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Objective: There is increasing evidence that the school food environment contributes to childhood obesity and health in various locations. We investigated the influence of fast-food stores and convenience food stores (FS and CS, respectively) on growth and body composition in a range of residential densities for North-east Asian food culture.Design: Anthropometrics and birth weight of schoolchildren were obtained. Geocoded mapping of schools and food outlets was conducted. Multivariable linear regression models, adjusted for father's ethnicity and education, as well as for household income, pocket money, birth weight, physical activity, television watching, food quality and region, were used to predict body composition from school food environments.Setting: Elementary schools and school neighbourhoods in 359 townships/districts of Taiwan.Subjects: A total of 2283 schoolchildren aged 6-13 years from the Elementary School Children's Nutrition and Health Survey in Taiwan conducted in 2001-2002.Results: Remote and socially disadvantaged locations had the highest prevalence of lower weight, BMI, waist circumference and triceps skinfold thickness. Food store densities, FS and CS, were highest in urban Taiwan and lowest in remote Taiwan. In the fully adjusted models, FS densities predicted weight and BMI in boys; there was a similar association for waist circumference, except when adjusted for region. FS densities also predicted height for girls. Except for weight and BMI in boys, CS did not have effects evident with FS for either boys or girls.Conclusions: A high FS density, more than CS density, in Taiwan increased the risk of general (BMI) and abdominal (waist circumference) obesity in boys and stature in girls. These findings have long-term implications for chronic disease in adulthood. [ABSTRACT FROM AUTHOR]

This article reports on one patient with a double uterus, unilateral vaginal obstruction, with hemi-haematocolpos and ipsilateral renal agenesis. Early accurate diagnosis followed by the excision of the obstructing vaginal septum offers complete relief of symptoms, while preserving reproductive capacity. Unlike conventional excision of vaginal septum, we used resectoscope excision with cutting electrode under continuous pure distilled water irrigation. The post-operative course was uneventful, and haematocolpos and severe dysmenorrhoea disappeared. The resected vaginal are revealed re-epithelialization by hysteroscope follow-up one year after resection. With advancements in resectoscopic operation, evaluation and treatment of vaginal disorders in babies and virgins is very feasible. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. METHODS: The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. FINDINGS: The national prevalence of chronic kidney disease was 11.93% (95% CI 11.66-12.28), but only 3.54% (3.37-3.68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19.87% [19.84-19.91] vs 7.33% [7.31-7.35]). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1.83 [1.73-1.93]) and 100% higher for cardiovascular diseases (2.00 [1.78-2.25]), in a cohort that was observed for 13 years with median follow-up of 7.5 years (IQR 4.0-10.1). 10.3% (95% CI 9.57-11.03) of deaths in the entire population were attributable to chronic kidney disease, but 17.5% (16.27-18.67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1.20 [1.16-1.24]) increased risk of developing chronic kidney disease. INTERPRETATION: The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic. [ABSTRACT FROM AUTHOR]

Leisure-time physical activity (LTPA) has been closely related to health improvement. The under-appreciation for energy output by nutritionists stems in part from limited data expressed in caloric equivalent. We converted the frequency, duration, and intensity of LTPA, reported from 15,390 adults in the Taiwan National Health Interview Survey 2001, into kilocalories (kcal). Half of Taiwanese adults admit to no LTPA. Women, lower education or income, younger age, smokers and chewers of betel quid; exercised significantly less than their counterparts. Less than 1/5 (18.9%) of the population in Taiwan was physically active at >or=750 kcal/week, and only 1/7 (13.9%) reached a more desirable goal of >or=1,000 kcal/week, compared with 1/3 in the U.S. The most disconcerting finding was the Taiwan unique U-shaped prevalence for males, with the 25-44 age group being the least active, >or=65 age group being the most active; and S-shaped for females, lowest at age 18-24 years and highest at the two older groups (45-64 and >or=65 years). LTPA was under-appreciated, particularly among the most productive work force (25-44-year group), who exercised with a prevalence only 1/4 of their U.S. counterparts. Expressing LTPA in kcal makes direct comparison easier. Invoking a goal of >or=750 kcal/week for Asians, attainable by exercising 4 hours/week, can facilitate nutritionists in assessing LTPA adequacy. Currently, 4/5 of adults in Taiwan failed to reach this goal. Recognizing the concept of cumulative energy expenditure, in contrast to disciplined daily work for 5 or more days, will encourage the infrequent exercisers such as 'weekend warriors' to continue with their activities. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is prevalent in Taiwan, primarily due to the high incidence of hepatitis B and C infections, with high recurrence rates of 50-70% within five years after initial treatment. Treatment options for recurrent HCC include salvage liver transplantation, trans-arterial chemoembolization, re-hepatectomy, and radiofrequency ablation. Repeat hepatectomy exhibits superior oncological outcomes compared with alternative approaches. Although laparoscopic liver resection has demonstrated safety and feasibility for primary HCC resection, the persistence of intrahepatic recurrence necessitates effective intervention. However, repeat liver resection poses several challenges including adhesions from previous surgeries, limited access to recurrent tumors, altered liver structure post-regeneration, difficulties in obtaining hilar control, and compromised liver reserves. Suggesting a laparoscopic approach for recurrent HCC is typically based on the surgeons' experience and confidence. In this study, we reconfirmed the safety, feasibility and oncological outcome of laparoscopic repeat liver resection and investigated the optimal timing for initiation of this procedure by a pioneering team in minimally invasive liver resection., Methods: We retrospectively reviewed our collective experience of 57 patients with recurrent HCC between January 2009 and December 2021.The patients were followed until June 30, 2024. Among them, 37 underwent laparoscopic approaches and 20 opted for open procedures., Results: Both groups exhibited similar operative times and perioperative outcomes, with significantly reduced hospital stays in the laparoscopic cohort (median: 5 vs. 7, p < 0.001). The median follow-up duration was 41.5 months (range, 2.8 to 112.6 months). Mortality occurred in 22 patients (38.6%) and recurrence occurred in 26 patients (45.6%) The overall survival and disease-free survival after the operation were similar in both groups and comparative to the literatures., Conclusion: Using a stepwise approach, laparoscopic repeat liver resection can be performed safely and effectively with a low incidence of conversion by an experienced surgical team with similar oncological outcomes. The introduction of laparoscopic techniques has also sparked a strategic shift in the surgical approach for recurrent HCC. This treatment option should be offered to patients by an experienced surgical team for minimally invasive liver resections., Competing Interests: Declarations. Ethical approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki because of the retrospective nature of this study, need for approval of the study was waived by ethics committee of Chang Gung Memorial Hospital. All methods were carried out in accordance with relevant guidelines and regulations in the ethics and consent to participate under declaration section. Due to the retrospective nature of this study, the informed consent was agreed to be waived by the Ethics Committee/Institutional Review Board of Chang Gung Memorial hospital. Consent for publication: Not applicable. Competing interest: The authors declare no competing interests., (© 2024. The Author(s).)

