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Summary: Background: Recently, a panel of multi‐society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction‐associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD). Aims: We compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all‐cause and cause‐specific mortality. Methods: A total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all‐cause/cause‐specific mortality. Results: During a median follow‐up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%–23% higher risk of all‐cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02–1.29 for SLD; HR: 1.23, 95% CI: 1.09–1.38 for MAFLD; HR: 1.13, 95% CI: 1.01–1.27 for metabolic dysfunction‐associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all‐cause (HR: 1.68, 95% CI: 1.10–2.57) and cancer‐related mortality (HR: 2.40, 95% CI: 1.23–4.66). MASLD with advanced fibrosis had an increased risk of all‐cause mortality compared to MASLD without advanced fibrosis. Conclusions: SLD, especially MASLD and MetALD, is associated with increased all‐cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all‐cause mortality, adopting the proposed SLD criteria may help identify a sub‐group of individuals with SLD who are at an increased risk for all‐cause mortality. [ABSTRACT FROM AUTHOR]

Summary Background Aim Methods Results Conclusions Economic hardship associated with chronic liver disease (CLD) may delay timely access to healthcare.To estimate the national burden of financial hardship across the spectrum of CLD in the United States (US) during the coronavirus disease 2019 (COVID‐19) pandemic.A cross‐sectional analysis was performed using the 2020–2021 US National Health Interview Survey database. The questionnaire defined financial hardship from medical bills and cost‐related nonadherence to medications in patients with CLD. We used weighted survey analysis to obtain the national estimates.While 6.9% (95% confidence interval [CI]: 6.7%–7.2%) out of 60,689 US adults (weighted sample: 251 million) reported financial hardship and inability to pay medical bills; 10.6% (95% CI: 8.3%–13.4%), 18.2% (95% CI: 14.5%–22.6%), 22.6% (95% CI: 11.0%–41.0%) with hepatitis, CLD/cirrhosis, and liver cancer experienced an inability to pay their medical bills due to financial hardship, respectively. 19.8% (95% CI: 15.9%–24.5%) and 23.3% (95% CI: 12.5%–39.3%) with CLD/cirrhosis and liver cancer, respectively experienced cost‐related nonadherence to medications, compared to a tenth of US adults (10.7%, 95% CI: 10.3%–11.2%). CLD/cirrhosis demonstrated an independent association with financial hardship from medical bills and cost‐related nonadherence to medications. Overall, these disparities were more pronounced in individuals aged <65 years old. In addition, over 40% of individuals with CLD/cirrhosis reported difficulties accessing medical care during the COVID‐19 pandemic. CLD/cirrhosis showed an independent association with difficulties accessing medical care due to COVID‐19.Financial hardship from medical bills and cost‐related nonadherence to medication can negatively impact individuals with CLD and need further evaluation. [ABSTRACT FROM AUTHOR]

Background: YouTube is a widely used video sharing and social networking platform among children and adolescents. However, research on YouTube usage among this population remains scarce. Specifically, studies on factors that influence children and adolescents' usage are clinically significant but largely lacking. Additionally, few studies have examined the association between usage and emotional/behavioral problems, which is fundamental to smartphone research. Therefore, this study explored the relationship between early childhood temperament, subsequent YouTube usage patterns, and emotional/behavioral problems. Methods: The Kids Cohort for Understanding Internet Addiction Risk Factors in Early Childhood (K-CURE) is the first long-term prospective cohort study in Korea aimed at understanding the long-term effects of media exposure on young children. The study included 195 children aged 8–11 years enrolled in the K-CURE study. Caregivers, predominantly mothers, who voluntarily participated during their visits to community centers for children's mental health in Korea's major cities, completed a detailed self-administered survey. Childhood temperament was measured in 2018 when the children were 5–8 years old. Subsequent YouTube usage patterns and emotional/behavioral problems were assessed in 2021. Data were analyzed using frequency analysis, correlation analysis, and multiple linear regression. Results: The study found that 21.0% of children started using YouTube before age 4, with the most common onset age being 8–9 years (30.3%). These children used YouTube on average 4.8 days per week for 68.5 min per day. Early childhood persistence was negatively associated with the subsequent YouTube usage duration, and the age at first YouTube use was negatively correlated with subsequent usage frequency. Furthermore, a younger age at first YouTube use and higher usage frequency were significantly associated with increased emotional/behavioral problems. Conclusions: In the YouTube environment, where content is automatically recommended based on user preferences, traits related to usage patterns may be associated with persistence, which is linked to self-regulation. Considering the current trend where children use smartphones, contents frequently for very short durations, our findings highlight the importance of self-regulation in the media usage of children who are still developing. Additionally, our results provide fundamental information for future YouTube studies and illustrate similarities and differences between smartphone and YouTube research. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion Several reports show a significant association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all‐cause/cause‐specific mortality.This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988–1994) and NHANES 2007–2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all‐cause/cause‐specific mortality among individuals with MASLD.During the follow‐up of a median of 26.3 years (interquartile range: 19.9–27.9), higher levels of ePWV among individuals with MASLD were associated with increased all‐cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32–1.58) increase in all‐cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32–1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer‐related mortality. Sensitivity analyses using the NHANES 2007–2014 dataset showed results identical to the original analysis.Higher ePWV in MASLD was associated with a higher risk of all‐cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all‐cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Purpose: Studies evaluating food insecurity and metabolic dysfunction-associated steatotic liver disease (MASLD) and significant hepatic fibrosis are currently scarce. We evaluated the characteristics of food insecure individuals and whether food insecurity was associated with MASLD and significant hepatic fibrosis in the US population. Methods: In this cross-sectional study from the National Health and Nutrition Examination Survey 2017–2018, 3441 participants with complete data were enrolled. We defined MASLD and significant hepatic fibrosis (≥ F2) by transient elastography in the absence of other causes of liver disease. The detailed questionnaire assessed and categorized food security as high, marginal, low, and very low food security. Results: Food-insecure subjects were more likely to be female, younger, more impoverished, non-Hispanic blacks, Hispanics, and less likely to be educated, married, and physically active. Food insecurity increased the odds of the prevalence of MASLD by 42% (odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.12–1.78) after adjustment for demographic, lifestyle, and metabolic risk factors. The addition of diabetes and obesity did not change this association (OR: 1.36, 95% CI: 1.03–1.78). The multivariable model showed an independent relationship between food insecurity and significant hepatic fibrosis (OR: 1.40, 95% CI: 1.04–1.88) after adjustment for demographic, lifestyle, and metabolic risk factors, although the association was attenuated and changed insignificantly after adjustment for diabetes and obesity. Conclusions: Food insecurity was associated with higher odds for MASLD. While there is a relationship between food insecurity and significant hepatic fibrosis, this relationship changed insignificantly after adjustment of diabetes and obesity. [ABSTRACT FROM AUTHOR]

