Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2.

The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half1 ( https://www.who.org/ ). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clinical outcomes2. Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approximately 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogues, the largest category of clinically used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogues synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clinical path forward.

Hepatitis C virus infection in patients undergoing surgery in a single tertiary academic center.

BACKGROUND AND AIM: Lack of awareness disturbs proper care for hepatitis C virus (HCV) infections in patients undergoing surgery. We investigated the status of HCV screening, confirmation, and treatment in patients who underwent surgery. METHODS: Patients who underwent surgery at a tertiary academic center between 2019 and 2021 were eligible for this retrospective study. RESULTS: Between 2019 and 2021, 96 894 patients (40 121 males; 41.4%) who underwent surgery under general anesthesia were recruited. The median age of the participants was 55.0 years. Of the 83 920 (86.6%) patients who tested positive for anti-HCV antibodies, 576 (0.7%) showed positive results, with a higher proportion of patients with diabetes mellitus (32.6% vs 18.5%), hypertension (50.5% vs 28.6%), liver cirrhosis (13.2% vs 1.7%), and unfavorable laboratory test results when compared with those with negative results (all P < 0.05). HCV RNA was tested in 215 patients (37.3%), with a positivity rate of 20.5% (n = 44). Of the 44 patients, 42 (95.5%) were referred for antiviral treatment, and 29 (69.0%) were successfully treated with direct-acting antiviral therapy. HCV RNA confirmation rates were higher in the Department of Hepatobiliary and Transplant Surgery (76.6%) than in the other surgical departments (25.0-33.5%) (P < 0.001). CONCLUSIONS: The proportion of patients who were positive for anti-HCV antibodies and failed to receive proper management after surgery was not negligible. Increased awareness of HCV infection among surgeons through appropriate education may be required.

Incidence of metabolic dysfunction-associated steatotic liver disease and advanced fibrosis and impact of overweight/obesity in elderly population: a nationwide cohort study.

BACKGROUND AND AIM: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, coinciding with aging population. However, limited studies have evaluated its incidence and progression to advanced fibrosis in the elderly population. Therefore, our study aimed to investigate the incidence of MASLD and advanced fibrosis in this age group. METHODS: We included 878 686 individuals aged ≥60 years from the Korea National Health Insurance Service-Senior cohort. After excluding participants with preexisting MASLD, 329 388 individuals were finally analyzed. Participants were categorized into four groups based on the presence of overweight/obesity and additional risk factors (aRF) included in the cardiometabolic diagnostic criteria of MASLD. RESULTS: The overall incidence of MASLD was 1.94 per 100 person-years, and the incidence of advanced fibrosis in MASLD patients was 1.78 per 100 person-years. MASLD development was significantly higher in overweight/obese patients (2.65 per 100 person-years) compared to lean patients (1.09 per 100 person-years), and this trend persisted after stratification by the presence of aRF. Similarly, the incidence of advanced fibrosis among MASLD patients was higher in overweight/obese individuals (2.06 per 100 person-years) compared to lean counterparts (0.87 per 100 person-years), irrespective of aRF. CONCLUSIONS: The lower incidence of MASLD in the elderly population compared to the general population underscores the importance of identifying age-specific risk factors. Overweight/obesity emerged as a robust predictor of MASLD development and advanced fibrosis. Additionally, the presence of additional cardiometabolic risk factors further increased the risk of incident MASLD and advanced fibrosis among the elderly.

Mobile App-Based Lifestyle Coaching Intervention for Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial.

