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Background: Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality. Methods: A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants’ serum samples. The cohort data were linked to Taiwan’s National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases. Results: In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect. Conclusion: Both intrahepatic and extrahepatic manifestations mediated approximately half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Summary: Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families. Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells. Cerebrovascular defects and mitochondrial respiration were also examined in CRISPR/Cas9-edited zebrafish. Findings: iPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation. In addition, proteomic analysis revealed a reduced abundance of mitochondrial proteins involved in ATP synthesis or coordinating TCA cycle and gluconeogenesis. Moreover, mitochondrial respiration was slightly decreased while ATP production from glycolysis was significantly increased. Furthermore, deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. Notably, homozygous iPSCs differentially expressed genes involved in glycolysis and response to hypoxia. Finally, the metabolic imbalance was evidenced by decreased oxygen consumption, increased level of hexokinase 2, and enhanced glycolysis in endothelial cells derived from the patient's iPSCs. Interpretation: These results revealed the essential role of TOMM7 in balancing cellular sources of energy production at both proteomic and transcriptomic levels and provided the molecular mechanisms through which TOMM7 p.P29L variant leads to an autosomal recessive microcephalic osteodysplastic dwarfism with moyamoya disease. Funding: This work is supported by National Science and Technology Council grants and National Cheng Kung University Hospital.

The diverse content of and ease of listening to podcasts have made podcasts popular, particularly during the COVID-19 pandemic. Advertisers have begun to recognize their marketing potential and are now hiring podcasters to recommend their products. This study sought to determine the factors influencing podcast commitment, parasocial interaction (PSI), and the intention to purchase podcaster-endorsed items. It was conducted in Taiwan with a sample size of 578 participants and an online questionnaire. Structural equation modeling and mediation analysis were applied to the collected data from the perspective of uses and gratifications theory. We found that podcast commitment is positively related to edutainment, storytelling transportation, and social engagement. Social engagement is positively related to PSI, while storytelling transportation has a negative relationship with PSI. Additionally, there is a strong positive correlation between podcast commitment and PSI and both factors positively influence the intention to purchase podcaster-endorsed items. PSI also significantly moderates the positive relationship between podcast commitment and the intent to buy podcaster-endorsed items.

Abstract Background Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach. Methods In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T. Results In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T. Conclusions CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant.

Abstract Cervical cancer is a significant public health concern, particularly in low‐ and middle‐income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21–65 from three medical centers in Taiwan. The findings indicated that the self‐sampling kit was as effective as physician‐collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self‐sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self‐sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.

This study investigated the motivations of Taiwanese consumers who choose to redistribute their possessions via Give Circle, a free collaborative redistribution platform. We aimed to understand why users prefer using a free platform to donate and solicit items over traditional second-hand exchange platforms. Additionally, we sought to identify the behavioral changes that occur from using this platform within the context of the sharing economy. A mixed-methods approach was adopted, starting with semi-structured interviews with frequent users of the platform to identify independent and dependent variables for the formal research framework. Based on this evidence, we selected the extended UTAUT2 model and gamification affordance theory to explore the factors of continued use intentions. We applied structural equation modeling to 691 valid questionnaires. Predictors of continued use intentions included performance expectations, convenience, time and effort investment, and autonomy and self-expression. Continued use intention positively influenced charitable donation behavior and consumers' minimalist tendencies. These findings represent a novel contribution to the literature on the sharing economy, filling gaps in research on non-monetary collaborative redistribution platforms, extending the application of the UTAUT2 model, and deepening our understanding of consumer psychology and behavioral patterns in Asian Chinese societies.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

The wearing of overly high high-heeled shoes can cause irreversible physiological damage. Doctors typically analyze the calcaneus when an individual is standing on tiptoes to observe changes in the Achilles tendon to determine the suitable high-heel height range. A mobile application system for evaluating the maximum heel height suitable for women was developed in this study. The system input is a smartphone-recorded video of an individual’s while standing on tiptoes. The trained artificial intelligence (AI) evaluation system outputs the maximum heel height suitable for the wearer. This study used three core technologies to implement this AI evaluation system. First, EfficientDet was used to realize object detection, and area of the left heel, right heel, and a red cube were bounded. These bounding region pictures were then input into the convolutional neural network (CNN) model for binary classification; the accuracy rate of the integrated EfficientDet and CNN models was 0.86. Finally, the mode algorithm was applied to correct errors in model evaluation and improve overall accuracy. The system developed in this study can evaluate the maximum heel height of a high-heeled shoe with a mean absolute error of 0.8 cm. Only the operation of a smartphone is required without additional platform assistance. Thus, this system has high practicability and usability.

