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[[alternative]]Author Correction: Identification of PTGR2 inhibitors as a new therapeutic strategy for diabetes and obesity
No full text[[abstract]]In this article the affiliation details for Teng-Kuang Yeh were incorrectly given as “AltruBio Taiwan R&D Center, Taipei 114063, Taiwan” but should have been “Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan”. The original article has been corrected. In this article the e-mail address of the corresponding author Lun Kelvin Tsou was incorrect. The original article has been corrected
[[alternative]]Aspalathin-rich unfermented Aspalathus linearsis extract mitigates vascular endothelial inflammation by inhibiting the TNF-α/Hexokinase 2/NF-κB signaling pathway
No full text[[abstract]]Inflammation of vascular endothelium initiates cardiovascular diseases. We investigated if unfermented green Aspalathus linearis (rooibos) extract (GRT) and its main flavonoid aspalathin may suppress inflammation in cardiovascular endothelial cells. Human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were used as cell models, while β-aminopropionitrile (BAPN)-induced inflammation in mice was used as animal models. Tube formation assay, transwell migration assay, wound healing assay and monolayer permeability assay were used to examine the inflammatory effects on vascular endothelial cells, while cytokine array, qRT-PCR, ELISA, reporter gene assay, fluorescent microscopy, western blot, IHC staining and Seahorse mitochondrial analyzer were used to dissect the molecular mechanisms lying underneath. TNF-α decreased angiogenesis and VE-cadherin expression but increased cellular migration, monolayer permeability, secretion of inflammation cytokines IL-6 and IL-8, as well as NF-κB activity in HCAEC and HUVEC cells. Treatment with GRT or aspalathin reversed these TNF-α-induced inflammatory effects. We discovered that hexokinase 2 (HK2) was essential in regulation of TNF-α-induced inflammation in vascular endothelial cells, but was inhibited by GRT or aspalathin. Overexpression of HK2 induced NF-κB phosphorylation, activity and inflammatory effects. However, these phenomenon was repressed by GRT, aspalathin or HK2 knockdown. GRT or aspalathin reversed the TNF-α-enhanced interaction between HK2 and YB-1, vimentin or drebrin. Gavage of GRT repressed the expression of IL-6 and HK-2 in aortic tissues in BAPN-induced inflammation murine model. Our study demonstrated that GRT or aspalathin can suppress the TNF-α-induced inflammation in human vascular endothelial cells via inhibition of TNF-α/HK2/NF-κB signaling axis
Telework practices and health risks of teleworkers: Survey findings from Taiwan after the COVID-19 pandemic
No full text[[abstract]]Objective To explore telework distributions after the COVID-19 pandemic, autonomy in work arrangements and health experiences of teleworkers in Taiwan. Methods A survey was conducted in March 2024 among 383 teleworkers. A comparison group of 750 age- and gender- matched conventional employees was extracted from a national survey. Regression analyses examined the associations of teleworking status with the risks of eye strain, musculoskeletal pain, poor self-rated health, and mental distress. Results A total of 54% of teleworkers started teleworking by their supervisors' arrangement, and 49% reported being digitally monitored. More than 90% of them were satisfied with teleworking arrangements, but they had significantly higher odds for eye strain (OR = 3.18), musculoskeletal discomfort (OR = 1.58), and mental distress (OR = 1.67) than general employees. Conclusions Teleworkers have high job satisfaction but reported higher ergonomic-related and mental health risks
Distance from the community to the city center is a vital determinant of dietary diversity score for rural community-dwelling older adults in Taiwan
No full text[[abstract]]Background: There was little knowledge of the dietary diversity of older adults in rural areas, with limited studies examining their nutritional status and related factors. This study aimed to assess the nutritional status of older adults in rural communities in Taiwan and explore the association between characteristics and the dietary diversity score (DDS). Methods: We collected data on sociodemographic, nutritional status, and DDS. The DDS was estimated based on nutritional intake using a 24 h dietary recall (24HR). Participants were grouped by distance from the city center into three categories (0–4 km, 4–8 km, and >8 km) to assess their correlation with food diversity. Results: A total of 567 participants were included, of whom 81.3% were women, and 65.5% were over 75 years of age. Of the participants, 154 lived within 4 km of the city center, 255 lived 4–8 km away, and 158 resided in remote communities (>8 km from the city center). Out of 538 participants who completed the dietary questionnaire, 274 (50.9%) were categorized as having low dietary diversity (DDS ≤ 4), while 264 (49.1%) were categorized as having high dietary diversity (DDS > 4). Conclusions: Our results showed the distance from the community to the city center significantly influences the DDS of the residents in rural communities. Nearly half of the rural population has a low DDS. The implementation of the research project aimed to determine the feasibility of daily nutrition evaluation and optimization programs for the elderly in rural areas is crucial in the future
Unraveling the complex genetic landscape of OTOF-related hearing loss: A deep dive into cryptic variants and haplotype phasing