BACKGROUND: Lifestyle modification in patients with nonalcoholic fatty liver disease (NAFLD) is key to improving health outcomes. Mobile health technologies may offer potential effective and efficient health care support to facilitate self-management. OBJECTIVE: This study aims to develop a lifestyle coaching intervention using a mobile app for patients with NAFLD and evaluate physiological and psychological health outcomes for 6 months. METHODS: This study was a randomized controlled trial. The personalized lifestyle coaching intervention using a mobile app was developed through established guidelines and literature reviews. This intervention consisted of information on NAFLD management, diet and physical activity self-monitoring, and coaching sessions based on patient records and SMS text messages. A total of 102 individuals were enrolled in the study and randomly assigned to the intervention group (n=48) or the control group (n=54). The outcomes were improvements in physiological (weight, liver fat score, aspartate aminotransferase, alanine transferase, and gamma-glutamyl transferase) and clinical outcomes (self-management, NAFLD self-management knowledge, self-efficacy, fatigue, depression, and quality of life). Data were analyzed using descriptive analysis and a linear mixed model to test the effects of the intervention. RESULTS: All participants completed the study. The mean age of the participants was 48.9 (SD 13.74) years, 38.2% (39/102) were female participants, and 65.7% (67/102) were married. There were no differences in baseline demographic and clinical data between the intervention and control groups. Changes from baseline to 6 months were significant only within the intervention group for weight (P<.001), liver fat score (P=.01), aspartate aminotransferase (P=.03), alanine transferase (P=.002), gamma-glutamyl transferase (P=.04), self-management (P<.001), fatigue (P=.005), depression (P=.003), and quality of life (P<.001). The differences between the 2 groups for the changes over the 6 months were significant in self-management (P=.004), self-management knowledge (P=.04), fatigue (P=.004), depression (P=.04), and quality of life (P=.01). However, the intervention-by-time interaction was significantly effective only for self-management (P=.006) and fatigue (P=.02). CONCLUSIONS: Nonpharmacological interventions using a mobile app may be effective in improving the physiological and psychological health outcomes of patients with NAFLD. TRIAL REGISTRATION: Clinical Research Information Service KCT0005549; http://tinyurl.com/y2zb6usy.

Correction: Mobile App-Based Lifestyle Coaching Intervention for Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/49839.].

ALT Is Not Associated With Achieving Subcirrhotic Liver Stiffness and HCC During Entecavir Therapy in HBV-Related Cirrhosis.

BACKGROUND & AIMS: We investigated whether baseline and on-treatment alanine aminotransferase (ALT) levels during entecavir (ETV) therapy are associated with achieving subcirrhotic liver stiffness (LS) and hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: We analyzed data from 347 treatment-naïve patients with HBV-related cirrhosis, who started ETV between 2006 and 2011 and were followed up for >5 years without developing HCC. The study outcomes were achieving subcirrhotic LS at 5 years of ETV, and risk of HCC development beyond 5 years of ETV. Subcirrhotic LS was defined as <12 kPa by transient elastography. RESULTS: After 5 years of ETV, 227 (65.4%) patients achieved subcirrhotic LS. During a median follow-up of 9.2 years, 49 (14.1%) patients developed HCC beyond 5 years of ETV. ALT levels at baseline, at 1 year of ETV therapy, and 5 years of ETV therapy were not associated with the probability of achieving subcirrhotic LS at 5 years of ETV therapy or risk of HCC development beyond 5 years of ETV therapy (all P > .05). Patients achieving subcirrhotic LS at 5 years of ETV therapy had significantly lower risk of HCC development than those who did not (adjusted hazard ratio, 0.33; 95% confidence interval, 0.17-0.64; P = .001). CONCLUSIONS: Baseline and on-treatment ALT levels were not associated with achieving subcirrhotic LS at 5 years of ETV therapy or with risk of HCC development beyond 5 years of ETV therapy in patients with HBV-related cirrhosis. Achieving subcirrhotic LS at 5 years of ETV therapy was independently associated with lower risk of HCC development beyond 5 years of ETV therapy.

Surface Functionalization and Reversible Disassembly of DNA-Assembly Nanoparticles for Sensitive and Multiplexed Detection of DNA Targets Without Enzymatic and Catalytic Amplification.