Background: The majority of English literature has reported on the somewhat conflicted outcomes of the effect of radiotherapy on immediate breast reconstruction. However, data specifically related to patients of Asian descent has been scarce. This retrospective study aims to shed light on this topic to aid in the management of this group of patients. Methods: All patients who received immediate free perforator flap-based breast reconstruction under a single surgeon over a 10-year period were included in the study. Patient characteristics, oncological and surgical data were collected. Patients were divided into post-mastectomy radiotherapy (PMRT) and non-PMRT groups. The final aesthetic outcome was assessed by a surgeon-reported outcome questionnaire. Patient satisfaction and psychological outcomes were assessed using validated patient-reported outcome (PRO) questionnaire (BREAST-Q), breast reconstruction, and postoperative module. Results: A total of 101 women, with an average age of 44.7 ± 8.4 underwent perforator flap-based reconstruction. Fifteen patients received PMRT, with remaining 86 patients in the non-PMRT group. The mean duration of follow-up was over 5 years (p = 0.514). The recurrence rate was acceptable in the PMRT group (3/15, p = 0.129). There were no significant differences in complication rates between the two groups (p = 1.000). The aesthetic outcomes were comparable (p = 0.342). PRO appears to be lower in the PMRT group. Conclusions: Immediate breast reconstruction with PMRT in the local patient cohort is oncologically safe, acceptable complication profile, revision rate, and aesthetic outcome. PRO showed lower scores in several categories, which differ from normative data generated in the Western population. Further studies will need to examine the confounding effects of radiation in this specific population.

Abstract Objective Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare malignancy with various treatment strategies and outcomes. The purpose of this study was to evaluate the clinical characteristics and survival outcomes and identify prognostic factors in patients with SCC of EAC. Methods Twenty‐one patients with SCC of EAC treated in a single tertiary center between 2009 and 2021 were retrospectively reviewed and analyzed. The modified Pittsburgh classification system was applied for staging. Factors associated with survival were identified by univariate survival analysis. Results The mean age at diagnosis was 61 years (range: 41–79 years). Early‐stage (T1 + T2) accounts for 38.1% of the series and advanced‐stage (T3 + T4) accounts for 61.9%. Eighteen (85.7%) patients underwent primary surgery with curative intent. The 5‐year overall survival rate of the 21 patients was 67.4%. Tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura were associated with poor prognosis in univariate analysis (p = .046; .008; .027; and .08, respectively). Conclusions Factors predictive of less favorable survival include the history of COM, tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura. It is important to make a precise and systemic preoperative evaluation of disease extent. Level of Evidence 4

Objective: To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. Materials and methods: In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. Results: The mean observation time was 14.1 ± 18.5 months (range, 1–162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (

Instagram Stories advertising has the advantages of precise targeting, diverse advertising formats, and a wide range of users; it has, thus, become an important medium for mobile game marketing. To find the most effective ad designs for mobile games on Instagram Stories, this study applied the stimulus-organism-response (S-O-R) theory to investigate how game involvement and ad designs affect users’ visual attention. Visual attention is an important physiological indicator of advertising effectiveness, and eye-tracking technology can accurately assess consumers’ visual attention. This study applied eye-tracking technology to 80 participants, grouped as follows: high-involvement gamers, low-involvement gamers, and nongamers. This study used the eye movement indicators for first fixation duration (FFD) and total fixation duration (TFD) to, respectively, evaluate the attentional salience and hold of mobile game ads. The ads were presented in three formats (5 s video, 15 s video, and 5 s image) with two types of content (gameplay and game characters). Results showed that the mobile game ads on Stories exerted the highest attentional hold on high-involvement gamers. In terms of ad format, video ads offered a higher attentional hold and attentional salience. In terms of ad content, ads that introduced game characters resulted in better attentional salience; however, ads that introduced gameplay exerted better attentional hold for nongamers. This study examined both individual differences in media users and ad design to provide recommendations for the personalization of mobile game ads for social media. For example, ads designed for a high-involvement gamer should incorporate more diverse and complex information. In addition, we found that when the marketing goal is the promotion of game characters, image ads are the most appropriate format.

