Search

Ya-Hsin Chou,1,* Chemin Lin,2– 4,* Shwu-Hua Lee,2,5,* Ya-Wen Chang Chien,6,* Li-Chen Cheng7,* 1Department of Psychiatry, Taoyuan Chang Gung Memorial Hospital, Taoyuan County, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan County, Taiwan; 3Department of Psychiatry, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan; 4Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; 5Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan County, Taiwan; 6Department of Photography and Virtual Reality Design, Huafan University, New Taipei, Taiwan; 7Department of Information and Finance Management, National Taipei University of Technology, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Li-Chen Cheng, National Taipei University of Technology, Department of Information and Finance Management, Taipei, 106, Taiwan, Email lijen.cheng@gmail.com Ya-Wen Chang Chien, Huafan University, Department of Photography and Virtual Reality Design, New Taipei, 223, Taiwan, Email ywcc@gm.hfu.edu.twAbstract: The rapid aging of the global population presents challenges in providing mental health care resources for older adults aged 65 and above. The COVID-19 pandemic has further exacerbated the global population’s psychological distress due to social isolation and distancing. Thus, there is an urgent need to update scholarly knowledge on the effectiveness of mHealth applications to improve older people’s mental health. This systematic review summarizes recent literature on chatbots aimed at enhancing mental health and well-being. Sixteen papers describing six apps or prototypes were reviewed, indicating the practicality, feasibility, and acceptance of chatbots for promoting mental health in older adults. Engaging with chatbots led to improvements in well-being and stress reduction, as well as a decrement in depressive symptoms. Mobile health applications addressing these studies are categorized for reference.Keywords: chatbot, mHealth application, older adults, mental health

A remarkable assortment of drug delivery systems became available in the last quarter of the 20th century, and even more are under investigation. What do they have to offer? [ABSTRACT FROM AUTHOR]

Background & Aims: Despite ongoing research, the optimal nutritional support strategy in the first week of intensive care unit (ICU) stay remains unclear, given the complex interplay of the dynamic metabolic change and evolving nutritional requirements. In this study, we assessed the impact of calorie deficiency during this period on the nutritional care of critically ill patients., Methods: In this retrospective study, we examined ICU admissions from January 2018 to September 2021, focusing on patients whose ICU stay exceeded 7 days. Data were collected from days 2 to 7 of ICU admission. The "average caloric intake (%)" was calculated as the actual calorie intake divided by the calculated calorie requirement over 6 days. Cox proportional hazard models were employed for analyzing the 28-day mortality, supplemented by sensitivity and subgroup analyses., Results: The analysis of 3,544 patients revealed that those receiving less than 60% of their target calories in the first ICU week experienced higher 28-day mortality (hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.19-1.67, p < 0.0001). Daily caloric intake below 30% of the goal from day 5 onward was associated with a gradual increase in mortality risk. Conversely, a significant reduction in 28-day mortality was noted in patients with a daily intake of >80% starting from day 6., Conclusion: Our study underscores the correlation between caloric deficit (< 60%) in the initial ICU week and heightened mortality risk. It suggests the potential benefits of aggressive nutritional intervention toward the end of the week. These insights offer valuable guidance for clinicians in critical care settings., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Colorectal cancer (CRC) leads to life loss and a significant economic burden, which could be reduced by CRC screening., Objective: We assessed the potential savings of lives and employment to evaluate the effectiveness of the Taiwan CRC Screening Programme., Methods: Through interlinkages among Taiwan Cancer Registry, National Mortality Registry, Taiwan CRC Screening Database, and National Health Insurance claim data, we enroled patients with colorectal adenocarcinoma, aged 50-74 years and diagnosed during 2004-2017, and followed them up to 2018. Life expectancy (LE), lifetime employment duration (LED), loss-of-LE and loss-of-LED were calculated, compared with age-, sex- and calendar year-matched cohorts. Assuming no difference within a specific stage for screen-detected versus non-screen detected CRC and weighting them by different stage distributions, we compared the total loss-of-LE and loss-of-LED., Results: The cohort enroled 77,169 patients with colorectal adenocarcinoma, which included 31,728 women (mean [SD] age, 62.5 [7.1] years) and 45,441 men (mean [SD] age, 62.8 [6.8] years). The mean loss-of-LE and loss-of-LED in women were 6.0 (95% confidence interval [CI] 5.7-6.3) and 1.0 (95% CI 0.8-1.1) year(s), whereas those in men were 5.1 (95% CI 4.9-5.4) and 1.1 (95% CI 1.0-1.2) years, respectively. Among the cohort, 53,678 cases had the screening information. On average, screening potentially saved 2.9 (95% CI 2.6-3.2) years of life expectancy plus 0.5 (95% CI 0.4-0.6) years of employment per case in women and 2.7 (95% CI 2.5-3.0) years plus 0.6 (95% CI 0.5-0.7) years in men, respectively., Conclusion: The Taiwan CRC Screening Programme is associated with the savings of lives and employment duration. Future studies are warranted to evaluate the cost-effectiveness of beginning screening at a younger age after accounting for saving employment loss and possibly adjusting lead time bias., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Dengue poses a significant public health concern. Secondary dengue infections with different dengue virus (DENV) serotypes have been linked to an increased risk of severe dengue. This study aimed to assess the risk of severe dengue during secondary infection in Taiwan., Methods: A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database to identify dengue cases with secondary dengue infection born after 1944 from 2014 to 2015. Ten matched patients with primary infection were selected as controls using propensity score matching for each secondary dengue infection case. The odds ratio (OR) for severe dengue in secondary versus primary infections was calculated using conditional logistic regression., Results: This study included 357 cases with secondary dengue infection and 3570 matched controls. The risk of severe dengue was found to be 7.8% in individuals with secondary infection, compared to 3.8% in those with primary dengue infection. Secondary infection significantly increased the risk of severe dengue (OR 2.13, 95% CI: 1.40-3.25, P = 0.0004). Notably, a significant association between secondary infection and severe dengue was observed only when the interval between the first and secondary infection was greater than two years (OR 3.19, 95% CI 2.04-5.00, P < 0.0001)., Conclusion: Secondary dengue infection significantly increases the risk of severe disease in Taiwan, particularly when the interval between infections is over two years. Healthcare professionals should maintain heightened vigilance for individuals with a history of previous dengue infection, particularly if their initial diagnosis was more than two years prior., (Copyright © 2024. Published by Elsevier B.V.)

