Structural basis for calcium-stimulating pore formation of Vibrio α-hemolysin.

Vibrio α-hemolysins (αHLs) are ß-pore-forming toxins secreted by Vibrio pathogens, crucial for the facilitation of bacterial infections through host cell lysis. These toxins are produced as inactive precursors, requiring proteolytic maturation and membrane association for activation within host tissues. Here, we investigate Vibrio campbellii αHL (VcαHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC50 that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcαHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcαHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcαHL's calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcαHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections.

Validating the Mandarin version of the Memorial delirium assessment scale in general medical hospital patients.

INTRODUCTION: Delirium is a common neuropsychiatric condition in the general hospital population. Thus, the goal of the present study is to extend the use of diagnostic tools for delirium by developing and validating a Mandarin version of the Memorial Delirium Assessment Scale (MDAS). METHODS: Participants were sampled from two general Mackay Memorial Hospital locations in Taipei and Danshui. Board-certified psychiatrists assessed patients using the MDAS, confusion assessment method (CAM), and Mini-Mental State Examination (MMSE). Another consultation-liaison psychiatrist confirmed the diagnosis of delirium. We assessed the reliability and validity of the MDAS, and the receiver operating characteristic curve was used to determine the optimal cut-off point for identifying delirium. RESULTS: Of the 61 patients assessed, 29 were diagnosed with delirium. The mean MDAS score was 16.7 for delirium patients and 4.1 for nondelirium patients. The MDAS has good internal consistency, with a Cronbach's alpha coefficient of 0.912. Interrater reliability was 0.996 (95% confidence interval [CI]: 0.992-0.998). The diagnostic cut-off value for the Mandarin version of the MDAS was 9, with a high sensitivity (93.1%) and specificity (96.9%). Factor analysis revealed a two-factor structure; these factors accounted for 58.37% and 14.42% of the variance. A high correlation was found between the MDAS and the CAM scores (r = -0.849, p < .001) as well as the MMSE (r = -0.875, p < .001). DISCUSSION: The Mandarin MDAS exhibited good reliability and validity for assessing general hospital patients.

Effect of tungsten doping on the variability of InZnO conductive-bridging random access memory.

The characteristics of conductive-bridging random access memory (CBRAM) with amorphous indium-tungsten-zinc-oxide (a-InWZnO) switching layer and copper (Cu) ion-supply layer were prepared by sputtering. It was found that the doping ratio of tungsten has a significant effect on the memory characteristics of the CBRAM, and the doping of tungsten acts as a suppressor of oxygen vacancies in the InWZnO film. The O 1s binding energy associated with the oxygen-deficient regions in the α-InWZnO thin film decreases with increasing tungsten doping ratio, which can be demonstrated by x-ray photoelectron spectroscopy. When the tungsten doping ratio is 15%, the a-InWZnO CBRAM can achieve the excellent memory characteristics, such as high switching endurance (up to 9.7 × 103 cycling endurance), low operating voltage, and good retention capability. Moreover, the electrical uniformity and switching behavior of InWZnO device are evidently improved as the doping ratio of tungsten in the switching layer increases. These results suggest that CBRAM based on novel material InWZnO have great potential to be used in high-performance memory devices.

Systematic review and meta-analysis of epidemiology of internet addiction.

BACKGROUND: The field of internet addiction has experienced significant debates on conflicting epidemiology. This meta-analysis investigated the prevalence rates of generalized internet addiction (GIA) and internet gaming disorder (IGD). METHODS: We included 113 epidemiologic studies covering 693,306 subjects published from 1996 to 2018 (for 31 nations) that reported prevalence rates for GIA or IGD. We examined pooled prevalence of GIA and IGD and the hypothesized moderators including year, geographic regions, types of scales, and sample representativeness. RESULTS: All 133 effect sizes included 53,184 subjects with GIA or IGD. Weighted average prevalence for GIA and IGD were 7.02 % (95 % CI, 6.09 %-8.08 %) and 2.47 % (95 % CI, 1.46 %-4.16 %) respectively. For GIA, prevalence was increased over time and prevalence rates variated among different scales. IGD prevalence was neither moderated by year, regions, nor sample representativeness. CONCLUSIONS: The prevalence of GIA was higher than the prevalence of IGD. The GIA prevalence was increasing over time and variated with different assessments. Our results reveal that GIA may reflect a pattern of increasing human-machine interaction.

Google searches for the keywords of "wash hands" predict the speed of national spread of COVID-19 outbreak among 21 countries.

This study hypothesized that national population health literacy might reflect on their keywords searching. We applied Google searches for "wash hands" and "face mask" during January 19 to February 18 as a surrogate of national population health literacy among 21 countries, and examine whether google searches for "wash hands" and "face masks" would protect from increased numbers of confirmed cases of among 21 countries We found the increased google searches for "wash hands" from January 19 to February 18, 2020, correlated with a lower spreading speed of COVID-19 from February 19 to March 10, 2020 among 21 countries (Pearson's correlation coefficient of -0.70, P < 0.001). The result highlights the importance of public awareness of hand washing in preventing COVID-19 disease spreading.

Brief Cognitive-based Psychosocial Intervention and Case Management for Suicide Attempters Discharged from the Emergency Department in Taipei, Taiwan: A Randomized Controlled Study.

OBJECTIVE: We examined the effectiveness of brief cognitive-based psychotherapy plus standard case management in the prevention of further suicide attempts, clinical severity, and treatment adherence in a randomized clinical trial compared with standard case management. METHOD: Among five hundred and ninety-seven patients presenting with suicide attempts, 147 participants were included. They were randomized into two groups. After a 6-session intervention over four months, all participants were re-evaluated at the 6th and 12th months. RESULTS: At a 6-month assessment, the intervention had approximately halved the odds of following suicide attempts and doubled the odds of outpatient visits in comparison with standard case management, although the differences did not attain statistical significance. At a 12-month assessment, the two groups did not differ significantly in any of the outcome variables. Generalized linear mixed models indicated that intervention did not significantly decrease the subsequent suicide risk and severity of clinical symptoms, but it did increase psychiatric outpatient treatment adherence. The subgroup analysis revealed that the intervention increased the outpatient clinic visits only for repetitive attempters, not for first-time attempters. CONCLUSIONS: Further studies are needed to test whether more intensive psychotherapy sessions might be more effective in decreasing the probability of further attempt and the severity of symptoms.

Development of an addiction index and delineation 15-year trends of illicit drugs from the Taiwan national drug enhancement database.

Illicit drug use contributes to substantial morbidity and mortality. Drug scheduling, a legal measure in drug enforcement, is often structured as a hierarchy based on addiction tendency, abuse trends, and harm, but may lack data-driven evidence when classifying substances. Our study aims to measure addiction tendency and use trends based on real-world data. We used the open access database of National Police Agency, Ministry of the Interior in Taiwan and analyzed all daily criminal cases of illicit drugs from 2013 to 2017 and monthly illicit drug enforcement data from the same database from 2002 to 2017. We hypothesized that repeat and frequent use despite legal consequence may be a reflection of addictive behavior, and empirical mode decomposition was applied in analysis to calculate addiction tendency indices and intrinsic 15-year use trends. Our analysis showed heroin has the highest addiction index, followed by methamphetamine. 3,4-Methyl enedioxy methamphetamine, marijuana, and ketamine had lower addictive propensities. This result is consistent with most drug scheduling hierarchies. 15-year use trends of substances were consistent with previous epidemiological studies.

Development of the Problematic Mobile Gaming Questionnaire and Prevalence of Mobile Gaming Addiction Among Adolescents in Taiwan.

Mobile gaming has gained popularity among adolescents, and an increase in problematic use has been reported. The aims of this study are as follows: (a) develop a self-report questionnaire, the Problematic Mobile Gaming Questionnaire (PMGQ); (b) establish a validated cutoff value using structured interviews; and (c) evaluate the prevalence of mobile gaming addiction in adolescents. The PMGQ was built as a 12-item questionnaire rated on a 4-point Likert scale to evaluate the symptoms of problematic mobile gaming (PMG). The construct validity of the PMGQ was examined using exploratory factor analysis. Overall, 10,775 students with smartphones from grade 4 to senior high school were recruited to complete the questionnaire. A total of 113 senior high school students were interviewed using previously developed criteria for PMG to develop an optimal cutoff point measuring sensitivity, specificity, and diagnostic accuracy. The cutoff point was determined using the Youden index and optimal diagnostic accuracy. The PMGQ showed good internal consistency (Cronbach's α = 0.92) and adequate diagnostic efficiency (area under the receiver operating characteristic curve = 0.802). The items revealed three factors of addiction: compulsion, tolerance, and withdrawal. For the PMGQ, a cutoff point of 29/30 demonstrated the most optimal Youden index and diagnostic accuracy. Demographic data showed that the proportion of PMG was 19.1 percent among elementary school students, 20.5 percent among junior high school students, and 19.0 percent among senior high school students. The PMGQ demonstrated appropriate validity and accuracy in the assessment for PMG.

Risk Score for Predicting Mortality in People With Dementia: A Nationwide, Population-Based Cohort Study in Taiwan With 11 Years of Follow-Up.

OBJECTIVE: Many researchers and physicians attempt to determine the prognosis and short- and long-term mortality risks of dementia for formulating suitable care plans for patients and their families. However, the published prediction models have been insufficient for this purpose and have worked only in certain specific populations. For medical autonomy and end-of-life decisions, an informative tool to predict 6-month, 1-year, 2-year, 3-year, and 5-year mortality rates for dementia patients merits further investigation. METHODS: Patients aged ≥ 65 years who received ICD-9-CM diagnoses of dementia between 2002 and 2009 were identified from Taiwan's National Health Insurance Research Database and followed until the end of 2013. Patient characteristics and comorbidities that were considered potential risk factors for mortality were assessed. Mortality-predicting risk scores were developed using a regression coefficient-based scoring approach. In total, 6,556 patients were identified and then randomly divided into a derivation cohort (n = 4,371) and validation cohort (n = 2,185). RESULTS: By the end of the study, 1,693 of the 4,371 dementia patients (38.7%) in the derivation cohort were deceased. Mean duration of follow-up was 6.26 years. Eleven acute and chronic factors were identified for building the predictive score model, which produced scores from 0 to 24 points (higher scores indicated higher mortality). The score model exhibited good predictive power for various life expectancies (area under receiver operating characteristic curve: 6-month = 0.852, 1-year = 0.779, 2-year = 0.725, 3-year = 0.721, 5-year = 0.703) and good calibration in the validation cohort (Hosmer-Lemeshow test, χ² = 4.709, P = .788). CONCLUSIONS: The developed predictive score model may be the first tool that uses the same clinical factors to determine both short- and long-term mortality risks in patients with dementia.

Performance Enhancement for Tungsten-Doped Indium Oxide Thin Film Transistor by Hydrogen Peroxide as Cosolvent in Room-Temperature Supercritical Fluid Systems.

In this study, hydrogen peroxide (H2O2) cosolvent, which was dissolved into supercritical-phase carbon dioxide fluid (SCCO2), is employed to passivate excessive oxygen vacancies of the high-mobility tungsten-doped indium oxide without any essential thermal process. With the detailed material analysis, the internal physical mechanism of the cosolvent effect or the interaction between the cosolvent solution and supercritical-phase fluid is well discussed. In addition, the optimized result has been applied for the thin film transistor device fabrication. As a result, the device with SCCO2 + H2O2 treatment exhibits the lowest subthreshold swing of 82 mV/dec, the lowest interface trap density of 8.76 × 1011 eV-1 cm-2, the lowest hysteresis of 47 mV, and an excellent reliability and uniformity characteristic compared with any other control groups. Besides, an extremely high field-effect mobility of 98.91 cm2/V s can also be observed, while there is even a desirable positive shift for the threshold voltage. Notably, compared with the untreated sample, the highest on/off current ratio of 5.11 × 107 can be achieved with at least four orders of magnitude enhancement by this unique treatment.

Validation of the Mobile App-Recorded Circadian Rhythm by a Digital Footprint.

BACKGROUND: Modern smartphone use is pervasive and could be an accessible method of evaluating the circadian rhythm and social jet lag via a mobile app. OBJECTIVE: This study aimed to validate the app-recorded sleep time with daily self-reports by examining the consistency of total sleep time (TST), as well as the timing of sleep onset and wake time, and to validate the app-recorded circadian rhythm with the corresponding 30-day self-reported midpoint of sleep and the consistency of social jetlag. METHODS: The mobile app, Rhythm, recorded parameters and these parameters were hypothesized to be used to infer a relative long-term pattern of the circadian rhythm. In total, 28 volunteers downloaded the app, and 30 days of automatically recorded data along with self-reported sleep measures were collected. RESULTS: No significant difference was noted between app-recorded and self-reported midpoint of sleep time and between app-recorded and self-reported social jetlag. The overall correlation coefficient of app-recorded and self-reported midpoint of sleep time was .87. CONCLUSIONS: The circadian rhythm for 1 month, daily TST, and timing of sleep onset could be automatically calculated by the app and algorithm.

Temporal Stability of Smartphone Use Data: Determining Fundamental Time Unit and Independent Cycle.

BACKGROUND: Assessing human behaviors via smartphone for monitoring the pattern of daily behaviors has become a crucial issue in this century. Thus, a more accurate and structured methodology is needed for smartphone use research. OBJECTIVE: The study aimed to investigate the duration of data collection needed to establish a reliable pattern of use, how long a smartphone use cycle could perpetuate by assessing maximum time intervals between 2 smartphone periods, and to validate smartphone use and use/nonuse reciprocity parameters. METHODS: Using the Know Addiction database, we selected 33 participants and passively recorded their smartphone usage patterns for at least 8 weeks. We generated 4 parameters on the basis of smartphone use episodes, including total use frequency, total use duration, proactive use frequency, and proactive use duration. A total of 3 additional parameters (root mean square of successive differences, Control Index, and Similarity Index) were calculated to reflect impaired control and compulsive use. RESULTS: Our findings included (1) proactive use duration correlated with subjective smartphone addiction scores, (2) a 2-week period of data collection is required to infer a 2-month period of smartphone use, and (3) smartphone use cycles with a time gap of 4 weeks between them are highly likely independent cycles. CONCLUSIONS: This study validated temporal stability for smartphone use patterns recorded by a mobile app. The results may provide researchers an opportunity to investigate human behaviors with more structured methods.

Development of a mobile application (App) to delineate "digital chronotype" and the effects of delayed chronotype by bedtime smartphone use.

The widespread use and deep reach of smartphones motivate the use of mobile applications to continuously monitor the relationship between circadian system, individual sleep patterns, and environmental effects. We selected 61 adults with 14-day data from the "Know Addiction" database. We developed an algorithm to identify the "sleep time" based on the smartphone behaviors. The total daily smartphone use duration and smartphone use duration prior to sleep onset were identified respectively. We applied mediation analysis to investigate the effects of total daily smartphone use on sleep through pre-sleep use (PS). The results showed participants' averaged pre-sleep episodes within 1 h prior to sleep are 2.58. The duration of three pre-sleep uses (PS1∼3) maybe a more representative index for smartphone use before sleep. Both total daily duration and the duration of the last three uses prior to sleep of smartphone use significantly delayed sleep onset, midpoint of sleep and reduced total sleep time. One hour of increased smartphone use daily, delays the circadian rhythm by 3.5 min, and reduced 5.5 min of total sleep time (TST). One hour of increased pre-sleep smartphone use delayed circadian rhythm by 1.7 min, and reduced 39 s of TST. The mediation effects of PS1∼3 significantly impacted on these three sleep indicators. PS1∼3 accounted for 14.3% of total daily duration, but the proportion mediated of delayed circadian rhythm was 44.0%. We presented "digital chronotype" with an automatic system that can collect high temporal resolution data from naturalistic settings with high ecological validity. Smartphone screen time, mainly mediated by pre-sleep use, delayed the circadian rhythm and reduced the total sleep time.

The Psychometric Properties in the Chinese Version of the Reasons for Living Inventory and the Relationship with Suicidal Behaviors Among Psychiatric Patients in Taiwan.

This study examines the reliability, factor structure, convergent, and construct validities of the Mandarin Chinese version of the Reasons For Living Inventory (RFL) among Taiwanese psychiatric patients. Demographical characteristics of patients who hold these adaptive cognitions and differences on the level of endorsement between suicidal and non-suicidal individuals were also investigated. All adult patients that had visited the psychiatric ambulatory clinic or had been admitted to the psychiatric ward in a general hospital in Taiwan over a 3-month period were consecutively invited to complete an inventory that included background information, the Mandarin Chinese versions of the RFL, the Suicidal Behaviors Questionnaire-Revised (SBQ-R), and the Beck Hopeless Scale (BHS). Of the 254 respondents aged 19 to 65 years, 47.2% had suicidal ideations or attempts within the past year. The original six-factor structure of the American version was confirmed to be acceptable. The Cronbach α was 0.964.Total scores on RFL were inversely and significantly correlated with that from BHS. Multivariate analysis with demographic data and items from SBQ-R revealed that higher scores on the RFL have been associated with married, have children or religious beliefs, fewer past and current suicidal ideations and attempts, fewer histories of suicidal threats, and a less self-reported likelihood of future suicide in our sample. The Mandarin version of the RFL inventory showed acceptable psychometric properties and could distinguish suicidal patients from non-suicidal ones.

Chinese adaptation of the Ten-Item Internet Gaming Disorder Test and prevalence estimate of Internet gaming disorder among adolescents in Taiwan.

BACKGROUND AND AIMS: Internet gaming disorder (IGD) is an increasingly important topic and has been included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) research criteria. This study aims to validate the Chinese version of the Ten-Item Internet Gaming Disorder Test (IGDT-10), a self-reported questionnaire based on DSM-5 IGD criteria, and to estimate the prevalence of IGD in adolescents. METHODS: The IGDT-10 was translated to Chinese as a 10-item questionnaire rated on a 3-point Likert scale to evaluate the symptoms of IGD. Overall, 8,110 students from grade four to senior high who played Internet games were administered the questionnaire. In addition, 76 senior high-school students were interviewed using DSM-5 criteria to determine the optimal cut-off point that ensures adequate sensitivity, specificity, and diagnostic accuracy. The cut-off point was determined using the Youden's index and optimal diagnostic accuracy. RESULTS: The Chinese version of the IGDT-10 showed good internal consistency (Cronbach's α = .85) and adequate diagnostic efficiency (area under the curve = 0.810). Through interviews, the optimal cut-off point was determined to be five out of the nine criteria (Youden's index: 42.1%, diagnostic accuracy: 86.8%, sensitivity: 43.8%, and specificity: 98.3%). In this study, the prevalence of IGD among adolescent gamers was 3.1%. CONCLUSION: Findings evidence the validity and diagnostic accuracy of the IGDT-10 in the assessment of IGD.

Association of Polypharmacy With Mild Cognitive Impairment and Cognitive Ability: A Nationwide Survey in Taiwan.

BACKGROUND: Polypharmacy, defined as the concomitant use of 5 or more medications, has a documented negative association with cognitive impairment such as delirium and is associated, potentially, with a higher risk of dementia. However, whether polypharmacy contributes to increased risk of mild cognitive impairment (MCI) or decreased cognitive capacity requires further investigation. This nationwide population survey investigated the association among polypharmacy, MCI, and dementia. METHODS: Through random sampling based on the proportion of all Taiwan counties, subjects were recruited and received in-person interviews between December 2011 and March 2013. Demographic data and clinical information included medical histories, medication use, and mental status measured by the Taiwanese Mini-Mental State Examination (TMSE) and Clinical Dementia Rating (CDR). Data on lifestyle and habits were collected, and subjects were distributed to cognitively normal, MCI, or all-cause dementia groups based on criteria by the National Institute on Aging and the Alzheimer's Association. RESULTS: A total of 7,422 people aged 65 years or older were recruited. After adjustment for age, sex, body mass index, education, medical comorbidities, and lifestyle and habits, polypharmacy was associated with a 1.75-fold increased odds of MCI and 2.33-fold increased odds of dementia. Polypharmacy was associated with a 0.51-point decrease in TMSE scores (P = .001) and a 0.10-point increase in CDR score (P < .001). Additionally, for those without specific vascular comorbidities, polypharmacy had a greatly more negative impact on cognitive capacity. CONCLUSIONS: Polypharmacy is common in the elderly and is associated with significantly lower cognitive capacity and higher risks of MCI and dementia, especially for persons without diabetes, hypertension, hyperlipidemia, or cerebrovascular diseases.

Aripiprazole in a Patient of PLA2G6-Associated Neurodegeneration With Psychosis.

PLA2G6-associated neurodegeneration is a major subtype of neurodegeneration with brain iron accumulation. Patients with PLA2G6-associated neurodegeneration usually present degenerative motor symptoms with neuropsychiatric disturbance. This report presents a patient with PLA2G6-related dystonia-parkinsonism, who had neuropsychiatric symptoms preceding movement symptoms. Antipsychotic drug was prescribed, and he developed parkinsonism years later. Differential diagnosis between drug-induced parkinsonism and PLA2G6-related dystonia-parkinsonism could be challenging. PLA2G6 sequencing has to be considered facing a patient with adulthood parkinsonism, especially when it is associated with initial psychiatric symptoms. Our case highlights a common problem treating psychiatric symptoms in neurodegenerative diseases that lead to parkinsonism. The use of antipsychotics requires a special caution in these patients because it may cause extrapyramidal symptoms. Aripiprazole had therapeutic effect on both mood and psychotic symptoms and less impact on motor features, which may be considered an ideal pharmacological approach in treating these patients.

Highly Responsive Blue Light Sensor with Amorphous Indium-Zinc-Oxide Thin-Film Transistor based Architecture.

A single layer of amorphous InZnO is chosen as the channel material for a thin film transistor (TFT)-based driver and sensing layer for a blue-light sensor, respectively, with a completely compatible process integrated into in-cell embedded photo sensor architecture. The photo sensor exhibits a high optical responsivity (1280 A/W) and excellent signal to noise ratio (~105) under the blue light illumination. Afterwards, the detail studies and important issues about the sensing and material characteristics of a-IZO thin film in the TFT sensor are well discussed. The results suggest that the numbers of the deep, neutral oxygen vacancy are the key factors for carrier generation under illumination. In addition, a positive gate pulse is applied on the devices to eliminate persistent photoconductivity in order to ensure the recover ability for the photo sensor application. The practical concepts of a sensor circuit, which can be integrated on RGB pixel with interactive display, are also proposed on the basis of photo sensor TFT.