The soaked white rice samples were subjected to microwave-assisted induction heating (MAIH) system consisting of a microwave heating unit (power = 1000 W, frequency: 2450 MHz) in the upper part and an induction unit (power = 1500 W) in the lower part at two set temperatures (120°C and 100°C) for different heating times. The aerobic plate count (APC), lightness (L*), redness (a*), yellowness (b*), whiteness (W), and hardness of the rice samples decreased significantly with prolonged heating, whereas the adhesiveness, cohesiveness, chewiness, moisture content, and water activity increased with increasing heating time. The rice samples subjected to MAIH at 120°C for 240 s or at 100 °C for 300 s had transparent cores with an absence of fine particles, indicating that the rice samples were fully cooked. The relevant microbial counts were below the detectable levels, and the preset target temperature could be attained at the maximum temperature of the rice samples. In addition, it is known from the temperature profile that the thermal lethality (F90°C) of MAIH 120°C for 240 s and MAIH 100°C for 300 s is 935 min and 14.1 min, respectively, which has exceeded the 6D value reduction requirements for the target microorganism non-proteolytic C. botulinum. (F90°C =10.0 min). In general, the optimum heating conditions for obtaining MAIH-prepared rice with color, texture, and sensory qualities similar to those of traditionally steamed rice were: heating at 120°C for 240 s or 100°C for 300 s. This study is the first to employ MAIH for rapid preparation of pre-packaged ready-to-eat (RTE) rice products, with at least 80 % reduction of the heating time compared with that of traditional steaming.

Abstract Background Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce. Methods We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing. Results Seventy-seven EB patients from 45 families were included: 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa. Conclusions The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.

Diabetes mellitus during pregnancy, which can be classified into pregestational diabetes and gestational diabetes, has become much more prevalent worldwide. Maternal diabetes fosters an intrauterine abnormal environment for fetus, which not only influences pregnancy outcomes, but also leads to fetal anomaly and development of diseases in later life, such as metabolic and cardiovascular diseases, neuropsychiatric outcomes, reproduction malformation, and immune dysfunction. The underlying mechanisms are comprehensive and ambiguous, which mainly focus on microbiota, inflammation, reactive oxygen species, cell viability, and epigenetics. This review concluded with the influence of intrauterine hyperglycemia on fetal structure development and organ function on later life and outlined potential mechanisms that underpin the development of diseases in adulthood. Maternal diabetes leaves an effect that continues generations after generations through gametes, thus more attention should be paid to the prevention and treatment of diabetes to rescue the pathological attacks of maternal diabetes from the offspring.

BackgroundAccurate estimation of prolonged length of hospital stay after acute ischemic stroke provides crucial information on medical expenditure and subsequent disposition. This study used artificial neural networks to identify risk factors and build prediction models for a prolonged length of stay based on parameters at the time of hospitalization.MethodsWe retrieved the medical records of patients who received acute ischemic stroke diagnoses and were treated at a stroke center between January 2016 and June 2020, and a retrospective analysis of these data was performed. Prolonged length of stay was defined as a hospital stay longer than the median number of days. We applied artificial neural networks to derive prediction models using parameters associated with the length of stay that was collected at admission, and a sensitivity analysis was performed to assess the effect of each predictor. We applied 5-fold cross-validation and used the validation set to evaluate the classification performance of the artificial neural network models.ResultsOverall, 2,240 patients were enrolled in this study. The median length of hospital stay was 9 days. A total of 1,101 patients (49.2%) had a prolonged hospital stay. A prolonged length of stay is associated with worse neurological outcomes at discharge. Univariate analysis identified 14 baseline parameters associated with prolonged length of stay, and with these parameters as input, the artificial neural network model achieved training and validation areas under the curve of 0.808 and 0.788, respectively. The mean accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of prediction models were 74.5, 74.9, 74.2, 75.2, and 73.9%, respectively. The key factors associated with prolonged length of stay were National Institutes of Health Stroke Scale scores at admission, atrial fibrillation, receiving thrombolytic therapy, history of hypertension, diabetes, and previous stroke.ConclusionThe artificial neural network model achieved adequate discriminative power for predicting prolonged length of stay after acute ischemic stroke and identified crucial factors associated with a prolonged hospital stay. The proposed model can assist in clinically assessing the risk of prolonged hospitalization, informing decision-making, and developing individualized medical care plans for patients with acute ischemic stroke.

Abstract Background For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication. Methods We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women’s Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH). Results Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant. Conclusions We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate.

Combining games with mobile commerce applications has been a trend in recent years. Mobile commerce is attracting a large number of people, especially females, to play mini games on the platform. The gamification of mobile commerce may affect users’ platform satisfaction. This study aims to explore the intention of female users to play mobile commerce games and its impact on platform satisfaction. We collected data from females in China who played mobile commerce games and then used a structural equation model to test the various hypotheses we made. The results showed that game use intention fully mediated the impact of performance expectation, hedonic motivation, and social influence on platform satisfaction. Effort expectation had no significant impact on game use intention but had a positive impact on platform satisfaction. Game use intention had a positive impact on platform satisfaction. The frequency of playing games and the amount of money spent on the platform were positively correlated with game use intention. Females over 25 years old preferred to play mobile commerce games. This study provides a theoretical reference and practical enlightenment and makes a specific contribution to the development of mobile commerce platform and the application of gamification. However, this study has limitations in terms of test samples, research methods and research content, and further research on mobile commerce is required in the future.

Idol-nurturing reality shows that aim to produce idol groups by audience-chosen have become a hotbed for nurturing celebrities. The unique concepts and designs of idol-nurturing reality shows have attracted a group of committed female fans. As a result, the idol-nurturing reality show has become an essential genre of reality shows in the Asian market and an essential part of idol culture. This study concerned the unique concepts and designs of idol-nurturing reality shows and the psychology and behavior of the fans throughout the shows. Results of structural equation modeling based on survey data with 3,352 young Chinese respondents revealed a significant relationship between prompts, motives, online fan engagement, celebrity worship, and program commitment. The data from this study show that the prompts ability, personality, and facial attractiveness positively impacted online fan engagement and that viewing motives social interaction, voyeurism, and suspense positively impacted online fan engagement. In addition, this study found that online fan engagement exerted a significant and positive effect on celebrity worship and program commitment; celebrity worship positively impacted program commitment. This study also provides suggestions on enhancing the fan stickiness of shows and idols.

Abstract Background To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. Methods A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. Results Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). Conclusion The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.

Background/Purpose: Typhoon Morakot in August 2009 caused significant damages and health and socio-economic impacts in Taiwan. Therefore, we evaluated the mental health status of adult and patients who lived in the affected area after the disaster. Methods: An observational, prospective population-based study was conducted. Adults living in the affected area were selected as the affected population in the National Health Insurance Database from January 2008 to December 2011. Prevalence and incidence of stress-associated illnesses, such as insomnia, anxiety, depressive, adjustment and mood disorders, post-traumatic stress disorder (PTSD) in the psychiatry department were analysed after the disaster. Results: A total of 897,689 adult patients were studied. Of the affected population without pre-existing chronic mental health illness, the monthly visits for stress-associated illnesses, such as insomnia, anxiety, depressive disorders and PTSD increased about twice after the disaster in elderly and non-elderly groups. Comparing to the non-elderly group, the elderly group has more increased in the incidence of insomnia (356% vs. 318% increase) and depressive disorders (308% vs. 245%) but was affected to a lesser extent increase in the anxiety (269% vs. 307%), PTSD, episodic mood disorders (82% vs. 158%), and adjustment reaction (160% vs. 202%). Conclusion: The mental health statuses of patients who experienced a major natural disaster deteriorated in the elderly population after the disaster. However, we still need pay more attentions on the elderly of the affected population to decrease the risk for insomnia and depressive disorders after the disaster.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the lowering in other atherogenic apolipoproteins and safety of PCSK9 inhibitors at different dosages as an add-on statins therapy in hypercholesterolemia patients.Methods: This study is a systematic review and network meta-analysis of randomized control trials to compare the efficacy of lipid reduction and adverse events of PCSK9 inhibitors in statin-treated hypercholesterolemia patients. PubMed, EMBASE, and Cochrane Library databases were searched till April 20, 2021, for randomized controlled trials. Random-effect network meta-analyses were undertaken to compare the differences in the percent reduction in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] levels and the risk of AEs among different PCSK9 inhibitors.Results: A total of 22 articles with 42,786 patients were included. The lipid reductions in LDL-C, ApoB, and Lp(a) with add-on PCSK9 inhibitors vs. placebo in statin-treated patients across all trials were 50–63%, 43–52%, and 23–31%, respectively. Evolocumab 140 mg Q2W was ranked the best among all treatment strategies for lowering LDL-C, ApoB, and Lp(a) levels, and the treatment difference was 68.05% (95% confidence interval (CI), 62.43% to 73.67) in LDL-C reduction, 54.95% (95% CI, 49.55% to 60.35%) in ApoB reduction, and 34.25% (95% CI, 27.59% to 40.91%) in Lp(a) reduction compared with the placebo. No significant risk difference of adverse events between PCSK9 inhibitors and placebo was found.Conclusion: PCSK9 inhibitors showed a significant effect on the reduction in LDL-C, ApoB, and Lp(a) levels in statin-treated patients. Evolocumab 140 mg Q2W showed significantly larger degrees of LDL-C, ApoB, and Lp(a) reduction.