Recently, DNA-assembly nanoparticles based on DNA-metal ion interactions are emerging as new building blocks for drug delivery and metal nanostructure synthesis. However, the surface modification of DNA-assembly nanoparticles using functional biomolecules that can identify specific targets has rarely been explored. In this study, we developed a new immobilization chemical strategy to efficiently functionalize the barcode DNA-assembly nanoparticles (bcDNA NPs) with thiolated probe DNA (pDNA) for synthesizing pDNA-functionalized bcDNA NPs (pDNA-bcDNA NPs). We used them as nanoprobes to successfully demonstrate the sensitive and selective detection of multiple DNA targets. Importantly, Au ions played an essential role as anchoring sites via their conjugation with both thiolated pDNA and bcDNA NPs. In addition, we could reversibly and rapidly disassemble the pDNA-bcDNA NPs into the initial bcDNA strands with a recovery rate of 91%; this process significantly amplified the signal by releasing a million bcDNA strands, which enabled DNA quantification from a single pDNA-bcDNA NP. The Au3+ concentration, pH, and surface passivation conditions were carefully investigated to maximize the pDNA loading to 8500 strands/bcDNA NP. The limit of detection was determined to be 221 fM, which is the most sensitive among the absorbance-based methods without polymerase chain reaction, hybridization chain reactions, catalytic hairpin assembly, and other reactions involving enzymes and catalysts. The reversible disassembly of DNA strands and Au ion-mediated conjugation chemistry could be extended for the detection of other types of targets, such as proteins, metal ions, and small molecules, using other organic functionalities that are or can be thiolated, including polypeptides, aptamers, and antibodies.

A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B.

BACKGROUND: Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an ML-based HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT). METHODS: Treatment-naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort (n = 960) to develop a novel ML model that predicted HCC development within 5 years and validated the model using an independent external cohort (n = 1937). ML algorithms consider all potential interactions and do not use predefined hypotheses. RESULTS: The mean age of the patients in the training cohort was 48 years, and most patients (68.9%) were men. During the median 59.3 (interquartile range 45.8-72.3) months of follow-up, 69 (7.2%) patients developed HCC. Our ML-based HCC risk prediction model had an area under the receiver-operating characteristic curve (AUC) of 0.900, which was better than the AUCs of CAMD (0.778) and REAL B (0.772) (both p < .05). The better performance of our model was maintained (AUC = 0.872 vs. 0.788 for CAMD and 0.801 for REAL B) in the validation cohort. Using cut-off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development differed significantly among the three risk groups (p < .001). CONCLUSIONS: Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.

Metabolic dysfunction associated fatty liver disease identifies subjects with cardiovascular risk better than non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the main cause of mortality in subjects with non-alcoholic fatty liver disease (NAFLD). We investigated the association between CVD risk and metabolic dysfunction-associated fatty liver disease (MAFLD) or NAFLD and the influence of significant liver fibrosis on the CVD risk. METHODS: Subjects who underwent a comprehensive medical check-up were recruited (2014-2019). Significant liver fibrosis was defined using NAFLD fibrosis score, fibrosis-4 index, aspartate aminotransferase to platelet ratio index, or FibroScan-aspartate aminotransferase score. High probability of atherosclerotic CVD (ASCVD) was defined as ASCVD risk score > 10%. RESULTS: Of the study population (n = 78 762), 27 047 (34.3%) and 24 036 (30.5%) subjects had MAFLD and NAFLD respectively. A total of 1084 (4.0%) or 921 (3.8%) subjects had previous CVD history in MAFLD or NAFLD subgroup respectively. The previous CVD history and high probability of ASCVD were significantly higher in MAFLD or NAFLD subgroup with significant liver fibrosis than in the other groups (all p < .001). In multivariable analysis, MAFLD was independently associated with previous CVD history after adjusting for confounders (adjusted odds ratio [aOR] = 1.10, p = .038), whereas NAFLD was not (all p > .05). MAFLD (aOR = 1.40) or NAFLD (aOR = 1.22) was independently associated with high probability of ASCVD after full adjustment respectively (all p < .001). Significant liver fibrosis was independently associated with previous CVD history and high probability of ASCVD after adjustment in MAFLD or NAFLD subgroup respectively (all p < .05). CONCLUSION: MAFLD might better identify subjects with CVD risk than NAFLD. Fibrosis assessment might be helpful for detailed prognostication in subjects with MAFLD.

Noninvasive risk assessment of hepatic decompensation in patients with hepatitis B virus-related liver cirrhosis.

