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Abstract Few studies included objective blood pressure (BP) to construct the predictive model of severe obstructive sleep apnea (OSA). This study used binary logistic regression model (BLRM) and the decision tree method (DTM) to constructed the predictive models for identifying severe OSA, and to compare the prediction capability between the two methods. Totally 499 adult patients with severe OSA and 1421 non‐severe OSA controls examined at the Sleep Medicine Center of a tertiary hospital in southern Taiwan between October 2016 and April 2019 were enrolled. OSA was diagnosed through polysomnography. Data on BP, demographic characteristics, anthropometric measurements, comorbidity histories, and sleep questionnaires were collected. BLRM and DTM were separately applied to identify predictors of severe OSA. The performance of risk scores was assessed by area under the receiver operating characteristic curves (AUCs). In BLRM, body mass index (BMI) ≥27 kg/m2, and Snore Outcomes Survey score ≤55 were significant predictors of severe OSA (AUC 0.623). In DTM, mean SpO2

Introduction: Overwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated the ability and underlying mechanism of ribociclib for treating ARDS and neutrophilic inflammation. Methods: Primary human neutrophils were used to determine the therapeutic effects of ribociclib on respiratory bursts, chemotactic responses, and inflammatory signaling. In vitro and silico analyses were performed to determine the underlying molecular mechanisms. The potential of ribociclib repurposing was evaluated using an in vivo ARDS model in lipopolysaccharide (LPS)-primed mice. Results: We found that treatment using ribociclib markedly limited overabundant oxidative stress (reactive oxygen species [ROS]) production and chemotactic responses (integrin levels and adhesion) in activated human neutrophils. Ribociclib was also shown to act as a selective inhibitor of phosphodiesterase 4 (PDE4), thereby promoting the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, leading to the inhibition of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation, and calcium influx. Notably, prophylactic administration and post-treatment with ribociclib ameliorated neutrophil infiltration, lung inflammation, accumulation of oxidative stress, pulmonary destruction, and mortality in mice with LPS-induced ARDS. Conclusion: We demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions.

Background: Though the artificial neural network (ANN) technique has been used to predict noise-induced hearing loss (NIHL), the established prediction models have primarily relied on cross-sectional datasets, and hence, they may not comprehensively capture the chronic nature of NIHL as a disease linked to long-term noise exposure among workers. Methods: A comprehensive dataset was utilized, encompassing eight-year longitudinal personal hearing threshold levels (HTLs) as well as information on seven personal variables and two environmental variables to establish NIHL predicting models through the ANN technique. Three subdatasets were extracted from the afirementioned comprehensive dataset to assess the advantages of the present study in NIHL predictions. Results: The dataset was gathered from 170 workers employed in a steel-making industry, with a median cumulative noise exposure and HTL of 88.40 dBA-year and 19.58 dB, respectively. Utilizing the longitudinal dataset demonstrated superior prediction capabilities compared to cross-sectional datasets. Incorporating the more comprehensive dataset led to improved NIHL predictions, particularly when considering variables such as noise pattern and use of personal protective equipment. Despite fluctuations observed in the measured HTLs, the ANN predicting models consistently revealed a discernible trend. Conclusions: A consistent correlation was observed between the measured HTLs and the results obtained from the predicting models. However, it is essential to exercise caution when utilizing the model-predicted NIHLs for individual workers due to inherent personal fluctuations in HTLs. Nonetheless, these ANN models can serve as a valuable reference for the industry in effectively managing its hearing conservation program.

Background: Recent outbreaks of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses in regions previously less affected since 2020 have raised global concerns. Implementing mass immunization or ring vaccination in poultry should be a countermeasure ready to contain disease outbreaks. This study focuses on developing a recombinant H5N2 vaccine based on virus-like particles (VLPs) against clade 2.3.4.4c, the predominant HPAI subclade in Taiwan since its emergence, leading to a large outbreak in 2015. Methods: The study aimed to confirm the effectiveness of clade 2.3.4.4c H5N2 VLPs in protecting chickens and identify the best adjuvants for the VLP vaccine. We used Montanide 71VG-adjuvanted inactivated RG6 to establish the immunization protocol, followed by prime-boost H5N2-VLP immunizations. We compared adjuvants: 71VG, 71VG with VP3, and Alum with VP3. Serum samples were tested for antibodies against homologous vaccine antigens and cross-clade antigens by hemagglutination inhibition (HI) assays. Finally, we evaluated the protective efficacy by lethally challenging immunized chickens with H5 viruses from clade 1 or 2.3.4.4c. Results: Poultry adjuvant 71VG significantly enhanced antibody responses in chickens with inactivated RG6 compared to unadjuvanted inactivated virus. While increasing antigen dosage enhanced 71VG adjuvanted RG6-induced antibody titers, the vaccine displayed minimal cross-reactivity against locally circulating HPAI H5N2. In contrast, H5N2-VLP containing the HA protein of clade 2.3.4.4c, adjuvanted with (FMDV) VP3 in 71VG, significantly promoted HI antibody responses. All H5N2-VLP immunized chickens survived lethal challenges with the local clade 2.3.4.4c H5 strain. Conclusion: The study demonstrated the immunogenic potential of the VLP vaccine in chickens. Our findings offer insights for optimizing VLP vaccines, allowing the incorporation of the HA of currently circulating H5 viruses to effectively mitigate the impact of the rapidly evolving clade 2.3.4.4 H5 outbreaks.

Abstract BackgroundControlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored. ObjectiveThis study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts. MethodsNutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]–Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t ResultsAcross the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from −13.8% to −40.3% (all PP< ConclusionsThe findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps’ reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves.

Abstract Background There is a great need for training and education in the nursing curriculum to improve nurses’ knowledge and skills to provide oral health care. Methods A pilot study was conducted to evaluate the use of a virtual reality (VR)-based Oral Health Care Learning System to train geriatric oral health care among nursing students. Fifty undergraduate nursing students were randomly assigned to experimental (n = 25) and control (n = 25) groups. The experimental group received the VR-based simulation training on geriatric oral health care and the training was implemented twice at two weeks apart from March to November 2021. The control group did not receive the training intervention. Knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adults were assessed at the beginning, second, and fourth weeks. Generalized estimating equations were used to analyze the effectiveness of the VR-based simulation training. Results After the first round of training, students in the experimental group had significantly greater improvements in knowledge and self-efficacy of geriatric oral health care than in the control group. After the second round of training, students in the experimental group had significantly greater improvements in knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adult than in the control group. Conclusions The VR-based simulation training was effective to improve undergraduate nursing students’ knowledge, attitudes and self-efficacy of geriatric oral health as well as the intention to assist oral health care for older adults. The VR-based simulation learning system is an effective tool to provide practice experiences to build confidence and skills and to bridge the gap of understudied geriatric oral health content in entry-level nursing curricula. Trial Registration ClinicalTrials.gov (NCT05248542; registration date 21/02/2022).

Abstract Background Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls. Methods A comparative study using matched case-control design was conducted. Men with HIV infection (case group) were enrolled from 2016 to 2019. A control group with HIV seronegative men were matched for SRBDs severity, and were selected from sleep medicine center database for comparison. Results The mean age of the 108 men (including 54 cases and 54 matched controls) was 33.75 years. Central-apnea index (CI) was higher in the case group rather than matched controls (mean CI, 0.34 vs. 0.17, p = 0.049). PLWH had a lower mean percentage of stage 3 sleep (10.26% vs. 13.94%, p = 0.034) and a higher percentage of rapid eye movement sleep (20.59% vs. 17.85%, p = 0.011) compared to matched controls. Nocturnal enuresis and sleepiness causing traffic accidents were more frequent complaint in PLWH compared to controls. Conclusions Early detected SRBDs and subtypes in PLWH to begin treatment for the underlying cause could reduce the risk of sleepiness-related traffic accidents.

Objectives: To explore the molecular characteristics of rpoB, encoding β-subunit of DNA-directed RNA polymerase, and unravel the link to rifabutin-resistance in patients with refractory Helicobacter pylori infection. Methods: From January 2018-March 2021, a total of 1590 patients were screened for eligibility to participate in the study. Patients with refractory H. pylori infection were confirmed by using the (13C)-urea breath assay. All enrolled patients underwent esophagogastroduodenoscopy, and biopsies were taken for H. pylori culture and antibacterial susceptibility testing. Sequence analysis of rpoB was conducted for all rifabutin-resistant isolates. Results: In total, 70 patients were diagnosed with refractory H. pylori infection, and 39 isolates were successfully cultured. Amongst, 10 isolates were identified as rifabutin-resistance and nine isolates exhibited at least one amino acid substitution in RpoB. Isolates with a minimal inhibitory concentration >32 mg/l displayed a higher number of mutational changes in RpoB than the others. Additionally, more amino acid substitutions in RpoB correlated with developing a higher minimal inhibitory concentration for H. pylori rifabutin-resistance. Conclusion: Our findings highlight the relationship between rifabutin-resistance in refractory H. pylori infection and specific mutations in RpoB, which will aid the clinical selection of appropriate antibacterial agents with better therapeutic effects.

Purpose: This observational study assessed sleep disturbance and autonomic dysfunction as risk factors for chronic subjective tinnitus through polysomnography (PSG) and autonomic function tests. Methods: Adult patients with chronic subjective tinnitus who visited the department of otolaryngology in our hospitals (n = 40), along with controls without tinnitus (n = 80), were recruited. Individuals with an average hearing threshold level (HL) exceeding 25 dB HL and a known diagnosis of insomnia were excluded. Objective assessments comprised pure-tone audiometry, PSG, and autonomic function tests (e.g., the cold pressor test). Results: Patients with prolonged sleep latency, lower sleep efficiency, and sympathetic hyperactivity had significantly higher risks of developing tinnitus. No interaction effect between poor sleep quality and sympathetic hyperactivity on tinnitus was detected. Conclusion: This is the first study to administer PSG and autonomic function tests to patients with chronic subjective tinnitus. Poor sleep quality and autonomic dysfunction were implicated as risk factors for tinnitus. PSG and the autonomic function tests helped identify tinnitus-related comorbidities and inform tinnitus treatment. Sleep disturbance and autonomic dysfunction did not exert an interaction effect on tinnitus. Further studies with a larger sample size and the inclusion of patients with more severe tinnitus are warranted.

Summary: While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.

Objective Healthcare assistants (HCAs) are frontline caregivers for older adults. This study evaluated the effectiveness of combining augmented reality (AR) and virtual reality (VR) to implement oral healthcare simulation training for HCAs. Methods An experimental design was adopted. HCAs were recruited and randomly assigned to an AR/VR group ( n = 40) or a control group ( n = 40). The AR/VR group received 2.5 h of AR/VR training. Participants were trained on the Bass brushing technique through AR and on scenario-based oral care procedures for various physical and oral health conditions in older adults through VR. A self-administered questionnaire was employed to collect data before and after the training. Generalized estimating equations were used to analyze the differences between pretest and posttest results. Results After the training, the HCAs in the AR/VR group achieved a significantly greater increase in their level of oral care-related knowledge (β = 2.55, effect size [ES] = 1.62), self-efficacy (β = 4.23, ES = 0.75), and behavioral intention (β = 2.10, ES = 0.55) relative to the control group. Conclusion This study revealed that the application of an AR/VR simulation system can effectively improve the geriatric oral care performance of HCAs.

Background: Amoxicillin resistance in Helicobacter pylori is mainly associated with mutations in penicillin-binding protein-1A (PBP-1A). However, the specific amino acid substitutions in PBP-1A that confer amoxicillin resistance in H. pylori remain to be investigated. Objective: This study aimed to investigate the molecular mechanism underlying amoxicillin resistance in patients with refractory H. pylori infection. Methods: Esophagogastroduodenoscopy (EGD) was performed in patients with persistent H. pylori infection after at least two courses of H. pylori eradication therapy between January-2018 to March-2021. Refractory H. pylori was cultured from the gastric biopsy specimens. Antibiotic susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs). Sequence analysis of pbp-1A was performed for amoxicillin-resistant strains. Results: Thirty-nine successfully cultured isolates were classified as refractory H. pylori isolates, and seventeen isolates were resistant to amoxicillin (MIC > 0.125 mg/L). Sequence analysis of resistant strains showed multiple mutations in the C-terminal region of PBP-1A that conferred amoxicillin resistance in H. pylori. However, the number of PBP-1A mutations did not correlate with the high MICs of amoxicillin-resistant isolates. Notably, some amino acid substitutions were identified in all Taiwanese isolates with history of eradication failure but not in published amoxicillin-susceptible strains, suggesting that the mutations may play a role in conferring antibiotic resistance to these strains. Conclusions: Our results show that amoxicillin resistance in refractory H. pylori is highly correlated with numerous PBP-1A mutations that are strain specific. Continuous improvements in diagnostic tools, particularly molecular analysis approaches, can help to optimize current antimicrobial regimens.

Background School principals have been reported to have a higher prevalence of burnout and psychological problems than their colleagues. During the pandemic, extra workload and pressure from unprecedented situations potentially cause fear, stress and depression. Therefore, we aimed to explore associated factors of stress, fear of COVID-19 (F-CoV-19S) and depressive symptoms among school principals.Methods A cross-sectional online survey was conducted in Taiwan from 23 June to 16 July 2021. Data of 413 school principals were collected, including socio-demographic factors, COVID-19-related factors, work-related information, health status, sense of coherence (SoC), health literacy (HL), F-CoV-19S, stress and depression. Multiple linear and logistic regression models were utilized to explore associations.Results School principals with symptoms like COVID-19 (S-COVID-19-S), or with health-related activity limitations had a higher score of stress (B = 0.92; p = .039) (B = 1.52; p

Abstract Background Inadequate sleep is a problem for teens world-wide. Identifying the biological and cultural factors that underlie this phenomenon is dependent on tools that can accurately query sleep-related behaviors. While there are many sleep-related questionnaires available in English, there are a paucity of validated Chinese language versions. As such, it was the purpose of this study to translate the Adolescent Sleep Wake Scale into Chinese and to provide a preliminary validation of this questionnaire. Methods We used a dual forward translation-back translation approach to translate the Adolescent Sleep Wake Scale into Chinese. We then tested the sensitivity, specificity, and internal consistency of the translated questionnaire using 517 adolescents from Taiwan. Preliminary criterion validity was examined through comparison with a measure of chronotype, with the a priori assumption that evening chronotypes would have worse sleep-related behavior. Results Internal consistency for both the overall scale (α = .86) and five subscales (α’s > .81) were good. These five subscales explained 62.6% of the total variance. Confirmatory Factory Analysis indicated a good fit of the data. The overall scale and each of the subscales also showed the expected relationship with chronotype, with worse sleep-related behavior in evening-types. Conclusion Our Chinese translation of the Adolescent Sleep Wake Scale is valid and has preliminary criterion validity. This can be a useful tool to explore sleep quality among Chinese-speaking adolescents as well as cross-cultural aspects of sleep behavior between Chinese- and English-speaking adolescents.

Background Digital health literacy (DHL) enables healthy decisions, improves protective behaviors and adherence to COVID-19 measures, especially during the era of the “infodemic”, and enhances psychological well-being. Objective We aimed to explore the mediating roles of fear of COVID-19, information satisfaction, and the importance of online information searching on the association between DHL and well-being. Methods A cross-sectional web-based survey was conducted among 1631 Taiwanese university students, aged 18 years and above, from June 2021 to March 2022. The collected data include sociodemographic characteristics (sex, age, social status, and financial satisfaction), the importance of online information searching, information satisfaction, fear of COVID-19, DHL, and well-being. A linear regression model was utilized to investigate factors associated with well-being, followed by a pathway analysis to assess the direct and indirect relationship between DHL and well-being. Results The scores of DHL and overall well-being were 3.1 ± 0.4 and 74.4 ± 19.7, respectively. Social status (B = 2.40, 95% confidence interval (CI) 1.73–3.07, p

Background/purpose: Sleep disturbance and psychological distress are among the most prevalent comorbidities of tinnitus. We aimed to clarify the dose–response effects of these phenomena with tinnitus severity. Methods: This study enrolled adult patients with subjective tinnitus for more than 6 months was conducted from January 2017 to December 2018 in one tertiary medical center and one local hospital. Data collected included demographic data and questionnaires, namely Tinnitus Handicap Inventory (THI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). Results: In total, 1610 patients with tinnitus (1105 male, 68.6%) with mean age of 48.3 ± 14.3 years completed all questionnaires. The average THI score was 9.2 ± 19.4, and 82.4% of patients reported to have slight tinnitus (THI ranged 0–16). The mean PSQI score was 8.4 ± 4.3, and 70.8% of participants had sleep difficulty (PSQI > 5). Compared with patients with slight tinnitus, those with catastrophic tinnitus were mostly old women with lower body mass index, and had higher scores in ESS, PSQI, and HADS (all P

This study investigated the antimicrobial resistance of isolates from patients with refractory Helicobacter pylori. The resistance rate was 34.1% for amoxicillin, 92.7% for clarithromycin, 65.9% for metronidazole, 85.4% for levofloxacin, and 29.3% for rifabutin. Dual resistance to both clarithromycin and levofloxacin was found in 73.2%. The antimicrobial resistance rate of refractory H. pylori was extremely high, which had become a major consideration in therapeutic challenge.

Abstract Background In Taiwan, illegal drug use is a critical health problem during adolescence. Schools playa vital role in preventing students’ illegal drug use. Accordingly, we developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and health literacy for junior high school students. Aim This study aimed to use a theory-based program to prevent students from illegal drug use in Taiwanese junior high school students. Methods We recruited 648 junior high school students aged around 13–14 years (grades 7 to 8 students) from 14 selected schools: N = 323 in the experimental group, N = 325 in the comparison group. The experimental group received 10 45-min sessions of a theory-based drug-use prevention program. The comparison group received traditional didactic teaching and drug refusal skill training. We used a generalized estimating equation (GEE) to analyze data. Results Results of paired t-tests indicated that drug-use health literacy and TPB-related variables improved in the experimental group. The GEE analyses indicated that participants in the experimental group also demonstrated significantly improved health literacy (p

Post-translational modification of mitochondrial proteins represents one mechanism by which the functional activity of mitochondria can be regulated. In the brain, these modifications can influence the functional properties of different neural circuitries. Given that the sirtuin family member Sirt3 represents the primary protein deacetylase enzyme in mitochondria, we tested whether brain mitochondrial proteome acetylation would increase in male or female mice lacking Sirt3. Our results confirm that whole brain mitochondrial proteome acetylation levels are indeed elevated in both sexes of Sirt3-KO mice relative to controls. Consistently, we found the mitochondria of mouse embryonic fibroblast (MEF) cells derived from Sirt3-KO mice were smaller in size, and fewer in number than in wild-type MEFs, and that mitochondrial free calcium levels were elevated within the mitochondria of these cells. As protein acetylation can influence mitochondrial function, and changes in mitochondrial function have been linked to alterations in neural circuit function regulating motor activity and anxiety-like behavior, we tested whether Sirt3-deficient mice would display sensitized responsiveness to the stimulant amphetamine. Both male and female Sirt3-KO mice displayed hyper-locomotion and attenuated anxiety-like behavior in response to a dose of amphetamine that was insufficient to promote any behavioural responses in wild-type mice. Collectively, these results confirm that Sirt3 regulates mitochondrial proteome acetylation levels in brain tissue, and that the absence of Sirt3 increases the sensitivity of neural systems to amphetamine-induced behavioural responses.

ABSTRACT Clostridioides difficile infection (CDI) is associated with high mortality rates among patients with chronic illnesses. We aimed to identify avoidable risk factors to reduce the mortality rate in CDI patients. A total of 306 patients with diarrhea and clinical suspicion of CDI were enrolled, and fecal samples were gathered from 145 patients. CDI was diagnosed by fecal positivity for the C. difficile tcdB gene. Risk factors associated with death within 180 days were identified using Cox regression analysis. The fecal microbiota was determined through bacterial 16S rRNA gene sequencing. Of the patients with diarrhea, 240 (mean age, 69.1 years) were positive for CDI, and 91 died within 180 days. Multivariate analysis revealed that male sex, high Charlson Comorbidity Index and McCabe scores, high serum C-reactive protein levels, low hematocrit levels, low absolute eosinophil counts, high neutrophil/lymphocyte ratios, and daily use of proton pump inhibitors (PPIs) were independent risk factors for overall mortality. Cumulative analyses confirmed the association of duration-dependent PPI use with a high mortality rate. Fecal microbiota analyses showed associations of decreased relative abundance of Ruminococcus gnavus (P = 0.001) and Prevotella copri (P = 0.025) and increased relative abundance of Parabacteroides merdae (P = 0.001) and Clostridioides difficile (P = 0.040) with higher mortality rates in patients with CDI. Moreover, these microbiota changes were correlated with the duration of PPI use. IMPORTANCE This article demonstrates that daily PPI use was the only avoidable risk factor for death. With more extended PPI use, the mortality rate was higher in patients with CDI. Decreases in Prevotella copri and Ruminococcus gnavus and increases in Parabacteroides merdae and Clostridioides difficile in line with daily PPI use duration were significantly associated with the death of CDI patients. Our findings provide in-depth insights into the cautious use of PPIs in chronically ill patients with CDI.

Background and Objective The Child and Adolescent Sleep Checklist (CASC) for parents was originally developed and published in Japanese and has served as a valid and effective tool for the assessment of a parent’s perspective of their adolescent child’s sleep behaviors. To allow for comparisons of such perspectives among parents of different cultures, and with different linguistic backgrounds, reliable and valid measurement tools are necessary. The purpose of this study was to translate and validate a Chinese language version of this questionnaire. Methods Internal consistency, factor structure, and criterion validity data were tested using 497 parent/adolescent dyads in Taiwan. Exploratory factor analysis (EFA) and internal consistency reliability were examined in a subset of the cohort (n = 241), while criterion validity and conduct confirmatory factor analysis (CFA) was examined in a second subset of the cohort (n = 256). Preliminary criterion validity was established through a comparison with a measure of chronotype, Morningness-Eveningness Scale for Children. Results EFA resulted in four factors, consistent with the original version, with the four factors accounting for 60% of the total variance. The results of CFA presented good fit to the data. The questionnaire demonstrated also acceptable to good internal consistency (α = 0.84–0.89). Preliminary criterion validity was evident as the total score and each of the subscale scores on the questionnaire were significantly higher (worse sleep-related behavior) in evening-types. Conclusions The Chinese language version of the CASC for parents appears to be a psychometrically sound measure to evaluate sleep behaviors in Chinese-speaking adolescents.

Background: Critically compromised by upper airway anatomical impaired properties, obstructive sleep apnea (OSA) can be categorized into different phenotypic traits, mainly including oropharyngeal muscle dysfunction. The upper airway muscle strength training was targeted on oropharyngeal muscle dysfunction by re-educating the oropharyngeal muscles to maintain the upper airway patency. OSA was characterized with multilevel collapsibility of the upper airway; however, the programs are still inconsistent and the effects are unknown. Therefore, the purpose of this study was to investigate the effects of a comprehensive physical therapy on OSA. Methods: Fifteen subjects with newly diagnosed moderate or severe OSA (AHI ≥ 15) were randomized into intervention and control groups. The intervention group underwent a 12-week-intervention of hospital based physical therapy, while the control group was kept on waiting for 12 weeks. Polysomnography (PSG) data, oropharyngeal and respiratory muscle performance were measured before and after intervention. Results: In intervention group (n = 8), AHI was significantly improved (from 46.96 ± 19.45 to 32.78 ± 10.78 events/h, p = 0.017); in control group (n = 7), AHI was significantly increased (from 35.77 ± 17.49 to 42.96 ± 17.32 events/h, p = 0.043). While the control group remained no change between pre- and post- intervention, the intervention group demonstrated that other PSG outcomes significantly improved, including arousal index (46.04 ± 18.9 versus 32.98 ± 8.35/h), mean SpO2 (92.88 ± 2.1 versus 94.13 ± 1.46%), and oxygen desaturation index (ODI) (31.13 ± 19.48 versus 20.57 ± 7.83/h). Conclusion: This comprehensive physical therapy can be prescribed for the significant clinical improvement on sleep apnea for the patients with moderate and severe OSA.

