Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma.

Background: Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment.

Methods: We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival.

Can mechanical heart valves perform similarly to tissue valves? An in vitro study.

Current surgical aortic valve (AV) replacement options include bioprosthetic and mechanical heart valves (MHVs), each with inherent limitations. Bioprosthetic valves offer superior hemodynamics but suffer from durability issues, typically initiating deterioration within 7-8 years. MHVs, while durable, necessitate lifelong anticoagulation therapy, presenting risks such as severe bleeding and thromboembolic events.

Analytical and Clinical Validation of a Non-Ristocetin Based VWF Assay on 2 Automated Analyzers in a Large Reference Laboratory.

Background: Historically, von Willebrand factor (VWF) activity assays utilized ristocetin despite limitations including poor limits of detection and high imprecision. Newer VWF activity assays such as the INNOVANCE® VWF Ac assay, however, do not rely on ristocetin to measure platelet-dependent VWF function. The purpose of this study was to evaluate the analytical and clinical performance of the Siemens Healthineers INNOVANCE VWF Ac Assay on the Siemens BCS® XP and the Sysmex® CS-2500 systems in a large reference laboratory setting.

Dequalinium chloride vaginal tablets for recalcitrant : A case report.

Treatment options for recalcitrant (TV), when very high dose systemic 5-nitroimidazole plus intravaginal therapy for over 14 days has failed, are very limited. They have poor efficacy, unpleasant side effects, and are difficult and expensive to acquire. We report successful treatment with 24 weeks of daily dequalinium chloride vaginal tablets.

Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins.

Background: Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes.

Plasma ctDNA enables early detection of temozolomide resistance mutations in glioma.

Background: Liquid biopsy based on circulating tumor DNA (ctDNA) is a novel tool in clinical oncology, however, its use has been limited in glioma to date, due to low levels of ctDNA. In this study, we aimed to demonstrate that sequencing techniques optimized for liquid biopsy in glioma patients can detect ctDNA in plasma with high sensitivity and with potential clinical utility.

Methods: We investigated 10 glioma patients with tumor tissue available from at least 2 surgical operations, who had 49 longitudinally collected plasma samples available for analysis.

Co-targeting BET, CBP, and p300 inhibits neuroendocrine signalling in androgen receptor-null prostate cancer.

There are diverse phenotypes of castration-resistant prostate cancer, including neuroendocrine disease, that vary in their sensitivity to drug treatment. The efficacy of BET and CBP/p300 inhibitors in prostate cancer is attributed, at least in part, to their ability to decrease androgen receptor (AR) signalling. However, the activity of BET and CBP/p300 inhibitors in prostate cancers that lack the AR is unclear.

Expression of MHC II in DRG neurons attenuates paclitaxel-induced cold hypersensitivity in male and female mice.

Chemotherapy is often a life-saving treatment, but the development of intractable pain caused by chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity that restricts cancer survival rates. Recent reports demonstrate that paclitaxel (PTX) robustly increases anti-inflammatory CD4+ T cells in the dorsal root ganglion (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. However, the mechanism by which CD4+ T cells are activated, and the extent cytokines released by CD4+ T cells target DRG neurons are unknown.

A review of the experimental methods and results of testing the mechanical properties of Tunica Albuginea.

The present work provides a comprehensive review of the literature on the mechanical properties and existing human tunica albuginea tissue testing methods. Assessments were completed on papers reporting experimental values of Young's modulus, tensile strength, puncture strength, stiffness, toughness, and strain at the ultimate tensile strength (UTS). A high degree of variability in the reported experimental values was found; Young's modulus ranged from 5 MPa to 118 MPa, and tensile strength went from 1.

PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma.

Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established.

Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models.

Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (Le)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer.

Spatial analysis with SPIAT and spaSim to characterize and simulate tissue microenvironments.

