Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation.

Female individuals have an increased prevalence of many Th17 cell-mediated diseases, including asthma. Androgen signaling decreases Th17 cell-mediated airway inflammation, and Th17 cells rely on glutaminolysis. However, it remains unclear whether androgen receptor (AR) signaling modifies glutamine metabolism to suppress Th17 cell-mediated airway inflammation.

HIF-2α expression and metabolic signaling require ACSS2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer driven by VHL loss and aberrant HIF-2α signaling. Identifying means to regulate HIF-2α thus has potential therapeutic benefit. Acetyl-CoA synthetase 2 (ACSS2) converts acetate to acetyl-CoA and is associated with poor patient prognosis in ccRCC.

Obesity induces PD-1 on macrophages to suppress anti-tumour immunity.

Obesity is a leading risk factor for progression and metastasis of many cancers, yet can in some cases enhance survival and responses to immune checkpoint blockade therapies, including anti-PD-1, which targets PD-1 (encoded by PDCD1), an inhibitory receptor expressed on immune cells. Although obesity promotes chronic inflammation, the role of the immune system in the obesity-cancer connection and immunotherapy remains unclear. It has been shown that in addition to T cells, macrophages can express PD-1.

VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.

Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated hypoxia signaling and a tumor microenvironment (TME) highly enriched in myeloid and lymphoid cells. Loss of the von Hippel Lindau (VHL) gene is a critical early event in ccRCC pathogenesis and promotes stabilization of HIF. Whether VHL loss in cancer cells affects immune cells in the TME remains unclear.

Survey Uses May Influence Survey Responses.

Traditional validation processes for psychological surveys tend to focus on analyzing item responses instead of the cognitive processes that participants use to generate these responses. When screening for invalid responses, researchers typically focus on participants who manipulate their answers for personal gain or respond carelessly. In this paper, we introduce a new invalid response process, discordant responding, that arises when participants disagree with the use of the survey and discuss similarities and differences between this response style and protective responding.

Tissue-Specific Dependence of Th1 Cells on the Amino Acid Transporter SLC38A1 in Inflammation.

Amino acid (AA) uptake is essential for T cell metabolism and function, but how tissue sites and inflammation affect CD4 T cell subset requirements for specific AA remains uncertain. Here we tested CD4 T cell AA demands with and multiple CRISPR screens and identify subset- and tissue-specific dependencies on the AA transporter SLC38A1 (SNAT1). While dispensable for T cell persistence and expansion over time and lung inflammation, SLC38A1 was critical for Th1 but not Th17 cell-driven Experimental Autoimmune Encephalomyelitis (EAE) and contributed to Th1 cell-driven inflammatory bowel disease.

The Inventory of Nonordinary Experiences (INOE): Evidence of validity in the United States and India.

Researchers increasingly recognize that the mind and culture interact at many levels to constitute our lived experience, yet we know relatively little about the extent to which culture shapes the way people appraise their experiences and the likelihood that a given experience will be reported. Experiences that involve claims regarding deities, extraordinary abilities, and/or psychopathology offer an important site for investigating the interplay of mind and culture at the population level. However, the difficulties inherent in comparing culture-laden experiences, exacerbated by the siloing of research on experiences based on discipline-specific theoretical constructs, have limited our ability to do so.

Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells.

Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and inhibition of glutamine metabolism alters T cell function in autoimmune disease and cancer. Multiple glutamine-targeting molecules are under investigation, yet the precise mechanisms of glutamine-dependent CD8 T cell differentiation remain unclear.

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy.

The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the delivery of a cyclic dinucleotide STING agonist, on the tumor vasculature and attendant effects on T cell infiltration and antitumor function. In multiple mouse tumor models, intravenous administration of STANs promoted vascular normalization, evidenced by improved vascular integrity, reduced tumor hypoxia, and increased endothelial cell expression of T cell adhesion molecules.

Immunogenicity in renal cell carcinoma: shifting focus to alternative sources of tumour-specific antigens.

Renal cell carcinoma (RCC) comprises a group of malignancies arising from the kidney with unique tumour-specific antigen (TSA) signatures that can trigger cytotoxic immunity. Two classes of TSAs are now considered potential drivers of immunogenicity in RCC: small-scale insertions and deletions (INDELs) that result in coding frameshift mutations, and activation of human endogenous retroviruses. The presence of neoantigen-specific T cells is a hallmark of solid tumours with a high mutagenic burden, which typically have abundant TSAs owing to non-synonymous single nucleotide variations within the genome.

dynamic : An R Package for Deriving Dynamic Fit Index Cutoffs for Factor Analysis.

