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<h3>Introduction</h3> Pegozafermin (PGZ), a long-acting fibroblast growth factor 21 (FGF21) analog, was evaluated for efficacy and safety in the Phase 2b ENLIVEN trial in metabolic dysfunction-associated steatohepatitis (MASH) patients with biopsy-proven F2/F3 fibrosis. Co-morbidities such as obesity and T2DM are common in patients with MASH and may be treated with glucagon-like peptide-1 receptor agonists (GLP-1 therapy). Primary histology endpoints and non-invasive tests (NITs) were assessed at week 24, followed by additional NIT evaluation at the end of a 24-week blinded extension for a total of 48 weeks. <h3>Methods</h3> Patients were randomized to PGZ 15mg QW, 30mg QW, or 44mg Q2W or placebo for 24 weeks (histology-based primary endpoints). During the 24-week extension, most patients continued their assigned treatment except for a subset of placebo patients who were re-randomized to receive PGZ 30mg QW. The full analysis set includes patients who were F2-F3 and NAS ≥4 at baseline (n=192 of which 163 continued into the extension phase). The GLP-1 therapy population included 36 patients who received a GLP-1 during the study with the majority having baseline utilization of ≥ 6 months. Twenty-six received PGZ (30 mg QW or 44 mg Q2W) and 10 received placebo. Changes in liver steatosis, fibrosis and inflammation, metabolic effects, as well as safety, and tolerability were assessed at 48 weeks. <h3>Results</h3> At 24-weeks, PGZ 30mg QW or 44mg Q2W led to statistically significant improvement in both primary histological endpoints compared to placebo. Non-invasive testing at weeks 24 and 48 demonstrated that PGZ treatment was associated with robust and sustained reductions in liver fat content (MRI-PDFF), biomarkers of fibrosis (VCTE, ELF, PRO-C3) and liver injury (ALT, AST). PGZ also improved metabolic parameters such as lipids and HbA1c at both 24 and 48 weeks. These results remained consistent in patients on background GLP-1 therapy. PGZ was generally safe and well tolerated with the most common treatment emergent adverse events (TEAEs) being mild/moderate nausea and diarrhea. <h3>Conclusion</h3> PGZ treatment in MASH patients with F2/F3 fibrosis led to significant fibrosis regression and MASH resolution, corroborated by improvement across a variety of non-invasive tests including liver fat, inflammation, fibrosis, and metabolic markers. Benefits on NITs were sustained across the full 48-weeks of the study, while maintaining a favorable safety and tolerability. Phase 3 studies in non-cirrhotic and cirrhotic patients are currently underway to confirm these results.

BackgroundDespite extensive literature on lumbar disc herniation and cauda equina syndrome, sexual dysfunction in these patients has been overlooked. We conducted a systematic review to gather scientific evidence on this issue following surgical treatment in this population.MethodsOn January 30, 2025, several databases, including PubMed, Web of Science, Scopus, and Google Scholar, were searched on the topic for English-language biomedical literature from 2014 to 2024. Two researchers assessed the quality of the articles using the Mixed Methods Appraisal Tool version 2018. The findings were narratively synthesized to effectively describe, compare, and combine the study results.ResultsA total of 5,893 studies were identified, but after removing duplicates and irrelevant documents, only 20 studies were eligible for analysis. Of these, 90% were rated as high quality, indicating a strong level of certainty in the evidence. The analysis revealed that the prevalence of sexual dysfunction in this population ranged from 26.6% to 100%. The most common sexual disorder among women was sexual desire and arousal disorder (35% to 60%), while erectile dysfunction was the most prevalent among men (14% to 100%). Overall, dissatisfaction with sexual activities was reported by 37% to 69% of women and 69% of men. Improvements in sexual function following surgery for lumbar disc herniation were noted in 83.33% of studies (5 out of 6), compared to only 7.14% in patients with cauda equina syndrome (1 out of 14 studies).ConclusionStudies indicated a considerable enhancement in sexual function post-surgery for lumbar disc herniation patients (68% to 99%). However, long-term follow-up of cauda equina syndrome patients revealed that many continued to experience sexual issues (14% to 100%).

This work is devoted to the construction and study of commutative gates for a two-qubit quantum system. Using four-dimensional algebra developed by the Kazakh mathematician Abenov M.M. all groups of commutative gates have been constructed, and among all states of a two-qubit quantum system, unitary states with which a specific gate is connected have been identified. An explicit type of gate is described that transfers a quantum system from one unitary state to another unitary state. The proposed approach opens up new possibilities for the design of quantum algorithms not only for two-qubit quantum systems, but also for $n$-qubit quantum systems.

