Gene-Environment Interactions and Gene-Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants.

PhenoAge and BioAge are two commonly used biological age (BA) measures. The author here searched for gene-environment interactions (GxE) and gene-gene interactions (GxG) on PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 111,996 Taiwan Biobank (TWB) participants, including a discovery set of 86,536 TWB2 individuals and a replication set of 25,460 TWB1 individuals. Searching for variance quantitative trait loci (vQTLs) provides a convenient way to evaluate GxE and GxG. A total of 4 nearly independent (linkage disequilibrium measure r2 < 0.01) PhenoAgeAccel-vQTLs are identified from 5,303,039 autosomal TWB2 SNPs (p < 5E-8), whereas no vQTLs are found from BioAgeAccel. These 4 PhenoAgeAccel-vQTLs (rs35276921, rs141927875, rs10903013, and rs76038336) are further replicated by TWB1 (p < 5E-8). They are located in the OR51B5, FAM234A, and AXIN1 genes. All 4 PhenoAgeAccel-vQTLs are significantly associated with PhenoAgeAccel (p < 5E-8). A phylogenetic heat map of the GxE analyses showed that smoking exacerbated the PhenoAgeAccel-vQTLs' aging effects, while higher educational attainment attenuated the PhenoAgeAccel-vQTLs' aging effects. Body mass index, chronological age, alcohol consumption, and sex do not prominently modulate PhenoAgeAccel-vQTLs' aging effects. Based on these vQTL results, rs141927875-rs35276921 interaction (p = 4.7E-61) and rs76038336-rs10903013 interaction (p = 3.3E-116) on PhenoAgeAccel are detected.

Searching for gene-gene interactions through variance quantitative trait loci of 29 continuous Taiwan Biobank phenotypes.

Introduction: After the era of genome-wide association studies (GWAS), thousands of genetic variants have been identified to exhibit main effects on human phenotypes. The next critical issue would be to explore the interplay between genes, the so-called "gene-gene interactions" (GxG) or epistasis. An exhaustive search for all single-nucleotide polymorphism (SNP) pairs is not recommended because this will induce a harsh penalty of multiple testing. Limiting the search of epistasis on SNPs reported by previous GWAS may miss essential interactions between SNPs without significant marginal effects. Moreover, most methods are computationally intensive and can be challenging to implement genome-wide. Methods: I here searched for GxG through variance quantitative trait loci (vQTLs) of 29 continuous Taiwan Biobank (TWB) phenotypes. A discovery cohort of 86,536 and a replication cohort of 25,460 TWB individuals were analyzed, respectively. Results: A total of 18 nearly independent vQTLs with linkage disequilibrium measure r 2 < 0.01 were identified and replicated from nine phenotypes. 15 significant GxG were found with p-values <1.1E-5 (in the discovery cohort) and false discovery rates <2% (in the replication cohort). Among these 15 GxG, 11 were detected for blood traits including red blood cells, hemoglobin, and hematocrit; 2 for total bilirubin; 1 for fasting glucose; and 1 for total cholesterol (TCHO). All GxG were observed for gene pairs on the same chromosome, except for the APOA5 (chromosome 11)-TOMM40 (chromosome 19) interaction for TCHO. Discussion: This study provided a computationally feasible way to search for GxG genome-wide and applied this approach to 29 phenotypes.

Microbiota-mediated metabolic perturbations in the gut and brain of mice after microplastic exposure.

Microplastics (MPs), emerging environmental toxicants, have drawn attention because of their wide distribution in the environment. Exposure to MPs induces gut microbiota dysbiosis, intestinal barrier dysfunction, metabolic perturbations, and neurotoxicity in different rodents. However, the relationship between MPs, gut microbiota, and the metabolome of the gut and brain in mice remains unclear. In this study, female C57BL/6 mice were orally gavaged with vehicle, 200 nm MP, and 800 nm MP three times per week for four weeks. Cecal contents were collected for gut microbiota analysis using 16S rRNA gene sequencing. Intestinal and brain tissues from mice were used to determine metabolic profiles using liquid chromatography-mass spectrometry (LC-MS). The results showed that MP altered microbiota composition, accompanied by metabolic perturbations in the mouse gut and brain. Specifically, Firmicutes and Bacteroidetes were suggested to be important phyla for MP exposure, partially dominating further metabolite alterations. Simultaneously, MP-induced metabolic profiles were associated with energy homeostasis and bile acid, nucleotide, and carnitine metabolic pathways. The results of the mediation analysis further revealed an MP-microbiota-metabolite relationship. Our results indicate that MPs can induce gut dysbiosis and disturb metabolic dysfunction in the mouse brain and/or intestine. Integrative omics approaches have the potential to monitor MP-induced molecular responses in various organs and systematically elucidate the complex mechanisms of human health effects.

The emergence and successful elimination of SARS-CoV-2 dominant strains with increasing epidemic potential in Taiwan's 2021 outbreak.

Taiwan's experience with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 guided its development of strategies to defend against SARS-CoV-2 in 2020, which enabled the successful control of Coronavirus disease 2019 (COVID-19) cases from 2020 through March 2021. However, in late-April 2021, the imported Alpha variant began to cause COVID-19 outbreaks at an exceptional rate in Taiwan. In this study, we aimed to determine what epidemiological conditions enabled the SARS-CoV-2 Alpha variant strains to become dominant and decline later during a surge in the outbreak. In conjunction with contact-tracing investigations, we used our bioinformatics software, CoVConvert and IniCoV, to analyze whole-genome sequences of 101 Taiwan Alpha strains. Univariate and multivariable regression analyses revealed the epidemiological factors associated with viral dominance. Univariate analysis showed the dominant Alpha strains were preferentially selected in the surge's epicenter (p = 0.0024) through intensive human-to-human contact and maintained their dominance for 1.5 months until the Zero-COVID Policy was implemented. Multivariable regression found that the epidemic periods (p = 0.007) and epicenter (p = 0.001) were two significant factors associated with the dominant virus strains spread in the community. These dominant virus strains emerged at the outbreak's epicenter with frequent human-to-human contact and low vaccination coverage. The Level 3 Restrictions and Zero-COVID policy successfully controlled the outbreak in the community without city lockdowns. Our integrated method can identify the epidemiological conditions for emerging dominant virus with increasing epidemiological potential and support decision makers in rapidly containing outbreaks using public health measures that target fast-spreading virus strains.

Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccine.

PURPOSE: We compared hypermetabolic lymphadenopathy (HLN) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group. RESULTS: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11). CONCLUSIONS: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines.

Epigenetic age acceleration mediates the association between smoking and diabetes-related outcomes.

BACKGROUND: Smoking can lead to the deterioration of lung function and susceptibility to diabetes. Recently, smoking was found to induce DNA methylation (DNAm) changes in some cytosine-phosphate-guanine sites (CpGs). As linear combinations of DNAm levels of aging-related CpGs, five measures of epigenetic age acceleration (EAA) have received extensive attention: HannumEAA, IEAA, PhenoEAA, GrimEAA, and DunedinPACE. It is of interest to explore whether some measures of EAA can mediate the associations of smoking with diabetes-related outcomes and indices of ventilatory lung function. METHODS AND RESULTS: In this study, we included self-reported smoking variables (smoking status, the number of pack-years, and years since smoking cessation), seven DNAm markers (HannumEAA, IEAA, PhenoEAA, GrimEAA, DNAm-based smoking pack-years, DNAm plasminogen activator inhibitor 1 [PAI-1] levels, and DunedinPACE), and four health outcomes (fasting glucose, hemoglobin A1C, forced expiratory volume in 1.0 s [FEV1], and forced vital capacity [FVC]) from 2474 Taiwan Biobank participants. Mediation analyses were conducted while adjusting for chronological age, sex, body mass index, drinking status, regular exercise status, educational attainment, and five cell-type proportions. We demonstrated that GrimEAA, DNAm-based smoking pack-years, DNAm PAI-1 levels, DunedinPACE, and PhenoEAA mediated smoking associations with diabetes-related outcomes. Moreover, current and former smoking both had an adverse indirect effect on FVC through DNAm PAI-1 levels. For former smokers, a long time since smoking cessation had a positive indirect impact on FVC through GrimEAA and on FEV1 through PhenoEAA. CONCLUSIONS: This is one of the first studies to comprehensively investigate the role of five measures of EAA in mediating the associations of smoking with the health outcomes of an Asian population. The results showed that the second-generation epigenetic clocks (GrimEAA, DunedinPACE, and PhenoEAA) significantly mediated the associations between smoking and diabetes-related outcomes. In contrast, the first-generation epigenetic clocks (HannumEAA and IEAA) did not significantly mediate any associations of smoking variables with the four health outcomes. Cigarette smoking can, directly and indirectly, deteriorate human health through DNAm changes in aging-related CpG sites.

Factors affecting the distribution of serum anti-müllerian hormone levels among infertile Asian women: a multi-nation, multi-centre, and multi-ethnicity prospective cohort study.

STUDY QUESTION: How do age, ethnicity, and other characteristics affect serum anti-mullerian hormone (AMH) levels in Asian women undergoing fertility treatment? SUMMARY ANSWER: Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS. WHAT IS KNOWN ALREADY: There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles. STUDY DESIGN, SIZE, DURATION: A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P < 0.001), ethnicity (P < 0.001), obesity (P = 0.007), PCOS (P < 0.001), and a history of endometrioma cystectomy (P = 0.01) were significantly associated with serum AMH values. Smoking status, pretreatment with GnRH agonist (GnRHa) or the oral contraceptive pill (OCP), freezing-thawing of blood samples, and sampling on Day 2 to Day 5 of the menstrual cycle or randomly did not appear to affect serum AMH levels. An AMH concentration of 4.0 ng/ml was the optimal cut-off for PCOS diagnosis with a sensitivity of 71.7% and specificity of 75.8% (AUC = 0.81, CI 95%: 0.79-0.83; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The incidence of PCOS was supposedly high in this cohort as some IVF clinics were tertiary referral centres for managing specific fertility issues encountered by women with PCOS. Treatment with GnRHa or OCP before AMH testing was regionally and ethnically confined, mostly in Hong Kong SAR and Japan. Moreover, this reference for serum AMH value is limited to Asian women of the ethnicities examined and may not apply to other ethnicities not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to collate and construct age-specific reference ranges for serum AMH levels using the same bioassay on Asian women of different ethnicities. The findings of this investigation can assist clinicians to counsel and prognosticate about Asian women's ovarian reserve and reproductive potential, thus providing better strategies for personalized fertility interventions. STUDY FUNDING/COMPETING INTEREST(S): This study was technically supported by Ferring Pharmaceuticals and received no specific grant from any funding agency. All authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: NCT04203355.

Short-Term Effects of a Therapeutic Diet on Biochemical Parameters in Hemodialysis Patients: A Randomized Crossover Trial.

OBJECTIVE: Although unhealthy diets exacerbate nutritional and metabolic derangements in patients with end-stage kidney disease (ESKD), how therapeutic diets that possess a variety of different dietary strategies acutely modify diverse biochemical parameters related to cardiovascular disease remains underexplored. METHODS: Thirty-three adults with end-stage kidney disease undergoing thrice-weekly hemodialysis participated in a randomized crossover trial comparing a therapeutic diet with their usual diets for 7 days, separated by a 4-week washout period. The therapeutic diet was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. The primary outcome measure was the mean difference in the change-from-baseline intact fibroblast growth factor 23 (FGF23) level between the 2 diets. The other outcomes of interest included changes in mineral parameters, uremic toxins, and high-sensitivity C-reactive protein (hs-CRP) levels. RESULTS: Compared with the usual diet, the therapeutic diet lowered intact FGF23 levels (P = .001), decreased serum phosphate levels (P < .001), reduced intact parathyroid hormone (PTH) levels (P = .003), lowered C-terminal FGF23 levels (P = .03), increased serum calcium levels (P = .01), and tended to lower total indoxyl sulfate levels (P = .07) but had no significant effect on hs-CRP levels. Among these changes, reduction in serum phosphate level achieved in 2 days, modifications of intact PTH and calcium levels in 5 days, and reductions in intact and C-terminal FGF23 levels in 7 days of therapeutic diet intervention. CONCLUSION: Within the 1-week intervention period, the dialysis-specific therapeutic diet rapidly reversed mineral abnormalities and tended to decrease total indoxyl sulfate levels in patients undergoing hemodialysis but had no effect on inflammation. Future studies to assess the long-term effects of such therapeutic diets are recommended.

Epigenetic clocks derived from western samples differentially reflect Taiwanese health outcomes.

