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Epigenetic alterations, including histone acetylation, contribute to the malignant transformation of hematopoietic cells and disease progression, as well as the emergence of chemotherapy resistance. Targeting histone acetylation provides new strategies for the treatment of cancers. As a pan-histone deacetylase inhibitor, panobinostat has been approved by the US Food and Drug Administration for the treatment of multiple myeloma and has shown promising antileukemia effects in acute lymphoblastic leukemia (ALL). However, the underlying drug resistance mechanism in ALL remains largely unknown. Using genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas)9 (CRISPR/Cas9) screening, we identified mitochondrial activity as the driver of panobinostat resistance in ALL. Mechanistically, ectopic SIRT1 expression activated mitochondrial activity and sensitized ALL to panobinostat through activating mitochondria-related apoptosis pathway. Meanwhile, the transcription level of SIRT1 was significantly associated with panobinostat sensitivity across diverse tumor types and thus could be a potential biomarker of panobinostat response in cancers. Our data suggest that patients with higher SIRT1 expression in cancer cells might benefit from panobinostat treatment, supporting the implementation of combinatorial therapy with SIRT1 or mitochondrial activators to overcome panobinostat resistance., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Since Wakefield et al. (1998), the public was exposed to mixed information surrounding the claim that measles-mumps-rubella vaccine causes autism. A persistent trend to delay the vaccination during 1998-2011 in the US was driven by children of college-educated mothers, suggesting that these mothers held biases against the vaccine influenced by the early unfounded claim. Consistent with confirmatory bias, exposures to negative information about the vaccine strengthened their biases more than exposures to positive information attenuated them. Positive online information, however, had strong impacts on vaccination decisions, suggesting that online dissemination of vaccine-safety information may help tackle the sticky misinformation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Driving a motor vehicle is an important aspect of mobility for older adults. Limited lower extremity functioning performance, as measured by the Short Physical Performance Battery (SPPB), has been associated with various negative health outcomes, but little is known about the association of SPPB scores with driving status., Objective: The purpose of this study was to evaluate whether lower (poorer) SPPB scores are associated with an increased rate for being a current nondriver among a nationally representative sample of community-dwelling older adults., Design: The National Health and Aging Trends Study is a longitudinal cohort study., Methods: A population of 5935 participants, surveyed annually from 2011 to 2014 for the National Health and Aging Trends Study, was used to examine the relationship between SPPB and driving status. Using weighted data, multivariable Poisson regression with generalized estimating equations was used to calculate the rate ratios, adjusting for covariates and clustering due to the complex survey design., Results: Participants with a low (poor) SPPB score (0-5) had a rate for being a current nondriver 2.01 times the rate (or 101% increase) of those with a high (good) SPPB score (10-12) (adjusted 95% confidence interval = 1.78-2.26)., Limitations: Current nondrivers were not asked whether they planned to resume driving if they had not driven in the previous year., Conclusions: Unlike other factors, such as cognitive decline, lower SPPB scores (poorer lower extremity functioning) are significantly associated with an increased rate of being a current nondriver and are a modifiable risk factor. Further research is needed to examine whether optimum exercises and other physical therapist interventions focused on improving lower extremity strength and balance ultimately improve driving outcomes., (© 2019 American Physical Therapy Association.)

Aims: There is debate on whether the beneficial effect of implantable cardioverter-defibrillators (ICDs) is attenuated in patients with non-ischaemic cardiomyopathy (NICM). We assess whether any ICD benefit differs between patients with NICM and those with ischaemic cardiomyopathy (ICM), using data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial., Methods and Results: We performed a post hoc analysis using WARCEF (N = 2293; ICM, n = 991 vs. NICM, n = 1302), where participants received optimal medical treatment. We developed stratified propensity scores for having an ICD at baseline using 41 demographic and clinical variables and created 1:2 propensity-matched cohorts separately for ICM patients with ICD (N = 223 with ICD; N = 446 matched) and NICM patients (N = 195 with ICD; N = 390 matched). We constructed a Cox proportional hazards model to assess the effect of ICD status on mortality for patients with ICM and those with NICM and tested the interaction between ICD status and aetiology of heart failure. During mean follow-up of 3.5 ± 1.8 years, 527 patients died. The presence of ICD was associated with a lower risk of all-cause death among those with ICM (hazard ratio: 0.640; 95% confidence interval: 0.448 to 0.915; P = 0.015) but not among those with NICM (hazard ratio: 0.984; 95% confidence interval: 0.641 to 1.509; P = 0.941). There was weak evidence of interaction between ICD status and the aetiology of heart failure (P = 0.131)., Conclusions: The presence of ICD is associated with a survival benefit in patients with ICM but not in those with NICM., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

