The N-degron pathway mediates the autophagic degradation of cytosolic mitochondrial DNA during sterile innate immune responses.

The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Response to ritlecitinib with or without narrow-band UVB add-on therapy in patients with active nonsegmental vitiligo: results from a phase 2b extension study.

Background: Ritlecitinib demonstrated efficacy in a phase 2b trial of nonsegmental vitiligo.

Objective: To evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band UVB (nbUVB) phototherapy in patients with nonsegmental vitiligo.

Methods: Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200mg for 4 weeks then 50mg for 20 weeks, with or without nbUVB phototherapy 2x/week.

The Association between Obesity and Efficacy of Psoriasis Therapies: An Expert Consensus Panel.

Background: Psoriasis is a chronic inflammatory skin disease often associated with obesity. Psoriasis therapies may be less effective in obese patients. The purpose of this expert consensus panel is to evaluate the relationship between obesity and efficacy of psoriasis therapies, thereby optimizing patient care.

Validation of a High Bleeding Risk Definition in Cancer Patients undergoing Percutaneous Coronary Intervention.

Aim: Due to the absence of validated bleeding risk tools in cancer patients undergoing percutaneous coronary intervention (PCI), we aimed to validate an adapted version of the Academic Research Consortium (ARC) High Bleeding Risk (HBR) criteria.

Methods: Consecutive patients with active or remission cancer undergoing PCI between 2012 and 2022 at Mount Sinai Hospital (New York, USA) were included. Patients were considered at HBR if they met at least one of the major ARC-HBR criteria, other than cancer, or two minor criteria.

Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.

Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.

Optimization of a Mobile Transdiagnostic Emotion Regulation Intervention for University Students: A Micro-Randomized Trial.

Increasing mental health problems among university students highlight the need for scalable, effective solutions. We have developed a transdiagnostic mobile intervention called ROOM, promoting adaptive emotion regulation (ER) skills among university students. Understanding how the intervention works and optimising content and delivery is essential for creating an effective and adaptive system.

Promoting early goals of care conversations in the CICU with a surprise question-based EHR workflow.

Background: The Surprise Question (SQ) - Would you be surprised if this patient died within the next 6 months? - is a validated tool for mortality prediction. The Mount Sinai Cardiac Intensive Care Unit (CICU) incorporated the SQ into a novel EHR workflow to identify patients who would benefit from early initiation of Palliative Care (PC).

Methods: Implementation of the SQ proceeded in two steps.

Intervention-Related Changes in Coping Ability Drives Improvements in Mood and Quality of Life for Patients Taking Adjuvant Endocrine Therapy.

Objective: A recent randomized trial of a group psychosocial telehealth intervention (STRIDE) improved anxiety, depression, quality of life (QOL), symptom distress, coping, and self-efficacy to manage symptoms related to taking adjuvant endocrine therapy (AET) in women with non-metastatic hormone receptor-positive breast cancer. This study examined whether changes in coping and self-efficacy mediated intervention effects on anxiety, depression, QOL, and symptom distress.

Method: Women (N = 100) were recruited between 10/2019-06/2021 from Massachusetts General Hospital and were randomized to STRIDE or to the medication monitoring control group.

Evaluating post-cardiac arrest blood pressure thresholds associated with neurologic outcome in children: Insights from the pediRES-Q database.

Background: Current Pediatric Advanced Life Support Guidelines recommend maintaining blood pressure (BP) above the 5th percentile for age following return of spontaneous circulation (ROSC) after cardiac arrest (CA). Emerging evidence suggests that targeting higher thresholds, such as the 10th or 25th percentiles, may improve neurologic outcomes. We aimed to evaluate the association between post-ROSC BP thresholds and neurologic outcome, hypothesizing that maintaining mean arterial pressure (MAP) and systolic blood pressure (SBP) above these thresholds would be associated with improved outcomes at hospital discharge.

Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies.

Background: Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.

Induction of Plasmalemmal vesicle-associated protein exacerbates glomerular endothelial injury in thrombotic microangiopathy.

Glomerular endothelial cell (GEnC) injury is a common feature across the wide spectrum of glomerular diseases. We recently reported that the endothelial-specific knockout of increases the susceptibility to GEnC injury and subsequent development of subacute thrombotic microangiopathy (TMA). However, the mechanism(s) mediating GEnCs response to injury in TMA are poorly understood.

The Winner and still champion: Nodule volume doubling times.