Background: To evaluate the association between maternal MVCs during pregnancy and neurodevelopmental disorders (NDDs, including intellectual disability, ADHD, ASD, and infantile cerebral palsy) in children., Methods: This population-based cohort of live births in Taiwan was analyzed, comparing children born to mothers involved in MVCs during pregnancy with those without such exposure. Children were linked to the insurance database to identify the possible diagnosis of NDDs. The Cox proportional hazards regression model was used to estimate the relative hazards., Results: A total of 19,277 children with maternal MVCs and 76,015 children without exposure were included. Children exposed to maternal MVCs during the first two trimesters or whose mothers sustained mild to severe injuries showed a higher risk of intellectual disability. Severe maternal injuries also increased the risk of infantile cerebral palsy (aHR = 3.86; 1.27-11.78). MVCs in the third trimester, or mild maternal injuries, were associated with a higher risk of ASD (third trimester: aHR = 1.40; 1.04-1.87; mild injuries: aHR = 1.38; 1.09-1.74)., Conclusion: Children exposed to maternal MVCs with severe injuries had a higher risk of intellectual disability and cerebral palsy. Third-trimester exposure may increase the risk of ASD. However, these findings should be interpreted cautiously as genetic factors may contribute to the observed association., Impact: There is some evidence linking maternal MVCs during pregnancy to the development of neurodevelopmental disorders in children. Children of mothers with severely injured were more likely to suffer from infantile cerebral palsy and intellectual disability. The risk of autism spectrum disorder is higher in children whose mothers are involved in MVCs during the late stage of pregnancy, and there is also an increased risk of intellectual disability during the first two trimesters., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate This study was approved by the Institutional Review Board of the National Cheng Kung University Hospital (No. B-ER-109-088)., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background/Objectives : Uvulopalatopharyngoplasty (UPPP), palatal plus nasal surgery (PNS), and continuous positive airway pressure (CPAP) are widely implemented treatments for obstructive sleep apnea (OSA). This study aims to explore the long-term effects on objective sleep parameters and patient-reported outcomes (PROs) following different therapeutic interventions for OSA. Methods : Data from patients with moderate-to-severe OSA were retrospectively collected from a medical center and a regional hospital, spanning from December 2011 to August 2018. Objective evaluations included the Apnea-Hypopnea Index (AHI), minimum O 2 saturation, and sleep efficiency. The PROs consisted of the Snore Outcomes Survey and Epworth Sleepiness Scale. Using mixed-effects models, we evaluated longitudinal changes in sleep parameters and PROs, accounting for repeated measures and variations within individuals over time. Results : Among 448 patients with moderate-to-severe OSA, follow-up data were collected for 42 patients undergoing UPPP surgery, 171 undergoing PNS, 127 using CPAP, and 108 in the non-treated group. The mean follow-up was 16.7 months (SD = 11.9, range: 1.6-77.3). Significant improvements were observed in AHI, minimum O 2 saturation, and hypersomnia immediately following interventions with UPPP, PNS, and CPAP therapy ( p < 0.05). Moreover, the analysis revealed no significant rate of change in these parameters over time, suggesting that the benefits of these treatments were sustained in the long term. Furthermore, all interventions exhibited a significant short-term effect on self-reported snoring when compared to the control group, with a p -value of less than 0.001. However, the magnitude of this improvement gradually decreased over time. The snore scores seemed to return to pre-treatment levels among the UPPP, PNS, and CPAP groups after averages of 46.4, 63.5, and 74.4 months, respectively (all p < 0.05). Conclusions : Surgical interventions and CPAP therapy showed potential long-term effectiveness in managing OSA. Snoring symptoms reappeared about 3.9-5.3 years after surgical treatments, which seemed earlier than the average of 6.2 years in patients receiving CPAP and should be considered in patient-participatory decision-making processes.

(1) Background: Adipose tissue serves as a central repository for energy storage and is an endocrine organ capable of secreting various adipokines, including leptin and adiponectin. These adipokines exert profound influences on diverse physiological processes such as insulin sensitivity, appetite regulation, lipid metabolism, energy homeostasis, and body weight. Given the integral role of adipose tissue in metabolic regulation, it is imperative to investigate the effects of varying proportions and types of dietary fats on adipocyte function. In addition, our previous study showed that P/S = 5 and MUFA = 60% appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in β-oxidation. Therefore, the objective of this study was to explore the effects of a polyunsaturated fatty acid (PUFA) to saturated fatty acid (SFA) ratio of 5 and varying levels of monounsaturated fatty acids (MUFA = 30% or 60%) on lipogenesis. (2) Methods: We cultured 3T3-L1 mouse embryo fibroblasts in Dulbecco's modified Eagle's medium (DMEM) containing 10% bovine calf serum until confluent. Varying ratios of palmitic acid (PA), oleic acid (OA), and linoleic acid (LA) were first bound with bovine serum albumin (BSA) before being applied to 3T3-L1 adipocytes in low doses and in high doses. (3) Results: Low doses of P/S ratio = 5, MUFA = 60% (M60) fatty acids decreased the accumulation of triglycerides in mature adipocytes by decreasing the mRNA expression of adipogenic factors, such as peroxisome proliferator-activated receptors (PPARs), lipoprotein lipase (LPL), and glucose transporter-4 (GLUT-4), while increasing lipolytic enzyme (hormone-sensitive lipase, HSL) expression when compared to high doses of P/S ratio = 5, MUFA = 60% (M60), low and high doses of P/S ratio = 5, MUFA = 30% (M30). Furthermore, the treatment of M60 in low doses also decreased the secretion of leptin and increased the secretion of adiponectin in adipocytes. (4) Conclusions: The composition of P/S = 5, MUFA = 60% fatty acid in low doses appeared to result in anti-adipogenic effects on 3T3-L1 adipocytes due to the down-regulation of adipogenic effects and the transcription factor.

