splenic fibroblasts regulated MZB cell pool size, migration, and function.

International prevalence patterns of low eGFR in adults aged 18-60 without traditional risk factors from a population-based cross-sectional disadvantaged populations eGFR epidemiology (DEGREE) study.

The disadvantaged populations eGFR (estimated glomerular filtration rate) epidemiology (DEGREE) study was designed to gain insight into the burden of chronic kidney disease (CKD) of undetermined cause (CKDu) using standard protocols to estimate the general-population prevalence of low eGFR internationally. Therefore, we estimated the age-standardized prevalence of eGFR under 60 ml/min per 1.73m in adults aged 18-60, excluding participants with commonly known causes of CKD; an ACR (albumin/creatinine ratio) over 300 mg/g or equivalent, or self-reported or measured (HT) hypertension or (DM) diabetes mellitus, stratified by sex and location.

(RPhP)[Mn(dca)]: A Family of Glass-Forming Hybrid Organic-Inorganic Materials.

ABX-type hybrid organic-inorganic structures have recently emerged as a new class of meltable materials. Here, by the use of phenylphosphonium derivatives as A cation, we study liquid- and glass-forming behavior of a new family of hybrid structures, (RPhP)[Mn(dca)] (R = Me, Et, Ph; dca = dicyanamide). These new compounds melt at 196-237 °C () and then vitrify upon cooling to room temperature, forming glasses.

Routine preoperative blood group and save is unnecessary for adult emergency appendicectomies: A retrospective multicentre study.

Background And Aims: Routine group and save (G&S) is commonly performed before appendicectomy despite limited evidence. This study aims to evaluate the necessity of preoperative G&S by determining perioperative blood transfusion rates.

Methods: A multicentre retrospective observational study of adult patients who had emergency appendicectomy across four hospitals between August 2018 and November 2020.

Independent SAGE as an example of effective public dialogue on scientific research.

The World Health Organization declared COVID-19 to be a public health emergency of international concern on 30 January 2020 and then a pandemic on 11 March 2020. In early 2020, a group of UK scientists volunteered to provide the public with up-to-date and transparent scientific information. The group formed the Independent Scientific Advisory Group for Emergencies (Independent SAGE) and provided live weekly briefings to the public via YouTube.

Modeling early phenotypes of Parkinson's disease by age-induced midbrain-striatum assembloids.

Parkinson's disease, an aging-associated neurodegenerative disorder, is characterised by nigrostriatal pathway dysfunction caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Human in vitro models are enabling the study of the dopaminergic neurons' loss, but not the dysregulation within the dopaminergic network in the nigrostriatal pathway. Additionally, these models do not incorporate aging characteristics which potentially contribute to the development of Parkinson's disease.

Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone.

Objective: The purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUV) in normal bone, to provide the reference value of metastatic lesions, and to evaluate the clinical implication of SUV changes of osseous metastasis during treatment.

Material And Methods: This prospective imaging sub-study was performed as part of a phase 2 clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to the combination of pembrolizumab plus radium-223 or to radium-223 alone (NCT03093428). The maximum standardized uptake value (SUV) and mean Hounsfield Unit (HU) of normal bone as well as metastases were measured using a 1.

Assessment of safety through mutagenicity and subchronic toxicity studies with black pepper extract preparation.

Introduction: Black pepper () is a rich source of natural and bioactive components such as N-trans-feruloyltyramine (NFT). In this paper, we discuss the results of the subchronic toxicity and mutagenicity studies conducted to understand the potential for adverse effects if any, of Black Pepper Extract Preparation (BPE).

Methods: To evaluate mutagenicity, an Ames test was conducted with BPE in the presence and absence of S9 metabolic activation.

2024 AAHA Community Care Guidelines for Small Animal Practice.

Community care is a creative way of thinking about health care that mobilizes resources within a community and consists of four core principles: recognition of the urgency of access-to-care for the veterinary profession, collaboration within community networks, family-centered health care, and redefining the gold standard of care. The AAHA Community Care Guidelines for Small Animal Practice offer strategies to help busy veterinary practitioners increase access to care within their practice and community by optimizing collaborative networks. While these guidelines do not claim to provide exhaustive solutions to access-to-care issues, they propose a starting point from which private practices can explore and implement workable solutions for their community and their practice.

Over-the-counter antibiotics compromising aminoglycoside activity.

Introduction: Antimicrobial resistance (AMR) is a global issue that needs addressing. While antibiotic stewardship has improved often by restricting antibiotic use, some antibiotics that are still sold legally over the counter (OTC), notably in sore throat medications. Recent findings suggest OTC antibiotics could trigger cross-resistance to antibiotics used in clinical treatments, whether systemic or topical.

Clinical Outcomes of Benzodiazepine Prescribing for People Receiving Opioid Agonist Treatment: A Systematic Review of the Evidence.

Many countries are experiencing an increased use of unregulated benzodiazepines in combination with opioids and other drugs, which contributes to drug-related harm. This descriptive review identifies and synthesises the outcomes of studies co-prescribing benzodiazepines and opioids. A systematic review was undertaken in Medline, CINAHL, PsychInfo, Embase, and the Cochrane databases covering publications from 1 January 1991 to 18 November 2021.