Introduction: Several epigenetic clocks have been developed, with five measures of epigenetic age acceleration (EAA) especially receiving extensive investigations: HannumEAA, IEAA, PhenoEAA, GrimEAA, and DunedinPACE. These epigenetic clocks were mainly developed by individuals of European or Hispanic ancestry. It remains unclear whether they can reflect disease morbidity and physiological conditions in Asian populations. Methods: I here investigated five measures of EAA of 2,474 Taiwan Biobank participants with DNA methylation data. Using logistic regressions, I sequentially regressed various health outcomes on each of the five measures of EAA while adjusting for chronological age, sex, body mass index, the number of smoking pack-years, drinking status, regular exercise, educational attainment, and six cell-type proportions. Results: Except for IEAA, all measures of EAA reflected the obesity of Taiwanese (p < 4.0E-4). Diabetes was reflected by DunedinPACE (p = 5.4E-6) and GrimEAA (p = 5.8E-5). Moreover, DunedinPACE was associated with dyslipidemia, including hypertriglyceridemia (p = 1.1E-5), low high-density lipoprotein cholesterol (HDL-C) (p = 4.0E-5), and high triglyceride to HDL-C ratio (p = 1.6E-7). Discussion: This is one of the first studies to show that epigenetic clocks (developed by individuals of European or Hispanic ancestry) can reflect Taiwanese physiological conditions. DunedinPACE was associated with more Taiwanese health outcomes than the other four measures of EAA.

Adverse events following the first, second and third doses of a COVID-19 vaccine in hemodialysis patients.

BACKGROUND: This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored. METHODS: Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses. RESULTS: The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05-2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions. CONCLUSIONS: COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

Identification of serum metabolic signatures of environmental-leveled phthalate in the Taiwanese child population using NMR-based metabolomics.

Phthalates have become important environmental pollutants due to their high exposure frequency in daily life; thus, phthalates are prevalent in humans. Although several epidemiologic surveys have linked phthalates with several adverse health effects in humans, the molecular events underlying phthalate exposure have not been fully elucidated. The purpose of this study was to reveal associations between phthalate exposure and the serum metabolome in Taiwanese children using a metabolomic approach. A total of 256 Taiwanese children (8-10 years old) from two cohorts were enrolled in this study. Twelve urinary phthalate metabolites were analyzed by high-performance liquid chromatography/tandem mass spectrometry, while a nuclear magnetic resonance-based metabolomic approach was used to record serum metabolic profiles. The associations between metabolic profiles and phthalate levels were assessed by partial least squares analysis coupled with multiple linear regression analysis. Our results revealed that unique phthalate exposures, such as mono-isobutyl phthalate, mono-n-butyl phthalate, and mono (2-ethyl-5-oxohexyl) phthalate, were associated with distinct serum metabolite profiles. These phthalate-mediated metabolite changes may be associated with perturbed energy mechanisms, increased oxidative stress, and lipid metabolism. In conclusion, this study suggests that metabolomics is a valid approach to examine the effects of environmental-level phthalate on the serum metabolome. This study also highlighted potentially important phthalates and their possible effects on children.

Using angle-selective optical film to enhance the light extraction of a thin-film encapsulated 3D reflective pixel for OLED displays.

Light extraction improvement is still an important issue for active-matrix organic light-emitting diode displays (AMOLEDs). In our previous work, a three-dimensional (3D) reflective pixel configuration embedding the OLED in the concave 3D reflector and patterned high-index filler had been proposed for significant enhancement of the pixel light extraction. In this work, influences of thin film encapsulation (TFE) on light extraction of such reflective 3D OLED pixels are considered as well by simulation studies. Unfortunately, the optical simulation reveals strong reduction of the light extraction efficiency induced by TFE layers. As such, an additional angle-selective optical film structure between the pixel and the encapsulation layers is introduced to control the angular distribution of the light coupled into the encapsulation layers and to solve TFE-induced optical losses. As a result, TFE-induced losses can be substantially reduced to retain much of light extraction efficiency. The results of this study are believed to provide useful insights and guides for developing even more efficient and power-saving AMOLEDs.

Associations of five obesity indicators with cognitive performance in 30,697 Taiwan Biobank participants.