(1) Background: According to the 2005~2008 Nutrition and Health Survey in Taiwan (NAHSIT), more than half of Taiwanese women (57.3%) had metabolic syndrome during menopause. Metabolic syndrome is a set of risk factors for cardiovascular disease (CVD) that increase the risk of cardiovascular disease, diabetes, and mortality. Epidemiological studies suggest that the consumption of tomato-based foods might reduce the risk factors for CVD. The aim of this study is to examine the effects of tomato consumption on lowering the metabolic syndrome risk factors among overweight postmenopausal women. (2) Methods: We conducted a randomized controlled trial using 8-week open-label dietary intervention. Overweight postmenopausal women aged 45-70 years old were recruited from Taipei Medical University in October 2013. They were randomly assigned into two groups (a control diet vs. a tomato diet). Blood samples were collected at the baseline and at the 4th and 8th weeks. The lipid profile, blood sugar, and antioxidant biomarkers, i.e., the ferric-reducing ability of plasma (FRAP) and serum carotenoids, were analyzed. Blood pressure, body weight, and body fat were also measured every week. (3) Results: After the 8-week dietary intervention, body weight, body mass index, waist circumference, and hip circumference were significantly lower in both groups ( p < 0.05). Body fat mass, body fat percentage, waist circumference, and hip circumference were significantly lower in the tomato diet group than in the control diet group. The tomato diet group had significantly lower serum total cholesterol, triglyceride, systolic blood pressure and blood sugar, and higher high-density lipoprotein cholesterol than the control diet group. The antioxidant biomarkers, FRAP, beta-carotenoids, and lycopene were significantly higher in the tomato diet group than in the control diet group. (4) Conclusions: Fresh tomato consumption can increase antioxidant biomarkers to reduce risks of metabolic syndrome in postmenopausal women.

Objective: Whether pregnancy is associated with severe injuries from motor vehicle crashes (MVCs) remains unclear. This study aimed to investigate the potential relationship between pregnancy and severity of injuries from MVCs., Methods: We identified a total of 23,559 pregnant women victims who encountered MVCs during pregnancy as well as 94,236 age- and calendar year-at MVC matched non-pregnant women victims that are also involved in MVCs. Injury severity was assessed using the Maximum Abbreviated Injury Scale (MAIS) based on the diagnosis of medical claims after MVCs. Multinomial logistic regression models were used to estimate the odds ratio and corresponding 95 % CI of injury severity levels associated with pregnancy., Results: Pregnant women had a significantly higher risk of both severe (adjusted odds ratio, aOR = 1.79, 95 % CI = 1.54-2.08) and mild injuries (aOR = 8.63, 95 % CI = 8.21-9.07) following MVCs as compared to non-pregnant women victims. Particularly, pregnant women who were riding scooters had an increased risk of severe injury (aOR = 4.25, 95 % CI = 3.58-5.04). In addition, pregnant women who experienced MVC but without any injury were more likely to visit a clinic than non-pregnant MVC victims., Conclusion: Pregnant women victims, particularly those who were riding scooters involved in MVCs suffered from a higher risk of severe injury as compared to their non-pregnant counterparts. Our findings suggest that women should consider avoiding riding a scooter and must use restrictive devices during pregnancy, which would help reduce the severity of injuries sustained following an MVC., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

To assess the effects of hydroxysafflor yellow A (HSYA) on ultraviolet A (UVA)-induced damage in HaCaT keratinocytes. HaCaT keratinocytes were UVA-irradiated, and the effects of HSYA on cell viability, reactive oxygen species (ROS) generation, lipid peroxidation, and messenger (m)RNA expression were measured. mRNA expressions of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and cyclooxygenase (COX)-2 were determined by a real-time polymerase chain reaction (RT-PCR). UVA exposure led to a decrease in cell viability and an increase in ROS generation in HaCaT keratinocytes. HSYA effectively increased the viability of HaCaT keratinocytes after UVA exposure and protected them from UVA-induced oxidative stress. Moreover, HSYA inhibited expressions of MMP-1, MMP-2, MMP-9, and COX-2 by HaCaT keratinocytes with UVA-induced photodamage. Our results suggest that HSYA can act as a free radical scavenger when keratinocytes are photodamaged. HSYA has the potential to be a skin-protective ingredient against UVA-induced photodamage.

Background: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied., Methods: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure., Results: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year., Conclusion: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates., Methods: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources., Results: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs., Conclusions: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact the clinical management of women with incidental STICs (without concurrent carcinoma) identified in cases of prophylactic or opportunistic salpingectomy. This study analyzed morphologic and molecular features of 171 STICs and 21 serous tubal intraepithelial lesions. We assessed their histologic features, Ki-67 and p53 staining patterns, and genome-wide DNA copy number alterations. We classified all precursor lesions into 2 morphologic subtypes, one with a flat surface (Flat) and the other characterized by budding, loosely adherent, or detached (BLAD) morphology. On the basis of pathology review by a panel of 8 gynecologic pathologists, we found 87 BLAD, 96 Flat, and 9 indeterminate lesions. As compared with Flat lesions, BLAD lesions were more frequently diagnostic of STIC ( P <0.0001) and were found concurrently with HGSC ( P <0.0001). BLAD morphology was also characterized by higher Ki-67 proliferation index ( P <0.0001), presence of epithelial stratification ( P <0.0001), and increased lymphocyte density ( P <0.0001). BLAD lesions also exhibited more frequent DNA copy number gain/amplification at the CCNE1 or CMYC loci canonical to HGSCs ( P <0.0001). Both BLAD morphology and STIC diagnoses are independent risk factors for an elevated Ki-67 proliferation index. No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline BRCA1/2 mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes., Competing Interests: Supported by the Break Through Cancer (BTC-IOC), the Richard W. TeLinde Endowment from the Johns Hopkins University, NIH/NCI (U2CCA271891, P50CA228991, R01CA260628, and R01CA215483). C.D. is a consultant to Exact Sciences and has been paid in equity and income. C.D. is a founder of Belay Diagnostics. C.D. is an inventor of some technologies. The companies named above as well as other companies have licensed previously described technologies related to the work described in this paper from Johns Hopkins University. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors as well as Johns Hopkins University. The terms of all of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This study aimed to investigate the effect of amorphous calcium carbonate (ACC) supplementation on bone growth in growing rats., Methods: We used 3-week-old male Wistar rats to simulate childhood and adolescent growth stages. Rats were divided into four groups as follows: a control group (C), a low-dose group (L, 20.65 mg/kg body weight (BW) ACC), a medium-dose group (M, 206.5 mg/kg BW ACC), and a high-dose group (H, 413 mg/kg BW ACC) administered by gavage. Body length (BL) and BW were measured weekly. The bone mineral density (BMD) of two lumbar vertebrae (L3 and L4) and the left femur were analyzed by micro-computed tomography (μCT) at 0, 4, 8, and 12 weeks. At the end of 12 weeks, the rats were sacrificed. After that, blood samples were collected from the abdominal aorta. Femurs and tibias were collected and weighed, and their lengths were measured. Then, bone samples were used to perform histopathological and histomorphometric analyses., Results: It showed that ACC supplementation in growing rats increased the trabecular bone thickness and serum bone formation biomarkers. Furthermore, high-dose ACC decreased serum bone resorption biomarkers and increased BMD., Conclusions: ACC supplementation can enhance osteoblast metabolism and inhibit osteoclast metabolism, resulting in a higher bone formation rate compared to bone resorption. This led to increased trabecular bone thickness, a higher BMD, and supported bone growth.

Purpose: Serous tubal intraepithelial carcinoma (STIC) is now recognized as the main precursor of ovarian high-grade serous carcinoma (HGSC). Other potential tubal lesions include p53 signatures and tubal intraepithelial lesions. We aimed to investigate the extent and pattern of aneuploidy in these epithelial lesions and HGSC to define the features that characterize stages of tumor initiation and progression., Experimental Design: We applied RealSeqS to compare genome-wide aneuploidy patterns among the precursors, HGSC (cases, n = 85), and histologically unremarkable fallopian tube epithelium (HU-FTE; control, n = 65). On the basis of a discovery set (n = 67), we developed an aneuploidy-based algorithm, REAL-FAST (Repetitive Element AneupLoidy Sequencing Fallopian Tube Aneuploidy in STIC), to correlate the molecular data with pathology diagnoses. We validated the result in an independent validation set (n = 83) to determine its performance. We correlated the molecularly defined precursor subgroups with proliferative activity and histology., Results: We found that nearly all p53 signatures lost the entire Chr17, offering a "two-hit" mechanism involving both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYC), or 8q arm, whereas proliferatively dormant STICs show 22q loss. REAL-FAST classified HU-FTE and STICs into 5 clusters and identified a STIC subgroup harboring unique aneuploidy that is associated with increased proliferation and discohesive growth. On the basis of a validation set, REAL-FAST showed 95.8% sensitivity and 97.1% specificity in detecting STIC/HGSC., Conclusions: Morphologically similar STICs are molecularly distinct. The REAL-FAST assay identifies a potentially "aggressive" STIC subgroup harboring unique DNA aneuploidy that is associated with increased cellular proliferation and discohesive growth. REAL-FAST offers a highly reproducible adjunct technique to assist the diagnosis of STIC lesions., (©2023 American Association for Cancer Research.)

Background: Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes., Methods: This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes., Results: Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04-1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose-response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects., Conclusions: In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan., Methods: A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test., Results: A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28-34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester., Conclusion: Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28-34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims., (© 2023. The Author(s).)

Dengue infection can affect the central nervous system and cause various neurological complications. Previous studies also suggest dengue was associated with a significantly increased long-term risk of dementia. A population-based cohort study was conducted using national health databases in Taiwan and included 37,928 laboratory-confirmed dengue patients aged ≥ 45 years between 2002 and 2015, along with 151,712 matched nondengue individuals. Subdistribution hazard regression models showed a slightly increased risk of Alzheimer's disease, and unspecified dementia, non-vascular dementia, and overall dementia in dengue patients than the nondengue group, adjusted for age, sex, area of residence, urbanization level, income, comorbidities, and all-cause clinical visits within one year before the index date. After considering multiple comparisons using Bonferroni correction, only overall dementia and non-vascular dementia remained statistically significant (adjusted SHR 1.13, 95% CI 1.05-1.21, p = 0.0009; E-value 1.51, 95% CI 1.28-NA). Sensitivity analyses in which dementia cases occurring in the first three or five years after the index dates were excluded revealed no association between dengue and dementia. In conclusion, this study found dengue patients had a slightly increased risk of non-vascular dementia and total dementia than those without dengue. However, the small corresponding E-values and sensitivity analyses suggest the association between dengue and dementia may not be causal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Changes in risk of motor vehicle crashes (MVCs) during pregnancy are less known, and very few studies have assessed this issue by using unselected population-based datasets and adopting a before-and-during design. The study aimed to address the risk of MVC events in association with pregnancy using a national pregnant women cohort in Taiwan., Methods: We conducted a self-matched design in which each woman served as a driver before and during pregnancy. A total of 1,372,664 pregnant women with live birth(s) at 18-50 years of age between 2008 and 2017 were identified from the Birth Notification dataset. MVC events as a driver were ascertained from the Police-reported Traffic Accident Registry dataset. We calculated the rate ratio (RR) with a 95 % confidence interval (CI) using the conditional Poisson regression model to compare the MVC event rates between pre-pregnancy and pregnancy periods., Results: The overall rate of MVC events was significantly reduced during pregnancy (RR = 0.69, 95 % confidence interval (CI) = 0.68-0.71). Mothers with alcoholism during pregnancy were associated with an increased RR at 2.00 but with a very wide CI. Reduction in RR was primarily attributed to the reduced MVC event rate involving scooter crashes (0.60, 95 % CI = 0.58-0.62)., Conclusion: Although MVC event rates decreased during women became pregnant, many women drivers were still involved in MVCs during pregnancy. Their potential maternal and perinatal conditions along with their offspring's health outcomes need further investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Dengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to investigate serum FLC levels in dengue patients. The findings revealed elevated serum λ FLCs, which were associated with the severity of dengue. Receiver operating characteristic curve (ROC) analysis demonstrated that λ FLCs may serve as a serum marker for identifying dengue disease (AUC: 0.7825, sensitivity: 80, specificity: 71.43) and classifying severe dengue (AUC: 0.8102, sensitivity: 75, specificity: 79.52). The viral protease, Dengue virus (DENV) nonstructural protein 3 (NS3), acts as a protease that cleaves viral polyproteins as well as host substrates. Therefore, we proposed that antibodies might be potential targets of NS3 protease, leading to an increase in FLCs. LC/MS-MS analysis confirmed that λ FLCs were the predominant products after antibody degradation by NS3 protease. Additionally, purified NS3 protease cleaved both human IgG and DENV2-neutralizing antibodies, resulting in the presence of λ FLCs. Moreover, NS3 protease administration in vitro led to a reduction in the neutralizing efficacy of DENV2-neutralizing antibodies. In summary, the elevated serum λ FLC levels effectively differentiate dengue patients from healthy individuals and identify severe dengue. Furthermore, the elevation of serum λ FLCs is, at least in part, mediated through NS3 protease-mediated antibody cleavage. These findings provide new insights for developing diagnostic tools and understanding the pathogenesis of DENV infection.

Background: Artificial intelligence (AI) holds significant potential to be a valuable tool in healthcare. However, its application for predicting bacteremia among adult febrile patients in the emergency department (ED) remains unclear. Therefore, we conducted a study to provide clarity on this issue., Methods: Adult febrile ED patients with blood cultures at Chi Mei Medical Center were divided into derivation (January 2017 to June 2019) and validation groups (July 2019 to December 2020). The derivation group was utilized to develop AI models using twenty-one feature variables and five algorithms to predict bacteremia. The performance of these models was compared with qSOFA score. The AI model with the highest area under the receiver operating characteristics curve (AUC) was chosen to implement the AI prediction system and tested on the validation group., Results: The study included 5,647 febrile patients. In the derivation group, there were 3,369 patients with a mean age of 61.4 years, and 50.7% were female, including 508 (13.8%) with bacteremia. The model with the best AUC was built using the random forest algorithm (0.761), followed by logistic regression (0.755). All five models demonstrated better AUC than the qSOFA score (0.560). The random forest model was adopted to build a real-time AI prediction system integrated into the hospital information system, and the AUC achieved 0.709 in the validation group., Conclusion: The AI model shows promise to predict bacteremia in adult febrile ED patients; however, further external validation in different hospitals and populations is necessary to verify its effectiveness., 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 Elsevier B.V. All rights reserved.)

Background: Dengue virus (DENV) infection is the most prevalent mosquito-borne viral disease. Stroke is a severe manifestation of dengue. However, few large-scale studies have investigated post-dengue risk of stroke., Methods: This population-based cohort study included 57,934 newly diagnosed, laboratory-confirmed dengue patients in Taiwan from 2002 to 2015; patients were matched to nondengue individuals by age, sex, and area of residence at a ratio of 1:4 (n = 231,736). We used subdistribution hazard regression to evaluate short-term (≤ 30 days), medium-term (31-365 days), and long-term (1-3 years) risk of stroke after DENV infection. The robustness of the results to unmeasured confounding was assessed with E-values., Results: DENV infection was associated with a significantly increased risk of overall stroke (aSHR 4.51; 95% CI: 3.23-6.32; P < 0.0001; E-value = 8.49), hemorrhagic stroke (aSHR 4.13; 95% CI: 2.20-7.76; P < 0.0001; E-value =7.73), and ischemic stroke (aSHR 3.80; 95% CI: 2.37-6.11; P < 0.0001; E-value = 7.06) within 30 days. Stratified analysis by age showed that the aSHRs for overall stroke, hemorrhagic stroke, and ischemic stroke were larger among dengue patients aged ≥ 65 during the first 30 days. The 30-day risks of overall stroke, hemorrhagic stroke, and ischemic stroke among elderly dengue patients were 6.71, 1.29, and 3.49 per 1000, respectively. No increased risk was observed after 30 days., Conclusion: DENV infection was associated with a significant short-term increased risk of stroke. Clinical practitioners should remain alert to patients with stroke-associated symptoms during epidemic seasons, especially elderly patients., Competing Interests: Declaration of Competing Interest The authors have not interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Health advocates and the media often use the rankings of the leading causes of death (CODs) to draw attention to health issues with relatively high mortality burdens in a population. The National Center for Health Statistics (NCHS) publishes "Deaths: leading causes" annually. The ranking list used by the NCHS and statistical offices in several countries includes broad categories such as cancer, heart disease, and accidents. However, the list used by the World Health Organization (WHO) subdivides broad categories (17 for cancer, 8 for heart disease, and 6 for accidents) and classifies Alzheimer disease and related dementias and hypertensive diseases more comprehensively compared to the NCHS list. Regarding the data visualization of the rankings of leading CODs, the bar chart is the most commonly used graph; nevertheless, bar charts may not effectively reveal the changes in the rankings over time., Objective: The aim of this study is to use a dashboard with bump charts to visualize the changes in the rankings of the leading CODs in the United States by sex and age from 1999 to 2021, according to 2 lists (NCHS vs WHO)., Methods: Data on the number of deaths in each category from each list for each year were obtained from the Wide-ranging Online Data for Epidemiologic Research system, maintained by the Center for Disease Control and Prevention. Rankings were based on the absolute number of deaths. The dashboard enables users to filter by list (NCHS or WHO) and demographic characteristics (sex and age) and highlight a particular COD., Results: Several CODs that were only on the WHO list, including brain, breast, colon, hematopoietic, lung, pancreas, prostate, and uterus cancer (all classified as cancer on the NCHS list); unintentional transport injury; poisoning; drowning; and falls (all classified as accidents on the NCHS list), were among the 10 leading CODs in several sex and age subgroups. In contrast, several CODs that appeared among the 10 leading CODs according to the NCHS list, such as pneumonia, kidney disease, cirrhosis, and sepsis, were excluded from the 10 leading CODs if the WHO list was used. The rank of Alzheimer disease and related dementias and hypertensive diseases according to the WHO list was higher than their ranks according to the NCHS list. A marked increase in the ranking of unintentional poisoning among men aged 45-64 years was noted from 2008 to 2021., Conclusions: A dashboard with bump charts can be used to improve the visualization of the changes in the rankings of leading CODs according to the WHO and NCHS lists as well as demographic characteristics; the visualization can help users make informed decisions regarding the most appropriate ranking list for their needs., (©Shu-Yu Tai, Ying-Chen Chi, Yu-Wen Chien, Ichiro Kawachi, Tsung-Hsueh Lu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 27.06.2023.)

