Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed‐Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are ...infected by Epstein‐Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV‐latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV‐LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation‐induced autophagic stress, and alleviated autophagy inhibition‐ or doxorubicin‐induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte‐predominant and lymphocyte‐rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1‐positive HL xenografts with better efficacy than LMP1‐negative HL xenografts. Collectively, these results suggest that EBV‐LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV‐positive cases.
EBV‐LMP1 enhances autophagy and promotes viability of Hodgkin lymphoma cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with Hodgkin lymphoma, especially EBV‐positive cases.
This systematic review and meta-analysis evaluated the outcomes of patients with osteoporosis-related fractures managed through fracture liaison services (FLS) programs.
Medline, PubMed, EMBASE, and ...the Cochrane Library were searched (January 2000–February 2017 inclusive) using the keywords ‘osteoporosis’, ‘fractures’, ‘liaison’, and ‘service’ to identify randomised controlled trials and observational studies of patients aged ≥50years with osteoporosis-related fractures in hospital, clinic, community, or home-based settings who were managed using FLS. Risk of bias was assessed at outcome level. Meta-analysis followed a random-effects and fixed-effects model. Outcomes of interest were incidence of bone mineral density (BMD) testing, treatment initiation, adherence, re-fractures, and mortality due to osteoporosis treatment.
A total of 159 publications were identified for the systematic literature review; 74 controlled studies (16 RCTs; 58 observational studies) were included in the meta-analysis. Overall, 41 of 58 observational studies and 12 of 16 RCTs were considered of high quality. Compared with patients receiving usual care (or those in the control arm), patients receiving care from an FLS program had higher rates of BMD testing (48.0% vs 23.5%) and treatment initiation (38.0% vs 17.2%) and greater adherence (57.0% vs 34.1%). Unweighted average rates of re-fracture were 13.4% among patients in the control arm and 6.4% in the FLS arm. Unweighted average rates of mortality were 15.8% in the control arm and 10.4% in the FLS arm. Meta-analysis revealed significant FLS-associated improvements in all outcomes versus non-FLS controls, with BMD testing increased by 24 percentage points (95% confidence interval CI 0.18–0.29), 20 percentage points for treatment rates (95% CI 0.16–0.25), and 22 percentage points for adherence (95% CI 0.13–0.31) and absolute risk of re-fracture reduced by five percentage points (95% CI –0.08 to −0.03) and mortality reduced by three percentage points (95% CI –0.05 to −0.01).
FLS programs improved outcomes of osteoporosis-related fractures, with significant increases in BMD testing, treatment initiation, and adherence to treatment and reductions in re-fracture incidence and mortality.
•FLS programs improve outcomes of osteoporosis-related fractures.•As FLS programs improve over time, patient outcomes will improve accordingly.•FLS play a significant role in reducing the disease burden of osteoporosis.
Background
Fibrosis‐4 score (FIB4) was a non‐invasive surrogate to estimate the amount of liver scarring in chronic hepatitis. Considering the presence of increased central venous pressure and ...congestive hepatopathy in patients with decompensated heart failure, we therefore investigated the prognostic values of FIB4 in acute heart failure (AHF) patients.
Method
Patients hospitalised primarily for HF were drawn from an intramural registry. FIB4 was calculated according to age, aspartate aminotransferase, alanine aminotransferase and platelet count. All‐cause mortality up to 5 years after discharge was obtained by linking to the national death registry.
Results
Among a total of 1854 participants, 940 patients died during a mean follow‐up of 28.3 ± 21.8 months. FIB4 score was related to mortality and the composite of cardiovascular death or HF rehospitalisation, independent of age, sex, left ventricular ejection fraction, left atrial dimension, sodium and haemoglobin levels, estimated glomerular filtration rate, comorbidities, and medications hazard ratio and 95% confidence interval of mortality: 1.009 (1.002–1.015), and the composite of cardiovascular death or HF hospitalisation: 1.020 (1.010–1.031). The prognostic value of FIB4 was predominantly in the subjects with heart failure and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF), or coronary artery disease (CAD) than the counterparts interaction p‐value <0.001, and 0.004, respectively.
Conclusions
FIB4 was an independent predictor of survival in AHF patients, irrespective of the phenotypes of HF. The higher predictive value of mortality of FIB4 was observed in the subjects with HFpEF, HFmrEF or CAD.
