Stent-Assisted Coil Embolization Versus Flow Diversion in Intracranial Vertebral Artery Dissecting Aneurysms: A Systematic Review and Meta-Analysis.

Introduction: Intracranial vertebral artery dissecting aneurysms (IVADAs) represent a rare but challenging condition associated with high morbidity and mortality. In the therapeutic landscape, endovascular interventions such as Flow Diversion (FD) and Stent-Assisted Coiling (SAC) are widely used for the management of IVADAs. The aim of this systematic review and meta-analysis is to compare the clinical outcomes and complications associated with FD and SAC techniques in the endovascular management of IVADAs.

Identification and Characterization of a TGF-β-Independent SMAD4-NFATc1-STAT3 Regulatory Axis.

SMAD4, a central mediator of the TGF-β signaling pathway, plays a critical role in regulating cellular processes such as proliferation, differentiation, and apoptosis. While SMAD4's canonical functions within TGF-β signaling are well-established, its non-canonical, TGF-β-independent roles remain poorly understood, particularly in the context of disease biology. Here, we investigate SMAD4's TGF-β-independent functions by identifying and characterizing its protein-protein interaction network.

MRD4U: A path to development for personalized liquid biopsy for children with central nervous system tumors.

Background: Liquid biopsy assays using cerebrospinal fluid (CSF) can revolutionize care for children with central nervous system (CNS) tumors by enabling precise monitoring of therapeutic responses and detecting recurrence or measurable residual disease (MRD). These assays can detect cell-free, circulating tumor DNA (ctDNA) via somatic alterations, though accurately measuring low-abundance ctDNA in CSF is challenging.

Methods: Our research focused on the optimization of next-generation sequencing library preparation from cell-free DNA (cfDNA), evaluating four commercial kits to address the low nucleic acid yield in CSF-derived cfDNA.

Quantitative Acid-Base: A Simplified Approach for the Emergency Physician.

Background: A deep understanding regarding acid-base physiology has been generally absent from what is considered the skill set of Emergency clinicians. The calculations needed to obtain a solid comprehension of acid-base are thought to be too complex and time consuming, making them impractical for the chaotic environment of the Emergency Department.

Objectives: Make acid-base more approachable and accessible for the Emergency Physician.

Efficacy and Safety of Mechanical Thrombectomy for Patients with Infective Endocarditis-Related Large Vessel Occlusion: a Systematic Review and Meta-Analysis.

Introduction: Acute ischemic stroke (AIS) is the most common neurological complication of infective endocarditis (IE), occurring in 20-40% of patients. In this context, while mechanical thrombectomy (MT) is the standard treatment for patients with AIS due to large-vessel occlusion (LVO), its efficacy and safety in patients with stroke secondary to IE remain unclear.

Objective: Therefore, a more robust analysis of the efficacy and safety of MT in patients with AIS due to IE was conducted to address the gaps identified in previous studies.

Subphenogroups of acute heart failure with preserved ejection fraction: comprehensive proteomics and pathway analysis.

Background: Heterogeneity of heart failure with preserved ejection fraction (HFpEF) results in significant challenges for treatment development. Identifying and characterising distinct HFpEF phenogroups may aid in tailoring therapeutic strategies for these patients. The objective of this study was to assess proteomic patterns of HFpEF phenogroups identified through a machine-learning-based clustering model, with the aim of uncovering specific biological pathways associated with each phenogroup.

Use of a Shoulder-Mounted Wearable Sensor Prototype Designed to Detect Opioid-Related Overdose: A Qualitative User Experience Study.

Background: For over a decade, drug overdose has been the leading cause of injury and accidental death in the United States. Most fatal overdoses involve opioids and occur during solitary drug use events when no one is available to initiate lifesaving responses (eg, naloxone). While there is a growing interest in devices providing early overdose detection and automated responses, little research has engaged end users in a device design process.

A global map for introgressed structural variation and selection in humans.

Genetic introgression from Neanderthals and Denisovan has shaped modern human genomes; however, introgressed structural variants (SVs ≥50 base pairs) remain challenging to discover. We integrated high-quality phased assemblies from four new Papua New Guinea (PNG) genomes with 94 published assemblies of diverse ancestry to infer an archaic introgressed SV map. Introgressed SVs are overall enriched in genes (44%, n=1,592), including critical genomic disorder regions, and most abundant in PNG.

Diversity, distribution, and population structure of Escherichia coli in the lower gastrointestinal tract of humans.

Several studies report the diversity, and population structure of Escherichia coli (E. coli) in the human gut, but most used faecal specimens as the source of E. coli for analysis.

Longitudinal Proteomic Profiling of T Cell Differentiation In Vivo Reveals Biochemical Remodeling Underlying Exhaustion.

CD8 T cell exhaustion impedes immune responses to cancer and chronic infections, and a biochemical understanding of exhaustion is essential to improving immunotherapy. Here, we present the first longitudinal protein abundance and phosphoproteomic analysis of antigen-specific CD8 T cells undergoing differentiation in vivo during acute (LCMV-Armstrong) and chronic (LCMV-Clone 13) infection. Comparing protein abundance across the two infection conditions identified over 180 known and novel exhaustion-associated proteins, including proteins missed by transcriptional analyses.

Safety and efficacy of the Woven EndoBridge (WEB) device in ruptured intracranial aneurysms: a systematic review and updated meta-analysis.

Background: The Woven EndoBridge (WEB; Terumo) device has gained increasing recognition for treating ruptured intracranial aneurysms (RIAs) due to its ability to disrupt flow with a single implant, avoiding long-term dual antiplatelet therapy. Despite multiple studies, a comprehensive synthesis of recent evidence remains lacking. This study addresses this gap through a systematic review and meta-analysis evaluating the WEB device's safety and efficacy in RIA management.

SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.

SARS-CoV-2 encodes numerous virulence factors, yet their precise mechanisms of action remain unknown. We provide evidence that the SARS-CoV-2 nonstructural protein 15 (nsp15) enhances viral virulence by suppressing the production of viral double-stranded (dsRNA), a potent inducer of antiviral signaling. The viral variants lacking nsp15 endoribonuclease activity elicited higher innate immune responses and exhibited reduced replication in human stem cell-derived lung alveolar type II epithelial cells, as well as in the lungs of infected hamsters.

Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.

Unlabelled: Histone deacetylases (HDAC) regulate diverse pathways in cancer cells. Previously, we identified that Ewing sarcoma tumors, which are caused by a translocation between the EWSR1 and FLI1 genes (EWS::FLI1), are sensitive to drugs that target DNA replication, including the RRM1 and RRM2 subunits of ribonucleotide reductase, and the ATR-checkpoint kinase 1 (CHK1)-WEE1 signaling pathway. In this study, we identified that multiple HDAC inhibitors, including fimepinostat, romidepsin, and panobinostat, downregulate the levels of the RRM1, RRM2, CHK1, and WEE1 proteins in Ewing sarcoma cells and impair DNA replication.

Drug-Coated Balloon Versus Stent Angioplasty in Patients with Intracranial Atherosclerotic Disease: A Systematic Review and Meta-Analysis.

Introduction: Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, particularly in high-risk populations. Endovascular treatment options, including drug-coated balloon (DCB) angioplasty and stent angioplasty (SA), have been explored as alternatives for patients with severe stenosis or refractory symptoms. However, the comparative efficacy and safety of these interventions remain a topic of debate.

Comprehensive assessment of the feasibility, safety, and efficacy of the pressure cooker technique in the treatment of brain arteriovenous malformations: Systematic review and meta-analysis.

Purpose: The Pressure Cooker Technique (PCT) is an endovascular technique for brain arteriovenous malformations (bAVMs) that can minimize reflux and inadvertent embolization compared with conventional techniques, leading to a safer and more controlled embolization. This systematic review and meta-analysis aimed to assess the feasibility, safety, and efficacy of PCT for bAVMs.

Methods: We searched PubMed, Embase, and Web of Science databases.

CAVaLRi: An Algorithm for Rapid Identification of Diagnostic Germline Variation.

Clinical exome and genome sequencing (ES/GS) have become indispensable diagnostic tools for rare genetic diseases (RGD). However, the interpretation of ES/GS presents a substantial operational challenge in clinical settings. Test interpretation requires the review of hundreds of genetic variants, a task that has become increasingly challenging given the rising use of ES/GS.

Middle meningeal artery embolization for chronic subdural hematoma: a meta-analysis of randomized controlled trials with trial sequential analysis.

Middle meningeal artery embolization (MMAE) has gained attention as an innovative approach for chronic subdural hematoma (cSDH). It can be utilized either as a standalone treatment or as an adjunct to surgical evacuation, with the primary goal of reducing the risk of cSDH recurrence. Therefore, we aim to investigate the efficacy and safety of MMAE in cSDH patients.

Integrated transcriptomic and regulatory RNA profiling reflects complex pathophysiology and uncovers a conserved gene signature in end stage heart failure.

Background: Heart failure (HF) is a complex syndrome. Despite availability of multiple treatment options, the mortality remains high and the quality of life poor. Better understanding of the underlying pathophysiological processes can lead to development of novel therapies.

Severe Cognitive Decline in Long-term Care Is Related to Gut Microbiome Production of Metabolites Involved in Neurotransmission, Immunomodulation, and Autophagy.

Aging-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment (CI) in 159 residents of long-term aged care.

Hydroxocobalamin for the treatment of vasoplegia after lung transplantation: A case series.

Background: The use of hydroxocobalamin following lung transplantation has not been previously reported. We present a series of 3 cases where hydroxocobalamin was used to treat postoperative vasoplegia.

Methods: We conducted a single-center, retrospective review of lung transplantation recipients from January 2016 to December 2020.

Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations.

Background: We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year.

Methods: Plasma samples from individuals with HF with reduced ejection fraction (HFrEF; ejection fraction <40%; training/validation n=1247/762) and preserved ejection fraction (HFpEF; ejection fraction ≥50%; training/validation n=725/785) from 3 independent studies were run on the SomaScan Assay measuring ≈5000 proteins. Machine learning techniques resulted in unique 17- and 14-protein models for HFrEF and HFpEF that predict 1-year mortality.

Systemic delivery of AAV5, AAV8, and AAV9 packaging a C5-12-microdystrophin-FLAG expression cassette in non-human primates.

Safely achieving therapeutic expression levels with adeno-associated virus (AAV) gene therapy is a significant challenge for treating the large muscle mass in humans. Non-human primates (NHPs) provide a more accurate assessment of the feasibility of achieving an effective and safe dose than rodents. Here, we compared a single systemic administration of AAV5, AAV8, or AAV9 in NHPs, each packaging the C5-12-microdystrophin-FLAG expression cassette.

Virtual simulation for flow-diverter selection and sizing in the endovascular treatment of intracranial aneurysms: A systematic review and meta-analysis.

Background: Endovascular treatment (EVT) of intracranial aneurysms (IAs) has improved significantly with the integration of virtual simulation software (VSS) in surgical planning and device selection. Despite promising outcomes, discrepancies remain between physician and VSS recommendations. This review synthesizes evidence on (1) comparisons between VSS-chosen and physician-chosen dimensions; (2) VSS-chosen and postoperative measured dimensions; and (3) the success rate of VSS-guided device deployment.