Accuracy and feasibility in building a personalized 3D printed femoral pseudoaneurysm model for endovascular training.

BACKGROUND: The use of three-dimensional(3D) printing is broadly across many medical specialties. It is an innovative, and rapidly growing technology to produce custom anatomical models and medical conditions models for medical teaching, surgical planning, and patient education. This study aimed to evaluate the accuracy and feasibility of 3D printing in creating a superficial femoral artery pseudoaneurysm model based on CT scans for endovascular training. METHODS: A case of a left superficial femoral artery pseudoaneurysm was selected, and the 3D model was created using DICOM files imported into Materialise Mimics 22.0 and Materialise 3-Matic software, then printed using vat polymerization technology. Two 3D-printed models were created, and a series of comparisons were conducted between the 3D segmented images from CT scans and these two 3D-printed models. Ten comparisons involving internal diameters and angles of the specific anatomical location were measured. RESULTS: The study found that the absolute mean difference in diameter between the 3D segmented images and the 3D printed models was 0.179±0.145 mm and 0.216±0.143mm, respectively, with no significant difference between the two sets of models. Additionally, the absolute mean difference in angle was 0.99±0.65° and 1.00±0.91°, respectively, and the absolute mean difference in angle between the two sets of data was not significant. Bland-Altman analysis confirmed a high correlation in dimension measurements between the 3D-printed models and segmented images. Furthermore, the accuracy of a 3D-printed femoral pseudoaneurysm model was further tested through the simulation of a superficial femoral artery pseudoaneurysm coiling procedure using the Philips Azurion7 in the angiography room. CONCLUSIONS: 3D printing is a reliable technique for producing a high accuracy 3D anatomical model that closely resemble a patient's anatomy based on CT images. Additionally, 3D printing is a feasible and viable option for use in endovascular training and medical education. In general, 3D printing is an encouraging technology with diverse possibilities in medicine, including surgical planning, medical education, and medical device advancement.

The Lived Experiences of Palliative Care Professionals in Cultivating Mindfulness: A Phenomenological Study.

Purpose: The aim of this study was to explore the essence of the lived experiences of palliative care professionals in cultivating mindfulness, with a focus on the meaning of mindfulness in their lives and how mindfulness is experienced throughout their process of caring for others. Design: This was a qualitative study using a phenomenological approach. Methods: Eleven palliative care professionals (three physicians, four nurses, three psychologists, and one spiritual care provider) partook in in-depth interviews. Data were collected from the in-depth interviews and analyzed according to the method of Giorgi. Findings: Two major themes emerged from this study. First, the palliative care professionals realized the need for self-care amid emotional burden, including recognizing their feelings of guilt and self-doubt, emotional contagion of grief, reflections of others' fragility on themself, and their self-imposed limitations. Second, they noticed the transformative impact of mindfulness on them, including detecting reconnection with their body, changes in their personal values, self-acceptance, and liberation. Conclusion: Palliative care professionals can cultivate self-acceptance and facilitate entirely new life experiences through the practice of mindfulness. For them, mindfulness is not merely a self-regulation technique but an existential epiphany, offering hope for self-care and empowerment.

Colorectal cancer-specific IFNß delivery overcomes dysfunctional dsRNA-mediated type I interferon signaling to increase the abscopal effect of radiotherapy.

BACKGROUND: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC. METHODS: Cytosolic dsRNA level and its sensors were evaluated via cell-based assays (co-culture assay, confocal microscopy, pharmacological inhibition and immunofluorescent staining) and in vivo experiments. Biopsies and surgical tissues from patients with CRC who received preoperative chemoradiotherapy (neoCRT) were collected for multiplex cytokine assays, immunohistochemical analysis and SNP genotyping. We also generated a cancer-specific adenovirus-associated virus (AAV)-IFNß1 construct to evaluate its therapeutic efficacy in combination with RT, and the immune profiles were analyzed by flow cytometry and RNA-seq. RESULTS: Our studies revealed that RT stimulates the autonomous release of dsRNA from cancer cells to activate TLR3-mediated IFN-I signatures to facilitate antitumor immune responses. Patients harboring a dysfunctional TLR3 variant had reduced serum levels of IFN-I-related cytokines and intratumoral CD8+ immune cells and shorter disease-free survival following neoCRT treatment. The engineered cancer-targeted construct AAV-IFNß1 significantly improved the response to RT, leading to systematic eradication of distant tumors and prolonged survival in defective TLR3 preclinical models. CONCLUSION: Our results support that increasing cancer-intrinsic IFNß1 expression is an immunotherapeutic strategy that enhances the RT-induced antitumor immune response in locally patients with advanced CRC with dysfunctional TLR3.

