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Chung-Hwan Chen,1 Seung-Jae Lim,2 Jong-Keon Oh,3 Tsan-Wen Huang,4 Yuhong H Zeng,5 Meng-Ting Wu,6 Huilin L Yang,7 Jason Pui-Yin Cheung,8 Ji Wan Kim,9 Jeong Hee Han,10 Li Huo,11 Tsung-Jung Lin,12 Gang Zhou,11 Wen-Shuo Wu12 1Department of Orthopedics and Orthopedic Research Center, Kaohsiung Municipal Ta-Tung Hospital and Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; 2Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Orthopedics, Korea University Guro Hospital, Seoul, South Korea; 4Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan; 5Department of Osteoporosis, Honghui Hospital, Xi ‘an Jiaotong University, Xian, People’s Republic of China; 6Division of Neurosurgery, Department of Surgery, Cheng Hsin General Hospital, Taipei, Taiwan; 7Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 8Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, People’s Republic of China; 9Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea; 10Department of Medical Quality and Regulatory Affairs, Lilly Korea Ltd., Seoul, South Korea; 11Lilly China Drug Development and Medical Affairs Center, Lilly Suzhou Pharmaceutical Co. Ltd, Shanghai, People’s Republic of China; 12Department of Medical Affairs, Eli Lilly and Company (Taiwan), Inc., Taipei, TaiwanCorrespondence: Wen-Shuo WuEli Lilly and Company (Taiwan), Inc., 11/F, No. 365 Fu Hsing N. Road, Taipei 105 R.O.C., TaiwanTel +886 2 2715 2950 ext 2234Email wu_marco@lilly.comPurpose: The aim of this analysis is to describe the baseline characteristics of patients who are prescribed teriparatide for the treatment of postmenopausal osteoporosis in a real-world setting in East Asia.Patients and Methods: The Asia and Latin America Fracture Observational Study (ALAFOS) is a prospective, multinational, observational study designed to evaluate real-world use of teriparatide in the treatment of postmenopausal osteoporosis in 20 countries across Asia, Latin America, the Middle East, and Russia. This subregional analysis focuses on the East Asian subpopulation of the ALAFOS study. Here we report baseline clinical characteristics, details regarding the history of fractures, risk factors for osteoporosis, comorbidities, osteoporosis treatment, and health-related quality of life in patients enrolled in China, Hong Kong, South Korea, and Taiwan.Results: The East Asian subgroup of ALAFOS included 1136 postmenopausal women, constituting 37.5% (1136/3031) of the overall ALAFOS patient population. The mean (SD) age was 75.0 (9.6) years. The mean (SD) bone mineral density T-scores were − 3.11 (1.54), − 2.58 (1.11), and − 2.86 (1.09) at the lumbar spine, total hip, and femoral neck, respectively; 69.6% of patients had experienced at least one fragility fracture and 40.4% had experienced ≥ 2 fragility fractures after 40 years of age. Overall, 63.3% of patients had used medications for osteoporosis in the past. The mean (SD) EQ-5D-5L Visual Analog Scale (VAS) score at baseline was 59.7 (20.8); the mean (SD) back pain numeric rating scale score for worst pain in the last 24 hrs was 5.2 (3.2).Conclusion: Our results indicate that patients who are prescribed teriparatide in East Asia were elderly women with severe osteoporosis, low bone mineral density, high prevalence of fractures, back pain and poor health-related quality of life. Most of the patients received teriparatide as a second-line treatment.Keywords: postmenopausal osteoporosis, teriparatide, observational study, fractures, East Asia

Ching-Chi Yen,1 Yi-Chen Chen,1 Ming-Tsang Wu,2 Chia-Chi Wang,1,3 Yu-Tse Wu1,4 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Chinese Medicine Department, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City, Taiwan; 3PhD Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Background: Andrographolide (AG), a compound with low water solubility, possesses various pharmacological activities, particularly anti-inflammatory activity. However, its low oral bioavailability is a major obstacle to its potential use. This study developed and optimized an AG-loaded nanoemulsion (AG-NE) formulation to improve AG oral bioavailability and its protective effects against inflammatory bowel disease. Methods: A high-pressure homogenization technique was used to prepare the AG-NE and solubility, viscosity, and droplet size tests were conducted to develop the optimized AG-NE composed of α-tocopherol, ethanol, Cremophor EL, and water. The permeability was assessed using everted rat gut sac method and in vivo absorption and anti-inflammatory effect in rats was also evaluated. The plasma concentration of AG was determined using our validated high performance liquid chromatography method, which was used to generate a linear calibration curve over the concentration range of 0.1–25 µg/mL in rat plasma (R2>0.999).Results: The optimized AG-NE had a droplet size of 122±11 nm confirmed using transmission electron microscopy and a viscosity of 28 centipoise (cps). It was stable at 4 and 25°C for 90 days. An ex vitro intestinal permeability study indicated that the jejunum was the optimal site for AG absorption from the optimized AG-NE, which was 8.21 and 1.40 times higher than that from an AG suspension and AG ethanol solution, respectively. The pharmacokinetic results indicate that the absorption of AG from AG-NE was significantly enhanced in comparison with that from the AG suspension, with a relative bioavailability of 594.3%. Moreover, the ulcer index and histological damage score of mice with indomethacin-induced intestinal lesions were significantly reduced by AG-NE pretreatment. Conclusion: We conclude that the developed AG-NE not only enhanced the oral bioavailability of AG in this study but may also prove to be an effective formulation of AG for preventing gastrointestinal inflammatory disorders. Keywords: andrographolide, nanoemulsion, intestinal permeability, oral bioavailability

Objective: This study aimed to determine whether characteristics detected by multi-detector computed tomography (MDCT) were predictive of highly infectious, smear-positive, active pulmonary tuberculosis (PTB).Methods: Among 124 patients with active PTB, 84 had positive (group 1) and 40 had negative (group 2) smear results for acid-fast bacilli. Multiplanar MDCT, axial conventional CT and chest X-ray images were analysed retrospectively for morphology, number, and segmental (lobe) distribution of lesions.Results: By multivariate analysis, consolidation over any segment of the upper, middle, or lingual lobes, cavitations, and clusters of nodules were associated with group 1, while centrilobular nodules were predictive of group 2. Using five independent variables associated with risk in group 1, a prediction model was created to distinguish between group 1 and group 2. ROC curve analysis showed an area under the curve of 0.951 +/- 0.021 for this prediction model. With the ideal cutoff point score of 1, the sensitivity, specificity, and positive predictive values were 84.5%, 97.5%, and 98.0%, respectively.Conclusions: A model to predict smear-positive active PTB on the basis of findings from MDCT may be a useful tool for clinical decisions about isolating patients pending sputum smear results. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the influence of pulmonary regurgitation inequality on differential perfusion of the lungs in tetralogy of Fallot (TOF) after repair. Background: Asymmetry of lung perfusion is one of the best predictors of outcome in TOF after repair. A recent phase-contrast magnetic resonance imaging (PC-MRI) study found prominent regurgitation inequality between the bilateral pulmonary arteries in TOF after repair. Methods: Forty-three TOF post-repair patients (median age = 51 months, 31 men) received PC-MRI and 99mTc-labeled macroaggregates of albumin perfusion scintigraphy (PS) in the same day. We took PC-MRI measurements of forward flow volume (FFV), backward flow volume (BFV), and net flow volume (NFV) (NFV = FFV - BFV) and regurgitation fraction (RF) (RF = BFV/FFV) at the left and right pulmonary arteries (LPA and RPA). The differential perfusion of the left lung (L%) (L% = left lung/left + right lung) as calculated by NFV ratio, by FFV ratio of PC-MRI, and by PS were compared. Results: The discrepancy between L% by NFV versus L% by PS was affected by the severity of RF of LPA (r = -0.51, p = 0.001); agreement between L% by NFV versus L% by PS was good (intraclass correlation coefficient [Ri] = 0.87) if RF of LPA <0.4 (n = 23) but downgraded (Ri = 0.51) and underestimated the L% (median of error = -14%, range = -25.3% to 5.5%) if RF of LPA > or =0.4 (n = 20). In contrast, agreement between L% by FFV versus L% by PS was high and unaffected by RF of LPA (Ri = 0.94, 0.92, respectively). Conclusions: While integrating PC-MRI of pulmonary artery as a comprehensive MRI evaluation of TOF after repair, conventional NFV ratio method tended to underestimate the left lung perfusion and may lead to unnecessary intervention. The FFV ratio method should be used for precise assessment of differential lung perfusion. [ABSTRACT FROM AUTHOR]

Background: As a result of metabolic syndrome becoming an important issue during recent decades, many studies have explored the risk factors contributing to its development. However, less attention has been paid to the risk associated with sedentary behavior, especially television viewing. This study examined the association between television viewing time and the risk of having metabolic syndrome in a population of Taiwanese subjects.Methods: This community-based cross-sectional study included 2,353 subjects (1,144 men and 1,209 women) aged 40 and over from October, 2004 to September, 2005. Information about the time spent watching TV was obtained using a self-administered questionnaire. The definition of metabolic syndrome was according to the Third Report of the National Cholesterol Education Program's Adult Treatment Panel modified for Asians.Results: Compared to subjects who viewed TV < 14 hr/week, those who viewed TV > 20 hr/week had a 1.50-fold (95% confidence intervals (CI): 1.10, 2.03) risk for men and a 1.93-fold (95% CI: 1.37, 2.71) risk for women of having metabolic syndrome, after adjusting for physical activity and other covariates. Stratifying by the three categories of total activity levels, TV viewing time > 20 hr/week was found to still hold a significant risk for having metabolic syndrome in the lowest of the three categories of total activity level for men and in all three categories of total activity level for women.Conclusion: The findings suggest that TV viewing is an independent risk factor associated with metabolic syndrome in Taiwanese people. [ABSTRACT FROM AUTHOR]

A large-scale, high-speed, long-runout landslide occurred in Xinmo Village, Maoxian, Sichuan Province, China, on June 24, 2017. It was characterized by fast sliding speed, rapid volume growth, and large impact area. The dynamic process of such landslides and the influence of erosion on the dynamic process are studied by field investigation, numerical inversion and simulation. The results showed that entrainment erosion was a major factor of landslide volumetric change and a salient feature of the landslide process. An exponential equation relating the erosion rate and the deposition volume was established. Moreover, the study found that a slight change of the erosion rate (1e-4) also had a significant impact on the lateral spreading, longitudinal runout, and vertical erosion. As the erosion rate increased, the lateral spreading, longitudinal runout, and vertical erosion of this type of landslide became more obvious. By using the coefficient of variation method, it was obtained that the erosion rate had a greater influence on the vertical erosion than on the lateral spreading and longitudinal runout. In the study of the velocity of the rock avalanche under different erosion conditions, it was found that the erosion amount and the landslide velocity were not strictly linearly related. This study has important significance for understanding the dynamic process and erosion effect of rock avalanche, and provides useful references and insights for future research in related fields., (© 2024. The Author(s).)

Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-β-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL 10 for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) μg/kg&#95;bw/day and 22.82 (18.09) μg/kg&#95;bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 μg/kg&#95;bw/day recommended by the WHO (EFSA).

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (k D , k N and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses., (© 2024. The Author(s).)

Background: Breath-hold volumetric interpolated breath-hold examination (BH-VIBE) of multiphase contrast-enhanced liver magnetic resonance imaging (MPCE-LMRI) requires good cooperative individuals to comply with multiple breath-holds., Purpose: To develop a free-breathing modified VIBE (FB-mVIBE) as a substitute of BH-VIBE in MPCE-LMRI., Material and Methods: We modified VIBE with a high acceleration factor (2 × 2) and four averages to produce the mVIBE scan. A total of 90 individuals (40 men; mean age = 54.6 ± 10.0 years) who had received MPCE-LMRI as part of a voluntary health check-up for oncology survey were enrolled. Each participant was scanned in four phases (pre-contrast, arterial phase, venous phase, and delay phase), and each phase had two sequential scans. To encounter the timing effect of contrast enhancement, three scan orders were designed: BH-VIBE and FB-mVIBE (group A, n = 30); BH-VIBE and FB-VIBE (group B, n = 30); and FB-mVIBE and BH-VIBE (group C, n = 30). The comparisons included the objective measurements and 25 visual-score by two abdominal radiologists independently., Results: Consistency between raters was observed for all three sequences (intraclass correlation coefficient [ICC] = 0.741-0.829). For rater 1, the mean scores of FB-mVIBE (23.67 ± 1.32) were equal to those of BH-VIBE (23.83 ± 1.98) in groups C and B (P = 0.852). The mean scores of FB-mVIBE (22.07 ± 3.02), but significantly higher than those of FB-VIBE (14.7 ± 3.41) in groups A and B ( P <0.001). Similar scores were found for rater 2. The objective measurement of FB-mVIBE were equal to or higher than BH-VIBE and markedly superior to FB-VIBE., Conclusion: FB-mVIBE is a practical alternative to BH-VIBE for individuals who cannot cooperate with multiple breath-holds for MPCE-LMRI., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups., (© 2024 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.)

Background: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image., Hypothesis: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets., Study Type: Retrospective., Population: 1071 MOLLI datasets from 392 human participants., Field Strength/sequence: Modified Look-Locker inversion recovery sequence at 3 T., Assessment: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique., Statistical Tests: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences., Results: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01)., Data Conclusion: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ - 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03-1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43-9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17-3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08-5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82-3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population., (© 2024. The Author(s).)

Background: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear., Object: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD)., Methods: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD., Results: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs., Conclusions: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Global ground-level measurements of elements in ambient particulate matter (PM) can provide valuable information to understand the distribution of dust and trace elements, assess health impacts, and investigate emission sources. We use X-ray fluorescence spectroscopy to characterize the elemental composition of PM samples collected from 27 globally distributed sites in the Surface PARTiculate mAtter Network (SPARTAN) over 2019-2023. Consistent protocols are applied to collect all samples and analyze them at one central laboratory, which facilitates comparison across different sites. Multiple quality assurance measures are performed, including applying reference materials that resemble typical PM samples, acceptance testing, and routine quality control. Method detection limits and uncertainties are estimated. Concentrations of dust and trace element oxides (TEO) are determined from the elemental dataset. In addition to sites in arid regions, a moderately high mean dust concentration (6 μg/m 3 ) in PM 2.5 is also found in Dhaka (Bangladesh) along with a high average TEO level (6 μg/m 3 ). High carcinogenic risk (>1 cancer case per 100000 adults) from airborne arsenic is observed in Dhaka (Bangladesh), Kanpur (India), and Hanoi (Vietnam). Industries of informal lead-acid battery and e-waste recycling as well as coal-fired brick kilns likely contribute to the elevated trace element concentrations found in Dhaka., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θ M-AP ), MPA with RPA (θ M-R ), and MPA with LPA (θ M-L ); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θ M-AP , sharper θ M-L angle, and a smaller θ M-L /θ M-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θ M-L /θ M-R ratio and the age at surgery (R 2  = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R 2  = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies., (© 2024. The Author(s).)

Apixaban and dabigatran are the two major direct oral anticoagulant drugs to treat thromboembolic disordered patients. Increasing the clinical application for the thromboembolic disorder and monitoring the concentrations of apixaban, dabigatran, and their metabolites are essential in most clinical circumstances. In this work, we developed a rapid analytical methodology comprising of vortex-assisted salt-enhanced liquid-liquid microextraction technique coupled with UHPLC-MS/MS for the extraction and simultaneous determination of two major direct oral anticoagulant drugs (apixaban, dabigatran), and their two major metabolites from plasma, serum, and urine samples of patients. The developed method was optimized with various procedural steps and validated to study the analytical merits. The developed method yielded a good detection limit of 0.01 ∼ 0.37 ng/mL, 0.01 ∼ 0.32 ng/ml, and 0.01 ∼ 0.27 ng/mL for four target analytes in the plasma, serum, and urine matrices. Moreover, extraction recoveries ranged from 85.11 - 113.57% (for plasma), 89.63 - 110.47% (for serum), and 87.44 -106.79% (for urine samples) with 8.78% RSD. In addition, the method exhibited good R 2 values of 0.999 for all four target analytes, and the specificity and carryover study revealed no carryover effect from the UHPLC-MS/MS system for determining the apixaban, dabigatran, and their metabolites. Due to the above advantages, the developed analytical technique was applied to examine 11 real-time clinical patients' samples, and the observed results were satisfactory for all three different sample matrices. Therefore, this analytical method can be applied for biomonitoring apixaban, dabigatran, and their two major metabolites with high sensitivity in a short time for various clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer., Methods: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ 2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing., Findings: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis., Interpretation: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer., Funding: Ministry of Health and Welfare of Taiwan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37-1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46-14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80-80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61-0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47-0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance.

Background: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery., Methods: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed., Results: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group., Conclusion: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Denosumab preceding elective surgery is an alternative option when parathyroidectomy is not immediately possible. Denosumab (an osteoprotegerin mimic) may play a role in the cardiovascular system, which is reflected in the features of epicardial adipose tissue (EAT) and coronary artery calcification (CAC)., Methods: We investigated the effects of denosumab on EAT attenuation (EATat) and CAC in dialysis patients with secondary hyperparathyroidism (SHPT). This cohort study included patients on dialysis with SHPT. The baseline characteristics of dialysis patients and propensity score-matched non-dialysis patients were compared. Computed tomography scans of the dialysis patients (dialysis group with denosumab, n = 24; dialysis group without denosumab, n = 21) were obtained at baseline and at 6 months of follow-up., Results: At baseline, the dialysis group patients had a higher EATat-median (-71.00 H ± 10.38 vs. -81.60 H ± 6.03; p &lt; 0.001) and CAC (1,223 A [248.50-3,315] vs. 7 A [0-182.5]; p &lt; 0.001) than the non-dialysis group. At follow-up, the dialysis group without denosumab showed an increase in Agatston score (1,319.50 A [238.00-2,587.50] to 1,552.00 A [335.50-2,952.50]; p = 0.001) without changes in EATat-median (-71.33 H ± 11.72 to -70.86 H ± 12.67; p = 0.15). The dialysis group with denosumab showed no change in Agatston score (1,132.2 A [252.25-3,260.5] to 1,199.50 A [324.25-2,995]; p = 0.19) but a significant decrease of EATat-median (-70.71 H ± 9.30 to -74.33 H ± 10.28; p = 0.01)., Conclusions: Denosumab may reverse EATat and retard CAC progression in dialysis patients with SHPT., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 μL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1β), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Cooking oil fumes (COFs) comprised of a mixture of cancer-causing volatile organic aldehydes (VOAs), particularly trans, trans-2,4-decadienal (t,t-DDE), 4-hydroxy-hexenal (4-HHE), and 4-hydroxy-nonenal (4-HNE). Monitoring toxic VOAs levels in people exposed to different cooking conditions is vital to predicting the cancer risk. For this purpose, we developed a fast tissue extraction (FaTEx) technique combined with UHPLC-MS/MS to monitor three toxic VOAs in mice lung tissue samples. FaTEx pre-treatment protocol was developed by combining two syringes for extraction and clean-up process. The various procedural steps affecting the FaTEx sample pre-treatment process were optimized to enhance the target VOAs' extraction efficiency from the sample matrix. Under the optimal experimental conditions, results exhibit good correlation coefficient values > 0.99, detection limits were between 0.5-3 ng/g, quantification limits were between 1-10 ng/g, and the matrix effect was <18.1%. Furthermore, the extraction recovery values of the spiked tissue exhibited between 88.9-109.6% with <8.6% of RSD. Cooking oil fume (containing t,t-DDE) treated mice at various time durations were sacrificed to validate the developed technique, and it was found that t,t-DDE concentrations were from 14.8 to 33.8 μg/g. The obtained results were found to be a fast, reliable, and semi-automated sample pre-treatment technique with good extraction efficiency, trace level detection limit, and less matrix effect. Therefore, this method can be applied as a potential analytical method to determine the VOAs in humans exposed to long-term cooking oil fumes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Coilin is a scaffold protein essential for the structure of Cajal bodies, which are nucleolar-associated, nonmembranous organelles that coordinate the assembly of nuclear ribonucleoproteins (RNPs) including spliceosomal snRNPs. To study coilin function in plants, we conducted a genetic suppressor screen using a coilin (coi1) mutant in Arabidopsis thaliana and performed an immunoprecipitation-mass spectrometry analysis on coilin protein. The coi1 mutations modify alternative splicing of a GFP reporter gene, resulting in a hyper-GFP phenotype in young coi1 seedlings relative to the intermediate wild-type level. As shown here, this hyper-GFP phenotype is extinguished in older coi1 seedlings by posttranscriptional gene silencing triggered by siRNAs derived from aberrant splice variants of GFP pre-mRNA. In the coi1 suppressor screen, we identified suppressor mutations in WRAP53, a putative coilin-interacting protein; SMU2, a predicted splicing factor; and ZCH1, an incompletely characterized zinc finger protein. These suppressor mutations return the hyper-GFP fluorescence of young coi1 seedlings to the intermediate wild-type level. Additionally, coi1 zch1 mutants display more extensive GFP silencing and elevated levels of GFP siRNAs, suggesting the involvement of wild-type ZCH1 in siRNA biogenesis or stability. The immunoprecipitation-mass spectrometry analysis reinforced the roles of coilin in pre-mRNA splicing, nucleolar chromatin structure, and rRNA processing. The participation of coilin in these processes, at least some of which incorporate small RNAs, supports the hypothesis that coilin provides a chaperone for small RNA trafficking. Our study demonstrates the usefulness of the GFP splicing reporter for investigating alternative splicing, ribosome biogenesis, and siRNA-mediated silencing in the context of coilin function., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Taiwan had the high incidence of chronic kidney disease (CKD) worldwide. Our objective was to examine associations between daily exposure of phthalates and melamine, two common nephrotoxins, and kidney damage risk in a well-established nationwide cohort. Study subjects were from Taiwan Biobank (TWB) with existing data of questionnaire and biochemical examinations. Average daily intake (ADI) levels of melamine and seven parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), DEP (Diethyl phthalate), and DMP (Dimethyl phthalate) were estimated using a creatinine excretion-based model from urine melamine and 10 phthalate metabolites. Urine microalbumin to creatinine ratio (ACR) was used to represent for the outcome of kidney damage. Two statistical strategies were used: First, a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with ACR; Second, to examine effects of those most important exposure variables on ACR in multivariable linear regression models. In total, 1153 eligible adults were left for analyses. Of them, 591 (51.3%) and 562 (48.7%) were men and women, respectively, with a median age of 49 years old. By WQS, a significant and positive association was found between ADI of melamine and phthalates and ACR (β = 0.14, p = 0.002). ADI levels of melamine had the highest weight (0.57), followed by DEHP (0.13). Next, examining the two most important exposures in association with ACR, we found that the higher the melamine and DEHP intakes, the higher the ACR levels were found. An interaction effect was also found between melamine and DEHP intakes on urine ACR (p = 0.015). This result was more prominent in men (p = 0.008) than in women (p = 0.651). Environmental co-exposure of melamine and DEHP can potentially affect ACR in the community-dwelling Taiwanese adult population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The controlled attenuation parameter (CAP) measurement obtained from FibroScan ® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan ® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan ® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m 2 to 34.9 kg/m 2 . Class 2 obesity is defined by a BMI ranging from 35 kg/m 2 to 39.9 kg/m 2 , while class 3 obesity is designated by a BMI of 40 kg/m 2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

Maternal exposure to di-(2-ethylhexyl)-phthalate (DEHP), an environmental endocrine disruptor, may lead to developmental immunotoxicity in offspring. The causal relationship and underlying mechanism require further study. A subset of Taiwan Maternal and Infant Cohort Study data (n = 283) was analyzed and found a significant association between urinary DEHP metabolite levels from the third trimester of pregnancy and plasma levels of IL-28A and IL-29, named IFNλs, in cord blood. A trans-maternal murine model mimicking human DEHP exposure way showed that bone marrow-derived dendritic cells from maternal DEHP-exposed F1 offspring secreted higher IL-28A levels than control cells, indicating a potential causal relationship. Human bronchial epithelial cell lines treated with DEHP or its primary metabolite, mono-(2-ethyl-5-hexyl) phthalate (MEHP), expressed significantly higher levels of IFNλs mRNA or protein than controls. MEHP's effect on IFNλs expression was blocked by peroxisome proliferator-activated receptor α (PPARα) and PPARγ antagonists, and inhibited by a histone acetyltransferase inhibitor or a histone methyltransferase inhibitor. Chromatin immunoprecipitation assay showed that MEHP treatment promoted histone modifications at H3 and H4 proteins at the promoter regions of Il28a and Il29 genes. These results suggest maternal DEHP exposure could result in high IFNλ expression in offspring, and the health risk of early-life exposure requires further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The objective of this study is to investigate the relationship between metabolic syndrome (MetS), and bone density in a 30- to 50-year-old Taiwanese population, and to explore the combined effects of BMI and health behaviors on this association. A total of 52,912 individuals aged 30-50 years from the Taiwan Biobank were included in this cross-sectional study. Bone density status was assessed using quantitative ultrasound (QUS). The joint effect was assessed by including an interaction term in the multi-logistic regression models to test the association between MetS, BMI, and bone density while controlling for potential confounders. MetS was associated with reduced bone density, with the risk of severe low bone density (SLBD) higher among BMI < 24 kg/m 2 individuals with MetS (adjusted odds ratio [aOR] 1.5, 95% confidence interval [CI] 1.09-2.16), while the risk was not significant among BMI ≥ 24 kg/m 2 individuals with MetS. Smoking, alcohol consumption, and lack of regular exercise among individuals with a BMI < 24 kg/m 2 and MetS were associated with higher risk of severe low bone density (SLBD), the aORs (95%CI) were 2.9 (1.59-5.20), 2.1 (1.06-4.22), and 1.8 (1.24-2.54) respectively. Our study suggests that metabolic syndrome could increase the risk of severe low bone density, but this risk can be minimized through higher BMI, non-smoking, no alcohol consumption, and regular exercise. Conversely, smoking, alcohol consumption or lack of regular exercise may exacerbate the risk of severe low bone density. These findings highlight the importance of a multifactorial approach in managing bone healthcare., (© 2023. Springer Nature Limited.)

Smoking is a risk factor for bladder cancer (BC), although the specific chemicals responsible for BC remain uncertain. Considerable research has focused on aromatic amines (AAs), including o -toluidine ( o -tol), o -anisidine ( o -anis), 2-naphthylamine (2-NA), and 4-aminobiphenyl (4-ABP), which are linked to human BC based on elevated BC incidence in occupationally exposed factory workers. These AAs arise at nanogram levels per combusted cigarette. The unambiguous identification of AAs, particularly low-molecular-weight monocyclic AAs in tobacco smoke extracts, by liquid chromatography-mass spectrometry (LC-MS) is challenging due to their poor performance on reversed-phase columns and co-elution with isobaric interferences from the complex tobacco smoke matrix. We employed a tandem liquid-liquid and solid-phase extraction method to isolate AAs from the basic fraction of tobacco smoke condensate (TSC) and utilized high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to high-resolution accurate mass (HRAM) Orbitrap LC-MS 2 to assay AAs in TSC. The employment of FAIMS greatly reduced sample complexity by removing precursor co-isolation interfering species at the MS 1 scan stage, resulting in dramatically improved signal-to-noise of the precursor ions and cleaner, high-quality MS 2 spectra for unambiguous identification and quantification of AAs in TSC. We demonstrate the power of LC/FAIMS/MS 2 by characterizing and quantifying two low-molecular-weight carcinogenic AAs, o -tol and o -anis, in TSC, using stable isotopically labeled internal standards. These results demonstrate the power of FAIMS in trace-level analyses of AA carcinogens in the complex tobacco smoke matrix.

In this study, we demonstrated a novel semi-automated in-syringe-based coagulant-assisted liquid-liquid microextraction (IS-CGA-LLME) as fast mycotoxin extraction (FaMEx) technique coupled with ultra-high-performance liquid chromatography connected with a tandem-mass spectrometer (UHPLC-MS/MS) for the quantification of mycotoxin (Ochratoxin A, OT-A) in coffee and tea samples. IS-CGA-LLME is a three-step extraction process that includes extraction of OT-A from sample matrix using low-volume solvent extraction, then the extractant was cleaned-up using a coagulation process, and finally, the decolorized/matrix removed sample solution was processed for LLME for target analyte's pre-concentration. The final extractant was analyzed using UHPLC-MS/MS for OT-A quantification. Under the optimized experimental conditions, highly sensitive detection and quantification limits were obtained at 0.001 and 0.003 ng g -1 for OT-A with excellent extraction recovery (93-111%) and precision <10%. These results proved that the developed method is a simple, highly sensitive, semi-automated, low-matrix effect and efficient procedure for the determination of mycotoxins in food samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We present an unsupervised learning denoising method, RepE (representation and enhancement), designed for nonlinear optical microscopy images, such as second harmonic generation (SHG) and two-photon fluorescence (TPEF). Addressing the challenge of effectively denoising images with various noise types, RepE employs an encoder network to learn noise-free representations and a reconstruction network to generate denoised images. It offers several key advantages, including its ability to (i) operate without restrictive statistic assumptions, (ii) eliminate the need for clean-noisy pairs, and (iii) requires only a few training images. Comparative evaluations on real-world SHG and TPEF images from esophageal cancer tissue slides (ESCC) demonstrate that our method outperforms existing techniques in image quality metrics. The proposed method provides a practical, robust solution for denoising nonlinear optical microscopy images, and it has the potential to be extended to other nonlinear optical microscopy modalities.

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m 2 /year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 μg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m 2 /year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m 2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Field-grown rice (Oryza sativa L.), when exposed to various environmental stresses, produces high amounts of reactive oxygen species, such as H 2 O 2 . MicroRNAs (miRNAs) play crucial roles in plant stress responses. This study characterized the functions of H 2 O 2 -regulated miRNAs in rice. Small RNA deep sequencing revealed that miR156 levels decreased following H 2 O 2 treatment. Searches of the rice transcriptome and degradome databases indicated that OsSPL2 and OsTIFY11b are miR156-target genes. Interactions between miR156 and OsSPL2 and OsTIFY11b were confirmed using transient expression assays through agroinfiltration. In addition, the levels of OsSPL2 and OsTIFY11b transcripts were lower in transgenic rice plants overexpressing miR156 than in wild-type plants. The OsSPL2-GFP and OsTIFY11b-GFP proteins were localized to the nucleus. Yeast two-hybrid and bimolecular fluorescence complementation assays indicated interactions between OsSPL2 and OsTIFY11b. Furthermore, OsTIFY11b interacted with OsMYC2 to regulate the expression of OsRBBI3-3, which encodes a proteinase inhibitor. The results suggested that H 2 O 2 accumulation in rice suppresses the expression of miR156, and induces the expression of its target genes, OsSPL2 and OsTIFY11b, whose proteins interact in the nucleus to regulate the expression of OsRBBI3-3, which is involved in plant defense., (© 2023 John Wiley & Sons Ltd.)

Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data obtained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I-IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial-mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.

Assessing the impact of human exposure to environmental toxicants is often crucial to biomonitoring the exposed dose. In this work, we report a novel fast urinary metabolites extraction (FaUMEx) technique coupled with UHPLC-MS/MS analysis for the highly sensitive and simultaneous biomonitoring of the five major urinary metabolites (thiodiglycolic acid, s-phenylmercapturic acid, t,t-muconic acid, mandelic acid, and phenyl glyoxylic acid) of common volatile organic compounds' (VOCs) exposure (vinyl chloride, benzene, styrene, and ethylbenzene) in human. FaUMEx technique comprises of two-steps, liquid-liquid microextraction was performed first in an extraction syringe using 1 mL of methanol (pH 3) as an extraction solvent and then, the extractant was passed through a clean-up syringe (pre-packed-with various sorbents including 500 mg anhydrous MgSO 4 , 50 mg C18, and 50 mg SiO 2 ) to obtain the high order of matrice clean-up and preconcentration efficiency. The developed method displayed excellent linearity, and the correlation coefficients were >0.998 for all the target metabolites with detection and quantification limits of 0.02-0.24 ng mL -1 and 0.05-0.72 ng mL -1 , respectively. Furthermore, the matrix effects were < ±5%, and inter and intra-day precision were <9%. Moreover, the presented method was applied and validated to real sample analysis for biomonitoring of VOC's exposure levels. The results showed that the developed FaUMEx-UHPLC-MS/MS method is fast, simple, low-cost, low-solvent consumption, high sensitivity with good accuracy and precision for five targeted urinary VOCs' metabolites. Therefore, the presented dual-syringe mode FaUMEx strategy with UHPLC-MS/MS technique can be applied to biomonitoring of various urinary metabolites to assess human exposure to environmental toxicants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Identifying the risk of ochratoxin A in our daily food has become fundamental because of its toxicity. In this work, we report a novel semi-automated in-syringe-based fast mycotoxin extraction (IS-FaMEx) technique coupled with direct-injection electrospray-ionization tandem mass spectrometer (ESI-MS/MS) detection for the quantification of ochratoxin A in coffee and tea samples. Under the optimized conditions, the results reveal that the developed method's linearity was more remarkable, with a correlation coefficient of > 0.999 and > 92% extraction recovery with a precision of 6%. The detection and quantification limits for ochratoxin A were 0.2 and 0.8 ng g -1 for the developed method, respectively, which is lower than the European Union regulatory limit of toxicity for ochratoxin-A (5 ng g -1 ) in coffee. Furthermore, the newly developed modified IS-FaMEx-ESI-MS/MS exhibited lower signal suppression of 8% with a good green metric score of 0.64. In addition, the IS-FaMEx-ESI-MS/MS showed good extraction recovery, matrix elimination, good detection, and quantification limits with high accuracy and precision due to the fewer extraction steps with semi-automation. Therefore, the presented method can be applied as a potential methodology for the detection of mycotoxins in food products for food safety and quality control purposes., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05733-z., (© Association of Food Scientists & Technologists (India) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Double-low CT aortography (DLCTA) is increasingly used in follow-up studies of aortic aneurysm after endovascular aneurysm repair (EVAR). However, whether DLCTA can reliably detect the presence of endoleak is not clear., Methods: From February 2014 to October 2019, patients who received EVAR, underwent CT surveillance, and had at least one standard CTA protocol (120 kVp, 400 mg I/kg) and one DLCTA (70-80 kVp, 200 mg I/kg) were included. The integrated findings of the standard CTA and sequential change were considered as the reference standard for the presence of endoleak., Results: In all, 36 patients received TEVAR and 24 patients received EVAR; 62 standard CTA and 167 DLCTA results were analyzed. There were 2 type I (3.3%) and 12 type II (20.0%) endoleaks in 14 patients (23.3%). The performance of DLCTA in the diagnosis of endoleak reached 100% accuracy compared to that of standard CTA in case of the correction of CT findings by an expert second reading. Compared to the standard CTA, DLCTA scan reduced the radiation dose by 71% and the iodine dose by 50%., Conclusions: DLCTA with 70-80 kVp and 200 mg I/kg can reliably detect the presence of endoleak after TEVAR/EVAR.

Objective: The participation of patients with advanced cancer(s) in clinical trials is vital for new drug development. We aimed to investigate patients' decision-making processes and satisfaction with their decision (SWD) to participate; the study's purpose was to provide results that can help support high-quality research in clinical trials. In addition, we explored how shared decision-making (SDM) mediates the relationship between understanding informed consent forms and SWD to participate in a clinical trial., Methods: A cross-sectional study was conducted. A purposive sample of 111 cancer patients was recruited, and they completed a questionnaire on demographic characteristics, SDM, and decision-making satisfaction to participate in a clinical trial. Correlation and mediation analyses were used., Results: Participants aged under 65 years and with higher education reported high SWDs, and SDM significantly mediated the relationship between self-assessed understanding of informed consent forms and SWDs related to clinical trials., Conclusions: SDM in patients with lung or liver cancer was a significant mediator between understanding the informed consent form and the patient's SWD. The higher the SWD level of participating in clinical trials, the better study team members' SDM involvement and the better the comprehension of informed consent forms. In addition, patients' age and education level should also be considered as influencing factors in SWD. This survey is the first in Taiwan to examine SDM in drug-related clinical trials. The study results provide evidence to support SDM in a clinical trial model and develop informed consent process policies in research facilities., (© 2023 The Authors.)