Global travel and climate change have drastically increased the number of countries with endemic or epidemic dengue. The largest dengue outbreak in Taiwan, with 43,419 cases and 228 deaths, occurred in 2015. Practical and cost-effective tools for early prediction of clinical outcomes in dengue patients, especially the elderly, are limited. This study identified the clinical profile and prognostic indicators of critical outcomes in dengue patients on the basis of clinical parameters and comorbidities. A retrospective cross-sectional study was conducted in a tertiary hospital from 1 July 2015 to 30 November 2015. Patients diagnosed with dengue were enrolled, and the initial clinical presentations, diagnostic laboratory data, details of the underlying comorbidities, and initial management recommendations based on 2009 World Health Organization (WHO) guidelines were used to evaluate prognostic indicators of critical outcomes in dengue patients. Dengue patients from another regional hospital were used to evaluate accuracy. A group B (4 points) classification, temperature < 38.5 °C (1 point), lower diastolic blood pressure (1 point), prolonged activated partial thromboplastin time (aPTT) (2 points), and elevated liver enzymes (1 point) were included in the scoring system. The area under the receiver operating characteristic curve of the clinical model was 0.933 (95% confidence interval [CI]: 0.905–0.960). The tool had good predictive value and clinical applicability for identifying patients with critical outcomes.

Introduction It is uncertain whether Assisted Reproductive Technology (ART) is associated with an increased risk of poor breastfeeding outcomes and what could be possible mechanisms. This study aimed to examine the effect of mode of conception on breastfeeding outcomes during the first two months postpartum and identify the potential mediating pathways for this relationship. Methods A retrospective cohort study was conducted in a sample of 3,565 women with live births. Participants were classified by mode of conception as follows: fertile women who conceived naturally (fertile women; n = 2,857), women with infertility who conceived naturally (sub-fertile women; n = 483), and women with infertility who conceived through ART (women with infertility; n = 310). The infant-feeding patterns were assessed with four-time points before two months postpartum. Binary and multinomial logistic regression and causal mediation analyses were performed. Results The rates of breastfeeding initiation and discontinuation across modes of conception were similar. However, infertile and sub-fertile women had 37% (95% CI 1.02, 1.83) and 56% (95% CI 1.06, 2.27) increased risks of introducing formula before the first week postpartum, respectively, and 35% (95% CI 1.01, 1.82) and 52% (95% CI 1.04, 2.24) higher risks of exclusive breastfeeding for less than one week, respectively, compared to fertile women. The relationships were mainly mediated through multiple gestation and admission to neonatal/pediatric intensive care units (NICU/PICU; proportions of mediation were over 50%). The effects of mode of conception on breastfeeding outcomes became not significant in cases of singleton birth. Conclusions Sub-fertile women and women with infertility intended to breastfeed but experienced higher perinatal risks in the early postpartum period. Multiple gestation and admission to NICU/PICU forced them to introduce formula earlier than preferred, thus leading to a shorter duration of exclusive breastfeeding. Single embryo transfer policy and breastfeeding support in NICU/PICU could help those women achieve positive early breastfeeding outcomes.

In recent years, studies on malware analysis have noticeably increased in the cybersecurity community. Most recent studies concentrate on malware classification and detection or malicious patterns identification, but as to malware activity, it still relies heavily on manual analysis for high-level semantic descriptions. We develop a sequence-to-sequence (seq2seq) neural network, called TagSeq, to investigate a sequence of Windows API calls recorded from malware execution, and produce tags to label their malicious behavior. We propose embedding modules to transform Windows API function parameters, registry, filenames, and URLs into low-dimension vectors, while still preserving the closeness property. Moreover, we utilize an attention mechanism to capture the relations between generated tags and certain API invocation calls. Results show that the most possible malicious actions are identified by TagSeq. Examples and a case study demonstrate that the proposed embedding modules preserve semantic-physical relations and that the predicted tags reflect malicious intentions. We believe this work is suitable as a tool to help security analysts recognize malicious behavior and intent with easy-to-understand tags.

