RNA Pol II inhibition activates cell death independently from the loss of transcription.

RNA Pol II-mediated transcription is essential for eukaryotic life. Although loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here, we show that death following the loss of RNA Pol II activity does not result from dysregulated gene expression.

Identification of CT features and laboratory indicators to aid in the management of patients with portal venous gas identified on imaging.

Background: It can be difficult to distinguish cases of benign portal venous gas (PVG) that can be managed conservatively from forms associated with ischaemic bowel.

Purpose: To identify CT, clinical and laboratory factors that may be assist in the decision-making regarding patient management.

Methods: All patients in whom PVG was demonstrated on CT imaging were identified over an 8-year period.

Spina bifida as a multifactorial birth defect: Risk factors and genetic underpinnings.

Spina bifida is a birth defect resulting from abnormal embryonic development of the neural tube. Though spina bifida is divided into several subtypes, myelomeningocele-the most severe form of spina bifida often associated with a markedly diminished quality of life-accounts for a significant portion of cases. A broad range of genetic and environmental factors, many of which are still unknown, influence spina bifida, making it difficult to provide a comprehensive etiology for the disorder.

Comprehensive Analysis of Drug Response using the FLICK Assay.

For understanding drug efficacy, a critical need is to characterize the extent of drug-induced cell death. Efforts to quantify the level of drug-induced cell death are challenged by the existence of more than a dozen molecularly distinct forms of regulated death, each with its own activation timing and biochemical hallmark features. Furthermore, for some necrotic death subtypes, hallmark features are only observed transiently and are rapidly lost due to cell rupture.

Natural History of True Renal Artery Aneurysms: A Multi-Centre Retrospective Cohort Study and Proposed Algorithm for Follow-Up.

Aim: To identify the pattern of growth of true renal artery aneurysms (RAA) in a multicentre cohort and to propose an algorithm for the follow-up of asymptomatic RAA.

Methods: A retrospective review of all patients identified to have true RAA with subsequent follow-up cross-sectional imaging at three centres over a 15-year period was performed. Aneurysm maximal diameter was measured on initial and latest imaging and growth pattern assessed by two radiologists in consensus.

Genome-wide profiling identifies the genetic dependencies of cell death following EGFR inhibition.

EGFR is a proto-oncogene that is mutationally activated in a variety of cancers. Small molecule inhibitors targeting EGFR can be effective in slowing the progression of disease, and in some settings these drugs even cause dramatic tumor regression. However, responses to EGFR inhibitors are rarely durable, and the mechanisms contributing to response variation remain unclear.

Fluorine-, Nitrogen-, and Boron-Functionalized Polymer Electrolytes for Advanced Lithium Metal Batteries.

Polymer electrolytes (PEs) have emerged as alternatives to conventional liquid electrolytes in lithium metal batteries (LMBs) by addressing critical safety and performance challenges, including flame hazards, dendrite growth, and interfacial instability. While oxygen-based PEs, such as poly(ethylene oxide), have been widely investigated, their limited ionic conductivity and susceptibility to electrochemical degradation under high-voltage operation have prompted the exploration of heteroatom-functionalized PEs. Incorporating heteroatoms significantly enhances ion transport, electrochemical stability, and mechanical properties─all critical factors for robust and reliable LMB performance.

Bilisense: An affordable sensor for on-site diagnosis of jaundice and prevention of kernicterus.

Bilirubin (BR) in blood serum is elevated during jaundice (a common complication among newborns). Accessible and frequent monitoring of BR is necessary for timely diagnosis and intervention. This work developed a low-cost electrochemical sensor for point-of-care and at-home measurement of BR.

An Intervertebral Disc (IVD) Regeneration Model Using Human Nucleus Pulposus Cells (iHNPCs) and Annulus Fibrosus Cells (iHAFCs).

Intervertebral disc (IVD) degeneration (IVDD), primarily caused by nucleus pulposus (NP) dehydration, leads to low back pain. While current treatments focus on symptom management or surgical intervention, tissue engineering using IVD-derived cells, biofactors, and scaffolds offers a promising regenerative approach. Here, human NP cells (NPCs) and annulus fibrosus cells (AFCs) are immortalized with human telomerase reverse transcriptase (hTERT), generating immortalized NPCs (iHNPCs) and AFCs (iHAFCs).

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data.

Systematic screening of gain- or loss-of-function genetic perturbations can be used to characterize the genetic dependencies and mechanisms of regulation for essentially any cellular process of interest. These experiments typically involve profiling from a pool of single gene perturbations and how each genetic perturbation affects the relative cell fitness. When applied in the context of drug efficacy studies, often called chemo-genetic profiling, these methods should be effective at identifying drug mechanisms of action.

Effective Bone Tissue Fabrication Using 3D-Printed Citrate-Based Nanocomposite Scaffolds Laden with BMP9-Stimulated Human Urine Stem Cells.