Background and Aims: Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone- to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults. Methods: A cross-sectional analysis using the 2013--2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease. Results: Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women. Conclusion: The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Depression has been associated with nonalcoholic fatty liver disease (NAFLD). Data addressing the impact of depression on NAFLD‐related mortality are evolving. We aim to study the association of depression in NAFLD and all‐cause/cause‐specific mortality in the United States. Methods: A total of 11,877 individuals with NAFLD in the 2007–2016 National Health and Nutrition Examination Survey with the availability of linked mortality through 2019 were analysed. NAFLD was defined by utilizing the hepatic steatosis index in the absence of known causes of chronic liver disease. Depression and functional impairment due to depression were assessed using the Patient Health Questionnaire. Results: During the median follow‐up of 7.6 years, individuals with depression among individuals with NAFLD had a 35% higher all‐cause mortality than those without depression (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03–1.75) after adjusting for demographic, lifestyle and clinical risk factors. NAFLD with functional impairment due to depression had a 62% higher all‐cause mortality than NAFLD without functional impairment (HR: 1.62, 95% CI: 1.10–2.39). Depression in NAFLD was associated with an approximately 50% increase in the risk for cardiovascular mortality, with a 2‐fold higher cardiovascular mortality in those with functional impairment compared to those without (HR: 2.07, 95% CI: 1.30–3.30). However, there was no significant difference in cancer‐ and accident‐related mortalities in NAFLD with or without depression. Conclusions: Depression among individuals with NAFLD was associated with a higher risk for all‐cause and cardiovascular mortality in the United States. [ABSTRACT FROM AUTHOR]

Aims and objectives: To identify the factors influencing the intent to provide care among nurses involved in coronavirus disease 2019 (COVID‐19) care. Background: COVID‐19 was first reported in Wuhan, China, in 2019. In 2020, the World Health Organisation declared it a pandemic, leading to 5,827,104 deaths and 421,203,495 confirmed cases as of 19 February 2022. The high transmissibility of COVID‐19 has prolonged the pandemic for over 2 years, resulting in deleterious effects on nurses' physical and mental health. The fear of infection and isolation may lead to negative experiences and perceptions among COVID‐19 frontline nurses, which may ultimately degrade the quality of patient care. Thus, it is essential to identify factors influencing of nurses' intent to provide care. Design: Cross‐sectional study. Methods: Data were collected from 169 nurses involved in direct COVID‐19 care at a hospital designated for infectious disease care in Korea from August to September 2021 using an online questionnaire. STROBE checklist was followed. Results: Nurses' intent to provide care significantly differed based on whether they lived with parents and had adequate availability of personal protection equipment. The correlation analysis indicated that the intent to provide care was significantly positively correlated with normative beliefs, control beliefs, attitude towards the behaviour, subjective norms and perceived behavioural control. Perceived behavioural control, control beliefs and attitude towards the behaviour were significant factors influencing nurses' intent to provide COVID‐19 care. Conclusion: This study showed that nurses perceived behavioural control and positive behaviour towards providing COVID‐19 care fundamentally influenced their intent to provide care. Relevance to clinical practice: In clinical practice, the safety and rights of individual nurses who participated in COVID‐19‐related patient care are promoted, and ultimately, the quality of patient care is improved. Furthermore, active support at the organisation and government level is needed to strengthen the capabilities necessary for nursing patients with infectious diseases. [ABSTRACT FROM AUTHOR]

We studied the trends in liver cancer‐related mortality before and during the COVID‐19 pandemic. Quarterly age‐standardized mortality and quarterly percentage change (QPC) for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) were estimated using the US national mortality database 2017–2021. Quarterly age‐standardized mortality from HCC decreased steadily with an average QPC of −0.4% (95% confidence interval [CI]: −0.6% to −0.2%). A decrease in hepatitis C virus and hepatitis B virus‐related HCC mortality of −2.2% (95% CI: −2.4% to −1.9%) and −1.1% (95% CI: −2.0% to −0.3%) was noted. In contrast, mortality for HCC from nonalcoholic fatty liver disease (3.0%, 95% CI: 2.0%–4.0%) and alcohol‐related liver disease (1.3%, 95% CI: 0.8%–1.9%) demonstrated a linear increase. There was a linear increase in the quarterly age‐standardized ICC‐related mortality (0.8%, 95% CI: 0.5%–1.0%). While ICC‐related mortality continued to increase, HCC‐related mortality tended to decline mainly due to a decline in mortality due to viral hepatitis. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Patients with pre‐existing cirrhosis and exposure to coronavirus disease‐19 (COVID‐19) may portend a poor prognosis. We evaluated the temporal trends in aetiology‐based hospitalisations and potential predictors of in‐hospital mortality in hospitalisation with cirrhosis before and during the COVID‐19 pandemic. Methods: Based on the US National Inpatient Sample 2019–2020, we determined quarterly trends in aetiology‐based hospitalisations with cirrhosis and decompensated cirrhosis and identified predictors of in‐hospital mortality in hospitalisation with cirrhosis. Results: We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID‐19 era. Hospitalisation rates for alcohol‐related liver disease (ALD)‐related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%–5.1%), with a notably higher rate during the COVID‐19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)‐related cirrhosis decreased steadily with a trend of −1.4% of QPC (95% CI: −2.5% to −0.1%). Quarterly trends in the proportion of ALD‐ (QPC: 1.7%, 95% CI: 0.9%–2.6%) and nonalcoholic fatty liver disease‐related (QPC: 0.7%, 95% CI: 0.1%–1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID‐19 era and COVID‐19 infection were independent predictors of in‐hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV‐related cirrhosis, ALD‐related cirrhosis was associated with a 40% higher risk of in‐hospital mortality. Conclusion: In‐hospital mortality in cirrhosis was higher in the COVID‐19 era than in the pre‐COVID‐19 era. ALD is the leading aetiology‐specific cause of in‐hospital mortality in cirrhosis with an independent detrimental impact of the COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Podocyte damage and renal inflammation are the main features and pathogenesis of diabetic nephropathy (DN). Inhibition of lysophosphatidic acid (LPA) receptor 1 (LPAR1) suppresses glomerular inflammation and improves DN. Herein, we investigated LPA-induced podocyte damage and its underlying mechanisms in DN. We investigated the effects of AM095, a specific LPAR1 inhibitor, on podocytes from streptozotocin (STZ)-induced diabetic mice. E11 cells were treated with LPA in the presence or absence of AM095, and the expression of NLRP3 inflammasome factors and pyroptosis were measured. A chromatin immunoprecipitation assay and Western blotting were performed to elucidate underlying molecular mechanisms. Gene knockdown by transfecting small interfering RNA was used to determine the role of the transcription factor Egr1 (early growth response protein 1) and histone methyltransferase EzH2 (Enhancer of Zeste Homolog 2) in LPA-induced podocyte injury. AM095 administration inhibited podocyte loss, NLRP3 inflammasome factor expression, and cell death in STZ-induced diabetic mice. In E11 cells, LPA increased NLRP3 inflammasome activation and pyroptosis via LPAR1. Egr1 mediated NLRP3 inflammasome activation and pyroptosis in LPA-treated E11 cells. LPA decreased H3K27me3 enrichment at the Egr1 promoter in E11 cells by downregulating EzH2 expression. EzH2 knockdown further increased LPA-induced Egr1 expression. In podocytes from STZ-induced diabetic mice, AM095 suppressed Egr1 expression increase and EzH2/H3K27me3 expression reduction. Collectively, these results demonstrate that LPA induces NLRP3 inflammasome activation by downregulating EzH2/H3K27me3 and upregulating Egr1 expression, resulting in podocyte damage and pyroptosis, which may be a potential mechanism of DN progression. [ABSTRACT FROM AUTHOR]