Intracellular trafficking, an extremely complex network, dynamically orchestrates nearly all cellular activities. A versatile method that enables the manipulation of target transport pathways with high spatiotemporal accuracy in vitro and in vivo is required to study how this network coordinates its functions. Here, a new method called RIVET (Rapid Immobilization of target Vesicles on Engaged Tracks) is presented. Utilizing inducible dimerization between target vesicles and selective cytoskeletons, RIVET can spatiotemporally halt numerous intracellular trafficking pathways within seconds in a reversible manner. Its highly specific perturbations allow for the real-time dissection of the dynamic relationships among different trafficking pathways. Moreover, RIVET is capable of inhibiting receptor-mediated endocytosis. This versatile system can be applied from the cellular level to whole organisms. RIVET opens up new avenues for studying intracellular trafficking under various physiological and pathological conditions and offers potential strategies for treating trafficking-related disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Primary hyperparathyroidism is typically caused by a single parathyroid adenoma. Ectopic parathyroid adenomas occur as well, with cases involving various sites, including the mediastinum, presenting in varying frequencies. Secondary hyperparathyroidism develops in the context of chronic kidney disease, primarily due to vitamin D deficiency, hypocalcemia, and hyperphosphatemia. It is frequently diagnosed in patients undergoing dialysis. This article presents a rare case of hyperparathyroidism involving multiple hyperplastic parathyroid glands with pulmonary seeding in a 50-year-old female patient undergoing hemodialysis (HD)., Case Summary: The patient had a history of parathyroidectomy 10 years prior but developed recurrent hyperparathyroidism with symptoms of pruritus and cough with sputum during a period of routine dialysis. Radiographic imaging revealed multiple nodules in both lungs, with the largest measuring approximately 1.35 cm. Surgical histopathology confirmed the presence of hyperplastic parathyroid glands within the pulmonary tissue. After tumor resection surgery via video-assisted thoracic surgery with wedge resection, the patient was discharged in stable condition and in follow-up her symptoms showed improvement., Conclusion: This article describes hyperparathyroidism presenting as pulmonary nodules in a patient undergoing post-parathyroidectomy HD, highlighting diagnostic challenges and a positive outcome from tumor resection surgery., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.

Background: Home blood pressure (BP) monitoring with lifestyle coaching is effective in managing hypertension and reducing cardiovascular risk. However, traditional manual lifestyle coaching models significantly limit availability due to high operating costs and personnel requirements. Furthermore, the lack of patient lifestyle monitoring and clinician time constraints can prevent personalized coaching on lifestyle modifications., Objective: This study assesses the effectiveness of a fully digital, autonomous, and artificial intelligence (AI)-based lifestyle coaching program on achieving BP control among adults with hypertension., Methods: Participants were enrolled in a single-arm nonrandomized trial in which they received a BP monitor and wearable activity tracker. Data were collected from these devices and a questionnaire mobile app, which were used to train personalized machine learning models that enabled precision lifestyle coaching delivered to participants via SMS text messaging and a mobile app. The primary outcomes included (1) the changes in systolic and diastolic BP from baseline to 12 and 24 weeks and (2) the percentage change of participants in the controlled, stage-1, and stage-2 hypertension categories from baseline to 12 and 24 weeks. Secondary outcomes included (1) the participant engagement rate as measured by data collection consistency and (2) the number of manual clinician outreaches., Results: In total, 141 participants were monitored over 24 weeks. At 12 weeks, systolic and diastolic BP decreased by 5.6 mm Hg (95% CI -7.1 to -4.2; P<.001) and 3.8 mm Hg (95% CI -4.7 to -2.8; P<.001), respectively. Particularly, for participants starting with stage-2 hypertension, systolic and diastolic BP decreased by 9.6 mm Hg (95% CI -12.2 to -6.9; P<.001) and 5.7 mm Hg (95% CI -7.6 to -3.9; P<.001), respectively. At 24 weeks, systolic and diastolic BP decreased by 8.1 mm Hg (95% CI -10.1 to -6.1; P<.001) and 5.1 mm Hg (95% CI -6.2 to -3.9; P<.001), respectively. For participants starting with stage-2 hypertension, systolic and diastolic BP decreased by 14.2 mm Hg (95% CI -17.7 to -10.7; P<.001) and 8.1 mm Hg (95% CI -10.4 to -5.7; P<.001), respectively, at 24 weeks. The percentage of participants with controlled BP increased by 17.2% (22/128; P<.001) and 26.5% (27/102; P<.001) from baseline to 12 and 24 weeks, respectively. The percentage of participants with stage-2 hypertension decreased by 25% (32/128; P<.001) and 26.5% (27/102; P<.001) from baseline to 12 and 24 weeks, respectively. The average weekly participant engagement rate was 92% (SD 3.9%), and only 5.9% (6/102) of the participants required manual outreach over 24 weeks., Conclusions: The study demonstrates the potential of fully digital, autonomous, and AI-based lifestyle coaching to achieve meaningful BP improvements and high engagement for patients with hypertension while substantially reducing clinician workloads., Trial Registration: ClinicalTrials.gov NCT06337734; https://clinicaltrials.gov/study/NCT06337734., (©Jared Leitner, Po-Han Chiang, Parag Agnihotri, Sujit Dey. Originally published in JMIR Cardio (https://cardio.jmir.org), 28.05.2024.)

Objectives: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC)., Materials and Methods: A total of 1755 individuals were identified through a nationwide population-based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new-onset head and neck cancers in patients with migraine versus non-migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine-associated HNC. Sub-outcome analyses were carried out to provide the subtypes of migraine-associated HNC. Propensity score matching was utilized to validate the findings., Results: A total of four patients out of 351 patients with migraine and seven out of 1404 non-migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non-migraine controls (108.93 vs. 48.77 per 100,000 person-years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808-10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948-26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755-8.473; p = 0.118) was revealed. The incidence of non-nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person-years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person-years)., Conclusion: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine-associated HNC included non-nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine., (© 2023 Wiley Periodicals LLC.)

Purpose: The purpose of this study was to conduct a large-scale genome-wide association study (GWAS) and construct a polygenic risk score (PRS) for risk stratification in patients with dry eye disease (DED) using the Taiwan Biobank (TWB) databases., Methods: This retrospective case-control study involved 40,112 subjects of Han Chinese ancestry, sourced from the publicly available TWB. Cases were patients with DED (n = 14,185), and controls were individuals without DED (n = 25,927). The patients with DED were further divided into 8072 young (<60 years old) and 6113 old participants (≥60 years old). Using PLINK (version 1.9) software, quality control was carried out, followed by logistic regression analysis with adjustments for sex, age, body mass index, depression, and manic episodes as covariates. We also built PRS prediction models using the standard clumping and thresholding method and evaluated their performance (area under the curve [AUC]) through five-fold cross-validation., Results: Eleven independent risk loci were identified for these patients with DED at the genome-wide significance levels, including DNAJB6, MAML3, LINC02267, DCHS1, SIRPB3P, HULC, MUC16, GAS2L3, and ZFPM2. Among these, MUC16 encodes mucin family protein. The PRS model incorporated 932 and 740 genetic loci for young and old populations, respectively. A higher PRS score indicated a greater DED risk, with the top 5% of PRS individuals having a 10-fold higher risk. After integrating these covariates into the PRS model, the area under the receiver operating curve (AUROC) increased from 0.509 and 0.537 to 0.600 and 0.648 for young and old populations, respectively, demonstrating the genetic-environmental interaction., Conclusions: Our study prompts potential candidates for the mechanism of DED and paves the way for more personalized medication in the future., Translational Relevance: Our study identified genes related to DED and constructed a PRS model to improve DED prediction.

Introduction: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined., Objectives: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP., Methods: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP., Results: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (r G  = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained., Conclusion: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from 27 October 2022 to 19 January 2023, this research examines AEs in 441 out of 1711 booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings revealed incidence rates (IRs) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster being five times more likely to report them again (incidence rate ratio, 5.02, p < 0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. This study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

Glutathione (GSH) is a major antioxidant in organisms. An alteration in GSH concentration has been implicated in a number of pathological conditions. Therefore, GSH sensing has become a critical issue. In this study, a disposable strip used for tyrosinase-modified electrochemical testing was fabricated for the detection of GSH levels in vivo . The system is based on tyrosinase as a biorecognition element and a screen-printed carbon electrode (SPCE) as an amperometric transducer. On the tyrosinase-SPCE strips, the oxidation reaction from catechol to o -quinone was catalyzed by tyrosinase. The tyrosinase-SPCE strips were modified with gold nanoparticles (AuNPs). In the presence of AuNPs of 25 nm diameter, the cathodic peak current of cyclic voltammetry (CV) was significantly enhanced by 5.2 fold. Under optimized conditions (250 μM catechol, 50 mM phosphate buffer, and pH 6.5), the linear response of the tyrosinase-SPCE strips ranged from 31.25 to 500 μM GSH, with a detection limit of approximately 35 μM (S/N > 3). The tyrosinase-SPCE strips have been used to detect real samples of plasma and tissue homogenates in a mouse experiment. The mice were orally administrated with N -acetylcysteine (NAC) 100 mg kg -1 once a day for 7 days; the plasma GSH significantly enhanced 2.8 fold as compared with saline-treated mice (1123 vs. 480 μM μg -1 protein). NAC administration also could alleviate the adverse effect of GSH reduction in the mice treated with doxorubicin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We have demonstrated the molecular-weight effects of adding homopolystyrene (hPS) on the evolution of perforated layers and double gyroids in polystyrene- block -poly(methyl methacrylate)-based films during isothermal annealing. Two homopolystyrenes of 2.8 and 17 kg mol -1 were used. To prepare blend films, PS- b -PMMA and hPS x ( x : 2.8 or 17) were mixed at a weight-fraction ratio of 75/25 in toluene and then spin-coated at SiO x /Si. Spin coating inevitably produced films with thick edges at the periphery of the substrate. The structural evolution of the spun films was in situ characterized by grazing incidence small-angle X-ray scattering (GISAXS). The annealed films were then characterized using a scanning electron microscope (SEM). We found that thin middle regions behaved differently from thick beads for the films. The middle of the blend films mainly formed perforated layers with different spatial orders and orientations, depending on the molecular weight of added hPS chains. Hexagonally perforated layers quickly formed at 205 °C for PS- b -PMMA/hPS 2.8 films. However, when hPS 17 was used instead of hPS 2.8 , perforated layers formed with defects in PS- b -PMMA/hPS 17 films annealed at 205 °C. Annealing at 240 °C improved the spatial order and orientation of perforated layers for a PS- b -PMMA/hPS 17 film. Nevertheless, annealing at 240 °C inversely depressed the in-plane spatial order of perforated layers for a PS- b -PMMA/hPS 2.8 film. The depression in the in-plane spatial order is ascribed to a dilution effect of added short chains. Compared to the middle regions, the thick beads went through several metastable phases, such as perpendicularly oriented perforated layers and double gyroids.

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially crossover helix ends is elucidated. This structural model aligns well with scanning tunneling microscopy (STM) imaging. The present work enhances the precision of nanoscale organic synthesis, offering prospects for controlled ligand positioning on scaffolds. This advancement paves the way for further applications in nanomedicine through selective protein interaction, manipulation of cell surface receptor functions, and developments of more complex polyproline-based nanostructures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. Although studies have reported that downregulation of HOXD10 expression may contribute to the migration and invasion abilities in EOC, much about its regulation remains to be fully elucidated. The present study aimed to identify different gene expression profiles associated with HOXD10 overexpression in EOC cells. The present study confirmed that HOXD10 overexpression effectively inhibited the proliferation and motility of the TOV21G and TOV112D cells. Further, we overexpress HOXD10 in TOV112D cells, the different gene expression (DEGs) profiles induce by HOXD10 was analyze by the Human OneArray microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), ingenuity pathway analysis (IPA) was used to perform the pathway enrichment analysis for the DEGs. Integrated bioinformatics analysis showed that the DEGs were enriched for terms related to oxidative phosphorylation and mitochondrial function pathways. Dysfunction oxidative phosphorylation metabolic pathway occurs frequently in many tumors. We validated the expression of NDUFA7 , UQCRB and CCL2 using qPCR, involving in metabolism-related pathway, were significantly changed by HOXD10 overexpression in EOC. The detailed regulatory mechanism that links HOXD10 and the oxidative phosphorylation genes is not yet fully understood, our findings provide novel insight into HOXD10-mediated pathways and their effects on cancer metabolism, carcinogenesis, and the progression of EOC. Thus, the data suggest that strategies to interfere with metabolism-related pathways associated with cancer drug resistance could be considered for the treatment of ovarian tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

PAST: Most prostate cancers are slow growing and are often diagnosed at an old age, which may result in treatment never being needed. However, definitive treatments such as radical prostatectomy and radiation therapy are often associated with many serious adverse effects, harming the physical and mental health of patients. PRESENT: In recent years, different types of minimally invasive therapy have been developed to achieve cancer control, continence, and even potency preservation, such as high-intensity focused ultrasound (HIFU). HIFU has been proposed for prostate cancer patients to provide an equivalent oncologic result to definitive treatment, with a reduced adverse effect profile, thus increasing the interest in HIFU for the treatment of localized prostate cancer. FUTURE: Sonablate ® HIFU performed an outstanding cancer control in treating localized prostate cancer, with low biochemical recurrence and complication rates. As further long-term follow-up data mature, we anticipate the routine application of HIFU for localized prostate cancer within the next few years., (© 2023. Society of Surgical Oncology.)

Purpose: We reported preliminary outcomes of high-intensity focused ultrasound (HIFU) [Sonablate ® ] in the combination of transurethral resection of the prostate for localized prostate cancer in Taiwan., Methods: Seventy-seven patients using Sonablate ® HIFU for localized prostate cancer were enrolled in this study from April 2021 to December 2022. Prostate-specific antigen biochemical recurrence, International Index of Erectile Function (IIEF)-5 scores, International Prostate Symptom Score (IPSS), quality of life (QoL) scores, and postoperative complications were recorded during follow-up., Results: Overall, 19.5% of patients were low-risk, 36.4% were intermediate-risk, and 44.1% were high-risk according to the D'Amico risk classification. The median follow-up was 12.09 ± 5.85 months, and the biochemical-free survival rates for the low-, intermediate-, and high-risk groups were 100% (15/15), 96.4% (27/28), and 79.4% (27/34), respectively. Four patients (5.2%) received salvage radiotherapy and all maintained biochemical-free survival. The mean IPSS and QoL scores before versus after HIFU were 10.4 versus 6.8 (p = 0.003) and 3.2 versus 3.0 (p = 0.096), respectively. There was no statistically significant change in preoperative and postoperative IIEF scores (20.6 vs. 19; p = 0.062) in patients who had an IIEF score of >15 at baseline and received nerve-sparing procedures (subtotal ablation)., Conclusions: The results of Sonablate ® HIFU in Taiwan indicated adequate short-term cancer control, excellent potency, and continence preservation. HIFU can achieve improvement of IPSS with low complication rates., (© 2023. Society of Surgical Oncology.)

Background and Objectives: The aim of this study was to evaluate the safety and efficacy of the 180-W GreenLight laser (GL) XPS™ plus bipolar transurethral resection of the prostate (TURP) for the treatment of a prostate volume (PV) beyond 100 ml., Study Design/materials and Methods: From January 2014 to December 2022, 79 patients with PV > 100 ml who underwent GL-XPS plus bipolar TURP were enrolled. The median follow-up time was 13.7 months. The International Prostate Symptom Score (IPSS), PV, uroflow study, post-void residual (PVR) volume, and prostate-specific antigen (PSA) before and after the operation were recorded. Subgroup analysis was performed to compare the outcomes between the patients with follow-up times of < 36 months and > 36 months., Results: Statistically significant improvements in all the postoperative parameters were observed in both < 36 months and > 36 months groups. There was no blood transfusion or transurethral resection (TUR) syndrome in this series. Most of all, a second TURP was unnecessary during the follow-up. Only one (1.3%) Clavien-Dindo grade 3b complication was noted., Conclusions: The hybrid technique of 180-W XPS™ GreenLight laser plus bipolar TURP can be safely and efficiently performed on patients with a prostate volume of > 100 ml., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

An accurate method for neural stimulation within the brain could be very useful for treating brain circuit dysfunctions and neurological disorders. With the aim of developing such a method, this study investigated the use of piezoelectric molybdenum disulfide nanosheets (MoS 2 NS) to remotely convert ultrasound energy into localized electrical stimulation in vitro and in vivo . The application of ultrasound to cells surrounding MoS 2 NS required only a single pulse of 2 MHz ultrasound (400 kPa, 1,000,000 cycles, and 500 ms pulse duration) to elicit significant responses in 37.9 ± 7.4% of cells in terms of fluxes of calcium ions without detectable cellular damage. The proportion of responsive cells was mainly influenced by the acoustic pressure, number of ultrasound cycles, and concentration of MoS 2 NS. Tests using appropriate blockers revealed that voltage-gated membrane channels were activated. In vivo data suggested that, with ultrasound stimulation, neurons closest to the MoS 2 NS were 3-fold more likely to present c-Fos expression than cells far from the NS. The successful activation of neurons surrounding MoS 2 NS suggests that this represents a method with high spatial precision for selectively modulating one or several targeted brain circuits.

Lymphovascular invasion (LVI) predicts poor survival in patients with pathologically localized or locally advanced upper urinary tract urothelial carcinoma (UT-UC). However, LVI is associated with high tumor grade, tumor necrosis, advanced tumor stage, tumor location, concomitant carcinoma in situ, lymph node metastasis, and sessile tumor architecture. These factors might interfere with the analysis of the impact of LVI on oncological prognosis. To address this, this study aimed to clarify the relationship between LVI and patient prognosis in UT-UC using propensity score weighting. Data were collected from 789 patients with UT-UC treated with radical nephroureterectomy without chemotherapy. We evaluated the significance of LVI in predicting metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) using propensity score weighting. All weighted baseline characteristics included in the propensity score model were balanced between the LVI (+) and LVI (-) groups. The MFS, CSS, and OS were all significantly poorer in the LVI (+) group. For patients without LVI, the 5-year MFS, CSS, and OS rates were 65.3%, 73.1%, and 67.3%, respectively, whereas the corresponding rates were 50.2%, 63.8 %, and 54.6%, respectively, for patients with LVI. (all P < .001). For patients without LVI, the 10-year MFS, CSS, and OS rates were 61.5%, 69.6%, and 59.2%, respectively, whereas those for patients with LVI were 44.5%, 57.0%, and 42.7%, respectively (all P < .001). LVI is an important pathological feature that predicts metastasis development and worse survival outcome after radical surgery in UT-UC patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Chronic kidney disease (CKD) has been considered to be a poor prognostic factor for hepatocellular carcinoma (HCC). However, few studies have focused on early HCC and the impact of CKD on survival, which should be considered in curative treatment for early HCC., Materials and Methods: Patients with BCLC stage 0/A were enrolled from 2009 to 2019. A total of 383 patients were divided into Control group and CKD group, based on estimated glomerular filtration rate. Overall survival (OS) and disease-free survival (DFS) of different treatments were determined using the Kaplan-Meier method., Results: The Control group had a significantly better OS than the CKD group (72.6 months vs. 56.7 months; p = 0.003). DFS was similar between the groups (62.2 months vs. 63.8 months, p = 0.717). In the Control group, the surgically treated (OP) group had significantly superior OS (65.0 months vs. 80.0 months, p = 0.014) and DFS (50.9 months vs. 70.2 months, p = 0.020) than the radiofrequency ablation-treated group. In the CKD group, the OP group showed a survival advantage in OS (70.6 months vs. 49.2 months, p = 0.004), while DFS was similar between treatment groups (56.0 months vs. 62.2 months, p = 0.097)., Conclusion: CKD should not be considered to be a poor prognostic factor in early HCC patients. Moreover, hepatectomy should be carried out in CKD patient with early HCC for better prognosis if feasible., (© 2023. The Author(s).)

While radium (Ra)-223 is among the multiple, known life-prolonging treatments in bone-predominant metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequencing has not been determined, particularly in the Asia-Pacific context. Hence, we aimed to compare treatment outcomes of docetaxel-naïve and post-docetaxel mCRPC patients undergoing Ra-223 therapy in Taiwan. Using a single-center retrospective cohort design, we reviewed records of adult patients receiving Ra-223 for bone-metastatic mCRPC from 2018 to 2021. Patients were categorized into docetaxel-naïve or post-docetaxel groups based on history of docetaxel use preceding Ra-223. We compared the 2 groups in terms of all-cause death, 6-cycle treatment completion, and the following secondary outcomes: pain control, change in biochemical parameters (prostate-specific antigen, lactate dehydrogenase, alkaline phosphatase), biochemical response, and treatment-emergent adverse events. We performed total population sampling and a complete case analysis. We included 48 patients (25 docetaxel-naïve, 23 post-docetaxel) in the study. The mean follow-up duration was 12.4 months for the entire cohort. The docetaxel-naïve group exhibited a significantly lower all-cause mortality rate versus the post-docetaxel group (40.0% vs 78.3%, P = .02), as well as a significantly higher treatment completion rate (72.0% vs 26.1%, P < .01). We did not find significant differences in pain control, change in biochemical parameters, biochemical response, or hematologic treatment-emergent adverse events between the 2 groups. However, the docetaxel-naïve group had a numerically higher pain control rate, numerically greater improvements in alkaline phosphatase and prostate-specific antigen, and numerically lower rates of grade ≥ 3 neutropenia and grade ≥ 3 thrombocytopenia than the post-docetaxel group. Use of Ra-223 in docetaxel-naïve patients with mCRPC led to lower mortality and higher treatment completion than post-docetaxel use. Our study adds preliminary real-world evidence that Ra-223 may be used safely and effectively in earlier lines of treatment for bone-predominant mCRPC. Further large-scale, longer-term, and controlled studies are recommended., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Current remote monitoring of COVID-19 patients relies on manual symptom reporting, which is highly dependent on patient compliance. In this research, we present a machine learning (ML)-based remote monitoring method to estimate patient recovery from COVID-19 symptoms using automatically collected wearable device data, instead of relying on manually collected symptom data. We deploy our remote monitoring system, namely eCOVID, in two COVID-19 telemedicine clinics. Our system utilizes a Garmin wearable and symptom tracker mobile app for data collection. The data consists of vitals, lifestyle, and symptom information which is fused into an online report for clinicians to review. Symptom data collected via our mobile app is used to label the recovery status of each patient daily. We propose a ML-based binary patient recovery classifier which uses wearable data to estimate whether a patient has recovered from COVID-19 symptoms. We evaluate our method using leave-one-subject-out (LOSO) cross-validation, and find that Random Forest (RF) is the top performing model. Our method achieves an F1-score of 0.88 when applying our RF-based model personalization technique using weighted bootstrap aggregation. Our results demonstrate that ML-assisted remote monitoring using automatically collected wearable data can supplement or be used in place of manual daily symptom tracking which relies on patient compliance.

Purpose: To evaluate the prognostic impact of the lowest level of tumor location for upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Materials and Methods: Data were collected from patients with UTUC treated with RNU (01/2005- 06/2020) at a single center in Taiwan. Patients were stratified by the lowest level of tumor location into three groups: renal pelvis only (RPO), above upper ureter (AUU), and below upper ureter (BUU). We compared characteristics between groups and examined the association of the lowest level of tumor involvement with intravesical recurrence (IVR), systemic metastasis (SM), and cancer-specific mortality (CSM)., Results: Overall, 1239 patients (542 RPO, 260 AUU, 437 BUU) were enrolled. Concurrent bladder cancer, multifocality, tumor architecture, lymphovascular invasion, carcinoma in situ , and variant histology were significantly different across different tumor locations. BUU had worse five-year intravesical recurrence (IVR), systemic metastasis (SM) and cancer-specific mortality (CSM) (p < 0.001, p = 0.056 and p = 0.13, respectively). In multivariable models, the lowest level of tumor involvement was an independent predictor of IVR (AUU hazard ratio (HR) = 1.52, p = 0.007; BUU HR = 1.75, p < 0.001), but only BUU was an independent predictor of SM (HR = 1.61, p = < 0.001) and CSM (HR = 1.51, p = 0.008)., Conclusion: The lowest level of tumor involvement in UTUC, especially BUU, was associated with a higher risk of IVR, SM and CSM. Assessment of the lowest level of tumor involvement after RNU may help identify patients who require more intensive follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Sung, Chuang, Chen, Cheng, Kang, Liu, Chang, Chiang and Luo.)