Effective repair of large bone defects through bone tissue engineering (BTE) remains an unmet clinical challenge. Successful BTE requires optimal and synergistic interactions among biocompatible scaffolds, osteogenic factors, and osteoprogenitors to form a highly vascularized microenvironment for bone regeneration and osseointegration. We sought to develop a highly effective BTE system by using 3D printed citrate-based mPOC/hydroxyapatite (HA) composites laden with BMP9-stimulated human urine stem cells (USCs).

Pol II degradation activates cell death independently from the loss of transcription.

Pol II-mediated transcription is essential for eukaryotic life. While loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here, we show that death following loss of Pol II is not caused by dysregulated gene expression.

Concomitant Diffuse Idiopathic Skeletal Hyperostosis and Cervical Ossification of the Posterior Longitudinal Ligament: A U.S. Database Study of Clinical Prevalence, Surgical Intervention, Patient Characteristics, and Postoperative Complications.

Background: Concomitant diffuse idiopathic skeletal hyperostosis (DISH) and cervical ossification of the posterior longitudinal ligament (cOPLL) are primarily investigated in radiographic studies of East Asian populations. This study aimed to determine clinical prevalence of concomitant DISH/cOPLL in a large U.S.

Rat Hepatitis E Virus Isolates Cluster among Urban Norway Rats (Rattus norvegicus) across a Roadway.

Hepatitis E virus (HEV) is a globally distributed pathogen that causes acute hepatitis in people. Recent human cases of HEV arising after contact with urban rats (Rattus spp.) have raised concerns regarding whether rats may be a source of HEV infection.

Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.

Background: Integrating molecular-targeted agents into combination chemotherapy is transformative for enhancing treatment outcomes in cancer. However, realizing the full potential of this approach requires a clear comprehension of the genetic dependencies underlying drug synergy. While the interactions between conventional chemotherapeutics are well-explored, the interplay of molecular-targeted agents with conventional chemotherapeutics remains a frontier in cancer treatment.

Extracranial Vertebral Artery Injuries.

Paired vertebral arteries (VAs) travel from the subclavian artery through the cervical spine and into the intracranial space where they contribute to posterior cerebral circulation. Blunt and penetrating injuries to the cervical spine risk injury to the VA. Among the most feared complications of vertebral artery injury (VAI) is posterior circulation stroke.

Civilian Ballistic Injuries to the Atlantoaxial Spine: A Single Institution Case Series.

Study Design: Retrospective case series.

Objective: Describe the injury characteristics of ballistic fractures involving the atlantoaxial spine.

Summary Of Background Data: Civilian gunshot wounds to the spine are an increasingly common injury in the United States.

A Qualitative Systematic Review of Endovascular Management of Renal Artery Aneurysms.

Purpose: To perform a qualitative systematic review of endovascular management of renal artery aneurysms (RAAs).

Materials And Methods: A comprehensive electronic search of PubMed, MEDLINE, Embase, Google Scholar, and Cochrane databases from 2000 to 2022 was performed using the search terms "renal artery," "aneurysm," and "endovascular." Means of outcome measures were calculated with a primary end point focused on RAA-related mortality and rupture.

Lean body mass in living kidney donors impacts postoperative renal function.

Purpose: A living donor kidney transplant is the optimal treatment for chronic renal impairment. Our objective is to assess if lean skeletal muscle mass and donor factors such as body mass index, hypertension, and age impact on renal function following donor nephrectomy.

Methods: Potential donors undergo CT angiography as part of their work-up in our institution.

Calcineurin promotes adaptation to chronic stress through two distinct mechanisms.

Adaptation to environmental stress requires coordination between stress-defense programs and cell cycle progression. The immediate response to many stressors has been well characterized, but how cells survive in challenging environments long-term is unknown. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in adaptation to chronic CaCl stress in We find that prolonged exposure to CaCl impairs mitochondrial function and demonstrate that cells respond to this stressor using two CN-dependent mechanisms - one that requires the downstream transcription factor Crz1 and another that is Crz1-independent.

Functional genomic screens with death rate analyses reveal mechanisms of drug action.

A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to several confounding influences related to variation in growth rates between clones. In this study, we developed Method for Evaluating Death Using a Simulation-assisted Approach (MEDUSA), which uses time-resolved measurements, along with model-driven constraints, to reveal the combination of growth and death rates that generated the observed drug response.

The health risks of marine biotoxins associated with high seafood consumption: Looking beyond the single dose, single outcome paradigm with a view towards addressing the needs of coastal Indigenous populations in British Columbia.

People who consume high quantities of seafood are at a heightened risk for marine biotoxin exposure. Coastal Indigenous peoples may experience higher levels of risk than the general population due to their reliance on traditional marine foods. Most evidence on the health risks associated with biotoxins focus on a single exposure at one point in time.