An approved therapy for nonalcoholic steatohepatitis (NASH) and fibrosis remains a major unmet medical need. To investigate the histological and metabolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy-confirmed NASH. This proof-of-concept, open-label, single-cohort study, part 2 of a phase 1b/2a clinical trial, was conducted at 16 centres in the United States. Adults (age 21-75 years) with NASH (stage 2 or 3 fibrosis, NAS≥4) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) ≥8% received subcutaneous pegozafermin 27 mg once weekly for 20 weeks. Primary outcomes were improvements in liver histology, and safety and tolerability. Of 20 enrolled subjects, 19 completed the study. Twelve subjects (63%) met the primary endpoint of ≥2-point improvement in NAFLD activity score with ≥1-point improvement in ballooning or lobular inflammation and no worsening of fibrosis. Improvement of fibrosis without worsening of NASH was observed in 26% of subjects, and NASH resolution without worsening of fibrosis in 32%. Least-squares mean relative change from baseline in MRI-PDFF was -64.7% (95% CI: -71.7, -57.7; p < 0.0001). Significant improvements from baseline were also seen in serum aminotransferases, noninvasive fibrosis tests, serum lipids, glycaemic control and body weight. Adverse events (AEs) were reported in 18 subjects (90%). The most frequently reported AEs were mild/moderate nausea and diarrhoea. There were no serious AEs, discontinuations due to AEs, or deaths. Pegozafermin treatment for 20 weeks had beneficial effects on hepatic and metabolic parameters and was well tolerated in subjects with NASH. gov: NCT04048135.

Sedentary behaviors are now prevalent as most modern jobs are done while seated. However, such sedentary behaviors have been found to increase the risk of several ailments including diabetes, cardiovascular disease, and all-cause mortality. Current interventions are mostly reactive and are triggered after the user has already been sedentary. Behavior change theory suggests that preventive sedentary interventions, which are triggered before a person becomes sedentary, are more likely to succeed. In this paper, we characterize user patterns of sedentary behaviors by analyzing smartphone-sensor data in a real-world dataset. Our work reveals location types (where), times of day/week (when), and smartphone contexts in which sedentary behaviors are most likely. Leveraging our findings, we then propose a set of context-aware probabilistic models that can predict sedentary behaviors in advance by analyzing smartphone sensor data. Our Context-Aware Predictive (CAP) models leverage smartphone-sensed contextual variables and the user's history of sedentary behaviors to predict their future sedentary behaviors. We rigorously analyze the performance of our models and discuss the implications of our work.

IntroductionThe COVID-19 pandemic has resulted in societal-level changes to sleep and other behavioral patterns. Objective, longitudinal data would allow for a greater understanding of sleep-related changes at the population level.MethodsN= 163,524 deidentified active Fitbit users from 6 major US cities contributed data, representing areas particularly hard-hit by the pandemic (Chicago, Houston, Los Angeles, New York, San Francisco, and Miami). Sleep variables extracted include nightly and weekly mean sleep duration and bedtime, variability (standard deviation) of sleep duration and bedtime, and estimated arousals and sleep stages. Deviation from similar timeframes in 2019 were examined. All analyses were performed in Python.ResultsThese data detail how sleep duration and timing changed longitudinally, stratified by age group and gender, relative to previous years’ data. Overall, 2020 represented a significant departure for all age groups and both men and women (P<0.00001). Mean sleep duration increased in nearly all groups (P<0.00001) by 5-11 minutes, compared to a mean decrease of 5-8 minutes seen over the same period in 2019. Categorically, sleep duration increased for some and decreased for others, but more extended than restricted. Sleep phase shifted later for nearly all groups (p<0.00001). Categorically, bedtime was delayed for some and advanced for others, though more delayed than advanced. Duration and bedtime variability decreased, owing largely to decreased weekday-weekend differences. WASO increased, REM% increased, and Deep% decreased. Additional analyses show stratified, longitudinal changes to sleep duration and timing mean and variability distributions by month, as well as effect sizes and correlations to other outcomes.ConclusionThe pandemic was associated with increased sleep duration on average, in contrast to 2019 when sleep decreased. The increase was most profound among younger adults, especially women. The youngest adults also experienced the greatest bedtime delay, in line with extensive school-start-times and chronotype data. When given the opportunity, the difference between weekdays and weekends became smaller, with occupational implications. Sleep staging data showed that slightly extending sleep minimally impacted deep sleep but resulted in a proportional increase in REM. Wakefulness during the night also increased, suggesting increased arousal despite greater sleep duration.Support (if any)This research was supported by Fitbit, Inc.

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.