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This study explored the views of 63 Taiwanese pre-service teachers who had participated in a workshop about the value of integrating drama-based approaches in their practical science learning. It was primarily designed to investigate the pedagogical approach of Heathcote and other founders of process drama. In addition, it examined specific claims that it immerses learners in an enjoyable and social learning environment (Poston-Anderson, 2008; Lin, 2017) and that learners can practice core scientific skills such as making predictions, observing, and then validating their predictions (Weisberg et al., 2016). Following the workshop, participants completed an anonymized online questionnaire. Descriptive data analysis indicated that most participants (75%) strongly agreed that integrating drama-based approaches into practical science teaching was satisfying. Of the remainder, 20.7% agreed, 2.1% neither agreed nor disagreed, 2.2% disagreed, and none strongly disagreed with this statement. Moreover, 34.9% of the participants lacked opportunities to experience improvisation and integration of drama-based teaching in practical science. The study indicated that a drama-based approach can be a highly effective strategy for enhancing practical science teaching among pre-service teachers. Furthermore, the findings provide valuable insights into the factors influencing drama-based teaching in practical science. They suggest it could be an excellent strategy to stimulate learners' interest in science and interdisciplinary science-related subjects and improve their science skills. Teachers could thus provide young children with similar drama-based teaching in practical science activities to promote their learning of science. Finally, the study offers a set of important recommendations for future pedagogical policymaking and further research by drama-based practitioners.

Flipped learning has attracted increasing attention in all grade levels in recent years and becomes an alternative to the traditional model. Even though there is a large body of research on flipped classrooms, they usually ignore the learning theories that were used to construct the curriculum and instead concentrate on the degree to which using such an approach affects student outcomes. The Realistic Mathematics Education (RME) theory provides a foundation for the development of tasks for students' collaborative learning. Therefore, this study proposes a flipped realistic mathematics education (F-RME) approach to support a mathematics classroom. To evaluate the effectiveness of the proposed approach, a quasi-experimental study, pretest--posttest non-equivalent group design, was implemented in a pre-engineering mathematics course. This design was chosen because randomization couldn't be done when getting the sample population. There were two groups of students: the students who adopted flipped realistic mathematics education (the F-RME group) and those who learned with conventional realistic mathematics education (the C-RME group). The finding revealed a significant increase in the posttest and post-questionnaire due to the implementation of the flipped learning-based approach in conjunction with realistic mathematics education. Moreover, the interview results of the experimental group revealed that students perceived adopting the FL-RME approach as an effective learning strategy that promotes "collaboration and interaction," "personalized learning" and "problem-solving ability." Accordingly, discussion of the findings, limitations of the present study, and suggestions for future research are provided.

The Expert-based Collective Advising Mechanism (ECAM) was embedded in the open online tutoring project to provide free tutoring for rural students and to help them improve their academic performance, and thus, to solve education inequity. Taking urban and rural students in Tongzhou District of Beijing as the objects, this study gathered data on the tutoring frequency, the durations students received tutoring, the number of teachers who tutored the same student, and the students' academic performance. The tutoring behavior and academic performance of rural and urban students were compared. The results showed that the ECAM could improve students' academic performance. Rural and urban students who received tutoring got the same degree of performance appreciation. Finally, gender, school type, and tutoring duration predicted academic performance positively.

Previous studies suggest that child behavior problems were associated with higher levels of parenting stress and depressive symptoms in parents of children with autism spectrum disorder (ASD). Parents' coping strategies have been found to provide potential buffering effects. Thus, this study investigated the mediation effect of coping strategies on the relationships between child behavior problems, parenting stress and depressive symptoms in Taiwanese mothers of children with ASD. Participants were 128 children with ASD (mean age = 32.32 months, SD = 10.43) and their mothers. All mothers completed a battery of questionnaires on parenting stress, depressive symptoms, coping strategies and child behavior problems. Principal components factor analysis identified three coping categories: Problem-focused coping, avoidance coping, and distraction coping. Problem-focused coping was correlated with decreased parenting stress and depressive symptoms, whereas avoidance coping was associated with increased parenting stress and depressive symptoms. In addition, problem-focused coping mediated the relationship between child externalizing behavior problems and parenting stress. In conclusion, problem-focused coping could be an effective strategy to deal with the stress issues on mothers of preschool-age children with ASD, and potentially may decrease the possibilities of negative outcomes.

