Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Precision fetal cardiology detects cyanotic congenital heart disease using maternal saliva metabolome and artificial intelligence.

Prenatal sonographic diagnosis of congenital heart disease (CHD) can lead to improved morbidity and mortality. However, the diagnostic accuracy of ultrasound, the sole prenatal screening tool, remains limited. Failed prenatal or early newborn detection of cyanotic CHD (CCHD) can have disastrous consequences.

Transcription factor EB (TFEB) activity increases resistance of TNBC stem cells to metabolic stress.

Breast cancer stem cells (CSCs) are difficult to therapeutically target, but continued efforts are critical given their contribution to tumor heterogeneity and treatment resistance in triple-negative breast cancer. CSC properties are influenced by metabolic stress, but specific mechanisms are lacking for effective drug intervention. Our previous work on TFEB suggested a key function in CSC metabolism.

Effect of electronic cigarette atomising power and flavour on aerosol size-segregated metal concentration and inhalation risk.

Introduction: Although numerous studies have estimated the inhalation dose of metals emitted from electronic cigarettes (e-cigs), the impact of factors including aerosol size and the atomising power of e-cig aerosols on estimating the inhalation dose of metals remains underexplored. A comprehensive understanding of these determinants is essential to assess the health risks associated with inhaling e-cig aerosols, which may contain potentially harmful metals.

Objectives: The aim of this study is to elucidate the mass and inhalation doses of potentially harmful metals in e-cig aerosols by different particle size and their association with the various atomising powers of e-cig devices and flavours.

Prolactin-induced sensitization of trigeminal nociceptors promotes migraine co-morbidity in endometriosis.

Background: Women with endometriosis are more likely to have migraine. The mechanisms underlying this co-morbidity are unknown. Prolactin, a neurohormone secreted and released into circulation from the anterior pituitary, can sensitize sensory neurons from female, but not male, rodents, monkeys and human donors.

Improvement in Distress Tolerance as a Mechanism of Symptom Reduction During Intensive Exposure and Response Prevention-Based Treatment for OCD.

Exposure and Response Prevention (ERP) is an effective treatment for obsessive-compulsive disorder (OCD), yet the specific underlying mechanisms by which ERP improves symptoms remain unclear. Initial theories suggested that habituation to triggering events and stimuli was the key therapeutic factor in ERP, while other theories highlight the role of developing the ability to tolerate distress, rather than reduction of distress. The current study examined improvements in distress tolerance as a mechanism of OCD, anxiety, and depressive symptom reductions during an ERP-based intensive program.

Did Finerenone Improve Health Status in the FINEARTS Trial?: A Critical Reevaluation of the Analysis of Patient-Reported Outcomes in Heart Failure.

Patient-reported health status is an important assessment of patients with heart failure, but current approaches have substantial methodological and analytical limitations. Changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) are commonly presented as a measure of the effect of drugs and devices, most often as the between-group difference in population means or as the odds of showing threshold changes of 5, 10, 15, and 20 points. However, the presentation of mean differences is based on statistical assumptions that are routinely violated in most trials.

Fitness for Purpose of Text-to-Image Generative Artificial Intelligence Image Creation in Medical Imaging.

The recent emergence of text-to-image generative artificial intelligence (AI) diffusion models such as DALL-E, Firefly, Stable Diffusion, and Midjourney has been touted with popular hype about the transformative potential in health care. This hype-driven, rapid assimilation comes with few professional guidelines and without regulatory oversight. Despite documented limitations, text-to-image generative AI creations have permeated nuclear medicine and medical imaging.

Psychometric Evaluation of the Scleroderma Skin Questionnaire: A Novel Patient Reported Outcome for Skin Disease in Patients with Systemic Sclerosis.

Objective: To evaluate the psychometric properties of the Scleroderma Skin Questionnaire (SSQ), a novel patient-reported outcome (PRO) to assess systemic sclerosis (SSc) related skin symptoms.

Methods: The SSQ was administered to 799 adults (mean age 52.7; 82% female) enrolled in the SSc Collaborative National Quality and Efficacy Registry (CONQUER).

Association between abatacept exposure levels and infection occurrence in patients with rheumatoid arthritis: post hoc analysis of the AVERT-2 study.

Objective: To determine if higher serum exposure during subcutaneous (SC) abatacept treatment was associated with an increased infection risk in adult patients with early rheumatoid arthritis (RA).

Methods: Data from AVERT-2 (Assessing Very Early Rheumatoid arthritis Treatment-2, NCT02504268), a randomized, placebo-controlled study in anticitrullinated protein antibody- positive patients with early RA, were analyzed. A post hoc population pharmacokinetic (PPK) analysis was performed.

An Update on the Clinical Management of Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is an infection caused by the Leishmania protozoa, which are primarily transmitted through bites of infected female sandflies. This article provides a comprehensive overview of the clinical management of CL, including an in-depth analysis of its epidemiology, prevention and control measures, diagnostic modalities - particularly molecular and serological, differential diagnosis with other lesions, and treatment options. Also discussed are recent concerns regarding the endemicity of CL, with a focus on the significant rise in travel-related cases as well as locally acquired cases, providing insight into the changing epidemiological landscape.

VvATG18a participates in grape resistance to gray mold induced by BR signaling pathway.

Autophagy plays an important role in responding to necrotrophic pathogens and plant signal hormones. Brassinosteroids (BRs) are a class of natural steroidal phytohormones that effectively regulated the disease resistance responses in grape. However, the molecular mechanism of BR-autophagy networks responsible for activation of host defense against gray mold remained to be elucidated.

Appropriate Use Criteria for Neoplastic Compression Fractures.

Background Context: Clinical outcomes are directly related to patient selection and treatment indications for improved quality of life. With emphasis on quality and value, it is essential that treatment recommendations are optimized.

Purpose: The purpose of the North American Spine Society (NASS) Appropriate Use Criteria (AUC) is to determine the appropriate (ie, reasonable) multidisciplinary treatment recommendations for patients with metastatic neoplastic vertebral fractures across a spectrum of more common clinical scenarios.

Targeted Endodontic Access Preparation: Comparing Grid-Guided and Freehand CBCT Techniques.

Introduction: Endodontic access is often one of the most challenging aspects of treatment, particularly in cases involving locating calcified or missed canals, or when performing selective retreatments of a targeted root. Therefore, the purpose of this study is to compare the accuracy of targeted accesses made using prefabricated grid to those made using freehand techniques with CBCT measurements METHODS: Twenty extracted maxillary molars were mounted into the TrueJaw maxillary model (PlanB Dental, CA). To replicate a clinical scenario where the tooth is extensively restored or has a calcified pulp chamber, the build-up material was intentionally placed directly over the canal orifices.

Pathogenesis of bovine H5N1 clade 2.3.4.4b infection in Macaques.

Since early 2022 highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the United States (US) with spillover into several mammalian species. In March 2024, HPAIV H5N1 clade 2.3.

Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.

Nicotinic Acetylcholine Receptor Expression in Merkel Cell Carcinoma Is Associated With Clinical and Histopathologic Parameters.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored.

Safety and Effectiveness of EUS-Guided Gallbladder Drainage in Patients with Cirrhosis: An International Multicenter Experience.

Introduction EUS-guided gall bladder drainage (EUS-GBD) for management of symptomatic gallbladder disease has been shown to be safe and effective in high surgical risk patients with data lacking in patients with cirrhosis. We sought to study the safety and effectiveness of EUS-GBD in cirrhotic compared to non-cirrhotic patients. Methods Retrospective review of patients who underwent EUS-GBD at four (3 US and 1 Spain) international tertiary care centers.

No evidence for sex-differential transcriptomes driving genome-wide sex-differential natural selection.

Sex differences in human transcriptomes have been argued to drive sex-differential selection (SDS). Here, we show that previous evidence supporting this hypothesis has been largely unfounded. We develop a method to test for a genome-wide relationship between sex differences in expression and selection on expression-influencing alleles (expression quantitative trait loci [eQTLs]).

Feasibility and acceptability of an online expressive writing intervention for rural breast cancer survivors: A randomized controlled trial.

Purpose: Rural breast cancer survivors (BCS) have unique unmet psychosocial needs that affect quality of life (QOL). Expressive writing (EW) has been shown to improve QOL in cancer survivors, however, its applicability is unclear among rural individuals. This pilot study explores the feasibility and acceptability of an online expressive writing (EW) intervention among rural breast cancer survivors (BCS).

Twenty-four-hour pattern of children with febrile seizures presenting to a United States Pediatric Emergency Department.

Background: Febrile seizure (FS) is the most common convulsive disorder in children. Understanding its time-of-day pattern can provide insight into mechanisms and prevention.

Purpose: We explored clock-time variation of FS presentations of children to a US pediatric emergency department (PED) in comparison to two control cohorts: one (n = 5719) like-aged children presenting solely with fever, i.

Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Background: Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.

Materials And Methods: We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages.

Gait during community ambulation and laboratory-based walking in people with mild traumatic brain injury.

Background: Gait impairments are common in individuals with mild traumatic brain injury (mTBI), presenting in the acute phase and often persisting in subtle ways over time. Despite the prominence of laboratory gait evaluations, a comprehensive understanding of gait deficits post-mTBI necessitates the examination of various gait domains in real-world environments. Assessing gait during a community ambulation task (CAT) may capture real-world challenges and influence focused interventions or rehabilitation in individuals with mTBI.