An association between depression and metabolic dysfunction-associated fatty liver disease (MAFLD) appears logical on the basis of previous observations linking depression to nonalcoholic fatty liver disease. We aim to investigate the association between depression and MAFLD and significant fibrosis. This cross-sectional study was conducted on data from National Health and Nutrition Examination Survey, 2017 to March 2020 Pre-pandemic dataset. Depression and depression-related functional impairment were assessed using the Patient Health Questionnaire (PHQ-9). MAFLD, based on the criteria proposed by an international expert panel, and significant fibrosis were defined by transient elastography. Of the 3327 individuals (mean age: 46.9 years, 50.2 % men), the prevalence of depression and functional impairment due to depression was higher among individuals with MAFLD or significant fibrosis than among those without. Individuals with depression were approximately 70 % more likely to have MAFLD than those without. In multivariable analyses, depression was associated with an increased risk of MAFLD (odds ratio [OR]: 1.77, 95 % confidence interval [CI]:1.33–2.36 for ≥263 dB/m and OR: 1.70, 95 % CI: 1.20–2.41 for ≥285 dB/m). These associations were more pronounced in postmenopausal women than premenopausal women. In terms of significant fibrosis, depression remained an independent predictor of significant fibrosis; however, it attenuated after adjustment for body mass index. Temporal causality and residual confounders could not be entirely investigated due to the study design. Depression was independently associated with MAFLD and significant fibrosis in a nationally representative sample of adults in the US. • Depression is a clinically significant and growing public health problem. • Depression increases the risk of diabetes and metabolic syndrome. • The prevalence of depression was significantly higher in MAFLD than in no MAFLD. • Depression is associated with MAFLD and significant fibrosis. [ABSTRACT FROM AUTHOR]

The impact of different types of physical activity (PA) on mortality in the context of nonalcoholic fatty liver disease (NAFLD) is not clearly defined and was investigated. This prospective study was performed using the 2007–2014 US National Health and Nutrition Examination Survey with mortality follow-up through 2019. Over a median follow-up of 8.6 years, leisure-time and transportation-related PA that fulfilled the criteria outlined in the PA guidelines (≥150 min/week) in NAFLD were associated with a risk reduction in all-cause mortality (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.59–0.98 for leisure-time PA; HR: 0.62, 95% CI: 0.45–0.86 for transportation-related PA). Leisure-time and transportation-related PA in NAFLD were inversely associated with all-cause mortality in a dose-dependent manner (p for trends <0.01). Furthermore, the risk for cardiovascular mortality was lower in those meeting the PA guidelines for leisure-time PA (HR: 0.63, 95% CI: 0.44–0.91) and transportation-related PA (HR: 0.38, 95% CI: 0.23–0.65). Increasing sedentary behavior was linked to an increased risk of all-cause and cardiovascular mortality (p for trend <0.01). Meeting PA guidelines (≥150 min/week) for leisure-time and transportation-related PA has beneficial health effects on all-cause and cardiovascular mortality among individuals with NAFLD. Sedentary behavior in NAFLD showed harmful effects on all-cause and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Adrenal medullary chromaffin (AMC) cells in the perinatal period and carotid body glomus cells after birth respond to hypoxia with catecholamine secretion. The hypoxia detection mechanism in such O 2 -sensitive cells is still not well defined. One hypothesis is that a decrease in cellular ATP may be involved in the hypoxia detection. This idea is based on ATP dependence of TASK channel activity that regulates the resting membrane potential and is suppressed by hypoxia in glomus cells. Mitochondrial ATPase inhibitor factor-1 (IF 1), a physiological regulator of ATP synthase, helps prevent ATP hydrolysis under hypoxic conditions. In cells where IF 1 expression is high, exposure to hypoxia is expected to have no effect on TASK channel activity. This possibility was electrophysiologically and immunocytochemically explored. Single channel recordings revealed that 36-pS TASK3-like channels contribute to the resting membrane potential in young rat adrenal cortical (AC) cells. TASK3-like channel activity in a cell-attached patch was not affected by bath application of mitochondrial inhibitors. Consistent with this finding, IF 1 -like immunoreactive material was well expressed in rat AC cells. In further support of our hypothesis, IF 1 -like immunoreactive material was well expressed in adult rat AMC cells that are known to be hypoxia-insensitive and minimally expressed in newborn AMC cells that are hypoxia-sensitive. These results provide evidence for the functional relevance of IF 1 expression in excitability in O 2 -sensitive cells in response to mitochondrial inhibition. • IF 1 was well expressed in adult rat adrenal medullary chromaffin (AMC) cells. • IF 1 expression was minimal in newborn AMC cells. • IF 1 was well expressed in both newborn and adult adrenal cortical (AC) cells. • 36-pS TASK3-like channels were active at rest in young AC cells. • Mitochondrial inhibitors did not affect TASK3-like channels in young AC cells. [ABSTRACT FROM AUTHOR]

Muscle strength in non-alcoholic fatty liver disease and all-cause and cause-specific mortality Keywords: death; handgrip strength; hepatic steatosis; nhanes; sarcopenia EN death handgrip strength hepatic steatosis nhanes sarcopenia 513 516 4 01/27/23 20230201 NES 230201 Abbreviations BMI body mass index CI confidence interval HIS hepatic steatosis index HR hazard ratio NAFLD non-alcoholic fatty liver disease NHANES National Health and Nutrition Examination Survey UCOD underlying cause of death Key points Higher muscle strength among individuals with non-alcoholic fatty liver disease is associated with a lower risk of all-cause and cardiovascular mortality independent of known demographic, clinical and metabolic risk factors. 8 Range of combined grip strength/body mass index for women: quartile 1: <1.437, quartile 2: >=1.437 and <1.712, quartile 3: >=1.712 and <2.025, quartile 4: >=2.025. First, we used a non-invasive marker to define NAFLD, which may misclassify the true prevalence of NAFLD, because NHANES 2011-2014 data lack radiological or histological information, which is considered the gold standard for the diagnosis of NAFLD. [Extracted from the article]

Backgrounds and Aims: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)‐related end‐stage liver disease (ESLD). We assess aetiology‐based hospitalizations for ESLD in the United States, 2016–2019. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. Results: National hospitalization rates for non‐alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (−6.5% AAPC). Hospitalizations for ESLD in alcohol‐related liver disease (ALD) increased as well. Conclusions: Hospitalization rates for NAFLD‐ and ALD‐related ESLD increased steadily, while those for HCV‐related ESLD decreased during the direct‐acting antivirals era. [ABSTRACT FROM AUTHOR]

Background: Mesangial cell fibrosis, a typical symptom of diabetic nephropathy (DN), is a major contributor to glomerulosclerosis. We previously reported that the pharmacological blockade of lysophosphatidic acid (LPA) signaling improves DN. Although LPA signaling is implicated in diabetic renal fibrosis, the underlying molecular mechanisms remain unclear. Here, the role of carbohydrate-responsive element-binding protein (ChREBP) in LPA-induced renal fibrosis and the underlying mechanisms were investigated. Methods: Eight-week-old wild-type and db/db mice were intraperitoneally injected with the vehicle or an LPAR1/3 antagonist, ki16425 (10 mg/kg), for 8 weeks on a daily basis, following which the mice were sacrificed and renal protein expression was analyzed. SV40 MES13 cells were treated with LPA in the presence or absence of ki16425, and the expression of ChREBP and fibrotic factors, including fibronectin, TGF-β, and IL-1β, was examined. The role of ChREBP in the LPA-induced fibrotic response was investigated by ChREBP overexpression or knockdown. The involvement of Smad ubiquitination regulatory factor-2 (Smurf2), an E3 ligase, in LPA-induced expression of ChREBP and fibrotic factors was investigated by Smurf2 overexpression or knockdown. To identify signaling molecules regulating Smurf2 expression by LPA, pharmacological inhibitors such as A6370 (Akt1/2 kinase inhibitor) and Ly 294002 (PI3K inhibitor) were used. Results: The renal expression of ChREBP increased in diabetic db/db mice, and was reduced following treatment with the ki16425. Treatment with LPA induced the expression of ChREBP and fibrotic factors, including fibronectin, TGF-β, and IL-1β, in SV40 MES13 cells, which were positively correlated. The LPA-induced expression of fibrotic factors increased or decreased following ChREBP overexpression and knockdown, respectively. The production of reactive oxygen species (ROS) mediated the LPA-induced expression of ChREBP and fibrotic factors, and LPA decreased Smurf2 expression via Traf4-mediated ubiquitination. The LPA-induced expression of ubiquitinated-ChREBP increased or decreased following Smurf2 overexpression and knockdown, respectively. Additionally, Smurf2 knockdown significantly increased the expression of ChREBP and fibrotic factors. The pharmacological inhibition of Akt signaling suppressed the LPA-induced alterations in the expression of ChREBP and Smurf2. Conclusion: Collectively, the results demonstrated that the ROS/Akt-dependent downregulation of Smurf2 and the subsequent increase in ChREBP expression might be one of the mechanisms by which LPA induces mesangial cell fibrosis in DN. [ABSTRACT FROM AUTHOR]

Summary: In the field of thermal energy, interest in carbon‐free fuels, such as H2, is increasing to reduce greenhouse gas emissions; simultaneously, efforts are being made to reduce NOx emissions. In this study, experimental and numerical methodologies were applied to analyze the characteristics of flameless combustion under oxygen enrichment conditions for the simultaneous reduction of greenhouse gases and fine dust precursors. Flameless combustion was achieved under all conditions, and numerical simulations using GRI‐mech 3.0 and the eddy dissipation concept were validated by comparison with the experimental temperature and NO values. With decreasing oxygen fraction in the oxidant, the main reaction zone of the 100% CH4 case is expanded owing to an increase in internal recirculation. Under the oxygen‐enriched conditions, when mixed with H2 and CO, fuel oxidation is promoted compared to the 100% CH4 case. Less than 25 ppm of NO was emitted for all but the H2 addition case, where the emission increased to approximately 95 ppm. During flameless combustion, NO formation by the N2O intermediate route is dominant regardless of the fuel composition and oxygen fraction, and the proportion of NO formation by prompt and NNH routes increases under N2 dilution and H2 addition. [ABSTRACT FROM AUTHOR]

Summary: Flameless combustion is a good alternative for a combustion technology that can simultaneously reduce CO and NOx, which generally have a trade‐off relationship with each other. The most important feature of flameless combustion is its ability to control the radical and intense combustion atmosphere and suppress the formation of flame hot spots. Existing flameless combustion technology requires an additional diluent or preheating of reactants; but in this study, flameless combustion was achieved by controlling the flow through a bluff‐body burner and inducing internal recirculation of the flue gas. In addition, the characteristics of flameless combustion using various fuels (CH4/CO/H2) were analyzed in detail. Consequently, in the flameless combustion atmosphere, the formation of hot zones was suppressed, and the amount of thermal NO was significantly reduced (>85% NO reduction). In the case of CO, most of the combustion characteristics were almost the same as those of methane, whereas when hydrogen was added, the amount of thermal NO generated was relatively large (<15% NO reduction) due to the influence of the hydrogen fuel in the chemical reaction. The effect of hydrogen on NO generation was found to be mainly a chemical reaction such as NNH and N2O intermediate route, which is especially noticeable in a flameless combustion atmosphere where the formation of a localized high‐temperature region is suppressed. In addition, stable complete combustion was achieved even at a very low excess air ratio in a flameless combustion atmosphere. These characteristics of flameless combustion can have positive influence in terms of low pollutant emission and fuel diversification. [ABSTRACT FROM AUTHOR]