Abstract Background This study aimed to identify DNA methylation biomarkers associated with myopia using summary-data-based Mendelian randomization (SMR). Methods A systematic search of the PubMed, Web of Science, Cochrane Library, and Embase databases was conducted up to March 27, 2024. SMR analyses were performed to integrate genome-wide association study (GWAS) with methylation quantitative trait loci (mQTL) and expression quantitative trait loci (eQTL) studies. The heterogeneity in the dependent instrument (HEIDI) test was utilized to distinguish pleiotropic associations from linkage disequilibrium. Results The systematic review identified 26 DNA methylation biomarkers in five studies, with no overlap observed among those identified by different studies. After integrating GWAS with multi-omics data of mQTL and eQTL, six genes were significantly associated with myopia: PRMT6 (cg00944433 and cg15468180), SH3YL1 (cg03299269, cg11361895, and cg13354988), ZKSCAN4 (cg01192291), GATS (cg17830204), NPAT (cg04826772), and UBE2I (cg03545757 and cg08025960). Conclusions We identified six methylation biomarkers associated with the risk of myopia that may be helpful to elucidate the etiology mechanisms of myopia. Further experimental validation studies are required to corroborate these findings.

Abstract Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism. Targeting NICD1 to mitochondria induces more EndMT compared with wild-type NICD1, and small molecule activation of PDH during pregnancy improves the phenotype in a mouse model of congenital heart defect. A NOTCH1 mutation observed in non-syndromic tetralogy of Fallot patients decreases NICD1 mitochondrial localization and subsequent PDH activity in heart tissues. Altogether, our findings demonstrate NICD1 enrichment in mitochondria of the developing mouse heart, which induces EndMT by activating PDH and subsequently improving mitochondrial metabolism.

Abstract This study explored the mechanism by which the m6A demethylase ALKBH5 mediates epithelial–mesenchymal transition (EMT) in sepsis‐associated acute kidney injury (SA‐AKI) and AKI‐chronic kidney disease (CKD) transition. HK‐2 cells were stimulated with lipopolysaccharide (LPS) to establish an in vitro model of SA‐AKI. ALKBH5 expression was reduced through the transfection of si‐ALKBH5. Cell viability, apoptosis, and migration were detected by CCK‐8 assay, TUNEL staining, and Transwell. The levels of TNF‐α, IL‐1β, and IL‐6 were measured by enzyme‐linked immunosorbent assay. Quantitative real‐time polymerase chain reaction or Western blotting was performed to determine the expressions of ALKBH5, miR‐205‐5p, DDX5, E‐cadherin, and α‐SMA. The m6A level was quantitatively analyzed. The expression of pri‐miR‐205 bound to DGCR8 and m6A‐modified pri‐miR‐205 after intervention with ALKBH5 expression was detected by RNA immunoprecipitation. A dual‐luciferase assay confirmed the binding between miR‐205‐5p and DDX5. ALKBH5 was highly expressed in LPS‐induced HK‐2 cells. Inhibition of ALKBH5 increased cell viability, repressed apoptosis, and reduced EMT. Inhibition of ALKBH5 increased the m6A modification level, thereby promoting DGCR8 binding to pri‐miR‐205 to increase miR‐205‐5p expression and eventually targeting DDX5 expression. Low expression of miR‐205‐5p or overexpression of DDX5 partially abolished the inhibitory effect of ALKBH5 silencing on EMT. In conclusion, ALKBH5 represses miR‐205‐5p expression by removing m6A modification to upregulate DDX5 expression, thereby promoting EMT and AKI‐CKD transition after SA‐AKI.

Objective: Kleefstra Syndrome (KS) is a rare genetic disorder caused by a deletion at 9q34.3. Studies showed that various heart defects are observed in 41–43% of patients and abnormal features on brain imaging in 58–63%. To date, the prenatal phenotype in KS has yet to be defined. Case report: We present the first prenatal diagnosis and chromosomal microarray analysis (CMA) of a case of 9q34.3 microdeletion in a fetus with increased amniotic fluid, supported by abnormal prenatal ultrasound findings, and confirmed via autopsy. CMA revealed a 2.1 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1, which is consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. Conclusion: When a fetus with normal karyotype presents with polyhydramnios or abnormalities noted during second-trimester prenatal ultrasound screening, CMA analysis can be considered as the next step to rule out or confirm the diagnosis of chromosomal or other genetic aberrations.

In order to study whether employee assistance programs have a significant impact on job performance, whether psychological contract and perceived organizational support play a mediating role in job performance, and thus provide practical operational strategies for relevant enterprises to propose human resource management suggestions to promote job performance, the implementation of employee assistance programs has been the subject of practical research. The findings indicate that addressing issues related to high turnover, job burnout, and absences cannot be separated from the importance of the psychological contract, perceived organizational support, and employee performance in organizational change. By applying structural equation modeling (SEM) to the data from front-line employees of several units in China, this research tested the relationships among employee assistance programs, psychological contracts, perceived organizational support, and job performance using SPSS and AMOS. The results indicate that employee assistance programs positively affect job performance; psychological contracts and perceived organizational support play a mediating role between employee assistance programs and employee job performance (JOP). Our research suggests that an employee assistance program can optimize frontline employee assistance work, build a mechanism to stimulate frontline employees' psychological contracts, and create an organizational environment full of perceived organizational support. This study innovatively uses the structural equation model for quantitative research. In addition, most previous studies on EPA were based on a single variable, psychological contract, and POS were used as the main intermediary variables to explore the mechanism of their impact on job performance so as to enhance the explanatory power of employee job performance. Doi: 10.28991/ESJ-2024-08-05-018 Full Text: PDF

Abstract Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005’s anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically.

Rhinovirus (RV) is a common pathogen that causes respiratory tract infection and can cause outbreaks in hospitals and welfare institutions. A cluster of respiratory diseases occurred in a primary school in Shenyang City, Liaoning Province, China, in 2022. In this outbreak, a total of 31 students had symptoms similar to those of upper respiratory tract infection, mainly cough and sore throat. Among them, 27 throat swabs were collected and identified for respiratory pathogens by TaqMan low-density array (TLDA), quantitative real-time polymerase chain reaction (PCR), reverse transcription-nested PCR and whole-genome sequencing. Out of the 27 specimens, 24 tested positive for RV, and 21 RV viral protein 1 sequences were obtained, of which 15 (71.43%) were identified as RV-A49, while 2 RV-A20 and 4 sequences from 2 specimens were RV-A30 coinfected with RV-C15. In addition, one whole-genome sequence (WGS) of RV-A49 was obtained, and three unique amino acid mutations were found compared to 23 WGS of RV-A49 from GenBank. In conclusion, this outbreak of upper respiratory tract infection is caused by RV, mainly RV-A49.

Abstract Background Video-assisted thoracic surgery decortication for phase 3 thoracic empyema is widely accepted, but its optimal timing has not been established. We aim to investigate and assess this timing, in terms of overall survival, for chronic empyema. Methods Two hundred four patients with pneumonia-caused phase 3 empyema were treated with video-assisted thoracic surgery decortication over 10-years at Changhua Christian Hospital. The 90-day post-operative survival status was analyzed, and we compared the survivor group versus the non-survivor group. A receiver operating characteristic curve was used to identify the optimal decortication timing. Results A comparison between survivors and non-survivors showed statistical differences among age (p=0.004), presence of cardiovascular disease (p=0.018), presence of end-stage renal disease (p=0.002), duration to surgery (p=0.013), length of intensive care unit stay (p=0.010), and overall length of hospital stay (p=0.015). ROC curve analysis determined the cut-off for video-assisted thoracic surgery decortication, based on optimal 90-day post-operative survival, to be 7.5 days after hospitalization; mortality increases threefold thereafter (14.2% vs 44.6%, p7.5 days negatively impacted 90-day post-operative survival. Conclusions Patients receiving decortication surgery within 7.5 days of hospital admission had better overall survival.