This article describes technology-assisted telesupervision-of-supervision, which is a component of a 2-year U.S.-China collaborative program designed to systematically train clinical supervisors in China. Using Zoom conferencing platform, several U.S.-based supervisors facilitated telesupervision-of-supervision groups, with six to ten participants in each group, from different geographic locations in China. This article employs the perspectives of both U.S.-based supervisors and group participants who are themselves supervision scholars in China, describing their experiences and insights about the rewards and challenges of this telesupervision-of-supervision project., (© 2018 Wiley Periodicals, Inc.)

Aims: Left atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments., Methods and Results: Two-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range >60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034)., Conclusions: In patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aims: We evaluated the added prognostic value of a multi-time point-based multimarker panel of biomarkers in patients with acute heart failure (AHF)., Methods and Results: Seven circulating biomarkers [NT-proBNP, high sensitivity cardiac troponin T (hs-cTnT), soluble ST2 (sST2), growth differentiation factor 15 (GDF-15), cystatin-C, galectin-3, and high sensitivity C-reactive protein (hs-CRP)] were measured at baseline and on days 2, 5, 14, and 60 in 1161 patients enrolled in the RELAX-AHF trial. Patients with BNP ≥350 ng/L or NT-proBNP ≥1400 ng/L, mild to moderate renal impairment, and systolic blood pressure >125 mmHg were included in the trial. Time-dependent Cox regression analysis was utilized to evaluate the incremental value of serial measurement of biomarkers. Added value of individual biomarkers and their combination, on top of a pre-specified baseline model, was quantified with the gain in the C-index. Serial biomarker evaluation showed incremental predictive value over baseline measurements alone for the prediction of 180-day cardiovascular mortality except for galectin-3. While a repeat measurement as early as day 2 was adequate for NT-proBNP and cystatin-C in terms of maximizing discriminatory accuracy, further measurements on days 14 and 60 provided added value for hs-cTnT, GDF-15, sST2, and hs-CRP. Individual biomarker additions on top of the baseline model showed additional prognostic value. The greatest prognostic gain was, however, attained with the combination of NT-proBNP, hs-cTnT, GDF-15, and sST2, which yielded 0.08 unit absolute increment in the C-index to 0.87 (95% confidence interval 0.83-0.91]., Conclusion: In patients with AHF and mild to moderate renal impairment, a multimarker approach based on a panel of serially evaluated biomarkers provides the greatest prognostic improvement unmatched by a single time point-based single marker strategy., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Shame has been observed to play an important role in social anxiety in China [Xu, 1982]. Shame and personality factors, such as neuroticism and introversion-extraversion, are also related to social anxiety symptoms in Chinese college students [Li et al., 2003]. The aim of this study was to explore cross-cultural differences of the effects of shame and personality on social anxiety using the Experience Scale of Shame, the Eysenck Personality Questionnaire-Revised Short Scale and Social Anxiety Inventory. Data were collected from both a Chinese sample (n=211, 66 males and 145 females, average ages 20.12+/-1.56 years) and an American sample (n=211, 66 males and 145 females, average ages 20.22+/-1.90 years) of college students. The structural equation modeling (SEM) was performed separately for the Chinese and American samples. The SEM results reveal a shame-mediating model, which is adaptive and only in the Chinese sample. This suggests that shame is a mediator between the Chinese personality and social anxiety. The shame factor did not play the same role in the American sample. This empirical study supports the hypothesis that shame has a more important effect on social anxiety in the Chinese culture compared to its effect on Americans., ((c) 2007 Wiley-Liss, Inc.)