The study examines how the remote associates test (RAT) has been used to examine theories of creativity through a review of recent studies on creativity. Creativity-related studies published between ...2000 and 2019 were retrieved from the SCOPUS database. A total of 172 papers were chosen for further analysis. Content analysis shows that research on creativity using RAT mainly concerns remote association, insight problem-solving, general creative process, test development, individual difference, effect of treatment, clinical case, social interaction effect, and predictor or criterion. The study constructs a theoretical framework based on the 4P (Product–Person–Process–Place) model and demonstrates how empirical studies using the RAT explore the individual differences, internal processes, and external influences of creative thinking. In addition, the most commonly used version of the RAT is the Compound Remote Associates Problems (Bowden and Jung-Beeman,
2003a
). Current research shows a trend whereby the creative thinking process has been receiving greater attention. In particular, a growing number of studies in this field have been carried out using cognitive neuroscience technologies. These findings suggest that the RAT provides researchers with a way to deepen their understanding of different levels of creativity.
This study investigates the intricate relationships among personality traits, well-being, and attitudes toward being ridiculed and laughed at in 379 young adults, who are typically sensitive to ...social feedback and peer evaluation. These Taiwanese university students completed the Big Five mini-markers, PhoPhiKat-TC, and Mental Health Continuum Short Form scales. Analysis of the resulting data focused on understanding the mediating effects of the respondents' laughter/ridicule orientations on the relationship between their Big Five traits and well-being. Most of the personality traits were found to be positively correlated with well-being and with gelotophobia, the fear of being laughed at. Extraversion emerged as the preeminent correlate with well-being. In accordance with Seligman's Learned Optimism hypothesis, knowledge of the outcomes of this study could heighten gelotophobes' awareness of their responses to laughter, and thus serve as a foundation for the development and refinement of strategies for their effective navigation of social situations involving laughter/ridicule.
Limited research has been conducted on humor among the indigenous Taiwanese (IND) population. This study attempted to identify the differential neural correlates of humor comprehension and ...appreciation between IND and Han Chinese (HAN) populations. Each participant was presented with jokes and non-jokes. IND participants when encountered with jokes displayed a greater activation of the mesolimbic dopaminergic reward system, including the amygdala, midbrain, and nucleus accumbens than HAN participants. This suggests a more pleasurable response and appreciation of humor. The IND group also displayed greater activation in the right temporoparietal junction (rTPJ) than HAN, suggesting that the IND group may experience a greater sense of novelty and be more involved in social understanding, thus exhibiting greater humor appreciation. In terms of humor comprehension, both IND and HAN showed greater activation in the superior temporal gyrus (STG) and dorsal anterior cingulate cortex (dACC). IND exhibited greater activation in the anterior STG (aSTG), while HAN showed greater activation in the posterior STG (pSTG). This suggests that the IND tends to integrate emotional messages, whereas the HAN focuses on comprehending semantic cognitive information. Interestingly, HAN did not show any greater activation than IND in terms of appreciation of humor. These group disparities have substantial implications for advancing our knowledge of the neural mechanisms underlying humor comprehension and appreciation.
Display omitted
•In humor appreciation, IND showed greater activation in AMG, midbrain, and NAc.•IND exhibited higher activation in aSTG, while HAN showed greater activation in pSTG.•IND showed greater activation in right TPJ.•IND perceived greater enjoyment and novelty perception.•HAN prioritize semantic cognitive information in humor comprehension.
Background
Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need.
Methods
We developed an ...integrated, multi‐tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)‐based anti‐cachectic agents. In the initial screening, we used inflammatory cytokine‐induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age‐related reduction of mobility and contractility, followed by the C‐26 colon adenocarcinoma mouse model of cachexia to confirm the anti‐muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL‐6). Transcriptome analysis, quantitative real‐time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour‐induced muscle atrophy.
Results
Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis‐à‐vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age‐associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C‐26 mouse model. MDP at 1000 mg/kg (MDP‐H) was effective in protecting body weight loss (P < 0.05) in C‐26 tumour‐bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP‐treated C‐26‐tumour‐bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL‐6 levels (P = 0.06) relative to vehicle control. This decreased serum IL‐6 was associated with the in vitro suppressive effect of MDP (25 and 50 μg/mL) on IL‐6 secretion into culture medium by C26 cells. RNA‐seq analysis, followed by quantitative real‐time polymerase chain reaction and/or immunoblotting, shows that MDP's anti‐cachectic effect was attributable to its ability to reverse the C‐26 tumour‐induced re‐programming of muscle homoeostasis‐associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin‐1), in skeletal muscles.
Conclusions
All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.
•High Dark Tetrad traits are positively associated with dark comic styles.•Sadism shows a robust relationship with sarcasm.•Sarcasm positively mediates the relationship between Dark Tetrad and ...NA.•Cynicism negatively mediates the relationship between psychopathy and PA.•Dark comic styles impede twofold on the well-being of people with high psychopathy.
PDF