Spatial proteomics technologies have revealed an underappreciated link between the location of cells in tissue microenvironments and the underlying biology and clinical features, but there is significant lag in the development of downstream analysis methods and benchmarking tools. Here we present SPIAT (spatial image analysis of tissues), a spatial-platform agnostic toolkit with a suite of spatial analysis algorithms, and spaSim (spatial simulator), a simulator of tissue spatial data. SPIAT includes multiple colocalization, neighborhood and spatial heterogeneity metrics to characterize the spatial patterns of cells.

Novel expression of major histocompatibility complex II in dorsal root ganglion neurons attenuates paclitaxel-induced cold hypersensitivity in male and female mice.

Chemotherapy is often a life-saving treatment, but the development of intractable pain caused by chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity that restricts survival rates. Recent reports demonstrate that paclitaxel (PTX) robustly increases anti-inflammatory CD4+ T cells in the dorsal root ganglion (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. However, the mechanism by which CD4+ T cells are activated, and the extent cytokines released by CD4+ T cells target DRG neurons are unknown.

A review of the factors influencing adoption of digital health applications for people living with dementia.

Objective: Researchers have used various theories and models to understand technology adoption, however, with the growing interest and availability of mobile applications (apps) for people living with dementia, it is desirable to have a broader insight into how technology adoption may be further improved. This paper aims to explore the factors influencing the adoption of digital health applications for people living with dementia and add to the current literature on this topic.

Methods: Searches were conducted in CINHAL, Web of Science, Psych Info, ProQuest Health and Medical, IEEE Xplore and Scopus.

Supporting older people following out of hours discharge from the Emergency Department: An integrative review of the literature.

Background: For many older people the emergency department (ED) is an important but sometimes difficult step in their healthcare journey. They often attend the ED with co and multi morbidities. Discharge home at evenings and weekends when post-discharge support services are limited can result in a delay or failure to follow through on their discharge plan leading to adverse health outcomes and in some cases, readmission to ED.

The future of patient-derived xenografts in prostate cancer research.

Patient-derived xenografts (PDXs) are generated by engrafting human tumours into mice. Serially transplantable PDXs are used to study tumour biology and test therapeutics, linking the laboratory to the clinic. Although few prostate cancer PDXs are available in large repositories, over 330 prostate cancer PDXs have been established, spanning broad clinical stages, genotypes and phenotypes.

A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.

Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global experiments have been conducted that identify their cell type and cell stage-specific activity within one developmental pathway and in a chromatin context. Here, we describe a high-throughput method that identifies thousands of differentially active cis-elements able to stimulate a minimal promoter at five stages of hematopoietic progenitor development from embryonic stem (ES) cells, which can be adapted to any ES cell derived cell type.

Computational study and validation of a novel passive hand tremor attenuator.

Tremors are a prevalent movement disorder due to a nervous system condition that leads to involuntary muscle movements observed in patients. This paper converts the tremorous anatomical human arm model to a single degree of freedom (SDOF) forced vibration problem. The mathematical modelling with Euler-Lagrange's equation is performed for the SDOF human arm model with two different potential vibration absorbers.

Care experiences of older people with mental health needs and their families in emergency medical services settings.

Background: There are challenges to person-centred care provision in Emergency Medical Services (EMS) settings. The environment is often busy and noisy which can influence the experience of older people and their carer/partners when they attend emergency departments. Older people with mental health needs are a vulnerable group of people who are at risk of not having their needs met in acute care settings.

Valve interstitial cells under impact load, a mechanobiology study.

Understanding the relationship between mechanobiology and the biosynthetic activities of the valve interstitial cells (VICs) in health and disease under severe dynamic loading conditions is of particular interest. The purpose of this study is to further understand the mechanobiology of heart valve leaflet tissue and the VICs under impact forces. Two novel computational and experimental platforms were developed to study the effect of impact load on the VICs to monitor for apoptosis.

Tumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes.

Background: Aberrations in homologous recombination repair (HRR) genes are emerging as important biomarkers for personalized treatment in prostate cancer (PCa). HRR deficiency (HRD) could affect the tumor immune microenvironment (TIME), potentially contributing to differential responses to poly ADP-ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors. Spatial distribution of immune cells in a range of cancers identifies novel disease subtypes and is related to prognosis.