Postmenopausal obesity is a rising problem. Melatonin (Mel) is a hormone secreted by the pineal gland that regulates the circadian rhythms and improves obesity. In this experiment, ovariectomized (OVX) rats were used as a menopause model to explore the effects of Mel supplementation on lipid metabolism, body fat accumulation, and obesity. Nine-week-old female rats underwent an OVX surgery and were assigned to the following groups: control group (C), low-dose group (L, 10 mg/kg body weight (BW) Mel), medium-dose group (M, 20 mg/kg BW Mel), and high-dose group (H, 50 mg/kg BW Mel), administered by gavage for 8 weeks. The results showed that the OVX rats supplemented with low, medium, and high doses of Mel for 8 weeks exhibited reduced BW gain, perirenal fat mass, and gonads fat mass, and an increased serum irisin level. Low and high doses of Mel induced brite/beige adipocytes in the white adipose tissues. In addition, the messenger RNA levels of the fatty acid synthesis enzymes were significantly reduced after the high-dose Mel supplementation. Thus, Mel can reduce the hepatic fatty acid synthesis and promote the browning of white adipose tissues through irisin; thereby, improving obesity and body fat accumulation in OVX rats.

Introduction: Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions., Methods: This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30 days), medium-term (31-365 days), and long-term (> 1 year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding., Results: This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95% CI 29.11-124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95% CI 7.66-38.29; P < 0.0001, E-value = 33.75) within the first 30 days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30 days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection., Conclusion: This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications., (© 2023. The Author(s).)

Introduction: We compared the ranking of Alzheimer's disease and related dementia (ADRD) among the leading causes of death (LCODs) between those according to the National Center for Health Statistics (NCHS) and the World Health Organization (WHO) lists by sex., Method: The number of deaths in each LCOD category was obtained from CDC WONDER., Results: According to the WHO list, ADRD was the second LCOD from 2005 to 2013, the first from 2014 to 2020, and the third in 2021, respectively, for women and was the second in 2018 and 2019, the third in 2020, and the fourth in 2021, respectively, for men. According to the NCHS list, Alzheimer's disease was the fourth in 2019 and 2020 for women and was the seventh from 2016 to 2019 for men., Discussion: The ranking of ADRD among the LCODs according to the WHO list was higher than those according to the NCHS list., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: Limited studies have assessed the association of motor vehicle crashes (MVCs) during pregnancy with adverse maternal outcomes using a population-based nationwide dataset that covers all MVCs., Methods: A total of 20 844 births from women who had been involved in MVCs during pregnancy were obtained from the National Birth Notification (BN) Database in Taiwan. We randomly selected 83 274 control births from women in the BN matched on age, gestational age and crash date. All study subjects were linked to medical claims and the Death Registry to identify the maternal outcomes after crashes. Conditional logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% CI of adverse outcomes associated with MVCs during pregnancy., Results: Pregnant women involved in MVCs had significantly higher risks of placental abruption (aOR=1.51, 95% CI 1.30 to 1.74), prolonged uterine contractions (aOR=1.31, 95% CI 1.11 to 1.53), antepartum haemorrhage (aOR=1.19, 95% CI 1.12 to 1.26) and caesarean delivery (aOR=1.05, 95% CI 1.02 to 1.09) than the controls. Such elevated risks tended to be higher in the MVCs with greater severity. Scooter riders had higher ORs of various adverse maternal outcomes than car drivers., Conclusions: Women involved in MVCs during pregnancy were at increased risk of various adverse maternal outcomes, especially in those with severe MVCs and riding scooters at MVCs. These findings suggest that clinicians should be aware of these effects, and educational materials that include the above information should be provided as part of prenatal care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort study was conducted using national health databases in Taiwan and included 63,814 newly diagnosed, laboratory-confirmed dengue patients between 2002 and 2015 and 1:4 controls (n = 255,256) matched by age, sex, area of residence and symptom onset time. Multivariate Cox proportional hazard regression models were used to investigate the risk of autoimmune diseases after dengue infection. Dengue patients had a slightly higher risk of overall autoimmune diseases than non-dengue controls (aHR 1.16; P = 0.0002). Stratified analyses by specific autoimmune diseases showed that only autoimmune encephalomyelitis remained statistically significant after Bonferroni correction for multiple testing (aHR 2.72; P < 0.0001). Sixteen (0.025%) dengue patients and no (0%) controls developed autoimmune encephalomyelitis in the first month of follow-up (HR >9999, P < 0.0001), but the risk between groups was not significantly different thereafter. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shih et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.

Background: The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018., Methods: We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard., Results: The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of "garbage codes" into relevant specific COD in IHME list., Conclusions: Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making., (© 2022. The Author(s).)

