L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy

Background: The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatinemonohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. Methods: After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea,4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-relatedgenes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). Results: MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube size, linkingMSTN treatment to atrophy independent of MPS. Remarkably, MSTN + Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibiteda 36% (p < 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL and MSTN-only treated myotubes, respectively. Conclusions: Leu, HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNAexpression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affectAkirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophyin vivo

Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study

BackgroundAlthough introduction of immune checkpoint inhibitors has revolutionized the treatment of cancer, their response rates are generally low. Preclinical and early phase clinical data suggest that MEK inhibition may sensitize tumors to immune checkpoint inhibitors by upregulating tumor antigen expression, programmed death-ligand 1 (PD-L1) expression, and tumor T-cell infiltration. We evaluated the efficacy and safety of cobimetinib plus atezolizumab in patients with advanced solid tumors in the open-label, multicohort phase II COTEST study.Patients and methodsThis analysis of the COTEST trial included patients from cohorts 1-4 [1-3: anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment-naive patients; 4: patients with disease progression on anti-PD-1/anti-PD-L1 treatment] who received cobimetinib 60 mg once daily for the first 21 days and intravenous infusions of atezolizumab 840 mg on days 1 and 15 of each 28-day cycle. Efficacy endpoints included objective response rate, overall survival, progression-free survival (PFS), and disease control rate.ResultsOverall, 77 patients were enrolled in cohorts 1-4 (78% male; median age 62.8 years). Objective response rate was 20% in cohort 1 [squamous cell carcinoma of the head and neck (SCCHN)], 30% in cohort 2 (urothelial carcinoma), and 18% in cohort 3 (renal cell carcinoma); there were no responders among 20 patients in cohort 4 (SCCHN). The disease control rates in cohorts 1-4 were 50%, 40%, 24%, and 25%, respectively. The median PFS was 5.5, 3.4, 3.4, and 3.6 months in cohorts 1-4, respectively, and the median overall survival was 16.8, 18.7, 21.7, and 7.7 months, respectively. Most adverse events were of grade 1/2 and were manageable.ConclusionsCobimetinib plus atezolizumab had moderate activity in patients with anti-PD-1/PD-L1 treatment-naive SCCHN and urothelial carcinoma, and weak activity in anti-PD-1/PD-L1 treatment-naive renal cell carcinoma, and no activity in checkpoint inhibitor-treated patients

Author Correction: COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic (Scientific Data, (2022), 9, 1, (331), 10.1038/s41597-022-01383-6)

The original version of this Article contained an error in the spelling of the author Krzysztof Hanusz, which was incorrectly given as Hanusz Krzysztof. This has now been corrected in both the PDF and HTML versions of the Article

COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic

During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals’ experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy