Caspase-4 Has Potential Utility as a Colorectal Tissue Biomarker for Dysplasia and Early-Stage Cancer.

Background And Aims: Colorectal cancer (CRC) is the second most deadly cancer globally. The rapidly rising incidence rate of CRC, coupled with increased diagnoses in individuals <50 years, indicates that early detection of CRC, and those at an increased risk of CRC development, is paramount to improve the survival rates of these patients. Here, we profile caspase-4 expression across 2 distinct CRC development pathways, sporadic CRC (sCRC) and inflammatory bowel disease-associated CRC (IBD-CRC), to examine its utility as a novel biomarker for CRC risk and diagnosis.

How and why do health system factors influence general dentists' participation in publicly funded, contracted primary dental care services: A realist review.

Objectives: To identify health system contexts and mechanisms influencing general dental practitioners' (GDPs) participation in state funded, contracted primary oral healthcare.

Methods: Peer-reviewed articles and other sources were identified via EMBASE, Medline (OVID), Web of Science and Google Scholar databases, grey literature search, citation tracking and expert recommendations. Studies meeting the inclusion criteria were assessed for rigour, relevance and richness, and coded to identify data relating to contexts, mechanisms and outcomes.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

A proposed framework of strategies to overcome challenges to surgical quality assurance in oncology trials (SQA-Onc.).

Introduction: Randomised controlled trials (RCTs) with surgical interventions frequently lack a framework to ensure surgical quality. We aimed to investigate surgical quality assurance (SQA) in oesophagogastric oncology trials and to develop a translatable framework of strategies to overcome challenges in the design and implementation of SQA.

Methods: Seventy-one peer-nominated, international, expert trial stakeholders included surgeons; oncologists; trial managers and trial methodologists.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

La dolce vita: fueling chimeric antigen receptor (CAR) T cells with Glut1 to improve therapeutic efficacy.

The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of hematological cancers has marked a new era in cancer care, with seven products being FDA approved since 2017. However, challenges remain, and while profound effects are observed initially in myeloma, the majority of patients relapse, which is concomitant with poor CAR T cell persistence. Similarly, the efficacy of CAR T cell therapy is limited in solid tumors, largely due to tumor antigen heterogeneity, immune evasion mechanisms, and poor infiltration and persistence.

The Association of Regular Dog Walking with Mobility, Falls and Fear of Falling in Later Life.

Background: It has been suggested that dog walking may protect against falls and mobility problems in later life, but little work to date has examined this.The aim of this study was to assess if regular dog walking was associated with reduced likelihood of falls, fear of falling and mobility problems in a large cohort of community-dwelling older people.

Methods: Participants ≥60 years at Wave 5 of The Irish Longitudinal Study on Ageing were included.

Evaluation of workload distribution and exposure factors in common use in ten general x-ray rooms in Ireland: An initial step towards protocol optimisation.

Introduction: This study aimed to assess current practice in general x-ray rooms in three Irish hospitals. Evaluating the extent to which x-ray protocols are currently standardised can be considered as a preparatory step towards the larger goal of implementing optimisation in a diagnostic radiology department.

Methods: Data on various aspects of general x-ray room exposures was manually collected and analysed to highlight variations with exposure factors in use and workload distribution across each of the ten hospital x-ray rooms included in the study.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

'Choosing Tuesday': establishing and sustaining regular clinical supervision in advanced nursing practice.

Clinical supervision is a valued learning tool for student nurses; however, there is a paucity of description around real-time experience of clinical supervision among qualified advanced nurse practitioners. Many qualified nurses claim delays in engaging with clinical supervision may be caused by staff shortages, time constraints, workload in busy clinical environments, or a reticence to engage in discussions that might reveal shortcomings in knowledge or practical skills. This article reviews a process of monthly clinical supervision that has been conducted among a group of qualified emergency department advanced nurse practitioners for 25 years.

Measuring Self-Reported Well-Being of Physicians Using the Well-Being Thermometer: Cohort Study.

Background: Advancements in medical science have focused largely on patient care, often overlooking the well-being of health care professionals (HCPs). This oversight has consequences; not only are HCPs prone to mental and physical health challenges, but the quality of patient care may also endure as a result. Such concerns are also exacerbated by unprecedented crises like the COVID-19 pandemic.

TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.

Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype.

Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models.

The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses ( wild-type, -mutated, -mutated, and -mutated).

Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.

A Technique for the Internalization of Nephroureteral Stents in Patients With Ileal Conduits.

We present a method of internalization of nephroureteral stents to internalized ureteral stents in a patient with an ileac conduit urostomy with radiation-induced ureteral strictures, and recurrent urinary tract infections (UTIs). This technique is applicable to patients requiring internalization of nephroureteral stents in the setting of an ileal conduit, emphasizing patient consent, preparation, position, imaging guidance, and antibiotic prophylaxis. The successful application of this technique offers a practical solution for managing recurrent UTIs in patients with similar medical histories, providing both clinical and procedural insights.

Chlorotoxin-functionalized mesoporous silica nanoparticles for pH-responsive paclitaxel delivery to Glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly aggressive brain cancer associated with poor survival rates. We developed novel mesoporous silica nanoparticles (MSNs)-based nanocarriers for pH-responsive delivery of a therapeutic drug Paclitaxel (PTX) to GBM tumor cells. The pores of MSNs are loaded with PTX, which is retained by β-cyclodextrin (CD) moieties covalently linked to the pore entrances through a hydrazone linkage, which is cleavable in weakly acidic environment.

Cellular and extracellular white matter alterations after childhood trauma experience in individuals with schizophrenia.

Background: Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al.

Harmonious ageing: a narrative review of music therapy in the biomedical literature.

Purpose: As the global population of older adults rises, the United Nations Decade of Healthy Ageing (2021-2030) advocates for disease prevention, management, and enhancing overall wellbeing in older adults. We reviewed the MEDLINE literature under the MeSH term "music therapy" (MT), for its role in promoting healthy ageing.

Methods: A systematic search of the MEDLINE biomedical database (Ovid) was conducted using "MT" and "Ageing" as keywords, retrieving relevant full-text studies in English.

Metabolic reprogramming, malignant transformation and metastasis: Lessons from chronic lymphocytic leukaemia and prostate cancer.

Metabolic reprogramming is a hallmark of cancer, crucial for malignant transformation and metastasis. Chronic lymphocytic leukaemia (CLL) and prostate cancer exhibit similar metabolic adaptations, particularly in glucose and lipid metabolism. Understanding this metabolic plasticity is crucial for identifying mechanisms contributing to metastasis.

Gender disparities in extreme psychological distress at cancer diagnosis and patients access to psycho-oncological care.

Background: Cancer has adverse consequences for mental health, especially in women. Lack of awareness of services and stigma diminish access to psycho-oncology services.

Aims: To assess psychological distress and willingness to engage in multidisciplinary psycho-oncological services among cancer patients.