Our study's main purpose is to emphasise the significance of medical knowledge of pathophysiology before machine learning. We investigated whether combining domain knowledge with machine learning results might increase accuracy and minimise the number of bio-features used to detect obstructive sleep apnea (OSA). The present study analysed data on 36 self-reported symptoms and 24 clinical features obtained from 3,495 patients receiving polysomnography at a regional hospital and a medical centre. The area under the receiver operating characteristic (AUC) curve was used to evaluate patients with and without moderate or severe OSA using three prediction models on the basis of various estimation methods: the multiple logistic regression (MLR), support vector machine (SVM), and neural network (NN) methods. Odds ratios stratified by gender and age were also measured to account for clinicians' common sense. We discovered that adding the self-reported snoring item improved the AUC by 0.01-0.10 and helped us to rapidly achieve the optimum level. The performance of four items (gender, age, body mass index [BMI], and snoring) was comparable with that of adding two or more items (neck and waist circumference) for predicting moderate to severe OSA (Apnea-Hypopnea Index ≥15 events/hr) in all three prediction models, demonstrating the medical knowledge value of pathophysiology. The four-item test sample AUCs were 0.83, 0.84, and 0.83 for MLR, SVM, and NN, respectively. Participants with regular snoring and a BMI of ≥25 kg/m 2 had a greater chance of moderate to severe OSA according to the stratified adjusted odds ratios. Combining domain knowledge into machine learning could increase efficiency and enable primary care physicians to refer for an OSA diagnosis earlier., (© 2021 European Sleep Research Society.)

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31-365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51-64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17-95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05-6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89-3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis., Competing Interests: The authors have declared that no competing interests exist.

The aim of the study was to provide a systematic review and meta-analysis of studies examining the association between mortality risk and motor vehicle crashes (MVCs) in pregnant women compared with nonpregnant women. We used relevant MeSH terms to identify epidemiological studies of mortality risk in relation to MVCs from PubMed, Embase, and MEDLINE databases. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. For comparison of mortality from MVCs between pregnant and nonpregnant women, the pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. The eight studies selected met all inclusion criteria. These studies included 14,120 injured victims who were pregnant at the time of the incident and 207,935 victims who were not pregnant. Compared with nonpregnant women, pregnant women had a moderate but insignificant decrease in mortality risk (pooled OR = 0.68, 95% CI = 0.38-1.22, I 2 = 88.71%). Subgroup analysis revealed that the pooled OR significantly increased at 1.64 (95% CI = 1.16-2.33, I 2 < 0.01%) for two studies with a similar difference in the mean injury severity score (ISS) between pregnant and nonpregnant women. Future studies should further explore the risk factors associated with MVCs in pregnant women to reduce maternal mortality.

Background: Obesity is a state of excess energy storage resulting in body fat accumulation, and postmenopausal obesity is a rising issue. In this study using ovariectomized (OVX) rats, we mimicked low estrogen levels in a postmenopausal state in order to investigate the effects of different amounts and types of dietary fatty acids on body fat accumulation and body lipid metabolism., Methods: At 9 weeks of age, rats ( n = 40) were given an ovariectomy, eight of which were sham-operated to serve as a control group (S). We then divided OVX rats into four different intervention groups: diet with 5% soybean oil (C), and diet with 5% (L), 15% (M), and 20% (H) ( w / w ) experimental oil, containing 60% monounsaturated fatty acids (MUFAs) and with a polyunsaturated/saturated fatty acid (P/S) ratio of 5., Results: After OVX, compared to the S group, the C group showed significantly higher body weight, and insulin and leptin levels. Compared to the C group, the H group had lower hepatic triglyceride level and FAS enzyme activity, and higher hepatic ACO and CPT-1 gene expressions and enzyme activities., Conclusions: An OVX leads to severe weight gain and lipid metabolism abnormalities, while according to previous studies, high fat diet may worsen the situation. However, during our experiment, we discovered that the experimental oil mixture with 60% MUFAs and P/S = 5 may ameliorate these imbalances.

Background: Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV through the placenta has been well documented, the evidence of cell-associated vertical transmission is still unknown. Whether DENV can infect umbilical cord blood (UCB) cells before reaching the fetus remains to be explored. Here, we proposed that human UCB cells were permissive to the DENV infection and DENV infected CD133+ and CD34+ HSCs are reservoir of the virus that could be reactivated upon re-culturing in suitable cells., Methods: Human UCB cells were freshly obtained and subjected to DENV infection. Multicolor flow cytometry (MFCM) was used to demonstrate the phenotypes of the infected HSC populations. Immunofluorescence analysis (IFA) and T-distributed Stochastic Neighbor Embedding (t-SNE) were used to show the association of the DENV antigen, non-structural protein1 (NS1) with HSCs., Key Findings: UCB cells were highly permissive to DENV infection. DENV altered the phenotype of the infected HSC population, increased the expression of HSCs, and affected the balance of transcription factors (TFs, GATA1/2/3). IFA revealed the association of the DENV antigen, non-structural protein1 (NS1), with CD34 + and CD133 + cells. T-distributed Stochastic Neighbor Embedding (t-SNE) analysis revealed heterogeneity in the distribution of CD133 + NS1 + , and CD34 + NS1 + cells. DENV particles were recovered from CD133 + and CD34 + cells even when virus production in the supernatant was negligible., Significance: We predict that infection of CD133+ and CD34+ cells in the UCB serve as reservoirs for the amplification of DENV in UCB prior to the virus reaching the fetus and facilitate vertical transmission., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

A shift in dengue cases toward the adult population, accompanied by an increased risk of severe cases of dengue in the elderly, has created an important emerging issue in the past decade. To understand the level of past DENV infection among older adults after a large dengue outbreak occurred in southern Taiwan in 2015, we screened 1498 and 2603 serum samples from healthy residents aged ≥ 40 years in Kaohsiung City and Tainan City, respectively, to assess the seroprevalence of anti-DENV IgG in 2016. Seropositive samples were verified to exclude cross-reaction from Japanese encephalitis virus (JEV), using DENV/JEV-NS1 indirect IgG ELISA. We further identified viral serotypes and secondary DENV infections among positive samples in the two cities. The overall age-standardized seroprevalence of DENV-IgG among participants was 25.77% in Kaohsiung and 11.40% in Tainan, and the seroprevalence was significantly higher in older age groups of both cities. Although the percentages of secondary DENV infection in Kaohsiung and Tainan were very similar (43.09% and 44.76%, respectively), DENV-1 and DENV-2 spanned a wider age range in Kaohsiung, whereas DENV-2 was dominant in Tainan. As very few studies have obtained the serostatus of DENV infection in older adults and the elderly, this study highlights the need for further investigation into antibody status, as well as the safety and efficacy of dengue vaccination in these older populations., Competing Interests: The authors have declared that no competing interests exist.

