mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.

Diffuseness of coronary artery disease impacts on immediate hemodynamic and predicted clinical outcomes.

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Role of transforming growth factor-β1 in regulating adipocyte progenitors.

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206 M2-like macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism, remains unknown.

Oxytocin levels in response to CRH administration in hypopituitarism and hypothalamic damage: a randomized, crossover, placebo-controlled trial.

Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in patients with hypopituitarism and hypothalamic damage (HHD), that might be associated with neuropsychological deficits and sexual dysfunction, leading to worse quality of life (QoL). Therefore, identifying a provocative test to diagnose an OXT-D will be important. Corticotropin-releasing hormone (CRH) is a candidate for such a test as it increases oxytocin secretion in animal models.

Multi-faceted examination of a deepwater seamount reveals ecological patterns among coral and sponge communities in the equatorial Pacific.

Spatial changes in benthic community structure have been observed across natural gradients in deep-sea ecosystems, but these patterns remain under-sampled on seamounts. Here, we identify the spatial composition and distribution of coral and sponge taxa on four sides of a single central Pacific equatorial "model" seamount within the US EEZ surrounding the Howland and Baker unit of the Pacific Islands Heritage Marine National Monument. This seamount rises from 5,000 + m to mesophotic depths of 196 m, and is influenced by the Equatorial Undercurrent.

Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung.

Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

How Pediatric Readiness can Impact Pediatric Trauma From Every Day to Mass Events.

Disaster events such as weather events and mass casualty events are increasing in frequency and severity. Caring for children during a surge requires a regional approach given limited pediatric inpatient capacity and expertise. During the 2024 American Academy of Pediatrics National Convention and Exhibition, the Section on Surgery and Council on Children and Disasters (COCD) partnered to present a joint symposium emphasizing importance of pediatric readiness and disaster preparedness and role of pediatric trauma surgeons in disaster preparedness and response in all communities.

Comprehensive Review of Multilingual Patient-Reported Outcome Measures for Dysphonia.

Introduction: Patient-reported outcome measures (PROMs) represent an important part of a comprehensive voice assessment for clinical care and research. Access to multilingual PROMs enables inclusion of information from diverse patient populations. This review compares available translated and validated PROMs for adult dysphonia.

Influence of edentulous areas on the accuracy of the maximum intercuspal position recorded by using different intraoral scanners or an artificial intelligence-based program.

Statement Of Problem: Intraoral scans can be articulated in maximum intercuspal position (MIP) by using an artificial intelligence (AI) based program; however, the impact of edentulous areas on the accuracy of the MIP located using this AI-based program is unknown.

Purpose: The purpose of this in vitro study was to assess the impact of edentulous areas (0, 1, 2, 3, and 4 posterior mandibular teeth) on the accuracy of the MIP located using 3 intraoral scanners (IOSs) and an AI-based program.

Material And Methods: Stone casts articulated in MIP in an articulator were digitized (T710).

Identifying Gaps in Detection of Heart Valve Disease in Australia: A Population Survey.

Background: Untreated severe heart valve disease (HVD) is associated with premature mortality. Research shows low population awareness of when to seek assessment and low focus on cardiac auscultation by physicians in primary care settings. We studied contemporary public knowledge of HVD and assessment by their general practitioner (GP) in Australia.

Differential impacts of strabismic and anisometropic amblyopia on the mesoscale functional organization of the human visual cortex.

We employed high-resolution fMRI to distinguish the impacts of anisometropia and strabismus amblyopia on the evoked ocular dominance (OD) response. Sixteen amblyopic participants (8 females) plus 8 individuals with normal vision (1 female), participated in this study for whom, we measured the difference between the response to stimulation of the two eyes, across areas V1-V4.In controls, the evoked OD response formed the expected striped pattern within V1.

Comparison of Imaging Findings between Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis on Sinus CT: Importance of High-Density Opacification of the Paranasal Sinuses.

Background And Purpose: Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) are the most common causes of chronic sinusitis from systemic granulomatous diseases. While both are small- to medium-sized vasculitis with necrotizing granulomas, they have different clinical courses and prognoses. High-density sinus opacification has been reported in allergic fungal sinusitis with eosinophilic infiltrates.

Cerebral blood volume index in the era of thrombectomy-treated large and medium vessel ischemic strokes.

The cerebral blood volume index (CBV index) is a perfusion-based marker of collateral status. Several real-world data analyses from observational stroke cohorts have established relationships between this parameter and a range of favorable and unfavorable stroke outcomes. In this review, an overview is provided of the CBV index, within the context of thrombectomy-treated large vessel and medium vessel occlusion ischemic strokes.

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Finding a constrained number of predictor phenotypes for multiple outcome prediction.

Background: Prognostic models help aid medical decision-making. Various prognostic models are available via websites such as MDCalc, but these models typically predict one outcome, for example, stroke risk. Each model requires individual predictors, for example, age, lab results and comorbidities.

Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer.

After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge.

T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice.

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance.

Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability.

Objective: Callous-unemotional traits (CU), characterized as a lack of guilt and empathy; and irritability, a tendency to show anger and frustration; are 2 risk factors for externalizing behavioral problems. Externalizing problems, CU and irritability are all heritable. However, there is a dearth of studies examining the genetic and environmental associations between the 3 domains.

Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages.