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Rickettsiosis includes a diversity of culture-negative non-specific systemic infections. Laboratory diagnosis of rickettsiosis is often not easy. In this 12-month study, six patients with a variety of rickettsia infections of the spotted fever group, typhus group and scrub typhus were diagnosed directly or indirectly by metagenomic next-generation sequencing (mNGS). The patient with Japanese spotted fever was rapidly made when mNGS analysis of the patient's blood revealed Rickettsia japonica sequences. For the two patients with Rickettsia felis chest infections, the bacterium was detected in the bronchoalveolar lavage of one case and lung biopsy of the other. Both patients had underlying malignancies, carcinoma of the breast and carcinoma of the lung respectively, and were on chemotherapy with immunosuppressive effect. For the remaining three patients who presented over a period of 13 weeks, all had fever, headache and the typical eschar. They also had increased serum transaminases and responded promptly to doxycycline. However, the Weil-Felix test results of all three patients were negative. Since we considered the three cases typical of rickettsiosis, we submitted their serum samples for mNGS analysis. Results showed that Orientia tsutsugamushi sequences were present in the serum of one case. In view of the positive mNGS results, we repeated the Weil-Felix test for the residual sera of all three patients and it revealed that those of the other two cases showed OX-19 titers of 1:640 and 1:160 respectively, inferring that these two patients probably had rickettsiosis of the typhus group. As for the patient positive for O. tsutsugamushi sequences, we also detected IgM for O. tsutsugamushi in the serum, which double confirmed that it was a case of scrub typhus. mNGS is an important molecular tool and can complement serology for laboratory diagnosis of rickettsiosis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PCYW has provided scientific advisory/laboratory services for Gilead Sciences, Incorporated; International Health Management Associates, Incorporated; Merck & Corporation, Incorporated; Micología Molecular S.L. and Pfizer, Incorporated. The other authors report no conflict of interest. The authors alone are responsible for the content and the writing of the manuscript., (Copyright: © 2024 Xing 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.)

As the effectiveness of current treatments against the development of antimicrobial resistance is declining, new strategies are required. A great source of novel secondary metabolites with therapeutics effects are the endophytic bacteria present in medicinal plants. In this study, Klebsiella aerogenes (an endophytic bacteria belonging to the Enterobacteriaceae family) was isolated from Kalanchoe blossfeldiana (a medicinal plant". The bacterial secondary metabolites were identified using GC-MS techniques. Furthermore, the antibacterial potentials were investigated against multi-drug resistance (MDR) Salmonella typhi and Staphylococcus aureus. The GC-MS chromatogram of K. aerogenes secondary metabolites extract displayed total of 36 compounds. Ethyl acetate extracts of K. aerogenes, showed mean zone of growth inhibition of 15.00 ± 1.00 against S. typhi and 7.00 ± 1.00mm against S. aureus, respectively. The extract demonstrated significant antibacterial effectiveness against S. typhi and moderate antibacterial efficacy against S. aureus, with minimum inhibitory concentration (MIC) values ranging from 0.089 to 0.39 mg/mL. The time-kill kinetics profile of the ethyl acetate extract against S. typhi revealed a decrease in the number of viable cells during the initial 5, 6, and 24 hours. Conversely, there was a sudden increase in viable cells up to 6 hours for S. aureus. The identified secondary metabolite with high percentage than others, benzeneethanamine exhibited favorable interactions (-7.2 kcal/mol) with the penicillin-binding protein (PBP2a) of S. aureus and (-7.5 kcal/mol) osmoporin (OmpC) of S. typhi, indicating its potential as a candidate for drug development against these MDR bacteria. This study reported for the first time, bacterial endophytes associated with K. blossfeldiana with antibacterial activities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shah 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.)

Introduction: Visceral metastasis is an important predictor for poor outcomes in prostate cancer, however, the prognostic significance surrounding the specific sites of visceral metastasis remains unclear. The aim of this study was to evaluate the impact of different visceral metastatic sites on survival in patients with prostate cancer., Methods: We identified patients with metastatic prostate cancer between January 1, 2010 and December 31, 2023 using the TriNetX database. Patients were divided into 4 cohorts according to their specific metastatic sites: lung metastases, brain metastases, liver metastases, and bone metastases. Survival analysis was calculated using the Kaplan-Meier method and Cox regression models., Results: In total, 59,875 patients diagnosed with metastatic prostate cancer were identified, with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) lung metastases, 5,240 (8.7%) brain metastases, and 7,567 (12.5%) liver metastases. The median overall survival was 44.4 months for patients with bone metastases, 31.9 months for lung metastases, 9.6 months for brain metastases, and 10 months for liver metastases. Lung metastases were associated with an improved survival when compared with liver and brain metastases. For patients with two visceral metastatic sites or concomitant bone metastases, liver metastases were related to worse outcomes. Asian patients experienced better OS than Caucasian and African American patients in visceral metastatic prostate cancer., Conclusion: Patients with lung metastases experienced better survival outcomes in prostate cancer with only one visceral metastatic site. Liver metastases were associated with worse outcomes when there were two visceral metastatic sites combined or concomitant bone metastases. Asian patients displayed improved survival rates when compared with both Caucasian and African American patients in visceral metastatic prostate cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lai 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.)

Lung cancer stands as the primary cause of cancer-related death across the globe. The standard therapeutic approach for lung cancer involves concurrent chemoradiotherapy, with consideration of prophylactic cranial irradiation for younger or well-performing patients. In this study, we aimed to investigate prognostic factors and the impacts of different treatment methods on overall survival for stage IIIA small cell lung cancer in Taiwan. We obtained data from the Taiwan Cancer Registry, which included clinical and pathology data of 579 stage IIIA small cell lung cancer patients from January 2010 to December 2018, for this retrospective study. The enrolled patients had data on age, sex, Charlson Comorbidity Index score, histologic grading, clinical T, clinical N, clinical stage, treatment modality, and overall survival time. We compared overall survival among different subgroups to assess the impacts of these prognostic factors. The five-year survival rate for all patients was 20.57%, with a median survival time of 15.79 months. The data suggest that Charlson Comorbidity Index score, histologic grade, and clinical stage subgroups did not reach statistically significant differences. During the multivariate analysis, age over 70 years, sex, and treatment method were determined to be statistically significant independent prognostic factors. Patients who underwent surgical intervention exhibited significantly better outcomes compared to those who did not undergo operation.. In conclusion, stage IIIA small cell lung cancer is a highly heterogeneous disease. Operation should be considered as one of the alternative treatments in stage IIIA Small cell lung cancer patients., Competing Interests: NO authors have competing interests, (Copyright: © 2024 Yu 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.)

Background: The lean soft tissue mass (LSTM) of the limbs is approximately 63% of total skeletal muscle mass. For athletes, measurement of limb LSTM is the basis for rapid estimation of skeletal muscle mass. This study aimed to establish the estimation equation of LSTM in Asian athletes using bioelectrical impedance analysis (BIA)., Methods: A total of 198 athletes (121 males, 77 females; mean age 22.04 ± 5.57 years) from different sports in Taiwan were enrolled. A modeling group (MG) of 2/3 (n = 132) of subjects and a validation group (VG) of 1/3 (n = 68) were randomly assigned. Using the InBody S-10, resistance and reactance were measured at 50 kHz from the right palm to the right sole while the participant was in the supine position. Predictor variables were height (h), weight (W), age, Sex, Xc, resistance index (RI; RI = h2 / R). LSTM of arms and legs measured by dual-energy X-ray absorptiometry (DXA) was the response variable. Multivariate stepwise regression analysis method was used to establish BIA estimation equations as ArmsLSTMBIA-Asian and LegsLSTMBIA-Asian. Estimation equations performance was confirmed by cross-validation., Results: Estimation equation "ArmsLSTMBIA-Asian = 0.096 h2/R- 1.132 Sex + 0.030 Weight + 0.022 Xc- 0.022 h + 0.905, r2 = 0.855, SEE = 0.757 kg, n = 132" and "LegsLSTMBIA Asian = 0.197h2/R" + 0.120 h- 1.242 Sex + 0.055 Weight- 0.052 Age + 0.033 Xc -16.136, r2 = 0.916, SEE = 1.431 kg, n = 132" were obtained from MG. Using DXA measurement results of VG for correlation analysis and Limit of Agreement (LOA) of Bland-Altman Plot, ArmsLST is 0.924, -1.53 to 1.43 kg, and LegsLST is 0.957, -2.68 to 2.90 kg., Conclusion: The established single-frequency BIA hand-to-foot (whole body) estimation equation quickly and accurately estimates LSTM of the arms and legs of Asian athletes., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Dr. Kuen-Chang Hsieh was employed by a commercial company, StarBIA Meditek Co. Ltd., during this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright: © 2024 Lai 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.)

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86-0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79-0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07-1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright: © 2024 Chang 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.)

Cancer immunotherapy enhances the body's natural immune system to combat cancer, offering the advantage of lowered side effects compared to traditional treatments because of its high selectivity and efficacy. Utilizing computational methods to identify tumor T cell antigens (TTCAs) is valuable in unraveling the biological mechanisms and enhancing the effectiveness of immunotherapy. In this study, we present ENCAP, a predictor for TTCA based on ensemble classifiers and diverse sequence features. Sequences were encoded as a feature vector of 4349 entries based on 57 different feature types, followed by feature engineering and hyperparameter optimization for machine learning models, respectively. The selected feature subsets of ENCAP are primarily composed of physicochemical properties, with several features specifically related to hydrophobicity and amphiphilicity. Two publicly available datasets were used for performance evaluation. ENCAP yields an AUC (Area Under the ROC Curve) of 0.768 and an MCC (Matthew's Correlation Coefficient) of 0.522 on the first independent test set. On the second test set, it achieves an AUC of 0.960 and an MCC of 0.789. Performance evaluations show that ENCAP generates 4.8% and 13.5% improvements in MCC over the state-of-the-art methods on two popular TTCA datasets, respectively. For the third test dataset of 71 experimentally validated TTCAs from the literature, ENCAP yields prediction accuracy of 0.873, achieving improvements ranging from 12% to 25.7% compared to three state-of-the-art methods. In general, the prediction accuracy is higher for sequences of fewer hydrophobic residues, and more hydrophilic and charged residues. The source code of ENCAP is freely available at https://github.com/YnnJ456/ENCAP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu 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.)

Background: Absolute lymphocyte count (ALC) is a crucial indicator of immunity in critical illness, but studies focusing on long-term outcomes in critically ill patients, particularly surgical patients, are still lacking. We sought to explore the association between week-one ALC and long-term mortality in critically ill surgical patients., Methods: We used the 2015-2020 critical care database of Taichung Veterans General Hospital (TCVGH), a referral hospital in central Taiwan, and the primary outcome was one-year all-cause mortality. We assessed the association between ALC and long-term mortality by measuring hazard ratios (HRs) with 95% confidence intervals (CIs). Furthermore, we used propensity score-matching and -weighting analyses, consisting of propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS), to validate the association., Results: A total of 8052 patients were enrolled, with their one-year mortality being 24.2%. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.140, 95% CI 1.091-1.192). Moreover, this association tended to be stronger among younger patients, patients with fewer comorbidities and lower severity. The association between low ALC and mortality in original, PSM, IPTW, and CBPS populations were 1.497 (95% CI 1.320-1.697), 1.391 (95% CI 1.169-1.654), 1.512 (95% CI 1.310-1.744), and 1.511 (95% CI 1.310-1.744), respectively. Additionally, the association appears to be consistent, using distinct cutoff levels to define the low ALC., Conclusions: We identified that early low ALC was associated with increased one-year mortality in critically ill surgical patients, and prospective studies are warranted to confirm the finding., Competing Interests: The authors declare no competing interest., (Copyright: © 2024 Ho 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.)

An accurate assessment of species diversity is a cornerstone of biology and conservation. The lynx spiders (Araneae: Oxyopidae) represent one of the most diverse and widespread cursorial spider groups, however their species richness in Asia is highly underestimated. In this study, we revised species diversity with extensive taxon sampling in Taiwan and explored species boundaries based on morphological traits and genetic data using a two-step approach of molecular species delimitation. Firstly, we employed a single COI dataset and applied two genetic distance-based methods: ABGD and ASAP, and two topology-based methods: GMYC and bPTP. Secondly, we further analyzed the lineages that were not consistently delimited, and incorporated H3 to the dataset for a coalescent-based analysis using BPP. A total of eight morphological species were recognized, including five new species, Hamataliwa cordivulva sp. nov., Hamat. leporauris sp. nov., Tapponia auriola sp. nov., T. parva sp. nov. and T. rarobulbus sp. nov., and three newly recorded species, Hamadruas hieroglyphica (Thorell, 1887), Hamat. foveata Tang & Li, 2012 and Peucetia latikae Tikader, 1970. All eight morphological species exhibited reciprocally monophyletic lineages. The results of molecular-based delimitation analyses suggested a variety of species hypotheses that did not fully correspond to the eight morphological species. We found that Hamat. cordivulva sp. nov. and Hamat. foveata showed shallow genetic differentiation in the COI, but they were unequivocally distinguishable according to their genitalia. In contrast, T. parva sp. nov. represented a deep divergent lineage, while differences of genitalia were not detected. This study highlights the need to comprehensively employ multiple evidence and methods to delineate species boundaries and the values of diagnostic morphological characters for taxonomic studies in lynx spiders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lo 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.)

The aim of this study is to develop a scoring platform to be used as a reference for both medical preparedness and research resource allocation in the prioritization of zoonoses. Using a case-control design, a comprehensive analysis of 46 zoonoses was conducted to identify factors influencing disease prioritization. This analysis provides a basis for constructing models and calculating prioritization scores for different diseases. The case group (n = 23) includes diseases that require immediate notification to health authorities within 24 hours of diagnosis. The control group (n = 23) includes diseases that do not require such immediate notification. Two different models were developed for primary disease prioritization: one model incorporated the four most commonly used prioritization criteria identified through an extensive literature review. The second model used the results of multiple logistic regression analysis to identify significant factors (with p-value less than 0.1) associated with 24-hour reporting, allowing for objective determination of disease prioritization criteria. These different modeling approaches may result in different weights and positive or negative effects of relevant factors within each model. Our study results highlight the variability of zoonotic disease information across time and geographic regions. It provides an objective platform to rank zoonoses and highlights the critical need for regular updates in the prioritization process to ensure timely preparedness. This study successfully established an objective framework for assessing the importance of zoonotic diseases. From a government perspective, it advocates applying principles that consider disease characteristics and medical resource preparedness in prioritization. The results of this study also emphasize the need for dynamic prioritization to effectively improve preparedness to prevent and control disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang 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.)

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.)

Background: Acute respiratory distress syndrome (ARDS) is a common life-threatening condition in critically ill patients. Itis also an important public health issue because it can cause substantial mortality and health care burden worldwide. The objective of this study was to investigate therisk factors that impact ARDS mortality in a medical center in Taiwan., Methods: This was a single center, observational study thatretrospectively analyzed data from adults in 6 intensive care units (ICUs) at Taichung Veterans General Hospital in Taiwan from 1st October, 2018to30th September, 2019. Patients needing invasive mechanical ventilation and meeting the Berlin definition criteria were included for analysis., Results: A total of 1,778 subjects were screened in 6 adult ICUs and 370 patients fulfilled the criteria of ARDS in the first 24 hours of the ICU admission. Among these patients, the prevalenceof ARDS was 20.8% and the overall hospital mortality rate was 42.2%. The mortality rates of mild, moderate and severe ARDS were 35.9%, 43.9% and 46.5%, respectively. In a multivariate logistic regression model, combination of driving pressure (DP) > 14cmH2O and oxygenation (P/F ratio)≤150 was an independent predictor of mortality (OR2.497, 95% CI 1.201-5.191, p = 0.014). Patients with worse oxygenation and a higher driving pressure had the highest hospital mortality rate(p<0.0001)., Conclusions: ARDS is common in ICUs and the mortality rate remains high. Combining oxygenation and respiratory mechanics may better predict the outcomes of these ARDS patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yu 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.)

Anaplasma marginale (A. marginale), Anaplasma ovis (A. ovis) and Theileria ovis (T. ovis) are among the most commonly reported intracellular tick borne pathogens that infect ruminants across the globe causing huge economic losses. This study aims to report the prevalence and phylogenetic evaluation of these three pathogens infecting sheep and goats (n = 333) that were enrolled from Fort Munro region in Pakistan by using msp1b, msp4 and 18S rRNA genes for A. marginale, A. ovis and T. ovis respectively. Results revealed almost similar infection rates in sheep and goats with an overall prevalence of 11% for A. marginale, 28% for A. ovis and 3% for T. ovis. Concurrent infection was also recorded, however, the number of animals infected with two pathogens (n = 24; 7.2%) was higher than infection with three pathogens (n = 2; 0.6%). Risk factor analysis revealed that sheep reared in small herds had higher A. marginale (P = 0.03) and A. ovis (P = 0.04) infection rates compared to those from large herds. In addition, it was observed that bucks (P ≤ 0.05) and tick-free goats (P ≤ 0.05) exhibited higher A. ovis infection rates than nannies. Phylogenetic analysis of all three pathogens showed that Pakistani isolates were clustered together and were closely related to previously deposited Pakistani isolates as well as with those that were reported from worldwide countries. In conclusion, we are reporting that Pakistani sheep and goats have A. marginale, A. ovis and T. ovis mediated infections and control measures should be taken against them to improve the productivity of the livestock sector., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arif 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.)

The rice GA biosynthetic gene OsGA3ox1 has been proposed to regulate pollen development through the gametophytic manner, but cellular characterization of its mutant pollen is lacking. In this study, three heterozygotic biallelic variants, "-3/-19", "-3/-2" and "-3/-10", each containing one null and one 3bp-deletion allele, were obtained by the CRISPR/Cas9 technique for the functional study of OsGA3ox1. The three homozygotes, "-19/-19", "-2/-2" and "-10/-10", derived from heterozygotic variants, did not affect the development of most vegetative and floral organs but showed a significant reduction in seed-setting rate and in pollen viability. Anatomic characterizations of these mutated osga3ox1 pollens revealed defects in starch granule accumulation and pollen wall development. Additional molecular characterization suggests that abnormal pollen development in the osga3ox1 mutants might be linked to the regulation of transcription factors OsGAMYB, OsTDR and OsbHLH142 during late pollen development. In brief, the rice GA3ox1 is a crucial gene that modulates pollen starch granule accumulation and pollen wall development at the gametophytic phase., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsieh 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.)

Allergic rhinitis (AR) is a common atopic disease worldwide, and it was found that babies with constipation in their early life might have an increased risk of atopic diseases, including AR. Furthermore, recent studies also indicate that the maternal gut microbiota may influence babies. Thus, we extended the definition of early life in utero and evaluated the association between maternal constipation and the risk of AR in their babies. Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 102,820 constipated mothers and 102,820 matched controls between 2005 and 2015. Propensity score analysis was used to match birth year, child sex, birth weight, gestational age, mode of delivery, maternal comorbidities, and children antibiotics taken. Multiple Cox regression and subgroup analyzes were conducted to estimate the adjusted hazard ratio of childhood AR. The incidence of childhood AR was 83.47 per 1,000 person-years in constipated mothers. Adjusting children's sex, birth weight, gestational age, mode of delivery, maternal comorbidities, and children antibiotic use, the results showed that the children whose mothers had constipation had a 1.20-fold risk of AR compared to children of mothers without constipation. Maternal constipation was associated with an increased risk of AR. Therefore, it is important to pay close attention to pregnant mothers with constipation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee 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.)

Abnormal accumulation of alpha-synuclein (αSyn) in the remaining nigra dopaminergic neurons is a common neuropathological feature found in patients with Parkinson's disease (PD). Antibody-based immunotherapy has been considered a potential approach for PD treatment. This study aims to investigate the effectiveness of active immunization against αSyn in a mouse model of PD. Adult mice were immunized with or without a synthetic peptide containing the C-terminal residues of human αSyn and activation epitopes, followed by an intranigral injection of adeno-associated virus vectors for overexpressing human αSyn. Upon the peptide injection, αSyn-specific antibodies were raised, accompanied by degeneration of dopaminergic neurons and motor deficits. Furthermore, the induction of neuroinflammation was postulated by the elevation of astroglial and microglial markers in the immunized mice. Instead of lessening αSyn toxicity, this peptide vaccine caused an increase in the pathogenic species of αSyn. Our data demonstrated the potential adverse effects of active immunization to raise antibodies against the C-terminal fragment of αSyn. This drawback highlights the need for further investigation to weigh the pros and cons of immunotherapy in PD. Applying the αSyn C-terminal peptide vaccine for PD treatment should be cautiously exercised. This study provides valuable insights into the intricate interplay among immune intervention, αSyn accumulation, and neurodegeneration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chiu 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.)

Both quercetin and leucine have been shown to exert moderately beneficial effects in preventing muscle atrophy induced by cancers or chemotherapy. However, the combined effects of quercetin and leucine, as well as the possible underlying mechanisms against cisplatin (CDDP)-induced muscle atrophy and cancer-related fatigue (CRF) remain unclear. To investigate the issues, male BALB/c mice were randomly assigned to the following groups for 9 weeks: Control, CDDP (3 mg/kg/week), CDDP+Q (quercetin 200 mg/kg/day administrated by gavage), CDDP+LL (a diet containing 0.8% leucine), CDDP+Q+LL, CDDP+HL (a diet containing 1.6% leucine), and CDDP+Q+HL. The results showed that quercetin in combination with LL or HL synergistically or additively attenuated CDDP-induced decreases in maximum grip strength, fat and muscle mass, muscle fiber size and MyHC level in muscle tissues. However, the combined effects on locomotor activity were less than additive. The combined treatments decreased the activation of the Akt/FoxO1/atrogin-1/MuRF1 signaling pathway (associated with muscle protein degradation), increased the activation of the mTOR and E2F-1 signaling pathways (associated with muscle protein synthesis and cell cycle/growth, respectively). The combined effects on signaling molecules present in muscle tissues were only additive or less. In addition, only Q+HL significantly increased glycogen levels compared to the CDDP group, while the combined treatments considerably decreased CDDP-induced proinflammatory cytokine and MCP-1 levels in the triceps muscle. Using tumor-bearing mice, we demonstrated that the combined treatments did not decrease the anticancer effect of CDDP. In conclusion, this study suggests that the combination of quercetin and leucine enhanced the suppressed effects on CDDP-induced muscle weakness and CRF through downregulating muscle atrophy and upregulating the glycogen level in muscle tissues without compromising the anticancer effect of CDDP. Multiple mechanisms, including regulation of several signaling pathways and decrease in proinflammatory mediator levels in muscles may contributed to the enhanced protective effect of the combined treatments on muscle atrophy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsu 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.)

Caprine theileriosis, caused by Theileria ovis is a serious production issue, especially in the areas that depend on goats and sheep for milk, meat, and other economic benefits. Pakistan has a large goat population, but few reports have been documented from this country regarding PCR-based detection of T. ovis. The molecular prevalence of T. ovis, on a seasonal basis, in various goat breeds enrolled from Muzaffar Garh district of Punjab in Pakistan was determined from October 2018 to September 2019. In this study, 1084 goat blood samples were screened for the detection of T. ovis DNA through PCR-based amplification of 18S rRNA gene. Out of 1084 goats, 12 (1.11%) were infected with T. ovis. The parasite prevalence varied with the sampling seasons (Chi square test, P = 0.008), and the parasite prevalence was highest in goat blood samples collected in summer (2.39%) followed by winter (1.88%). DNA sequencing and BLAST analysis confirmed the presence of T. ovis, and the amplified isolates from the 18S rRNA gene of T. ovis were found to be highly conserved during phylogenetic analysis. Young goats (Fischer exact test, P = 0.022) were found more infected with T. ovis during the winter season. Infected goats had elevated white blood cell counts (Two-sample t-test, P = 0.04), blood urea nitrogen to Creatinine ratio (Two-sample t-test, P = 0.02) and decreased serum Creatinine (Two-sample t-test, P = 0.001) as compared to T. ovis negative goats. We report a relatively low molecular prevalence of T. ovis in goats from the Muzaffar Garh district. However, it is recommended that control measures to eradicate T. ovis infection in goats in this area should be taken., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Irfan 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.)

The progression of allergic diseases from atopic dermatitis in childhood to other allergic conditions such as asthma in later life is often referred to as the atopic march. In order to study the relationship between cutaneous sensitization by aeroallergen and atopic march, we established a mouse model to test the hypothesis using American cockroaches and house dust mites as the model allergens. Mice were sensitized via skin with native cockroach extract (CraA) or recombinant Per a 2 and Der p 2 proteins without adjuvant. Each mouse was subjected to a total of three 1-week patching sensitizations with a 2-week interval in between each application. The resulting immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of skin lesions and nasal mucosa were evaluated. In mice, application of CraA, rPer a 2, and rDer p 2 aeroallergens through skin patching induced significantly high levels of both total IgE and specific IgEs. The epicutaneous sensitization after a subsequent allergen challenge showed a significant increase in scratch bouts, AHR, epidermal thickness, and eosinophil counts in the skin compared with the control mice. In addition, stimulation of murine splenocytes with allergens increased higher levels of Th2 cytokines, anti-inflammatory cytokines, and chemokines excretion. Our study provides evidence supporting that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. We hope this new allergy model will be useful in the development of new preventive and therapeutic strategies aimed at stopping the atopic march., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Lee 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.)

Theileria annulata (T. annulata) and Anaplasma marginale (A. marginale) are among the most extensively reported tick borne pathogens and are associated with huge economic losses worldwide. A total of 298 cattle blood samples were screened to report the presence of these two pathogens. The samples were collected from apparently healthy cattle (Achai, n = 155, Jersy, n = 88 and crossbred, n = 55) in Bajaur district of Khyber Pakhtunkhwa (KPK) during June and July of 2022. A total of 31 out of 298 cattle (10.4%) were found infected with T. annulata as PCR amplified a 156 base pair fragment from Tams-1 gene of T. annulata from their blood. While 16/298 animals (5.4%) were found infected with A. marginale as they amplified a 382 base pair fragment specific for msp5 gene of this bacterium. Three animals (1%) were found co infected. Cattle susceptibility to T. annulata infection was significantly higher than A. marginale infection (P < 0.001). Phylogenetic analysis revealed that Pakistani isolates of both detected pathogen clustered together and were closely related isolates from worldwide countries. Prevalence of T. annulata varied significantly among the sampling sites (P = 0.05) while no such association was observed for A. marginale among the tested cattle. Epidemiological data analysis revealed that none of the studied risk factors was found associated either with the prevalence of T. annulata or A. marginale (P > 0.05) among enrolled cattle. In conclusion, our study has revealed a relatively higher prevalence of T. annulata than A. marginale in cattle from the Bajaur district in KPK. This information is important for improving the productivity of the livestock sector, which is one of the main sources of income in the country. It is recommended that this data be taken into account for the development and implementation of effective tick control programs, as well as for the improvement of livestock management practices to prevent and manage TBDs in Pakistan., Competing Interests: The authors declare no competing interests with anyone., (Copyright: © 2023 Jamil 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.)

Aims: Previous studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D)., Methods: A cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations., Results: 2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49-1.34) nor LLT (aOR, 1.10; 95% CI, 0.58-2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2-2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2-2.79), statin (aOR, 1.09; 95% CI, 0.59-2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33-1.61) was associated with DPN., Conclusion: Our results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chang 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.)

Background: Studies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs., Methods: A cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively., Results: Our result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps., Conclusions: Our study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chiang 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.)

Introduction: In Taiwan, six venomous snake species with medical importance have been found; however, long-term epidemiological data of snakebite envenomation (SBE) is lacking. This study aimed to explore the epidemiology of SBE based on the distribution and use of different antivenoms in different parts of Taiwan to facilitate the development of prevention strategies and resource allocation., Methods and Results: This retrospective study was conducted using the Taiwan National Health Insurance Research Database from 2002 to 2014. A total of 12,542 patients were treated with antivenoms. The directly standardized cumulative incidence was 3.6 cases per 100,000 individuals based on the 2000 World Standard Population. The incidence of SBEs peaked in the summer (35.9%). The relative risk (RR) of male patients versus female patients was 2.5 (p < 0.0001). The RRs of patients aged 18-64 and ≥65 years versus those aged <18 years were 6.0 (p < 0.0001) and 14.3 (p < 0.0001), respectively. Furthermore, the RR of eastern Taiwan versus northern Taiwan was 6.8 (p < 0.0001). The RR of agricultural workers versus laborers was 5.5 (p < 0.0001). Compared with patients envenomed by Trimeresurus stejnegeri stejnegeri or Protobothrops mucrosquamatus, those envenomed by Naja atra or Bungarus multicinctus multicinctus were more likely to occur in central (adjusted odds ratio [aOR] = 2.6, p < 0.0001) or southern (aOR = 3.2, p < 0.0001) Taiwan, but less frequently among agricultural workers (aOR = 0.6, p < 0.0001). The overall case-fatality rate was 0.11%., Conclusions: Among Asian countries, Taiwan had low incidence and case-fatality rates of SBE. Risk factors included male gender, old age, summer season, being in eastern Taiwan, and being an agricultural worker. Differences of the epidemiological findings between snake species should be focused on when developing strategies for snakebite prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsu 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.)

Background: The prevalence of violence in acute psychiatric wards is a critical concern. According to a meta-analysis investigating violence in psychiatric inpatient units, researchers estimated that approximately 17% of inpatients commit one or more acts of violence during their stay. Inpatient violence negatively affects health-care providers and patients and may contribute to high staff turnover. Therefore, predicting which psychiatric inpatients will commit violence is of considerable clinical significance., Objective: The present study aimed to estimate the violence rate for psychiatric inpatients and establish a predictive model for violence in psychiatric inpatients., Methods: We collected the structured and unstructured data from Chinese nursing electronic medical records (EMRs) for the violence prediction. The data was obtained from the psychiatry department of a regional hospital in southern Taiwan, covering the period between January 2008 and December 2018. Several text mining and machine learning techniques were employed to analyze the data., Results: The results demonstrated that the rate of violence in psychiatric inpatients is 19.7%. The patients with violence in psychiatric wards were generally younger, had a more violent history, and were more likely to be unmarried. Furthermore, our study supported the feasibility of predicting aggressive incidents in psychiatric wards by using nursing EMRs and the proposed method can be incorporated into routine clinical practice to enable early prediction of inpatient violence., Conclusions: Our findings may provide clinicians with a new basis for judgment of the risk of violence in psychiatric wards., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu 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.)

Hyperoxia plays a significant role in the pathogenesis of lung injury, such as bronchopulmonary dysplasia (BPD), in premature infants or newborns. BPD management aims to minimize further injury, provide an optimal environment to support growth and recovery. In clinic neonatal care, we need a new therapy for BPD. Heat shock protein 70 (Hsp70) inhibit cell apoptosis and promote cell repair allowing cells to survive lethal injury. We hypothesized that Hsp70 could be used to prevent hyperoxia related BPD in the neonatal rat model through its anti-apoptotic and anti-inflammatory effects. In this study, we explored the effect of Hsp70 on hyperoxia-induced lung injury using neonatal rats. Neonatal Wistar rats were delivered naturally at full term of gestation and were then pooled and randomly assigned to several groups to receive heat stimulation (41°C for 20 min) or room temperature conditions. The Hsp70 group received recombinant Hsp70 intraperitoneally (200 μg/kg, daily). All newborn rats were placed under hyperoxic conditions (85% oxygen) for 21 days. Survival rates in both heat-hyperoxia and Hsp70-hyperoxia groups were higher than those in the hyperoxia group (p < 0.05). Both endogenous and exogenous Hsp70 could reduce early apoptosis of alveolar cells under hyperoxia. Additionally, there were less macrophage infiltration in the lung of the Hsp70 groups (p < 0.05). Heat stress, heat shock proteins, and exogenous recombinant Hsp70 significantly increased the survival rate and reduced pathological hyperoxia induced lung injuries in the development of BPD. These results suggest that treating hyperoxia-induced lung injury with Hsp70 may reduce the risk of developing BPD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee 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.)

Background: Amiodarone is commonly used during therapeutic hypothermia (TH) following cardiac arrest due to ventricular arrhythmias. However, electrophysiological changes and proarrhythmic risk after amiodarone treatment have not yet been explored in TH., Methods: Epicardial high-density bi-ventricular mapping was performed in pigs under baseline temperature (BT), TH (32-34°C), and amiodarone treatment during TH. The total activation time (TAT), conduction velocity (CV), local electrogram (LE) duration, and wavefront propagation from pre-specified segments were analyzed during sinus rhythm (SR) or right ventricular (RV) pacing (RVP), along with tissue expression of connexin 43. The vulnerability to ventricular arrhythmias was assessed., Results: Compared to BT, TH increased the global TAT, decreased the CV, and generated heterogeneous electrical substrate during SR and RVP. During TH, the CV reduction and LE duration prolongation were greater in the anterior mid RV than in the other areas, which changed the wavefront propagation in all animals. Compared to TH alone, amiodarone treatment during TH further increased the TAT and LE duration and decreased the CV. Heterogeneous conduction was partially attenuated after amiodarone treatment. After TH and amiodarone treatment, the connexin 43 expression in the anterior mid RV was lower than that in the other areas, compatible with the heterogeneous CV reduction. The animals under TH and amiodarone treatment had a higher incidence of inducible ventricular arrhythmias than those under BT or TH without amiodarone., Conclusion: Electrical heterogeneity during amiodarone treatment and TH was associated with vulnerability to ventricular arrhythmias., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin 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.)

We developed a pain management system over a 3-year period. In this project, "Towards a pain-free hospital", we combined evidence-based medicine and medical expertise to develop a series of policies. The intervention mainly included the development of standard procedures for inpatient pain management, the implementation of hospital-wide pain medicine education and training, the establishment of a dashboard system to track pain status, and regular audits and feedback. This study aimed to gain an understanding of the changes in the prevalence of pain in inpatients under the care of the pain management system. The subjects of the survey are inpatients over 20 years old, and who had been hospitalized in the general ward for at least 3 days. The patients would be excluded if they were unable to respond to the questions. We randomly selected eligible patients in the general ward. Our trained interviewers visited inpatients to complete the questionnaires designed by our pain care specialists. A total of 3,094 inpatients completed the survey from 2018 to 2020. During the three-year period, the prevalence of pain was 69.5% (2018) (reference), 63.3% (2019) (OR:0.768, p<0.01), and 60.1% (2020) (OR:0.662, p <0.001). The prevalence rates of pain in patients undergoing surgery during the 3-year period were 81.4% (2018), 74.3% (2019), and 68.8% (2020), respectively. As for care-related causes of pain, injection, change in position/chest percussion, and rehabilitation showed a decreasing trend over the 3-year period of study. Our pain management system provided immediate professional pain management, and achieved a good result in the management of acute moderate to severe pain, especially perioperative pain. Studies on pain prevalence and Pain-Free Hospitals are scarce in Asia. With the aid of the policies based on evidence-based medicine and the dashboard information system, from 2018 to 2020, the prevalence of pain has decreased year by year., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen 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.)

For the assessment of sarcopenia or other geriatric frailty syndromes, psoas major area may be one of the primary indicators. Aim to develop and cross-validate the psoas cross-sectional area estimation equation of L3-L4 of the elderly over 60 years old by bioelectrical impedance analysis (BIA). Ninety-two older adults with normal mobility were enrolled (47 females, 45 males), and were randomly divided into a modeling group (MG, n = 62) and validation group (VG, n = 30). Computed tomography (CT) was used to measure the psoas major area at the' L3-L4 lumbar vertebrae height as a predictor. Estimated variables were height (h), whole body impedance (Zwhole), whole body impedance index (h2/Zwhole, WBI), age, gender (female = 0, male = 1), and body weight (weight) by standing BIA. Relevant variables were estimated using stepwise regression analysis. Model performance was confirmed by cross-validation. BIA estimation equation for PMM obtained from the MG was: (PMMBIA = 0.183 h2/Z- 0.223 age + 4.443 gender + 5.727, r2 = 0.702, n = 62, SEE = 2.432 cm2, p < 0.001). The correlation coefficient r obtained by incorporating the VG data into the PMM equation was 0.846, and the LOA ranged from -4.55 to 4.75 cm2. PMMBIA and PMMCT both correlate highly with MG or VG with small LOA. The fast and convenient standing BIA for measuring PMM may be a promising method that is worth developing., Competing Interests: One of the authors (KCH) is employed by Starbia Meditek Co., Ltd. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials. There are no patents, products in development nor marketed products to be declared. The other authors declare no conflict of interest., (Copyright: © 2023 Chu 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.)

Objectives: Transurethral resection of prostate (TURP) and laser prostate surgery are common surgeries for benign prostate hyperplasia (BPH). We conducted an investigation using hospital database to evaluate the clinical factors associated with post-operative usage of alpha-blockers and antispasmodics., Methods: This study was conducted using retrospective clinical data from the hospital database, which contained newly diagnosed BPH patients between January 2007 and December 2012 who subsequently received prostate surgery. The study end-point was the use of alpha-blockers or antispasmodics for at least 3 months duration after 1 month of surgery. The exclusion criteria was prostate cancer diagnosed before or after the surgery, recent transurethral surgeries, history of open prostatectomy, and history of spinal cord injury. Clinical parameters, including age, body mass index, preoperative prostate specific antigen value, comorbidities, preoperative usage of alpha-blockers, anstispasmodics and 5-alpha reductase inhibitors, surgical methods, resected prostate volume ratios, and preoperative urine flow test results, were evaluated., Results: A total of 250 patients receiving prostate surgery in the database and confirmed pathologically benign were included. There was significant association between chronic kidney disease (CKD) and the usage of alpha-blockers after prostate surgery (OR = 1.93, 95% CI 1.04-3.56, p = 0.036). Postoperative antispasmodics usage was significantly associated with preoperative usage of antispasmodics (OR = 2.33, 95% CI 1.02-5.36, p = 0.046) and resected prostate volume ratio (OR = 0.12, 95% CI 0.02-0.63, p = 0.013)., Conclusions: BPH patients with underlying CKD were more likely to require alpha-blockers after surgery. In the meantime, BPH patients who required antispasmodics before surgery and who received lower prostate volume resection ratio were more liable to antispasmodics after prostate surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hsueh 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.)

Purpose: Androgen deprivation therapy (ADT) is the standard of care in advanced prostate cancer. We conducted a Taiwan National Health Insurance Research Database (NHIRD) study to evaluate the association between ADT and fracture risk in patient with prostate cancer in Taiwan., Methods: Between 2001 and 2008, data from the Taiwan NHIRD was collected. We separated newly diagnosed prostate cancer patients into four groups: the injection of gonadotropin-releasing hormone agonists and antagonists group, the orchiectomy group, the oral antiandorgens group and the radical prostatectomy only group. A non-cancer matched control group was also assigned for comparison. T tests, chi-squared tests, multivariate Cox proportional hazard regression were performed. A subsequent fracture event was defined according to the appropriate diagnosis codes (ICD9-CM 800-829) with hospitalization. Patients with fracture before their diagnosis with prostate cancer were excluded., Results: Overall, 22517 newly diagnosed patients with prostate cancer were enrolled in the study. After exclusion criteria were applied, 13321 patients were separated into the injection group (5020 subjects), the orchiectomy group (1193 subjects), the oral group (6059 subjects) and the radical prostatectomy only group (1049 subjects). The mean age of the overall study population was 74.4 years. Multi-variant analysis disclosed a significantly increased risk of fracture in the injection group, the orchiectomy group, and the oral group (hazard ratio [HR] = 1.55, 95%, confidence interval [CI] 1.36 to 1.76, p<0.001, HR = 1.95, 95%, CI 1.61 to 2.37, p<0.001, HR = 1.37, 95%, CI 1.22 to 1.53, p<0.001, respectively). In contrast, a significantly decreased fracture risk was noted in the radical prostatectomy only group (HR = 0.51, 95%, CI 0.35 to 0.74, p = 0.001). Patients receiving osteoporosis medication had a significantly decreased fracture risk (HR = 0.26, 95%, CI 0.19-0.37, p<0.001)., Conclusions: ADT is associated with an increased risk of fracture. For patients receiving long-term prostate cancer castration therapy, doctors should always keep this complication in mind and arrange proper monitoring and provide timely osteoporosis medication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen 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.)

We apply a heterogeneous graph convolution network (GCN) combined with a multi-layer perceptron (MLP) denoted by GCNMLP to explore the potential side effects of drugs. Here the SIDER, OFFSIDERS, and FAERS are used as the datasets. We integrate the drug information with similar characteristics from the datasets of known drugs and side effect networks. The heterogeneous graph networks explore the potential side effects of drugs by inferring the relationship between similar drugs and related side effects. This novel in silico method will shorten the time spent in uncovering the unseen side effects within routine drug prescriptions while highlighting the relevance of exploring drug mechanisms from well-documented drugs. In our experiments, we inquire about the drugs Vancomycin, Amlodipine, Cisplatin, and Glimepiride from a trained model, where the parameters are acquired from the dataset SIDER after training. Our results show that the performance of the GCNMLP on these three datasets is superior to the non-negative matrix factorization method (NMF) and some well-known machine learning methods with respect to various evaluation scales. Moreover, new side effects of drugs can be obtained using the GCNMLP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Chen 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.)

Monitoring and investigating temporal trends in antimicrobial data is a high priority for human and animal health authorities. Timely detection of temporal changes in antimicrobial resistance (AMR) can rely not only on monitoring and analyzing the proportion of resistant isolates based on the use of a clinical or epidemiological cut-off value, but also on more subtle changes and trends in the full distribution of minimum inhibitory concentration (MIC) values. The nature of the MIC distribution is categorical and ordinal (discrete). In this contribution, we developed a particular family of multicategory logit models for estimating and modelling MIC distributions over time. It allows the detection of a multitude of temporal trends in the full discrete distribution, without any assumption on the underlying continuous distribution for the MIC values. The experimental ranges of the serial dilution experiments may vary across laboratories and over time. The proposed categorical model allows to estimate the MIC distribution over the maximal range of the observed experiments, and allows the observed ranges to vary across labs and over time. The use and performance of the model is illustrated with two datasets on AMR in Salmonella., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Aerts 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.)

Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n  =  13) and the non-complete response group (n  =  19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Early confirmation or ruling out biliary atresia (BA) is essential for infants with delayed onset of jaundice. In the current practice, percutaneous liver biopsy and intraoperative cholangiography (IOC) remain the golden standards for diagnosis. In Taiwan, the diagnostic methods are invasive and can only be performed in selective medical centers. However, referrals from primary physicians and local pediatricians are often delayed because of lacking clinical suspicions. Ultrasounds (US) are common screening tools in local hospitals and clinics, but the pediatric hepatobiliary US particularly requires well-trained imaging personnel. The meaningful comprehension of US is highly dependent on individual experience. For screening BA through human observation on US images, the reported sensitivity and specificity were achieved by pediatric radiologists, pediatric hepatobiliary experts, or pediatric surgeons. Therefore, this research developed a tool based on deep learning models for screening BA to assist pediatric US image reading by general physicians and pediatricians., Methods: De-identified hepatobiliary US images of 180 patients from Taichung Veterans General Hospital were retrospectively collected under the approval of the Institutional Review Board. Herein, the top network models of ImageNet Large Scale Visual Recognition Competition and other network models commonly used for US image recognition were included for further study to classify US images as BA or non-BA. The performance of different network models was expressed by the confusion matrix and receiver operating characteristic curve. There were two methods proposed to solve disagreement by US image classification of a single patient. The first and second methods were the positive-dominance law and threshold law. During the study, the US images of three successive patients suspected to have BA were classified by the trained models., Results: Among all included patients contributing US images, 41 patients were diagnosed with BA by surgical intervention and 139 patients were either healthy controls or had non-BA diagnoses. In this study, a total of 1,976 original US images were enrolled. Among them, 417 and 1,559 raw images were from patients with BA and without BA, respectively. Meanwhile, ShuffleNet achieved the highest accuracy of 90.56% using the same training parameters as compared with other network models. The sensitivity and specificity were 67.83% and 96.76%, respectively. In addition, the undesired false-negative prediction was prevented by applying positive-dominance law to interpret different images of a single patient with an acceptable false-positive rate, which was 13.64%. For the three consecutive patients with delayed obstructive jaundice with IOC confirmed diagnoses, ShuffleNet achieved accurate diagnoses in two patients., Conclusion: The current study provides a screening tool for identifying possible BA by hepatobiliary US images. The method was not designed to replace liver biopsy or IOC, but to decrease human error for interpretations of US. By applying the positive-dominance law to ShuffleNet, the false-negative rate and the specificities were 0 and 86.36%, respectively. The trained deep learning models could aid physicians other than pediatric surgeons, pediatric gastroenterologists, or pediatric radiologists, to prevent misreading pediatric hepatobiliary US images. The current artificial intelligence (AI) tool is helpful for screening BA in the real world., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The purpose of the current study is to compare definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with cT1-3/N0-3 esophageal squamous cell carcinoma in survival., Methods: Records from 2008 to 2014 of 4931 patients with clinical T1-3/N0-3 esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or esophagectomy with adjuvant chemoradiotherapy were obtained from the Taiwan Cancer Registry. Univariable and multivariable analyses were performed and propensity score matching was used to minimize the bias. Overall survival was compared between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy, and also in the three different clinical stages., Results: Definitive chemoradiotherapy was performed on 4381 patients, and 550 patients received esophagectomy adjuvant chemoradiotherapy. Each group produced 456 patients for comparison after propensity score matching. The 1-year, 2-year, and 3-year overall survival rates for matched patients in with definitive chemoradiotherapy group were 57.18%, 31.92%, and 23.8%. The 1-year, 2-year, and 3-year overall survival rates for matched patients treated in the esophagectomy with adjuvant chemoradiotherapy group were 72.35%, 45.74%, and 34.04%(p<0.0001). In multivariable analysis, treatment modality was an independent prognostic factor. Esophagectomy with adjuvant chemoradiotherapy provided better survival outcome than definitive chemoradiotherapy for patients with clinical stage II/III disease. As for patients with clinical stage I disease, there was no significant survival difference between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy., Conclusions: Esophagectomy with adjuvant chemoradiotherapy provided better survival than definitive chemoradiotherapy in clinical II/III esophageal squamous cell carcinoma. However, more data are needed to conduct a convincing conclusion in clinical stage I patients., Competing Interests: The authors have declared that no competing interests exist.

Nucleotide excision repair is the primary repair mechanism that removes UV-induced DNA lesions in placentals. Unrepaired UV-induced lesions could result in mutations during DNA replication. Although the mutagenesis of pyrimidine dimers is reasonably well understood, the direct effects of replication fork progression on nucleotide excision repair are yet to be clarified. Here, we applied Damage-seq and XR-seq techniques and generated replication maps in synchronized UV-treated HeLa cells. The results suggest that ongoing replication stimulates local repair in both early and late replication domains. Additionally, it was revealed that lesions on lagging strand templates are repaired slower in late replication domains, which is probably due to the imbalanced sequence context. Asymmetric relative repair is in line with the strand bias of melanoma mutations, suggesting a role of exogenous damage, repair, and replication in mutational strand asymmetry., Competing Interests: The authors have declared that no competing interests exist.

Osteoporotic fractures have a tremendous impact on quality of life and may contribute to fatality, but half of patients may discontinue their anti-osteoporosis medication. The study aimed to investigate the factors associated with the persistence of anti-osteoporosis medication. Between June 2016 and June 2018, we recruited 1195 participants discontinuing prior anti-osteoporosis medication. Telephone interviews were conducted to discern the reasons for discontinuation. Comparisons among groups and risks of self-discontinuation were analyzed. Among 694 patients who have no records of continuing anti-osteoporosis medication, 374 (54%) self-discontinued, 64 (9.2%) discontinued due to physicians' suggestion, and 256 (36.8%) with unintended discontinuation. Among patients with self-discontinuation, 173 (46.3%) forgot to visit outpatient clinics; 92 (24.5%) discontinued because of medication-related factors; 57 (15.2%) thought the severity of osteoporosis had improved and therefore discontinued; 30 (8%) stopped due to economic burden; 22 (5.9%) were lost to follow-up because of newly diagnosed diseases other than osteoporosis. Additionally, older age, male gender, calcium supplement, teriparatide therapy and hip fractures in teriparatide users were associated with adherence to anti-osteoporosis drugs. In conclusion, our results indicate that younger age, female gender, non-use of calcium supplements, and anti-resorptive medication were independent risk factors associated with drug discontinuation. Identifying high-risk patients and providing timely health education are crucial for adherence to anti-osteoporosis medication., Competing Interests: The authors have declared that no competing interests exist.

Background: COVID-19 vaccination is essential. However, no study has reported adverse events (AEs) after ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease (ESRD) on hemodialysis (HD). This study investigated the AEs within 30-days after the first dose of ChAdOx1 nCoV19 (Oxford-AstraZeneca) in ESRD patients on HD., Methods and Findings: A total of 270 ESRD patients on HD were enrolled in this study. To determine the significance of vascular access thrombosis (VAT) post vaccination, we performed a self-controlled case study (SCCS) analysis. Of these patients, 38.5% had local AEs; local pain (29.6%), tenderness (28.9%), and induration (15.6%) were the most common. Further, 62.2% had systemic AEs; fatigue (41.1%), feverishness (20%), and lethargy (19.9%) were the most common. In addition, post-vaccination thirst affected 18.9% of the participants with female predominance. Younger age, female sex, and diabetes mellitus were risk factors for AEs. Five patients had severe AEs, including fever (n = 1), herpes zoster (HZ) reactivation (n = 1), and acute VAT (n = 3). However, the SCCS analysis revealed no association between vaccination and VAT; the incidence rate ratio (IRR)-person ratio was 0.56 (95% CI 0.13-2.33) and 0.78 (95% CI 0.20-2.93) [IRR-event ratio 0.78 (95% CI 0.15-4.10) and 1.00 (95% CI 0.20-4.93)] in the 0-3 months and 3-6 months period prior to vaccination, respectively., Conclusions: Though some ESRD patients on HD had local and systemic AEs after first-dose vaccination, the clinical significance of these symptoms was minor. Our study confirmed the safety profile of ChAdOx1 nCoV-19 in HD patients and presented a new viewpoint on vaccine-related AEs. The SCCS analysis did not find an elevated risk of VAT at 1 month following vaccination. Apart from VAT, other vaccine-related AEs, irrespective of local or systemic symptoms, had minor clinical significance on safety issues. Nonetheless, further coordinated, multi-center, or registry-based studies are needed to establish the causality., Competing Interests: The authors have declared that no competing interests exist.

Background: Retinitis pigmentosa (RP) is the most frequent retinal hereditary dystrophy and result in blindness if progresses. Several case reports have revealed the possible association between RP and primary angle-closure glaucoma (PACG). We conducted a population-based study to explore whether RP significantly increased the risk of PACG development., Methods: Using the Taiwan National Health Insurance Research Database, we enrolled patients with RP into the RP group from 2001 to 2013 and included a comparison group of 1:4 age- and sex-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) of RP for PACG after adjustment for hypertension, diabetes, hyperlipidaemia, chronic kidney disease, and lens subluxation., Results: We enrolled 6223 subjects with RP and 24892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of PACG in patients with RP was 1.61%, which was significantly higher than that in the comparison group (0.81%, p < 0.0001). According to the univariate Cox regression analysis, the hazard of PACG development was significantly greater in the RP group, with an unadjusted HR of 2.09 (95% confidence interval [CI], 1.64-2.65). The increased risk persisted after adjusting for confounders (adjusted HR = 2.18; 95% CI, 1.76-2.72)., Conclusion: This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing PACG than individuals without RP., Competing Interests: The authors have declared that no competing interests exist.

Species of colourful arboreal snails of the genus Amphidromus from Southeast Asia commonly exhibit high intraspecific variation in shell morphology. Although highly polymorphic Amphidromus specimens with different colouration have been collected at the same locality and were revealed to possess similar genital organs, there is yet no morphometric or DNA analyses of these different shell morphs. This study is the first to reveal that both striped and stripeless morphs of A. cruentatus from Laos and Vietnam belong to the same mitochondrial (COI and 16S rRNA) lineage. Although the shell colouration between the striped and stripeless morphs is markedly different, morphometric and shell outline-based analyses indicated an overall similarity in shell shape. We also revised the systematics of A. cruentatus, in which we treated similar related species, namely A. eudeli, A. fuscolabris, A. thakhekensis, A. gerberi bolovenensis, A. goldbergi, A. pengzhuoani, A. eichhorsti and A. pankowskiae as junior synonyms of A. cruentatus. Amphidromus daoae, A. anhdaoorum, A. stungtrengensis, A. yangbayensis and A. yenlinhae, which were formerly regarded as junior synonyms, are considered as species different from A. cruentatus based on shell morphology and morphometric analyses. Preliminary phylogenetic analyses also retrieved some Amphidromus species groups as distinct mitochondrial lineages., Competing Interests: The authors have declared that no competing interests exist.

Diabetes mellitus (DM) is an important risk factor in patients with end-stage renal disease (ESRD). DM is associated with the development of cardiovascular diseases, such as atrial fibrillation (AF), due to poor glycemic control. However, few studies have focused on the risk of developing ESRD among DM patients with and without AF. This study evaluated ESRD risk among DM patients with and without AF in Taiwan. Data were retrieved from one million patients randomly sampled from Taiwan's National Health Insurance Research Database, including 6,105 DM patients with AF propensity score-matched with 6,105 DM patients without AF. Both groups were followed until death, any dialysis treatment, or December 31, 2013, whichever occurred first. AF was diagnosed by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnostic code 427.31. Patients aged <20 years or diagnosed with ESRD before the index date were excluded. A Cox proportional hazard regression model was used to calculate the relative ESRD risk. Among DM patients, those with AF have more comorbidities than those without AF. We also found a 1.18-fold (95% confidence interval [CI]: 1.01-1.46) increase in ESRD risk among patients with AF compared with those without AF. In addition, DM patients with hypertension, chronic kidney disease (CKD), or higher Charlson Comorbidity Index scores also have significantly increased ESRD risks than those without these complications. A 1.39-fold (95% CI: 1.04-1.86) increase in risk was observed for patients with AF among the non-CKD group. Our findings suggest that patients with DM should be closely monitored for irregular or rapid heart rates., Competing Interests: The authors have declared that no competing interests exist.

We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10-4.88], P = 0.027 and 2.33 [95% CI 1.11-4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16-5.75], P = 0.020 and 2.44 [95% CI 1.11-5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72-4.34], P < 0.001 and 1.93 [95% CI 1.13-3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To conduct stratified analysis of the association between periodontitis exposure and the risk of female breast cancer based on age, comorbidities and level of urbanization., Methods: Using claims data taken from the 1997-2013 Taiwanese National Health Insurance Research Database (NHIRD), we identified 60,756 newly-diagnosed female breast cancer patients during the period 2003-2013 from all beneficiaries. We then randomly selected 243,024 women without breast cancer matching (1:4) for age and the year of the index date during 1997-2013 from a one million representative population acting as the control group. A conditional logistic regression analysis was used to examine the association between periodontitis (ICD-9-CM codes 523.3-4) and the risk of breast cancer, shown as an odds ratio (OR) with a 95% confidence interval (CI) after adjustments for the Charlson Comorbidity Index (CCI) and level of urbanization. Subgroup analyses were conducted based on age, CCI and level of urbanization., Results: The mean ± standard deviation age was 53 ± 14 years. After adjusting for potential confounders, the risk of female breast cancer was found to be associated with a history of periodontitis (OR, 1.12; 95% CI, 1.10-1.14). Such an association was significantly different between patients aged < 65 years (OR, 1.09; 95% CI, 1.06-1.11) and patients aged ≥ 65 years (OR, 1.23; 95% CI, 1.18-1.28; p for interaction <0.001), as well as between patients where the CCI = 0 (OR, 1.17; 95% CI, 1.15-1.20) and patients with CCI > 0 (OR, 0.99; 95% CI, 0.96-1.03; p for interaction <0.001). The highest level of urbanization was also associated with the risk of breast cancer., Conclusions: This population-based nested case-control study demonstrated that periodontitis was significantly associated with the risk of female breast cancer and such an association was modified by both age and comorbidities., Competing Interests: NO authors have competing interests.

Euryhaline teleosts can survive in environments with different salinities. Cortisol is an important hormone for acclimation to seawater (SW) of euryhaline teleosts. Osmotic stress transcription factor 1 (OSTF1), also called the transforming growth factor-beta stimulated clone 22 domain 3 (tsc22d3), was first reported in tilapia as an acute response gene and protein under hyperosmotic stress, and it is regulated by cortisol. To date, most studies on OSTF1 have focused on freshwater inhabitants, such as tilapia, medaka, and catadromous eel. The expression of OSTF1 and the correlation between OSTF1 and cortisol in marine inhabitant euryhaline teleosts, to our knowledge, remain unclear. This study reveals the changes in the expression levels of branchial OSTF1, plasma cortisol levels, and their correlation in the marine inhabitant milkfish with ambient salinities. The two sequences of milkfish TSC22D3 transcripts were classified as OSTF1a and OSTF1b. Both genes were expressed universally in all detected organs and tissues but were the most abundant in the liver. Similar gene expression levels of ostf1a and ostf1b were found in SW- and fresh water (FW)-acclimated milkfish gills, an important osmoregulatory organ. Within 12 hours of being transferred from FW to SW, the gene expression level of ostf1b increased significantly (4 folds) within 12 h, whereas the expression level of ostf1a remained constant. Moreover, cortisol levels increased rapidly after being transferred to a hyperosmotic environment. After an intraperitoneal injection of cortisol, the gene expression levels of ostf1a and ostf1b were elevated. However, under hyperosmotic stress, ostf1a gene expression remained stable. Overall, the results revealed that ostf1b was the primary gene in milkfish responding to hypertonic stress, and cortisol concentration increased after the transfer of milkfish from FW to SW. Furthermore, cortisol injection increased the expression of ostf1a and ostf1b. As a result, factors other than cortisol may activate ostf1b in milkfish gills in response to an environmental salinity challenge., Competing Interests: The authors have declared that no competing interests exist.

Enzalutamide, a nonsteroidal antiandrogen, significantly prolonged the survival of patients with metastatic castration-resistant prostate cancer (CRPC). However, patients receiving enzalutamide frequently develop drug resistance. Rooibos (Aspalathus linearis) is a shrub-like leguminous fynbos plant endemic to the Cedarberg Mountains area in South Africa. We evaluated the possibility of using a pharmaceutical-grade green rooibos extract (GRT, containing 12.78% aspalathin) to suppress the proliferation and survival of enzalutamide-resistant prostate cancer (PCa) cells. Treatment with GRT dose-dependently suppressed the proliferation, survival, and colony formation of enzalutamide-resistant C4-2 MDV3100r cells and PC-3 cells. Non-cancerous human cells were more resistant to GRT treatment. GRT suppressed the expression of proteins involved in phosphoinositide 3-kinase (PI3K)-Akt signaling, androgen receptor (AR), phospho-AR (Ser81), cyclin-dependent kinase 1 (Cdk1), c-Myc and Bcl-2 but increased the expression of apoptotic proteins. Overexpression of c-Myc antagonized the suppressive effects of GRT, while knockdown of c-Myc increased the sensitivity of PCa cells to GRT treatment. Expression level of c-Myc correlated to resistance of PCa cells to GRT treatment. Additionally, immunofluorescence microscopy demonstrated that GRT reduced the abundance of AR proteins both in nucleus and cytoplasm. Treatment with cycloheximide revealed that GRT reduced the stability of AR. GRT suppressed protein expression of AR and AR's downstream target prostate specific antigen (PSA) in C4-2 MDV3100r cells. Interestingly, we observed that AR proteins accumulate in nucleus and PSA expression is activated in the AR-positive enzalutamide-resistant PCa cells even in the absence of androgen. Our results suggested that GRT treatment suppressed the cell proliferation and survival of enzalutamide-resistant PCa cells via inhibition of c-Myc, induction of apoptosis, as well as the suppression of expression, signaling and stability of AR. GRT is a potential adjuvant therapeutic agent for enzalutamide-resistant PCa., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Androgen Deprivation Therapy (ADT) is the mainstay treatment in advanced prostate cancer. We conducted a nationwide population-based study to evaluate the association of ADT and cardiovascular diseases., Methods: Between 2005 and 2009, patient data from the National Health Insurance database were obtained. We divided newly diagnosed prostate cancer patients into four groups, injection of gonadotropin-releasing hormone agonists and antagonists, oral antiandrogens, orchiectomy and radical prostatectomy only. Another matched non-cancerous control group was also assigned for comparison purposes. Study outcomes were newly onset Cardiovascular Diseases (CVD) and hospital admissions. Multi-variant Cox proportional regression analysis and the Kaplan-Meier method for cumulative incidence were performed., Results: A total of 17,147 newly diagnosed prostate cancer patients were found. After exclusion criteria was considered, the 2,565 remaining patients were then divided into 1,088 subjects in the injection group, 286 in the orchiectomy group, 812 in the oral group and 379 in the radical prostatectomy only group. The mean age of all the patients was 71.2 years. Multi-variant analysis showed a significantly increased risk of CVD in the injection group, orchiectomy group, oral group and radical prostatectomy group (HR = 2.94, 95% CI 2.51 to 3.45, p<0.001, HR = 3.43, 95% CI 2.69 to 4.36, p<0.001, HR = 2.87, 95% CI 2.42 to 3.39, p<0.001, HR = 1.93, 95% CI 1.5 to 2.48, p<0.001, respectively). A time dependent increased risk of CVD was also observed amongst the study groups (p<0.001)., Conclusions: ADT is associated with an increased risk of CVD. For long-term prostate cancer castration therapy, doctors should be aware of this complication and arrange for proper management., Competing Interests: The authors have declared that no competing interests exist.

Information on the insecticide resistance profiles of Aedes aegypti in Indonesia is fragmentary because of the lack of wide-area insecticide resistance surveillance. We collected Ae. aegypti from 32 districts and regencies in 27 Indonesian provinces and used WHO bioassays to evaluate their resistance to deltamethrin, permethrin, bendiocarb, and pirimiphos-methyl. To determine the possible resistance mechanisms of Ae. aegypti, synergism tests were conducted using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioates (DEF). The Ae. aegypti from all locations exhibited various levels of resistance to pyrethroids. Their resistance ratio (RR50) to permethrin and deltamethrin ranged from 4.08× to 127× and from 4.37× to 72.20×, respectively. In contrast with the findings of other studies, most strains from the highly urbanized cities on the island of Java (i.e., Banten, Jakarta, Bandung, Semarang, Yogyakarta, and Surabaya) exhibited low to moderate resistance to pyrethroids. By contrast, the strains collected from the less populated Kalimantan region exhibited very high resistance to pyrethroids. The possible reasons are discussed herein. Low levels of resistance to bendiocarb (RR50, 1.24-6.46×) and pirimiphos-methyl (RR50, 1.01-2.70×) were observed in all tested strains, regardless of locality. PBO and DEF synergists significantly increased the susceptibility of Ae. aegypti to permethrin and deltamethrin and reduced their resistance ratio to less than 16×. The synergism tests suggested the major involvement of cytochrome P450 monooxygenases and esterases in conferring pyrethroid resistance. On the basis of our results, we proposed a 6-month rotation of insecticides (deltamethrin + synergists ➝ bendiocarb ➝ permethrin + synergists ➝ pirimiphos-methyl) and the use of an insecticide mixture containing pyrethroid and pyrimiphos-methyl to control Ae. aegypti populations and overcome the challenge of widespread Ae. aegypti resistance to pyrethroid in Indonesia., Competing Interests: The authors have declared that no competing interests exist.

Potential association between oral levofloxacin use and hypoglycemic emergency (HE) have been established. However, a large epidemiological study is required to verify this observation. This study aimed to determine if use of oral levofloxacin increased the risk of HE. The nationwide database between 1999 and 2013, including 1.6 million patients with type 2 diabetes (T2D), was used to conduct a nested case-control study. Cases and controls comprised of patients with and without HE, respectively. To avoid indication bias the control subjects were chosen through propensity score matching with cases in a 10-fold ratio. T2D severity was classified based on the adjusted diabetic complication severity index score. 26,695 and 266,950 matched patients with T2D, were finally used as cases and controls, respectively, for the analysis. Multivariate logistic regression analysis showed that antibiotic use was associated with an increased risk for HE (adjusted odds ratio (aOR) = 6.08, 95% confidence interval (95% CI): 5.79-6.38). When compared with antibiotic non-users, those who used fluoroquinolones and sulfonamides displayed the highest (aOR = 12.05, 95% CI: 10.66-13.61) and second highest (aOR = 7.20, 95% CI: 6.29-8.24) risks of HE, respectively. The associated risk for HE was significantly higher with levofloxacin than that with cephalosporins (aOR = 5.13, 95% CI: 2.28-11.52) and penicillin (aOR = 9.40, 95% CI: 2.25-39.24). In the joint effect analyses, the risk for HE increased with the combination of levofloxacin with insulin (aOR = 8.42, 95% CI: 1.91-37.00) or sulfonylurea (aOR = 3.56, 95% CI: 1.12-11.33). Use of oral levofloxacin, compared to that of other antibiotics, was found to be significantly associated with HE in T2D patients. Clinicians should exercise caution while prescribing levofloxacin, especially when combined with insulin or sulfonylurea., Competing Interests: The authors have declared that no competing interests exist.

Heritage managers often reuse heritage sites to attract tourists and conserve the sites. Not all adaptive heritage reuses achieve sustainable development. Biophilia is an innate, biological tendency to be close to natural and cultural elements, which may be a critical motivation for achieving sustainable heritage management. Past studies used qualitative and quantitative methods to extract participants' pull and push motivations toward heritage tourism and captured the six motivations of the biophilia framework that should be confirmed: heritage architecture; art activity; wide nature; regional attraction; recreational benefits; and long-term values. The purpose of this study was to conduct a confirmatory factor analysis to test the biophilia framework for understanding biophilic heritage tourism. A questionnaire with 18 items of heritage tourism motivation was used to explore the purpose of this study. A total of 193 valid questionnaires were obtained. Confirmatory factor analysis was used to examine the six motivations of the biophilia framework. The results indicated that heritage tourism motivation consisted of a second-order six-factor structure with high validity and reliability. These six dimensions reflected the biophilic requirements and provided a biophilic planning principle to achieve sustainable heritage management to satisfy the needs of the participants., Competing Interests: The authors have declared that no competing interests exist.

A wide range of phytobiotic feed additives are available on the market claiming to have beneficial effects on the growth of the host animal and to promote the development of a balanced microflora. The present study investigated the effects of the phytobiotic-prebiotic mixture of curcumin, wheat germ, and chicory on the growth performance and on the intestinal microflora composition of weaning piglets. Post weaning diarrhea causes significant losses for the producers, most commonly it is prevented by feeding high doses of zinc oxide (ZnO). The effect of a phytobiotic-prebiotic feed additive (1 kg T-1) was compared to a positive control (3.1 kg T-1 ZnO) and to a negative control (no feed supplement) in an in vivo animal trial. There was no significant difference in the final body weight and average daily gain of the trial and positive control groups, and both groups showed significantly (P<0.05) better results than the negative control. The feed conversion ratio of the phytobiotic-prebiotic supplemented group was significantly improved (P<0.05) compared to both controls. Both phytobiotic-prebiotic mixture and ZnO were able to significantly reduce (P<0.05) the amount of coliforms after weaning, even though ZnO reduced the amount of coliforms more efficiently than the trial feed additive, it also reduced the amount of potentially beneficial bacteria. Metagenomic data also corroborated the above conclusion. In the trial and positive control groups, the relative abundance of Enterobacteriaceae decreased by 85 and 88% between 3 weeks and 6 weeks of age, while in the negative control group a slight increase occurred. Lactobacillaceae were more abundant in the trial group (29.98%) than in the positive (8.67%) or in the negative (22.45%) control groups at 6 weeks of age. In summary, this study demonstrated that a phytobiotic-prebiotic feed additive may be a real alternative to ZnO for the prevention of post weaning diarrhea and promote the development of a balanced gut system., Competing Interests: The authors have declared that no competing interests exist.