Effects of Virtual Reality on Pain and Anxiety During Children's Circumcision: A Systematic Review and Meta-Analysis.

BACKGROUND: Circumcision-a common pediatric procedure-can cause significant pain and anxiety. Virtual reality has been proposed as a nonpharmacological intervention to alleviate these negative experiences. OBJECTIVE: This systematic review and meta-analysis was conducted to evaluate the effects of virtual reality interventions on pain and anxiety in children undergoing circumcision. METHODS: This study comprehensively searched PubMed, Embase, and Cochrane Library for articles published from database inception to October 2, 2023. Randomized controlled trials that investigated the effects of virtual reality interventions on pain and anxiety during circumcision in children were included. The Cochrane risk-of-bias tool was used to appraise the included studies. The primary outcomes were pain and anxiety scores. RESULTS: Three randomized controlled trials and four data sets involving a total of 224 children were included in our meta-analysis. Virtual reality interventions significantly reduced children's pain and anxiety scores. CONCLUSIONS: Virtual reality interventions are promising nonpharmacological strategies for alleviating children's pain and anxiety during circumcision. Pediatric healthcare professionals use virtual reality interventions to create a child-friendly and healthy healthcare environment.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

The changes and the potential clinical applications of cytokines in Taiwan's major venomous snakebites patients.

BACKGROUND: Taiwan habu (Protobothrops mucrosquamatus), green bamboo viper (Viridovipera stejnegeri), and Taiwan cobra (Naja atra) are the most venomous snakebites in Taiwan. Patients commonly present with limb swelling but misdiagnosis rates are high, and currently available diagnostic tools are limited. This study explores the immune responses in snakebite patients to aid in differential diagnosis. METHODS: This prospective observational study investigated the changes in cytokines in snakebite patients and their potential for diagnosis. RESULTS: Elevated pro-inflammatory cytokines IL-6 and TNF-α were observed in all snakebite patients compared to the healthy control group. While no significant disparities were observed in humoral immune response cytokines, there were significant differences in IFN-γ levels, with significantly higher IL-10 levels in patients bitten by cobras. Patients with TNF-α levels exceeding 3.02 pg/mL were more likely to have been bitten by a cobra. CONCLUSION: This study sheds light on the immune responses triggered by various venomous snakebites, emphasizing the potential of cytokine patterns for snakebite-type differentiation. Larger studies are needed to validate these findings for clinical use, ultimately improving snakebite diagnosis and treatment.

Impact of Fruit and Vegetable Enzyme Supplementation on Aerobic Performance and Lactate Response in Older Adults Following High-Intensity Interval Exercise Through Exergaming: Randomized Experimental Matched-Pair Study.

Background: Exercise offers substantial health benefits but can induce oxidative stress and inflammation, especially in high-intensity formats such as high-intensity interval exercise (HIIE). Exergaming has become an effective, enjoyable fitness tool for all ages, particularly older adults. Enzyme supplements may enhance exercise performance by improving lactate metabolism and reducing oxidative stress. Objective: This study investigates the efficacy of fruit and vegetable enzyme supplementation in modulating fatigue and enhancing aerobic capacity in older adults following HIIE through exergaming. Methods: The study recruited 16 older adult female participants and allocated them into 2 distinct groups (enzyme and placebo) based on their pretest lactate levels. This division used pairwise grouping to guarantee comparability between the groups, ensuring the integrity of the results. They engaged in HIIE using Nintendo Switch Ring Fit Adventure, performing 8 sets of 20 seconds of maximum effort exercise interspersed with 30 seconds of rest, totaling 370 seconds of exercise. Key metrics assessed included blood lactate levels, heart rate, rating of perceived exertion, and training impulse. Participants in the enzyme group were administered a fruit and vegetable enzyme supplement at a dosage of 30 mL twice daily over a period of 14 days. Results: The enzyme group showed significantly lower blood lactate levels compared to the placebo group, notably after the fourth (mean 4.29, SD 0.67 vs mean 6.34, SD 1.17 mmol/L; P=.001) and eighth (mean 5.84, SD 0.63 vs mean 8.20, SD 1.15 mmol/L; P<.001) exercise sessions. This trend continued at 5 minutes (mean 6.85, SD 0.82 vs mean 8.60, SD 1.13 mmol/L; P=.003) and 10 minutes (mean 5.91, SD 1.16 vs mean 8.21, SD 1.27 mmol/L; P=.002) after exercise. Although both groups exceeded 85% of their estimated maximum heart rate during the exercise, enzyme supplementation did not markedly affect the perceived intensity or effort. Conclusions: The study indicates that fruit and vegetable enzyme supplementation can significantly reduce blood lactate levels in older adults following HIIE through exergaming. This suggests a potential role for these enzymes in modulating lactate production or clearance during and after high-intensity exercise. These findings have implications for developing targeted interventions to enhance exercise tolerance and recovery in older adults.

