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Background: Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP)., Materials and Methods: 333 OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42, n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis., Results: 9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction)., Conclusion: To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Data discretization aims to transform a set of continuous features into discrete features, thus simplifying the representation of information and making it easier to understand, use, and explain. In practice, users can take advantage of the discretization process to improve knowledge discovery and data analysis on medical domain problem datasets containing continuous features. However, certain feature values were frequently missing. Many data-mining algorithms cannot handle incomplete datasets. In this study, we considered the use of both discretization and missing-value imputation to process incomplete medical datasets, examining how the order of discretization and missing-value imputation combined influenced performance. The experimental results were obtained using seven different medical domain problem datasets: two discretizers, including the minimum description length principle (MDLP) and ChiMerge; three imputation methods, including the mean/mode, classification and regression tree (CART), and k-nearest neighbor (KNN) methods; and two classifiers, including support vector machines (SVM) and the C4.5 decision tree. The results show that a better performance can be obtained by first performing discretization followed by imputation, rather than vice versa. Furthermore, the highest classification accuracy rate was achieved by combining ChiMerge and KNN with SVM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Anorexia nervosa (AN) is a serious and potentially life-threatening eating disorder characterized by starvation and malnutrition, a high prevalence of coexisting psychiatric conditions, marked treatment resistance, frequent medical complications, and a substantial risk of death. Body mass index (BMI) is a key measure of treatment outcome of AN and it is necessary to evaluate the long-term prognosis of AN. This study aimed to better assess the BMI course trend between different medications and timepoints in order to improve AN treatment in clinical practice., Methods: During the period 2010-2021, we retrospectively reviewed historical data of all patients diagnosed with AN. There were two groups in this study, which were based on the duration of follow-up. Group A was a 6-month follow-up group, comprising 93 patients (mean age 19.6 ± 6.8 years), with BMI assessed at three consecutive time points: first outpatient visit (T0), three months follow-up (T3), and six months follow-up (T6). Group B was a 12-month follow-up group comprising 36 patients (mean age 17.0 ± 5.2 years) with BMI assessed at five consecutive time points: first outpatient visit (T0), three months follow-up (T3), six months follow-up (T6), nine months follow-up (T9), and twelve months follow-up (T12). In our study, we retrospectively compared BMI courses based on patients' usage of medication using the following variables: single medication, switching medications, combined medications, and without medications. The primary outcome measurement was BMI recorded at the 6-month follow-up and the 12-month follow-up respectively. In our study, which was conducted at Taichung Veterans General Hospital, we reviewed outpatient medical records of all patients with AN who were seen at the hospital during the period 2010-2021., Results: In Group A (6-month follow-up), patients treated with antidepressants showed a mean BMI increase of 1.3 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 1.1 (p = 0.01); patients treated with switching medications showed a mean BMI increase of 0.1 (p = 0.397); patients treated with combined medications showed a mean BMI increase of 0.5 (p = 0.208); and patients treated without medications showed a mean BMI increase of 0.1 (p = 0.821). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants and antipsychotics in the 6-month follow-up group. In Group B (12-month follow-up), patients treated with antidepressants showed a mean BMI increase of 2.7 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 2.8 (p = 0.168); patients treated with switching medications showed a mean BMI decrease of 0.8 (p = 0.595); patients treated with combined medications showed a mean BMI increase of 1.6 (p = 0.368); and patients treated without medications showed a mean BMI increase of 1.0 (p = 0.262). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants at the 12-month follow-up., Conclusions: AN is a complex disease caused by multiple factors. Evaluating its long-term prognosis is crucial. Our study provides insights and highlights three key findings: 1) medication adherence is crucial in treating AN, 2) frequent switching of medications may not promote weight gain and may also require a re-establishment of rapport with patients with AN, and 3) pharmacotherapy, especially antidepressants, is more effective than no treatment. Further research is needed to confirm these findings., (© 2023. The Author(s).)

Objective: T cells are critical in the pathogenesis of systemic lupus erythematosus (SLE) in that they secrete inflammatory cytokines, help autoantibody production, and form autoreactive memory T cells. Although the contribution of T cells to several forms of organ-mediated damage in SLE has been previously demonstrated, the role of T cells in neuropsychiatric SLE (NPSLE), which involves diffuse central nervous system manifestations and is observed in 20-40% of SLE patients, is not known. Therefore, we conducted this study to evaluate how behavioral deficits are altered after depletion or transfer of T cells, to directly assess the role of T cells in NPSLE., Methods: MRL/lpr mice, an NPSLE mouse model, were either systemically depleted of CD4+ T cells or intracerebroventricularly injected with choroid plexus (CP)-infiltrating T cells and subsequently evaluated for alterations in neuropsychiatric manifestations. Our study end points included evaluation of systemic disease and assessment of central nervous system changes., Results: Systemic depletion of CD4+ T cells ameliorated systemic disease and cognitive deficits. Intracerebroventricular injection of CP-infiltrating T cells exacerbated depressive-like behavior and worsened cognition in recipient mice compared with mice who received injection of splenic lupus T cells or phosphate buffered saline. Moreover, we observed enhanced activation in CP-infiltrating T cells when cocultured with brain lysate-pulsed dendritic cells in comparison to the activation levels observed in cocultures with splenic T cells., Conclusion: T cells, and more specifically CP-infiltrating antigen-specific T cells, contributed to the pathogenesis of NPSLE in mice, indicating that, in the development of more targeted treatments for NPSLE, modulation of T cells may represent a potential therapeutic strategy., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed., Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed., Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31-2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users., Conclusion: There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein-Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.

Background: Whilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs)., Objectives: To compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms., Search Methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant., Selection Criteria: All RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms., Data Collection and Analysis: two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study., Main Results: Out of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial.   There were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/- estimated standard deviation; 0.68 +/- 4.58; N = 8) than the risperidone group (6.04 +/- 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol.  Although no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis.  Our results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported., Authors' Conclusions: We found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples.  High-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125 I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125 I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate ( HR =38.40, 95% CI : 4.87-302.52, P =0.001). Within 3 months after 125 I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125 I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125 I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

Objectives: This study was performed to examine changes in the number of patient visits and types of oral services in an oral emergency department from the beginning to the control stage of the coronavirus disease 2019 (COVID-19) outbreak in Beijing., Methods: The numbers of daily oral emergency visits from January 20 to March 24, 2020, at a dental university hospital in Beijing and daily newly confirmed COVID-19 cases in Beijing during the same period were collected and analysed. All oral emergency patient information (including sex, age, and oral diagnosis) was also collected and analysed. Patients with incomplete medical data were excluded., Results: In total, 12,416 patients were included in this study. The number of daily emergency visits was negatively correlated with the number of newly confirmed local COVID-19 cases in Beijing (P < .001). The number of daily emergency visits during the COVID-19 stable period in Beijing was greater than that during the outbreak period (P < .001). Compared to those in the COVID-19 outbreak period, the percentages of females, children and adolescents, patients with acute toothache, and patients with nonurgent cases were higher in the stable period, and the numbers of patients with toothache, trauma, infection, and nonemergency conditions increased in the COVID-19 stable period (P < .001)., Conclusions: COVID-19 significantly influenced the number of patient visits and the percentages of patients with oral emergency situations in the oral emergency department. There were obvious differences in treatment seeking for oral emergencies between the COVID-19 periods in Beijing. There was an inverse relationship between daily oral emergency visits and daily confirmed COVID-19 cases in Beijing., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics., Methods: Patients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency., Results: There were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94-9.11) and 9.93 (5.88-15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32-2.99) and 3.10 (1.14-6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide., Discussion: No increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/ lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/ lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/ lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/ lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Stock and Putterman.)

Sickle cell disease and β-thalassemia are common monogenic disorders that cause significant morbidity and mortality globally. The only curative treatment currently is allogeneic hematopoietic stem cell transplantation, which is unavailable to many patients due to a lack of matched donors and carries risks including graft-versus-host disease. Genome editing therapies targeting either the BCL11A erythroid enhancer or the HBG promoter are already demonstrating success in reinducing fetal hemoglobin. However, where a single locus is targeted, reliably achieving levels high enough to deliver an effective cure remains a challenge. We investigated the application of a CRISPR/Cas9 multiplex genome editing approach, in which both the BCL11A erythroid enhancer and HBG promoter are disrupted within human hematopoietic stem cells. We demonstrate superior fetal hemoglobin reinduction with this dual-editing approach without compromising engraftment or lineage differentiation potential of edited cells post-xenotransplantation. However, multiplex editing consistently resulted in the generation of chromosomal rearrangement events that persisted in vivo following transplantation into immunodeficient mice. The risk of oncogenic events resulting from such translocations therefore currently prohibits its clinical translation, but it is anticipated that, in the future, alternative editing platforms will help alleviate this risk., Competing Interests: H.P.K. has received support as the inaugural recipient of the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Stephanus Family Endowed Chair for Cell and Gene Therapy. H.P.K is or was a consultant to and has or had ownership interests with Rocket Pharmaceuticals, Homology Medicines, VOR Biopharma, and Ensoma. H.P.K has also been a consultant to CSL and Magenta. Other authors have no competing interests., (© 2021 The Authors.)

As the proportion of elderly people continues to grow, so does the concern about age-related cognitive decline. Serious games have been developed for cognitive training or treatment, but measuring the activity of the autonomic nervous system (ANS) has not been taken to account. However, cognitive functioning has been known to be heavily influenced by the autonomic nervous system (ANS), and ANS activity can be quantified using heart rate variability (HRV). This paper aims to analyze the physiological response in normal elderly people as they play two types of serious games using HRV features from electrocardiography (ECG). A wearable device designed in-house was used to measure ECG, and the data from this device was pre-processed using digital signal processing techniques. Ten HRV features were extracted, including time-domain, nonlinear, and frequency-domain features. The experiment proceeds as follows: rest for three minutes, play a cognitive aptitude game, rest for another three minutes, followed by two reaction time games. Data from thirty older adults (age: 65.9 ± 7.34; male: 15, female: 15) were analyzed. The statistical results show that there was a significant difference in the HRV between the two types of games. From this, it can be concluded that the type of game has a significant effect on the ANS response. This can be further used in designing games for the elderly, either for training or mood management.

Taiwan was successful in containing the spread of the novel coronavirus (COVID-19) in 2020. One major factor in this success was the compilation and provision of comprehensive information about the pandemic. The present study proposes a pandemic intelligence system that provides data on the number of epidemic prevention professionals in each county and city, as well as daily confirmed cases, the demographics of the confirmed cases, and available resources (negative-pressure room beds and artificial ventilation apparatuses) in hospitals. Furthermore, the system provides the location of pharmacies selling masks and their current inventories, as well as the distribution of crowds at popular tourist destinations and social-distance monitoring. The most frequently used map layer in the thematic map of the pandemic is that of crowd distribution during the study period from March 2020 until the end of the same year. The case study used in this investigation for applying the system is represented by the 4-day weekend for Tomb-Sweeping Day of 2020. Through the real-time analysis of dynamic data and the integration of intelligence, the system offers a clear insight into changes in relevant information and, thus, enables the preemptive deployment of control measures by the county/city governments regarding pandemic management.

Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies.

