Cell-Cell Fusion in NSCLC Confers a Fitness Benefit Under Drug Selection.

Cell-cell fusion has been implicated in various physiological and pathological processes, including cancer progression. This study investigated the role of cell-cell fusion in non-small cell lung cancer (NSCLC), focusing on its contribution to chemoresistance and tumor evolution. By co-culturing drug-sensitive and drug-resistant NSCLC cell lines, we observed spontaneous cell-cell fusion events, particularly under gefitinib selection.

Exercise referral schemes increase Patients' cardiorespiratory Endurance: A systematic review and Meta-Analysis.

Introduction: The efficacy of exercise referral schemes (ERS) involving primary care providers to an exercise specialist on patients' physical activity is uncertain and primarily based on self-report outcomes. Cardiorespiratory endurance carries clinically relevant information and is an objective outcome measure that has been used to evaluate ERS, but this literature has not been amalgamated. We determined the effectiveness of ERS involving qualified exercise professionals (QEPs) on patients' cardiorespiratory endurance.

Navigating competing tensions: A qualitative study of experiences and perceptions of leadership among emergency medicine doctors.

Objectives: Emergency medicine (EM) doctors are often required to manage a diverse set of complex challenges; navigating direct patient care, systemic issues and inter-professional interactions. Leadership is well recognised as crucial in optimising both the delivery and the quality of patient care. There is a clear need to gain greater understanding of the reality of EM leadership through exploring doctors' experience and perception of leadership in EM, yet there is a paucity of research focusing on this area.

Elevated TFPI is a prognostic factor in hepatocellular carcinoma: Putative role of miR-7-5p and miR-1236-3p.

Background: Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC).

Under pressure: integrated endothelial cell response to hydrostatic and shear stresses.

Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses are not fully understood. Specifically, the role of hydrostatic pressure in the EC flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow.

A Single Bout of Prolonged Sitting Augments Very Short-Term Blood Pressure Variability.

Background: More habitual time spent engaging in prolonged sedentary behaviors increases the risk of developing hypertension. Beat-by-beat systolic (SBPV) and diastolic blood pressure variability (DBPV) are more pronounced in persons with hypertension and may be an early manifestation of blood pressure dysregulation. We tested the hypothesis that a single bout of prolonged sitting augments very short-term SBPV and DBPV.

Faster stepping cadence partially explains the higher metabolic cost of walking among females versus males.

The metabolic cost of walking (MCOW), or oxygen uptake normalized to distance, provides information on the energy expended during movement. There are conflicting reports as to whether sex differences in MCOW exist, with scarce evidence investigating factors that explain potential sex differences. This study ) tested the hypothesis that females exhibit a higher MCOW than males, ) determined whether normalizing to stepping cadence ameliorates the hypothesized sex difference, and ) explored whether more habitual step counts and time in intensity-related physical activity, and less sedentary time were associated with a decreased MCOW.

Understanding age-related pathologic changes in TDP-43 functions and the consequence on RNA splicing and signalling in health and disease.

TAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and limbic-predominant age-related TDP-43 encephalopathy, TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circular RNA.

Cyclin F can alter the turnover of TDP-43.

Previously, we demonstrated that the SCF complex directly mediates the poly-ubiquitylation of TDP-43, raising the question of whether cyclin F can be used to enhance the turnover of TDP-43. A hurdle to the use of cyclin F, however, is that the overexpression of cyclin F can lead to the initiation of cell death pathways. Accordingly, the aim of this study was to identify and evaluate a less toxic variant of cyclin F.

Premorbid weight in pulmonary arterial hypertension.

Relationships between obesity and outcomes in pulmonary arterial hypertension (PAH) are complex. Previous work suggested obesity, occurring alongside PAH, may be associated with better survival. In our work, we suggest obesity prior to PAH development is associated with worse survival.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension due to septic emboli.

We present the case of a 28-year-old woman with a history of tricuspid valve endocarditis leading to chronic thromboembolic pulmonary hypertension (CTEPH) with multiple pulmonary artery chronic total occlusions (CTOs) due to septic emboli. Following a multidisciplinary care discussion, the patient was brought forward for balloon pulmonary angioplasty (BPA) with successful revascularization of all chronically occluded territories. This case highlights advances in pulmonary artery CTO interventions and demonstrates the feasibility of BPA for CTEPH patients with a history of septic emboli.

ALS/FTD-associated mutation in cyclin F inhibits ER-Golgi trafficking, inducing ER stress, ERAD and Golgi fragmentation.

Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative condition that is part of the same disease spectrum as frontotemporal dementia (FTD). Mutations in the CCNF gene, encoding cyclin F, are present in both sporadic and familial ALS and FTD. However, the pathophysiological mechanisms underlying neurodegeneration remain unclear.

TDP-43 as a therapeutic target in neurodegenerative diseases: Focusing on motor neuron disease and frontotemporal dementia.

A common feature of adult-onset neurodegenerative diseases is the presence of characteristic pathological accumulations of specific proteins. These pathological protein depositions can vary in their protein composition, cell-type distribution, and intracellular (or extracellular) location. For example, abnormal cytoplasmic protein deposits which consist of the TDP-43 protein are found within motor neurons in patients with amyotrophic lateral sclerosis (ALS, a common form of motor neuron disease) and frontotemporal dementia (FTD).

Digital health and inpatient palliative care: a cohort-controlled study.

Objectives: End of life has unacceptable levels of hospital admission and death. We aimed to determine the association of a novel digital specific system (Proactive Risk-Based and Data-Driven Assessment of Patients at the End of Life, PRADA) to modify such events.

Methods: A cohort-controlled study of those discharged alive, who died within 90 days of discharge, comparing PRADA (n=114) with standard care (n=3730).

The E3 Ubiquitin Ligase SCF Cyclin F Promotes Sequestosome-1/p62 Insolubility and Foci Formation and is Dysregulated in ALS and FTD Pathogenesis.

Amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD)-linked mutations in CCNF have been shown to cause dysregulation to protein homeostasis. CCNF encodes for cyclin F, which is part of the cyclin F-E3 ligase complex SCF known to ubiquitylate substrates for proteasomal degradation. In this study, we identified a function of cyclin F to regulate substrate solubility and show how cyclin F mechanistically underlies ALS and FTD disease pathogenesis.

ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that share pathological features, including the aberrant accumulation of ubiquitinated protein inclusions within motor neurons. Previously, we have shown that the sequestration of ubiquitin (Ub) into inclusions disrupts Ub homeostasis in cells expressing ALS-associated variants superoxide dismutase 1 (SOD1), fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43). Here, we investigated whether an ALS/FTD-linked pathogenic variant in the CCNF gene, encoding the E3 Ub ligase Cyclin F (CCNF), also perturbs Ub homeostasis.

Lung pericytes as mediators of inflammation.

Pericytes are microvascular mural cells that directly contact endothelial cells. They have long been recognized for their roles in vascular development and homeostasis, but more recently have been identified as key mediators of the host response to injury. In this context, pericytes possess a surprising degree of cellular plasticity, behaving dynamically when activated and potentially participating in a range of divergent host responses to injury.

SOX2 downregulation of PML increases HCMV gene expression and growth of glioma cells.

The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas.

Establishing a balloon pulmonary angioplasty program for chronic thromboembolic pulmonary hypertension: A United States single-center experience.

Introduction: Balloon pulmonary angioplasty (BPA) is a less invasive treatment alternative for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are unable to move forward with pulmonary thromboendarterectomy. This report describes a single-center experience with a nascent BPA program in the United States (US).

Methods: All patients who underwent BPA between August 2018-2021 were included in this retrospective, single-center observational cohort.

Inter-Regional Proteomic Profiling of the Human Brain Using an Optimized Protein Extraction Method from Formalin-Fixed Tissue to Identify Signaling Pathways.

Proteomics offers vast potential for studying the molecular regulation of the human brain. Formalin fixation is a common method for preserving human tissue; however, it presents challenges for proteomic analysis. In this study, we compared the efficiency of two different protein-extraction buffers on three post-mortem, formalin-fixed human brains.