Store-operated Ca2+ entry (SOCE) is an essential pathway for Ca2+ signaling, and regulates various vital cellular functions. It is triggered by the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1). Illustration of STIM1 spatiotemporal structure at the nanometer scale during SOCE activation provides structural and functional insights into the fundamental Ca2+ homeostasis. In this study, we used direct stochastic optical reconstruction microscopy (dSTORM) to revisit the dynamic process of the interaction between STIM1, end-binding protein (EB), and microtubules to the ER-plasma membrane. Using dSTORM, we found that“powder-like”STIM1 aggregates into “trabecular-like” architectures toward the cell periphery during SOCE, and that an intact microtubule network and EB1 are essential for STIM1 trafficking. After thapsigargin treatment, STIM1 can interact with EB1 regardless of undergoing aggregation. We generated STIM1 variants adapted from a real-world database and introduced them into SiHa cells to clarify the impact of STIM1 mutations on cancer cell behavior. The p.D76G and p.D84Y variants locating on the Ca2+ binding domain of STIM1 result in inhibition of focal adhesion turnover, Ca2+ influx during SOCE and subsequent cell migration. Inversely, the p.R643C variant on the microtubule interacting domain of STIM1 leads to dissimilar consequence and aggravates cell migration. These findings imply that STIM1 mutational patterns have an impact on cancer metastasis, and therefore could be either a prognostic marker or a novel therapeutic target to inhibit the malignant behavior of STIM1-mediated cancer cells. Altogether, we generated novel insight into the role of STIM1 during SOCE activation, and uncovered the impact of real-world STIM1 variants on cancer cells.

Abstract Background No data are available to assess the learning curve for transvaginal natural orifice transluminal endoscopic hysterectomy for non-prolapsed uteri in benign gynecologic diseases. The lack of exposure to transvaginal natural orifice transluminal endoscopic hysterectomy during training, in addition to a poorly defined learning curve, further deters interested physicians from applying this technique to daily practice. The aim of this study was to evaluate the learning curve and perioperative outcome of transvaginal natural orifice transluminal endoscopic hysterectomy by an experienced endoscopist. Methods A total of 240 cases of transvaginal natural orifice transluminal endoscopic hysterectomies with or without adnexectomy for various benign gynecologic diseases were included. Demographic data and various perioperative parameters were reviewed from the prospectively collected database. Operative time was set as a surrogate marker for surgical competency. The learning curve was evaluated using the cumulative sum method. Results The overall mean operative time (OT) was 76.5 min ± 22.4. Four unique phases of the learning curve were derived using cumulative sum analysis: the mean OT of phase I (the initial learning curve of 20 cases) was 86.3 ± 23.7 min, phase II (acquisition of competence of 80 cases) was 71.0 ± 21.4 min, phase III (proficiency and plateau of 80 cases) was 76.0 ± 20.4 min, and phase IV (post-learning in which more challenging cases were managed) was 81.3 ± 23.6 min. No major complications were encountered. One case in phase III converted to laparoscopy due to difficulty in performing anterior colpotomy. Conclusion Our data demonstrated four distinct phases of the learning curve of transvaginal natural orifice transluminal endoscopic hysterectomy. In a well-trained endoscopist, surgical competence in transvaginal natural orifice transluminal endoscopic hysterectomy can be reached after 20 cases.

Abstract Background Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins. Methods A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling. Results Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (β = − 0·04, P = 0·015; β = − 0·05, P = 0.003; β = − 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (β = − 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (β = − 0·01, P = 0·003; β = − 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = − 0·12; P = 0·043). Conclusions This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.