Abstract Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/β receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Abstract Background Collaborative learning is an essential pedagogy in medical education, within which small group learning constitutes an integral component. Online small group teaching has been widely applied and blended with in-person sessions in the aftermath of the Covid-19 pandemic. This study examined whether group metacognition was associated with teamwork satisfaction in an online small group teaching curriculum for medical students. Methods We enrolled medical students of the 2nd and 4th years during the 2021 fall semester after they participated in 3 consecutive sessions of online small group tutorials (SGTs), which have been implemented in our medical school for more than 20 years. The students completed a group metacognitive scale (GMS) and a teamwork satisfaction scale (TSS) after the sessions. We analyzed whether group metacognition in 4 dimensions (knowledge of cognition, planning, evaluating, and monitoring) could be connected with medical students’ teamwork satisfaction using partial least squares-structural equation modeling (PLS-SEM). Results A total of 263 medical students participated in this study. Both GMS and TSS exhibited good reliability and validity. Three of the 4 dimensions of group metacognition (cognition, planning, and evaluating) positively correlated with teamwork satisfaction (path coefficients 0.311, 0.279, and 0.21; p = 0.002, 0.002, and 0.043, respectively) following the online SGT curriculum, whereas the monitoring dimension did not (path coefficient 0.087; p = 0.357). The model achieved an adjusted R square of 0.683. Conclusion We discovered that group metacognition correlated positively with better teamwork satisfaction, supporting the importance of group metacognitive competency for online collaborative learning.

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa_circ_0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5′ UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy.

Abstract Background Apnea is common in preterm infants and can be accompanied with severe hypoxic damage. Early assessment of apnea risk can impact the prognosis of preterm infants. We constructed a prediction model to assess apnea risk in premature infants for identifying high-risk groups. Methods A total of 162 and 324 preterm infants with and without apnea who were admitted to the neonatal intensive care unit of Xiamen University between January 2018 and December 2021 were selected as the case and control groups, respectively. Demographic characteristics, laboratory indicators, complications of the patients, pregnancy-related factors, and perinatal risk factors of the mother were collected retrospectively. The participants were randomly divided into modeling (n = 388) and validation (n = 98) sets in an 8:2 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate logistic regression analyses were used to independently filter variables from the modeling set and build a model. A nomogram was used to visualize models. The calibration and clinical utility of the model was evaluated using consistency index, receiver operating characteristic (ROC) curve, calibration curve, and decision curve, and the model was verified using the validation set. Results Results of LASSO combined with multivariate logistic regression analysis showed that gestational age at birth, birth length, Apgar score, and neonatal respiratory distress syndrome were predictors of apnea development in preterm infants. The model was presented as a nomogram and the Hosmer-Lemeshow goodness of fit test showed a good model fit (χ 2 =5.192, df=8, P=0.737), with Nagelkerke R 2 of 0.410 and C-index of 0.831. The area under the ROC curve and 95% CI were 0.831 (0.787-0.874) and 0.829 (0.722-0.935), respectively. Delong's test comparing the AUC of the two data sets showed no significant difference (P=0.976). The calibration curve showed good agreement between the predicted and actual observations. The decision curve results showed that the threshold probability range of the model was 0.07-1.00, the net benefit was high, and the constructed clinical prediction model had clinical utility. Conclusions Our risk prediction model based on gestational age, birth length, Apgar score 10 min post-birth, and neonatal respiratory distress syndrome was validated in many aspects and had good predictive efficacy and clinical utility.

Objective(s): Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper 17 (Th17)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th17/Treg cell balance.Materials and Methods: The UC mouse model was established by administering 3% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th17/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF2BP1 in Th17/Treg balance.Results: We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th17 cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp3 but suppressed RORγt and interleukin-10 mRNA expression. PCR array of RNA modification-related genes revealed that the m6A binding protein IGF2BP1 was a key molecule in CCM regulation of Th17/Treg balance. IGF2BP1 overexpression dramatically repressed the CCM-induced balance of Th17/Treg cell differentiation. Mechanically, IGF2BP1 targeted LRP5 and regulated LRP5 through m6A modification. Furthermore, the silencing of LRP5 canceled the suppressive effect of IGF2BP1 on Th17/Treg cell percentage.Conclusion: CCM modulated the Th17/Treg balance through IGF2BP1-mediated m6A modification, thereby alleviating UC, and providing new ideas for the treatment of UC.

Agritourism is an alternative approach to distributing economic and social advantages and fostering sustainable development in rural regions. This research aims to identify critical success factors of agritourism to comprehend the obstacles and problems associated with Thailand and examine the essential factors of achieving success. The research adopts a mixed-method approach to collect, analyze, and interpret qualitative and quantitative aspects. The data was collected by reviewing documents, conducting in-depth interviews, conducting questionnaires, making onsite observations, and conducting focus group discussions. The questionnaires were sent to a panel of experts from educational institutions, the Ministry of Agriculture and Cooperatives, the Ministry of Tourism and Sports, and the tour operators. The data analysis involved paired t-tests and factor analysis to provide a comprehensive analytical output. The findings revealed four critical success factors in the Thai agritourism industry: geographical location, the entrepreneurial mindset of the farm operators, the quality of products and stories, and social media and publicity strategies. Agritourism sites in famous areas were found to have more potential for success, and an entrepreneurial mindset allows farmers to create attractions and diversify products. Therefore, knowing how to use new communication channels helps farmers deal with customers and better understand customer needs. Doi: 10.28991/HEF-2024-05-03-08 Full Text: PDF

Abstract We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone‐to‐renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non‐diagnosed PA (n = 147) were 4.54 (95% CI: 2.78‐7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64‐0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63‐3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90‐4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20‐2.86) for a 0.3 mmol/l higher serum high‐density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Abstract To elucidate the mechanisms underlying photoperiodic responses, we investigated the genomic and metabolomic responses of two broomcorn millet (Panicum miliaceum L.) genotypes. For this purpose, light-insensitive (D32) and light-sensitive (M51) genotypes were exposed to a 16 h photoperiod (long-day (LD) conditions) and an 8 h photoperiod (short-day (SD) conditions), and various transcriptomic and metabolomic changes were investigated. A total of 1664, 2564, 13,017, and 15548 DEGs were identified in the SD-D, LD-D, LD-M, and SD-M groups, respectively. Furthermore, 112 common DEGs were identified as well. Interestingly, most DEGs in the different groups were associated with photosynthesis and phenylpropanoid and carotenoid biosynthesis. In addition, 822 metabolites were identified under different treatments. The main metabolites, including L-malic and fumaric acids, were identified in the negative mode, whereas brucine and loperamide were identified in the positive mode. KEGG analysis revealed that the metabolites in the different groups were enriched in the same metabolic pathway of the TCA cycle. Furthermore, in negative mode, the metabolites of M51 were mainly D-glucose, whereas those of D32 were mainly L-malic and fumaric acids. One photoperiod candidate gene (C2845_PM11G01290), annotated as ATP6B, significantly increased the levels of L-malic and fumaric acids. In conclusion, our study provides a theoretical basis for understanding the molecular mechanisms of photoperiodic response regulation and can be used as a reference for marker development and resource identification in Panicum miliaceum L..

Abstract Background Type A aortic dissection (TAAD) with coronary involvement is rare but potentially fatal. Proper myocardial protection during surgery is essential. Case presentation Here, we describe a 52-year-old woman who presented with sudden chest pain. CT angiography revealed TAAD with right coronary artery involvement. During surgery, the proximal intima of the right coronary artery was found to be completely severed and everted. Conventional myocardial perfusion methods were inadequate. A patented perfusion tip for coronary artery orifice perfusion was used, resulting in favourable surgical outcomes. The patient was discharged without complications. Conclusions This case emphasizes the need for careful preoperative assessment of coronary involvement in TAAD patients. The myocardial protection method used here is very helpful and can be applied effectively in similar cases encountered by surgeons.

Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. Methods We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. Results USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. Conclusions Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.

Background: This study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methods: Adult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results: 1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P

Abstract Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction.

