Bioluminescence Assay of Lysine Deacylase Sirtuin Activity.

Lysine acylation can direct protein function, localization, and interactions. Sirtuins deacylate lysine towards maintaining cellular homeostasis, and their aberrant expression contributes to the pathogenesis of multiple pathological conditions, including cancer. Measuring sirtuins' activity is essential to exploring their potential as therapeutic targets, but accurate quantification is challenging.

Validation and meaningful within-patient change in work productivity and activity impairment questionnaire (WPAI) for episodic or chronic migraine.

Background: No available studies demonstrate validity and meaningful change thresholds of Work Productivity and Activity Impairment (WPAI) questionnaire in patients with migraine. In this post-hoc analysis, we assessed reliability, validity, responsiveness, and meaningful within-patient change from baseline to Month 3 for Work Productivity and Activity Impairment (WPAI) domain scores in patients with episodic migraine (EM) or chronic migraine (CM).

Method: The Phase 3, multicenter, randomized, double-blind, placebo-controlled CONQUER study (NCT03559257, N = 462) enrolled patients with EM or CM who failed two to four categories of prior preventive medication in past ten years.

Long-term treatment with lasmiditan in patients with migraine: Results from the open-label extension of the CENTURION randomized trial.

Background: Following the CENTURION phase 3 randomized controlled trial's four-month double-blind phase, this 12-month open-label extension collected data for up to one year about dose optimization, patterns of use, migraine-related disability, and quality of life during lasmiditan treatment.

Methods: Migraine patients ≥18 years completing the double-blind phase and treating ≥3 migraine attacks could continue into the 12-month open-label extension. The initial oral lasmiditan dose was 100 mg; the dose could subsequently be adjusted to 50 mg or 200 mg at the investigator's discretion.

TXNIP loss expands Myc-dependent transcriptional programs by increasing Myc genomic binding.

The c-Myc protooncogene places a demand on glucose uptake to drive glucose-dependent biosynthetic pathways. To meet this demand, c-Myc protein (Myc henceforth) drives the expression of glucose transporters, glycolytic enzymes, and represses the expression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake. A Mychigh/TXNIPlow gene signature is clinically significant as it correlates with poor clinical prognosis in triple-negative breast cancer (TNBC) but not in other subtypes of breast cancer, suggesting a functional relationship between Myc and TXNIP.

Multivariate analysis of grain amaranth ( spp.) accessions to quantify phenotypic diversity.

Twelve amaranth accessions were evaluated in a randomized complete block design with three replications in the research field of the Institute of Agriculture and Animal Science, Lamjung, Sundarbazar, Lamjung, Nepal from March to July 2021 to assess the phenotypic diversity. Principal Component Analysis (PCA) showed that only two principal components were significant with their eigenvalues >1 and combinedly accounted for 88.3% of the total variance.

Rouviere's sulcus - An anatomical landmark for safe laparoscopic cholecystectomy: A cross-sectional study.

Introduction: Laparoscopic cholecystectomy (LC) has been established as the gold standard treatment for symptomatic gallstones, however surgeons face the risk of injuring bile ducts and vessels due to the inherent limitations of laparoscopy.

Methods: This is a cross-sectional study done in the Department of Surgery, Shree Birendra Hospital (SBH) on patients who were posted for LC. The study period was through April 2021 to September 2021.

Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis.

Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here, we identify the transcription factor, MondoA, as a regulator of cellular senescence, autophagy, and mitochondrial homeostasis.

The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes.

Preparing historically underrepresented trainees for biomedical cancer research careers at Huntsman Cancer Institute/University of Utah Health.

Given the well-documented inequities in health care outcomes by race, ethnicity, and gender, many health career pipeline programs have focused on supporting the development of a diverse and inclusive workforce. The State of Utah, is vast, but sparsely populated outside the Salt Lake City metropolitan area. More than 96% of our nearly 85,000 square miles is designated rural (<100 people/square mile) or frontier (<7 people/square mile).

Psychometric validation and meaningful within-patient change of the Migraine-Specific Quality of Life questionnaire version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine.

Objective: To evaluate the measurement properties of all three domains of the Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) electronic patient-reported outcome (ePRO) to assess the functional impact of migraine in patients with episodic or chronic migraine (CM); and identify meaningful within-patient change thresholds for the Role Function-Restrictive (RFR), Role Function-Preventive (RFP), and Emotional Function (EF) domains.

Associating gene expressions with curcuminoid biosynthesis in turmeric.

Background: Biologically important curcuminoids viz curcumin, demethoxycurcumin, and bisdemethoxycurcumin in turmeric rhizome have several health benefits. Pharmaceutical industries synthesize curcuminoids manipulating gene expressions in vitro or in vivo because of their medicinal importance. In this experiment, we studied the gene expressions involved in the curcuminoid biosynthesis pathway in association with curcuminoid yield in turmeric rhizome to study the impact of individual gene expression on curcuminoid biosynthesis.

Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate.

Background: Protein synthesis is regulated by the availability of amino acids, the engagement of growth factor signaling pathways, and adenosine triphosphate (ATP) levels sufficient to support translation. Crosstalk between these inputs is extensive, yet other regulatory mechanisms remain to be characterized. For example, the translation initiation inhibitor rocaglamide A (RocA) induces thioredoxin-interacting protein (TXNIP).