Whole-body computed tomography (WBCT) serves as the first-line imaging modality for breast cancer follow-up. To investigate the imaging characteristics and diagnostic accuracy of WBCT for incidental ovarian tumors in patients with prior breast cancer, we retrospectively reviewed a consecutive cohort of 13,845 patients with breast cancer, of whom 149 had pathologically-proven ovarian lesions. We excluded patients with ovarian diagnosis before breast cancer, CT scan not including ovary, CT-pathology interval >30 days, and severe CT artifact. Among our 60 breast cancer patients (median age, 46 years) with pathologically proven ovarian lesions, 49 patients had benign diseases, seven had primary ovarian cancer and four had ovarian metastasis from breast cancer. The histologic types of breast cancer with ovarian metastases included invasive ductal carcinoma, lobular carcinoma and angiosarcoma. Cystic ovarian lesions identified on WBCT during the breast cancer follow-up are more likely to be benign, while solid-cystic lesions are likely to be primary ovarian cancers, and solid lesions may indicate ovarian metastasis. The diagnostic accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve of WBCT were 98.3%, 100.0%, 98.0%, and 0.99 (malignant vs. benign); 90.0%, 100.0%, 85.7%, and 0.93 (metastasis vs. primary ovarian cancer), respectively. The only false positive solid lesion was a Sertoli–Leydig tumor. In conclusion, WBCT may help diagnose incidental ovarian tumors in patients with prior breast cancers and guide disease management.

Feline mammary tumor is a relatively commonly diagnosed neoplasm in the cat. Development of new veterinary cancer therapies is limited by the shortage of in vivo models that reproduce tumor microenvironment and metastatic progression. Four feline mammary tumor orthotopic patient-derived xenograft model (PDX) successfully established in NOD-SCID gamma (NSG) mice. The overall success rate of PDX establishment was 36% (4/11). Histological, immunohistochemical, and short tandem repeat analysis showed a remarkable similarity between patient’s tumor and xenograft. The tumor grafts conserve original tumor essential features, including distant metastasis. Primary FMT-1807 cell line isolated from FMT-1807PDX tumor tissue. Tumorigenicity of FMT-1807 cells expanded from PDX was assessed by orthotopic injection into NSG mice. Mice yielded tumors which preserve the lung and liver metastasis ability. This work provides a platform for FMT translational investigation.

BackgroundReal-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations.ObjectivesOur aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan.MethodsWe retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan.ResultsA total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers.ConclusionsThis real world data showed differential efficacy and safety of the four biological agents.

Due to the rapid prominence and popularity of social media, social broadcasting networks with voluntary information sharing have become one of the most powerful ways to spread word-of-mouth opinions, and thus, have influence on consumers’ preferences toward products. Therefore, sentiment analysis data from social media have become more important in forecasting product sales. For the movie industry, the opinions expressed on social media have increasing impacts on movie sales. In addition, some databases, such as the Box Office Mojo and Internet Movie Database (IMDb), contain structured data for predicting movie sales. Thus, three categories of data—data of movie databases, data of tweets, and hybrid data including movies databases and tweets—are employed symmetrically in this study. The aim of this study is to employ the least squares support vector regression (LSSVR) to forecast movie sales worldwide according to these three forms of data. In addition, three other forecasting techniques—namely, the back propagation neural network (BPNN), the generalized regression neural network (GRNN), and the multivariate linear regression (MLR) model—were used to forecast movie sales with the three types of data. The empirical results show that the LSSVR model with hybrid data can obtain more accurate results than the other forecasting models with all data types. Thus, forecasting movie sales using the LSSSVR model with data containing movie databases and tweets is a feasible and prospective method to forecast movie sales.

This study used observation and interviews with participants in “PunCar Action” to understand how participatory design methods can be applied to the education of rural individuals in information and communication technology (ICT). PunCar Action is a volunteer program in which ICT educators tour the rural communities of Taiwan, offering courses on the use of digital technology. This paper makes three contributions: First, we found that participatory design is an excellent way to teach ICT and Web 2.0 skills, co-create community blogs, and sustain intrinsic motivation to use Web applications. Second, PunCar Action provides an innovative bottom-up intergenerational ICT education model with high penetrability capable of enhancing the confidence of rural residents in the use of ICT. Third, the content of basic courses was based on applications capable of making the lives of elderly individuals more convenient, and the advanced course was based on the co-creation of community blogs aimed at reviving the core functions of communities and expanding local industry. Our research was conducted with the use of a non-quantitative index to measure ICT learning performance of participants from a rural community. The results show that PunCar Action emphasizes interpersonal communication and informational applications and creates a collaborative process that encourages rural residents to take action to close the digital divide.

