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Yong Li,1,* Sheng-Chun Fang,2,* Lan Zhou,1 Xue-Mei Mo,3 Hao-Dong Guo,3 Yan-Bo Deng,3 Hong-Hao Yu,1 Wei-Yi Gong3 1College of Biotechnology, Guilin Medical University, Guilin, Guangxi, 541100, People’s Republic of China; 2Department of Anesthesiology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430015, People’s Republic of China; 3Department of Pain Management, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Hao Yu, College of Biotechnology, Guilin Medical University, Guilin, Guangxi, 541100, People’s Republic of China, Email geneyhh@126.com Wei-Yi Gong, Department of Pain Management, Affiliated Hospital of Guilin Medical University, Guilin, 541000, Guangxi, People’s Republic of China, Email 942261597@qq.comBackground: Neuropathic pain (NP) after spinal cord injury (SCI-evoked NP) is clinically challenging; the underlying mechanisms are not fully understood, leading to a lack of promising treatment options. NP occurs in only a subset of patients with SCI. The injured spinal cord exhibits a series of histopathological changes, and the complement system has been shown to play an important role in these processes. In addition, NMDA receptor subunit 2B (NR2B) is involved in the development and maintenance of NP. This preliminary study was performed to investigate the correlations of the complement receptor 3/complement component 3 (CR3/C3) pathway and NR2B with SCI-evoked NP.Methods: A trauma-induced SCI animal model was established and SCI-evoked NP was evaluated by behavioural analysis. Transcriptome analysis was performed to identify genes in the CR3/C3 pathway related to synaptic modification, while the expression and distribution of NR2B in the injured spinal cord, and the relation to NP, were examined by immunohistochemical analysis.Results: Nine of seventeen SCI rats (52.9%) developed NP. C3 mRNA expression was significantly decreased in SCI-evoked NP rats and significantly increased in the non-NP SCI rats. C1q mRNA and CR3 mRNA expression were significantly increased in all SCI rats, but higher levels of expression were observed in the non-NP SCI rats. NR2B mRNA expression was significantly increased in the SCI-evoked NP rats and significantly decreased in the non-NP SCI rats. In addition, significantly elevated expression of NR2B-positive cells was seen in lamina II of the superficial dorsal horn in SCI-evoked NP rats in comparison with non-NP SCI rats.Conclusion: NP occurred in only a subset of SCI rats, and the CR3/C3 pathway and NR2B were involved in SCI-evoked NP. Further studies are required to determine the mechanisms underlying the SCI-evoked NP associated with the CR3/C3 pathway and NR2B.Keywords: spinal cord injury, neuropathic pain, complement receptor 3, complement component 3, NMDA receptor 2B subunit

Katrina Wilcox Hagberg,1 Hozefa A Divan,2 Shona C Fang,2 J Curtis Nickel,3 Susan S Jick1 1Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, 2New England Research Institutes, Inc., Watertown, MA, USA; 3Kingston General Hospital, Queen’s University, Kingston, ON, Canada Background: Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited. Patients and methods: We conducted a cohort study with nested case–control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age ≥40 years and at least 3 years after the start of their electronic medical record. We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated. Results: Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05–4.14) and case–control analyses (OR=3.31, 95% CI 2.66–4.10), whereas the risk was null for users of AB only. The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia. The risk was higher for dutasteride than for finasteride. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61–3.80). Conclusion: In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure. Keywords: 5ARIs, benign prostatic hyperplasia, gynecomastia, male breast cancer

Background: To better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM2.5 and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.Methods: Twenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00-7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM2.5 metal exposures both with and without adjustment for total PM2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM2.5 and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM2.5 as surrogates for the differential effects of metal exposures in models for night rMSSD.Results: The median PM2.5 exposure was 650 microg/m3; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 microg/m3 to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 microg/m3 increase in manganese. However, even after adjusting for individual metals, increases in total PM2.5 exposures were associated with declines in night rMSSD.Conclusion: These results support the cardiotoxicity of PM2.5 metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components. [ABSTRACT FROM AUTHOR]

Objective: Methamphetamine causes considerable short- and long-term adverse health effects. Our aim was to assess the effects of methamphetamine use on pulmonary hypertension and lung diseases at the population level., Methods: This population-based retrospective study used data from the Taiwan National Health Insurance Research Database between 2000 and 2018 that included 18,118 individuals with methamphetamine use disorder (MUD) and 90,590 matched participants of the same age and sex without substance use disorder as the non-exposed group. A conditional logistic regression model was used to estimate associations of methamphetamine use with pulmonary hypertension and lung diseases such as lung abscess, empyema, pneumonia, emphysema, pleurisy, pneumothorax, or pulmonary hemorrhage. Incidence rate ratios (IRRs) of pulmonary hypertension and hospitalization due to lung diseases were determined between the methamphetamine group and non-methamphetamine group using negative binomial regression models., Results: During an 8-year observation period, 32 (0.2%) individuals with MUD and 66 (0.1%) non-methamphetamine participants suffered from pulmonary hypertension, and 2652 (14.6%) individuals with MUD and 6157 (6.8%) non-methamphetamine participants suffered from lung diseases. After adjusting for demographic characteristics and comorbidities, individuals with MUD were 1.78 times (95% confidence interval (CI) = 1.07-2.95) more likely to have pulmonary hypertension and 1.98 times (95% CI = 1.88-2.08) more likely to have a lung disease, especially emphysema, lung abscess, and pneumonia in descending order. Furthermore, compared to the non-methamphetamine group, the methamphetamine group was associated with higher risks of hospitalization caused by pulmonary hypertension and lung diseases. The respective IRRs were 2.79 and 1.67. Individuals with polysubstance use disorder were associated with higher risks of empyema, lung abscess, and pneumonia compared to individuals with MUD alone, with respective adjusted odds ratios of 2.96, 2.21, and 1.67. However, pulmonary hypertension and emphysema did not differ significantly between MUD individuals with or without polysubstance use disorder., Conclusions: Individuals with MUD were associated with higher risks of pulmonary hypertension and lung diseases. Clinicians need to ensure that a methamphetamine exposure history is obtained as part of the workup for these pulmonary diseases and provide timely management for this contributing factor., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM)., Methods: 824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m 2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays., Results: Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44-2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68-0.76) to 0.74 (95 %CI 0.70-0.78), p = 0.099., Conclusions: Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Evaluating the risk of relapse is a pivotal step in the treatment of patients with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS for patients with MUD., Methods: 247 patients with MUD self-rated the Chinese version of the SRRS. Cronbach's alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of the scores of the Chinese version of the SRRS with the relapse rate within 3, 6, and 12 months of follow-up., Results: CFA revealed satisfactory model fit estimates for the 22-item Chinese version of the SRRS that consisted of four subscales. The four-factored 22-item Chinese version of the SRRS had adequate internal consistency with Cronbach's alphas ranging from 0.76 to 0.92. The 22-item Chinese version of the SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between participants with (SDS score ≥ 4) and without (SDS score < 4) methamphetamine dependence (area under the curve = 0.71, p < 0.01)., Conclusions: The 22-item Chinese version of the SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD., (© 2024. The Author(s).)

In epiphytes, aerial roots are important to combat water-deficient, nutrient-poor, and high-irradiance microhabitats. However, whether aerial roots can respond to gravity and whether auxin plays a role in regulating aerial root development remain open-ended questions. Here, we investigated the gravitropic response of the epiphytic orchid Phalaenopsis aphrodite. Our data showed that aerial roots of P. aphrodite failed to respond to gravity, and this was correlated with a lack of starch granules/statolith sedimentation in the roots and the absence of the auxin efflux carrier PIN2 gene. Using an established auxin reporter, we discovered that auxin maximum was absent in the quiescent center of aerial roots of P. aphrodite. Also, gravity failed to trigger auxin redistribution in the root caps. Hence, loss of gravity sensing and gravity-dependent auxin redistribution may be the genetic factors contributing to aerial root development. Moreover, the architectural and functional innovations that achieve fast gravitropism in the flowering plants appear to be lost in both terrestrial and epiphytic orchids, but are present in the early diverged orchid subfamilies. Taken together, our findings provide physiological and molecular evidence to support the notion that epiphytic orchids lack gravitropism and suggest diverse geotropic responses in the orchid family., (© 2024 The Author(s). Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Objective: The Penn Alcohol Craving Scale (PACS) is a five-item, single-dimension questionnaire that is used to measure a patient's alcohol craving. We sought to develop the Chinese version of the PACS (PACS-C) and assess its reliability and validity., Methods: A total of 160 Taiwanese patients with alcohol use disorder were enrolled in this study. The internal consistency and concurrent validity of the PASC-C with the visual analogue scale (VAS) for craving, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd), and the Severity of Alcohol Dependence Questionnaire (SADQ) were assessed. The test-retest reliability of the PASC-C was evaluated 1 day after the baseline measurements. Confirmatory factor analysis (CFA) was performed to examine the psychometric properties of the PACS-C., Results: The PACS-C exhibited good internal consistency (Cronbach's α=0.95) and test-retest reliability (r=0.97). This scale showed high correlations with the VAS (r=0.81) and YBOCS-hd (r=0.81 and 0.79 for the obsession and compulsion subscales, respectively), and moderate correlation with the SADQ-C (r=0.47). Furthermore, CFA results revealed that the PACS-C had good fit indices under various models., Conclusion: The PACS-C appears to be a reliable and valid tool for assessing alcohol craving in patients with alcohol use disorder in Taiwan.

Objectives: To assess the effectiveness of cold therapy for pain and anxiety associated with chest tube removal., Design: A Systematic review and meta-analysis of randomized controlled trials., Data Sources: Articles were searched from Cochrane Library, PubMed, Embase, CINAHL, ProQuest, Airiti Library, China National Knowledge Infrastructure, and the National Digital Library of Theses and Dissertations in Taiwan., Review/analysis Methods: Eight electronic databases were searched from inception to August 20, 2022. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of the included studies. Using a random-effects model, we calculated Hedges' g and its associated confidence interval to evaluate the effects of cold therapy. Cochrane's Q test and an I 2 test were used to detect heterogeneity, and moderator and meta-regression analyses were conducted to explore possible sources of heterogeneity. Publication bias was assessed using a funnel plot, Egger's test, and trim-and-fill analysis., Results: We examined 24 trials involving 1,821 patients. Cold therapy significantly reduced pain during and after chest tube removal as well as anxiety after chest tube removal (Hedges' g: -1.28, -1.27, and -1.80, respectively). Additionally, the effect size of cold therapy for reducing anxiety after chest tube removal was significantly and positively associated with that of cold therapy for reducing pain after chest tube removal., Conclusions: Cold therapy can reduce pain and anxiety associated with chest tube removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

This study proposes a multi-level model of institutional innovation in the healthcare sector-in other words, field-level institutional change pressures that start as network-level institutional innovation by hospitals and government for their organizational performance, with an emphasis on the effect of organizational-level construct-knowledge creation capabilities. A case study using in-depth interviews and a historical inquiry approach has been used to qualitatively analyze our cases during the development of Taiwan's National Health Insurance (NHI). Our results propose a multi-level explanation of institutional innovation by showing how field-level institutional change pressures can stimulate the government's institutional innovation at the network level. Moreover, knowledge creation capabilities may positively influence the government hospitals' ongoing institutional change pressures induced institutional innovation activity for their performance at the organizational level in an institutional setting. This study contributes to health organization management researchers and administrators by developing explanations of institutional innovation and creating a much-needed multi-level insight into hospital behavior in the highly institutionalized healthcare sector., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Although studies in Western countries have investigated the quality of life (QoL) of heroin users, limited research on this topic has been conducted in Asia. The present study assessed QoL in patients with heroin dependence receiving medications to treat opioid use disorder., Methods: We performed a cross-sectional study of patients with heroin dependence receiving methadone and buprenorphine treatment. The demographic and substance use variables of patients receiving methadone and buprenorphine were compared. The Chinese Health Questionnaire (CHQ-12), Obsessive Compulsive Drug Use Scale (OCDUS), and World Health Organization Quality of Life Short Form Taiwan version (WHOQOL-BREF-T) were administered to measure patient mental health problems, addiction severity, and QoL, respectively. Multivariate regression was used to identify the factors associated with QoL., Results: A total of 149 patients receiving methadone and 31 receiving buprenorphine completed the questionnaires. Individuals in the buprenorphine group were more likely to be married (p = 0.024) or employed (p = 0.024), have a higher educational level (p = 0.013), have lower drug craving (OCDUS: p = 0.035), or have higher QoL (WHOQOL-BREF-T: p = 0.004) than those in the methadone group. After adjustment for other variables, employment was positively associated with the physical, psychological, and environmental domains of QoL. Receiving buprenorphine treatment (p = 0.032) and longer treatment duration (p = 0.016) were associated with higher psychological QoL., Conclusion: Several factors were associated with QoL in patients with heroin dependence. Some measures may improve their QoL, such as reducing employment barriers, improving treatment adherence, or increasing accessibility to buprenorphine treatment., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form and in complexed forms bound to either the conjugated sex hormones β-estradiol 17-(β-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site-directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate-binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate-binding pocket of MRPs and provide a structural platform for the rational design of inhibitors., (© 2023 The Authors.)

Background: Methamphetamine (METH) is a Schedule II illicit drug in Taiwan. A 12-month legal-medical joint intervention program has been developed for first-time METH offenders during deferred prosecution. Risk factors associated with METH relapse use among these individuals were unknown., Methods: We enrolled a total of 449 METH offenders referred by the Taipei District Prosecutor's Office to Taipei City Psychiatric Center. The study defines relapse as having any positive urine toxicology result or self-report of METH use during 12-month treatment. We compared demographic and clinical variables between a relapse group and nonrelapse group and used a Cox proportional hazards model to determine variables associated with time to relapse., Results: Of all participants, 37.8 % relapsed to use METH and 23.2 % were noncompleters in the one-year follow-up. Compared to the nonrelapse group, the relapse group had lower educational attainment, more severe psychological symptoms, longer duration of METH use, higher odds of polysubstance use, higher craving severity, and higher odds of positive baseline urine. The Cox analysis revealed individuals with positive urine results and higher craving severity at baseline were at higher risks of METH relapse (hazard ratio [95 % CI]: 3.85 [2.61-5.68] and 1.71 [1.19-2.46], respectively, p < 0.001). Baseline positive urine results and high craving could also predict a shorter length of time to relapse than their respective counterparts., Conclusions: Positive urine screening for METH at baseline and high craving severity are two indicators of an increased risk of drug relapse. Tailored treatment plans incorporating these findings to prevent relapse are warranted in our joint intervention program., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare in this study., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy., Methods: From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria)., Results: All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation( P <0.05)., Conclusion: The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

Background: Our prior open trial showed the feasibility of a smartphone-based support system coupled with a Bluetooth breathalyzer (SoberDiary) in assisting recovery for patients with alcohol dependence (AD). In this 24-week follow-up study, we further explored the efficacy of supplementing SoberDiary to treatment as usual (TAU) over 12 weeks of intervention and whether the efficacy persisted in the post-intervention 12 weeks., Methods: 51 patients who met the DSM-IV criteria of AD were randomly assigned to the technological intervention group (TI group, receiving technology intervention of SoberDiary plus TAU, n  = 25) or those receiving only TAU (TAU group, n  = 26). After 12 weeks of intervention (Phase I), all participants were followed for another post-intervention 12 weeks (Phase II). We collected the drinking variables and psychological assessment data every 4 weeks (i.e., weeks 4, 8, 12, 16, 20, and 24). In addition, the cumulative abstinence days and retention rates were recorded. We used mixed-model analysis to compare the difference in outcomes between groups., Results: In Phase I or Phase II, we did not find differences in drinking variables, alcohol craving, depression, or anxiety severity between the two groups. However, the TI group showed greater self-efficacy for drinking refusal in Phase II than the TAU group., Conclusions: Although our system (SoberDiary) did not demonstrate benefits in drinking or emotional outcomes, we found the system holds promise to enhance self-efficacy on drinking refusal. Whether the benefit in promoting self-efficacy persists longer than 24 weeks requires further investigation., Competing Interests: All authors declare that they have no conflicts of interest., (© 2023 The Authors.)

Electrocardiogram (ECG) biometric provides an authentication to identify an individual on the basis of specific cardiac potential measured from a living body. Convolutional neural networks (CNN) outperform traditional ECG biometrics because convolutions can produce discernible features from ECG through machine learning. Phase space reconstruction (PSR), using a time delay technique, is one of the transformations from ECG to a feature map, without the need of exact R-peak alignment. However, the effects of time delay and grid partition on identification performance have not been investigated. In this study, we developed a PSR-based CNN for ECG biometric authentication and examined the aforementioned effects. Based on a population of 115 subjects selected from the PTB Diagnostic ECG Database, a higher identification accuracy was achieved when the time delay was set from 20 to 28 ms, since it produced a well phase-space expansion of P, QRS, and T waves. A higher accuracy was also achieved when a high-density grid partition was used, since it produced a fine-detail phase-space trajectory. The use of a scaled-down network for PSR over a low-density grid with 32 × 32 partitions achieved a comparable accuracy with using a large-scale network for PSR over 256 × 256 partitions, but it had the benefit of reductions in network size and training time by 10 and 5 folds, respectively.

Background: Improper or insufficient treatment of mental health illness harms individuals, families, and society. When psychiatric treatment shifts from a hospital-based to a community-based health care system, risk management is essential to the provision of effective care., Objective: We examine whether an upgrade in home visit frequency of psychiatric patients as identified by public health nurses can predict the subsequent need for emergency escort services for medical treatment., Design: A 2-year retrospective medical record review., Settings: A district of New Taipei City in Taiwan., Participants: A total of 425 patients with a diagnosed mental health illness cared for through home visits by public health nurses from January 2018 to December 2019., Methods: We accessed the Ministry of Health and Welfare's psychiatric care management information system to identify a set of medical records, and analyzed these records using chi-square and regression analyses., Results: The analyses indicated that the groups experiencing the greatest need for emergency escort services were: male, 35-49 years old, with a senior high school level of education, without a disability identification card, with a schizophrenia diagnosis, and had been reported by the nurse as having progressed to a serious level. Nurses' increased frequency of home visits (an indicator that the patient's overall condition was worsening) and nurses' reports of increased severity of problems were significant predictors of the need for emergency escort services., Conclusions: The nurses' adjustment of visit frequency based on the results of the visit assessment predicts the need for emergency escort services for mental patients. The findings support not only the professional roles and functions of public health nurses, but also the importance of strengthening psychiatric health community support services., 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 © 2023 Wu, Hung, Fang and Lee.)

Aim: The study examined the differences in nursing student empathy, caring behavior and competence between the experimental and control groups before and after educational intervention and to predict the factors affecting their core competencies., Background: Educating nursing students in empathy and caring behaviors before entering clinical practice is challenging., Design: We used a two-group pretest and post-test quasi-experimental design., Methods: First-year nursing students from medical schools in Taiwan participated in our study. Data were collected between March and May 2022. The learning method used with the intervention group was role-playing with videos and guided reflection. The control group was exposed to traditional curriculum. Empathy, caring behavior and competence were measured using the Jefferson Scale of Empathy- Healthcare Providers, the Caring Behaviors Scale and the Nursing Student Competence Scale., Result: A total of 72 participants (40 in the experimental group and 32 in the control group) were included in the final statistical analysis. The response rate was 92%. Statistically significant differences in nursing student empathy, caring behavior and competence were observed between the experimental and control groups (p < .05). The η 2 effect levels were 0.083, 0.223 and 0.270. Higher caring behavior scores were significantly associated with higher nursing student competence scores (β = 0.81, 95% CI:0.66-0.97)., Conclusions: Education based on video role-play and guided reflection improved empathy, caring behavior and nursing competence in first-year nursing students., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

RGB and CYMK are two major coloring schemes currently available for light colors and pigment colors, respectively. Both systems use letter-based color codes that require a large range of values to represent different colors. The problem is that these two systems are hard to use for manipulating any operations involving combinations of colors, and they lack the capacity for inter-changeability or unification. Based on prime number theory and Goldbach's conjecture, this study presents a universal color system (C 235 ) using a number-based structure to encode, compute and unify all colors on a color wheel. The proposed C 235 system offers a unified representation for the efficient encoding and effective manipulation of color. It can be applied to designing a high-rate LCD system and colorizing objects with multiple attributes and DNA codons, opening the door to manipulating colors and lights for even broader applications., (© 2023. The Author(s).)

