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We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma.We retrospectively analyzed theEntropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, 0.001, and = 0.224, respectively).The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy

ObjectiveTo determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake.MethodsParticipants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007–2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases.ResultsVegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.08–0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33–0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19–0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12–1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046).ConclusionTaiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

BackgroundSystematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination.ObjectiveTo investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet.DesignA one-arm pilot intervention study.Participants/SettingNine patients with dyslipidemia participated in this 12-week vegan program.Main Outcome MeasuresNuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors.Statistical Analyses PerformedWilcoxon signed-rank test.ResultsIn this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: −23 μmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median −24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median −75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (−23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (−0.7 kg/m2, p = 0.03), waist circumferences (−2.0 cm, p < 0.001), HbA1c (−0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (−0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status.ConclusionsA dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Key Points Question Is the use of Bcr-Abl tyrosine kinase inhibitors (TKIs) associated with subsequent hepatitis B virus reactivation? Findings In this nationwide nested case-control study with 733 691 individuals carrying the hepatitis B virus, Bcr-Abl TKIs were associated with overt HBV reactivation that required antiviral treatment. Women receiving Bcr-Abl TKIs had higher odds of reactivation than men. Meaning To our knowledge, this was the first population-based study that found that Bcr-Abl TKIs were associated with increased risk of HBV reactivation., This case-control study examines the association between hepatitis B flare and exposure to Bcr-Abl tyrosine kinase inhibitors (TKIs) compared with non–Bcr-Abl TKIs., Importance The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. Objective To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non–Bcr-Abl TKIs. Design, Setting, and Participants This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. Exposure Use of Bcr-AbL TKIs. Main Outcomes and Measures Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non–Bcr-Abl TKIs. Results Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex–matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). Conclusions and Relevance These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.

To investigate the role of the traditional and radiomic parameters of 18F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC). Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology. A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0–1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0–1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p

Objectives Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. Methods Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). Results The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23–2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07–6.72), rheumatoid arthritis (2.89, 1.97–4.23), dermatomyositis (5.85, 1.32–25.94) and autoimmune vasculitis (2.44, 1.17–5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. Conclusions This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.

Introduction Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea (OSA). To date, the link between CPAP usage and incident stroke has been inconsistent. Objective This nationwide population study is designed to examine the effect of CPAP on stroke incidence in OSA patients. Methods Using Taiwan's National Health Insurance Research Database (NHIRD), this study collected data from 4275 OSA patients diagnosed between 2000 and 2011 and divided them into two groups according to whether they received CPAP treatment. After matching baseline demographics and comorbidities, both cohorts contained 959 OSA patients and were followed to a newly diagnosed stroke or until the end of 2013. Cox regression analysis was performed to examine the incidence of stroke between patients with OSA receiving CPAP or no CPAP treatment. Results CPAP treatment for OSA patients predicted a lower incidence rate (3.41 vs 5.43 per 1000 person-years) and tended to protect against the development of stroke (hazard ratio (HR): 0.68, 95% confidence interval (95% CI): 0.38-1.23) compared to those without CPAP treatment, but the estimate was not statistically significant. Similar results were also observed by dividing stroke into ischemic (2.65 vs 4.30 per 1000 person-years; HR: 0.67, 95% CI: 0.35-1.31) or hemorrhagic origin (0.76 vs 1.12 per 1000 person-years; HR: 0.67, 95% CI: 0.19-2.40). Conclusions It is possible that treatment with CPAP might be beneficial for protection against stroke, but this conclusion should be interpreted with caution. Future studies with satisfactory CPAP quality and duration are needed to validate this observation.