BACKGROUND AND AIM: Hepatic decompensation is a major complication of liver cirrhosis. We validated the predictive performance of the newly proposed CHESS-ALARM model to predict hepatic decompensation in patients with hepatitis B virus (HBV)-related cirrhosis and compared it with other transient elastography (TE)-based models such as liver stiffness-spleen size-to-platelet (LSPS), portal hypertension (PH), varices risk scores, albumin-bilirubin (ALBI), and albumin-bilirubin-fibrosis-4 (ALBI-FIB-4). METHODS: Four hundred eighty-two patients with HBV-related liver cirrhosis between 2006 and 2014 were recruited. Liver cirrhosis was clinically or morphologically defined. The predictive performance of the models was assessed using a time-dependent area under the curve (tAUC). RESULTS: During the study period, 48 patients (10.0%) developed hepatic decompensation (median 93 months). The 1-year predictive performance of the LSPS model (tAUC = 0.8405) was higher than those of the PH model (tAUC = 0.8255), ALBI-FIB-4 (tAUC = 0.8168), ALBI (tAUC = 0.8153), CHESS-ALARM (tAUC = 0.8090), and variceal risk score (tAUC = 0.7990). The 3-year predictive performance of the LSPS model (tAUC = 0.8673) was higher than those of the PH risk score (tAUC = 0.8670), CHESS-ALARM (tAUC = 0.8329), variceal risk score (tAUC = 0.8290), ALBI-FIB-4 (tAUC = 0.7730), and ALBI (tAUC = 0.7451). The 5-year predictive performance of the PH risk score (tAUC = 0.8521) was higher than those of the LSPS (tAUC = 0.8465), varices risk score (tAUC = 0.8261), CHESS-ALARM (tAUC = 0.7971), ALBI-FIB-4 (tAUC = 0.7743), and ALBI (tAUC = 0.7541). However, there was no significant difference in the predictive performance among all models at 1, 3, and 5 years (P > 0.05). CONCLUSIONS: The CHESS-ALARM score was able to reliably predict hepatic decompensation in patients with HBV-related liver cirrhosis and showed similar performance to the LSPS, PH, varices risk scores, ALBI, and ALBI-FIB-4.

The clinical effect of antiviral therapy in patients with hepatitis B virus-related decompensated cirrhosis and undetectable DNA.

BACKGROUND AND AIM: Antiviral therapy (AVT) is the mainstay of hepatitis B virus (HBV) management. We investigated whether AVT improves the outcomes of HBV-related decompensated cirrhosis and undetectable HBV-DNA. METHODS: Between 2000 and 2017, treatment-naïve patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA were recruited from two tertiary hospitals. The endpoints included death and hepatocellular carcinoma (HCC). RESULTS: A total of 429 patients were analyzed (50 and 379 patients in the AVT and non-AVT groups, respectively). Patients in the AVT group were significantly younger and had higher alanine aminotransferase and alpha-fetoprotein levels than those in the non-AVT group (all P < 0.05). During follow-up (median 49.6 months), 98 patients died and 105 developed HCC. The cumulative incidence rates of death (2.0%, 4.1%, and 6.4%, and 4.9%, 7.2%, and 10.2% at 6 months, 1 year, and 2 years, respectively) and HCC (8.6%, 15.8%, and 26.4% vs 1.6%, 7.7%, and 24.4% at 1, 2, and 5 years, respectively) were statistically comparable between the AVT and non-AVT groups (all P > 0.05). Using Cox regression analysis, AVT was not significantly associated with death nor HCC (all P > 0.05). Similar results were observed after balancing baseline characteristics with inverse probability of treatment weighting. In the non-AVT group, the cumulative incidence rates of HBV-DNA detection at 6 months, 1 year, and 2 years were 2.0%, 3.1%, and 6.4%, respectively. CONCLUSIONS: Antiviral therapy did not attenuate the risk of death nor HCC in patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA.

MAFLD might be better in identifying subjects with sarcopenia or cardiovascular risk than NAFLD: A nationwide study.

BACKGROUND AND AIM: Clinical features of non-alcoholic fatty liver disease (NAFLD), but not fulfilling the diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD), remain unclear. We investigated the risk of sarcopenia and cardiovascular disease (CVD) in MAFLD and non-metabolic risk (MR) NAFLD. METHODS: Subjects were selected from the Korean National Health and Nutrition Examination Surveys 2008-2011. Liver steatosis was assessed using fatty liver index. Significant liver fibrosis was defined using fibrosis-4 index, categorized by age cut-offs. Sarcopenia was defined as the lowest quintile sarcopenia index. Atherosclerotic CVD (ASCVD) risk score > 10% was defined as high probability. RESULTS: A total of 7248 subjects had fatty liver (137 with non-MR NAFLD, 1752 with MAFLD/non-NAFLD, and 5359 with overlapping MAFLD and NAFLD). In non-MR NAFLD group 28 (20.4%) had significant fibrosis. The risk of sarcopenia (adjusted odds ratio [aOR] = 2.71, 95% confidence index [CI] = 1.27-5.78) and high probability of ASCVD (aOR = 2.79, 95% CI = 1.23-6.35) was significantly higher in MAFLD/non-NAFLD group than in non-MR NAFLD group (all P < 0.05). The risk of sarcopenia and high probability of ASCVD was similar between subjects with and without significant fibrosis in non-MR NAFLD group (all P > 0.05). However, the risk was significantly higher in MAFLD group than in non-MR NAFLD group (aOR = 3.38 for sarcopenia and 3.73 for ASCVD; all P < 0.05). CONCLUSIONS: The risks of sarcopenia and CVD were significantly higher in MAFLD group but did not differ according to fibrotic burden in non-MR NAFLD group. The MAFLD criteria might be better for identifying high-risk fatty liver disease than the NAFLD criteria.

How has COVID-19 impacted the economic resilience of retail clusters?: Examining the difference between neighborhood-level and district-level retail clusters.

The spread of COVID-19 greatly restricted physical and economic activities in global cities due to growing fears of infection and lockdown policies. Accordingly, the transfer of shopping activities from traditional markets to e-commerce has accelerated. Urban retail has substantially declined by competing with these disrupting factors, but resilience capabilities are known to vary by scale and regional characteristics. This study identifies which types of retail clusters were more resilient to the economic shock caused by the pandemic. This research focuses on the changes in online and in-store sales and how retailers recovered differently at the neighborhood and district levels in 2019 and 2020. This research compares the resilience of two types of retail clusters by calculating the loss of resilience and online adaptivity. The findings suggest that neighborhood-level retail areas were more resilient and bounced back in sales at a faster rate than district-level retail areas during the pandemic. These findings suggest that retail clusters are more resilient if they have steady populations and low-rent loads and can accommodate online shopping. The study contributes theoretical insights into how sales have changed and how e-commerce has increased the resilience of retail clusters throughout the pandemic by examining in-store and online sales.

Predictive Performance of CAGE-B and SAGE-B Models in Asian Treatment-Naive Patients Who Started Entecavir for Chronic Hepatitis B.

BACKGROUND & AIMS: Cirrhosis and age (CAGE-B) and stiffness and age (SAGE-B) models assess the risk of hepatocellular carcinoma (HCC) development in white patients with chronic hepatitis B (CHB) undergoing sustained antiviral therapy (AVT). Herein, we checked the predictive performance of these models in Asian patients with CHB. METHODS: We reviewed 734 treatment-naive patients with CHB who started entecavir between 2006 and 2011 and were followed up for more than 5 years without HCC development during AVT. The predictive performance of CAGE-B and SAGE-B models was calculated using area under the receiver operating characteristic curves (AUROCs). RESULTS: Median liver stiffness assessed using transient elastography after 5 years of AVT was 6.8 kPa. Median CAGE-B and SAGE-B models after 5 years of AVT were 7.0 and 6.0, respectively. More than 5 years after AVT initiation, 66 patients (9.0%) developed HCC. The AUROCs of the CAGE-B and SAGE-B models were 0.764 and 0.785 after 7 years and 0.799 and 0.802 after 10 years of AVT, respectively. The cumulative incidence of HCC was significantly higher in the high-risk groups according to CAGE-B and SAGE-B risk stratification than in the medium- and low-risk groups (P < .05 in all cases). The SAGE-B model showed a higher likelihood ratio (χ2) (76.2 vs 71.4) and linear trend (χ2) (74.1 vs 58.6) than the CAGE-B model, whereas the CAGE-B model showed higher Akaike information criteria (64.3 vs 50.3). CONCLUSIONS: Both SAGE-B and CAGE-B showed acceptable performance in predicting HCC after 5 years of AVT in Asian patients with CHB.

Episodic Detectable Viremia Does Not Affect Prognosis in Untreated Compensated Cirrhosis With Serum Hepatitis B Virus DNA <2,000 IU/mL.

INTRODUCTION: The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history. METHODS: From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels <2,000 IU/mL; LLV was defined as having at least 1 detectable serum HBV-DNA (20-2,000 IU/mL) episode, whereas maintained virological response (MVR) was defined as having persistently undetectable serum HBV-DNA (<20 IU/mL). When serum HBV-DNA was ≥2,000 IU/mL during follow-up, AVT was administered according to guidelines. Study end points were development of cirrhotic complication event (CCE) or hepatocellular carcinoma (HCC). RESULTS: Among 567 patients analyzed, cumulative HCC risk at 3, 5, and 7 years was comparable between LLV (n = 391) vs MVR (n = 176) groups (5.7%, 10.7%, and 17.3% vs 7.2%, 15.5%, and 19.4%, respectively [P = 0.390]). CCE risk was also comparable between 2 groups (7.5%, 12.8%, and 13.7% vs 7.8%, 12.3%, and 14.6%, respectively [P = 0.880]). By multivariate analysis, LLV (vs MVR) was not associated with HCC or CCE risks, with adjusted hazard ratios of 1.422 (95% confidence interval [CI] 0.694-2.913; P = 0.336) and 1.816 (95% CI: 0.843-3.911; P = 0.128), respectively. Inverse probability of treatment weighting analysis yielded comparable outcomes between 2 groups, regarding HCC and CCE risks with hazard ratios of 0.903 (95% CI: 0.528-1.546; P = 0.711) and 1.192 (95% CI: 0.675-2.105; P = 0.545), respectively. DISCUSSION: Episodic LLV among untreated patients with compensated cirrhosis does not increase the risk of disease progression compared with MVR status. Thus, the benefits of AVT for episodic LLV should be re-evaluated.

Long-term renal safety between patients with chronic hepatitis B receiving tenofovir vs. entecavir therapy: A multicenter study.

Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Treatment-naive CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. At the beginning of the observation, the ETV group had more unfavorable conditions than the TDF group: lower eGFR and higher FIB-4 and APRI than the TDF group (all p < .001). After 6 years of antiviral therapy, the mean eGFR in the ETV group (n = 1793) was maintained (96.0 at first year to 95.6 ml/min/1.73 m2 at sixth year; AAPC -0.09%; p = .322), whereas that in the TDF group (n = 1240) significantly decreased annually (101.9 at first year to 96.9 ml/min/1.73 m2 at sixth year; AAPC -0.88%; p < .001). Notably, in the TDF group, even patients without diabetes (AAPC -0.80%; p = 0.001) or hypertension (AAPC -0.87%; p = .001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC -1.59%; p = .011) or hypertension (AAPC -1.00%; p = .002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, p < .001), along with eGFR<60 ml/min/1.73 m2 , serum albumin<3.5 mg/dl, and hypertension, were independently associated with ongoing renal dysfunction, defined as a negative slope of the mean eGFR change. In conclusion, compared with ETV, long-term TDF treatment induced slow, but progressive renal dysfunction. Although the annual eGFR change by TDF was small, careful monitoring is necessary, especially in patients requiring life-long therapy.

In Situ Tetraalkylammonium Ligand Engineering of Organic-Inorganic Hybrid Perovskite Nanoparticles for Enhancing Long-Term Stability and Optical Tunability.