Deep storage tunnels (DSTs) are used in densely urbanized areas to relieve stormwater collection systems, thereby reducing urban floods and runoff pollution, due to their substantial storage capacity. The computation of the hydraulic characteristics and flow trajectories of DSTs under rapid filling scenarios can help to predict sediment deposition and pollutant accumulation associated with the stored runoff, as well as the likelihood of operational problems, such as excessive surging. However, such assessments are complicated by various inflow scenarios encountered in tunnel systems during their operation. In this study, the Suzhou River DST in China is selected as a study case. Particles were tracked, and hydraulic analysis was conducted with scaled model experiments and numerical models. The flow field, particle movement, air‒water phase, and pressure patterns in the DST were simulated under various one- and two-sided inflow scenarios. The results showed that with regards to the design conditions involving two-sided inflows, flow reversals occurred with stepwise increases in the water surface and pressure. In contrast, this phenomenon was not observed under the one-sided inflow scenario. Under the asymmetric two-sided inflow scenarios, water inflows led to particle accumulation near the shaft, reducing the received inflows. However, under the symmetric inflow conditions, particles were concentrated near the middle of the tunnel. Compared to those under the symmetric inflow scenario, asymmetric inflow caused surface wave and entrapped air reductions. This study could provide support for regulation of the inflow of the Suzhou River DST and for prediction of sediment and pollutant accumulation.

Teacher networks and communities have played an important role in teacher professional development. In such contexts, teachers often receive extensive feedback from peers as part of social learning. However, many teachers have difficulty identifying essential information from a large amount of peer feedback, which may impede self-reflection and peer learning. This study proposes the use of computer-assisted visual analytics of peer feedback to address this challenge. A visualisation-based analytical dashboard was designed and applied to help teachers analyse and reflect on peer feedback in a lesson study community for Technological Pedagogical Content Knowledge (TPACK) development. Primary school teachers participated in the lesson study, in which they collaborated to discuss lesson plans, observe recorded lessons, and give peer ratings and comments using an online platform. By comparing the performance between those using the analytical dashboard and others not using it, the results show that the approach has promising effects on improving teachers' TPACK as reflected in the lesson plans and their perceived confidence in TPACK. The implications of the findings are also discussed.

With the popularity of online one-to-one tutoring, there are emerging concerns about the quality and effectiveness of this kind of tutoring. Although there are some evaluation methods available, they are heavily relied on manual coding by experts, which is too costly. Therefore, using machine learning to predict instruction quality automatically is an effective way to reduce human costs. Three classification methods are analyzed in this article: (1) random forest algorithm with human-engineered descriptive features; (2) long and short-term memory algorithm with acoustic features generated by open speech and music interpretation by large space extraction toolkit; and (3) convolutional neural network algorithm with Mel spectrogram of the audio. The results show that the three approaches can complete the prediction task well, with the second approach exhibiting the best accuracy. The importance of the features in these classification models is analyzed according to eXplainable Artificial Intelligence techniques (i.e., XAI) and statistical feature analysis methods. In this way, key indicators of high-quality tutoring are identified. This study demonstrated the usefulness of XAI techniques in understanding why some tutoring sessions are of good quality and others are not. The results can be potentially used to guide the improvement of online one-to-one tutoring in the future.

One of the characteristics of individuals on the autism spectrum is the restricted, repetitive patterns of behaviors, interests, or activities which have been considered the result of a direct deficit in self-regulation skills. Peer-mediated intervention (PMI) is one of the ways to support young children on the autism spectrum for following school routines independently. PMI is an evidence-based practice based on behavioral principles to train typical peers to help with students on the autism spectrum. By using PMI, students on the autism spectrum can have more interaction opportunities with typical peers. Students on the autism spectrum can become less dependent on adult support to complete the expectations independently or with peers' support. The aim of this study is to use PMI to support students with autism and ADHD aged 7-8 in a regular classroom to complete the behavioral expectations in Taiwan. This study used a multiple probe design across three participants to determine the effects of the intervention. The researchers trained seven typically developing peers on how to prompt and reinforce the target children. This study took both peers and target children's data. The data shows a positive result for target children to follow the expectations independently and most peer models can prompt and reinforce the target children after being trained. Our study has extended the effectiveness and usage of PMI in teaching behavioral expectations in Taiwan.