Background & Aims: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (a) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (b) identify at‐risk populations for HCV infection in the United States (US) general population. Methods: Population‐based analyses using the National Health and Nutrition Examination Survey (2013‐2018) were performed with a focus on HCV infection. We analysed the prevalence of HCV infection based on the health insurance status before the direct‐acting antiviral (DAA) era (2013‐2014) and during the DAA era (2015‐2018). Results: The age‐adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval, 0.71%‐1.19%) in the US non‐institutionalized civilian population. Although the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40‐69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion and not having private health insurance. Conclusion: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era. [ABSTRACT FROM AUTHOR]

Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults. We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors. During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD. In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors. Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death. [Display omitted] • Metabolic dysfunction-associated fatty liver disease (MAFLD) was associated with increased all-cause and cardiovascular mortality. • NAFLD was associated with increased all-cause mortality among individuals with known metabolic risk factors. • Advanced fibrosis in MAFLD was associated with higher estimates for all-cause mortality than in NAFLD. [ABSTRACT FROM AUTHOR]

Summary: Hydrogen, a renewable energy source, is attracting interest because it does not emit the greenhouse gases and air pollutants generated by the use of fossil fuels. This study aims to analyze the effects of a hydrogen blend on pressurized oxy‐fuel combustion (POFC) to support hydrogen infrastructure and reduce greenhouse gas emissions. A counter‐flow diffusion flame model was used to analyze the characteristics of POFC. Purified and unpurified natural gas and hydrogen gas were used as fuels. Increased reactivity of the reactants and high flame stability can be simultaneously achieved through POFC. Pressure is a more important parameter for controlling the flame temperature dominantly than the hydrogen content and should be prioritized in the design of POFC systems. The third‐body reaction is activated in pressurized methane‐oxy combustion, promoting chemical reactions that contribute to the combustion process. In particular, it was confirmed that hydrogen blending inhibits the dehydrogenation of hydrocarbons and activates an exothermic reaction based on H radicals. As the hydrogen content increases to up to 30%, the adiabatic flame temperature and the increase in OH radicals enhance the NO‐production rate when the fuel or oxidant contains some impurity (N2). The nitrogen oxides produced by impurities have a higher rate of formation when present in the oxidant. Therefore, the NO‐reduction method for the cofiring of unpurified methane and hydrogen in POFC should be considered. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD‐related sarcopenia remains undefined. We aim to determine the all‐cause and cause‐specific mortality from sarcopenia among adults with NAFLD in the USA. Methods: 11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all‐cause mortality and cause‐specific mortality, and hazard ratio (HR) adjusted for known risk factors. Results: During a median follow‐up of 23 years or more, sarcopenia was associated with increased all‐cause mortality (HR 1.27, 95% confidence interval [CI] 1.11‐1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all‐cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all‐cause mortality (HR 1.28 95% CI 1.06‐1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer‐ and diabetes‐related mortality among those with NAFLD. This association was not noted in those without NAFLD. Conclusion: In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all‐cause, cancer‐ and diabetes‐related mortality in individuals with NAFLD. [ABSTRACT FROM AUTHOR]

We examined trends in mortality from hepatitis C virus (HCV) infection and alcoholic liver disease (ALD) in the setting of drug overdose. Using US Census and national mortality records (2009‐2018), we identified deaths with HCV infection, ALD and drug overdose. HCV‐related mortality without drug overdose increased up to 2014, followed by a marked decrease. Mortality from HCV and drug overdose increased significantly. Whereas ALD‐related mortality without drug overdose continued to rise, no significant trend from ALD with drug overdose was noted. HCV‐related mortalities reduced after the introduction of DAA agents, while drug overdose‐related mortality in HCV was constantly increased. [ABSTRACT FROM AUTHOR]

Background: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging. Aims: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA. Methods: We performed a retrospective analysis using the National Inpatient Sample, 2005–2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality. Results: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44–1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of − 3.1% (95% CI − 5.7% to − 0.3%). Conclusions: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade. [ABSTRACT FROM AUTHOR]

Background: Patients from rural and low‐income households may have suboptimal access to liver disease care, which may translate into worse HCC outcomes. The authors provide a comprehensive update of HCC incidence and outcomes among US adults, focusing on the effect of rural geography and household income on tumor stage and mortality. Methods: The authors retrospectively evaluated adults with HCC using Surveillance, Epidemiology, and End Results data from 2004 to 2017. HCC incidence was reported per 100,000 persons and was compared using z‐statistics. Tumor stage at diagnosis used the Surveillance, Epidemiology, and End Results staging system and was evaluated with multivariate logistic regression. HCC mortality was evaluated using Kaplan‐Meier and multivariate Cox proportional hazards methods. Results: HCC incidence plateaued for most groups, with the exception of American Indians/Alaska Natives (2004‐2017: APC, 4.17%; P <.05) and patients in the lowest household income category (<$40,000; 2006‐2017: APC, 2.80%; P <.05). Compared with patients who had HCC in large metropolitan areas with a population >1 million, patients in more rural regions had higher odds of advanced‐stage HCC at diagnosis (odds ratio, 1.10; 95% CI, 1.00‐1.20; P =.04) and higher mortality (hazard ratio, 1.05; 95% CI, 1.01‐1.08; P =.02). Compared with the highest income group (≥$70,000), patients with HCC who earned <$40,000 annually had higher odds of advanced‐stage HCC (odds ratio, 1.15; 95% CI, 1.01‐1.32; P =.03) and higher mortality (hazard ratio, 1.23; 95% CI, 1.16‐1.31; P <.001). Conclusions: Patients from rural regions and lower‐income households had more advanced tumor stage at diagnosis and significantly higher HCC mortality. These disparities likely reflect suboptimal access to consistent high‐quality liver disease care, including HCC surveillance. Patients from rural and low‐income households have suboptimal access to high‐quality liver disease care, which affects timely receipt of surveillance for hepatocellular carcinoma (HCC). This study of a large national cancer registry demonstrates that patients from rural regions and low‐income households have more advanced HCC tumor stage at diagnosis and overall lower HCC survival. [ABSTRACT FROM AUTHOR]