Purpose: The present study retrospectively evaluated the effectiveness and safety of iodine-125 interstitial brachytherapy for treatment of primary locally advanced adenoid cystic carcinoma (ACC) of the base of tongue (BOT)., Material and Methods: This study was a retrospective analysis of data of 19 patients with ACC, who were treated with iodine-125 interstitial brachytherapy between March 2008 and April 2018. Overall survival (OS), disease-free survival (DFS), local control (LC), and radiation-related toxicities were determined. Factors affecting the outcomes were evaluated., Results: Six males and 13 females were included in our study, with a median follow-up time of 35 months. 3- and 5-year OS rates were 71.5% and 47.6%, respectively. 3- and 5-year LC rates were 88.5% and 34.5%, respectively. 3- and 5-year DFS rates were 54.7% and 21.9%, respectively. A significant difference was observed in patients with or without brain metastases for OS rate. No severe acute toxicity was observed, while severe late toxicity was observed in one patient., Conclusions: The results suggest that iodine-125 interstitial brachytherapy is an effective and safe option for the treatment of primary locally advanced ACC of the base of the tongue, with reasonably satisfactory LC and OS., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

For decades, scientists have been trying to solve the problem of dementia, with no cure currently available. Semantic-lexical impairment is well established as the early critical sign of dementia, although there are still gaps in knowledge that must be investigated. In this study, we used fMRI to observe the neural activity of 31 subjects, including 16 HC (Healthy Control) and 15 AD (Alzheimer's Disease), who participated in the naming task. The neuropsychology profile of HC (Healthy Control) and AD (Alzheimer's Disease) are discussed in this study. The involvement of FG (Fusiform Gyrus) and IFG (Inferior Frontal Gyrus) shows dominant activation in both of the groups. We observed a decrease in neural activity in the AD group, resulting in semantic deficit problems in this preliminary study. Furthermore, ROI analysis was performed and revealed both hyperactivation and hypoactivation in the AD group. The compensatory mechanism demonstrated during the task, due to the effort required to identify an animal's name, represents the character profile of AD.

Background: The experiences of professionals in well-established recovery-oriented programs are valuable for professionals in similar practice settings. This study explored professionals' experiences with providing recovery-oriented services in community psychiatric rehabilitation organizations., Methods: Semi-structured interviews were conducted with 14 professionals from five recovery-oriented psychiatric rehabilitation organizations in Taiwan. The interviews were recorded and transcribed verbatim. Thematic analysis was used for the qualitative data analysis., Results: The analyses documented three main themes with 13 subthemes. Recovery-oriented service implementation included seven subthemes: Enabling clients to set their own goals and make decisions, using a strengths-based approach, establishing partnerships with clients, improving individuals' self-acceptance, encouraging community participation, seeking family, peer, and organizational support, and building team collaboration. Problems with implementing recovery-oriented services included limited policy and organizational support, a lack of understanding of recovery among professionals, stigma, clients' lack of motivation or self-confidence in their own ability to achieve recovery, and passive or overprotective family members. Strategies to resolve implementation problems included policy changes and organizational support, improving the recovery competence and confidence of professionals, and family and public education., Conclusions: To date, this is the first known study examining the perspectives of mental health professionals who have experience implementing recovery-oriented services in Asia. The participants identified family collaboration, anti-stigma efforts, and changes in policy and attitudes as critical to successful implementation and delivery of recovery-oriented services.

Objective: To retrospectively review the impact of the outbreak of coronavirus disease 2019 (COVID-19) on services in the oral emergency room., Materials and Methods: A statistical analysis of epidemiological characteristics and the patients' diagnoses and treatments in the Emergency Department of Peking University Hospital of Stomatology during the outbreak of COVID-19 in 2020 compared with those in 2019 in Beijing, China., Results: There were fewer total visits in 2020 than in 2019 (P = 0.001), and the proportions of patients who were children, adolescents and elderly people were lower in 2020 than in 2019 (P < 0.001). The proportions of patients with acute toothache and infections were higher in 2020 than in 2019, and the proportions of patients with maxillofacial trauma and non-emergencies were lower in 2020 than in 2019 (P < 0.001). Drug treatment for acute pulpitis was used more often in 2020 than in 2019, and endodontic treatment and examination consultations were less common in 2020 than in 2019 (P = 0.022)., Conclusions: The outbreak of COVID-19 affected the patient population and structure of disease types and oral services in the emergency room. The number of visits to the oral emergency room and the proportions of the patients who were children, adolescents and elderly people were reduced, meanwhile the percentage of emergency cases, except trauma, and conservative treatments increased during the outbreak of COVID-19., Competing Interests: Conflict of interest The authors have no conflict of interest in relation to this work., (Copyright © 2021. Published by Elsevier Inc.)

Human herpes simplex viruses (HSV) 1 and 2 are extremely common human pathogens with overlapping disease spectra. Infections due to HSV-1 and HSV-2 are distinguished in clinical settings using sequence-based "typing" assays. Here we describe a case of HSV mistyping caused by a previously undescribed HSV-1 × HSV-2 recombination event in UL27, the HSV gene that encodes glycoprotein B. This is the first documented case of HSV mistyping caused by an HSV-1 × HSV-2 recombination event and the first description of an HSV interspecies recombination event in UL27, which is frequently used as a target for diagnostics and experimental therapeutics. We also review the primer and probe target sequences for a commonly used HSV typing assay from nearly 700 HSV-1 and HSV-2 samples and find that about 4% of HSV-1 samples have a single nucleotide change in at least one of these loci, which could impact assay performance. Our findings illustrate how knowledge of naturally occurring genomic variation in HSV-1 and HSV-2 is essential for the design and interpretation of molecular diagnostics for these viruses.

Objective: In systemic lupus erythematosus (SLE), widespread T cell infiltration into target organs contributes to inflammation and organ damage. Autoreactive T cells become aberrantly activated in this disease due to dysfunctional T cell receptor signaling that lowers the activation threshold. Characterizing the T cell repertoire can provide further insight into the specific homing and proliferation of these T cells into lupus target organs. In the spontaneous lupus model, MRL/lpr, the TCR repertoire has not been fully elucidated, especially for T cells infiltrating the brain. Our aim was to investigate and compare the TCR repertoire between MRL/lpr mice and its congenic controls, MRL/MpJ, and within MRL/lpr tissues. Methods: Spleen, salivary gland, and brain choroid plexus were isolated from female MRL/lpr mice and MRL/MpJ mice. The TCRβ CDR3 region was analyzed by multiplex PCRs and sequencing. Results: Significant differences were seen not only between the MRL/lpr and MRL/MpJ spleens, but also between MRL/lpr tissues. The TCR repertoire in MRL/lpr choroid plexus tissues had significantly increased clonality and sequence homology compared to MRL/lpr spleen and salivary gland. The consensus sequence, CASSQDWGGYEQYFF, was identified in the MRL/lpr choroid plexus repertoire. Conclusions: The TCR repertoire in lupus prone mice is not uniform between target organs, and suggests that T cells are specifically recruited into the choroid plexus of MRL/lpr mice. Further studies are needed to determine the antigen specificities for these infiltrating T cells in target organs of lupus mice, and their possible contribution to the pathogenesis of neuropsychiatric disease and other lupus manifestations., (Copyright © 2020 Moore, Huang, Jain, Chalmers, Macian and Putterman.)

Nearly 400,000 people worldwide are known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beginning in December 2019. The virus has now spread to over 168 countries including the United States, where the first cluster of cases was observed in the Seattle metropolitan area in Washington. Given the rapid increase in the number of cases in many localities, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we evaluated assays using seven different primer-probe sets and one assay kit. We found that the most sensitive assays were those that used the E-gene primer-probe set described by Corman et al. (V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25:2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set developed by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer-probe set or kit used. These results will provide valuable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide., (Copyright © 2020 Nalla et al.)

Background: The incidence of placenta accreta spectrum (PAS) disorders has increased rapidly in recent years and is associated with several maternal and neonatal complications. Intravoxel incoherent motion (IVIM) imaging is a method which can assess placental perfusion quantitatively. Therefore, the first aim of this study was to investigate whether patients with adverse maternal and neonatal outcomes of PAS disorders differed in the parameters from IVIM. A second aim was to identify these parameters for adverse peripartum outcome in gravid patients at risk for PAS., Methods: The subject group consisted of patients with placenta previa, in which 75 patients had PAS disorders and 24 patients did not have PAS disorders between 28+0 and 39+6 weeks, respectively. All women underwent magnetic resonance imaging (MRI) examination including an IVIM sequence with 8 b values on a 1.5T scanner. The perfusion fraction (f), pseudodiffusion coefficient (D*), and standard diffusion coefficient (D) were calculated. All medical records were received postpartum. The final degree of placental invasion was established either by placental villi alterations from a placental sample or from maternity records of the women's general practitioners., Results: Women with PAS disorders had a higher perfusion fraction (34.12%) than women without the disease (29.39%) (P<0.05). The perfusion fraction was 36.86% in women with massive blood loss and was 35.15% in women requiring transfusion, which was higher than women without massive blood loss and not requiring transfusion (P<0.05). The D value was 1.65×10 -3 mm 2 /s in women with low birth weight, which was lower than that in women with appropriate birth weight (1.70×10 -3 mm 2 /s) (P<0.05)., Conclusions: Patients with PAS disorders differed in placental perfusion fraction from women without PAS disorders. The f and D value may be used to recognize patients with certain adverse clinical outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Andrology and Urology. All rights reserved.)

Background: The incidence of PAS disorders increased rapidly in recent years, and introvoxel incoherent motion (IVIM) MRI has been applied in the assessment of placenta. The study aims to investigate whether the parameters from IVIM can be used to differentiate patients with PAS disorders complicating placenta previa and secondly to differentiate different categories of PAS disorders., Methods: The study participants were comprised of 99 patients with placenta previa, including 16 patients with placenta accreta, 51 patients with increta, 8 patients with percreta and 24 patients without PAS disorders between 28 + 0 and 39 + 6 weeks. IVIM MRI was performed on a 1.5 T scanner. Perfusion fraction (f), pseudodiffusion coefficient (D*) and diffusion coefficient (D) were calculated., Results: Women with PAS disorders had a higher perfusion fraction (p = 0.019) than women without the disease. Multiple comparisons showed perfusion fraction in patients without PAS disorders was significantly lower than in patients with placenta accreta and percreta(P = 0.018 and 0.033 respectively), but was not lower than in patients with increta(p = 1)., Conclusion: Patients with placenta accreta and percreta differed in placental perfusion fraction from women with increta and without PAS disorders.

Background: The aim of this study was to evaluate the prognostic value of positron emission tomography (PET) parameters and the PET texture features of fluorine 18-fluorodeoxyglucose ([ 18 F]FDG) uptake on pretreatment PET/computed tomography (CT) in patients with locally advanced salivary gland carcinoma treated with interstitial brachytherapy., Methods: Forty-three patients with locally advanced salivary gland carcinoma of the head and neck were treated with 125 I interstitial brachytherapy as the sole modality and underwent [ 18 F]FDG PET/CT scanning before treatment. Tumor segmentation and texture analysis were performed using the 3D slicer software. In total, 54 features were extracted and categorized as first-order statistics, morphology and shape, gray-level co-occurrence matrix, and gray-level run length matrix. Up to November 2018, the follow-up time ranged from 6 to 120 months (median 18 months). Cumulative survival was calculated by the Kaplan-Meier method. Factors between groups were compared by the log-rank test. Multivariate Cox regression analysis with a backward conditional method was used to predict progression-free survival (PFS)., Results: The 3- and 5-year locoregional control (LC) rates were 55.4% and 37.0%, respectively. The 3- and 5-year PFS rates were 51.2% and 34.1%, respectively. The 3- and 5-year overall survival (OS) rates were 77.0% and 77.0%, respectively. Univariate analysis revealed that minimum intensity, mean intensity, median intensity, root mean square, and long run emphasis (LRE) were significant predictors of PFS, whereas clinicopathological factors, conventional PET parameters, and PET texture features failed to show significance. Multivariate Cox regression analysis showed that minimum intensity and LRE were significant predictors of PFS., Conclusions: The texture analysis of pretreatment [ 18 F]FDG PET/CT provided more information than conventional PET parameters for predicting patient prognosis of locally advanced salivary gland carcinoma treated with interstitial brachytherapy. The minimum intensity was a risk factor for PFS, and LRE was a favorable factor in prognostic prediction according to the primary results.

The synthesis of functionalized pyroglutamates 15 and 16 could be achieved by the application of recently developed diastereodivergent asymmetric Michael addition reaction of iminoglycinate 7 to ethyl γ-silyloxycrotonate with >98:<2 diastereoselectivity followed by hydrolysis and lactamization. Formal syntheses of (-)-isoretronecanol and (+)-laburnine as well as a concise enantioselective synthesis of (+)-turneforcidine could be achieved from functionalized pyroglutamates 15 or 16.

Objective: To retrospectively analyze the results of treatment outcome by surgery combined with 125 I brachytherapy and correlative factors of adenoid cystic carcinoma (ACC)., Methods: In the study, 75 patients with primary ACC of oral and maxillofacial region were treated by surgery combined with 125 I seeds brachytherapy. Radical resection or subtotal resection was applied for the tumor. The brachytherapy treatment planning system was used to create implant plans with the prescribed dose of 60 Gy to 120 Gy. The 125 I seeds were implanted intraoperatively or postoperatively. The regular follow-up was required. The Kaplan-Meier method was used to assess the tumor control rate and the patients' survival rates. Meanwhile, the Cox regression analysis was used to find out the prognostic factors., Results: Local control rates at the end of 3 and 5 years were as follows: T1-T2, 92.2% and 82.0%; T3-T4, 82.6% and 82.6%; and overall, 90.0% and 78.8%. The disease-free survival rates were 74.9% and 54.3%, respectively. The overall survival rates for all the patients were 86.0% and 79.6%, respectively at the end of 3 and 5 years and were 91.3% and 91.3% for T1-T2 patients vs. 73.9% and 59.7% for T3-T4 patients. Distant metastasis-free survival rates at the end of 3 and 5 years were 84.4% and 76.7%, respectively. The distant metastasis-free survival rates at the end of 3 and 5 years were 83.4% and 79.6% with T1-T2 lesion compared with 86.0% and 67.8% with T3-T4 lesion. According to the COX univariate analysis and multivariate analysis, the risk of local recurrence would be raised by the age. Tumor stage and tumor site were the prognostic factors of the overall survival rates., Conclusion: 125 I brachytherapy conducted as an adjuvant therapy postoperatively of ACC of oral and maxillofacial region can acquire satisfactory localregional control, distant metastasis-free survival, disease-free survival and overall survival. Tumors are prone to recur on the older patients. Patients having advanced tumor stage or tumor located in the nasal cavity or sinuses will suffer lower survival rates.

The complete genome sequence of Morganella morganii DG56-16 was sequenced. This strain was isolated from the liver of a dead crocodile lizard (Shinisaurus crocodilurus). The genome size was 3.9 Mb, with a G+C content of 50.9%.

Austwickia chelonae, a species of Actinobacteria, is one of the pathogens that cause dermatophilosis in animals. Here, we report the complete genome sequence of Austwickia chelonae LK16-18, which was isolated from cutaneous granulomas in crocodile lizards.

Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART. Transplant results in ~100% myeloid donor chimerism, and up to 100% T-cell chimerism. Between 9 and 47 days post-transplant, terminal analysis shows that while cell-associated SHIV DNA levels are reduced in the blood and in lymphoid organs post-transplant, the SHIV reservoir persists in multiple organs, including the brain. Sorting of donor-vs.-recipient cells reveals that this reservoir resides in recipient cells. Moreover, tetramer analysis indicates a lack of virus-specific donor immunity post-transplant during continuous cART. These results suggest that early post-transplant, allo-HCT is insufficient for recipient reservoir eradication despite high-level donor chimerism and GVHD.

Depressive disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous papers in the literature investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial.We explored the relationship between depressive disorder and the subsequent development of STIs including human immunodeficiency virus (HIV) infection, primary, secondary, and latent syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.We identified patients who were diagnosed with the depressive disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without the depressive disorder who were matched according to age and sex. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.The depression cohort consisted of 5959 patients, and the comparison cohort consisted of 23,836 matched control patients without depressive disorder. The incidence of subsequent STIs (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.34-1.76) was higher among the depressed patients than among the patients in the comparison cohort. Furthermore, female gender compared to male (HR 1.58, 95% CI 1.24-2.01) and young age <40-year-old (HR 1.79, 95% CI 1.38-2.32) are both risk factors for acquisition of STIs in depression patient. For individual STI, the results indicated that the patients with depressive disorder exhibited a markedly higher risk for subsequent STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.Depressive disorder might increase the risk of subsequent newly diagnosed STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis in Taiwan population. Clinicians should pay particular attention to STIs in depression patients. Depression patients, especially those with the history of high-risk sexual behaviors, should be routinely screened for STIs.

Rationale: Although molecular investigations of regulator of G-protein signaling 4 (RGS4) alterations in schizophrenia patients yielded partially inconsistent findings, the previous studies suggested that RGS4 is both a positional and functional candidate gene for schizophrenia and is significantly decreased in the prefrontal cortex. However, the exact role of RGS4 in the pathophysiology of schizophrenia is unclear. Moreover, a whole genome transcription profile study showed the possibility of RGS4-regulated expression of SLC7A11(xCT), a component of cysteine/glutamate transporter or system x c - . We hypothesized that system x c - is a therapeutic target of RGS4 deficit-mediated schizophrenia. Methods: Pharmacological and genetic manipulation of RGS4 in organotypic brain slice cultures were used as an ex vivo model to investigate its role in system x c - and glutamatergic function. Lentiviral-based mouse models with RGS4 deficit in the prefrontal cortex and treatment with system x c - activator, N-acetyl cysteine (NAC), were utilized to observe their impacts on glutamatergic function and schizophrenic behaviors. Results: Genetic and pharmacological inhibition of RGS4 resulted in a significant decrease in SLC7A11 (xCT) expression and hypofunction of system x c - and reduced glutamatergic function in organotypic brain slice cultures. However, NAC restored the dysregulation of RGS4-mediated functional deficits of glutamate. Moreover, knockdown of RGS4 specifically in the prefrontal cortex caused mice to exhibit behaviors related to schizophrenia such as increased stereotypy, impaired prepulse inhibition, deficits in social interactions, working memory, and nesting behavior, while enhancing sensitivity to the locomotor stimulatory effect of MK-801. These mice displayed glutamatergic dysfunction in the prefrontal cortex, which may have contributed to the behavioral deficits. RGS4 knockdown mice that received NAC treatment had improved glutamatergic dysfunction and schizophrenia behaviors. Conclusion: Our results suggest that RGS4 deficit induces dysregulation and dysfunction of system x c - , which further results in functional deficits of the glutamatergic system and subsequently to schizophrenia-related behavioral phenotypes. Activation of system x c - offers a promising strategy to treat RGS4 deficit-mediated schizophrenia., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity cases are preventable, which motivated us to improve the treatment outcomes of digoxin. The objective of this study is to apply machine learning techniques to predict the appropriateness of initial digoxin dosage. A total of 307 inpatients who had their conditions treated with digoxin between 2004 and 2013 at a medical center in Taiwan were collected in the study. Ten independent variables, including demographic information, laboratory data, and whether the patients had CHF were also noted. A patient with serum digoxin concentration being controlled at 0.5-0.9 ng/mL after his/her initial digoxin dosage was defined as having an appropriate use of digoxin; otherwise, a patient was defined as having an inappropriate use of digoxin. Weka 3.7.3, an open source machine learning software, was adopted to develop prediction models. Six machine learning techniques were considered, including decision tree (C4.5), k -nearest neighbors (kNN), classification and regression tree (CART), randomForest (RF), multilayer perceptron (MLP), and logistic regression (LGR). In the non-DDI group, the area under ROC curve (AUC) of RF (0.912) was excellent, followed by that of MLP (0.813), CART (0.791), and C4.5 (0.784); the remaining classifiers performed poorly. For the DDI group, the AUC of RF (0.892) was the best, followed by CART (0.795), MLP (0.777), and C4.5 (0.774); the other classifiers' performances were less than ideal. The decision tree-based approaches and MLP exhibited markedly superior accuracy performance, regardless of DDI status. Although digoxin is a high-alert medication, its initial dose can be accurately determined by using data mining techniques such as decision tree-based and MLP approaches. Developing a dosage decision support system may serve as a supplementary tool for clinicians and also increase drug safety in clinical practice.

Background: Bipolar disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous studies have investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial., Objective: We explored the association between bipolar disorder and the subsequent development of STIs, including human immunodeficiency virus infection; primary, secondary, and latent syphilis; genital warts; gonorrhea; chlamydial infection; and trichomoniasis., Results: The bipolar cohort consisted of 1293 patients, and the comparison cohort consisted of 5172 matched control subjects without bipolar disorder. The incidence of subsequent STIs (hazard ratio (HR) = 2.23, 95% confidence interval (CI) 1.68-2.96) was higher among the patients with bipolar disorder than in the comparison cohort. Furthermore, female gender is a risk factor for acquisition of STIs (HR = 2.36, 95% CI 1.73-4.89) among patients with bipolar disorder. For individual STIs, the results indicated that the patients with bipolar disorder exhibited a markedly higher risk for subsequently contracting syphilis, genital warts, and trichomoniasis., Conclusions: Bipolar disorder might increase the risk of subsequent newly diagnosed STIs, including syphilis, genital warts, and trichomoniasis. Clinicians should pay particular attention to STIs in patients with bipolar disorder. Patients with bipolar disorder, especially those with a history of high-risk sexual behaviors, should be routinely screened for STIs., Methods: We identified patients who were diagnosed with bipolar disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without bipolar disorder who were matched with the bipolar cohort according to age and gender. The occurrence of subsequent new-onset STIs was evaluated in both cohorts., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Many real-world medical datasets contain some proportion of missing (attribute) values. In general, missing value imputation can be performed to solve this problem, which is to provide estimations for the missing values by a reasoning process based on the (complete) observed data. However, if the observed data contain some noisy information or outliers, the estimations of the missing values may not be reliable or may even be quite different from the real values. The aim of this paper is to examine whether a combination of instance selection from the observed data and missing value imputation offers better performance than performing missing value imputation alone. In particular, three instance selection algorithms, DROP3, GA, and IB3, and three imputation algorithms, KNNI, MLP, and SVM, are used in order to find out the best combination. The experimental results show that that performing instance selection can have a positive impact on missing value imputation over the numerical data type of medical datasets, and specific combinations of instance selection and imputation methods can improve the imputation results over the mixed data type of medical datasets. However, instance selection does not have a definitely positive impact on the imputation result for categorical medical datasets.

Background: In this study, the international affective picture system was used to evoke emotion, and then the corresponding signals were collected. The features from different points of brainwaves, frequency, and entropy were used to identify normal, moderately, and markedly ill schizophrenic patients., Methods: The signals were collected and preprocessed. Then, the signals were separated according to three types of emotions and five frequency bands. Finally, the features were calculated using three different methods of entropy. For classification, the features were divided into different sections and classification using support vector machine (principal components analysis on 95%). Finally, simple regression and correlation analysis between the total scores of positive and negative syndrome scale and features were used., Results: At first, we observed that to classify normal and markedly ill schizophrenic patients, the identification result was as high as 81.5%, and therefore, we further explored moderately and markedly ill schizophrenic patients. Second, the identification rate in both moderately and markedly ill schizophrenic patient was as high as 79.5%, which at the Fz point signal in high valence low arousal fragments was calculated using the ApEn methods. Finally, the total scores of positive and negative syndrome scale were used to analyze the correlation with the features that were the five frequency bands at the Fz point signal. The results show that the p value was less than .001 at the beta wave in the 15-18 Hz frequency range.

Background: Endothelial inflammation is an increasingly prevalent condition in the pathogenesis of many cardiovascular diseases. (-)-7(S)-hydroxymatairesinol (7-HMR), a naturally occurring plant lignan, possesses both antioxidant and anti-cancer properties and therefore would be a good strategy to suppress tumor necrosis factor-α (TNF-α)-mediated inflammation in vascular endothelial cells (VECs)., Purpose: The objective of this study is to evaluate for its anti-inflammatory effect on TNF-α-stimulated VECs and underling mechanisms., Study Design/methods: The effect of the 7-HMR on suppression of TNF-α-induced inflammation mediators in VECs were determined by qRT-PCR and Western blot. MAPKs and phosphorylation of Akt, HO-1 and NF-κB p65 were examined using Western blot. Nuclear localisation of NF-κB was also examined using Western blot and immunofluorescence., Results: Here we found that 7-HMR could suppress TNF-α-induced inflammatory mediators, such as vascularcelladhesion molecule-1, interleukin-6 and inducible nitric oxide synthase expression both in mRNA and protein levels, and concentration-dependently attenuated reactive oxidase species generation. We further identified that 7-HMR remarkably induced superoxide dismutase and heme oxygenase-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (keap1) and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, 7-HMR time- and concentration-dependently attenuated TNF-α-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) and Akt, but not p38, or c-Jun N-terminal kinase 1/2. Moreover, 7-HMR significantly suppressed TNF-α-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65., Conclusion: Our results demonstrated that 7-HMR inhibited TNF-α-stimulated endothelial inflammation, at least in part, through inhibition of NF-κB activation and upregulation of Nrf2-antioxidant response element signaling pathway, suggesting 7-HMR might be used as a promising vascular protective drug., (Copyright © 2017. Published by Elsevier GmbH.)

Background: Schizophrenia is a neurological disease characterized by alterations to patients' cognitive functions and emotional expressions. Relevant studies often use magnetic resonance imaging (MRI) of the brain to explore structural differences and responsiveness within brain regions. However, as this technique is expensive and commonly induces claustrophobia, it is frequently refused by patients. Thus, this study used non-contact infrared thermal facial images (ITFIs) to analyze facial temperature changes evoked by different emotions in moderately and markedly ill schizophrenia patients., Methods: Schizophrenia is an emotion-related disorder, and images eliciting different types of emotions were selected from the international affective picture system (IAPS) and presented to subjects during ITFI collection. ITFIs were aligned using affine registration, and the changes induced by small irregular head movements were corrected. The average temperatures from the forehead, nose, mouth, left cheek, and right cheek were calculated, and continuous temperature changes were used as features. After performing dimensionality reduction and noise removal using the component analysis method, multivariate analysis of variance and the Support Vector Machine (SVM) classification algorithm were used to identify moderately and markedly ill schizophrenia patients., Results: Analysis of five facial areas indicated significant temperature changes in the forehead and nose upon exposure to various emotional stimuli and in the right cheek upon evocation of high valence low arousal (HVLA) stimuli. The most significant P-value (lower than 0.001) was obtained in the forehead area upon evocation of disgust. Finally, when the features of forehead temperature changes in response to low valence high arousal (LVHA) were reduced to 9 using dimensionality reduction and noise removal, the identification rate was as high as 94.3%., Conclusions: Our results show that features obtained in the forehead, nose, and right cheek significantly differed between moderately and markedly ill schizophrenia patients. We then chose the features that most effectively distinguish between moderately and markedly ill schizophrenia patients using the SVM. These results demonstrate that the ITFI analysis protocol proposed in this study can effectively provide reference information regarding the phase of the disease in patients with schizophrenia.

To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for 5 consecutive days. Patients treated with SMD and acupuncture experienced significantly shorter hospital stay, shorter time to first flatus and shorter time to defecation than patients in the other groups (all P < 0.05). Incidence of grade I and II complications was also significantly lower in patients treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no intervention in terms of hospital stay, incidence of complications, and time to first bowel motion, flatus, and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum does not appear to affect recovery of bowel function or hospital stay, though it may benefit patients who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).

Breast cancer is an all too common disease in women, making how to effectively predict it an active research problem. A number of statistical and machine learning techniques have been employed to develop various breast cancer prediction models. Among them, support vector machines (SVM) have been shown to outperform many related techniques. To construct the SVM classifier, it is first necessary to decide the kernel function, and different kernel functions can result in different prediction performance. However, there have been very few studies focused on examining the prediction performances of SVM based on different kernel functions. Moreover, it is unknown whether SVM classifier ensembles which have been proposed to improve the performance of single classifiers can outperform single SVM classifiers in terms of breast cancer prediction. Therefore, the aim of this paper is to fully assess the prediction performance of SVM and SVM ensembles over small and large scale breast cancer datasets. The classification accuracy, ROC, F-measure, and computational times of training SVM and SVM ensembles are compared. The experimental results show that linear kernel based SVM ensembles based on the bagging method and RBF kernel based SVM ensembles with the boosting method can be the better choices for a small scale dataset, where feature selection should be performed in the data pre-processing stage. For a large scale dataset, RBF kernel based SVM ensembles based on boosting perform better than the other classifiers., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the clinical application and preliminary results of 125 I radioactive seeds brachytherapy in the comprehensive treatment of the pediatric soft tissue sarcoma in head and neck. Methods: A total of 24 pediatric patients with soft tissue sarcoma in head and neck were treated at Peking University School of Stomatology from April 2012 to July 2015. The data was collected and analyzed through statistical methods, which included the pathological type, gender, age, tumor location, volume, treatment and the clinical results after the application of 125 I radioactive seeds brachytherapy. Results: Among the 24 patients, there were 18 patients of rhabdomyosarcoma, 2 Ewing's sarcoma, 2 fibrosarcoma, 1 synovial sarcoma and 1 malignant fibrous histiocytoma. After a follow-up of 9-48 months, 1 case of temporal rhabdomyosarcoma was observed to have a progression to the the lateral cranial base at the time of 12 months, 2 cases realized local control and systemic progression, the rest were completely relieved, and there was no recurrence during the follow-up period.The Kaplan-Meier survival analysis showed that the 1-year and 3-year local control rate were both 94.1%, the 1-year and 3-year event-free survival rate were 87.4% and 77.7%. Conclusion: The preliminary results indicate that 125 I radioactive seeds brachytherapy play a very important role in the improvement of the local control rate and survival quality of the pediatric soft tissue sarcoma patient in head and neck, and it's a minimally invasive treatment with the advantage of accuracy andsmall side effects.

Objective:: Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder., Methods:: We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder., Results:: The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26-1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11-1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders., Conclusions:: Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture.

Despite an increasing number of reports on the associations between chronic occupational stress and structural and functional changes of the brain, the underlying neural correlates of perceived occupational stress is still not clear. Perceived stress reflects the extents to which situations are appraised as stressful at a given point in one's life. Using near-infrared spectroscopy, we investigated the associations between perceived occupational stress and cortical activity over the bilateral frontotemporal regions during a verbal fluency test. Sixty-eight participants (17 men, 51 women), 20-62 years of age were recruited. Perceived occupational stress was measured using the Chinese version of Job Content Questionnaire, and the Chinese version of the Copenhagen Burnout Inventory. We found statistically significant negative associations between occupational burnout and brain cortical activity over the fronto-polar and dorsolateral prefrontal cortex during the VFT (r = -0.343 to -0.464). In conclusion, our research demonstrated a possible neural basis of perceived occupational stress that are distributed across the prefrontal cortex.

To transfer the preplan for the head and neck brachytherapy to the clinical implantation procedure, a preplan-based 3D-printed individual template for needle insertion guidance had previously been designed and used. The accuracy of needle insertion using this kind template was assessed in vivo In the study, 25 patients with head and neck tumors were implanted with 125 I radioactive seeds under the guidance of the 3D-printed individual template. Patients were divided into four groups based on the site of needle insertion: the parotid and masseter region group (nine patients); the maxillary and paranasal region group (eight patients); the submandibular and upper neck area group (five patients); and the retromandibular region group (six patients). The distance and angular deviations between the preplanned and placed needles were compared, and the complications and time required for needle insertion were assessed. The mean entrance point distance deviation for all 619 needles was 1.18 ± 0.81 mm, varying from 0.857 ± 0.545 to 1.930 ± 0.843 mm at different sites. The mean angular deviation was 2.08 ± 1.07 degrees, varying from 1.85 ± 0.93 to 2.73 ± 1.18 degrees at different sites. All needles were manually inserted to their preplanned positions in a single attempt, and the mean time to insert one needle was 7.5 s. No anatomical complications related to inaccurately placed implants were observed. Using the 3D-printed individual template for the implantation of 125 I radioactive seeds in the head and neck region can accurately transfer a CT-based preplan to the brachytherapy needle insertion procedure. Moreover, the addition of individual template guidance can reduce the time required for implantation and minimize the damage to normal tissues., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Previous research has suggested a link between antidepressants use and the development of cerebrovascular events, but there has never been any study investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients treated with a selective serotonin reuptake inhibitor (SSRI)., Methods: A retrospective observational cohort study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2001 and 2009. A total of 527 OCD patients with 412 subjects in the SSRI use group and 115 in the non SSRI use group were included. Multivariable Cox proportional-hazards models were used to explore the associations between SSRI use and the occurrence of stroke, controlling for age, gender, concomitant medications, and comorbid medical illnesses., Results: A total of nineteen OCD patients were diagnosed with new onset of stroke during the follow-up period including six cases in the SSRI group and thirteen in the non SSRI use group. SSRI use was demonstrated to be associated with a decreased risk of stroke (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.10-0.86, P = 0.02). The increase in age-related risk of strokes was 2.55 per decade (HR = 2.55; 95% CI = 1.74-3.75, P<0.001). Alternatively, sex, concomitant use of aspirin and non-steroidal anti-inflammatory drugs, and comorbidities with angina pectoris, diabetes mellitus, hypertension, and hyperlipidemia were not found to be associated with an increased risk for stroke in OCD patients., Conclusions: Our study showed that SSRI use was associated with decreased risk of stroke in OCD patients. Further investigation into the possible biological mechanisms underlying the relationship between stroke and SSRI use in OCD patients is warranted., Competing Interests: All authors declared no conflicts of interest regarding this study.

Background: We investigated whether variation in the dopamine D2 receptor gene (DRD2) and tri-dimensional personality questionnaire (TPQ) scores could be used to aid adjustment of daily methadone requirements of heroin addicts. DRD2 TaqI B polymorphisms and TPQ scores were determined in 138 male Taiwanese heroin addicts who were receiving methadone treatment. Borderline index (harm avoidance + novelty seeking-reward dependence) was calculated for each subject, and three groups were defined: high (mean from all subjects plus 1 standard deviation, or greater), low (half of the calculated high score, or lower) and medium (all values between the high and low scores)., Results: No significant differences in age (p = 0.60), mean methadone dose (p = 0.75) or borderline index group (p = 0.25) were observed between subjects bearing the B1/B1, B1/B2 and B2/B2 DRD2 TaqI genotypes. Among the individuals with low (≤10), medium (11-20) and high (≥21) borderline index scores, there was a significant difference in mean methadone dose (p = 0.04), but not age (p = 0.90). Further analysis showed that mean methadone dose was significantly higher in subjects with low borderline index scores than in those with high scores (62.5 vs. 47.0 mg/day, p = 0.03). The odds ratio for a daily methadone requirement ≥60 mg (median dose across the 138 subjects) was 2.64-fold greater in the low borderline index group than in the high group (p = 0.04)., Conclusions: Although the DRD2 TaqI B genotype was not associated with methadone use requirements, borderline index was revealed as a potential predictive marker for the adjustment of methadone dosage requirements in heroin addicts.

Introduction: K-nearest neighbor (k-NN) classification is conventional non-parametric classifier, which has been used as the baseline classifier in many pattern classification problems. It is based on measuring the distances between the test data and each of the training data to decide the final classification output., Case Description: Since the Euclidean distance function is the most widely used distance metric in k-NN, no study examines the classification performance of k-NN by different distance functions, especially for various medical domain problems. Therefore, the aim of this paper is to investigate whether the distance function can affect the k-NN performance over different medical datasets. Our experiments are based on three different types of medical datasets containing categorical, numerical, and mixed types of data and four different distance functions including Euclidean, cosine, Chi square, and Minkowsky are used during k-NN classification individually., Discussion and Evaluation: The experimental results show that using the Chi square distance function is the best choice for the three different types of datasets. However, using the cosine and Euclidean (and Minkowsky) distance function perform the worst over the mixed type of datasets., Conclusions: In this paper, we demonstrate that the chosen distance function can affect the classification accuracy of the k-NN classifier. For the medical domain datasets including the categorical, numerical, and mixed types of data, K-NN based on the Chi square distance function performs the best.