BackgroundHow anti-mitochondrial antibody (AMA) and liver biochemistry levels change in primary biliary cholangitis (PBC) patients treated with ursodeoxycholic acid (UDCA) remains unclear.MethodsA 28-year cohort of 157 PBC patients was conducted. Patients with alkaline phosphatase (Alk-p) levels >1.67 × upper limit of normal after 1 year of UDCA treatment were considered nonresponders.ResultsAt baseline, of 157 (mean age: 54.41 years), 136 (86.6%) were female, 51 (32.5%) had cirrhosis, and 128 (81.5%) had detectable AMAs (immunoglobulin G). UDCA nonresponders (n=61) were younger and had higher Alk-p and total bilirubin levels and cirrhosis rates than UDCA responders (n=84). Alk-p levels and cirrhosis were negatively associated with UDCA response. Regardless of cirrhosis and UDCA response, most PBC patients had decreased Alk-p and γ-glutamyltransferase levels at last follow-up (up to 28.73 years) compared with baseline levels. Patients with baseline cirrhosis (2.78 ± 2.56 vs. 6.84 ± 9.00 mg/dL, p=0.024) and UDCA nonresponders (2.54 ± 2.19 vs. 4.51 ± 6.99 mg/dL, p=0.006) had increased total bilirubin levels while patients without cirrhosis (AST: 91.5 ± 84.5 vs. 58.9 ± 43.7 U/L, p

Abstract Background There is no current standard rescue treatment for dual drug-resistant strains of Helicobacter pylori (H. pylori). This aim of this study was to investigate the efficacy of rifabutin-based triple therapy for patients infected with dual drug-resistant strains to clarithromycin and levofloxacin. Methods After 2 or 3 H. pylori treatment failures, patients underwent upper endoscopy with tissue biopsies. Phenotypic and genotypic resistances were determined using agar dilution test and polymerase chain reaction with direct sequencing, respectively. Patients infected with dual drug-resistant (clarithromycin and levofloxacin) strains and receiving rifabutin-based triple therapy (rifabutin 150 mg bid, amoxicillin 1 g bid and esomeprazole 40 mg bid for 10 days) were enrolled. Eradication status was determined by 13C-urea breath test 4 weeks after treatment completion. Results A total of 39 patients infected with dual drug-resistant strains were enrolled in this study, with a mean age of 55.9 years. The eradication rate was 79.5% (31/39) (95% confidence intervals: 54.96% ~ 111.40%). Adverse event was reported in 23.1% (9/39) of patients but they were mild and tolerable. In univariate analysis, no factor was identified as an independent predictor of eradication failure. Conclusions Our current study demonstrated that rifabutin-based triple therapy was well tolerated and yielded an acceptable eradication rate for patients infected with dual drug-resistant strains of H. pylori.

Abstract Purpose Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a dismal prognosis. Vascular invasion, among others, is the most robust indicator of postoperative recurrence and overall survival after liver resection for HCC. Few studies to date have attempted to search for effective markers to predict vascular invasion before the operation. The current study would examine the plasma metabolic profiling via 1H-NMR of HCC patients undergoing liver resection and aim to search for potential biomarkers in the early detection of HCC with normal alpha-fetoprotein (AFP) and the diagnosis of vascular invasion preoperatively. Materials and methods HCC patients scheduled to receive liver resections for their HCC were recruited and divided into two separate groups, investigation cohort and validation cohort. Their preoperative blood samples were collected and subjected to a comprehensive metabolomic profiling using 1H-nuclear magnetic resonance spectroscopy (NMR). Results There were 35 HCC patients in the investigation group and 22 patients in the validation group. Chronic hepatitis B remained the most common etiology of HCC, followed by chronic HCV infection. The two study cohorts were essentially comparable in terms of major clinicopathological variables. After 1H-nuclear NMR analysis, we found in the investigation cohort that HCC with normal alpha-fetoprotein (AFP < 15 ng/mL) had significantly higher serum level of O-acetylcarnitine than those with higher AFP (AFP ≥ 15 ng/mL, P = 0.025). In addition, HCC with microscopic vascular invasion (VI) had significantly higher preoperative serum level of formate than HCC without microscopic VI (P = 0.023). These findings were similar in the validation cohort. Conclusion A comprehensive metabolomic profiling of HCC demonstrated that serum metabolites may be utilized to assist the early diagnosis of AFP-negative HCC patients and recognition of microvascular invasion in order to facilitate preoperative surgical planning and postoperative follow-up. Further, larger scale prospective studies are warranted to consolidate our findings.

Abstract Background Chemotherapy with gemcitabine and cisplatin has been the standard of care in first-line chemotherapy for advanced biliary tract cancer (BTC) since the trial ABC-02 was published in 2010. We aimed to investigate the prognostic and predictive factors of this regimen in a cohort of Taiwanese patients with advanced BTC. Methods A total of 118 patients with histologically confirmed BTC treated at Chang Gung Memorial Hospital at Linkou from 2012 to 2017 were retrospectively reviewed. Results The median progression-free survival (PFS) and overall survival (OS) were 3.6 months and 8.4 months, respectively. In the multivariate analysis, neutrophil to lymphocyte ratio (NLR) > 7.45, biliary drainage requiring both percutaneous transhepatic cholangiography drainage (PTCD) and internal stenting, and tumor responses with progressive diseases and not assessed were independent poor prognostic factors for PFS. Male sex, NLR > 7.45, alkaline phosphatase> 94 U/L, biliary drainage requiring both PTCD and internal stenting, and tumor responses with stable disease, progressive diseases and not assessed were independent poor prognostic factors for OS. Monocyte to lymphocyte ratio (MLR) ≤ 0.28 was the only significant predictive factor for the tumor response. Patients with complete response/partial response had significantly lower MLR than patients with other tumor responses. Conclusion We identified three important prognostic factors, namely tumor response, NLR, and biliary drainage requiring both PTCD and internal stenting for both PFS and OS. MLR was the only significant predictive factor for the tumor response. These findings could provide physicians with more information to justify the clinical outcomes in patients with advanced BTC in real-world practice.

過去許多根據自我決定理論的研究皆指出，內在動機是促使學生努力學習、提高學習表現以及獲得滿足感的關鍵。然而，研究指出，包括臺灣在內的東亞儒家文化圈的國家中，基於盡責的外在動機也是激發學生投入學習的重要因素。為檢視這項理論上的歧義，本研究針對內、外在動機如何促動學習投入並引發不同滿足感，建構並驗證雙元學習動機的取徑。本研究針對511名高中生進行問卷調查，瞭解其學習動機、學習投入、學業表現，以及學習滿足感。經由結構方程式進行路徑分析與整體測量模式的配適度檢驗，本研究發現學生具有雙元的學習動機，並擁有兩種不同的心理滿足感。具體而言，基於個人興趣的內在動機需要透過「學習滿足感」預測學習投入，而基於個人盡責的外在動機能直接預測學習投入。無論內在或外在動機，受試者皆會因為學習投入而產生「道德滿足感」。研究結果對瞭解東亞儒家社會中學生的學習動機深具價值，本研究也進一步針對家庭與學校教育提出建議。 In the context of Self-Determination Theory (SDT), numerous published studies have argued that intrinsic motivation is the key to engaging students with their academic work, improving school performance, and acquiring psychological well-being. By contrast, an increasing body of research focusing on Eastern Asian Confucian societies, including Taiwan, has shed light on the salience of extrinsic motivation centered around role obligation and duty fulfillment. Scholars have argued that extrinsic motivation has a high value of encouraging students’ effort making, enhancing their academic performance and providing them with psychological fulfillment. To help settle this theoretical dissonance, this research constructed and validated the two learning paths of Taiwanese students, the first, learning for duty, and the second, learning for enjoyment. A self-developed questionnaire on students’ learning motivation, effort-making, academic performance, and acquired satisfaction was administered to 511 students in northern Taiwan. Structural equation modeling generated path analysis and model fit results that demonstrated that Taiwanese students possess two learning motivations followed by two types of psychological fulfillment. Specifically, intrinsic motivation based on personal interest predicted effort-making, with mediation of “learning satisfaction.” Extrinsic motivation based on duty fulfillment directly predicted effort-making. Furthermore, “obligation satisfaction” emerged as a result of effort-making, regardless of students’ different motivations. These findings regarding different learning motivations and satisfaction are valuable in reshaping the theoretical conception of learning motivation in a Confucian cultural setting. Relevant implications and suggestions for parenting and teaching are discussed.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. Methods We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. Results A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46–2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12–1.54), age 40–59 years (AHR = 1.49, 95%CI: 1.21–1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08–3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05–4.77) and without (AHR = 1.77, 95%CI: 1.46–2.15) sleep apnea had an increased risk of NAFLD. Conclusions Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

Lands reserved for indigenous people in Taiwan are mostly located at junctions between forestry compartments and hillside lands. After heavy rains, sediment disasters can easily occur in such locations. Therefore, identifying primary and derived disaster landslide areas of watersheds in lands reserved for indigenous people is imperative. This study used landslide-prone slopes to correct the vulnerability variable in the model proposed by Lin et al. (), and recalculated the landslide risks of watersheds. In addition, the study used protected objects as study subjects, and considered the likelihood of landslide disaster occurrence and its scale. Risk models for assessing the derived disasters caused by watershed landslides were constructed according to the spatial distribution of sediment delivery ratio. Comparisons between the present model and the original model regarding the relationship between landslide risks and landslide ratios in watershed subdivisions reveal that the corrected model shows significant positive correlation (R2 increased from 0.59 to 0.91). Risk models for assessing the derived disasters caused by watershed landslides indicate that the risk and the disaster ratio of the watershed subdivisions show significant and positive correlation (R2=0.84), indicating that the model developed in this study can effectively estimate the likelihood of protected objects encountering sediment disasters.

Data mining is a critical technology for extracting valuable knowledge from databases. It has been used in many fields, like retail, finance, biology, etc. In computational intelligence, fuzzy logic has been applied in many intelligent systems widely because it is simple and similar to human inference. Fuzzy utility mining combines utility mining and fuzzy logic for getting linguistic utility knowledge. In this paper, we study a more challenging, complicated, but practical topic called temporal fuzzy utility data mining, which considers the temporal periods in transactions, purchased amounts, item profits, and understandable linguistic terms as important factors. Although an Apriori-based algorithm was proposed previously, its execution was not efficient. We thus use a modified tree structure based on the classical frequent-pattern tree to improve its performance. A tree-based mining algorithm is also proposed to mine temporal fuzzy utility itemsets from quantitative transactional databases. The tree structure is built to keep all temporal fuzzy utility 1-itemsets in a database. All the high temporal fuzzy utility itemsets in a database can be obtained by traversing the tree-based structure. The proposed algorithm gets the final results through two phases. In the first phase, a procedure like FP-Growth is used to find the candidate itemsets. In the second phase, the temporal fuzzy utility database is scanned to decide whether the candidate itemsets are desired. Experimental results show that the proposed algorithm is superior to the existing algorithm for temporal fuzzy utility mining in terms of processing time and used memory.

Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2’-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.

In this study, EFL learners who listened to four short context-rich audio files each delivered in an unfamiliar English accent were required to produce best-attempt transcriptions and accent imitation recordings. Results indicate that exposure alone does not suffice to eliminate accent impact on EFL listeners. Importantly, results from one-way ANOVA analyses reveal between-participants differences in residual accent impact, vocabulary knowledge, and quality of accent imitation. Results from a linear mixed-effects model analysis, while suggesting that other unidentified factors may also assist EFL listeners in processing unfamiliar accented English, demonstrate that the more able mimics cope more successfully with unfamiliar accents than the less able mimics. Counter-intuitively, vocabulary knowledge is rejected as a predictor for success in reducing accent impact. A logical explanation for this particular finding is that a larger vocabulary repertoire aids listeners where there is no interference from unfamiliar accents. Given these findings, to better prepare EFL listeners for the English-as-an-International-Language world, training should include both listening to a variety of native and non-native accents and performing accent imitation (reproduction) exercises to further expand listeners' phonological-phonetic flexibility.

English orthographic learning, among Chinese-L1 children who were beginning to learn English as a foreign language, was documented when: (1) "only" visual memory was at their disposal, (2) visual memory and either "some" letter-sound knowledge or "some" semantic information was available, and (3) visual memory, "some" letter-sound knowledge and "some" semantic information were all available. When "only" visual memory was available, orthographic learning (measured via an orthographic choice test) was meagre. Orthographic learning was significant when either semantic information or letter-sound knowledge supplemented visual memory, with letter-sound knowledge generating greater significance. Although the results suggest that letter-sound knowledge plays a more important role than semantic information, letter-sound knowledge alone does not suffice to achieve perfect orthographic learning, as orthographic learning was greatest when letter-sound knowledge and semantic information were "both" available. The present findings are congruent with a view that the orthography of a foreign language drives its orthographic learning more than L1 orthographic learning experience, thus extending Share's ("Cognition" 55:151-218, 1995) self-teaching hypothesis to include non-alphabetic L1 children's orthographic learning of an alphabetic foreign language. The little letter-sound knowledge development observed in the experiment-I control group indicates that very little letter-sound knowledge develops in the absence of dedicated letter-sound training. Given the important role of letter-sound knowledge in English orthographic learning, dedicated letter-sound instruction is highly recommended.

Background: Acute lung injury (ALI) is a severe life-threatening inflammatory disease. Neutrophil activation is a major pathogenic factor in ALI. Protein kinase B (PKB)/AKT regulates diverse cellular responses, but the significance in neutrophilic inflammation and ALI remains unknown. Methods: Human neutrophils and neutrophil-like differentiated HL-60 (dHL-60) cells were used to examine the anti-inflammatory effects of 5,7-dimethoxy-1,4-phenanthrenequinone (CLLV-1). The therapeutic potential of CLLV-1 was determined in a mouse model of lipopolysaccharide (LPS)-induced ALI. Findings: CLLV-1 inhibited respiratory burst, degranulation, adhesion, and chemotaxis in human neutrophils and dHL-60 cells. CLLV-1 inhibited the phosphorylation of AKT (Thr308 and Ser473), but not of ERK, JNK, or p38. Furthermore, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT309–313 peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The alkylation agent-conjugated AKT (reduced form) level was also inhibited by CLLV-1. Significantly, CLLV-1 ameliorated LPS-induced ALI, neutrophil infiltration, and AKT activation in mice. Interpretation: Our results identify CLLV-1 as a covalent allosteric AKT inhibitor by targeting AKT Cys310. CLLV-1 shows potent anti-inflammatory activity in human neutrophils and LPS-induced mouse ALI. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation. Keywords: Acute lung injury, AKT, 5,7-dimethoxy-1,4-phenanthrenequinone, Inflammation, Neutrophil