BACKGROUND: Obesity adversely influences the central nervous system and cognitive functions. However, the relationship between various obesity indicators and cognitive performance remains controversial. It is unclear which obesity indicator is more relevant to cognitive impairment. METHODS: The Taiwan Biobank (TWB) administered the Chinese version of the Mini-Mental State Examination (MMSE) to 30,697 participants (12,094 males and 18,603 females) aged 60 to 70 years. A total of 3,454 (11.25%) individuals with MMSE < = 24 were classified as having poor cognitive performance. This cross-sectional study investigates the associations of five obesity indicators with cognitive performance. Five separate logistic regression models were fitted for males and another five for females. Covariates adjusted in all models included age, smoking status, drinking status, regular exercise, chronic disease status (diabetes, cardiovascular diseases, heart diseases, stroke, or Parkinson's disease), depression status, blood pressure level, total cholesterol, fasting glucose, and educational attainment. The five obesity indicators included body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR). RESULTS: Abdominal obesity defined by WHR was significantly associated with poor cognitive performance. Male WHR > = 0.90 had a higher risk of poor cognitive performance than male WHR < 0.90 (odds ratio [OR] = 1.233; p = 0.007); female WHR > = 0.85 had an increased risk of poor cognitive performance compared with female WHR < 0.85 (OR = 1.221; p = 3.9E-4). HC and general obesity (defined by BMI and BFP) were not significantly associated with cognitive performance. CONCLUSION: The results consistently agreed that preventing abdominal obesity is associated with better cognitive performance in both males and females.

The most effective exercise to prevent obesity: A longitudinal study of 33,731 Taiwan biobank participants.

Regular physical exercise is recommended to reduce the risk of obesity. However, it remains unclear which activities are more effective in preventing obesity. In this study, five obesity indices and lifestyle factors of 33,731 Taiwan Biobank adults were measured/collected twice with a mean time interval of 4.06 years. A linear mixed effects model was fitted to assess the associations of exercises with obesity indices, in which a random intercept term was used to account for individual differences. The five obesity indices included body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR). Among 23 exercises, jogging and yoga were consistently the most effective choices across all five obesity indices. One more weekly hour to jog was associated with a 0.093 kg/m2 decrease in BMI (p = 4.2E-20), a 0.297% decrease in BFP (p = 3.8E-36), a 0.398 cm decrease in WC (p = 1.6E-21), and a 2.9E-3 decrease in WHR (p = 1.3E-17). One more weekly hour to perform yoga was associated with a 0.225 cm decrease in HC (p = 6.4E-14). Jogging is an exercise for the entire body. Arms swing, waist turn, legs and feet run, and shoulders and abdomen are also involved in this act. By contrast, many yoga poses use muscles around the hips and pelvis, and therefore yoga is the most effective exercise to reduce HC.

Nanoscale plasmonic wires with maximal figure of merits as a superior flexible transparent conducting electrode for RGB colors.

Based on incredibly increasing applications in modern optoelectronic devices, the demand for securing a superior conductive transparent electrode (TCE) candidate becomes significant and urgent. However, boosting both transmittance and conductance simultaneously is an intrinsic limitation. In this work, we present silver nanoscale plasmonic wires (Ag NPWs) to function as TCEs in the visible light region by lowering their corresponding plasma frequencies. By carefully designing geometric dimensions of the Ag NPWs, we also optimize the performance for red, green, and blue colors, respectively. The demonstrated figure of merits for RGB colors appeared respectively 443.29, 459.46, and 133.78 in simulation and 302.75, 344.11, and 348.02 in experiments. Evidently, our Ag NPWs offer much greater FoMs beyond conventional TCEs that are most frequently comprised of indium tin oxide and show further advantages of flexibility and less Moire effect for the applications of flexible and high-resolution optoelectronic devices.

Cardiovascular health and four epigenetic clocks.

BACKGROUND: Cardiovascular health (CVH) was defined by the American Heart Association as an integrative idealness of seven clinical or lifestyle factors. Based on populations of European ancestry, recent studies have shown that ideal CVH is associated with a slower aging rate. The aging rate is measured by levels of epigenetic age acceleration (EAA), usually obtained from the residuals of regressing DNA methylation (DNAm) age on chronological age. However, little has been known about the association of CVH with biological aging in Asian populations. METHODS AND RESULTS: We here analyzed blood DNAm data and clinical/lifestyle factors of 2474 Taiwan Biobank (TWB) participants, to investigate the association of CVH with EAA. CVH was assessed by seven components: smoking status, physical activity, dietary habits, body mass index, total cholesterol, fasting glucose, and blood pressure levels. Four measures of EAA were applied, among which two were based on the first-generation DNAm clocks (HannumEAA and IEAA) and two were based on the second-generation clocks (PhenoEAA and GrimEAA). After excluding 276 individuals with cardiovascular diseases, we regressed EAA on the CVH score (ranging from 0 to 7, integrating the abovementioned seven components) while adjusting for sex, drinking status, and educational attainment. Our results showed that a decrease in one point in the CVH score was associated with a 0.350-year PhenoEAA (p = 4.5E-4) and a 0.499-year GrimEAA (p = 4.2E-15). By contrast, HannumEAA and IEAA were not significantly associated with the CVH score. We have obtained consistent results within each generation of epigenetic clocks. CONCLUSIONS: This is one of the first studies to comprehensively investigate the associations of CVH with four epigenetic clocks. Our TWB data showed that ideal CVH is associated with lower levels of EAA calculated according to the second-generation epigenetic clocks (PhenoEAA and GrimEAA). Having an ideal CVH status can lower EAA and reduce the risk of aging-related disorders.

Interpreting the Evidence of Body Mass Index in Relation to Mental Health Status in Community-Dwelling Older Adults.

INTRODUCTION: Maintaining a better physical and mental health status is an important issue for older adults in their later life. Thus, the study's purpose was to evaluate the association between body mass index (BMI) and mental health status in older adults aged 65 years old or above residing in communities of Taipei City, Taiwan. METHODS: We carried out secondary data analysis with data from a volunteer-based health examination project for older adults >65 years old residing in Taipei City from 2006 to 2010 with a retrospective study design. BMI, calculated by standardized measuring procedures for height and weight, and mental health status, evaluated by 5-item Brief Symptom Rating Scale (BSRS-5), were collected at their first visits of health examination. A BSRS-5 score ≥6 was considered an inferior mental health status for the outcome. In statistical analysis, univariable and multivariable logistic regressions were adopted to estimate the relative risk of inferior mental health status, treating BMI as the major exposure of interest. RESULTS: A total of 90,576 subjects were involved, with a mean age of 73.38 years old (SD = 6.64 years) and 49.21% females. With confounders controlled, compared to normal or overweight (23 ≤ BMI <30), an adjusted OR of 1.23 (95% CI: 1.18, 1.29) on inferior mental health status was detected for the underweight group (BMI <23) significantly. Adjusted OR for those obese (BMI ≧30) was 0.87 (95% CI: 0.79, 0.96). Significantly elevated ORs of underweight were found for both genders, but the significantly protective effect of obese was only detected for females. CONCLUSION: Keeping an appropriate weight or even being overweighted might be beneficial for older adults dwelling in the community, especially for males.

Humoral antibody response to the first dose of the ChAdOx1 nCoV-19 vaccine in Asian patients undergoing hemodialysis.

BACKGROUND AND OBJECTIVES: The immunogenicity of vaccines is known to be attenuated in patients with end-stage kidney disease due to uremia. Patients on dialysis were excluded from coronavirus disease 2019 (COVID-19) vaccine trials; thus, the effectiveness of vaccines for this population is unclear. The aim of this study was to explore whether Asian dialysis patients can effectively produce an immune response after being vaccinated with the first dose of the ChAdOx1 nCoV-19 vaccine. DESIGN SETTING, PARTICIPANTS, AND MEASUREMENTS: In this prospective cohort study, we included Asian hemodialysis patients who received the ChAdOx1 nCoV-19 vaccine. At 3 weeks after the first dose of vaccination, we assessed the humoral immune response by measuring anti-SARS-CoV-2 S antibody titers. The primary outcome was the seropositive rate following vaccination, defined as an antibody titer greater than or equal to 0.8 U/ml. Factors associated with seropositivity were explored in multivariate logistic regression analyses. RESULTS: In total, 434 participants were included. The mean age was 64 years, the mean dialysis vintage was 6 years, and 61% of the participants were men. At a mean time of 22 days from vaccination, 56% of the participants were seropositive. The vast majority (88%) had low antibody titers (< 15 U/ml). The multivariate logistic regression analyses showed that older age (every increase of 10 years, odds ratio [OR] 0.80, 95% CI 0.65-0.98, p = 0.03) was negatively associated with seropositivity and that higher Kt/V (every increase of 0.1, OR 1.14, 95% CI 1.01-1.28, p = 0.03) and higher serum albumin level (every increase of 0.1 g/dl, OR 1.09, 95% CI 1.02-1.18, p = 0.02) were positively associated with seropositivity. CONCLUSIONS: In Asian hemodialysis patients, the seropositive rate was low, and most had low antibody titers after the first dose of the ChAdOx1 nCoV-19 vaccine. Younger age, better dialysis adequacy, and higher albumin levels were associated with seropositivity.

Taiwan's Response to Influenza: A Seroepidemiological Evaluation of Policies and Implications for Pandemic Preparedness.

OBJECTIVES: To evaluate class suspension and mass vaccination implemented among Taipei schoolchildren during the 2009 influenza pandemic and investigate factors affecting antibody responses. METHODS: We conducted 2 cohort studies on: (1) 972 schoolchildren from November 2009-March 2010 to evaluate pandemic policies and (2) 935 schoolchildren from November 2011-March 2012 to verify factors in antibody waning. Anti-influenza H1N1pdm09 hemagglutination inhibition antibodies (HI-Ab) were measured from serum samples collected before vaccination, and at 1 and 4 months after vaccination. Factors affecting HI-Ab responses were investigated through logistic regression and generalized estimating equation. RESULTS: Seroprevalence of H1N1pdm09 before vaccination was significantly higher among schoolchildren who experienced class suspensions than those who did not (59.6% vs 47.5%, p<0.05). Participating in after-school activities (adjusted odds ratio [aOR]=2.47, p=0.047) and having ≥3 hours per week of exercise (aOR=2.86, p=0.019) were significantly correlated with H1N1pdm09 infection. Two doses of the H1N1pdm09 vaccine demonstrated significantly better antibody persistence than 1 dose (HI-Ab geometric mean titer: 132.5 vs 88.6, p=0.047). Vaccine effectiveness after controlling for preexisting immunity was 86% (32%-97%). Exercise ≥3 hours per week and preexisting immunity were significantly associated with antibody waning/maintenance. CONCLUSIONS: This study is the first to show that exercise and preexisting immunity may affect antibody waning. Further investigation is needed to identify immune correlates of protection.

Lifestyle Factors and Genetic Variants on 2 Biological Age Measures: Evidence From 94 443 Taiwan Biobank Participants.

BACKGROUND: Biological age (BA) can be estimated by phenotypes and is useful for predicting life span and health span. Levine et al. proposed a PhenoAge and a BioAge to measure BA. Although there have been studies investigating the genetic predisposition to BA acceleration in Europeans, little has been known regarding this topic in Asians. METHODS: I have estimated PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 94 443 Taiwan Biobank (TWB) participants, wherein 25 460 TWB1 participants formed a discovery cohort and 68 983 TWB2 individuals constructed a replication cohort. Lifestyle factors and genetic variants associated with PhenoAgeAccel and BioAgeAccel were investigated through regression analysis and a genome-wide association study. RESULTS: A unit (kg/m2) increase of body mass index was associated with a 0.177-year PhenoAgeAccel (95% confidence interval [CI] = 0.163-0.191, p = 6.0 × 10-129) and 0.171-year BioAgeAccel (95% CI = 0.165-0.177, p = 0). Smokers on average had a 1.134-year PhenoAgeAccel (95% CI = 0.966-1.303, p = 1.3 × 10-39) compared with nonsmokers. Drinkers on average had a 0.640-year PhenoAgeAccel (95% CI = 0.433-0.847, p = 1.3 × 10-9) and 0.193-year BioAgeAccel (95% CI = 0.107-0.279, p = 1.1 × 10-5) relative to nondrinkers. A total of 11 and 4 single-nucleotide polymorphisms (SNPs) were associated with PhenoAgeAccel and BioAgeAccel (p < 5 × 10-8 in both TWB1 and TWB2), respectively. CONCLUSIONS: A PhenoAgeAccel-associated SNP (rs1260326 in GCKR) and 2 BioAgeAccel-associated SNPs (rs7412 in APOE; rs16998073 near FGF5) were consistent with the finding from the UK Biobank. The lifestyle analysis shows that prevention from obesity, cigarette smoking, and alcohol consumption is associated with a slower rate of biological aging.