Organic-inorganic hybrid perovskite nanoparticles (OIHP NPs) have attracted scientific attention owing to their efficient photoluminescence with optical tunability, which is highly advantageous for optoelectronic applications. However, the limited long-term stability of OIHP NPs has significantly hindered their practical application. Despite several synthetic strategies and encapsulation methods to stabilize OIHP NPs, complicated multi-step procedures are often required. In this study, we introduce an in situ ligand engineering method for stabilizing and controlling the optical properties of OIHP NPs using tetraalkylammonium (TAA) halides with various molecular structures at different concentrations. Our one-pot ligand engineering substantially enhanced the stability of the OIHP NPs without post-synthetic processes. Moreover, in certain cases, approximately 90% of the initial photoluminescence (PL) intensity was preserved even after a month under ambient conditions (room temperature, 20-50% relative humidity). To determine the role of ligand engineering in stabilizing the OIHP NPs, the surface binding properties of the TAA ligands were thoroughly analyzed using Raman spectroscopy. Specifically, the permanent positive charge of the TAA cations and consequent effective electrostatic interactions with the surfaces of the OIHP NPs are pivotal for preserving the initial PL intensity. Our investigation is beneficial for developing OIHP nanomaterials with improved stability and controlled photoluminescence for various optoelectronic applications, such as light-emitting devices, photosensitizers, photodetectors, photocatalysis, and solar cells.

Spaces Eliciting Negative and Positive Emotions in Shrinking Neighbourhoods: a Study in Seoul, South Korea, Using EEG (Electroencephalography).

Although shrinking neighbourhoods are places where urban citizens experience negative emotions, some evidence suggests that people in some shrinking neighbourhoods feel less negative emotions than in other areas. Nevertheless, empirical studies that analyse environmental and personal elements that affect people's emotions in a shrinking neighbourhood remain insufficient. This is rather surprising, considering an increasing interest in the effects of negative emotions on individuals' health. Thus, this study used electroencephalography (EEG) to examine the impacts of environmental and personal characteristics on people's emotional levels in a shrinking area of Seoul, South Korea. A multilinear regression model was used to analyse emotional valence levels between sites with different urban designs and management levels. The results revealed that people felt positive emotions at sites where both urban design factors and their management were both satisfactory at appropriate levels. The results also found that people who had lived or worked in the neighbourhood for a long time and were women experienced more positive emotions than visitors and men. This finding implies that a shrinking neighbourhood can maintain a sense of satisfaction as long as the area is carefully managed. Revealing the emotional effects of environmental and personal characteristics in a shrinking neighbourhood can be used for planning practices and policy-making to create healthy and liveable urban neighbourhoods.

Prevalence and Risk Factors of Cardiovascular Disease in Patients with Chronic Hepatitis B.

BACKGROUND: The association between chronic hepatitis B (CHB) and cardiovascular disease (CVD) remains unclear. We investigated the prevalence and risk factors of CVD in patients with CHB. METHODS: Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analyzed. Significant liver fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile, highest Forns index quintile, or fibrosis-4 ≥ 2.67. The CVD risk was calculated using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score from the 2013 ACC/AHA Guidelines. RESULTS: Among the 506 subjects with CHB, 15 (3.0%) and 150 (29.6%) patients had a CVD history and significant liver fibrosis, respectively. Patients with CVD history were significantly older; showed a significantly higher prevalence of hypertension, metabolic syndrome, and significant liver fibrosis; and had a significantly higher platelet count, lower aspartate and alanine aminotransferase levels, higher triglyceride level, lower high-density lipoprotein level, and higher ASCVD risk than those without (all p < 0.05). In multivariate analysis, higher ASCVD risk (odds ratio [OR] = 1.090) and significant liver fibrosis (OR = 4.341) independently predicted the risk of CVD history (p < 0.05). The prevalence of CVD risk (6.7% vs. 1.4%; OR = 5.014) and high ASCVD risk (> 15%) (34.0% vs. 7.3%; OR = 6.538) was significantly higher in patients with significant liver fibrosis than in those without (all p < 0.05). CONCLUSIONS: Significant liver fibrosis was independently associated with the risk of CVD history in patients with CHB. Prospective studies are needed to validate the longitudinal association between fibrotic burden and CVD development in patients with CHB.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.