The current approach of delivering chemotherapy via pH-sensitive amorphous calcium carbonate-doxorubicin silica nanoparticles (ADS NPs) faces the challenge of insufficient drug dose due to drug instability within the bloodstream and poor tumor penetration. To overcome these long-standing obstacles, we proposed a superhydrophobic coating on the surface of the ADS NPs that could be easily modified via fluorination (ADSF NPs). The surface of fluorinated ADS NPs was further modified with a phospholipid layer to reduce aggregation and improve biocompatibility (ADSFL NPs). The contact angle and mean size of ADSFL NPs were 30.2 ± 4.4° and 353.1 ± 54.2 nm, respectively. The superhydrophobic layer generated interfacial nanobubbles on the outer shell of the NPs that reduced water-induced leakage of doxorubicin (DOX) sevenfold compared with the uncoated group and induced a cavitation effect upon ultrasound (US) sonication. Moreover, release of DOX from the ADSFL NPs could be triggered by US, and this release was further improved 1.6-fold in acidic aqueous conditions, indicating that the ADSFL NPs retained pH responsiveness. Enhanced sonography contrast and histological examination demonstrated that US could trigger cavitation activities from ADSFL NPs in vivo to induce vessel disruption and enhance the fluorescence intensity of DOX within the tumor region threefold under US imaging guidance compared with the ADSFL NPs-only group.

Various magnetic deep brain stimulation (DBS) methods have been developing rapidly in the last decade for minimizing the invasiveness of DBS. However, current magnetic DBS methods, such as magnetothermal and magnetomechanical stimulation, require overexpressing exogeneous ion channels in the central nervous system (CNS). It is unclear whether magnetomechanical stimulation can modulate non-transgenic CNS neurons or not. Here, we reveal that the torque of magnetic nanodiscs with weak and slow alternative magnetic field (50 mT at 10 Hz) could activate neurons through the intrinsic transient receptor potential canonical channels (TRPC), which are mechanosensitive ion channels widely expressed in the brain. The immunostaining with c-fos shows the increasement of neuronal activity by wireless DBS with magnetomechanical approach in vivo. Overall, this research demonstrates a magnetic nanodiscs-based magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in vivo without implants or genetic manipulation., (© 2022. The Author(s).)

Cataracts, characterized by crystalline lens opacities in human eyes, is the leading cause of blindness globally. Due to its multifactorial complexity, the molecular mechanisms remain poorly understood. Larger cohorts of genome-wide association studies (GWAS) are needed to investigate cataracts’ genetic basis. In this study, a GWAS was performed on the largest Han population to date, analyzing a total of 7079 patients and 13,256 controls from the Taiwan Biobank (TWB) 2.0 cohort. Two cataract-associated SNPs with an adjustment of p < 1 × 10−7 in the older groups and nine SNPs with an adjustment of p < 1 × 10−6 in the younger group were identified. Except for the reported AGMO in animal models, most variations, including rs74774546 in GJA1 and rs237885 in OXTR, were not identified before this study. Furthermore, a polygenic risk score (PRS) was created for the young and old populations to identify high-risk cataract individuals, with areas under the receiver operating curve (AUROCs) of 0.829 and 0.785, respectively, after covariate adjustments. Younger individuals had 17.45 times the risk while older people had 10.97 times the risk when comparing individuals in the highest and lowest PRS quantiles. Validation analysis on an independent TWB1.0 cohort revealed AUROCs of 0.744 and 0.659.

Introduction: Delivering sufficient therapeutics at the target site without off-target effects is a major goal of drug delivery technology innovation. Among the established methods, ultrasound (US) with US-responsible carriers holds great promise and demonstrates on-demand delivery of a variety of functional substances with spatial precision of several millimeters in deep-seated tissues in animal models and humans. These properties have motivated several explorations of US with US responsible-responsible carriers as a modality for neuromodulation and the treatment of various diseases, such as stroke and cancer., Areas Covered: We briefly discuss three specific mechanisms that enhance in vivo drug delivery via US with US-responsible carriers: 1) permeabilizing cellular membrane, 2) increasing the permeability of vessels, and 3) promoting cellular endocytotic uptake. We then reviewed the state-of-the-art materials for US-triggered drug delivery, including conventional US contrast agents, and nanocarrier formulations, such as inorganic nanoparticles and gas vesicles., Expert Opinion: In this article, we summarized recent progress for each of US-responsible drug carrier, focusing on the routes of enhancing delivery and applications. The mechanisms of interaction between US-responsible carriers and US waves, such as cavitation, streaming, hyperthermia, and ROS, as well as how those interactions can improve drug release and cell/tissue uptake.

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6−12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment., (© 2022. The Author(s).)