This article presents time-resolved analysis of SF6 arc plasma generated in a laboratory-scale model chamber prepared for studying the characteristics of a circuit breaker. During the arc discharge, the optical emission spectra are measured by a high-speed spectrometer under various operating conditions. The time-resolved electron temperature and density values are determined using the well-known Boltzmann plot and Stark broadening methods, respectively, for the measured Cu I, S II, and F I emission lines. Moreover, the temporal evolution of the electrical conductivity of the arc plasma is deduced from the measured electron temperature and density values, depending on the operating conditions. In our experimental conditions, it is revealed that the electrical conductivity of arc plasmas is mainly determined by Coulomb (electron–ion) collisions as opposed to electron–neutral collisions due to the much higher Coulomb collision frequency compared to the electron–neutral collision frequency. Both the electron temperature and density were found to increase when the discharge current is increased at a fixed gas pressure, resulting in an increase of the electrical conductivity. When the gas pressure inside the model chamber is increased, the electron density is increased as well, but the electrical conductivity does not change significantly due to the slight change in the electron temperature. The present study will be helpful for investigating the performance capabilities of circuit breakers because the electrical conductivity, the most important parameter to guarantee successful circuit breaking at points near the current-zero, is determined by the temperature and density of the electrons. [ABSTRACT FROM AUTHOR]

Our findings support the existing notion that patients with diabetes and prediabetes are at-risk population and can be screened for NAFLD and NAFLD-related fibrosis. Fibrosis and cirrhosis were found in approximately one-fourth of patients with diabetes and one-sixth of those with prediabetes among individuals with NAFLD. INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. [Extracted from the article]

Polygonum multiflorum Thunb. (PM) root extracts have been used for treating graying hair in Oriental medicine; however, the molecular mechanisms underlying the melanogenic effects of PM root have not been fully understood. In the present study, we investigated the melanogenic effects of an ethanolic extract of PM root (PME) and the mechanisms involved. We examined the effects of PME on cell viability, cellular melanin content, and tyrosinase activity in B16F10 cells. The melanogenic mechanism of PME was explored using signaling inhibitors and examining the expression of melanogenic genes and signaling molecules by western blot and RT-qPCR analyses. PME did not exhibit any cytotoxicity in B16F10 cells compared to that in control cells. PME treatment significantly increased melanin production and tyrosinase activity. In addition, PME induced the expression of cyclooxygenase-2 (COX2) as well as that of melanogenic genes, such as microphthalmia-associated transcription factor (MiTF), tyrosinase-related protein (Trp) 1, Trp2, and tyrosinase, in B16F10 cells. PME treatment increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), and pretreatment with SB 203580, a p38 MAPK inhibitor, significantly suppressed this PME-induced increase in the expression of COX2 and melanogenic genes. These results indicate that PME induced the expression of melanogenic genes by inducing COX2 expression via the activation of the p38 MAPK pathway, thereby contributing to the enhancement of melanogenesis. [ABSTRACT FROM AUTHOR]

Background & Aims: Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD. Methods: We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis. Results: Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose‐dependent manner. During the median follow‐up of 23 years, having a higher diet quality was associated with reduction in risk of all‐cause mortality in the age, sex, Race/ethnicity‐adjusted hazard ratio (HR) (Q4, HR: 0.60, 95% CI: 0.52‐0.68) and the multivariate model (Q4, HR: 0.81, 95% CI: 0.71‐0.92). Higher diet quality was associated with a lower risk for all‐cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer‐related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD. Conclusions: High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer‐related and all‐cause mortality in those without NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis.Methods: Our cross-sectional study included 559 subjects (mean age of 53 years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25 kg/m2) or non-obese (< 25 kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+ , (3) obese MS-, and (4) obese MS+.Results: Obese MS- and non-obese MS+ groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+ group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+ group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+ groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis.Conclusion: The non-obese MS+ group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+ individuals who develop NASH with significant hepatic fibrosis.Clinical Trial Number: NCT02206841. [ABSTRACT FROM AUTHOR]

The current study presents the experimental results investigating combustion characteristics of sewage sludge fuels (SS) reference to coal and wood pellet as the two typical base fuels. Two types of SS were produced by drying and hydrothermal carbonization technology. The composition analysis and the thermogravimetric analysis (TGA) showed that SS were highly volatile with low ignition temperature than coal and wood pellet. In the lab-scale bubbling fluidized bed experiments, the combustion gas composition and bed temperature were measured for the cases of single fuel and blended fuel. The morphology and the composition of fly ash collected at the cyclone were analyzed using particle size analyzer, ICP-OES, and SEM-EDS. In the single fuel cases, NO x and SO 2 emission of SS were several times higher than the base fuels, but those could be reduced in the blend fuel cases while maintaining overall thermal input and bed temperature. The different size distribution and overall composition of fly ash for the single fuel cases became similar in the blend fuel cases. The change in the characteristics of fly ash was considered to be related to the distribution of mineral matters, such as Ca, K, and P in particular. • DSS and HTCSS showed the high reactivity with two-step reactions in TGA. • Fuel composition of DSS and HTCSS resulted in the higher gaseous emission. • HTCSS showed the lower SO 2 concentration and higher NO x concentration than DSS. • Mean size and mineral composition of fly ash became similar with co-firing of SS. [ABSTRACT FROM AUTHOR]

Computer Aided Engineering (CAE) software has become an essential element in design, simulation, manufacturing and even marketing in the automotive industry as well as in other major manufacturing companies. Multi-physics simulation of IC engines may be one of the most challenging areas both technically and scientifically, since it requires sound basis and experience for diverse physical phenomena. There are quite a few commercial softwares currently available for various elements of CAE, which require substantial investment cost for licensing, personnel and computing facilities. There is a current consensus for the need of low cost CAE based on open sources through which professionals may contribute to new modeling features and validation through a free access web-based platform. There are several high quality open sources available under General Public Licence (GNU-GPL) which allow free utilization and development. Some of them have features as competitive as their commercial counterparts, whereas their interface in general may not be as user-friendly as most commercial software. In this work, we introduce a web-based platform with selected open source programs and their performance will be shown for some example cases. All these programs are downloadable, while remote job access and post-processing can be performed by cloud computing facilities. [ABSTRACT FROM AUTHOR]

Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38–0.47 and 0.38, 95% CI: 0.34–0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p < 0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p < 0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions. [ABSTRACT FROM AUTHOR]