The purpose of this study was to compare the safety and efficacy of an electrothermal bipolar vessel sealing device (LigaSure™) and traditional electrical cauterization in laparoscopic myomectomy (LM). A total of 756 patients with symptomatic uterine myomas who underwent LM were reviewed retrospectively. A total of 225 cases of LM using LigaSure™ (LML group) were compared with a control group treated with traditional electrical cauterization (LME group) under propensity-matched analysis. Outcome measures for both groups were compared, such as operative time, blood loss (BL), complications, need for blood transfusion, hospital expenses, and hospital stay. Six subgroups were divided according to main myoma size and energy source. No cases required switching to abdominal myomectomy. The number of myomas removed, BL, need for blood transfusion, and complications were not significantly different, whereas hospital stay was longer in the LME group than in the LML group and total hospital expenses were higher in the LML group (p < 0.001). The overall operation duration was significantly longer in the LML group but was not significantly different for main myoma >10 cm (LML vs LME, 121.58 ± 41.77 vs 121.69 ± 44.95, p = 0.99); this likely reflects the operative efficiency on using LigaSure™ to manage large tumors. Significant linear correlations between myoma weight and operative time and BL were seen in both groups. Conventional diathermy is more effective for small-to-medium myomas. Use of the LigaSure™ was efficient for myomas >10 cm.

Background/Aims: Water channels, also named aquaporins (AQPs), play crucial roles in cellular water homeostasis. Methods: RT-PCR indicated the mRNA expression of AQPs 1-5, 7, 9, and 11-12, but not AQPs 0, 6, 8, and 10 in the 2∼8-cell stage human embryos. AQP3 and AQP7 were further analyzed for their mRNA expression and protein expression in the oocyte, zygote, 2-cell embryo, 4-cell embryo, 8-cell embryo, morula, and blastocyst from both human and mouse using RT-PCR and immunofluorescence, respectively. Results: AQP3 and AQP7 were detected in all these stages. Knockdown of either AQP3 or AQP7 by targeted siRNA injection into 2-cell mouse embryos significantly inhibited preimplantation embryo development. However, knockdown of AQP3 in JAr spheroid did not affect its attachment to Ishikawa cells. Conclusion: These data demonstrate that multiple aquaporins are expressed in the early stage human embryos and that AQP3 and AQP7 may play a role in preimplantation mouse embryo development.

Instagram is currently the most popular social media app among young people around the world. More than 70% of people between the ages of 12 and 24 are Instagram users. The research framework of this study was constructed based on smartphone addiction and the uses and gratifications theory. We used 27 question items divided into five factors, namely social interaction, documentation, diversion, self-promotion, and creativity, to investigate the motives for Instagram use and topics of interest among university students in Taiwan. A total of 307 valid questionnaires were obtained. The results revealed that on the whole, the motives for Instagram use were mostly to look at posts, particularly involving social interaction and diversion motives. The level of agreement expressed toward motives for creating posts was lower. Gender, professional training background, and level of addiction to Instagram all exert influence on motives for Instagram use. Over half of the students majoring in design followed artisans and celebrities (including designers), and female students noticed ads on Instagram more than male students did.

Renal cell carcinoma (RCC) originates in the lining of the proximal convoluted tubule and accounts for approximately 3% of adult malignancies. The RCC incidence rate increases annually and is twofold higher in males than in females. Female hormones such as estrogen may play important roles during RCC carcinogenesis and result in significantly different incidence rates between males and females. In this study, we found that estrogen receptor β (ERβ) was more highly expressed in RCC cell lines (A498, RCC-1, 786-O, ACHN, and Caki-1) than in breast cancer cell lines (MCF-7 and HBL-100); however, no androgen receptor (AR) or estrogen receptor α (ERα) could be detected by western blot. In addition, proliferation of RCC cell lines was significantly decreased after estrogen (17-β-estradiol, E2) treatment. Since ERβ had been documented to be a potential tumor suppressor gene, we hypothesized that estrogen activates ERβ tumor suppressive function, which leads to different RCC incidence rates between males and females. We found that estrogen treatment inhibited cell proliferation, migration, invasion, and increased apoptosis of 786-O (high endogenous ERβ), and ERβ siRNA-induced silencing attenuated the estrogen-induced effects. Otherwise, ectopic ERβ expression in A498 (low endogenous ERβ) increased estrogen sensitivity and thus inhibited cell proliferation, migration, invasion, and increased apoptosis. Analysis of the molecular mechanisms revealed that estrogen-activated ERβ not only remarkably reduced growth hormone downstream signaling activation of the AKT, ERK, and JAK signaling pathways but also increased apoptotic cascade activation. In conclusion, this study found that estrogen-activated ERβ acts as a tumor suppressor. It may explain the different RCC incidence rates between males and females. Furthermore, it implies that ERβ may be a useful prognostic marker for RCC progression and a novel developmental direction for RCC treatment improvement.