Currently, neck ultrasound is the preferred preoperative imaging in patients with secondary/tertiary hyperparathyroidism, and the use of Tc-99m sestamibi scan is limited in these patients. We conducted this study to compare the diagnostic utilities of F-18 fluorocholine PET/CT, Tc-99m sestamibi scintigraphy, and neck ultrasound for localizing hyperfunctioning parathyroid glands in secondary/tertiary hyperparathyroidism. We prospectively enrolled 30 dialysis patients with a diagnosis of secondary/tertiary hyperparathyroidism; of these, 27 participants underwent all three imaging modalities, including dual-phase F-18 fluorocholine PET/CT (PET acquired 5 and 60 min after tracer injection), dual-phase Tc-99 m sestamibi SPECT/CT, and neck ultrasound. All patients underwent parathyroidectomy after imaging. We compared the lesion-based sensitivity, specificity, and accuracy of the three image tools using histopathology as the reference. A total of 27 patients (107 lesions) underwent all three imaging modalities and entered the final analysis. The lesion-based sensitivities of F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound were 86%, 55%, and 62%, respectively (both p

To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p

Obstructive sleep apnea (OSA), a sleep disorder, results in decreased daytime alertness and neurocognitive dysfunction. Obesity is considered a major risk factor for the development and progression of OSA and the resulting cognitive dysfunction. However, the effect of obesity on neurocognitive dysfunction in OSA has been rarely investigated. Eighty-three patients with moderate to severe OSA syndrome were recruited in our study. After matching for education, age, and body mass index (BMI), 40 patients were enrolled into our study with matched obese (BMI ≧ 30) and non-obese (BMI

CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms, which mediates different biological activities. Recent studies have revealed the potential of CX3CL1 signaling pathway as a target for the treatment of inflammation and cancer. The correlation between expression of CX3CL1 and prognosis of patients varies among cancers. In this study, based on CX3CL1 immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively associated with cancer stage (Pearson chi-square, P = 0.048) and lymph node status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027), but not in patients with squamous cell carcinoma (SQ). The median survival time of patients with smoking history and low level CX3CL1 expressing AD was 1538 days, while that of patients with smoking history and high level CX3CL1 expressing AD was 396 days. Cox regression models showed adverse effects of high CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p = 0.034), but not in AD patients without smoking history or in SQ patients with smoking history. The results of this study suggest that CX3CL1 plays different roles in lung tumorigenesis in smokers and non-smokers, and different CX3CL1-based therapeutic strategies are needed depending on patient smoking status and tumor type. Furthermore, high level of CX3CL1 expression enhances nodal metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.

Background Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. Methods Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. Results The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. Limitations The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. Conclusion This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

• Mindfulness intervention using the MBSR program effectively reduces stress among newly graduated nurses.

To investigate the role of the traditional and radiomic parameters ofForty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwentA pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0-1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0-1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS).The

Introduction Violent motor tics or severe self-harm behaviors have been reported in patients with Tourette's syndrome (TS) and leading to traumatic brain injury (TBI). The study aimed to determine the risk of TBI in TS patients, the effects associated with concurrent psychiatric disorders (attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or depressive disorder), and the effects of medication treatment (antipsychotics, antidepressants, or clonidine) on the risk of TBI. Methods Using the National Health Insurance Research Database of Taiwan, 2261 TS patients and 20349 non-TS controls matched by gender and age were enrolled between 2000 and 2012, and followed until the end of 2013. Participants who developed TBI during the follow-up period were identified. Cox regression analysis was performed to examine the risk of TBI between TS patients and non-TS controls. Results TS patients were associated with an increased risk of TBI compared to non-TS controls (hazard ratio (HR): 1.59, 95% confidence interval (95% CI): 1.37–1.85). Also, this study revealed TS patients with ADHD, OCD, or depressive disorder predicted a higher TBI incidence rate than those who did not, but the estimate was not statistically significant. Moreover, this study found that TS patients with frequent use of antipsychotics were associated with a lower risk of TBI than infrequent users (HR: 0.76, 95% CI: 0.57–0.99). Conclusions This study highlights the need to pay more attention to the risk of TBI in TS patients, and the importance of adequate antipsychotic medication may reduce the risk of TBI.

BackgroundSeveral features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population.ObjectiveThe study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan.MethodsOverall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls.ResultsPatients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18–34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4).ConclusionGiven the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan’s mental health clinics.

To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) usingSixty patients with primary NPC were prospectively enrolled. All patients underwentA total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p 0.001 versus p = 0.175).Early evaluation of response to CCRT using

Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31–0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44–1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.

Background Previous studies have suggested that sexually transmitted infections (STI) tend to increase in patients with bipolar disorder during a manic or hypomanic episode. However, in the long-term course of this disease, it is unclear whether patients with bipolar disorder have a higher risk of incident STI. Methods Using the National Health Insurance Research Database of Taiwan, 3721 patients with bipolar disorder and 14,884 controls without bipolar disorder matched by gender and age were enrolled between 2000 and 2010 and followed up until the end of 2013. Participants who developed any STI (human immunodeficiency virus [HIV], syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between patients with bipolar disorder and comparative controls. Results Patients with bipolar disorder were prone to develop STI (hazard ratio [HR], 1.67, 95% confidence interval [95% CI], 1.27-2.18) especially for HIV (HR, 3.59; 95% CI, 1.16-11.08) and syphilis (HR, 2.26; 95% CI, 1.06-4.85). In addition, this study found that the incidence of STI was higher among women than men (HR, 1.83; 95% CI, 1.41-2.39). Conclusions This study shows that bipolar disorder is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in patients with bipolar disorder.

Obstructive sleep apnoea (OSA) is a sleep disorder involving repeated nocturnal desaturation and sleep fragmentation. OSA can result in decreased daytime alertness and neurocognitive dysfunction. Hypercapnia status is also related to neurocognitive dysfunction in patients with pulmonary diseases. We evaluated the effects of hypercapnia on cognitive performance and memory function in a prospective case-controlled study. We enrolled thirty-nine obese patients with OSA and collected their arterial blood samples. All the participants provided arterial blood samples, and completed two questionnaires (the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale) and six cognitive tasks (the psychomotor vigilance task [PVT], the Stroop task, the Eriksen flanker task, processing speed [DSST], and verbal and visual memory [LM&FM]), which were used to evaluate daytime sleepiness, cognitive function, and memory function within one week of a polysomnographic study. When compared to the OSA without diurnal hypoventilation, the patients with stable hypercapnia (OHS) had increased reaction times in the PVT, Stroop task, and flanker task. Hypercapnic obese patients with OSA also had comparatively significantly lower scores in the processing speed and logical memory tests. OHS had increased reaction times in the attention and cognitive function assessments, and deficits in the logical memory, when compared to those with OSA without diurnal hypoventilation.

Studies suggested autoimmunity plays a role in the etiology of obsessive–compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41–2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07–2.54) dermatomyositis (3.25, 1.04–10.17), and Sjogren’s syndrome (2.38, 1.53–3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Purpose: Previous studies have observed cognitive inflexibility in depressed patients may be associated with suicide risk, gaps exist in knowledge of cognitive flexibility in different gradations of suicidal ideation (SI). This study examined whether cognitive flexibility differed between depressed patients with passive and active SI. Methods: Depressed patients currently experiencing a major depressive episode with either passive (n = 35) or active (n = 18) SI completed assessments of cognitive flexibility using perseverative errors of Wisconsin Card Sorting Test (WCST-PE). Multivariate logistic regression was used to estimate the odds ratio (OR) for cognitive flexibility (WCST-PE) between active and passive SI patients after adjustment for gender, age, diagnostic composition, and depression severity. Results: Patients with active SI are associated with greater cognitive inflexibility compared to passive SI after adjusting for other covariates (OR: 1.26, 95% confidence interval: 1.01-1.58, p=0.04). Conclusions: This study found that patients with active SI are associated with greater cognitive inflexibility than those with passive SI, which can provide insight into improved prevention.

This paper presents a novel algorithm and architecture design for 18-band quasi-class-2 ANSI S1.11 1/3 octave filterbank. The proposed design has several advantages such as lower group delay, lower computational complexity, and lower matching error. The technique we developed in this paper can be summarized as follows: 1) a simple low-pass filter (LPF) and discrete cosine transform (DCT) modulation are utilized to generate a uniform 9-band filterbank first, and then all elements of ${\rm z}^{-1}$ are replaced by all-pass filters to obtain a non-uniform filterbank; 2) a fast recursive structure and variable-length algorithm is further developed to efficiently accomplish DCT modulation. Thus, the spectrum of LPF can be easily spanned and flexibly extended to the location of the desired central frequency; 3) after employing the multi-rate algorithm, an 18-band non-uniform filterbank is generated from two 9-band sub filterbanks by following the proposed design steps and parameter determinations. Compared with the latest Liu 's quasi-class-2 ANSI S1.11 design, the proposed method-I (Proposed-I) totally has 72.8% reduction for multiplications per sample, 11.25-ms group delay, and 59 additions decreased per sample. Moreover, the maximum matching error of the proposed method-II (Proposed-II) is averagely equal to 1.79 dB much smaller than that of the latest Wei 's design. For the proposed variable-length DCT modulation, only 2 adders, 2 multipliers, 2 multiplexers, and 5 registers are required for hardware implementation after applying VLSI retiming scheme. Overall, the proposed filterbank design would be a new solution for future applications in the area of hearing aids.

Background It has been shown that metabolic syndrome is associated with lower levels of plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP) in the general population. However, there is no study about the association between Nt-proBNP and metabolic syndrome in hypertensive patients. Aim To elucidate the relationship between Nt-proBNP and components of metabolic syndrome in hypertensive patients. Methods Fasting blood samples were obtained from 74 hypertensive patients in our institution. Plasma levels of Nt-proBNP and other biochemical data were measured. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Forty-four hypertensive patients met the criteria for metabolic syndrome. We found that plasma Nt-proBNP levels were lower in hypertensive patients with metabolic syndrome attributable to inverse relationships between Nt-proBNP and albumin, triglyceride, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). We further performed a multivariable linear regression analysis. The result showed that HOMA-IR is the independent predictor of plasma Nt-proBNP levels in hypertensive patients. Conclusions Plasma Nt-proBNP levels are inversely associated with metabolic syndrome in hypertensive patients. HOMA-IR is the independent predictor of Nt-proBNP in hypertensive patients.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder with systemic complications and has been a worldwide epidemic. Ophiopogon japonicus is a traditional Chinese medicine used to treat diabetes for thousands of years. From our previous work, we know that MDG-1, a water-soluble β-D-fructan polysaccharide from O. japonicas could treat T2DM experimentally. However, MDG-1 is poorly absorbed and its mechanism of action is still unknown. Therefore, a GC TOF/MS-based metabonomic approach in combination with multivariate statistical analysis was performed to investigate the mechanism of MDG-1 in a spontaneous diabetic model. Female diabetic KKay mice (21 weeks old) were randomly divided into a diabetic group (n = 6, gavaged with distilled water) and a MDG-1-Diabetic group (n = 7, gavaged with MDG-1, 300 mg kg(-1)) and female C57BL/6 mice (21 weeks old) were set as controls (n = 6, gavaged with distilled water). After 8-weeks of treatment, feces samples were collected for GC-TOF/MS analysis. Consequently, 12 potential biomarkers were identified, including monosugars (D-tagatose, D-lyxose, D-erythrose, xylo-hexos-5-ulose, 2-deoxy-galactose), butanedioic acid, amino acids (phenylalanine, L-lysine, L-methionine, L-aspartic acid) and purine derivatives (7H-purine, 2'-deoxyinosine). We assume the monosugars and butanedioic acid were the fermentation products of MDG-1 by intestinal microbes and MDG-1 actions against diabetes might be accomplished through the absorbable monosugars and butanedioic acid via suppressing intestinal glucose absorption, enhancing liver glycogenesis, inhibiting glycogenolysis and promoting GLP-1 secretion. Besides, MDG-1 might alleviate diabetes and diabetic nephropathy by reducing 7H-purine and 2'-deoxyinosine. Further omics-driven studies including genomics, proteomics and metabonomics were considered to be carried out to provide direct evidence of gut microbiome contribution to MDG-1 actions.

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) is associated with nosocomial infections worldwide. Here, we used phage as a potential agent to evaluate the efficacy of daily cleaning practices combined with a bacteriophage-containing aerosol against CRAB. Methods A two-phase prospective intervention study was performed at a 945-bed public teaching hospital. From March to December 2013, we performed terminal cleaning using standard procedures plus an aerosol with active bacteriophage in the intensive care units to evaluate the impact on nosocomial incidence density, carbapenem-resistance rates and antimicrobial drug consumption amounts. Patients with culture proven CRAB infection were transferred to the isolation room when the phage aerosol cleaning had been completed. Results A total of 264 new acquisitions of CRAB were identified in the intensive care units (191 in the pre-intervention period and 73 in the intervention period). The rates of new acquisitions of CRAB in the intensive care units decreased from 8.57 per 1000 patient-days in the pre-intervention period to 5.11 per 1000 patient-days in the intervention period (p = 0.0029). The mean percentage of resistant isolates CRAB decreased from 87.76% to 46.07% in the intensive care units (p = 0.001). All of the antimicrobials showed a significant reduction in consumption except imipenem. Conclusions The bacteriophage was successful in decreasing the rates of infection caused by CRAB across intensive care units in a large teaching hospital.

Infective endocarditis (IE) is a common and potentially serious disease. Although it is an illness that affects populations around the world, narrower descriptions of this disease as it impacts specific regions are uncommon. We analyzed the clinical characteristics of IE patients from two eastern counties in Taiwan and studied the relationship between the isolated pathogens and clinical outcomes in these patients.This is a retrospective chart review study which enrolled patients who received services between January 2007 and December 2010. Subsequent to chart review, IE was confirmed in a total of 55 patients by the modified Duke criteria.Of these patients, 17 (31%) had previous traumatic open skin wounds. Pre-existing cardiac abnormalities were found in 47 (85%) patients, 28 of whom had valvular abnormalities. Staphylococcus aureus was isolated from the blood as the leading pathogen in 25 (45%) patients (including 23 methicillin-sensitive and 2 methicillin-resistant). Septic emboli and shock occurred in 27 (49%) of 55 patients; surgery was performed on 11 (20%) of those patients, and 4 (36%) of them died post-operatively. The total in-hospital mortality rate was 40% (n = 22). Staphylococcus aureus infection was associated with significantly higher complication and mortality rate than non-Staphylococcus aureus infection (59% vs. 41% and 64% vs. 36%, respectively; p0.05). In addition, patients with complications had a very high mortality rate (81.5%).We found that Staphylococcus aureus was the most common pathogen of IE in Eastern Taiwan, and was associated with higher rates of morbidities and mortality.Infective endocarditis; Septic shock; Staphylococcus aureus; Systemic embolization.

Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed the anti-ischemic properties of a water-soluble β-D-fructan (MDG-1) from O. japonicus. The sphingosine 1-phosphate (S1P) signaling pathway is involved in its cytoprotective effects. Herein, we explore the role of the S1P signaling pathway in the anti-ischemic effect of MDG-1 and assess one possible mechanism by which it induces S1P release and sphingosine 1-phosphate receptor 1 (S1P(1)) expression in human microvascular endothelial cells (HMEC-1) and cardiomyocytes. Our evidence demonstrates that MDG-1 promotes sphingosine kinase (SPHK) activity in HMEC-1 cells. An analytical method for measuring the mass of S1P using ESI/MS/MS was developed and we found that MDG-1 increases intracellular S1P levels. Meanwhile, MDG-1 is protective during hypoxia and ischemia through mechanisms that require S1P(1) receptor activation, which was confirmed both in oxygen glucose deprivation (OGD) and coronary artery ligation models by using transfection of cloned human S1P(1) receptor and RNA interference. These data indicate that the increase of intracellular S1P generation, particularly by activation of the SPHK enzyme, coupled with the autocrine and paracrine stimulation of cell surface S1P receptors, is a potential mechanism in the anti-ischemic and cell protective effect of MDG-1.

Objectives: It is understood that children and adolescents with autism spectrum disorders (ASDs) have difficulty in receiving dental treatment. This study explores the differences in dental utilization and expenditure between two groups: children and adolescents with and without ASD. Different conditions that affect these results will be examined, including area of residence, category of treatment, and preferences concerning type of dental institution in Taiwan. Materials and Methods: The health service research database of the National Health Research Institutes, which features population-based, randomly selected samples collected from 2001 to 2010, was utilized in this study. In particular, we recruited samples from 2005 in accordance with the codes of the International Classification of Diseases, 9th revision, Clinical Modification from 299.0 to 299.9. The population-based cohort study measured mean expenditures and mean numbers of medical visits with regard to different dental institution classifications, areas of residence, and categories of dental treatment for children (under 18 years old) with and without ASD. Results: The mean number of annual visits was 6.58 and 5.70 for children and adolescents with and without ASD, respectively, with mean annual visit expenditures of NT$2401.20 and NT$1817.99, respectively. A higher percentage of children (91.32%) and adolescents (72.66%) with ASD had experienced dental treatment than those without ASD. Children (93.23%) and adolescents (90.83%) without ASD visited dental clinics more often than those with ASD. The percentage of dental visits to academic medical centers in Eastern Taiwan was significantly lower for the ASD group than visits to other types of dental institutions. The use of restorative treatment was significantly higher among all samples, with periodontology having the lowest percentage. Conclusions: Children and adolescents with ASD had greater dental utilization, expenditures, and preferences for high-level dental institutions. The discrepancies in dental utilization indicate differences in the distribution of medical resources in different dental institution levels and residence areas in Taiwan.

This study examined the amorphization behavior and thermal stability of mechanically alloyed Cu 60 Zr 24 Ti 10 Y 6 alloy powders synthesized by using high-energy ball mill. Complete amorphization is feasible after 5 h of milling. The thermal stability of the Cu 60 Zr 24 Ti 10 Y 6 amorphous powders was investigated by differential thermal analysis. As the results demonstrated, the temperature interval of the supercooled liquid region defined by the difference between glass transition temperature ( T g ) and crystallization temperature ( T x ), i.e. Δ T x = T x − T g , is 82 K for Cu 60 Zr 24 Ti 10 Y 6 . The glass transition and crystallization temperatures of mechanically alloyed samples are different from those reported in the literature for samples prepared by melt spinning techniques. The different thermal stability is believed to be due to the introduction of impurities into the ball-milled samples during mechanical alloying (MA) process.

The role of Slit/Robo signaling has extended from initial axon repulsion in the developing nervous system to organ morphogenesis, cancer development and angiogenesis. Slit/Robo signaling regulates similar pathways within these processes. Slit/Robo ensures the homeostasis of the dynamic interaction between cell-cell and cell-matrix interactions. The dysregulation of Slit/Robo signaling damages the tissue barrier, resulting in developmental abnormalities or disease. Here, we summarize how Slit/Robo controls kidney morphogenesis and describe the dual roles of Slit/Robo signaling in the regulation of tumorigenesis and angiogenesis.

Objective Patients with osteoporotic vertebral compression fracture (OVCF) have postural changes and increased risk of falling. The aim of this study is to compare balance characteristics between patients with OVCF and healthy control subjects. Methods Patients with severe OVCF and control subjects underwent computerised dynamic posturography (CDP) in this case-control study. Results Forty-seven OVCF patients and 45 controls were recruited. Compared with the control group, the OVCF group had significantly decreased average stability; maximal stability under the `eye open with swayed support surface' (CDP subtest 4) and 'eye closed with swayed support surface' conditions (subtest 5); and decreased ankle strategy during subtests 4 and 5 and under the `swayed vision with swayed support surface' condition (subtest 6). The OVCF group fell more frequently during subtests 5 and 6 and had longer overall reaction time and longer reaction time when moving backward during the directional control test. Conclusion OVCF patients had poorer static and dynamic balance performance compared with normal control. They had decreased postural stability and ankle strategy with increased fall frequency on a swayed surface; they also had longer reaction times overall and in the backward direction. Therefore, we suggest balance rehabilitation for patients with OVCF to prevent fall.

To investigate possible correlations between the incidence and severity of Bell's palsy and seasonal variations in Taiwan.We studied data on the incidence of Bell's palsy over a 3-year period in Taiwan. The electroneurographic quotient was used as an index for the severity of nerve involvement. A higher electroneurographic quotient indicates less severe disease.Data were collected from 775 patients. We analyzed the data using the chi-square goodness-of-fit test, and the results showed that seasonality was significantly associated with the incidence of Bell's palsy among men, with the incidence increasing during the cold months (p = 0.012). A significant association was evident between age and incidence, with a higher incidence among patients aged 50 years or younger (p = 0.027). By contrast, no significant relationship was found between seasonality and either female sex or older age. No statistical association was found between the degree of nerve involvement and season of onset in patients with Bell's palsy.Bell's palsy increased among men and among younger patients during the cold seasons in Taiwan. No association emerged between the severity of Bell's palsy and the season of onset.

Cristobalite-fused silica powder was prepared from a mixture of fused silica and cristobalite seed with a high-speed stirrer at 2400 r.p.m. for five minutes. Mixtures were then heated to the soaking temperature, between 1275 °C and 1350 °C, for different time periods. The formation of cristobalite was determined by a quantitative X-ray diffraction (QXRD). Cristobalite, as a phase transformation inhibitor, could affect the rate of transformation of fused silica to cristobalite. In the initial stage of the heating, the presence of cristo-balite seed assists the crystallization of fused silica. However, it retards the crystallization as the soaking time is increased, the evidence shows that the cristobalite seed could induce a compressive stress due to the abrupt volume increase as cristobalite transformed from α phase to β phase at elevated temperature. From the kinetic analysis, the time exponent, n , decreases with increasing cristobalite seed additions, suggesting that the transformation kinetics is controlled by a long-range diffusion mechanism from a two-dimensional plate-like growth to a one dimensional needle-like growth. The activation energy calculation shows that the nucleation and growth process of cristobalite crystals is not similar to the incubation process of cristobalite nucleation in the solid-state reaction of fused silica-cristobalite.

SiO2-ZrSiO4 powder mixture was prepared from powders of fused silica and zircon with a high-speed stirrer at 2400rpm for 5min. Mixtures were, then, heated at the soaking temperature between 1275°C and 1350°C for different time periods. The fraction of cristobalite precipitated was determined by a quantitative X-ray diffraction (QXRD). It was found that zircon affects the rate of transformation of fused silica to cristobalite. In the initial stage of the heating, the presence of zircon assists the crystallization of fused silica. However, it retards the crystallization as the soaking time is increased. The EDS analysis shows that zirconium diffuses into the surface layer of silica particle to form a solid solution, resulting in the lattice distortion which may generate a compressive stress on the surface layer. From the kinetic analysis, the time exponent, n, in Avrami equation decreases with increasing zircon additions suggesting that the transformation kinetic is controlled by long-range diffusion mechanism from two dimensional plate-like growth to one dimensional needle-like growth.

Ethnopharmacological relevance Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action. Aim of study In this study, we examined the effects of a water-soluble β- d -fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model. Materials and methods MDG-1 was extracted from the tube root of O. japonicus and purified as described previously ( Xu et al., 2005 ). The KKAy mice were gavaged once daily with either distilled water, MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined. Results MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300 mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3-kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3β expression. Conclusions These data indicate that MDG-1 has remarkable anti-diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM.

The value of a developed prediction model depends on its performance outside the development sample. The key is therefore to externally validate the model on a different but related independent data. In this study, we propose a permutation method to assess heterogeneity in external validation for risk prediction models. The permutation p value measures the extent of homology between development and validation datasets. If p < 0.05, the model may not be directly transported to the external validation population without further revision or updating. Monte-Carlo simulations are conducted to evaluate the statistical properties of the proposed method, and two microarray breast cancer datasets are analyzed for demonstration. The permutation method is easy to implement and is recommended for routine use in external validation for risk prediction models.