Background & Aims: Current estimates of the population‐based disease burden of liver failure or end‐stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in‐hospital mortality among patients with ESLD in the United States (US). Methods: A retrospective analysis was performed utilizing the National Inpatient Sample from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in‐hospital mortality were analysed from 2005 to 2014. Results: Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100 000 persons to 159.9/100 000 persons. In terms of HCC, hospitalization rates increased from 13.6/100 000 to 22.1/100 000. In patients with non‐alcoholic fatty liver disease (NAFLD)‐related decompensated cirrhosis, the hospitalization rate increased from 13.4/100 000 to 32.1/100 000 with an annual incremental increase of 10.6%, a magnitude twofold higher than other aetiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (from 29.3% to 27.6% for HCV; from 39.0% to 37.4% for ALD). Although the overall in‐hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD‐related decompensated cirrhosis showed no significant change. Conclusions: Among aetiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non‐HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD‐related hospitalizations and its impact on resource utilization. [ABSTRACT FROM AUTHOR]

Summary: Background: Currently, the relationship between depression and non‐alcoholic fatty liver disease (NAFLD) is not clearly defined. Aim: To determine whether depression is associated with NAFLD and NAFLD‐related advanced fibrosis in a large population sample. Methods: We performed a cross‐sectional analysis using the 2007‐2016 National Health and Nutrition Examination Survey database among adults (20 years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ‐9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis‐4 score. Results: Of the 10 484 subjects (mean age 47.0 years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6‐2.2‐fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17‐1.87), HSI (OR 1.51 95% CI 1.04‐2.19) and FLI (OR 2.01 95% CI 1.65‐2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD‐related advanced fibrosis. Conclusions: In a nationally representative sample of US adults, depression was independently associated with NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: The relationship between bisphenol A (BPA) and non‐alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD. Methods: We performed a cross‐sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005‐2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data. Results: Of the first 7605 participants (mean age 47 years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P < 0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39‐2.04) and 1.44 (95% CI 1.19‐1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05‐1.98, P for trend = 0.012). Conclusions: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation. [ABSTRACT FROM AUTHOR]

Aims: We compared (a) demographic and clinical characteristics and (b) determinants of nonalcoholic steatohepatitis and significant fibrosis in non‐obese and obese nonalcoholic fatty liver disease. Methods: A cross‐sectional study of 664 Asian subjects (mean age 53.1 years; men 50.3%) with biopsy‐proven nonalcoholic fatty liver disease and controls was conducted. Subjects were divided by their body mass index into obese (body mass index ≥25 kg/m2) and non‐obese (body mass index <25 kg/m2). Results: Observations in subjects with non‐obese nonalcoholic fatty liver disease were in between non‐obese controls and subjects with obese nonalcoholic fatty liver disease for body mass index, sagittal abdominal diameter, aminotransferase levels, insulin resistance and abdominal visceral adipose tissue area. There was no significant difference in histology between non‐obese and obese subjects with nonalcoholic fatty liver disease except for lower grade of hepatic steatosis in nonobese nonalcoholic fatty liver disease and higher severity of hepatic fibrosis in nonobese nonalcoholic steatohepatitis. Predictors of nonalcoholic steatohepatitis in nonobese subjects included females (odds ratio 2.49), higher alanine aminotransferase (odds ratio 1.03), lower high‐density lipoprotein cholesterol (odds ratio 0.96), higher prevalence of diabetes (odds ratio 3.65) and higher visceral adipose tissue area (odds ratio 1.63 per standard deviation increase of visceral adipose tissue area) while age (odds ratio 1.04), higher aspartate aminotransferase (odds ratio 1.02), diabetes (odds ratio 2.76) and higher visceral adipose tissue area (odds ratio 1.57 per standard deviation increase) were associated with significant fibrosis in the non‐obese. Sagittal abdominal diameter was independently associated with nonalcoholic steatohepatitis or significant fibrosis among subjects with non‐obese nonalcoholic fatty liver disease. Conclusion: While there were a few phenotypic differences from obese subjects, non‐obese subjects with nonalcoholic fatty liver disease displayed a similar severity of histological liver damage. Potential factor(s) beyond obesity may play a role as non‐obese nonalcoholic fatty liver disease advances to more severe disease. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is one of the most serious complications of diabetes. Lipotoxicity in glomerular mesangial cells is associated with the progression of diabetic nephropathy. Paper mulberry, Broussonetia kazinoki Siebold (BK), has been used in oriental medicine for human health problems. However, to date, the beneficial effect of BK fruit has not been studied. In this study, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against palmitate- (PA-) induced toxicity in mesangial cells. BKFE significantly increased the viability of PA-treated SV40 MES13 cells. BKFE significantly inhibited PA-induced apoptosis and decreased the expression of apoptotic genes, cleaved caspase-3, and cleaved PARP. Moreover, BKFE inhibited the expression of endoplasmic reticulum (ER) stress-related genes, such as BiP, phosphorylated eIF2α, cleaved ATF6, and spliced XBP-1, in PA-treated SV40 MES13 cells. BKFE decreased PA-induced ROS production. In addition, BKFE activated the transcription factor Nrf2 and increased the expression of antioxidant enzymes. However, knockdown of Nrf2 using siRNA suppressed this BKFE-induced increase in antioxidant enzyme expression. Furthermore, the protective effect of BKFE on PA-induced apoptosis was significantly reduced by Nrf2 knockdown. In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells. [ABSTRACT FROM AUTHOR]

Summary: The Asian American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically meaningful heterogeneity. We performed a population‐based study using data from the US National Vital Statistics System. We determined the trends in age‐standardized mortality rates for chronic liver disease stratified by aetiology among the most populous US‐based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean and Vietnamese) and compared it to non‐Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis. Hepatitis C virus‐related mortality rates were higher in non‐Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non‐Hispanic whites and all Asian subgroups. Age‐standardized hepatitis B virus‐related mortality rates were higher in all Asian subgroups as compared to non‐Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age‐standardized cirrhosis‐related mortality rates were highest in non‐Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma‐related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non‐Hispanic whites. In this population‐based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of aetiology‐specific chronic liver disease among Asian subgroups in the United States. [ABSTRACT FROM AUTHOR]