Prevalence of Anal Human Papillomavirus Infection and Anal High-Grade Squamous Intraepithelial Lesions Among Men Who Have Sex With Men 50 Years and Older Living With or Without HIV.

BACKGROUND: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). SETTING: We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. METHODS: One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. RESULTS: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. CONCLUSION: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

Exploring the Cellular Impact of Size-Segregated Cigarette Aerosols: Insights into Indoor Particulate Matter Toxicity and Potential Therapeutic Interventions.

Exposure to anthropogenic aerosols has been associated with a variety of adverse health effects, increased morbidity, and premature death. Although cigarette smoke poses one of the most significant public health threats, the cellular toxicity of particulate matter contained in cigarette smoke has not been systematically interrogated in a size-segregated manner. In this study, we employed a refined particle size classification to collect cigarette aerosols, enabling a comprehensive assessment and comparison of the impacts exerted by cigarette aerosol extract (CAE) on SH-SY5Y, HEK293T, and A549 cells. Exposure to CAE reduced cell viability in a dose-dependent manner, with organic components having a greater impact and SH-SY5Y cells displaying lower tolerance compared to HEK293T and A549 cells. Moreover, CAE was found to cause increased oxidative stress, mitochondrial dysfunction, and increased levels of apoptosis, pyroptosis, and autophagy, leading to increased cell death. Furthermore, we found that rutin, a phytocompound with antioxidant potential, could reduce intracellular reactive oxygen species and protect against CAE-triggered cell death. These findings underscore the therapeutic potential of antioxidant drugs in mitigating the adverse effects of cigarette aerosol exposure for better public health outcomes.

Evaluating the clinical impact of resuscitative endovascular balloon occlusion of the aorta in patients with blunt trauma with hemorrhagic shock and coexisting traumatic brain injuries: a retrospective cohort study.

BACKGROUND: The impact of resuscitative endovascular balloon occlusion of the aorta (REBOA) on traumatic brain injuries remains uncertain, with potential outcomes ranging from neuroprotection to exacerbation of the injury. The study aimed to evaluate consciousness recovery in patients with blunt trauma with shock and traumatic brain injuries. MATERIAL AND METHODS: Data were obtained from the American College of Surgeons Trauma Quality Improvement Program from 2017-2019. During the study period, 3,138,896 trauma registries were examined, and 16,016 adult patients with blunt trauma, shock, and traumatic brain injuries were included. Among these, 172 (1.1%) underwent REBOA. Comparisons were conducted between patients with and without REBOA after implementing 1:3 propensity score matching to mitigate disparities. The primary outcome was the highest Glasgow Coma Scale score during admission. The secondary outcomes encompassed the volume of blood transfusion, the necessity for hemostatic interventions and therapeutic neurosurgery, and mortality rate. RESULTS: Through well-balanced propensity score matching, a notable difference in mortality rate was observed, with 59.7% in the REBOA group and 48.7% in the non-REBOA group (P=0.015). In the REBOA group, the median 4-hour red blood cell transfusion was significantly higher (2800 mL [1500, 4908] vs. 1300 mL [600, 2500], P<0.001). The REBOA group required lesser hemorrhagic control surgeries (31.8% vs. 47.7%, P<0.001) but needed more transarterial embolization interventions (22.2% vs 15.9%, P=0.076). The incidence of therapeutic neurosurgery was 5.1% in the REBOA group and 8.7% in the non-REBOA group (P=0.168). Among survivors in the REBOA group, the median highest Glasgow Coma Scale score during admission was significantly greater for both total (11 [8, 14] vs. 9 [6, 12], P=0.036) and motor components (6 [4, 6] vs. 5 [3, 6], P=0.037). The highest GCS score among the survivors with predominant pelvic injuries was not different between the two groups (11 [8, 13] vs. 11 [7, 14], P=0.750). CONCLUSIONS: Patients experiencing shock and traumatic brain injury have high mortality rates, necessitating swift resuscitation and prompt hemorrhagic control. The use of REBOA as an adjunct for bridging definitive hemorrhagic control may correlate with enhanced consciousness recovery.