No full text[[abstract]]Background Pathogenic variants in OTOF are a major cause of auditory synaptopathy. However, challenges remain in interpreting OTOF variants, including difficulties in confirming haplotype phasing using traditional short-read sequencing (SRS) due to the large gene size, the potential incomplete penetrance of certain variants, and difficulties in assessing variants at non-canonical splice sites. This study aims to revisit the genetic landscape of OTOF variants in a Taiwanese non-syndromic auditory neuropathy spectrum disorder (ANSD) cohort using a combination of sequencing technologies, predictive tools, and experimental validations. Methods We performed SRS to analyze OTOF variants in 65 unrelated Taiwanese patients diagnosed with non-syndromic ANSD, complemented by long-read sequencing (LRS) for haplotype phasing. A prediction-to-validation pipeline was implemented to assess the pathogenicity of cryptic variants using SpliceAI software and minigene assays. Results Biallelic pathogenic OTOF variants were identified in 33 patients (50.8%), while monoallelic variants were found in five patients. Three novel variants, c.3864G > A (p.Ala1288 =), c.4501G > A (p.Ala1501Thr), and c.5813 + 2T > C, were detected. The pathogenicity of two non-canonical mis-splicing variants, c.3894 + 5G > C and c.3864G > A (p.Ala1288 =), was confirmed by minigene assays. LRS-based haplotype phasing revealed that the common missense variant c.5098G > C (p.Glu1700Gln) and the novel variant c.5975A > G (p.Lys1992Arg) are in cis and form a founder pathogenic allele in the Taiwanese population. Conclusions Our study highlights the genetic heterogeneity of DFNB9 and emphasizes the importance of population-specific variant interpretation. The integration of advanced sequencing technologies, predictive algorithms, and functional validation assays will improve the accuracy of molecular diagnosis and inform personalized treatment strategies for individuals with DFNB9
Simplifying sarcopenia screening: A community-based evaluation of screening and assessment combinations
No full text[[abstract]]OBJECTIVES: Sarcopenia is a serious condition in older individuals, characterized by muscle loss and physical decline. Early detection is crucial but challenging due to subtle symptoms. The Asian Working Group for Sarcopenia (AWGS) 2019 consensus recommends detection for possible sarcopenia, but the effectiveness of the suggested tools varies, and the ideal screening combination remains unclear. This study aims to identify the most suitable screening pathway for early sarcopenia detection in community settings. DESIGN: Prospective cross-sectional study. SETTING AND PARTICIPANTS: Participants were recruited from locations offering congregated meal services between October 2018 and November 2019. Eligible participants were community-dwelling residents aged 50 years or older who were capable of completing the full sarcopenia survey. METHODS: All assessments recommended in the AWGS 2019 algorithm were conducted. We organized these tests into 12 distinct pathways, each combining a case-finding method with an assessment, either a muscle strength test or a physical performance test. Skeletal muscle mass was measured using bioelectrical impedance analysis. The validity of different combinations was then compared. RESULTS: A total of 567 participants were enrolled in this study. Among the 3 case-finding tools, calf circumference had the highest sensitivity and the SARC-F (strength, assistance with walking, rising from a chair, climbing stairs, and falls) had the lowest (80% vs 8%). Across the 12 different screening combinations tested, pathways involving calf circumference outperformed those involving the SARC-F or the SARC-F combined with calf circumference (SARC-CalF). Notably, the combination of calf circumference and hand grip strength emerged as the optimal pathway, offering the best sensitivity and satisfactory specificity, along with superior discrimination ability (indicated by receiver operating characteristic analysis) and prediction accuracy (indicated by Brier score). CONCLUSIONS AND IMPLICATIONS: The combination of calf circumference and hand grip strength is the most effective screening pathway for detecting sarcopenia in community settings. Its performance is even close to conducting all the tests outlined in the AWGS 2019 consensus. This simplified pathway may serve as a practical screening option in community settings
Spatiotemporal estimation of ambient forest phytoncides: Unveiling patterns through geospatial-based machine learning approach
No full text[[abstract]]This study investigated biogenic volatile organic compounds (BVOCs) emitted by tree species, with a specific focus on estimating their ambient air concentrations within the Xitou Nature Education Area, Taiwan. Employing geospatial-based machine learning approaches, which are rarely applied in this context, we aimed to estimate the ambient levels of key forest phytoncides which are representative compounds within the BVOC group. Data on phytoncide, including camphene and α-pinene, were directly collected from the study area. Geospatial data including meteorological factors, topography, land cover, and nearby landmarks were additionally collected and set as predictor variables influencing phytoncides. Random Forest (RF), Gradient Boosting (GB), Extreme Gradient Boosting (XGB), and Light Gradient Boosting Machine (LGBM) were integrated with an explainable artificial intelligence tool to develop the model estimates. To evaluate model performance, we conducted overfitting tests, 10-fold cross-validation, and stratified analysis. The results showed that RF and XGB were the most effective algorithms, explaining approximately 83.3% and 98.4% of the spatiotemporal variability in camphene and α-pinene, respectively. The robustness of these models was confirmed through extensive validation. Spatial pattern analysis revealed that variations in these biogenic compound concentrations were linked to meteorological conditions and vegetation types. Finally, this study presented an innovative approach to accurately estimating and mapping the spatial distribution of forest phytoncides, providing valuable insights to support environmental management, urban planning, and public health