There have been enormous advances in the approach to assessing malignancy status of indeterminate pulmonary nodules including risk models, image based biomarkers and numerous types of biologic and molecular markers. All of these have the advantage of guiding further workup once the nodule is identified. The traditional method, especially for smaller nodules relies primarily on assessing whether a nodule changes in size over time and is a feature in virtually every management protocol for both screen detected as well as incidentally detected nodules.

Development of Etf-3-specific nanobodies to prevent Ehrlichia infection and LNP-mRNA delivery in cellular and murine models.

Ehrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and causes human monocytic ehrlichiosis. Ehrlichia translocated factor-3 (Etf-3) is a type IV secretion system effector that binds host-cell ferritin light chain and induces ferritinophagy, thus increasing cellular labile iron pool for Ehrlichia proliferation. To further characterize roles of Etf-3 in Ehrlichia infection, we produced immune libraries of Etf-3-specific nanobodies (Nbs).

Vitamin D binding protein genetic isoforms, serum vitamin D, and cancer risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Associations between vitamin D biochemical status and cancer may be modified by vitamin D binding protein isoforms which are encoded by GC (group-specific component). We examined interactions between serum 25-hydroxyvitamin D [25(OH)D], the Gc isoforms Gc1-1, Gc1-2, and Gc2-2, and cancer risk within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort based on 3,795 cases and 3,856 controls. Multivariable-adjusted logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer risk according to 25(OH)D quantiles, stratified by Gc isoform.

Does the outcome of acupuncture differ according to the location of sham needling points in acupuncture trials for migraine? A systematic review and network meta-analysis.

Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023.

Loculated Fluid Visualized in Hepatorenal Space with Point-of-care Ultrasound in Patient with Pelvic Inflammatory Disease Caused by Group A Streptococcus: Case Report.

Introduction: Point-of-care ultrasound (POCUS) is a screening and diagnostic modality frequently used in the emergency department to assess patients with abdominal pain.

Case Report: We present a case describing the unusual finding of intraperitoneal fluid with loculations visualized in the right upper quadrant of the abdomen in a patient ultimately diagnosed with pelvic inflammatory disease (PID) with ruptured tubo-ovarian abscess caused by group A streptococcus (GAS), a pathogen rarely implicated in the disease.

Conclusion: Uncommon findings on abdominal POCUS should trigger further investigation.

RTN1A mediates diabetes-induced AKI-to-CKD transition.

Diabetic patients have increased susceptibility to acute kidney injury (AKI), and AKI could progress to chronic tubulointerstitial injury and fibrosis, referred to as AKI-to-chronic kidney disease (AKI-to-CKD) transition. However, whether diabetes directly promotes AKI-to-CKD transition is not known. We previously showed that reticulon-1A (RTN1A), a gene highly upregulated in injured renal tubular epithelial cells (RTECs), promotes AKI-to-CKD transition in nondiabetic settings.

American Association of Bronchology and Interventional Pulmonology Essential Knowledge in Interventional Pulmonology Series: Selected Topics in Malignant Pleural Disease.

The goal of the American Association of Bronchology and Interventional Pulmonology Essential Knowledge in Interventional Pulmonology Series is to provide clinicians with concise, up-to-date reviews of important topics in the field of interventional pulmonology. This 3-year alternating rotation of primary topics will start with a focus on selected topics in malignant pleural disease. In this article, we update the reader on malignant pleural effusion in 3 parts: part 1-diagnosis, focusing on imaging and fluid biomarkers; part 2-management, with review of multimodal approaches, cost considerations, and evolving targeted therapies; and part 3-pleural mesothelioma.

Estimates of walking prevalence and volume for U.S. cancer survivors and those without cancer: overall, by sex, and by race and ethnicity.

Purpose: This paper estimated overall, by sex, and by race and ethnicity walking behaviors in the cancer survivor population, where prevalence is not known, compared to those without cancer.

Methods: Data from the 2015 and 2020 National Health Interview Survey (n = 54,542) were used to estimate walking behaviors. Multivariable logistic regression models estimated walking behavior prevalence with predictive margins and volume of weekly minutes overall and stratified by sex and race/ethnicity.

Gender, Race, and Regional Disparities in Leading Authorships of Gastroenterology and Hepatology Randomized Controlled Trials.

Background And Aims: To investigate gender, racial, ethnic, and regional disparities in first and senior authorship positions in gastroenterology/hepatology-related randomised controlled trials (RCT).

Method: Retrospective bibliometric analysis of PubMed-indexed RCTs published between January 2000 to December 2022 in leading journals with an impact factor of at least five.

Results: 943 RCTs met our inclusion criteria, providing a participant pool of 301 female (15.