Hernia repair techniques have evolved recently; however sac handling remains a critical step. Transection of the herniated sac as opposed to total sac reduction may simplify the procedure. However, residual sac tissue may increase the risk for seroma formation. We performed a systemic review and meta-analysis to evaluate the safety and feasibility of transecting the hernia sac during laparoscopic herniorrhaphy. Relevant literature search was performed in PubMed, EMBASE, SCORPUS, and the Cochrane Library databases. Relevant studies that compared total reduction with transection of the herniated sac during laparoscopic herniorrhaphy were included. The primary outcome measure was the incidence of seromas. We also analyzed secondary outcomes including operative duration, postoperative pain scores, complications, and hernia recurrence rate. Of the 330 studies identified, four studies published between 2002 and 2020, with sample sizes ranging from 70 to 520 patients, met the inclusion criteria. Overall, 848 hernias were evaluated. We observed a high incidence of seroma formation in the sac transection group compared to that in the sac reduction group (OR 2.41; 95% CI 1.39 to 4.17, P = 0.002), but the groups did not differ significantly with respect to factor such as operative duration, postoperative complications, and pain score. Herniated sac transection during laparoscopic herniorrhaphy might be associated with a higher risk of seroma formation than that observed with sac reduction. The former approach did not show any significant benefits compared to the latter approach with respect to operative duration and postoperative complications., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Background: We aimed to evaluate the impact of tumor location on cancer outcomes in patients with pT3N0M0 upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU) with bladder cuff excision., Materials and Methods: We retrospectively reviewed 302 patients with pT3N0M0 UTUC who underwent RNU with bladder cuff excision at our institution between 2005 and 2019, including 191 renal pelvis tumors and 111 ureteral tumors. Clinicopathologic characteristics were compared between renal pelvis and ureter urothelial carcinomas. Multivariate Cox proportional hazard regression was used to assess the association between outcomes and clinical factors. Outcomes of interest included intravesical recurrence-free survival (IVRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS), which were measured using the Kaplan-Meier curve with a log-rank test., Results: A total of 302 patients underwent RNU with bladder cuff excision. During the median follow-up of 42.7 months, 70 (23.2%), 95 (31.5%), and 99 (32.8%) patients experienced intravesical recurrence, local recurrence, and distant metastasis, respectively. Seventy (23.2%) patients died from UTUC. Multivariate Cox regression analysis showed that tumor location was an independent predictor of local recurrence (HR = 2.05, p = 0.001), with borderline independent significance in intravesical recurrence (HR = 1.54, p = 0.074) and distant metastasis (HR = 1.45, p = 0.08). Kaplan-Meier analysis showed that ureter tumors had a worse 5-year local recurrence (log-rank p < 0.001) and borderline worse 5-year intravesical recurrence (log-rank p = 0.055) and 5-year distant metastasis (log-rank p = 0.073)., Conclusion: Ureter tumors seem to be associated with worse oncological outcomes, especially with local recurrence in UTUC. Further large and long-term studies are warranted for investigating biological differences based on tumor location., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chen, Wang, Chiang, Yang, Lee, Chuang, Cheng, Kang, Lee, Chen, Shen, Liu, Liu, Chang, Su, Huang and Luo.)

Purpose: Hepatocellular carcinoma (HCC) is a major malignancy and the common cause of cancer-related deaths. Surgical intervention provides superior long-term survival outcomes; however, perioperative mortality is a major concern for clinicians while making treatment decisions, especially for major hepatectomy. Scoring systems for predicting 90-day mortality in patients with HCC undergoing major hepatectomy are not available., Methods: This study used the Taiwan Cancer Registry Database that is linked to the National Health Insurance Research Database to analyze data of 60,250 patients with HCC who underwent major hepatectomy and determine risk factors to establish a novel predictive scoring system. By using the stepwise selection of the multivariate Cox proportional hazards model, we divided the patients with HCC undergoing major hepatectomy into four risk groups., Results: The Chang Gung-PohAi predictive scoring system exhibited significant differences in the 90-day mortality rate among the four risk groups (very low risk: 2.42%, low risk: 4.09%, intermittent risk: 17.1%, and high risk: 43.6%)., Conclusion: The Chang Gung-PohAi predictive scoring system is a promising tool for predicting 90-day perioperative mortality in patients with HCC undergoing major hepatectomy.

In this paper, we present a personalized deep learning approach to estimate blood pressure (BP) using the photoplethysmogram (PPG) signal. We propose a hybrid neural network architecture consisting of convolutional, recurrent, and fully connected layers that operates directly on the raw PPG time series and provides BP estimation every 5 seconds. To address the problem of limited personal PPG and BP data for individuals, we propose a transfer learning technique that personalizes specific layers of a network pre-trained with abundant data from other patients. We use the MIMIC III database which contains PPG and continuous BP data measured invasively via an arterial catheter to develop and analyze our approach. Our transfer learning technique, namely BP-CRNN-Transfer, achieves a mean absolute error (MAE) of 3.52 and 2.20 mmHg for SBP and DBP estimation, respectively, outperforming existing methods. Our approach satisfies both the BHS and AAMI blood pressure measurement standards for SBP and DBP. Moreover, our results demonstrate that as little as 50 data samples per person are required to train accurate personalized models. We carry out Bland-Altman and correlation analysis to compare our method to the invasive arterial catheter, which is the gold-standard BP measurement method.

Glaucoma is a progressive and irreversible blindness-causing disease. However, the underlying genetic factors and molecular mechanisms remain poorly understood. Previous genome-wide association studies (GWAS) have made tremendous progress on the SNP-based disease association and characterization. However, most of them were conducted for Europeans. Since differential genetic characteristics among ethnic groups were evident in glaucoma, it is worthwhile to complete its genetic landscape from the larger cohorts of Asian individuals. Here, we present a GWAS based on the Taiwan Biobank. Among 1013 glaucoma patients and 36,562 controls, we identified a total of 138 independent glaucoma-associated SNPs at the significance level of p < 1 × 10 -5 . After clumping genetically linked SNPs (LD clumping), 134 independent SNPs with p < 10 -4 were recruited to construct a Polygenic Risk Score (PRS). The model achieved an area under the receiver operating characteristic curve (AUC) of 0.8387 (95% CI = [0.8269-0.8506]), and those within the top PRS quantile had a 45.48-fold increased risk of glaucoma compared with those within the lowest quantile. The PRS model was validated with an independent cohort that achieved an AUC of 0.7283, thereby showing the effectiveness of our polygenic risk score in predicting individuals in the Han Chinese population with higher glaucoma risks.