Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer.

Colorectal cancer is the second leading cause of cancer mortality in the United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful in treating a subset of patients with colorectal cancer, the response rates remain low. We have found that riluzole, a well-tolerated FDA-approved oral medicine for treating amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth of colon cancer cells in syngeneic immune-competent mice.

Nucleolin acute degradation reveals novel functions in cell cycle progression and division in TNBC.

Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Technical obstacles still limit our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis. Since most nucleolar proteins are essential, their abrogation cannot be achieved through conventional approaches.

Outcome of Patients With Systolic Heart Failure Who Underwent Sympathectomy for Ventricular Arrhythmia.

Cardiac sympathetic denervation (CSD) is a surgical procedure increasingly used for managing ventricular arrhythmia refractory to conventional medical therapy. Long-term outcomes of CSD in patients with systolic heart failure has not been well studied. This observational study aimed to evaluate the medical co-morbidities and outcomes of patients with systolic heart failure who underwent CSD performed as treatment for ventricular arrhythmia refractory to conventional therapy.

Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.

Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions.

Outcomes of a same day discharge protocol in patients undergoing mastectomy and implant reconstruction.

Background: Finite hospital resources has required a closer look at resource allocation. This has prompted a shift toward same day surgeries and a focus on reducing hospital readmissions. Following the institution of a same day discharge protocol for mastectomy and mastectomy with immediate reconstruction, we sought to assess differences in the length of stay and readmission rates.

SIX4 Controls Anti-PD-1 Efficacy by Regulating STING Expression.

Unlabelled: The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective in many types of cancer. We have identified SIX4 as a significant regulator of STING expression in colon cancer cells.

Physiologic Variants of Cardiac Conduction (Aberration, Gap, Supernormal Conduction).

Wide QRS complexes during supraventricular rhythms can be caused by fixed bundle branch block, functional (intermittent) bundle branch block, preexcitation, or toxic/metabolic causes. Functional bundle branch block can be caused by long-short aberrancy (usually physiologic), or acceleration/deceleration dependent aberrancy (usually pathologic). Electrocardiogram criteria have been proposed to differentiate aberration from ventricular tachycardia; they are not always accurate.

Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation.

Objective: Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention.

Methods: A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure.

Left Atrial Appendage Clip Reentry: The Case for Ablation From the Appendage to Left Pulmonary Veins.

Convergent hybrid atrial fibrillation ablation combines epicardial posterior left atrial ablation with catheter pulmonary vein isolation. Concomitant left atrial appendage AtriClip placement has recently been included to mitigate stroke risk. We describe a 72-year-old woman with long-standing persistent atrial fibrillation in whom atrial flutter with reentry encircling the AtriClip developed 18 months after a successful convergent procedure.

Progression of ECG in hydroxychloroquine overdose.

Hydroxychloroquine overdose is associated with myocardial toxicity and conduction disorders. We report a case of hydroxychloroquine overdose that demonstrated a rapid progressive intraventricular conduction delay and QT prolongation resulting in significant bradycardia and shock despite aggressive treatment. We describe the rare capture of abrupt abnormalities of this overdose in sequential electrocardiograms in the immediate hours post-ingestion.

Shift in HPAI infection dynamics causes significant losses in seabird populations across Great Britain.

This focus article has been prepared by Marco Falchieri, Scott M. Reid, Craig S. Ross, Joe James, Alexander M.

Why is the patient still symptomatic after myectomy for HCM!

We describe the case of a young female patient with hypertrophic cardiomyopathy (HCM) with a dual chamber implantable cardioverter defibrillator (ICD), and complete heart block from a prior septal ablation procedure. Due to persistent left ventricular outflow tract (LVOT) obstruction and symptoms, she underwent surgical myectomy. Her exertional symptoms continued despite improved LVOT flow parameters.

Slit2/Robo1 signaling inhibits small-cell lung cancer by targeting β-catenin signaling in tumor cells and macrophages.

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue.

PUMILIO competes with AUF1 to control DICER1 RNA levels and miRNA processing.

DICER1 syndrome is a cancer pre-disposition disorder caused by mutations that disrupt the function of DICER1 in miRNA processing. Studying the molecular, cellular and oncogenic effects of these mutations can reveal novel mechanisms that control cell homeostasis and tumor biology. Here, we conduct the first analysis of pathogenic DICER1 syndrome allele from the DICER1 3'UTR.

Variation and correlation in the timing of breeding of North Atlantic seabirds across multiple scales.

Timing of breeding, an important driver of fitness in many populations, is widely studied in the context of global change, yet despite considerable efforts to identify environmental drivers of seabird nesting phenology, for most populations we lack evidence of strong drivers. Here we adopt an alternative approach, examining the degree to which different populations positively covary in their annual phenology to infer whether phenological responses to environmental drivers are likely to be (a) shared across species at a range of spatial scales, (b) shared across populations of a species or (c) idiosyncratic to populations. We combined 51 long-term datasets on breeding phenology spanning 50 years from nine seabird species across 29 North Atlantic sites and examined the extent to which different populations share early versus late breeding seasons depending on a hierarchy of spatial scales comprising breeding site, small-scale region, large-scale region and the whole North Atlantic.

Drivers of genomic loss of heterozygosity in leiomyosarcoma are distinct from carcinomas.

Leiomyosarcoma (LMS) is a rare, aggressive, mesenchymal tumor. Subsets of LMS have been identified to harbor genomic alterations associated with homologous recombination deficiency (HRD); particularly alterations in BRCA2. Whereas genomic loss of heterozygosity (gLOH) has been used as a surrogate marker of HRD in other solid tumors, the prognostic or clinical value of gLOH in LMS (gLOH-LMS) remains poorly defined.

Workup for Suspected Brugada Syndrome: Two Case Reports for the General Practitioner.

While a large proportion of ST-segment elevation on EKG is related to myocardial ischemia, the differential diagnosis must include pericarditis, channelopathies, and various genetic conditions. Identifying and working up such abnormalities present a challenge to primary care providers (PCPs). We present two clinical cases of young male patients with ST-segment elevation in anteroseptal leads suspicious for Brugada syndrome and show how to risk stratify and manage them.

Mass COVID-19 patient screening using UvsX and UvsY mediated DNA recombination and high throughput parallel sequencing.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions.

Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.

Purpose: Soft tissue and bone sarcomas are rare malignancies that exhibit significant pathologic and molecular heterogeneity. Deregulation of the CDKN2A-CCND-CDK4/6-retinoblastoma 1 (Rb) pathway is frequently observed in about 25% of unselected sarcomas and is pathognomonic for specific sarcoma subtypes. This genomic specificity has fueled the clinical evaluation of selective CDK4/6 inhibitors in sarcomas.