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Abstract To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.

Abstract Background It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear. Methods This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970–1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa. Results Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively. Conclusions There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.

Abstract Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan’s insurance claims from adults newly diagnosed with type 2 diabetes during 2006–2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018’s end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91–2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59–1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33–2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29–2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

Objectives: The World Health Organization’s Integrated Care for Older People (ICOPE) framework launched in 2019 is used to assess the intrinsic capacity of older individuals. Older women may face greater socioeconomic disadvantages, which can impact their physical and mental well-being. Therefore, we examined sex differences in intrinsic capacity and the influence of socioeconomic status. Methods: We conducted a cross-sectional study in Tainan, Taiwan, recruiting 1,268 adults aged 60 or older in 2022. The ICOPE screening assessed cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Intrinsic capacity scores ranged from 0 to 6 and were categorized as impairment (1 or higher) or no impairment (0). Binary logistic regression models were used to analyze sex differences in intrinsic capacity, adjusting sequentially for demographics, lifestyle, and socioeconomic factors. Results: The prevalence of intrinsic capacity impairment was 34 %. Women had significantly higher odds of intrinsic capacity impairment (women vs. men, odds ratio [OR] = 1.39, 95 % CI = 1.10–1.75). After sequentially adjusting for demographic characteristics, lifestyle, and socioeconomic factors, the ORs were 1.46 (95 % CI = 1.12–1.90), 1.69 (95 % CI = 1.23–2.31), and 1.24 (95 % CI = 0.88–1.73), respectively. Stratified analyses showed that higher odds of impairment in women than in men was evident only in the financially dependent group (P for interaction = 0.059). Conclusions: Older women in Taiwan have poorer intrinsic capacity than men, a disparity largely attributable to women’s lower socioeconomic status. Strategies to promote healthy aging among women from disadvantaged socioeconomic backgrounds may help mitigate this sex difference in intrinsic capacity.

Freshwater pollution is a global challenge that citizens recognise as unacceptable, despite professional efforts to monitor, manage, and regulate it. Water quality is difficult to observe at high spatial and temporal resolutions; it is costly and typically requires trained specialists in the field and in laboratories. However, the rise in citizen science monitoring has generated opportunities to overcome many barriers and fill data gaps. Citizens want access to actionable water quality information that can provide early warnings and drive change. Our bibliographic analysis emphasises that citizen science is rarely paired with the use of continuous sensors, and many monitoring schemes involving the public are unable to offer the detail required. This study has explored the practicalities and competencies associated with community-led (near) continuous water quality monitoring (CWQM), and has generated an extensive checklist containing technical, social, economic, and wider responsibilities that stakeholders should consider. The “UpStream” project has provided a testbed for this exploratory work and the development and deployment of the “WaterBox” CWQM device. Case studies from the UK and Taiwan, where community-led CWQM programmes have been piloted, have provided novel methodological insights. Lessons learnt have enabled researchers to determine whether, and to what extent, community-led CWQM is achievable in practice. Results confirm that 75% of the practicalities observed fall under the “technical” category, despite offering a social and inclusive methodology. Through observational work, it was found that only 34% of the 104 practicalities were led by community groups and community champions. Communities require significant support owing to the sheer number of technical barriers, although some of this could be provided by skilled community champions. These findings have surfaced despite the WaterBox equipment being open, accessible, cost-effective, and adaptable. Unless support is in place and/or technology significantly evolves to reduce the number of challenges, it is unlikely that communities will lead and take full ownership of CWQM programmes. Despite this, the generation of site-specific CWQM data are welcomed by citizens, who can co-design schemes, interpret trends and offer valuable local information that trained scientists cannot achieve alone. These transferable findings are relevant to monitoring initiatives across the environmental sector.

As obesity has raised heightening awareness, researchers have attempted to identify potential targets that can be treated for therapeutic intervention. Focusing on the central nervous system (CNS), the key organ in maintaining energy balance, a plethora of ion channels that are expressed in the CNS have been inspected and determined through manipulation in different hypothalamic neural subpopulations for their roles in fine-tuning neuronal activity on energy state alterations, possibly acting as metabolic sensors. However, a remaining gap persists between human clinical investigations and mouse studies. Despite having delineated the pathways and mechanisms of how the mouse study-identified ion channels modulate energy homeostasis, only a few targets overlap with the obesity-related risk genes extracted from human genome-wide association studies. Here, we present the most recently discovered CNS-specific metabolism-correlated ion channels using reverse and forward genetics approaches in mice and humans, respectively, in the hope of illuminating the prospects for future therapeutic development.

Abstract Background The association between obesity indicators and mortality in individuals with diabetes remains unclear, and data on cardiovascular mortality are scarce. Therefore, we investigated the associations between the five adiposity indices and both all-cause and cardiovascular mortality in patients with diabetes. Methods This cohort study included 34,686 adults with diabetes who underwent a standard health-screening program between 1996 and 2017 in Taiwan. The dates and causes of death till January 2022 were retrieved from the National Death Registry. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality in relation to body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), and A Body Shape Index (ABSI), using the third quintile as the reference group. Results During a median follow-up of 15 years, there were 8,324 deaths, of which 1,748 were attributed to cardiovascular disease. After adjusting for demographics, lifestyle factors and comorbidities, ABSI was associated with all-cause mortality in an exposure-response manner; the HR (95% CI) for first and fifth vs. third quintile was 0.78 (0.69–0.89) and 1.24 (1.14–1.35), respectively. A similar but weaker exposure-response relationship was found between WHR and mortality. People with a lower BMI and BF% had an increased risk of mortality (HR [95% CI] for the first vs. third quintiles, 1.33 [1.22, 1.44] and 1.42 [1.30, 1.56], respectively). No association was observed between waist circumference categories and risk of mortality. Similar results were observed for the association of BF%, waist circumference, and ABSI with cardiovascular mortality. However, no significant association was observed between BMI and cardiovascular mortality. The association between WHR and cardiovascular mortality was stronger than that between WHR and all-cause mortality. Conclusions ABSI demonstrated a consistent exposure-response relationship with both all-cause and cardiovascular mortality in this Asian cohort with diabetes. Our findings highlight the importance of monitoring ABSI, a surrogate index of central adiposity, in patients with diabetes.

Abstract Background Prenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development. Methods We simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs. Results Exposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA. Conclusions Our findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC—NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

ObjectiveCongenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations.MethodsWe combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (KATP) channel variants were assessed using patch clamp recording and Western blot.ResultsNine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8, 2 in KCNJ11 and 1 in GCK) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F KATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C KATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient.ConclusionPathogenic variants in KATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) KATP channels are also associated with the diazoxide-unresponsive phenotype.

Abstract Background Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis. Methods This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher’s exact test. The Mann–Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases. Results Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p

Abstract Blood Pressure (BP) is an important cardiovascular health indicator. BP is usually monitored non-invasively with a cuff-based device, which can be bulky and inconvenient. Thus, continuous and portable BP monitoring devices, such as those based on a photoplethysmography (PPG) waveform, are desirable. In particular, Machine Learning (ML) based BP estimation approaches have gained considerable attention as they have the potential to estimate intermittent or continuous BP with only a single PPG measurement. Over the last few years, many ML-based BP estimation approaches have been proposed with no agreement on their modeling methodology. To ease the model comparison, we designed a benchmark with four open datasets with shared preprocessing, the right validation strategy avoiding information shift and leak, and standard evaluation metrics. We also adapted Mean Absolute Scaled Error (MASE) to improve the interpretability of model evaluation, especially across different BP datasets. The proposed benchmark comes with open datasets and codes. We showcase its effectiveness by comparing 11 ML-based approaches of three different categories.

Abstract Background Evidences have shown that the stroke risk associated with long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) varies among people in North America, Europe and Asia, but studies in Asia rarely evaluated the association by stroke type. We examined whether long-term exposure to PM2.5 is associated with developing all strokes, ischemic stroke and hemorrhagic stroke. Methods The retrospective cohort study consisted of 1,362,284 adults identified from beneficiaries of a universal health insurance program in 2011. We obtained data on air pollutants and meteorological measurements from air quality monitoring stations across Taiwan in 2010–2015. Annual mean levels of all environmental measurements in residing areas were calculated and assigned to cohort members. We used Cox proportional hazards models to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing stroke associated with 1-year mean levels of PM2.5 at baseline in 2010, and yearly mean levels from 2010 to 2015 as the time-varying exposure, adjusting for age, sex, income and urbanization level. Results During a median follow-up time of 6.0 years, 12,942 persons developed strokes, 9919 (76.6%) were ischemic. The adjusted HRs (95% CIs) per interquartile range increase in baseline 1-year mean PM2.5 were 1.03 (1.00–1.06) for all stroke, 1.06 (1.02–1.09) for ischemic stroke, and 0.95 (0.89–1.10) for hemorrhagic stroke. The concentration-response curves estimated in the models with and without additional adjustments for other environmental measurements showed a positively linear association between baseline 1-year mean PM2.5 and ischemic stroke at concentrations greater than 30 μg/m3, under which no evidence of association was observed. There was an indication of an inverse association between PM2.5 and hemorrhagic stroke, but the association no longer existed after controlling for nitrogen dioxide or ozone. We found similar shape of the concentration-response association in the Cox regression models with time-varying PM2.5 exposures. Conclusion Long-term exposure to PM2.5 might be associated with increased risk of developing ischemic stroke. The association with high PM2.5 concentrations remained significant after adjustment for other environmental factors.

Background Although sex differences in the epidemiological features of aortic dissection (AD) are known, whether there were sex differences in the associations of comorbidities and risk factors with AD is unclear. We evaluated the temporal trends and risk factors of AD by sex. Methods and Results Using claims data from a universal health insurance program linked to the National Death Registry in Taiwan, we identified 16 368 men and 7052 women with newly diagnosed AD from 2005 to 2018. In the case‐control analysis, a matched control group without AD was selected for men and women separately. Conditional logistic regression was used to evaluate risk factors of AD and sex differences. Over the 14 years, the annual incidence of diagnosed AD was 12.69 and 5.34 per 100 000 in men and women, respectively. The 30‐day mortality was greater in women than in men (18.1% versus 14.1%; adjusted odds ratio [95% CI], 1.19 [1.10–1.29]), and the sex difference was observed mainly in patients not treated with surgery. The 30‐day mortality declined over time in male patients undergoing surgical treatments, but no significantly temporal change was found in other patient groups stratified by sex and surgery. After multivariable adjustments, atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery were associated with a greater increase in the odds of AD occurrence in women than in men. Conclusions Greater 30‐day mortality and stronger associations of atrial fibrillation, chronic kidney disease, and coronary artery bypass graft surgery with AD in women than in men require further attention.

ObjectivesThis study applied the theory of planned behavior (TPB) in shared decision making (SDM) to understand behavioral intention in patients with type 2 diabetes with regard to injection therapy for blood sugar control.MethodsA cross sectional study was conducted. Two hundred and fifty-four patients with type 2 diabetes participated this study and were interviewed by pharmacists in different clinics. A patient decision aid (PDA) entitled “Should I receive injection therapy regarding my type 2 diabetes condition?” was developed for this study and served as interview agenda which comprised 18 items to inquire their willingness to use injection therapy and related considerations during the SDM process.ResultsThe questionnaires were revised using item analysis, exploratory factor analysis, and a criteria of Cronbach's α > 0.7. This resulted in three constructs for all questionnaires that fit the TPB model. Attitude (β = 0.432; P < 0.001) and PBC (β = 0.258; P < 0.001) were directly correlated with intention. TPB explained 35.2% of the variance in intention toward the use of injection therapy.ConclusionsAttitude and PBC toward injection therapy positively and significantly influence the patients' intention to use injection therapy.Practical implicationsThese findings identify a key association for understanding behavioral intention in patients with type 2 diabetes with regard to blood sugar control during SDM.

Abstract The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan’s herbal medicines adverse reaction database and facilitate epidemiological analysis.

Helicobacter pylori infection is associated with the development of several gastric diseases including gastric cancer. To reach a long-term colonization in the host stomach, H. pylori employs multiple outer membrane adhesins for binding to the gastric mucosa. However, due to the redundancy of adhesins that complement the adhesive function of bacteria, targeting each individual adhesin alone usually achieves nonideal outcomes for preventing bacterial adhesion. Here, we report that key adhesins AlpA/B and BabA/B in H. pylori are modified by glycans and display a two-step molecular weight upshift pattern from the cytoplasm to the inner membrane and from the inner membrane to the outer membrane. Nevertheless, this upshift pattern is missing when the expression of some enzymes related to lipopolysaccharide (LPS) biosynthesis, including the LPS O-antigen assembly and ligation enzymes WecA, Wzk, and WaaL, is disrupted, indicating that the underlying mechanisms and the involved enzymes for the adhesin glycosylation are partially shared with the LPS biosynthesis. Loss of the adhesin glycosylation not only reduces the protease resistance and the stability of the tested adhesins but also changes the adhesin-binding ability. In addition, mutations in the LPS biosynthesis cause a significant reduction in bacterial adhesion in the in vitro cell-line model. The current findings reveal that H. pylori employs a general protein glycosylation system related to LPS biosynthesis for adhesin modification and its biological significance. The enzymes required for adhesin glycosylation rather than the adhesins themselves are potentially better drug targets for preventing or treating H. pylori infection.

Freshwater pollution is a global challenge that citizens recognise as unacceptable, despite professional efforts to monitor, manage, and regulate it. Water quality is difficult to observe at high spatial and temporal resolutions; it is costly and typically requires trained specialists in the field and in laboratories. However, the rise in citizen science monitoring has generated opportunities to overcome many barriers and fill data gaps. Citizens want access to actionable water quality information that can provide early warnings and drive change. Our bibliographic analysis emphasises that citizen science is rarely paired with the use of continuous sensors, and many monitoring schemes involving the public are unable to offer the detail required. This study has explored the practicalities and competencies associated with community-led (near) continuous water quality monitoring (CWQM), and has generated an extensive checklist containing technical, social, economic, and wider responsibilities that stakeholders should consider. The "UpStream" project has provided a testbed for this exploratory work and the development and deployment of the "WaterBox" CWQM device. Case studies from the UK and Taiwan, where community-led CWQM programmes have been piloted, have provided novel methodological insights. Lessons learnt have enabled researchers to determine whether, and to what extent, communityled CWQM is achievable in practice. Results confirm that 75% of the practicalities observed fall under the "technical" category, despite offering a social and inclusive methodology. Through observational work, it was found that only 34% of the 104 practicalities were led by community groups and community champions. Communities require significant support owing to the sheer number of technical barriers, although some of this could be provided by skilled community champions. These findings have surfaced despite the WaterBox equipment being open, accessible, cost-effective, and adaptable. Unless support is in place and/or technology significantly evolves to reduce the number of challenges, it is unlikely that communities will lead and take full ownership of CWQM programmes. Despite this, the generation of site-specific CWQM data are welcomed by citizens, who can co-design schemes, interpret trends and offer valuable local information that trained scientists cannot achieve alone. These transferable findings are relevant to monitoring initiatives across the environmental sector. [ABSTRACT FROM AUTHOR]

Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA1c and HbA1c trajectories are associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a “Pre-ESKD Program” at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA1c levels and HbA1c trajectories. In the analysis related to baseline HbA1c (n = 4543), the adjusted HRs [95% confidence interval (CI)] of all-cause mortality were 1.06 (0.95–1.18) and 1.25 (95% CI, 1.07–1.46) in patients with an HbA1c level of 7%–9% (53–75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (

This study evaluated the risks of childhood acute bronchitis and bronchiolitis (CABs) for children with asthma or allergic rhinitis (AR). Using insurance claims data of Taiwan, we identified, from children of ≤12 years old in 2000–2016, cohorts with and without asthma (N = 192,126, each) and cohorts with and without AR (N = 1,062,903, each) matched by sex and age. By the end of 2016, the asthma cohort had the highest bronchitis incidence, AR and non-asthma cohorts followed, and the lowest in the non-AR cohort (525.1, 322.4, 236.0 and 169.9 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratios (aHRs) of bronchitis were 1.82 (95% confidence interval (CI), 1.80–1.83) for the asthma cohort and 1.68 (95% CI, 1.68–1.69) for the AR cohort, relative to the respective comparisons. The bronchiolitis incidence rates for these cohorts were 42.7, 29.5, 28.5 and 20.1 per 1000 person-years, respectively. The aHRs of bronchiolitis were 1.50 (95% CI, 1.48–1.52) for the asthma cohort and 1.46 (95% CI, 1.45–1.47) for the AR cohort relative to their comparisons. The CABs incidence rates decreased substantially with increasing age, but were relatively similar for boys and girls. In conclusion, children with asthma are more likely to develop CABs than are children with AR.

Background Few studies have evaluated the prognostic significance of diameter‐based carotid sonographic measurements for mortality. We investigated whether a reduction in diameter of different carotid anatomical segments is associated with cardiovascular and all‐cause mortality in a hospital‐based cohort with universal health care. Methods and Results We conducted a retrospective cohort study of 38 201 patients who underwent carotid duplex ultrasound at a medical center in Taiwan. Carotid sonographic parameters were the diameter reduction percentage in carotid bifurcation, the internal carotid artery, the common carotid artery, and the external carotid artery and the overall carotid atherosclerotic burden score, determined by summing the scores from all segments. The vital status was ascertained by linking data to National Death Registry until 2017. During a median follow‐up of 4.2 years, 5644 participants died, with 1719 deaths attributable to cardiovascular diseases. The multivariable‐adjusted hazard ratios (HRs; 95% CIs) for cardiovascular mortality were 1.33 (1.16‒1.53), 1.58 (1.361.84), and 1.89 (1.58, 2.26) for participants with 30% to

BackgroundAn association between thyroid disease and tinnitus has been described previously but further longitudinal, population-based studies are limited.ObjectiveTo investigate the incidence of tinnitus in patients with hyperthyroidism in a national sample, and to identify risk level and associated factors for tinnitus in hyperthyroidism patients.DesignRetrospective cohort study. Patient data were collected from the Longitudinal Health Insurance Database (LHID 2000), which includes national claims data of patient expenditures for admissions or ambulatory care from 1996 to 2011.SettingTaiwan hospitals and clinics providing healthcare nationwide.ParticipantsPatients aged 20 years and older with newly diagnosed hyperthyroidism (ICD-9-CM code 242) between 2000-2010 were selected as the study cohort. Hyperthyroidism patient cohort were identified from the LHID2000. Those with tinnitus history (ICD-9-CM code 388.3) before the index date (first hyperthyroidism diagnosis), younger than 20 years, and with incomplete demographic data were excluded. The non-hyperthyroidism cohort included patients with no history of hyperthyroidism and no documented tinnitus.Main Outcomes and MeasuresIncidence of tinnitus was the primary outcome. Baseline demographic factors and comorbidities possibly associated with tinnitus, including age, sex, and comorbidities of hearing loss, vertigo, insomnia and anxiety, were retrieved from the LHID 2000. Patients were followed until end of 2011.ResultsDuring the study period, 780 (4.9%) hyperthyroidism patients and 2007 (3.2%) non-hyperthyroidism controls developed tinnitus. Incidence rate of tinnitus in the hyperthyroidism cohort was significantly higher in hyperthyroidism cohort (7.86 vs. 5.05 per 1000 person-years) than that in non-hyperthyroidism cohort. A higher proportion of patients with hyperthyroidism had comorbid insomnia (45.1% vs. 30.9%) and anxiety (14.0% vs. 5.73%) than those without hyperthyroidism. After adjusting for age, gender and comorbidities (vertigo, insomnia, anxiety, hearing loss), hyperthyroidism patients had 1.38-fold higher risk of tinnitus (95% CI = 1.27-1.50) than those without hyperthyroidism.ConclusionsThis large population-based study suggests patients with diagnosed hyperthyroidism was more prone to develop tinnitus. Our findings suggest evaluation for comorbid vertigo, insomnia, anxiety and/or hearing loss may identify patients who are at high risk of developing tinnitus in patients with hyperthyroidism.

Microglia and astrocytes are the glial cells of the central nervous system (CNS) to support neurodevelopment and neuronal function. Yet, their activation in association with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called as gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices. In this study, we reported that acute peripheral challenge by inflammagen lipopolysaccharide (LPS) upregulated the expression of hypothalamic dopamine type 2 receptor (D2R) mRNA, and chronic feeding by high-fat-diet (HFD) significantly caused increased levels of D2R in the ARC. The in vitro and in vivo studies indicated that an FDA-approved antipsychotic drug named trifluoperazine (TFP), a D2R inhibitor was able to suppress LPS-stimulated activation of microglia and effectively inhibited LPS-induced peripheral inflammation, as well as hypothalamic inflammation. Further findings showed daily peripheral administration intraperitoneally (i.p.) by TFP for 4 weeks was able to reduce the levels of plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in accompany with lower levels of plasma glucose and insulin in obese mice receiving HFD for 16 weeks when compared those in obese mice without TFP treatment. In parallel, the activation of microglia and astrocytes in the ARC was also inhibited by peripheral administration by TFP. According to our results, TFP has the ability to suppress HFD-induced ARC gliosis and inflammation in the hypothalamus.

Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population.Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30–70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored.Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11–2.72, p

The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.

Background and Purpose Preceding episodes of paroxysmal atrial fibrillation (AF) among stroke patients can be easily overlooked in routine clinical practice. We aim to determine whether an unrecognized history of paroxysmal AF is associated with an increased risk of recurrent stroke. Methods We retrospectively identified all adult patients hospitalized with a primary diagnosis of ischemic stroke who had no AF diagnosis on their discharge records, using the Taiwan National Health Insurance Research Database between January 2001 and December 2012. Patients were categorized into two groups: unrecognized AF history and no AF. Patients with unrecognized AF history were defined as having documented AF preceding the index ischemic stroke hospitalization, but not recording at the index ischemic stroke. Primary endpoint was recurrent stroke within 1 year after the index stroke. Results Among 203,489 hospitalized ischemic stroke patients without AF diagnosed at discharge, 6,731 patients (3.3%) had an unrecognized history of prior transient AF. Patients with an unrecognized AF history, comparing to those without AF, had higher adjusted risk of all recurrent stroke ([original cohort: hazard ratio (HR), 1.41; 95% confidence interval [CI], 1.30 to 1.53], [matched cohort: HR, 1.51; 95% CI, 1.37 to 1.68]) and recurrent ischemic stroke ([original cohort: HR, 1.42; 95% CI, 1.30 to 1.55], [matched cohort: HR, 1.56; 95% CI, 1.40 to 1.74]) during the 1-year follow-up period. Conclusions Unrecognized history of AF among patients discharged after an index ischemic stroke hospitalization is associated with higher recurrent stroke risk. Careful history review to uncover a paroxysmal AF history is important for ischemic stroke patients.

Abstract Introduction Atrial fibrillation (AF) often occurs in patients with acute coronary syndrome (ACS). It remains unclear whether pre-existing or new-onset AF confers different risk in patients with ACS. Methods We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database. Patients who were hospitalized with a primary diagnosis of ACS from 2005 to 2009 were studied. Major outcomes were mortality, heart failure, and combined ischemic stroke/systemic embolism (IS/SE). The date of the first ACS diagnosis was defined as the index date. Pre-existing AF was defined as AF occurring before the index date. New-onset AF was defined as AF that started after or at the same time as the ACS diagnosis. Results Among 6663 patients with ACS, 488 (7.3%) had pre-existing AF and 479 (7.2%) had new-onset AF. Compared to patients with pre-existing AF, those with new-onset AF were younger, less likely to have co-morbidities, and more likely to receive evidence-based therapy. The un-adjusted risks of adverse outcomes in both groups were similar. Compared to pre-existing AF, new-onset AF was significantly associated with a higher adjusted risk of death (hazard ratio 1.27, 95% confidence interval 1.06–1.52) and IS/SE (hazard ratio 1.49, 95% confidence interval 1.01–2.20). The significant associations between new-onset AF and adverse outcomes were more likely to be observed in elderly patients with ACS. Conclusions New-onset AF during ACS was associated with a significantly increased risk of adverse outcomes, especially in the elderly patients.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006–2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June–August). The highest incidence was 698 cases/day at 2.5 > 37.0 μg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97–1.04) compared to 568 cases/day at 2.5 < 15.0 μg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85–1.06) with PM2.5 > 37.0 μg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58–0.65) when PM2.5 was 3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18–2.76]) and 1.45 (95% CI [0.67–3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.