SLC10A1 rs2296651 variant (S267F mutation) predicts biochemical traits, hepatitis B virus infection susceptibility and the risk of gallstone disease.

Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.

Interrogation of 3d Transition Bimetallic Nanocrystal Nucleation and Growth Using In Situ Electron Microscope and Synchrotron X-ray Techniques.

Understanding the nucleation and growth mechanism of 3d transition bimetallic nanocrystals (NCs) is crucial to developing NCs with tailored nanostructures and properties. However, it remains a significant challenge due to the complexity of 3d bimetallic NCs formation and their sensitivity to oxygen. Here, by combining in situ electron microscopy and synchrotron X-ray techniques, we elucidate the nucleation and growth pathways of Fe-Ni NCs. Interestingly, the formation of Fe-Ni NCs emerges from the assimilation of Fe into Ni clusters together with the reduction of Fe-Ni oxides. Subsequently, these NCs undergo solid-state phase transitions, resulting in two distinct solid solutions, ultimately dominated by γ-Fe3Ni2. Furthermore, we deconvolve the interplays between local coordination and electronic state concerning the growth temperature. We directly visualize the oxidation-state distributions of Fe and Ni at the nanoscale and investigate their changes. This work may reshape and enhance the understanding of nucleation and growth in atomic crystallization.

Comparative analysis of machine learning algorithms for Alzheimer's disease classification using EEG signals and genetic information.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairments, and behavioral changes. The presence of abnormal beta-amyloid plaques and tau protein tangles in the brain is known to be associated with AD. However, current limitations of imaging technology hinder the direct detection of these substances. Consequently, researchers are exploring alternative approaches, such as indirect assessments involving monitoring brain signals, cognitive decline levels, and blood biomarkers. Recent studies have highlighted the potential of integrating genetic information into these approaches to enhance early detection and diagnosis, offering a more comprehensive understanding of AD pathology beyond the constraints of existing imaging methods. Our study utilized electroencephalography (EEG) signals, genotypes, and polygenic risk scores (PRSs) as features for machine learning models. We compared the performance of gradient boosting (XGB), random forest (RF), and support vector machine (SVM) to determine the optimal model. Statistical analysis revealed significant correlations between EEG signals and clinical manifestations, demonstrating the ability to distinguish the complexity of AD from other diseases by using genetic information. By integrating EEG with genetic data in an SVM model, we achieved exceptional classification performance, with an accuracy of 0.920 and an area under the curve of 0.916. This study presents a novel approach of utilizing real-time EEG data and genetic background information for multimodal machine learning. The experimental results validate the effectiveness of this concept, providing deeper insights into the actual condition of patients with AD and overcoming the limitations associated with single-oriented data.

Stromal Rigidity Stress Accelerates Pancreatic Intraepithelial Neoplasia Progression and Chromosomal Instability via Nuclear Protein Tyrosine Kinase 2 Localization.

Because the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and phosphorylated Ser-139 residue of the histone variant H2AX (γH2AX) foci linked to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3-µm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell data sets revealed that the extracellular matrix shaped an alternate route of acinar-ductal transdifferentiation of acinar cells into topoisomerase II α (TOP2A)-overexpressing cancer cells and derived subclusters with copy number amplifications in MYC-PTK2 (protein tyrosine kinase 2) locus and PIK3CA. High-PTK2 expression is associated with 171 differentially methylated CpG loci, 319 differentially expressed genes, and poor overall survival in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort. Abolished RGD-integrin signaling by disintegrin KG blocked the PTK2 phosphorylation, increased cancer apoptosis, decreased vav guanine nucleotide exchange factor 1 (VAV1) expression, and prolonged overall survival in the KPC mice. Reduction of α-smooth muscle actin deposition in the CD248 knockout KPC mice remodeled the tissue stroma and down-regulated TOP2A expression in the epithelium. In summary, stromal stiffness induced the onset of cancer cells-of-origin by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment.

GAT TransPruning: progressive channel pruning strategy combining graph attention network and transformer.