Willingness of Patients With End-Stage Renal Disease to Accept a Kidney Transplant and Related Factors.

BACKGROUND: The prevalence of end-stage renal disease (ESRD) in Taiwan is among the highest in the world. Although kidney transplant is the most effective treatment for ESRD, the willingness of patients with ESRD to undergo kidney transplantation is low in Taiwan. The factors associated with willingness to accept kidney transplantation remain unclear, and studies on kidney transplant willingness and associated factors among Taiwanese patients with ESRD are scarce. PURPOSE: The aim of this study was to assess willingness to undergo a kidney transplant and related factors among patients with ESRD in Taiwan. METHODS: A cross-sectional design was employed. Two hundred fourteen participants from a single medical center in Taiwan were recruited, and 209 valid questionnaires were collected (valid response rate: 97.7%). The study instruments included a kidney transplant knowledge scale, a kidney transplant attitude scale, and a kidney transplant willingness scale. Data were analyzed using Pearson's product-moment correlations, t tests, one-way analyses of variance, and multiple regressions. RESULTS: The mean kidney transplant willingness in the sample was 13.23 (out of 20). Being male, younger, married, or employed; having a college education or above; and having a shorter dialysis duration were all associated with higher kidney transplant willingness. Sociodemographics, dialysis duration, knowledge, and attitudes explained 45.4% of the variance in kidney transplant willingness, with two of these, kidney transplant attitudes (ß = .61, p < .001) and dialysis duration (ß = -.11, p = .041), identified as significant. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings support the important role of cultivating positive attitudes in patients with ESRD to increasing willingness to undergo kidney transplantation interventions.

3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases.

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

Fecal Carriage of Multidrug-Resistant Organisms Increases the Risk of Hepatic Encephalopathy in Cirrhotic Patients: Insights from Gut Microbiota and Metabolite Features.

Background: Impact of fecal colonization by multidrug-resistant organisms (MDROs) on changes in gut microbiota and associated metabolites, as well as its role in cirrhosis-associated outcomes, has not been thoroughly investigated. Methods: Eighty-eight cirrhotic patients and 22 healthy volunteers were prospectively enrolled with analysis conducted on plasma metabolites, fecal MDROs, and microbiota. Patients were followed for a minimum of one year. Predictive factors for cirrhosis-associated outcomes were identified using Cox proportional hazards regression models, and risk factors for fecal MDRO carriage were assessed using logistic regression model. Correlations between microbiota and metabolic profiles were evaluated through Spearman's rank test. Results: Twenty-nine (33%) cirrhotic patients exhibited MDRO carriage, with a notably higher rate of hepatic encephalopathy (HE) in MDRO carriers (20.7% vs. 3.2%, p = 0.008). Cox regression analysis identified higher serum lipopolysaccharide levels and fecal MDRO carriage as predictors for HE development. Logistic regression analysis showed that MDRO carriage is an independent risk factor for developing HE. Microbiota analysis showed a significant dissimilarity of fecal microbiota between cirrhotic patients with and without MDRO carriage (p = 0.033). Thirty-two metabolites exhibiting significantly different expression levels among healthy controls, cirrhotic patients with and without MDRO carriage were identified. Six of the metabolites showed correlation with specific bacterial taxa expression in MDRO carriers, with isoaustin showing significantly higher levels in MDRO carriers experiencing HE compared to those who did not. Conclusion: Fecal MDRO carriage is associated with altered gut microbiota, metabolite modulation, and an elevated risk of HE occurrence within a year.

A comprehensive study of pre-eclampsia in IVF and natural conceptions: clinical phenotypes, perinatal outcomes and neonatal echocardiography.