De novo missense variants of KCNA3, KCNA4, and KCNA6 cause early onset developmental epileptic encephalopathy
No full text[[abstract]]Shaker-type potassium channel genes (Kv1) have been linked to human epilepsies, including KCNA1 (Kv1.1), KCNA2 (Kv1.2), and more recently, KCNA3 (Kv1.3) and KCNA6 (Kv1.6). In this study, we report three early-onset epilepsy cases with de novo missense mutations in Shaker-type channel genes, including Kv1.3, KCNA4 (Kv1.4), and Kv1.6, identified through whole exome sequencing trio study. The newly identified Kv1.3-V478M, Kv1.6-T421I, and Kv1.4-V558L mutations are located within the channel selectivity filter or S6 hinge, both critical for channel gating. These variants are in paralogous locations of previously reported pathogenic variant in KCNA2. These mutations do not significantly affect trafficking and plasma membrane localization of the Kv channels. In contrast, our patch-clamp analysis in a cell-based system reveals that all three mutations cause severe loss-of-function channel properties. Additionally, our Drosophila model highlights the detrimental effects of Kv1.3-V478M on neural circuit activity. Current findings suggest that, similar to Kv1.1, Kv1.2, and Kv1.3, both loss-of-function and gain-of-function mutations in Kv1.6 may contribute to the phenotypic variability in epilepsy severity. Our study also extends the list of potassium channel genes implicated in human epilepsy, introducing Kv1.4 as a novel epilepsy-related gene
Retirement, reemployment, and bio-psycho-social health among older adults in Taiwan
No full text[[abstract]]Objectives: This study examined the associations between retirement, reemployment, and health outcomes—covering physical, mental, and social domains—among middle-aged and older adults in Taiwan. Study design: Data were drawn from the Healthy Aging Longitudinal Study in Taiwan (HALST), with 4015 participants (mean age 68.2 ± 7.7) and two waves of follow-up. We applied difference-in-differences analyses to evaluate the effects of retirement and reemployment on health outcomes. Main outcome measures: Quality of life was assessed using the 12-item Short Form (SF-12) survey. Physical health was assessed using the Short Physical Performance Battery (SPPB) and Fried's frailty criteria. Mental health was measured via the Mini-Mental State Examination (MMSE), CES-D scale, and self-reported insomnia. Social networks were also evaluated. Results: Newly retired individuals, especially men and those under 65, experienced declines in physical health, including lower SF-12 physical scores (−1.62), poorer SPPB performance (−0.52), and greater risk of frailty (1.66). In contrast, reemployment, particularly full-time, was linked to better physical health (SF-12 1.78; SPPB 0.39), with stronger effects among women and older adults. Part-time reemployment was associated with enhanced social networks, though physical gains were limited. No consistent mental health effects were observed, except for higher depressive symptoms in those retiring for non-voluntary reasons. Conclusions: Retirement was linked to physical health decline, while reemployment, especially full-time, offered protective effects. Policies should be tailored to the diverse needs of retirees, accounting for age, gender, and reasons for retirement, to support healthier aging across populations
Rest-activity rhythm patterns and their associations with depression and obesity: A study using actigraphy and human-smartphone interactions
No full text[[abstract]]Background: This study aimed to empirically derive subgroups based on both actigraphy- and app-measured rest-activity rhythm (RAR) patterns and investigate the relationship between these profiles and health outcomes, including depression and obesity. Methods: We developed a mobile app, Rhythm, to record human-smartphone interactions and calculate RAR patterns alongside standard actigraphy in 135 participants (mean age: 43.8 +/- 12.3 years, 64% women) with and without major depressive disorder and/or obesity. Wrist actigraphy and Rhythm app recorded activity data for at least 4 weeks, totaling 3978 person-days. Person-centered clustering was conducted to identify subgroups based on RAR characteristics, and their associations with clinical outcomes were evaluated using multivariable regression models. Results: Three distinct groups with different RAR patterns were identified based on acrophase, interdaily stability (IS), and intradaily variability (IV), measured by actigraphy and human-smartphone interactions, respectively. The "earlier" group exhibited earlier acrophase both by actigraphy and the app and had lower depressive symptom severity than the other two groups. The "later" group showed a later acrophase and a lower body mass index (BMI) compared to the "earlier" group. The "irregular" group, characterized by higher IV, lower IS, and desynchronized actigraphy- and app-measured acrophase, was associated with higher levels of depressive symptom severity and BMI. Conclusions: Our study highlights the usefulness of human-smartphone interaction patterns in providing a comprehensive understanding of individuals' circadian rhythms beyond standard actigraphy measurements. Identifying distinct RAR profiles based on both actigraphy and app measurements contributes to a better understanding of the associations between circadian disruptions and mental and physical health outcomes