Inclusion in neurological research: empowering people living with neurological diseases.

The value of involving people living with diseases in the research process is increasingly recognized by professional associations and regulatory agencies alike. Patient contributions range from disease prevention and diagnosis to medication planning, and from advocacy to guideline production and clinical trial design. Thanks to the efforts of activists and advocates, new models of patient inclusion in medical research are being developed to replace outdated non-participative and tokenistic paradigms.

Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization.

Acute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed a two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration of genetic variants across the genome in a study population of 10,630 AP cases and 844,679 non-AP individuals revealed multiple lipidome entities significantly associated with AP risk.

Regulation of fibronectin and collagens type I, III and VI by TNF-α, TGF-β, IL-13, and tofacitinib.

Understanding how inflammatory cytokines influence profibrogenic wound healing responses in fibroblasts is important for understanding the pathogenesis of fibrosis. TNF-α and IL-13 are key cytokines in Th1 and Th2 immune responses, respectively, while TGF-β1 is the principal pro-fibrotic mediator. We show that 12-day fibroblast culture with TNF-α or IL-13 induces fibrogenesis, marked by progressively increasing type III and VI collagen formation, and that TGF-β1 co-stimulation amplifies these effects.

Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80 liver-associated macrophages.

Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study investigated the impact of mRNA/LNP administration on liver-associated macrophages at the transcriptomic and epigenetic levels in a mouse model.

Usage of double injector for efficient mixing of the fuel behind the ramp injector at supersonic combustion chamber.

This investigation presents extensive computational analyses of the compressible flow near ramp injector with double circular injectors at supersonic combustor of scramjet engine. Comparison of the fuel mixing and fuel jet penetration of hydrogen jet are done for two injector configurations at free stream Mach number of 2. The simulation of the supersonic flow near ramp injector is done via solving RANS equations with computational fluid dynamic technique.

Speciation and historical invasions of the Asian black-spined toad (Duttaphrynus melanostictus).

Animal translocations provide striking examples of the human footprint on biodiversity. Combining continental-wide genomic and DNA-barcoding analyses, we reconstructed the historical biogeography of the Asian black-spined toad (Duttaphrynus melanostictus), a toxic commensal amphibian that currently threatens two biodiversity hotspots through biological invasions (Wallacea and Madagascar). The results emphasize a complex diversification shaped by speciation and mitochondrial introgression that comprises two distinct species.

Individual differences in temporal order judgment.

Large individual differences can be observed in studies reporting spectral TOJ. In the present study, we aimed to explore these individual differences and explain them by employing Warren and Ackroff (1976) framework of direct identification of components and their order (direct ICO) and holistic pattern recognition (HPR). In Experiment 1, results from 177 participants replicated the large variance in participants' performance and suggested three response patterns, validated using the K-Means clustering algorithm.

Trauma history and persistent poor objective and subjective sleep quality among midlife women.

Objectives: Whereas some work links trauma exposure to poor subjective sleep quality, studies largely rely upon limited trauma measures and self-reported sleep at one time point. It is unknown whether trauma is related to persistent poor sleep, whether associations differ based on childhood versus adulthood trauma, and whether trauma exposure is related to poorer objectively assessed sleep. We tested whether childhood or adult trauma associated with persistent poor objectively and subjectively measured sleep at two time points in midlife women.

Longitudinal response to standard of care in pediatric metabolic dysfunction-associated steatotic liver disease: Rates of improvement and worsening, and factors associated with outcomes.

Background Aims: Longitudinal outcomes in children with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear due to the absence of a standardized monitoring approach. This study aimed to 1) define improvement and worsening in children with MASLD, 2) estimate rates of improvement or deterioration with standard of care (SOC) over one and two years, and 3) identify baseline and longitudinal factors associated with improvement or worsening.

Approach And Results: Using data from two large randomized controlled trials, we derived definitions for composite improvement and worsening of MASLD based on associations between changes in ALT, GGT, and liver histology after one and two years.

Comparing the cost of cirrhosis to other common chronic diseases: A longitudinal study in a large national insurance database.

Background Aims: Cirrhosis prevalence is increasing, yet costs associated with its chronic, complex care are poorly understood. The aim was to characterize the costs of care for patients with cirrhosis and compare them to other chronic diseases such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), for which the public health burden is better recognized.

Approach: Patients enrolled in Medicare Advantage plans from a large national insurer between 2011-2020 with cirrhosis, HF, and COPD were identified by ICD-9/-10 codes.

Role of follicular homing natural killer cells in HIV infection.

Purpose Of Review: Natural killer (NK) cells are integral components of the innate immune system, serving a vital function in eliminating virally infected cells. This review highlights the significance of CXCR5+ NK cells in the context of chronic HIV/SIV infection and viral control.