RESEARCH QUESTION: What differences exist in the phenotypes of pre-eclampsia, perinatal outcomes and neonatal echocardiography between pregnancies conceived naturally and through IVF? DESIGN: Six hundred and ten women diagnosed with pre-eclampsia between January 2002 and December 2022 were included in this study. This research was conducted within the IVF and Maternal-Fetal Medicine Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan. Participants were divided into two groups: those who achieved pregnancy through IVF, and those who conceived naturally. The phenotypes of pre-eclampsia and perinatal outcomes were assessed using a propensity-matched sample (n = 218), along with neonatal echocardiography. RESULTS: After conducting propensity score matching, the natural conception group had a higher prevalence of early-onset pre-eclampsia (53.9% versus 37.7%, P = 0.04) and exhibited more severe features of pre-eclampsia (89.1% versus 69.8%, P = 0.01) compared with the IVF group. Regarding perinatal outcomes, neonates in the IVF group had higher placental weights compared with the natural conception group (580 versus 480 g, P = 0.031). The prevalence of abnormal findings on neonatal echocardiography was similar between the groups. Multivariate analysis showed that greater gestational age at delivery reduced the likelihood of abnormal findings on echocardiography [adjusted risk ratio (aRR) 0.950, P = 0.001], while pregestational diabetes mellitus increased the likelihood of abnormal findings (aRR 1.451, P = 0.044). Septal defects were the most common type of defect, occurring in 16.1% of infants. CONCLUSION: The impact of IVF conception on the severity of pre-eclampsia is not as expected. Neonatal echocardiography revealed a higher prevalence of abnormalities in offspring of women with pre-eclampsia compared with the general population. However, these issues were not linked to the method of conception, suggesting the existence of undisclosed factors that could influence the clinical features and perinatal outcomes of pre-eclampsia.

Conventional and machine-learning based risk score for patients with early-stage hepatocellular carcinoma.

Background/Aims: The performance of machine-learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-to-monocyte ratio, and albumin bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATS-INF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Effects of hypertension and use of antihypertensive drugs in pregnancy on the risks of childhood cancers in Taiwan.

BACKGROUND: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks. OBJECTIVE: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. METHODS: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers. RESULTS: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth. CONCLUSIONS: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 µM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.

Safety assessment of a proprietary fermented soybean solution, Symbiota®, as an ingredient for use in foods and dietary supplements: Non-clinical studies and a randomized trial.

A safety evaluation was performed of Symbiota®, which is made by a proprietary anaerobic fermentation process of soybean with multistrains of probiotics and a yeast. The battery of genotoxicity studies showed that Symbiota® has no genotoxic effects. Safety and tolerability were further assessed by acute or repeated dose 28- and 90-day rodent studies, and no alterations in clinical observations, ophthalmological examination, blood chemistry, urinalysis, or hematology were observed between the control group and the different dosing groups (1.5, 5, and 15 mL/kg/day). There were no adverse effects on specific tissues or organs in terms of weight and histopathology. Importantly, the Symbiota® treatment did not perturb hormones and other endocrine-related endpoints. Of note, the No-Observed-Adverse-Effect-Level was determined to be 15 mL/kg/day in rats. Moreover, a randomized, double-blind, placebo-controlled clinical trial was recently conducted with healthy volunteers who consumed 8 mL/day of placebo or Symbiota® for 8 weeks. Only mild adverse events were reported in both groups, and the blood chemistry and blood cell profiles were also similar between the two groups. In summary, this study concluded that the oral consumption of Symbiota® at 8 mL/day by the general population does not pose any human health concerns.

Microwave-assisted dehydration, long-term storage at non-freezing temperatures, and rehydration of cat germinal vesicles.

Germinal vesicles (GVs) are alternative targets for female fertility preservation due to their availability and high resilience against non-physiological conditions. Preserved GVs can then be transferred to fresh cytoplasts to reconstitute viable oocytes. Here, we describe a GV preservation method that employs non-ionizing microwave radiations imparting energy to water molecules, which results in rapid and homogeneous drying of the sample. Trehalose is added as a xero-protectant before the radiations, enabling isothermal vitrification of the disaccharide sugar during drying. While the technique is still considered experimental, studies have shown that DNA and structural integrity can be effectively maintained in dried/rehydrated GVs. Importantly, the dry-preservation approach allows supra-zero temperature storage of the samples, offering a cost-effective and energy-saving alternative to traditional methods relying on ultra-low freezing temperatures. The protocol outlines a comprehensive procedure involving GV oocyte collection, trehalose loading, microwave drying, storage, and rehydration. The simplicity of the protocol facilitates ease of manipulation, making it an accessible method for researchers. While initially developed for domestic cats, the protocol can be adapted for other species with necessary modifications, considering potential species-specific responses to dehydration stress.