Summary: Background: Long term renal safety of antiviral agents against hepatitis B virus (HBV) has been debated. Aim: To compare longitudinal trends of renal function among HBV mono‐infected patients receiving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and adefovir (ADV) in comparison to untreated subjects. Methods: A retrospective cohort consisting of 815 patients with chronic HBV infection was constructed. Serial estimated glomerular filtration rate (eGFR) was compared to the expected rate of age‐dependent decline in eGFR, derived from the National Health and Nutrition Examination Survey (NHANES) data. Generalised estimating equations and linear mixed‐effects models were used to compare trends in eGFR (in mL/min/1.73m2 as a "unit"). Results: In NHANES data (n = 23 051), each year of age was associated with a 0.86 unit decrease in eGFR in subjects without hypertension and 0.96 units with hypertension. The Stanford cohort consisted of patients who received ETV (n = 207), TDF (n = 191), ADV (n = 46) or no therapy (n = 371). After a median follow‐up 4.0 (interquartile range: 1.9‐6.5) years, there was no significant difference in the expected and observed rates of eGFR decline in untreated HBV patients. Patients receiving antiviral treatment experienced steeper reduction in renal function than expected. In the multivariable model, ETV was associated with eGFR loss at 1.81 units per year (P = 0.06, compared to untreated patients). TDF‐ and ADV‐treated patients experienced significantly higher rate of eGFR loss at 2.21 and 2.63 units per year, respectively (both P < 0.01). Conclusion: In this longitudinal cohort study, HBV patients receiving antiviral therapy, particularly TDF and ADV, experienced more rapid loss in eGFR. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aim: Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood. Methods: Cross‐sectional data from the National Health and Nutrition Examination Survey 1999‐2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB‐4 score. Results: Of the 6738 participants (mean age 46.3 years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20‐39 years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32‐4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13‐3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high‐density lipoprotein cholesterol (P for trend <.05 respectively). Conclusions: In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors. [ABSTRACT FROM AUTHOR]

Key points: We studied the role of the large‐conductance Ca2+‐activated K+ channel (BK) and voltage‐dependent K+ channels (Kv) on [Ca2+]i responses to a wide range of hypoxia at different resting cell membrane potential (Em). BK/Kv were mostly closed at rest in normoxia. BK/Kv became basally active when cells were depolarized by elevated [KCl]o (>12 m m). Regardless of whether BK/Kv were closed or basally open, hypoxia‐induced elevation of [Ca2+]i was enhanced 2‐ to 3‐fold by inhibitors of BK/Kv. Hypoxia‐induced elevation of [Ca2+]i was enhanced ∼2‐fold by an inhibitor of Kv2, a major Kv in rat glomus cells. Hypoxia did not inhibit BK in inside‐out patches. Our study supports a scheme in which activation of BK/Kv strongly limits the magnitude of hypoxia‐induced [Ca2+]i rise, with Kv having a much greater effect than BK. Abstract: Large‐conductance KCa (BK) and other voltage‐dependent K+ channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia‐induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4‐AP) on [Ca2+]i responses to a wide range of hypoxia at different levels of resting cell membrane potential (Em). IBTX and TEA/4‐AP did not affect the basal [Ca2+]i in isolated glomus cells bathed in 5 m m KClo, but elicited transient increases in [Ca2+]i in cells that were moderately depolarized (11–20 mV) by elevation of [KCl]o (12–20 m m). Thus, BK and Kv were mostly closed at rest and activated by depolarization. Four different levels of hypoxia (mild, moderate, severe, anoxia) were used to produce a wide range of [Ca2+]i elevation (0–700 n m). IBTX did not affect the rise in [Ca2+]i, but TEA/4‐AP strongly (∼3‐fold) enhanced [Ca2+]i rise by moderate and severe levels of hypoxia. Guangxitoxin, a Kv2 blocker, inhibited the whole‐cell current by ∼50%, and enhanced 2‐fold the [Ca2+]i rise elicited by moderate and severe levels of hypoxia. Anoxia did not directly affect BK, but activated BK via depolarization. Our findings do not support the view that hypoxia inhibits BK/Kv to initiate or maintain the hypoxic response. Rather, our results show that BK/Kv are activated as glomus cells depolarize in response to hypoxia, which then limits the rise in [Ca2+]i. Inhibition of Kv may provide a mechanism to enhance the chemosensory activity of the CB and ventilation. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world's adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index ("lean individuals with MASLD"). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Verma et al papers. To view these articles, visit https://doi.org/10.1111/apt.17891 and https://doi.org/10.1111/apt.17913 [ABSTRACT FROM AUTHOR]

With the growing dependence on smartphones for everyday activities, a large number of pedestrians nowadays are constantly fixated on their smartphone screens, and hence are susceptible to walking off pavements or colliding with other pedestrians. Reduced attention and situational awareness can render smartphone-occupied users, or smombies, oblivious to potential risks when using their smartphones while walking or driving. In this paper, we introduce a smartphone application, called Smombie Guardian, that detects obstacles and alerts smombies as they walk while viewing their smartphone screens to prevent potential collisions. Based on a user study with 74 participants who used Smombie Guardian in a real-life scenario, we highlight the effectiveness, usefulness, and unobtrusiveness of the algorithm and Smombie Guardian in helping users to avoid potential obstacles. [ABSTRACT FROM AUTHOR]

In this study, we introduce hydrophobic and hydrophilic graphene oxide nanosheet (GON) catalysts prepared by consecutive ligand replacement of hydrophobically stabilized magnetic and catalytic nanoparticles (NPs); it exhibits high catalytic activity, fast magnetic response, and good dispersion in both nonpolar and aqueous media, allowing high loading amount of magnetic and catalytic NPs onto GON sheets. More specifically, these GON catalysts showed a high product yield of 66–99% and notable recyclability (93% of the initial product yield after 10 reaction cycles) in a Suzuki–Miyaura reaction in nonpolar media, outperforming the performance of the conventional hydrophilic GON catalysts. Additional coating of a hydrophilic layer onto GON catalysts also showed the notable performance (product yield ∼99%) in catalytic reactions performed in aqueous media. Given that ligand-controlled catalytic NPs adsorbed onto 2D nanosheets can be used as hydrophobic and hydrophilic stabilizers as well as catalysts, our approach can provide a tool for developing and designing 2D-nanosheet catalysts with high performance in nonpolar and polar media. [ABSTRACT FROM AUTHOR]

Background & aims: The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005–2014 and NHANES III (1988–1994). Methods: Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005–2014). In NHANES III cohort, NAFLD was defined based on ultrasonography. Results: Of the 14,080 (NHANES 2005–2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82–0.99 for past user; OR: 0.68, 95% CI: 0.58–0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57–0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58–0.98) and 0.70 (95% CI 0.56–0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59–1.00 for current user; OR: 0.71, 95% CI: 0.51–0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD. Conclusions: In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation. [ABSTRACT FROM AUTHOR]