Bacterial fruit blotch, caused by the seedborne gram-negative bacterium Acidovorax citrulli , is one of the most destructive bacterial diseases of cucurbits (gourds) worldwide. Despite its prevalence, effective and reliable means to control bacterial fruit blotch remain limited. Transcriptomic analyses of tissue culture-based regeneration processes have revealed that organogenesis-associated cellular reprogramming is often associated with upregulation of stress- and defense-responsive genes. Yet, there is limited evidence supporting the notion that the reprogrammed cellular metabolism of the regenerated tissued confers bona fide antimicrobial activity. Here, we explored the anti-bacterial activity of protocorm-like-bodies (PLBs) of Phalaenopsis aphrodite . Encouragingly, we found that the PLB extract was potent in slowing growth of A. citrulli , reducing the number of bacteria attached to watermelon seeds, and alleviating disease symptoms of watermelon seedlings caused by A. citrulli . Because the anti-bacterial activity can be fractionated chemically, we predict that reprogrammed cellular activity during the PLB regeneration process produces metabolites with antibacterial activity. In conclusion, our data demonstrated the antibacterial activity in developing PLBs and revealed the potential of using orchid PLBs to discover chemicals to control bacterial fruit blotch disease., Competing Interests: S-CF and B-LH are named inventors on a patent application pertaining to the technology that was filed by Academia Sinica. The remaining 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 © 2022 Ho, Chen, Huang and Fang.)

This study aims to describe the relationship between physical activity, suboptimal health status based on traditional Chinese medicine, and psychological health in older people in Taiwan. A total of 4,497 older individuals were selected from the Taiwan Biobank Research Database. Suboptimal health status was assessed using a body constitution questionnaire to measure yang deficiency, yin deficiency, and stasis. The results showed that older adults involved in physical activity had a lower likelihood of yang/yin deficiency and stasis constitutions than physically inactive people. Participants with yang deficiency or stasis constitutions had a higher likelihood of poor psychological health, whereas those with yin deficiency had a greater likelihood of depression. People involved in physical activity had a lower likelihood of depression than physically inactive people. Compared with male older adults, females had a lower percentage of physical activity habits, poorer body constitutions, and poorer psychological health.

Background/purpose: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities., Methods: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression., Results: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine., Conclusion: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

The protocorm is a structure that is formed upon germination of an orchid seed. It lacks cotyledons and is ovoid in shape. The protocorm-like body (PLB), on the other hand, is a protocorm-like organ induced from somatic tissues. PLBs have been widely used for orchid micropropagation. Because of its unique structure and its application in the orchid industry, PLB development has drawn considerable interest from orchid and developmental biologists. Our previous genome-wide comparative transcriptome study demonstrated that protocorms and PLBs share similar molecular signatures and suggested that SHOOT MERISTEMLESS (STM)-dependent organogenesis is important for PLB development. Here, we show that overexpression of Phalaenopsis aphrodite STM (PaSTM) greatly enhances PLB regeneration from vegetative tissue-based explants of Phalaenopsis orchids, confirming its regulatory role in PLB development. Expression of PaSTM restored shoot meristem function of the Arabidopsis (Arabidopsis thaliana) stm-2 mutant. Moreover, we identified class S11 MYB transcription factors (TFs) as targets downstream of PaSTM. A cis-acting element, TTGACT, identified in the promoters of S11 MYB TFs was found to be important for PaSTM binding and activation. Overexpression of PaSTM or its downstream targets, PaMYB13, PaMYB14, and PaMYB17, enhanced de novo shoot regeneration in Arabidopsis, indicating the active role of the PaSTM-S11 PaMYB module in organogenesis. In summary, our data demonstrate that PaSTM is important for PLB development. The STM-S11 MYB regulatory module is evolutionarily conserved and may regulate shoot or shoot-related organ development in plants., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Long-acting injectable antipsychotics (LAIs) may potentially benefit patients requiring psychiatric hospitalization during the early stages of schizophrenia. However, few studies have compared the long-term effectiveness between patients who switched to LAIs and those who remained on oral antipsychotics (OAPs)., Methods: Using the Taiwan National Health Insurance Research Database, we constructed a population-based cohort with 19,813 new OAP users with ICD-9-CM- defined schizophrenia who were hospitalized from 2002 to 2005. Within this cohort, 678 patients who switched to LAIs during their hospitalization were identified. The LAI group was matched to patients who remained on OAPs (n = 678). The LAI cohort was further subdivided for analysis into patients who switched to LAIs within 3 years of OAP initiation ("an early stage") and those who switched after 3 years ("a late stage"). Conditional Cox regressions and conditional negative binomial regressions were used to estimate the risk of death and the number of hospital visits between the two groups., Results: During the 13-year study period, 312 patients switched to LAIs within the first 3 years of OAP initiation. All- and natural-cause mortalities in these patients were significantly lower than in those who remained on OAPs. The hazard ratios (HRs) for all- and natural-cause mortalities were 0.49 (95% confidence interval [CI], 0.27-0.87) and 0.30 (95% CI, 0.15-0.60), respectively. No significant decrease associated with LAIs was observed in unnatural-cause mortality. Patients receiving LAIs had lower risks of rehospitalization (incidence rate ratio [IRR] = 0.56, 95% CI, 0.45-0.69), psychiatric hospitalization (IRR = 0.63, 95% CI, 0.50-0.81), and psychiatric emergency room visits (IRR = 0.58, 95% CI, 0.45-0.75) compared to patients who remained on OAPs. Use of LAIs in the late stage of treatment did not decrease the risk of relapse or mortality., Conclusions: Switching to LAIs during the first 3 years of treatment improved antipsychotic adherence, decreased relapses, and reduced long-term mortality. Our results provide evidence to support the benefits of early LAI treatment in schizophrenia., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Background: Nursing competence refers to the core abilities that are required for fulfilling one's role as a nurse. A specific instrument comprehensively measuring competence among nursing students has not yet been developed. The purpose of the study was to develop and validate a nursing competence instrument for nursing students in bachelor training., Methods: A descriptive and explorative study design was used. Data were collected from students at one medical college in Taiwan in 2020 and 2021. A total of 241 nursing students participated in this study. We developed the initial instrument through systematic review, expert evaluations, and pilot versions. Its validity was then tested using confirmatory factor analysis (CFA) and criterion-related validity, while its reliability was tested using Cronbach's alpha and test-retest analysis., Results: The final fit indexes of CFA were as follows: chi-square = 860.1 (p < 0.01), normed chi-square = 2.24, SRMR = 0.04, RMSEA = 0.07, CFI = 0.94, and TLI = 0.94. Cronbach's alpha values for the subscales observed ranged from 0.91 to 0.98. The test-retest reliability coefficient for the Nurse Competence Scale was 0.515 (n = 30, p < 0.01)., Conclusions: The instrument exhibited acceptable psychometric properties, thereby proving itself a valuable tool for evaluating nursing students' competence at bachelor training. Further assessments of its reliability, validity, and generality from mentors' and scholars' views in different contexts and cultures are recommended., (© 2022. The Author(s).)

This paper demonstrated the influences of initiation, development, turn-down, and reinitiation of the dynamic capability of an entrepreneurial firm in the solar energy industry. The focus is on the impact of entrepreneurial hubris, which may affect the decision of ambidexterity that can vitalize dynamic capability. The findings indicate that, when the major decision maker (the founder entrepreneur) has the trait of hubris, the decision-making process may be overly arbitrary, and a decision of being exploratory or exploitative alone is likely to be made. On the contrary, when the founder entrepreneur is aware of the hubris and shares decisive power, the decision of being ambidextrous as a dynamic capability is more freely achieved. This paper contributes by discovery of the cognitive-based microfoundation of entrepreneurial ventures and linkage of such microfoundation to organizational ambidexterity., 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 © 2022 Guo, Huang, Ciu, Fang and Tsai.)

Background: Patient-centred e-health (PCEH) focusses on the interaction between patients and physicians. However, only a limited number of studies have focussed on the design of physician-patient value cocreation mechanisms in the PCEH context. Thus, we extend Grönroos' concept of value cocreation to understand how PCEH might improve the quality of care., Objectives: This study proposes a theoretical framework to embody PCEH-supported value cocreation and presents some empirical validation. We expect that PCEH-supported value cocreation should comprise capabilities for patient empowerment, intention for information sharing, complementation for checking and verifying information, and interaction for shared understanding., Methods: This study surveyed a small group of patients that have used PCEH, 'My Health Bank' in Taiwan. The questionnaires were delivered to patients in hospitals (n = 167 questionnaires, 98% response rate)., Results: Results indicate that certain PCEH-supported value cocreation mechanisms-capabilities for patient empowerment and interaction for shared understanding-affect the perceived quality of medical care., Limitations: The survey only considered patient perceptions of value cocreation., Conclusion: This study shows the patient perception of value cocreation in patient-centred e-Health. Further research needs to validate the framework for health professionals and in other e-Health record information sharing settings., (© 2021 Health Libraries Group.)

Against the backdrop of economic internationalization and market globalization, the world has witnessed faster competitive contents with a more dynamic market environment, a more rapid technological innovation, and more diverse customer needs. Thus, for every enterprise especially led by entrepreneurs, the focus is to maintain the sustainability of competitive advantages and dynamically transform core capacity to avoid rigidity. This paper introduces the process of the deepened rigidity in WS Co. Company, which occurs due to the wrong cognition of Dr. S and his teams who managed or failed to respond to the rigidity encountered by the company during different periods. The rigidity of its capacity is believed to be caused by the cognitive errors of the entrepreneur and his team facing every period of potential rigidity, which makes them fail to deal with it (or choose the wrong methods), thus leading to complete rigidity. This paper intends to explain how rigidity takes shape from the cognitive aspect of senior managers, which may serve as illuminations for the similar enterprises led by entrepreneurs., 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 © 2022 Guo, Huang, Chou, Fang and Tsai.)

The reverse cholesterol transport pathway is responsible for the maintenance of human cholesterol homeostasis, an imbalance of which usually leads to atherosclerosis. As a key component of this pathway, the ATP-binding cassette transporter ABCG1 forwards cellular cholesterol to the extracellular acceptor nascent high-density lipoprotein (HDL). Here, we report a 3.26-Å cryo-electron microscopy structure of cholesterol-bound ABCG1 in an inward-facing conformation, which represents a turnover condition upon ATP binding. Structural analyses combined with functional assays reveals that a cluster of conserved hydrophobic residues, in addition to two sphingomyelins, constitute a well-defined cholesterol-binding cavity. The exit of this cavity is closed by three pairs of conserved Phe residues, which constitute a hydrophobic path for the release of cholesterol in an acceptor concentration-dependent manner. Overall, we propose an ABCG1-driven cholesterol transport cycle initiated by sphingomyelin-assisted cholesterol recruitment and accomplished by the release of cholesterol to HDL., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fibromyalgia is a chronic widespread pain condition that is associated with sleep disturbances and cognitive impairments. Neurofeedback has been demonstrated to improve pain, sleep quality, and fatigue. However, few studies have examined the effect of neurofeedback for patients with fibromyalgia., Aim: To determine the effects of neurofeedback on pain intensity, symptom severity, sleep quality, and cognitive function in patients with fibromyalgia., Design: This study was a randomized controlled trial., Method: Eighty participants were randomized to a neurofeedback group (N = 60), receiving sensorimotor and alpha rhythm feedback for 8 weeks, or a telephone support group (N = 20)., Results: Results from the generalized estimating equation modelling revealed significant group-by-time interactions for Brief Pain Inventory pain severity (B = -1.35, SE = 0.46, p = .003) and pain interference (B = -1.75, SE = 0.41, p < .001), Revised Fibromyalgia Impact Questionnaire total scores (B = -16.41, SE = 3.76, p < .001), sleep onset latency (B = -25.33, SE = 9.02, p = .005), and Psychomotor Vigilance Test error (B = -1.38, SE = 0.55, p = .013) after adjustments for age, sex, duration of illness, and group differences at baseline., Conclusions: An 8-week neurofeedback training regimen of sensorimotor rhythm and alpha brain waves significantly improved pain severity and interference, fibromyalgia symptom severity, sleep latency, and sustained attention in patients with fibromyalgia., (Copyright © 2021 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Objective: Methamphetamine (METH) use and adverse childhood experiences (ACEs) has been associated with an increased risk of suicidal behaviour. However, whether METH use underlies the risk of suicide attributable to ACEs is unknown and warrants investigation to inform preventive interventions. In this study, we examined the mediating role of METH use in the relationship between attempted suicide and ACEs., Method: METH users recruited from a mandatory detoxification center (n = 346) and healthy controls (n = 342) both completed a survey related to 9 types of ACE, which was based the Family Health Questionnaire. A lifetime history of attempted suicide was obtained using the Chinese version of the Composite International Diagnostic Interview. We conducted a bootstrapped mediation analysis to examine the mediating effect of METH use on the association between ACEs and attempted suicide., Results: Female gender, METH use, and having multiple (≥3) ACEs were associated with an increased risk of attempted suicide. A dose-response relationship between the number of ACEs and suicide rate was observed among individuals with METH use. METH use significantly mediated the association between ACEs and attempted suicide in those with multiple (2 and 3 ACEs respectively with proportion mediated 0.16 and 0.42) and specific types of ACEs (physical abuse, witnessing maternal battering, household substance abuse, sexual abuse, and parental separation with proportion mediated 0.25, 0.35, 0.38, 0.48, 0.47 respectively)., Conclusion: Our study is the first to demonstrate that METH use partially mediates the association between ACEs and attempted suicide. Addressing METH use in people with ACEs could reduce their suicide risk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Taiwan has deemed driving under the influence of alcohol (DUI) to be criminal, and offenders are subjected to fines and jail penalties without being offered alcohol-related treatment, although alcohol use problems are prevalent in this population. We followed the recidivism records of DUI repeat offenders for one year after they had received a newly established legal-medical joint intervention program for alcohol treatment and examined factors related to postintervention recidivism. In this study, 231 DUI repeat offenders with alcohol use problems screened out by the Alcohol Use Disorder Identification Test were referred from the prosecutors' office to one psychiatric hospital for SBIRT-based alcohol treatment. We divided the participants into two groups based on the official recidivism records within the year following the end of treatment. The study used a Cox proportional hazards model to examine the hazard ratio of the baseline clinical characteristics and intervention duration for post-treatment recidivism. The study used generalized estimation equation models to examine changes in psychological symptoms and drinking behaviors over time. We found that participants who recidivated in the next year after intervention did not differ from those without recidivism records in all measurements except for the length of duration they stayed in treatment. Survival analysis determined that participants who had received the intervention for >4 months showed significantly lower rates of one-year postintervention recidivism rates The study participants showed improved psychological symptoms and drinking behaviors during the follow-up period. In conclusion, adequate duration of alcohol treatment is a significant factor associated with a lower risk of postintervention recidivism. The results provide some insight into the design of a collaborative program between legal and medical systems to reduce DUI recidivism and improve mental health of DUI repeat offenders., (Copyright © 2021. Published by Elsevier Inc.)

Background: Our previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLT 1 R) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer's disease (AD); however, whether CysLT 1 R upregulation has deleterious effects on AD remains elusive., Methods: In this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLT 1 R overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLT 1 R), into the bilateral dentate gyri (DG) of the hippocampus or CysLT 1 R activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.p., for 28 d)., Results: The behavior data showed that overexpression of CysLT 1 R in hippocampal DG or administration of YM-17690 deteriorated behavioral performance in Morris water maze (MWM), Y-maze tests, and novel object recognition (NOR) in young APP/PS1 mice. The further studies showed that these treatments significantly destroyed synaptic function, as evidenced by impaired hippocampal long-term potentiation (LTP), decreased spine density, low number of synapses, and decreased postsynaptic protein (PSD95), and promoted the generation of amyloid β (Aβ) through increased expression of BACE1 and PS1 in the hippocampus of young APP/PS1 mice., Conclusions: Together, our results indicate that CysLT 1 R upregulation accelerates memory impairment in young APP/PS1 mice, which is associated with promoting synaptic dysfunction and amyloidogenesis in the hippocampus., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4518). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Importance: Schizophrenia is generally considered to be among the most severe psychiatric disorders because of the excessive mortality associated with it. Research to find means to reduce this excessive mortality is warranted., Objective: To investigate associations of long-acting injectable antipsychotics (LAIs) with all-cause, natural-cause, and suicide mortality risks as well as the impacts of early use of LAIs in patients with newly diagnosed schizophrenia., Design, Setting, and Participants: This cohort study used data from the Taiwan National Health Insurance Research Database to construct a population-based cohort of patients with schizophrenia who received oral antipsychotics (OAPs) from January 1, 2002, to December 31, 2017. Within this cohort, the LAI group was defined as patients who switched to LAIs and were prescribed LAIs at least 4 times within 1 year. The LAI group was propensity matched 1:1 to patients who continued receiving OAPs of the same compounds. All patients were followed up until switching the antipsychotic administration route, death, or the end of the study (December 31, 2018), whichever occurred first. Data analysis was performed from January 2002 to December 2018., Main Outcomes and Measures: All-cause mortality, natural-cause mortality, suicide mortality, and suicide attempts., Results: In total, 2614 patients who switched to LAIs (median [interquartile range] {IQR} age, 30 [23-39] years) and 2614 who received OAPs (median [IQR] age, 30 [23-39] years) were included (1333 male patients [51.0%] in each group). During the 16-year follow-up period (median [IQR] follow-up of 14 [10-17] years), patients who switched to LAIs had lower risks of all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.54-0.81), natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93) compared with patients who received the corresponding OAPs. A 47% lower suicide mortality risk (aHR, 0.53; 95% CI, 0.30-0.92) was observed in patients who switched to LAIs within the first 2 years of OAP initiation., Conclusions and Relevance: These findings suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Furthermore, early treatment with LAIs within the first 2 years of OAP initiation was associated with a decrease in suicide mortality risk. Thus, LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia.

Objective: Prostate cancer (PCa) incidence has stabilized but not in patients at a young age. We assessed patient characteristics and disease progression in early-onset PCa., Methods: A retrospective cohort of 28,039 newly diagnosed PCa patients aged ≥35 years was constructed using the Taiwan Cancer Registry in 2008-2016. Patients were categorized by age at diagnosis (≤54, 55-59, 60-69, 70-74, and ≥75 years). The clinical stage at diagnosis, Gleason score, prostate-specific antigen level at diagnosis, Charlson's comorbidity index, and primary and secondary treatments for PCa were included in the analysis. All-cause mortality and prostate cancer-specific mortality (PCSM) were reported. Hazard ratios (HRs) and 95% confidence intervals (CIs) estimating the risks of death and of receiving secondary cancer treatment were generated by Cox hazard models., Results: In patients aged ≤54, 55-59, and 60-69 years, about 60% of them in each group were classified into the high-risk, very high-risk, or metastatic group. However, young patients ≤54 years had a higher risk of PCSM than patients aged 60-69 years (HR = 1.22; 95% CI = 1.10-1.49). This trend of an increased risk in PCSM remained for high-risk, very high-risk, or metastatic patients (HR = 1.24; 95% CI = 1.01-1.51), but not in low- or intermediate-risk patients. Besides, young patients diagnosed with high-risk diseases had the highest risk of receiving secondary cancer treatment within 180 days after completing primary treatment among all age groups (HR = 1.32; 95% CI = 1.07-1.63)., Conclusions: PCa arising in young patients ≤54 years of age, especially those with a high risk or metastatic form, might be more aggressive than that in other age groups., (© 2020 Wiley Periodicals LLC.)

Using the constrained-path quantum Monte Carlo method, we systematically study the half-filled Hubbard model on AA-stacked honeycomb lattice. Our simulations demonstrate that a dominant chiral d + id wave superconductivity can be induced by a perpendicular electric field. At a fixed electric field, the effective pairing interaction of chiral d + id superconductivity exhibits an increasing behavior with increasing the on-site Coulomb interaction. We attribute the electric field-induced d + id superconductivity to an increased density of states near the Fermi energy and robust antiferromagnetic spin correlation upon turning on electric field. Our results strongly suggest that the AA-stacked graphene system is a good candidate for chiral d + id superconductor.

Small ubiquitin-like modifier (SUMO) conjugation, or SUMOylation, is a reversible post-translational modification that is important for regulation of many cellular processes including cell division cycle in the eukaryotic kingdom. However, only a portion of the components of the Chlamydomonas SUMOylation system are known and their functions and regulation investigated. The present studies are aimed at extending discovery and characterization of new components and improving the annotation and nomenclature of all known proteins and genes involved in the system. Even though only one copy of the heterodimerized SUMO-activating enzyme, SAE1 and SAE2 , was identified, the number of SUMO-conjugating enzymes ( SCE s) and SUMO proteases/isopeptidase was expanded in Chlamydomonas. Using the reconstituted SUMOylation system, we showed that SCE1, SCE2, and SCE3 have SUMO-conjugating activity. In addition to SUMOylation, components required for other post-translational modifications such as NEDDylation, URMylation, and UFMylation, were confirmed to be present in Chlamydomonas. Our data also showed that besides isopeptidase activity, the SUMO protease domain of SUPPRESSOR OF MAT3 7/SENTRIN-SPECIFIC PROTEASE 1 (SMT7/SENP1) has endopeptidase activity that is capable of processing SUMO precursors. Moreover, the key cell cycle regulators of Chlamydomonas E2F1, DP1, CDKG1, CYCD2, and CYCD3 were SUMOylated in vitro, suggesting SUMOylation may be part of regulatory pathway modulating cell cycle regulators., Competing Interests: All authors declare no competing financial interests., (© 2020 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)