Migraine Headache Day Response Rates and the Implications to Patient Functioning: An Evaluation of 3 Randomized Phase 3 Clinical Trials of Galcanezumab in Patients With Migraine.

Objective: This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient-reported outcomes of health-related quality of life (HRQoL) and disability categories.

Background: Migraine causes considerable disease-related disability and negatively impacts HRQoL of patients. Calcitonin gene-related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients.

Functional impairment and disability among patients with migraine: evaluation of galcanezumab in a long-term, open-label study.

Purpose: Migraine can negatively impact patient functioning and quality of life. Here, we report the effects of galcanezumab (GMB), a humanized monoclonal antibody that binds to calcitonin gene-related peptide, on patient-reported outcome (PRO) measures in migraine.

Methods: CGAJ was a Phase III, randomized, open-label study (12-month open-label and 4-month post-treatment follow-up) in patients with episodic or chronic migraine.

Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN).

Purpose: To evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine.

Methods: Patients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.

A Qualitative Study to Assess the Content Validity of the 24-Hour Migraine Quality of Life Questionnaire in Patients with Migraine.

Objective: A concept elicitation, cognitive debriefing, and usability study was undertaken to: (1) explore migraine symptoms and day-to-day impacts; (2) determine the comprehensiveness and comprehensibility of the previously developed 24-Hour Migraine Quality of Life Questionnaire electronic patient-reported outcome (24-Hr MQoLQ ePRO) items, and the appropriateness and understanding of the recall period, response options, and instructions; and (3) assess the usability on an electronic hand-held device.

Methods: Eleven United States English-speaking people with episodic migraine were recruited to participate in one-on-one interviews, which followed methods appropriate for concept elicitation, cognitive debriefing, and usability testing. Interviews were audio-recorded, transcribed, and analyzed following the constant comparative method.

Content validity of the Migraine-Specific Quality of Life Questionnaire version 2.1 electronic patient-reported outcome.

Purpose: A concept elicitation, cognitive debriefing, and usability study was undertaken to: 1) ascertain the migraine experience with a particular focus on the impact on roles and daily functioning; 2) determine the comprehensiveness and comprehensibility of the Migraine-Specific Quality of Life Questionnaire version 2.1 electronic patient-reported outcome Role Function-Restrictive (MSQ v2.1 ePRO RFR) domain items, and the appropriateness and understanding of the recall period, response options, and instructions; and 3) assess the usability on an electronic tablet device.

MondoA drives muscle lipid accumulation and insulin resistance.

Obesity-related insulin resistance is associated with intramyocellular lipid accumulation in skeletal muscle. We hypothesized that in contrast to current dogma, this linkage is related to an upstream mechanism that coordinately regulates both processes. We demonstrate that the muscle-enriched transcription factor MondoA is glucose/fructose responsive in human skeletal myotubes and directs the transcription of genes in cellular metabolic pathways involved in diversion of energy substrate from a catabolic fate into nutrient storage pathways including fatty acid desaturation and elongation, triacylglyeride (TAG) biosynthesis, glycogen storage, and hexosamine biosynthesis.

Two randomized migraine studies of galcanezumab: Effects on patient functioning and disability.

Objective: To evaluate changes from baseline in patient-reported outcomes for measures of functioning and disability among patients with migraine treated with galcanezumab or placebo.

Methods: Patients with episodic migraine (4-14 monthly migraine headache days) were treated with either galcanezumab (Evaluation of LY2951742 in the Prevention of Episodic Migraine [EVOLVE]-1: 120 mg n = 210, 240 mg n = 208; EVOLVE-2: 120 mg n = 226, 240 mg n = 220) or placebo (EVOLVE-1 n = 425; EVOLVE-2 n = 450) during 6 months of treatment. Migraine-Specific Quality of Life Questionnaire v2.

Psychometric Validation of the Role Function Restrictive Domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 Electronic Patient-Reported Outcome in Patients With Episodic and Chronic Migraine.

Objectives: To assess the measurement properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain to evaluate the functional impact of migraine in patients with episodic (EM) or chronic migraine (CM) enrolled in clinical trials.

Cellular acidosis triggers human MondoA transcriptional activity by driving mitochondrial ATP production.

Human MondoA requires glucose as well as other modulatory signals to function in transcription. One such signal is acidosis, which increases MondoA activity and also drives a protective gene signature in breast cancer. How low pH controls MondoA transcriptional activity is unknown.

Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP Destabilization.

The metabolic state of a cell is influenced by cell-extrinsic factors, including nutrient availability and growth factor signaling. Here, we present extracellular matrix (ECM) remodeling as another fundamental node of cell-extrinsic metabolic regulation. Unbiased analysis of glycolytic drivers identified the hyaluronan-mediated motility receptor as being among the most highly correlated with glycolysis in cancer.

Measures of Functioning in Patients With Episodic Migraine: Findings From a Double-Blind, Randomized, Placebo-Controlled Phase 2b Trial With Galcanezumab.

Objective - To evaluate 12-week changes from baseline of 2 disease-specific patient-reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene-related peptide (CGRP), or placebo. Background - Preventing headache-related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden.