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BackgroundDisaster-related psychiatric disorders (DRPD) present a significant challenge to mental health professionals, yet there is a notable lack of emphasis on the preparedness of psychiatrists in managing these conditions within post-graduate medical education.MethodsThis study utilized a questionnaire to collect data from psychiatrists, focusing on their prior involvement in managing DRPD, perceived competence, medication preferences, and factors influencing their experiences in handling such disorders. Analysis included distribution and ranking of variables, alongside cross-analysis examining associations between demographic factors (age, gender, hospital levels, years of practice, board certification) and treatment experiences, as well as readiness for in-hospital or outside-hospital mobilization in DRPD management.ResultsOne hundred and three Taiwanese psychiatrists participated in the study, with the majority reporting involvement in managing DRPD (71.8%), particularly in post-traumatic stress disorder (PTSD) and depression. Antidepressants, specifically serotonin selective reuptake inhibitors, were commonly preferred for DRPD treatment, including PTSD and depression. Psychiatrists aged over 40, with more than 10 years of practice, and hold the board-certified status, showed greater experiences for outside- or inside- the hospital mobilization in DRPD management.ConclusionFindings suggest that within post-graduate medical education, Taiwanese psychiatrists demonstrate significant experience, willingness, and capacity to effectively manage DRPD. However, there is a need to integrate comprehensive training on disaster psychiatry into post-graduate psychiatric education programs to further enhance preparedness and optimize outcomes in managing these challenging conditions.

Abstract Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03–1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81–1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.

Objectives: The study aimed to demonstrate the performance of anal atresia ultrasound screening in the second trimester and to describe associated experiences in a primary care fetal medicine clinic. Materials and methods: We retrospectively analyzed the medical records of fetuses who underwent a second-trimester screening at the Taiji clinic between November 2019 and May 2022. Fisher's exact test was conducted to investigate potential risk factors. Results: There were 28 459 fetuses screened in our clinic during the study period; eventually, 6 cases were diagnosed with anal atresia after birth. The incidence of anal atresia in our sample was 2.11 in 10 000. Based on our findings, potential risk factors significantly associated with anal atresia included: multiple pregnancies (p-value = 0.0185) and in-vitro fertilization (p-value = 0.038). Half of the anal atresia cases were associated with abnormalities affecting other organ systems, most frequently the genitourinary system (66.7%) and cardiovascular system (66.7%), especially persistent left superior vena cava (2 cases). Conclusion: Anal atresia is a malformation that requires extensive care; the clinical management after the prenatal discovery of its signs should include testing for chromosomal abnormalities and close monitoring of the amniotic fluid volume. Therefore, prenatal ultrasound screening for anal atresia in the second trimester is critical, particularly in the cases of multiple and IVF pregnancies, and multiple abnormalities. The fetuses with ultrasound signs of anal atresia should be followed at a later gestational period and referred to a specialized institution for postnatal management planning and parental counseling.

Objective: We present prenatal ultrasound images of two high anal atresia cases. The main screening tool used in our clinic is the “target sign” in the tangential view of the fetal perineum. In the current report, we discuss some challenges in the existing screening practices. Case report: Case 1: A 28-year-old woman (gravida 1, para 0) with a twin pregnancy underwent ultrasound screening at 21 weeks of gestation when an absent “target sign” in twin A was discovered. At the same time, we were able to present evidence that if the wrong plane was visualized, other structures could be mistaken as the “target sign”. Eventually, high-type anal atresia was confirmed postnatally in Twin A. Case 2: A 29-year-old woman (gravida 1, para 0) came to our clinic for routine screening at 23 weeks of gestation. In the standard tangential view at the level of the perineum, a low-high concentric circle structure resembling a “target sign” was visualized during a prenatal scan. However, anal atresia was discovered postnatally. A retrospective review of prenatal images revealed discrepancies from the typical “target sign”. Conclusion: High-type anal atresia may present as a pseudo “target sign” on prenatal ultrasound. Visualization of a “target sign” on fetal ultrasound does not always exclude the diagnosis of anal atresia. It is crucial to evaluate the size, shape, level, and position of the “target sign”. The appearance of the bilateral hyperechoic perianal tissue is a hint for the screening of anal atresia.

Abstract Background Proton pump inhibitors (PPIs) are common and widely used for gastrointestinal-related disorders. Lansoprazole is one of PPIs with potential benefits of anti-inflammation, reduced oxidative stress, and anti-diabetes. The aims of this study are to determine whether lansoprazole imparts differential risk of type 2 diabetes as compared with other PPIs. Methods A population-based retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients who received lansoprazole more than 90 days and without records of use of other PPIs between January 1, 2000 and December 31, 2005 (the exposure period) were considered as the exposed cohort (n = 1668). In comparison, patients who received other PPIs more than 90 days and without use of lansoprazole in the exposure period were treated as the comparison cohort (n = 3336).The primary outcome was the new-onset of type 2 diabetes mellitus (T2DM). The association between use of lansoprazole and the risk of T2DM was determined by hazard ratios (HRs) and 95% confidence intervals (CIs) derived from multivariable Cox proportional hazards models. Results The lansoprazole cohort showed a significantly reduced risk of T2DM with an adjusted HR of 0.65 (95% CI 0.56–0.76). Interestingly, the inverse association between use of lansoprazole and risk of T2DM was observed in both genders and in various age groups. Conclusion The present study findings suggest that lansoprazole was associated with a reduced risk of T2DM compared with other PPIs. Further studies are needed to determine the clinical implications of the present study.

Objective: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. Methods: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000–2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan–Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Results: Kaplan–Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10–3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04–3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08–4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51–6.14). Conclusion: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Background: Homicidal offenders with schizophrenia who went through psychiatric evaluations are a small but significant group during a criminal appeal. Aim: Our aims are to explore whether the types of crime, such as homicide or not, would be related to the verdicts for the alleged offenders with schizophrenia in Taiwan. Our hypothesis was that homicide cases, rather than other alleged offenses, would be more likely to be regarded as no responsibility (legal insanity) or diminished responsibility for those defendants in the forensic psychiatric evaluation opinions or the court verdicts. Methods: A retrospective comparison of the homicide offenders with the nonhomicide offenders with schizophrenia, registered between December 2000 and November 2009, was conducted in the web-based, national, open-access court verdict databank. Results: There were 33 (3.4%) in 9691 criminal homicide offenders that had a diagnosis of schizophrenia. There were 33 in the homicide group and 22 in the nonhomicide group. Among these defendants in the homicide group, 3 (9.1%) were regarded as legal insanity, and 21 (63.6%) were regarded as diminished responsibility in comparison to the zero (0%) as legal insanity and nine (40.9%) as diminished responsibility in the nonhomicide group (P = 0.029). In addition, the group with multiple evaluations tended to receive forensic psychiatric opinions as legal insanity (N = 3; 33.3%), and the group with single evaluation tended to receive forensic psychiatric opinions as diminished responsibility (N = 16; 66.67%) (P = 0.017). The group with multiple evaluations tended to be ruled as legal insanity in the court (P = 0.001). Conclusion: Homicide cases would be more likely to be regarded as legal insanity or diminished responsibility for the defendants with schizophrenia in the forensic psychiatric evaluation opinions or the court verdicts.

Abstract Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.

Abstract Background To investigate the risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, self-inflicted injury, and mortality after adult violence from 2000 to 2015 in Taiwan. Methods This study used data from National Health Insurance Research Database (NHIRD) on outpatient, emergency, and inpatient visits for two million people enrolled in the National Health Insurance (NHI) from 2000 to 2015. The case study defined ICD-9 diagnosis code N code 995.8 (abused adult) or E code E960-E969 (homicide and intentional injury of another). It analyzed first-time violence in adults aged 18–64 years (study group). 1:4 ratio was matched with injury and non-violent patients (control group). The paired variables were sex, age (± 1 year), pre-exposure to the Charlson comorbidity index, and year of medical treatment. Statistical analysis was conducted using SAS 9.4 and Cox regression for data analysis. Results In total, 8,726 individuals experienced violence (case group) while34,904 did not experienced violence (control group) over 15 years. The prevalence of poor prognosis among victims of violence was 25.4/104, 31.3/104, 10.5/10,4 and 104.6/104 for schizophrenic disorders, psychotic disorders, suicide or self-inflicted injury and mortality, respectively. Among adults, the risks of suicide or self-inflicted injury, schizophrenic disorders, psychotic disorders, and mortality after exposure to violence (average 9 years) were 6.87-, 5.63-, 4.10-, and 2.50-times (p

Objective: We aimed to identify the genetic cause of one hydrops fetalis with Noonan syndrome (NS) manifestations including increased nuchal translucency (INT) and ascites through prenatal whole exome sequencing (WES). Case report: The case is a gestational age (GA) 18 fetus of two healthy parents with a normal child. We proceeded the genomic DNA from both fetus amniotic cells and parents to WES and identified a RIT1 mutation (c.268A>G) as the pathogenic cause of the hydrops fetalis by automatic prioritization algorithm after array-comparative genomic hybridization results showing negative. Conclusion: Mutations in RIT1 have been reported as the causes for different fetus structural abnormities in the recent years. This case contributes to the summary delineations of the prenatal NS phenotypes related to RIT1 mutation. In addition, the fast WES application, in this case, has demonstrated its advantage in prenatal disorder diagnosis when conventional karyotyping or chromosomal microarray testing result is negative.

Abstract Background The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB. Methods This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67). Results The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan–Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups. Conclusions The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

Background: Liver resection (LR) is considered the main therapeutic strategy for small hepatocellular carcinomas (HCCs) (

BackgroundToxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii (T. gondii), and may cause miscarriage and birth defects during pregnancy. This study aimed to assess the epidemiological features, epidemic trends, and correlations between the before number of confirmed toxoplasmosis cases in Taiwan from 2007 to 2020 in gender, age, season, and residential area, and hypothesized the environmental and climate factors also might affect the disease in Taiwan.MethodsThis study reviewed publicly available annual summary data on reported toxoplasmosis cases in the Taiwan Centers for Diseases Control (TCDC) between 2007 and 2020.ResultsThis study collected 150 confirmed domestic and nine patients with imported toxoplasmosis. There was an increasing trend in the incidence of toxoplasmosis, 0.09-0.89 cases per 1,000,000 people, peaking in 2017. The average annual toxoplasmosis incidence was 4.4, 13, and 18 during 2007-2011, 2012-2016, and 2017-2020, respectively. Comparing sex, age, season, and place of residence, the incidence rate was highest in male, 20-39 years-old patients, summer, and the eastern region, with 1.02, 1.72, 0.38, and 3.63 cases per million population, respectively. Additionally, comparing the distribution of cases by age group in Taiwan, there were significant differences between 40-59 years-old in the northern region (odds ratio (OR) = 0.343, 95% confidence interval (CI) = 0.167-0.705, p = 0.004) and 40-59 years-old in the southern region (OR = 4.488, and 95% CI = 2.149-9.374, p< 0.001), respectively. Linear regression analysis also showed that PM (particulate matter) 2.5 (μg/m3) concentration was positively associated with toxoplasmosis (β = 0.095, p = 0.037). CO concentration was negatively correlated with toxoplasmosis (β = -14.001, p = 0.021).ConclusionsThis study is the first to report domestic and confirmed cases of imported toxoplasmosis from the surveillance data of the TCDC between 2007 and 2020. It identified that residence and age were associated with an increased risk of toxoplasmosis in Taiwan. This study confirmed that toxoplasmosis remains a prevalent infectious disease in Taiwan, its epidemic is gradually increasing and becoming more severe. These findings might be useful for policy-makers and clinical experts to direct prevention and control activities to patients with T. gondii, which causes the most severe illness and greatest burden to Taiwanese people.

Objective: To compare the prevalence of congenital fetal anomalies or intrauterine fetal growth restriction (IUGR) diagnosed prenatally between two in-vitro fertilization (IVF) methods—fresh embryo transfer (ET) and frozen embryo transfer (FET). Materials and methods: We retrospectively reviewed medical records of patients that had conceived via IVF, and had a fetal anatomical scan performed at Taiji Clinic between 2015 and 2019. The prevalence of fetal anomalies or IUGR between both IVF methods were compared. Prevalence of congenital anomalies or IUGR by maternal age and embryo transfer type were compared by means of Chi-square analysis. Using multivariate logistic regression, we investigated factors that might be associated with higher rates of fetal anomalies or IUGR, such as parity and number of embryos transferred. Results: A total of 2441 cases were selected (ET: n = 627 and FET: n = 1814). There was non-significant difference in the prevalence of fetal anomalies or IUGR between ET and FET groups (6.4% vs. 5.5%, p = 0.39). However, among women younger than 34 years of age, prevalence of fetal anomalies or IUGR was significantly higher in ET group (4.6% vs. 9.9%, p = 0.03). Conclusions: Our findings suggest an age-specific effect of IVF method on the rate of fetal anomalies or IUGR and may provide useful information for physicians and infertile couples to optimize their IVF treatment plans and improve birth outcomes.

Background: Better labial closure strength (LCS) may improve eating, swallowing, and quality of life. Patakara is an efficient device to enhance lip strength. In this study, we analyzed differences in LCS and quality of life between before and after training with Patakara in people with intellectual disabilities. Methods: We recruited twenty participants with intellectual disabilities who had poor eating status, lower LCS, or poor oral hygiene status. These participants performed training using Patakara three times a day (3 min each time for five times/week) for 3 months. Oral examination was performed twice, and structural questionnaires and lip force measurements were performed five times. Cheek temperature was also recorded. Results: The maximum value of lip force showed a significant increase during the 3-month training period. In addition, the proportion of participants who kept food in the mouth for a long time when eating significantly reduced. Moreover, the physical functioning and mental health scores of SF-36 showed a significant increase. Conclusions: Patakara training effectively increased lip muscle strength and improved dietary function. Nevertheless, further studies with a longer training duration to investigate the long-term effects of Patakara training are needed.

Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis.

This paper introduces a nonlinear, magnetically charged, singularity-free black hole model. The Ricci scalar, Kretschmann scalar, horizon, energy conditions, and Hawking radiation corresponding to the singularity-free metric are presented, and the asymptotic behavior and quantum correction of the model are examined. The model was constructed by coupling a mass function with the regular black hole solution under nonlinear electrodynamics in general relativity. Aside from resolving the problem of singularities in Einstein’s theory of general relativity, the model asymptotically meets the quantum correction under an effective field theory. This obviates the need for additional correction terms; in this regard, the model outperforms the black hole models developed by Bardeen and Hayward. Regarding the nonlinear magnetic monopole source of the gravitational field of the black hole, the energy–momentum tensors fulfill weak energy conditions. The model constitutes a novel, spherically symmetric solution to regular black holes.

Sepsis causes platelet activation, systemic inflammation, organ dysfunction, and mortality. Endotoxins play an important role in the manifestation of the symptoms of septic shock. As fish oil exert well known anti-inflammatory effects and sunflower seed oil exert less anti-inflammatory properties than fish oil, both oils are widely used. We aimed to test the hypothesis that dietary supplementation of these two oils before endotoxemia modulates the consequences of illness. Nine- to ten-week-old male Wistar rats (N = 55) were divided into four groups: group A (N = 6), control; group B (N = 17), saline + lipopolysaccharide (endotoxin); group C (N = 17), fish oil + lipopolysaccharide; and group D (N = 15), sunflower seed oil + lipopolysaccharide. After 28 days of feeding the designated diet, the rats in all groups were intraperitoneally injected with lipopolysaccharide. After 24 h, survival rate, endotoxemia severity, levels of platelet activation markers, organ function and biochemical variables were evaluated. Platelet-leukocyte aggregation was significantly high in group C (p = 0.005), and platelet-monocyte aggregation was significantly high in groups C (p = 0.003) and D (p = 0.016) than in group B. The survival rate, endotoxemia severity, expression of platelet P-selectin, CD40L, and TLR4, pulmonary function, renal function, liver function, or biochemical variables did not significantly differ among groups B, C, and D. Instead of an anti-inflammatory effect, the dietary supplementation of fish and sunflower seed oils exerted a pro-inflammatory effect, especially via platelet-monocyte aggregation, suggesting a rebound effect of the dietary supplementation of the oils. The oils did not affect other inflammatory platelet markers or improve the outcome of endotoxemic rats. However, further studies are required to understand the underlying mechanisms of such effects and to elaborate the clinical significance of these findings.

Abstract Background Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson’s disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. Methods A population-based matched cohort study was performed using data from the 2000–2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. Results This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p

Abstract Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem‐like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient‐derived malignant glioblastoma cells with the PTV95 (PTV coverage of more than 95%) program (GBM‐MG1 cells) and the Non‐PTV95 (poor PTV coverage of less than 95%) program (GBM‐MG2 cells). The clinical results of PTV95 and Non‐PTV95 showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM‐MG1 (PTV95 program) cells exhibited higher radioresistance than GBM‐MG2 (Non‐PTV95 program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM‐MG1 (PTV95 program) cells. GBM patients receiving RT with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program.

Background/purpose: There is conflicting data regarding the utility of measuring apolipoproteins in addition to traditional lipid measures in risk assessment of cardiometabolic diseases. The aim of this study was to determine whether apolipoprotein measurements can improve the ability to predict the future development of type 2 diabetes beyond what is possible based on traditional type 2 diabetes risk factors and clinical routine lipid measurements. Methods: A total of 4,223 Chinese adults without diabetes were followed for a mean duration of 5.42 years. The hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to analyze the longitudinal associations of apolipoprotein B (apo B), apolipoprotein A-I (apo A-I), and the apo B/apo A-I ratio with the risk of type 2 diabetes. Further, the analysis of the area under receiver operating characteristics curves (AUC) was performed to test the predictive value of apolipoprotein measurements. Results: After adjusting for potential confounders, the HRs of diabetes consistently showed an increasing trend across both the apo B and the apo B/apo A-I ratio quartiles (p for trend = 0.004). In analyses of AUC, the predictive ability for type 2 diabetes risk for the apo B and the apo B/apo A-I ratio was superior to that of routine lipid and lipoprotein measurements. Conclusion: Apolipoprotein measurements significantly predict diabetes risk in an Asian population. Furthermore, the predictive ability of apo B alone to detect diabetes was comparable with that of the apo B/apo A-I ratio and better than the routine lipid measurements. Keywords: Apolipoproteins, Cohort study, Lipid parameters, Type 2 diabetes

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19). However, the long-term health consequences of COVID-19 are not fully understood. We aimed to determine the long-term lung pathology and blood chemistry changes in Syrian hamsters infected with SARS-CoV-2. Syrian hamsters (Mesocricetus auratus) were inoculated with 105 PFU of SARS-CoV-2, and changes post-infection (pi) were observed for 20 days. On days 5 and 20 pi, the lungs were harvested and processed for pathology and viral load count. Multiple blood samples were collected every 3 to 5 days to observe dynamic changes in blood chemistry. Infected hamsters showed consistent weight loss until day 7 pi At day 5 pi, histopathology of the lungs showed moderate to severe inflammation and the virus could be detected. These results indicate that SARS-CoV-2 has an acute onset and recovery course in the hamster infection model. During the acute onset, blood triglyceride levels increased significantly at day 3 pi During the recovery course, uric acid and low-density lipoprotein levels increased significantly, but the total protein and albumin levels decreased. Together, our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. IMPORTANCE COVID-19 is now considered a multiorgan disease with a wide range of manifestations. There are increasing reports of persistent and long-term effects after acute COVID-19, but the long-term health consequences of COVID-19 are not fully understood. This study reported for the first time the use of blood samples collected continuously in a SARS-CoV-2-infected hamster model, which provides more information about the dynamic changes in blood biochemistry during the acute and recovery phases of SARS-CoV-2 infection. Our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. The study may be used by several researchers and clinicians, especially those who are studying potential treatments for patients with post-acute COVID-19 syndrome.

Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000–2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02–3.62). Furthermore, the significant HPV–CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar’s test were used for group comparisons, and Kaplan–Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38–7.73 for RFS, HR = 2.35 and 95% CI = 1.17–4.71 for PFS, HR = 4.32 and 95% CI = 1.8–10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07–5.08 for RFS, HR = 2.42 and 95% CI = 1.19–4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Background Heart failure (HF) is a major health problem worldwide because of its high morbidity and mortality. Recently, the role of the microvasculature in HF has gained more attention. Age‐related macular degeneration (AMD) is manifested through geographic atrophy or the development of neovascularization. However, there are limited data on investigations about the association between AMD and HF. The purpose of this study was to examine the association of AMD with the risk of HF in a large population‐based cohort of men and women. Methods and Results A nested case‐control study using Taiwan’s National Health Insurance Research Database was conducted between 2000 and 2012. Newly diagnosed heart failure cases (n=13 721) and matched controls (n=54 884) in the database were recruited. Patients who had ≥2 clinical visits with a diagnosis of AMD at least 1 year before the diagnosis of HF were identified as patients with AMD. Conditional logistic regressions were performed to calculate odds ratios and 95% CIs to assess the association between AMD and risk of HF. AMD was associated with a 1.58‐fold increased risk of HF (95% CI, 1.16–1.87) (P

Abstract Background Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort. Methods We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan’s National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan–Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients. Results The Kaplan–Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P

Background: Colonic angiodysplasia (AGD) is a common cause of gastrointestinal bleeding. However, information on the characteristics and prevalence of colonic AGD is limited. We determined the clinical features of and risk factors for active bleeding in colonic AGD in a Taiwanese population. Methods: From February 2007 to December 2016, 13,047 patients undergoing 16,760 colonoscopies at the Tri-Service General Hospital were included in this study. Eighty-four patients were diagnosed with AGD. We conducted a retrospective study by analyzing the medical records of these patients. The clinical features and endoscopic findings were evaluated. Furthermore, we distinguished colonic AGD into bleeding and non-bleeding types and identified the risk factors for bleeding in colonic AGD. Results: In our study, the prevalence of colonic AGD was 0.6% among all patients who received colonoscopy. Among patients with colonic AGD, we found that many were aged; in all, 58.3% of patients with colonic AGD were older than 65 years. More than half of the patients had hypertensive cardiovascular disease (53.6%) and the AGD lesions were predominantly located in the left-sided colon (41.7%). We analyzed several factors to identify those associated with bleeding colonic AGD. Our results indicated that age (p

Background: The aim of this study is to investigate the validity of the coin-in-the-hand (CIH) test with other neuropsychological tests for the detection of malingering in the memory. Materials and Methods: A simulated scenario design was developed to investigate the validity of the CIH test, entitled the Test of Memory Malingering (TOMM), associated with the Clinical Dementia Rating, the cognitive abilities screening instrument, the Mini-Mental Status Examination, and the WHO Quality of Life-BREF. The performances of the patients with dementia (n = 25) were compared with one group of normal controls (n = 9), and another group instructed to simulate malingering dementia (n = 19). Results: The CIH test demonstrated good validity and displayed a better sensitivity and a positive likelihood ratio than the TOMM, while patients with dementia could provide, on average, more than nine correct answers, in comparison to only more than six correct answers in the simulated malingering group. The optimal cutoff score of the CIH test is ≤8. Conclusions: This pilot study showed that the CIH test is a quick and practical test for detecting malingering in the memory.

Platelets play a role in transfusion reaction via reactive oxygen species (ROS) generation and CD40 ligand (CD40L) expression. In this study, we aimed to test the hypothesis that the mixing of packed red blood cells (pRBCs) and washed platelets has a causal effect on platelet ROS generation and CD40L expression. Thus, a better understanding of this causality relationship may help interrupt the chain of events and avoid an uncontrollable transfusion reaction. We simulated transfusion in vitro by mixing pRBCs and washed platelets. Donor cross-matched stored pRBCs) from our blood bank and recipient whole blood from patients undergoing coronary artery bypass graft surgery prepared into washed platelets were used. Briefly, donor pRBCs were added to washed recipient platelets to form 1%, 5%, or 10% (v/v) mixtures. The mixed blood sample was used to determine platelet ROS generation (dichlorofluorescein fluorescence levels) and CD40L expression. The effect of antioxidants (20 mM glutamine and 20 mM dipeptiven) on ROS generation and CD40L expression was also evaluated. Platelet ROS generation was not significantly associated with the mixing of pRBCs and washed platelets (p = 0.755), glutamine treatment (p = 0.800), or dipeptiven treatment (p = 0.711). The expression of CD40L by platelets increased significantly (p < 0.001), and no significant difference was noted after treatment with glutamine (p = 0.560) or dipeptiven (p = 0.618). We observed that the mixing pRBCs and washed platelets had no effect via ROS, whereas CD40L could directly induce transfusion reactions. Furthermore, platelets did not causally express ROS or CD40L after being mixed with pRBCs. Although antioxidants are more accessible than anti-CD40L antibodies, platelet ROS may not serve as a therapeutic target for antioxidants. Nevertheless, CD40L expression may be a valuable therapeutic target for managing transfusion reactions.

Background and Objectives: Amebiasis remains an important public health problem worldwide, and immigration and increased international travel have affected incident disease cases. This study assesses the prevalence of Entamoeba histolytica in Taiwan between 2011 and 2020 by analyzing data from surveillance programs conducted by the Centers for Disease Control of Taiwan (TCDC) on laboratory-confirmed cases. Materials and Methods: The E. histolytica infection-related data reported to the National Infectious Diseases Statistics System at the TCDC from 1 January 2011 to 31 December 2020 were collected, including age, gender, place of residence, and the geographic season of exposure for each case. Results: In total, 3066 cases with E. histolytica infections were included in our analysis. Among them, 1735 (57%) cases were imported, and 1331 (43%) were locally acquired. The average annual incidence rate of E. histolytica infections in Taiwan between 2011 and 2020 was 10.6 and 16.1 per 1,000,000 patients. There were statistical differences in gender, age group, and place of residence (p < 0.001) by the source distribution of cases. Also, these differences were found every year (p < 0.05). There were statistical differences in gender and age group (p < 0.001) by place of residence (p < 0.001). The only difference between the distribution of cases and age group was in gender (p < 0.001). Eight patients with amebiasis died, and the fatality rate was 0.3% (8/3066), of whom 75% (6/8) were male, and 75% (6/8) were over 45 years old. This study demonstrates that multiple linear regression analysis shows positive associations between NO2 concentration and amebiasis cases (B value = 2.569, p = 0.019), O3 concentration and amebiasis cases (B value = 0.294, p = 0.008), and temperature and amebiasis cases (B value = 1.096, p = 0.046). Conclusions: This study is the first report of confirmed E. histolytica cases from TCDC surveillance data between 2011 and 2020. This study showed the importance of long periods, air pollutants, and geographically comprehensive analysis for estimating the effect of amebiasis transmission in Taiwan’s populations.

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.

This study aimed to determine the rates of overall survival and recurrence-free survival among elderly Taiwanese women (>65 years old) according to breast cancer subtype and lymph node status. We identified 554 eligible patients who were >65 years old and had been treated based on international recommendations at our center between June 2005 and June 2015. Patients with the luminal A subtype had the highest rates of overall survival (90.6%) and recurrence-free survival (97.0%), while the lowest overall survival rate was observed in those with the triple-negative subtype (81.3%) and the lowest recurrence-free survival rate was observed in those with the luminal B subtype (84.0%). Multivariate Cox proportional hazard analysis, using the luminal A subtype as the reference, revealed significant differences in recurrence-free survival among luminal B patients according to lymph node status. Among elderly Taiwanese women with breast cancer, the breast cancer subtype might help predict survival outcomes. The luminal B subtype was associated with poor recurrence-free survival, and lymph node status was useful for predicting recurrence-free survival in this subset of patients.

Clusters of acute upper respiratory tract infections are mainly caused by type A or B influenza virus. Numerous factors modify the risk of upper respiratory tract infection (URTI) cluster transmission. The purpose of this study was to investigate the epidemiological characteristics, differences, and epidemic trends in influenza viruses and in non-influenza respiratory pathogens, and the distribution of the sites of URTI cluster events in Taiwan from 2011 to 2019. We examined the publicly available annual summary data on 1864 confirmed URTI clusters in the Taiwan Centers for Disease Control (Taiwan CDC) from 2011 to 2019. URTI clusters were mainly divided into 1295 clusters of influenza virus infections, 149 clusters of non-influenza respiratory pathogen infections, 341 clusters of pathogens not detected by routine tests, and 79 clusters of unchecked samples. There were statistically significant differences (p < 0.001) in the event numbers of URTI clusters among influenza and non-influenza respiratory pathogens between 2011 and 2019. There were statistically significant differences (p = 0.01) in instances of URTI clusters among non-influenza respiratory pathogens between 2011 and 2019. There were also statistically significant differences (p < 0.001) in instances of URTI clusters in different locations between 2011 and 2019. In all the pathogens of URTI clusters (odds ratio (OR) = 1.89–2.25, p = 0.002–0.004), most single infections were influenza A viruses (64.9%, 937/1444). Respiratory syncytial virus single infections were most numerous (43.0%, 64/149) among the non-influenza respiratory pathogens of URTI clusters. Of the institutions where URTI clusters occurred, schools had the most cases (50.1%, 933/1864) (OR = 1.41–3.02, p < 0.001–0.04). After the categorization of isolated virus strains by gene sequencing, it was found that, of the seasonal influenza A viruses, the H1N1 subtype viruses were predominantly A/California/07/2009, A/Michigan/45/2015, and A/Brisbane/02/2018, and the H3N2 subtype viruses were predominantly A/Hong Kong/4801/2014, A/Singapore/INFIMH-16–0019/2016, and A/Switzerland/8060/2017, during 2017–2019. Of the influenza B viruses, B/Brisbane/60/2008 (B/Vic) was the dominant type, and some were B/Massachusetts/02/2012 (B/Yam) and B/PHUKET/3073/2013 (B/Yam). This study is the first report of confirmed events of URTI clusters from surveillance data provided by the Taiwan CDC (2011–2019). This study highlights the importance of long-term, geographically extended studies, particularly for highly fluctuating pathogens, for understanding the implications of the transmission of URTI clusters in Taiwanese populations. Knowledge gaps and important data have been identified to inform future surveillance and research efforts in Taiwan.

Carbapenem-resistant Acinetobacter nosocomialis (CRAn) is a significant public health concern. Tigecycline non-susceptible CRAn (Tn-CRAn) isolates have emerged worldwide. Tigecycline resistance is mainly related to the overexpression of AdeABC efflux pump controlled by AdeRS two-component system (TCS). Two novel tetracycline derivatives, omadacycline and eravacycline, may present a treatment option for CRAn. This study investigated the in vitro antimicrobial activity of tigecycline, omadacycline and eravacycline against clinical CRAn isolates and the contribution of efflux pumps in their resistance. Eighty-nine clinical CRAn isolates, including 57 Tn-CRAn isolates were evaluated for minimum inhibitory concentrations (MICs) by the broth microdilution. The relationship between the antimicrobial resistance and efflux pump expression was assessed by their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). The contribution of the AdeABC efflux pump in their resistance was determined by the complementation of the AdeRS two-component system in wild-type, adeRS operon and adeB gene knockout strains. Among the 89 isolates, omadacycline and eravacycline MICs were correlated closely with those of tigecycline. They demonstrated improved potency, based on MIC90 values, by showing a 4 to 8-fold greater potency than tigecycline. The synergetic effects of tigecycline, omadacycline and eravacycline with NMP were observed in 57 (100%), 13 (22.8%), and 51 (89.5%) of Tn-CRAn isolates, respectively. Further analysis showed that the laboratory strain carrying the Type 1 adeRS operon increased the tigecycline, omadacycline and eravacycline MICs by 4–8-folds, respectively. Eravacycline demonstrated improved potency over tigecycline against populations of CRAn, including Tn-CRAn isolates. The over-expression of AdeABC efflux pumps was directly activated by the AdeRS two-component system and simultaneously reduced the susceptibilities of tigecycline, eravacycline, and omadacycline. Omadacycline and eravacycline MICs were correlated closely with those of eravacycline.

Currently available fetal echocardiographic reference values are derived mainly from North American and European population studies, and there is a lack of reference z-score for fetal echocardiographic measurement in Asian populations. The aim of this study was to establish normal ranges of echocardiographic measurements and z-scores in healthy Asian fetuses. A total of 575 healthy pregnant Taiwanese with an estimated gestational age from 14 to 38 weeks were enrolled voluntarily for this observational study. Standard two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries of the developing fetuses. In contrast to past studies, our sample was more evenly distributed for estimated gestational age (p

This study proposes an axisymmetric generalization of the Vaidya metric, namely the Vaidya–Kerr metric, to describe a radiating rotating black hole, and presents its Hawking radiation temperature. This study is an improved version of our previous research via ellipsoid coordinate transformation, and the Einstein field equations are solved concisely and intuitively by an orthogonal ansatz. The results demonstrate that the energy–momentum tensor of the derived radiating Kerr metric satisfies the energy-conservation law and is classified as a Petrov type II fluid, whereas the stationary Kerr metric is a Petrov type IV vacuum. The inner and outer event-horizon radii, the ergosphere radii, as well as the angular velocity at the event horizon are solved, and then, surface gravity, entropy, and Hawking radiation are derived. We estimate the Hawking-radiation temperature of the black holes with the angular momentum and the same mass of Pluto and the sun, as well as the supermassive black hole in the core of the M87 galaxy to be 9.42K, 6.08×10−8K, and 8.78×10−18K, respectively. Only the value of the rotating Pluto-mass black hole is slightly greater than the 3K cosmic microwave background radiation and may be detected by high-resolution tools in the future.

Context: Breast cancer subtype (BCS) and lymphovascular invasion (LVI) have both been independently demonstrated as prognostic factors.Aims: The objective of this investigation was to evaluate the prognostic power of LVI among BCSs.Settings and Design: From an institutional database, 2017 women with a histopathologically confirmed the diagnosis of breast cancer treated between January 2006 and December 2014 were consecutively selected.Subjects and Methods: Information recorded for each patient included age at diagnosis, year of diagnosis, and date of death or last contact. Total incidences of recurrence or death from breast cancer were ascertained from follow-up lasting until 31 June 2013. Institutional review board approval was obtained through our institution's human investigations committee.Statistical Analysis Used: Univariate and multivariate survival analysis were performed using the Kaplan–Meier analysis and Cox proportional hazards model with a stepwise backward elimination to derive a final model of variables with a significant independent relationship with overall survival (OS) and recurrent-free survival (RFS). All statistical analyses were two-sided with significance defined as P < 0.05.Results: For the entire cohort, the median follow-up OS period was 43.2 months. Tumor size, LVI, lymph node status, and treatment factors (operation type, chemotherapy, and hormone therapy) differed among subtypes with respect to OS and RFS. The highest incidence of LVI positivity (26.4% vs. 26.9%, respectively) and lymph node involvement (39.7% vs. 36.4%, respectively) occurred in the luminal B and luminal HER2 subtypes. There were significant differences in the OS and RFS rates according the LVI among the BCS. On multivariate analysis, there were significant differences in OS according to the status of lymph node-negative and LVI-positive in the luminal HER2 subtype, as well as lymph node-positive and LVI-positive in the triple negative (TN) subtype. There were also significant differences in RFS according to the status of lymph node-negative and LVI-positive in the luminal A subgroup.Conclusions: LVI in BCS was an important prognostic factor for OS and RFS. LVI and lymph node status were important prognostic factor for OS and RFS among BCSs. There were significant differences in OS according to the lymph node-negative and LVI-positive in the distribution of luminal HER2, the lymph node-positive, and LVI-positive in the distribution of TN. There were also significant differences in the RFS according to the lymph node-negative and LVI-positive in the luminal A.

Background: In this study, we aimed to identify the association between chronic periodontal disease (CPD) and erectile dysfunction (ED) in a large young population. Patients and Methods: Totally 2191 male participants aged 18–28 years attended the Army Training Center in Taiwan between August 2012 and May 2013. All 1932 included participants filled in the International Index of Erectile Function-5 (IIEF-5) questionnaire and received a comprehensive dental examination to classify whether CPD. Results: There was a statistically significant correlation between the presence of ED and CPD (P < 0.001). Multivariate logistic regression analysis indicated that men with CPD were 1.6 (95% confidence interval = 1.280–2.009, P < 0.001) times more likely to have ED than men without CPD after adjusting confounders. Conclusion: This study demonstrates a link between ED and CPD, and it may be attributed to a combination of psychogenic and organic etiologies, such as systemic inflammation, oxidative stress, and endothelial dysfunction. This study highlights the significance of oral health, which may take a role in sexual function, even in young males. In clinical practice, more comprehensive management strategies to address participants with ED and CPD need to be investigated.

Scrub typhus is a zoonotic disease caused by the bacterium Orientia tsutsugamushi. In this study, the epidemiological characteristics of scrub typhus in Taiwan, including gender, age, seasonal variation, climate factors, and epidemic trends from 2010 to 2019 were investigated. Information about scrub typhus in Taiwan was extracted from annual summary data made publicly available on the internet by the Taiwan Centers for Disease Control. From 2010 to 2019, there were 4352 confirmed domestic and 22 imported cases of scrub typhus. The incidence of scrub typhus ranged from 1.39 to 2.30 per 100,000 from 2010–2019, and peaked in 2013 and 2015–2016. Disease incidence varied between genders, age groups, season, and residence (all p < 0.001) from 2010 to 2019. Risk factors were being male (odds ratio (OR) =1.358), age 40 to 64 (OR = 1.25), summer (OR = 1.96) or fall (OR = 1.82), and being in the Penghu islands (OR = 1.74) or eastern Taiwan (OR = 1.92). The occurrence of the disease varied with gender, age, and place of residence comparing four seasons (all p < 0.001). Weather, average temperature (°C) and rainfall were significantly correlated with confirmed cases. The number of confirmed cases increased by 3.279 for every 1 °C (p = 0.005) temperature rise, and 0.051 for every 1 mm rise in rainfall (p = 0.005). In addition, the total number of scrub typhus cases in different geographical regions of Taiwan was significantly different according to gender, age and season (all p < 0.001). In particular, Matsu islands residents aged 20–39 years (OR = 2.617) and residents of the Taipei area (OR = 3.408), northern Taiwan (OR = 2.268) and eastern Taiwan (OR = 2.027) were affected during the winter. Males and females in the 50–59 age group were at high risk. The total number of imported cases was highest among men, aged 20–39, during the summer months, and in Taipei or central Taiwan. The long-term trend of local cases of scrub typhus was predicted using the polynomial regression model, which predicted the month of most cases in a high-risk season according to the seasonal index (1.19 in June by the summer seasonal index, and 1.26 in October by the fall seasonal index). The information in this study will be useful for policy-makers and clinical experts for direct prevention and control of chigger mites with O. tsutsugamushi that cause severe illness and are an economic burden to the Taiwan medical system. These data can inform future surveillance and research efforts in Taiwan.

The risk of the geographic transmission of emerging infectious diseases through air travel varies greatly. In this study, we collected data on cases of food-borne diseases between the years 2011 and 2020 in Taiwan to access the epidemiological features, differences, and trends in domestic and imported cases of typhoid and paratyphoid in terms of patient sex, age, month of confirmation, and area of residence. In this study, we made use of the open data website provided by Taiwan’s Centers for Disease Control (TCDC) to extract the reported numbers of cases of typhoid and paratyphoid between January and December from 2011 to 2020 for comparison. Univariate analysis was performed using the Chi-square test for categorical variables. Fisher’s exact test was performed if an expected frequency was less than 5. A total of 226 typhoid cases and 61 paratyphoid cases were analyzed from the database. The incidences of typhoid and paratyphoid per million of the population were 0.42–2.11 and 0–0.39, respectively. There was a significant difference in the incidence of the diseases between the age groups (p = 0.019), with a gradual increase in the 20–40 years group. A distinct seasonal (between fall and spring) variation was also observed (p = 0.012). There were 34 cases of children with typhoid in the period 2011–2015 and 12 cases of children with typhoid in the period 2016–2020. During these periods, there were two cases of paratyphoid. This study indicated that the risk of children suffering from typhoid has been significantly reduced in the last five years. Furthermore, we found that more women have acquired typhoid and paratyphoid than men, and that living in the Taipei metropolitan area and the northern area was a potential risk factor. Furthermore, the number of imported cases of typhoid (n = 3) and paratyphoid (n = 0) reported during the COVID-19 pandemic was lower than that reported for the same disease from 2011 to 2020. More typhoid and paratyphoid cases were imported from Indonesia, India, Myanmar, and Cambodia. This study represents the first report on confirmed cases of acquired typhoid and paratyphoid from surveillance data from Taiwan’s CDC for the period 2011–2020. This study also demonstrates that the cases of typhoid and paratyphoid decreased in Taiwan during the COVID pandemic. Big data were used in this study, which may inform future surveillance and research efforts in Taiwan.

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.

Acute diarrhea is mainly caused by norovirus and rotavirus. Numerous factors modify the risk of diarrhea cluster infections and outbreaks. The purpose of this study was to explore the epidemiological characteristics, differences, and trends in the distribution of viral and bacterial pathogens that cause diarrhea cluster events as well as the public places where diarrhea cluster events took place in Taiwan from 2011 to 2019. We examined publicly available, annual summary data on 2865 diarrhea clusters confirmed by the Taiwan Centers for Disease Control (CDC) from 2011 to 2019. There were statistically significant differences (p < 0.001) in event numbers of diarrhea clusters among viral and bacterial pathogens, and statistically significant differences (p < 0.001) in event numbers of diarrhea clusters among bacterial pathogens. There were also statistically significant differences (p < 0.001) in the event numbers of diarrhea clusters among public places. Norovirus infections were the first most numerous (77.1%, 1810/2347) diarrhea clusters among viral and bacterial infections. Among bacterial infections, Staphylococcus aureus infections accounted for the greatest number of diarrhea clusters (35.5%, 104/293). Schools were the places with the greatest number of diarrhea clusters (49.1%, 1406/2865) among various institutions. Norovirus single infection (odds ratio, OR = 4.423), Staphylococcus aureus single infection (OR = 2.238), and school (OR = 1.983) were identified as risk factors. This is the first report of confirmed events of diarrhea clusters taken from surveillance data compiled by Taiwan’s CDC (2011–2019). This study highlights the importance of long-term and geographically extended studies, particularly for highly fluctuating pathogens, to understand the implications of the transmission of diarrhea clusters in Taiwan’s populations. Importantly, big data have been identified that can inform future surveillance and research efforts in Taiwan.

Anal atresia can be divided into high type and low type depending on the relationship between the distal rectal pouch and the puborectalis muscle. Prenatal diagnosis of anal atresia is very challenging. Indirect findings include dilated distal bowel segments and calcified intraluminal meconium in 2nd & 3rd trimester. Direct findings include no PAMC (perianal muscular complex) and no target sign (hypoechoic anal sphincter and echogenic anal mucosa). PAMC is intact in low atresia, no PAMC can only be applied to high atresia. A visible echogenic anal mucosa excludes all cases of high atresia and most cases of low atresia, with the exception of the mildest cases with only a thin membrane covering the anal opening.

Abstract Recently, a few small reports with short follow-up period have shown clinical benefits of platelet-rich plasma (PRP) for peripheral neuropathy including one pilot study and one small, non-randomized trial in patients with carpal tunnel syndrome (CTS). Therefore, we conducted a randomized, single-blind, controlled trial to assess the 6-month effect of PRP in patients with CTS. Sixty patients with unilateral mild-to-moderate CTS were randomized into two groups of 30, namely the PRP and control groups. In the PRP group, patients were injected with one dose of 3 mL of PRP using ultrasound guidance and the control group received a night splint through the study period. The primary outcome measure was the visual analog scale (VAS) and secondary outcome measures included the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score, the cross-sectional area (CSA) of the median nerve (MN), electrophysiological findings of the MN, and finger pinch strength. The evaluation was performed before treatment and at 1, 3, and 6 months post-injection. The PRP group exhibited a significant reduction in the VAS score, BCTQ score, and CSA of MN compared to the those of control group 6 months post-treatment (p

We aimed to explore the associations between different lipid profiles and semen quality in a large-scale general male population. Sperm concentration, total sperm motility, progressive motility, and normal sperm morphology of total 7601 participants were recorded. The association of these semen parameters with the triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein of serum lipid profiles was analyzed. Sperm concentration was statistically positively correlated with triglyceride and very low-density lipoprotein (adjusted P = 0.001 and P = 0.005, respectively). Total sperm motility and progressive motility were statistically increased with increasing low-density lipoprotein and cholesterol levels (both adjusted P = 0.008 and P < 0.001, respectively). The similar J-shaped associations (high-low-low-high) were noted between individual lipid profile and normal sperm morphology, especially low-density lipoprotein and cholesterol with statistical significance (adjusted P = 0.017 and P = 0.021, respectively). The prevalence of abnormal total sperm motility and progressive motility was decreased in participants with high levels of cholesterol (P = 0.008 and P = 0.019, respectively), and the reverse J-shaped associations (low-high-high-low) were noted between high-density lipoprotein, triglyceride, very low-density lipoprotein, and the prevalence of abnormal normal sperm morphology (P = 0.010, P = 0.037, and P = 0.025, respectively). A high cholesterol level was associated with better sperm motility. Similar J-shaped associations were noted between all lipid profiles and normal sperm morphology; meanwhile, the reverse J-shaped trends were identified between them and abnormal normal sperm morphology prevalence.

Background Recent studies have raised concerns about the reduced efficacy of citalopram when used concurrently with proton pump inhibitors. The aim of this study was to evaluate the associations between clinical use of citalopram and omeprazole and the risk of sudden cardiac arrest (SCA) in an Asian population. Methods and Results A retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 3882 patients with citalopram use alone, 31 090 patients with omeprazole use alone, and 405 patients with concomitant use of citalopram and omeprazole (as the exposed cohort), and 141 508 patients received treatment with antidepressants without the risk of SCA and/or proton pump inhibitors other than omeprazole (as the comparison cohort). The primary outcome was the occurrence of SCA. The hazard ratios and 95% CIs derived from the time‐dependent Cox regression model were used to assess the association between the proposed drug treatments and risk of SCA. The adjusted hazard ratios of SCA was 1.32 (95% CI, 1.17–1.50) for citalopram use alone, 1.08 (95% CI, 0.98–1.20) for omeprazole use alone, and 2.23 (95% CI, 1.79–2.78) for concomitant use of citalopram and omeprazole. The cumulative incidence of SCA over the Kaplan‐Meier curves was more pronounced in patients with concomitant use of citalopram and omeprazole than those treated with citalopram alone and omeprazole alone. Conclusions This cohort study demonstrated use of citalopram and omeprazole either in isolation use or in concomitant use to be at increased risk for SCA.

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

There are various methods of fixation for anterior pelvic ring fractures. We report our experience with modified pedicle screw-rod fixation (MPSRF) via a minimally invasive method. Fourteen patients with anterior pelvic ring fracture were treated by internal fixation (conventional plate fixation, n = 7; MPSRF, n = 7). Intraoperative blood loss, operative time, post-operative fracture reduction grading by radiography, and complication rates were compared and statistically analyzed. Patients treated with MPSRF had a shorter operative time (-36 min, P = 0.378) and significantly less blood loss (-264 ml, P = 0.026) than patients in the conventional plate fixation group. Postoperative radiological evaluations were similar between the groups (P > 0.05). The complication rate was lower in the MPSRF group (1/7 patients) than in the plate fixation group (2/7 patients). Modified pedicle screw-rod fixation is a viable treatment for anterior pelvic ring fixation and can reduce blood loss.

Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified NKX6.1 hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through the epigenetic regulation of the epithelial-to-mesenchymal transition (EMT) in cervical cancer. More recently, we have demonstrated that NKX6.1 methylation is related to the chemotherapy response in colorectal cancer (CRC). Nevertheless, the biological function of NKX6.1 in the tumorigenesis of CRC remains unclear. In this study, we showed that NKX6.1 suppresses tumorigenic and metastatic ability both in vitro and in vivo. NKX6.1 represses cell invasion partly through the modulation of EMT. The overexpression of NKX6.1 enhances chemosensitivity in CRC cells. To further explore how NKX6.1 exerts its tumor-suppressive function, we used RNA sequencing technology for comprehensive analysis. The results showed that differentially expressed genes (DEGs) were mainly related to cell migration, response to drug, transcription factor activity, and growth factor activity, suggesting that these DEGs are involved in the function of NKX6.1 suppressing cancer invasion and metastasis. Our results demonstrated that NKX6.1 functions as a tumor suppressor partly by repressing EMT and enhancing chemosensitivity in CRC, making it a potential therapeutic target.

Background: Electroconvulsive therapy (ECT) is an effective treatment for schizophrenia, bipolar disorder, and major depressive disorder, and a temporary memory loss may occur after ECT. However, the association between ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, and the risk of dementia is yet to be examined.Objective: This study aimed to clarify as to whether ECT is associated with the risk of dementia after ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, using Taiwan's National Health Insurance Research Database (NHIRD).Methods: A total of 3,796 enrolled participants (schizophrenia, 46.68%; bipolar disorder, 11.77%; and major depressive disorder, 41.55%) with 994 patients who had received ECT and 2,982 controls matched for sex and age, between January 1, and December 31, 2000, were selected from the NHIRD. After adjusting for confounding factors, Fine and Gray's survival analysis was used to compare the risk of developing dementia during the 10 years of follow-up.Results: Of the study patients, 45 (4.53%) of them developed dementia when compared to 149 (5.0%) in the control group. Fine and Gray's survival analysis revealed that the study patients were not associated with an increased risk of dementia [hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.438–1.854, P = 0.325]. After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 0.633 (95% CI = 0.448 – 1.895, P = 0.304).Conclusion: This study supports that ECT was not associated with the increased risk of dementia in patients with schizophrenia, bipolar disorder, and major depressive disorder, using the NHIRD.