To evaluate the fit of a confirmatory factor analysis model, researchers often rely on fit indices such as SRMR, RMSEA, and CFI. These indices are frequently compared to benchmark values of .08, .

Who Opts In to Alcohol Feedback and How Does That Impact Behavior? A Pilot Trial.

Objective: Personalized feedback interventions are effective in reducing alcohol consumption and related problems. However, little is known about the role of choice in outcomes. The current study sought to (a) characterize individuals who opt in for brief alcohol-related feedback, (b) assess participants' consistency in that choice over two time points, and (c) evaluate changes in peak alcohol consumption among those who did and did not receive feedback.

Dynamic fit index cutoffs for one-factor models.

Assessing whether a multiple-item scale can be represented with a one-factor model is a frequent interest in behavioral research. Often, this is done in a factor analysis framework with approximate fit indices like RMSEA, CFI, or SRMR. These fit indices are continuous measures, so values indicating acceptable fit are up to interpretation.

MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function.

Antigenic stimulation promotes T cell metabolic reprogramming to meet increased biosynthetic, bioenergetic, and signaling demands. We show that the one-carbon (1C) metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) regulates de novo purine synthesis and signaling in activated T cells to promote proliferation and inflammatory cytokine production. In pathogenic T helper-17 (Th17) cells, MTHFD2 prevented aberrant upregulation of the transcription factor FoxP3 along with inappropriate gain of suppressive capacity.

Dynamic fit index cutoffs for confirmatory factor analysis models.

Model fit assessment is a central component of evaluating confirmatory factor analysis models and the validity of psychological assessments. Fit indices remain popular and researchers often judge fit with fixed cutoffs derived by Hu and Bentler (1999). Despite their overwhelming popularity, methodological studies have cautioned against fixed cutoffs, noting that the meaning of fit indices varies based on a complex interaction of model characteristics like factor reliability, number of items, and number of factors.

Cell-programmed nutrient partitioning in the tumour microenvironment.

Cancer cells characteristically consume glucose through Warburg metabolism, a process that forms the basis of tumour imaging by positron emission tomography (PET). Tumour-infiltrating immune cells also rely on glucose, and impaired immune cell metabolism in the tumour microenvironment (TME) contributes to immune evasion by tumour cells. However, whether the metabolism of immune cells is dysregulated in the TME by cell-intrinsic programs or by competition with cancer cells for limited nutrients remains unclear.

Fine-Needle Aspiration-Based Patient-Derived Cancer Organoids.

Patient-derived cancer organoids hold great potential to accurately model and predict therapeutic responses. Efficient organoid isolation methods that minimize post-collection manipulation of tissues would improve adaptability, accuracy, and applicability to both experimental and real-time clinical settings. Here we present a simple and minimally invasive fine-needle aspiration (FNA)-based organoid culture technique using a variety of tumor types including gastrointestinal, thyroid, melanoma, and kidney.

Thinking twice about sum scores.

A common way to form scores from multiple-item scales is to sum responses of all items. Though sum scoring is often contrasted with factor analysis as a competing method, we review how factor analysis and sum scoring both fall under the larger umbrella of latent variable models, with sum scoring being a constrained version of a factor analysis. Despite similarities, reporting of psychometric properties for sum scored or factor analyzed scales are quite different.

Modeling clear cell renal cell carcinoma and therapeutic implications.

Renal cell carcinoma (RCC) comprises a diverse group of malignancies arising from the nephron. The most prevalent type, clear cell renal cell carcinoma (ccRCC), is characterized by genetic mutations in factors governing the hypoxia signaling pathway, resulting in metabolic dysregulation, heightened angiogenesis, intratumoral heterogeneity, and deleterious tumor microenvironmental (TME) crosstalk. Identification of specific genetic variances has led to therapeutic innovation and improved survival for patients with ccRCC.

A naturalistic study exploring mental health outcomes following trauma-focused treatment among diverse survivors of crime and violence.

Background: Although considerable research has tested evidence-based practices in clinical trials, research is needed on the use of trauma-focused treatments by victims of crime and violence in naturalistic settings. This study investigated four trauma-focused treatments, prolonged exposure therapy (PE), cognitive behavioral therapy (CBT), eclectic therapy, and person-centered therapy (PCT), and assessed treatment dropout and symptom improvement over five assessment time-points.

Methods: Descriptive comparisons and pattern mixture multigroup growth models were used to assess differences between treatments on time in treatment, rate of dropout, and improvement in posttraumatic stress (PTSD) and depression symptoms in an outpatient sample of 526 clients seeking routine clinical care.

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.

Activated T cells differentiate into functional subsets with distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in T cell activation and specification.