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.

Melatonin, a pivotal photoperiodic signal transducer, may work as a brown-fat inducer that regulates energy balance. Our study aimed to investigate the effects of melatonin treatment on the body fat accumulation, lipid profiles, and circulating irisin of rats with high-fat diet-induced obesity (DIO). Methods: 30 male Sprague-Dawley rats were divided into five groups and treated for 8 weeks: vehicle control (VC), positive control (PC), MEL10 (10 mg melatonin/kg body weight (BW)), MEL20 (20 mg/kg BW), and MEL50 (50 mg/kg BW). The vehicle control group was fed a control diet, and the other groups were fed a high-fat and high-calorie diet for 8 weeks to induce obesity before the melatonin treatment began. Melatonin reduced weight gain without affecting the food intake, reduced the serum total cholesterol level, enhanced the fecal cholesterol excretion, and increased the circulating irisin level. Melatonin downregulated the fibronectin type III domain containing 5 (FNDC5) and lipoprotein lipase (LPL) mRNA expressions of inguinal white adipose tissue (iWAT) and induced the browning of iWAT in both the MEL10 and MEL20 groups. Conclusion: Chronic continuous melatonin administration in drinking water reduced weight gain and the serum total cholesterol levels. Additionally, it enhanced the circulating irisin, which promoted brite/beige adipocyte recruitment together with cholesterol excretion and contributed to an anti-obesity effect.

Perceived stress is the degree of stress experienced by an individual in the face of a stressor. Studies have shown that stress affects emotions, leads to behavioral changes, and is likely to trigger physical illnesses. According to the World Health Organization (WHO), stress is classified as a health epidemic of the 21st century; in the meantime, the percentage of adults being overweight and with obesity has continued to grow after reaching 38.9% in 2016. Hence, it is unclear whether perceived stress has become a factor affecting progressive obesity and whether food addiction (FA) is an intermediate factor. The purposes of this study were to (1) investigate the FA prevalence among young adults in Taiwan, (2) understand correlations among perceived stress, FA, and the body mass index (BMI), and (3) determine the potential mediating effect of FA due to perceived stress on BMI. The study was conducted through an online questionnaire, composed of a basic data form, the Perceived Stress Scale (PSS), and the Yale Food Addiction Scale (YFAS). We received 1994 responses and analyzed 1780 valid samples. Results showed that 231 participants met the FA criteria, accounting for 12.98%. Perceived stress was positively correlated with BMI (95% confidence interval (CI) 0.013~0.088, p -value 7.8 × 10 -3 ), and perceived stress was positively associated to FA (95% CI 1.099~1.154, p -value < 10 -4 ), which was also positively correlated with BMI (95% CI 0.705~2.176, p -value 10 -4 ). FA significantly mediated the relationship between PSS and BMI with an indirect effect size of 25.18% and 25.48% in the group that scored 31~40 on the PSS. The study concluded that among people seeking weight loss, proper stress management and screening for FA in order to apply related therapies may be an effective method for weight management.

Research indicates that high sugar intake in early childhood may increase risks of tooth decay, obesity and chronic disease later in life. In this sugar fact study, we explored whether an online intervention which focused on comprehensive and useful information about nutrition labels impacted mother's choice of low sugar food. The intervention was developed on the basis of the theory of planned behavior. In total, 122 mothers were recruited. Mothers were divided into an online-only group and a plus group. Knowledge of sugar and nutrition labels, behavioral attitudes, perceived behavioral control, behavioral intentions and behavior towards purchasing low-sugar products with nutrition labels were collected. After the intervention, both groups exhibited significantly enhanced sugar and nutrition label knowledge, perceived behavioral control, behavioral intentions and behavior. Compared to the online-only group, knowledge, perceived behavioral control and behavior of the plus group significantly improved. After the intervention, about 40% of the plus group and 80% of the online-only group still did not know the World Health Organization (WHO) sugar recommendations. Understanding sugar recommendations and using nutrition labels are crucial to help people control calorie and sugar intake. Further research with a larger sample is warranted to evaluate the effects of the intervention on long-term changes in shopping behavior. More efficient and convenient nutrition education is required to increase public awareness of sugar recommendations and help people control calorie and sugar intake.

This study explored the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy (CCRT).Between January 2006 and December 2016, 184 patients with newly-diagnosed rectal cancer receiving neoadjuvant CCRT were enrolled. Risk of overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method and Cox proportional hazard models. Stratified survival analyses were also performed between post-neoadjuvant pathological (yp) stage.The mean follow-up time was 72.73 ± 36.82 months. High- and low-NLR patients differed significantly in both 5-year DFS (P = .026) and OS (P = .016). High- and low-PLR patients differed significantly in 5-year DFS (P = .011) but not OS (P = .185). Multivariate analyses revealed worse 5-year DFS (adjusted HR [aHR] = 2.8; 95% CI: 1.473-5.41; P = .002) and 5-year OS (aHR = 1.871; 95%CI: 1.029-3.4; P = .04) in the high-NLR group after adjusting for covariates. After adjustments, the high-PLR group had inferior 5-year DFS (aHR = 2.274; 95%CI: 1.473-5.419; P = .038) but not 5-year OS (aHR = 1.156; 95%CI: 0.650-2.056; P = .622). Further stratified analysis indicated that yp stage II and III patients with high NLR had worse 5-year DFS (aHR = 2.334; 95% CI: 1.158-4.725; P = .018) and OS (aHR = 2.226; 95% CI: 1.165-4.251; P = .015). Additionally, yp stage II and III patients with high PLR had inferior 5-year DFS (aHR = 2.012; 95% CI: 1.049-3.861; P = .036).Pre-CCRT NLR and PLR are independent prognostic factors for rectal cancer patients and could be used as a potential biomarker to identify high-risk patients for more intense treatment and care.