Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Huntingtin plays an essential role in the adult hippocampus.

The consequences of non-pathogenic huntingtin (HTT) reduction in the mature brain are of substantial importance as clinical trials for numerous HTT-lowering therapies are underway; many of which are non-selective in that they reduce both mutant and wild type protein variants. In this study, we injected CaMKII-promoted AAV-Cre directly into the hippocampus of adult HTT floxed mice to explore the role of wild-type huntingtin (wtHTT) in adult hippocampal pyramidal neurons and the broader implications of its loss. Our findings reveal that wtHTT depletion results in profound macroscopic morphological abnormalities in hippocampal structure, accompanied by significant reactive gliosis.

Schizophrenia and retention in HIV care among adults insured through Medicaid in the United States: a population-based retrospective cohort study.

Background: People with schizophrenia spectrum disorders are at elevated risk of HIV, and people with both HIV and schizophrenia are at elevated risk of death compared to individuals with either diagnosis alone. Limited research has assessed the HIV care cascade, and in particular retention in care, among people with HIV (PWH) and schizophrenia in the U.S.

Transcatheter Aortic Valve Replacement in Patients With Interventricular Membranous Septal Aneurysms.

Aneurysms of the interventricular membranous septum are a rare anatomical feature that can be detected incidentally on computed tomography or echocardiography. Such aneurysms can pose challenges in the treatment of patients with aortic valve stenosis. A case series of 2 patients with membranous septal aneurysms treated successfully with current-generation balloon-expandable and self-expanding transcatheter heart valves is presented here.

Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial.

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, Setting, And Participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion.

Outcomes of Stereotactic Body Radiotherapy Compared with Surgical Resection in Patients with Hepatocellular Carcinoma and Macrovascular Invasion: A Propensity Score-Matched Analysis.

Introduction: Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) are recommended to receive systemic therapy according to guidelines. Stereotactic body radiotherapy (SBRT) and surgery are increasingly used in this patient population. This study compares outcomes from these local treatments.

Male Down syndrome Ts65Dn mice have impaired bone regeneration.

Trisomy of human chromosome 21 (Ts21) individuals present with a spectrum of low bone mineral density (BMD) that predisposes this vulnerable group to skeletal injuries. To determine the bone regenerative capacity of Down syndrome (DS) mice, male and female Dp16 and Ts65Dn DS mice underwent amputation of the digit tip (the terminal phalanx (P3)). This is a well-established mammalian model of bone regeneration that restores the amputated skeletal segment and all associated soft tissues.

The use of precision radiotherapy for the management of cancer related pain in the abdomen.

Purpose Of Review: Abdominal pain due to cancer is a significant and debilitating symptom for cancer patients, which is commonly undertreated. Radiotherapy (RT) for the management of abdominal cancer pain is underused, with limited awareness of its benefit. This review presents a discussion on current precision RT options for the management of cancer pain in the abdomen.

Co-production in practice: A qualitative study of the development of advance care planning workshops for South Asian elders.

Background: Advance care planning can improve patient and family outcomes; however, minoritised ethnic communities experience access barriers. Co-production offers a way to design culturally appropriate information and support, but evidence is needed to understand its implementation in palliative care.

Aim: To explore and describe how two charities used co-production to develop and deliver community-based advance care planning workshops for South Asian elders.

Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.

Adenoviruses typically cause mild illnesses, but severe diseases may occur primarily in immunodeficient individuals, particularly children. Recently, adenoviruses have garnered significant interest as a versatile tool in gene therapy, tumor treatment, and vaccine vector development. Over the past two decades, the advent of recombineering, a method based on homologous recombination, has notably enhanced the utility of adenoviral vectors in therapeutic applications.

Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation.

Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin-stimulated AMPK increases eNOS (also known as NOS3) activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake.

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial.

Background: CVN424 is a GPR6 inverse agonist that provides selective pharmacological control of the indirect striatopallidal pathway. We assessed the safety and efficacy of CVN424 as an adjunctive treatment to levodopa for reducing OFF-time in individuals with Parkinson's disease (PD) experiencing motor-fluctuations.

Methods: This was a randomised, double-blind, placebo-controlled study conducted at 21 sites across the United States to evaluate two doses of CVN424 (NCT04191577).

Recognising and supporting authentic learning in a changing world: the opportunities and threats of AI.

Since the term AI (artificial intelligence) was first coined, it has become embedded in modern life, with debate focusing on its challenges. In dentistry, AI is being used in clinical and education practice; however, many educators have limited knowledge or skills in its use. The British Alliance of Researchers in Dental Education and Scholarship hosted an AI-themed conference in November 2023.

"Should I Let Them Know I Have This?": Multifaceted Genetic Discrimination and Limited Awareness of Legal Protections among Individuals with Hereditary Cancer Syndromes.

Introduction: Hereditary cancer syndromes (HCS), such as hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS), represent approximately 10% of all cancers. Along with medical burdens associated with the genetic risk of developing cancer, many individuals face stigma and discrimination. Genetic discrimination refers to negative treatment, unfair profiling, or harm based on genetic characteristics, manifesting as "felt" stigma (ostracization without discriminatory acts) or "enacted" stigma (experiencing discriminatory acts).

Prehospital factors predicting mortality in patients with shock: state-wide linkage study.

Background: Patients with shock treated by emergency medical services (EMS) have high morbidity and mortality. Knowledge of prehospital factors predicting outcomes in patients with shock remains limited. We aimed to describe the prehospital predictors of mortality in patients with non-traumatic shock transported to hospital by EMS.

ADEVO: Proof-of-concept of adenovirus-directed EVOlution by random peptide display on the fiber knob.

Directed evolution of viral vectors involves the generation of randomized libraries followed by artificial selection of improved variants. Directed evolution only yielded limited results in adenovirus (AdV) engineering until now, mainly due to insufficient complexities of randomized libraries. Meanwhile, clinical applications of AdVs as gene therapy or oncolytic vectors are still hampered by the predetermined tropism of natural types.