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.

Small intestine angioleiomyoma as a rare cause of perforation: A case report.

BACKGROUND: Angioleiomyoma is a rare and benign stromal tumor typically found in subcutaneous tissue. It rarely occurs in the gastrointestinal tract. Among the reported cases, the most common complication was gastrointestinal bleeding. Perforation has only been reported as a complication in the last few decades. CASE SUMMARY: This case report detailed the discovery of intestinal angioleiomyoma in a 47-year-old male presenting with abdominal pain that had persisted for 3 d. After suspecting hollow organ perforation, surgical intervention involving intestinal resection and anastomosis was performed. CONCLUSION: The report underscores the significance of early surgical intervention in effectively treating angioleiomyoma while emphasizing the pivotal role of timely and appropriate measures for favorable outcomes.

The Hippo kinases control inflammatory Hippo signaling and restrict bacterial infection in phagocytes.

The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this report, we generated Mst1/2 knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) regulated by MST1/2 that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis. Surprisingly, pharmacological inhibition of the downstream components LATS1/2 in the canonical Hippo pathway did not affect the expression of a set of immune DEGs, suggesting that MST1/2 control these genes via alternative inflammatory Hippo signaling. Moreover, MST1/2 may affect immune communication by influencing the release of cytokines, including TNFα, CXCL10, and IL-1ra. Comparative analyses of the single- and double-knockout macrophages revealed that MST1 and MST2 differentially regulate TNFα release and expression of the immune transcription factor MAF, indicating that the two homologous Hippo kinases individually play a unique role in innate immunity. Notably, both MST1 and MST2 can promote apoptotic cell death in macrophages upon stimulation. Lastly, we demonstrate that the Hippo kinases are critical factors in mammalian macrophages and single-cell amoebae to restrict infection by Legionella pneumophila, Escherichia coli, and Pseudomonas aeruginosa. Together, these results uncover non-canonical inflammatory Hippo signaling in macrophages and the evolutionarily conserved role of the Hippo kinases in the anti-microbial defense of eukaryotic hosts. IMPORTANCE: Identifying host factors involved in susceptibility to infection is fundamental for understanding host-pathogen interactions. Clinically, individuals with mutations in the MST1 gene which encodes one of the Hippo kinases experience recurrent infection. However, the impact of the Hippo kinases on innate immunity remains largely undetermined. This study uses mammalian macrophages and free-living amoebae with single- and double-knockout in the Hippo kinase genes and reveals that the Hippo kinases are the evolutionarily conserved determinants of host defense against microbes. In macrophages, the Hippo kinases MST1 and MST2 control immune activities at multiple levels, including gene expression, immune cell communication, and programmed cell death. Importantly, these activities controlled by MST1 and MST2 in macrophages are independent of the canonical Hippo cascade that is known to limit tissue growth and tumor formation. Together, these findings unveil a unique inflammatory Hippo signaling pathway that plays an essential role in innate immunity.

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.

Elemental Characterization of Ambient Particulate Matter for a Globally Distributed Monitoring Network: Methodology and Implications.

Global ground-level measurements of elements in ambient particulate matter (PM) can provide valuable information to understand the distribution of dust and trace elements, assess health impacts, and investigate emission sources. We use X-ray fluorescence spectroscopy to characterize the elemental composition of PM samples collected from 27 globally distributed sites in the Surface PARTiculate mAtter Network (SPARTAN) over 2019-2023. Consistent protocols are applied to collect all samples and analyze them at one central laboratory, which facilitates comparison across different sites. Multiple quality assurance measures are performed, including applying reference materials that resemble typical PM samples, acceptance testing, and routine quality control. Method detection limits and uncertainties are estimated. Concentrations of dust and trace element oxides (TEO) are determined from the elemental dataset. In addition to sites in arid regions, a moderately high mean dust concentration (6 µg/m3) in PM2.5 is also found in Dhaka (Bangladesh) along with a high average TEO level (6 µg/m3). High carcinogenic risk (>1 cancer case per 100000 adults) from airborne arsenic is observed in Dhaka (Bangladesh), Kanpur (India), and Hanoi (Vietnam). Industries of informal lead-acid battery and e-waste recycling as well as coal-fired brick kilns likely contribute to the elevated trace element concentrations found in Dhaka.

Impact of nutritional support routes on mortality in acute pancreatitis: A network meta-analysis of randomized controlled trials.

BACKGROUND: Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta-analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model. METHODS: This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta-analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random-effects model. Subgroup analyses accounted for AP severity and nutrition support initiation. RESULTS: A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n = 1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR = 0.34; 95%CI: 0.16-0.73) and nasojejunal (NJ) feeding (RR = 0.46; 95%CI: 0.25-0.84) in comparison to nil per os. Similarly, NG (RR = 0.45; 95%CI: 0.24-0.83) and NJ (RR = 0.60; 95%CI: 0.40-0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48 h, particularly in severe cases. CONCLUSION: For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24 h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP.

MicroRNA­155­5p inhibits trophoblast cell proliferation and invasion by disrupting centrosomal function.

Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently observed in recurrent miscarriage. Several microRNAs (miRs), including miR­155­5p, are aberrantly upregulated in recurrent miscarriage; however, the underlying molecular mechanisms remain unclear. The centrosome orchestrates microtubule networks and coordinates cell cycle progression. In addition, it is a base for primary cilia, which are antenna­like organelles that coordinate signaling during development and growth. Thus, deficiencies in centrosomal functions can lead to several disease, such as breast cancer and microcephaly. In the present study, the signaling cascades were analyzed by western blotting, and the centrosome and primary cilia were observed and analyzed by immunofluorescence staining. The results showed that overexpression of miR­155­5p induced centrosome amplification and blocked primary cilia formation in trophoblast cells. Notably, centrosome amplification inhibited trophoblast cell growth by upregulating apoptotic cleaved­caspase 3 and cleaved­poly (ADP­ribose) polymerase in miR­155­5p­overexpressing trophoblast cells. In addition, overexpression of miR­155­5p inhibited primary cilia formation, thereby inhibiting epithelial­mesenchymal transition and trophoblast cell invasion. All phenotypes could be rescued when cells were co­transfected with the miR­155­5p inhibitor, thus supporting the role of miR­155­5p in centrosomal functions. It was also found that miR­155­5p activated autophagy, whereas disruption of autophagy via the depletion of autophagy­related 16­like 1 alleviated miR­155­5p­induced apoptosis and restored trophoblast cell invasion. In conclusion, the present study indicated a novel role of miR­55­5p in mediating centrosomal function in recurrent miscarriage.

Validity and Reliability of a Smartphone Application for Home Measurement of Four-Meter Gait Speed in Older Adults.

The four-meter gait speed (4MGS) is a recommended physical performance test in older adults but is challenging to implement clinically. We developed a smartphone application (App) with a four-meter ribbon for remote 4MGS testing at home. This study aimed to assess the validity and reliability of this smartphone App-based assessment of the home 4MGS. We assessed the validity of the smartphone App by comparing it against a gold standard video assessment of the 4MGS conducted by study staff visiting community-dwelling older adults and against the stopwatch-based measurement. Moreover, we assessed the test-retest reliability in two supervised sessions and three additional sessions performed by the participants independently, without staff supervision. The 4MGS measured by the smartphone App was highly correlated with video-based 4MGS (r = 0.94), with minimal differences (mean = 0.07 m/s, ± 1.96 SD = 0.12) across a range of gait speeds. The test-retest reliability for the smartphone App 4MGS was high (ICC values: 0.75 to 0.93). The home 4MGS in older adults can be measured accurately and reliably using a smartphone in the pants pocket and a four-meter strip of ribbon. Leveraging existing technology carried by a significant portion of the older adult population could overcome barriers in busy clinical settings for this well-established objective mobility test.