Recent Findings: Controlled HIV/SHIV infection results in a substantial increase in the population of CXCR5+ NK cells within the B-cell follicles of secondary lymphoid organs (SLOs).

Observer-rated environmental sensitivity and its characterization at behavioral, genetic, and physiological levels.

This study investigated the psychometric properties of the Highly Sensitive Child-Rating System (HSC-RS), the existence of sensitivity groups, and the characterization of sensitivity at behavioral, genetic, and physiological levels in 541 preschoolers (() = 3.56(0.27); 45%male; 87%Caucasian).

Reconsidering remission in recurrent late-life depression: clinical presentation and phenotypic predictors of relapse following successful antidepressant treatment.

Background: Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Methods: Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing.

Association between cytokines and progression-free survival in ovarian cancer following CRS/HIPEC treatment.

Background: The benefit of cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for epithelial ovarian cancer (EOC) remains uncertain. This study investigated the relationship between serum cytokines, particularly monocyte chemoattractant protein-1 (MCP-1), a key inflammatory mediator, and recurrence risk in EOC patients undergoing CRS/HIPEC.

Methods: From January 2018 to January 2023, serum cytokine levels were analyzed in 34 EOC patients (17 primary, 17 recurrent) before and after CRS/HIPEC using MILLIPLEX Magnetic Bead Panels.

5-methoxytryptophan protects against toll-like receptor 2 mediated renal tissue inflammation and fibrosis in a murine unilateral ureteral obstruction model.

Introduction: 5-methoxytryptophan (5-MTP) is an anti-inflammatory metabolite. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis.

Evaluating an urgent care antibiotic stewardship intervention: a multi-network collaborative effort.

Objective: Urgent care centers (UCCs) have reported high rates of antibiotic prescribing for acute respiratory tract infections. Prior UCC studies have generally been limited to single networks. Broadly generalizable stewardship efforts targeting common diagnoses are needed.

Circulating immune biomarkers correlating with response in patients with metastatic renal cell carcinoma on immunotherapy.

As multiple front-line immune checkpoint inhibitor (ICI)-based combinations are approved for metastatic renal cell carcinoma, biomarkers predicting for ICI responses are needed past clinical prognostication scores and transcriptome gene expression profiling. Circulating markers represent opportunities to assess baseline and dynamic changes in immune cell frequency and cytokine levels while on treatment. We conducted an exploratory prospective correlative study of 33 patients with metastatic clear cell renal cell carcinoma undergoing treatment with ICIs and correlated changes in circulating immune cell subsets and cytokines with clinical responses to treatment.

Impact of Prior Biologic Exposure on Ozanimod Efficacy and Safety in the Phase 3 True North Clinical Trial.

Introduction: Patients with ulcerative colitis (UC) and prior biologic failure may have reduced or delayed efficacy with subsequent advanced therapies. This analysis evaluated the efficacy and safety of ozanimod during the True North (TN) study and its open-label extension (OLE) in biologic-exposed patients with UC.

Methods: TN was a randomized, placebo-controlled 52-week trial (10-week induction, 42-week maintenance period).

Efficacy of umbilical cord-derived mesenchymal stem cells and exosomes in conjunction with standard IBD drug on immune responses in an IBD mouse model.

Background: Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model.

Method: In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized.

Learning from Hindsight: Examining Autonomic, Inflammatory, and Endocrine Stress Biomarkers and Mental Health in Healthy Terrorism Survivors Many Years Later.

Introduction: Terrorism and trauma survivors often experience changes in biomarkers of autonomic, inflammatory and hypothalamic-pituitary-adrenal (HPA) axis assessed at various times. Research suggests interactions of these systems in chronic stress.

Study Objective: This unprecedented retrospective study explores long-term stress biomarkers in three systems in terrorism survivors.

Immune-related adverse events not associated with survival in advanced or metastatic gastroesophageal cancers.

Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of gastric and oesophageal cancers (GEC). Despite their promising efficacy, ICIs have been associated with unique side effects known as immune-related adverse events (IRAEs). Several studies have shown improved treatment responses in patients with IRAEs compared to those without IRAEs in various cancer types such as melanoma and non-small cell lung cancer.

Student and Physician Views of How the Dobbs Decision Affects Training and Practice Location Preferences: Cross-Sectional Questionnaire Study.

Background: By allowing for abortion bans and restrictions to take effect in the majority of US states, the 2022 Dobbs v Jackson Women's Health Organization decision portends to have lasting impacts on patient care and the physician workforce. Notably, it is already beginning to impact practice location preferences of US health care workers, evidenced by declining application rates to residency programs in abortion-restrictive states since 2022. Yet, there remains a gap in the literature regarding why this trend exists.