Recently, large-scale artificial intelligence models with billions of parameters have achieved good results in experiments, but their practical deployment on edge computing platforms is often subject to many constraints because of their resource requirements. These models require powerful computing platforms with a high memory capacity to store and process the numerous parameters and activations, which makes it challenging to deploy these large-scale models directly. Therefore, model compression techniques are crucial role in making these models more practical and accessible. In this article, a progressive channel pruning strategy combining graph attention network and transformer, namely GAT TransPruning, is proposed, which uses the graph attention networks (GAT) and the attention of transformer mechanism to determine the channel-to-channel relationship in large networks. This approach ensures that the network maintains its critical functional connections and optimizes the trade-off between model size and performance. In this study, VGG-16, VGG-19, ResNet-18, ResNet-34, and ResNet-50 are used as large-scale network models with the CIFAR-10 and CIFAR-100 datasets for verification and quantitative analysis of the proposed progressive channel pruning strategy. The experimental results reveal that the accuracy rate only drops by 6.58% when the channel pruning rate is 89% for VGG-19/CIFAR-100. In addition, the lightweight model inference speed is 9.10 times faster than that of the original large model. In comparison with the traditional channel pruning schemes, the proposed progressive channel pruning strategy based on the GAT and Transformer cannot only cut out the insignificant weight channels and effectively reduce the model size, but also ensure that the performance drop rate of its lightweight model is still the smallest even under high pruning ratio.

Effectiveness of Exercise Interventions on Body Composition, Exercise Capacity, Fatigue, and Quality of Life in Patients with Liver Cirrhosis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Diminished muscle protein synthesis in cirrhosis leads to reduced strength and mass, impacting daily activities and overall quality of life. AIMS: This study aimed to examine the effectiveness of exercise intervention in body composition, exercise capacity, fatigue, and quality of life in patients with liver cirrhosis. METHODS: A systematic search of medical databases, including PubMed, Embase, Cochrane, and CINAHL, was executed from their inception to November 2022. The inclusion criteria were randomized controlled trials comparing exercise interventions with a control group that did not receive exercise interventions. RESULTS: From the initially identified 2,565 articles, eight studies with a total of 220 patients were eligible for inclusion in this meta-analysis. According to the meta-analysis, exercise significantly improved the six-minute walk distance (6MWD) by 68.93 m (95% CI 14.29-123.57) compared to the control group. Furthermore, the subgroup analysis revealed that combing exercise with amino acid supplementation had a greater positive effect on the 6MWD (MD = 144.72, 95% CI 87.44-202.01). Exercise also significantly increased thigh circumference (MD = 1.26, 95% CI 0.12-2.39) and the thigh ultrasound average compression index (MD = 0.07, 95% CI 0.00-0.14). Moreover, exercise significantly decreased fatigue levels by 0.7 points in patients with liver cirrhosis (95% CI 0.38-1.03). However, no significant effects were observed on body mass index (BMI), fat mass, fat-free mass, and quality of life. CONCLUSIONS: Exercise can improve exercise capacity, thigh muscle thickness, and fatigue in patients with cirrhosis, but it does not have a significant impact on fat mass, BMI, or quality of life.

Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling.

Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores' ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10-19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

Experimental Validation of Comprehensive Calculation for High-Resolution Linear MALDI-TOF Mass Spectrometry.

This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI3 and angiotensin I ions in low to medium m/z range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low m/z range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.

Endothelial ZIP8 plays a minor role in BMP6 regulation by iron in mice.

ABSTRACT: Iron-mediated induction of bone morphogenetic protein (BMP)6 expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for the metal-ion transporter ZIP8 in regulating BMP6 expression under high-iron conditions.

Influence of Cigarette Aerosol in Alpha-Synuclein Oligomerization and Cell Viability in SH-SY5Y: Implications for Parkinson's Disease.

Although cigarette aerosol exposure is associated with various adverse health issues, its impact on Parkinson's disease (PD) remains elusive. Here, we investigated the effect of cigarette aerosol extract (CAE) on SH-SY5Y cells for the first time, both with and without α-synuclein (α-Syn) overexpression. We found that α-Syn aggravates CAE-induced cell death, oxidative stress, and mitochondrial dysfunction. Fluorescence cross-correlation spectroscopy (FCCS) revealed a dual distribution of α-Syn within the cells, with homogeneous regions indicative of monomeric α-Syn and punctated regions, suggesting the formation of oligomers. Moreover, we observed colocalization of α-Syn oligomers with lysosomes along with a reduction in autophagy activity. These findings suggest that α-Syn overexpression exacerbates CAE-induced intracellular cytotoxicity, mitochondrial dysfunction, and autophagy dysregulation, leading to elevated cell mortality. Our findings provide new insights into the pathogenic mechanisms linking exposure to cigarette aerosols with neurodegenerative diseases.