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Association of plasma IgA with bowel wall thickness and disease activity in IBD patients assessed by intestinal ultrasound
No full text[[abstract]]Background: IgA, the primary immunoglobulin secreted by gut B cells, plays a key role in defending against pathogen invasion. Elevated plasma IgA levels have been observed in inflammatory bowel disease (IBD) patients, particularly those undergoing biologic therapy. However, direct evidence linking plasma IgA levels to bowel wall inflammation is lacking. This study investigates the relationship between plasma IgA levels and intestinal inflammation, using parameters from intestinal ultrasound (IUS). Methods: We enrolled 30 IBD patients (20 with ulcerative colitis (UC) and 10 with Crohn’s disease (CD)) for IUS evaluation starting in July 2023. Ultrasound scores were based on the Milan ultrasound criteria (MUC) for UC and the bowel ultrasound score (BUSS) for CD. Plasma levels of ESR, CRP, albumin, IgA, partial Mayo score, and CDAI were collected at baseline, during treatment, and after 52 weeks of advanced therapy (Adalimumab, Vedolizumab, or Tofacitinib). IUS findings and plasma IgA levels were analyzed for correlations with clinical parameters using the Student’s t-test and linear regression. Results: IUS findings were closely correlated with disease activity. In UC, the MUC score was positively correlated with CRP (P < 0.0001, R² = 0.4888), partial Mayo score (P = 0.0002, R² = 0.3652), and negatively with albumin levels (P = 0.0002, R² = 0.3747). In CD, the BUSS score showed a positive correlation with CDAI (P = 0.0394, R² = 0.2694). Plasma IgA levels were significantly associated with bowel wall thickness (BWT) in both UC and CD (P = 0.0041, R² = 0.1759) (Figure 1). Notably, when BWT exceeded 3.5 mm, plasma IgA levels increased significantly (P = 0.0021) (Figure 2). Interestingly, in CD, plasma IgA was strongly correlated with the BUSS score (P = 0.0001, R² = 0.6585), while no such relationship was observed between MUC score and plasma IgA in UC. Conclusion: Plasma IgA levels are positively correlated with bowel wall thickness in both UC and CD patients, particularly when BWT exceeds 3.5 mm. In CD patients, IgA levels also show a strong correlation with the BUSS score, highlighting IgA as a potential biomarker for bowel wall inflammation. These findings suggest that plasma IgA could serve as a biomarker of disease activity, particularly in CD, and could aid in monitoring therapeutic response and disease progression in IBD. Further research is warranted to validate these results and explore the potential for IgA-targeted therapies
Betaine alleviates cue-induced reinstatement of ketamine seeking via ampk activation in the nucleus accumbens core
No full text[[abstract]]Background: Betaine is a functional nutrient with a variety of potential health benefits1.2. It has been shown to attenuate the reinstatement of ketamine-seeking behavior in rats3. Moreover, betaine activates AMP-activated protein kinase (AMPK) and functions as a partial agonist of the NMDA receptor glycine binding site, both of which have been associated with reducing cue-induced reinstatement4.5.6. Aims & Objectives: The study aimed to both identify the brain regions associated with betaine's reduction effect on cue-induced reinstatement of ketamine seeking and to explore the involvement of NMDA receptor and AMPK in the potential underlying mechanisms. Methods: Male Sprague-Dawley rats were trained to respond for intravenous ketamine (0.5 mg/kg/infusion) self-administration, followed by extinction. Prior to cue-induced reinstatement, rats received bilateral microinjection of betaine (100 μ g/μ l/side) either into the prelimbic cortex (PrL) or the nucleus accumbens (NAc) core. The impact of pretreatment of 7-chlorokynurenate (7-CK) (20 μ g/μ l/side), an antagonist of NMDA receptor glycine binding site, or dorsomorphin (6 μ g/μ l/side), an AMP-activated protein kinase (AMPK) inhibitor, on betaine's effects in the NAc core regarding cue-induced reinstatement were examined. Results: Our data demonstrated a significant reduction in cue-induced reinstatement of ketamine-seeking behavior when betaine was administered into the NAc core, with no such effect observed in the PrL. In addition, dorsomorphin, but not 7-CK, blocked the effect of betaine on cue-induced reinstatement of ketamine- seeking behavior. Discussion & Conclusions: These findings suggest the potential benefits of betaine supplementation for individuals with ketamine use disorder. Moreover, it sheds light on betaine's capacity to mitigate cue-induced reinstatement of ketamine-seeking behavior by activating AMPK in the NAc core
Health benefits of a reduction in ambient fine particulate matter levels for post-neonatal infant survival in Taiwan
No full text[[abstract]]Infants' and children's health is particularly susceptible to exposure to various environmental contaminant insults as their immune systems are immature and daily activities may present differing patterns of exposure. Although some studies noted an association between long-term exposure to ambient fine particulate matter (PM2.5) and increased infant mortality frequency, few investigations examined the relationship between reduced exposure to PM2.5 and changes in infant mortality rates. Therefore, this study was conducted to determine whether diminished levels of PM2.5 in Taiwan improved post-neonatal infant health. Avoidable premature post-neonatal infant mortality was employed as an indicator of health impact. A mean value was calculated for annual PM2.5 levels across Taiwan for the years 2006, 2015, and 2023. Using these averages and following WHO methodology, differences in the number of post-neonatal infant deaths attributed to ambient PM2.5 exposure were determined. PM2.5 concentrations fell markedly throughout Taiwan over the 20-year study period. In conjunction with this decline, a lowered health burden was noted, which was represented as a fall in post-neonatal infant deaths (14.8% in 2006 to 10.3% in 2023). Reduction in annual levels of PM2.5 to 10 mu g/m(3) was associated with a decrease in the total burden of post-neonatal infant mortality occurrence, with a 5.58-9.31% decline in PM2.5-related deaths during that period. Evidence indicates that exposure to PM2.5 air pollution poses a significant burden to Taiwan children's health. Our findings indicate that the potential benefits to children's health need to be given importance when considering improving air quality policies
Physical and mental demands of work associated with dementia risk in later life
No full text[[abstract]]BACKGROUND: Work occupies a significant portion of adult life, and both cognitive stimulation and physical activity have been suggested as factors that may lower dementia risk in later life. OBJECTIVES: To examine the association between mental and physical demands at work and the risk of dementia. DESIGN: A cohort study. SETTING: Seven selected districts in Taiwan, covering both urban and rural areas. PARTICIPANTS: 4,083 community-dwelling healthy adults aged 55 and older from the Healthy Aging Longitudinal Study. MEASUREMENTS: A job matrix of work conditions by occupation was generated using data from a representative national survey. Mental demands were assessed by job control and psychological demands from the Job Content Questionnaire, as well as skill levels. Physical demands were assessed using a 4-point Likert scale and dichotomized into high and low levels. Dementia diagnoses were identified based on physician diagnosis registered in the National Health Insurance database. RESULTS: Over a follow-up period of 6.2 years, 513 participants were diagnosed with dementia. After adjusting for confounding factors in cox regression models, high (vs. low) job control, high -skilled jobs (vs. low), and high physical demands (vs. low) were associated with a reduced future risk of dementia. Psychological demands were not associated with dementia risk. CONCLUSIONS: Greater utilization of job skills and engagement in physically demanding activities at work may help mitigate the risk of developing dementia. The effects of different dimensions of psychological demands on cognitive health warrant further investigation
Incorporating polygenic liability and family history for predicting psychiatric diseases in the Taiwan biobank
No full text[[abstract]]BACKGROUND: This study investigated the interplay between molecular measures of polygenic risk score (PRS) and conventional measures of family history (FH) on the risk of four psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD) in community samples of East Asian populations. We examined the individual and joint associations and relative contributions of PRS and FH and evaluated the potential of combining transdiagnostic PRSs and FHs to improve risk prediction. METHODS: The genotyping of 106,581 unrelated participants from the Taiwan Biobank was linked to the National Health Insurance Research Database to retrieve information on ICD-defined diseases and FH. A logistic regression model was used to examine the association between PRS and FH in fathers, mothers, and siblings with a risk of psychiatric disorders. RESULTS: The PRS for SCZ, BPD, MDD, and OCD explained 2.0%, 0.4%, 0.6%, and 0.6%, respectively, and FH explained 1.3%, 1.4%, 2.3%, and 3.4%, respectively, of the variance in the corresponding disease. Incorporating PRS and FH increased the explained variances in SCZ, BPD, MDD, and OCD by 3.2%, 1.7%, 2.8%, and 4.1%, respectively. The effect sizes for PRS and FH in the PRS/FH alone and PRS-FH combined models were generally similar. Simultaneously incorporating the four PRSs and FHs increased the explained variances of SCZ, BPD, MDD, and OCD to 4.7%, 4.7%, 3.3%, and 7.3%, respectively. CONCLUSIONS: PRS and FH provide independent and complementary information for the identification of psychiatric disorders. The incorporation of transdiagnostic PRSs and FHs improved risk identification
Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03)
No full text[[abstract]]Background: T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg is approved for pts with metastatic HER2+ gastric/GEJA who have received a prior trastuzumab-based regimen. Dual PD-1 and HER2 blockade together with fluoropyrimidine (FP; 5-fluorouracil or capecitabine)/platinum has improved outcomes vs chemotherapy/trastuzumab in the first-line (1L) setting. We explored T-DXd in combination with FP and an anti-PD-1 in 1L esophageal/gastric/GEJA. Methods: DG-03 Part 2 (dose expansion; NCT04379596) enrolled pts with 1L HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization-positive by local testing) esophageal/gastric/GEJA globally, irrespective of PD-L1 status. Pts were randomized (except to arm F), as feasible, to standard of care (SOC), T-DXd monotherapy or T-DXd-based combinations, and stratified by HER2 status (Table). Primary endpoint was investigator-assessed (INV) confirmed objective response rate (ORR) per RECIST 1.1. Safety and tolerability were assessed. Results: At data cutoff (Jan 31, 2024), 307 pts were enrolled; 229 pts received treatment. Baseline/disease characteristics were not balanced across arms. Combining T-DXd with FP/pembrolizumab (pembro) 200 mg showed durable clinical benefit in pts with HER2+ central PD-L1 CPS ≥1 esophageal/gastric/GEJA. Adjudicated drug-related interstitial lung disease (ILD)/pneumonitis occurred in 21 (11%) T-DXd-treated pts (arm B [6.4 mg/kg], n=4; arm C [6.4 mg/kg + FP], n=4; arm D [6.4 mg/kg + FP + pembro], n=8; arm E [6.4 mg/kg + pembro], n=5), with 3 deaths (arm D, n=2; arm E, n=1). Summary efficacy and safety are in the table
Innovating Taiwan's greenhouse gas estimation: A case study of atmospheric methane using GeoAI-Based ensemble mixed spatial prediction model
No full text[[abstract]]This study addresses a gap in atmospheric greenhouse gas research, focusing on methane (CH(4)), a gas with a global warming potential 80 times greater than carbon dioxide (CO(2)). Unlike prior studies that focus on emission sources and reduction strategies, this research emphasizes the spatiotemporal variations in atmospheric CH(4) concentrations, providing new perspectives on global climate mitigation efforts. A novel GeoAI-based ensemble mixed spatial prediction model was developed, integrating multiple machine learning algorithms and considering various factors to accurately estimate CH(4) concentrations across Taiwan. In the context of global net-zero emissions, this study offers a robust approach to assess spatial variations in CH(4) concentrations, providing valuable insights into the effectiveness of greenhouse gas reduction policies and climate strategies. Key factors influencing CH(4) levels include aquaculture, livestock, transportation land use, wind speed, national CH(4) emissions, net greenhouse gas emissions, population density, quarry sites, solar radiation, seasonal variations, residential areas, temples, CO(2) removal levels, and primary pollutants (e.g., NO(2), NO(x), PM(2).(5), PM(10), CO, CO(2), SO(2), and O(3)). Seasonal analysis revealed higher CH(4) concentrations in spring and winter, and lower levels in summer and autumn. The model demonstrated high explanatory power with R(2) values of 0.99, 0.82, 0.98, and 0.67 across training, testing, cross-validation, and external validation datasets. This study presents a model that enhances the understanding of the dynamic factors influencing methane concentration variations. The methodology developed in this research can serve as a reference for other regions and timeframes, potentially offering key insights for the formulation of effective global climate mitigation strategies
[[alternative]]Immunogenic peptide and use thereof
No full text[[abstract]]本發明係關於一種免疫原性胜肽，其包含一衍生自腫瘤壞死因子受體相關蛋白1(TRAP1)的T細胞抗原決定位胜肽，其能誘發細胞毒性T淋巴細胞。另外，本發明亦關於一種包含上述免疫原性胜肽的藥物，其用於治療過量表現TRAP1之相關癌症
[[alternative]]Composition comprising antigen and dna and use thereof
No full text[[abstract]]本發明提供了一種組成物，其中組成物包括一次單元疫苗，包括一第一劑量之一次單元；以及一核酸疫苗，包括一第二劑量之一載體
[[alternative]]Method and composition for treatment of hair loss
No full text[[abstract]]本發明係關於一種用於治療掉髮之方法，包含將一Notch訊息傳遞路徑之活化劑投藥予有其需要的個體