Background The aging of our population is a growing problem, and depression is one of the more common psychiatric disorders in the elderly population, leading to a significantly increased risk of disability and death. The studies found a significant association between depression and cognitive disorders, and that this association may be influenced by sex. Sex differences in the associations between depression with cognitive functions and different cognitive domains are not clear in the elderly population. Objective Population ageing has become a common global phenomenon, and psychiatric problems associated with ageing are of great concern. This study investigated the status of depression and cognitive function in the urban elderly and examined the associations and sex differences between depression and cognitive function. Methods From September to October 2022, a stratified sampling method was used to select elderly residents aged 65 years and above in a community within the city of Hefei, Anhui province as the participants. General information was collected and depression and cognitive function status were assessed using the Geriatric Depression Scale (GDS) and the Brief Screening Scale for Dementia (BSSD), respectively. We explored the factors associated with depression in the elderly and analyzed the effects of depression, sex factors and their interactions on cognitive functioning. Results A total of 328 older adults were included and the overall detection rate for depression was 14.9 %. Regression analyses showed that drinking (OR=0.362, 95%CI=0.155-0.847), and living with children (OR=2.445, 95%CI=1.021-5.853) were independently associated with depression (P

This study investigates the efficacy of silane-modified zeolite powder in enhancing the early age crack resistance of concrete. Three concrete mixes were evaluated: a reference mix, a 20 % zeolite replacement mix, and a silane-modified zeolite mix. The silane-zeolite mix demonstrated significant improvements, extending the time to crack by 70 % compared to the reference mix (from 11.2 to 19.1 hours). Mechanical strength tests revealed a 58 % increase in first-crack strength for the silane-zeolite mix over the reference mix. Water absorption tests showed that the silane-zeolite mix absorbed 42 % less water than the reference mix, indicating a denser microstructure. Microscopic analyses confirmed these findings, revealing a more refined pore structure with reduced microcrack frequency and width in the silane-zeolite mix. These results highlight the potential of silane-modified zeolite in improving concrete durability and longevity.

ABSTRACTIntroduction Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both mucosal and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in the evaluation of mucosal immunity, which directly impedes the development and application of respiratory mucosal vaccines.Areas Covered This study summarizes the characteristics of immune responses in the respiratory mucosa and reviews the current status and challenges in evaluating immune response to respiratory mucosal vaccines.Expert Opinion Secretory Immunoglobulin A (S-IgA) is a major effector molecule at mucosal sites and a commonly used indicator for evaluating respiratory mucosal vaccines. However, the unique physiological structure of the respiratory tract pose significant challenges for the clinical collection and detection of S-IgA. Therefore, it is imperative to develop a sampling method with high collection efficiency and acceptance, a sensitive detection method, reference materials for mucosal antibodies, and to establish a threshold for S-IgA that correlates with clinical protection. Sample collection is even more challenging when evaluating mucosal cell immunity. Therefore, a mucosal cell sampling method with high operability and high tolerance should be established. Targets of the circulatory system capable of reflecting mucosal cellular immunity should also be explored.

Host-pathogen interactions (HPIs) are vital in numerous biological activities and are intrinsically linked to the onset and progression of infectious diseases. HPIs are pivotal in the entire lifecycle of diseases: from the onset of pathogen introduction, navigating through the mechanisms that bypass host cellular defenses, to its subsequent proliferation inside the host. At the heart of these stages lies the synergy of proteins from both the host and the pathogen. By understanding these interlinking protein dynamics, we can gain crucial insights into how diseases progress and pave the way for stronger plant defenses and the swift formulation of countermeasures. In the framework of current study, we developed a web-based R/Shiny app, Deep-HPI-pred, that uses network-driven feature learning method to predict the yet unmapped interactions between pathogen and host proteins. Leveraging citrus and CLas bacteria training datasets as case study, we spotlight the effectiveness of Deep-HPI-pred in discerning Protein-protein interaction (PPIs) between them. Deep-HPI-pred use Multilayer Perceptron (MLP) models for HPI prediction, which is based on a comprehensive evaluation of topological features and neural network architectures. When subjected to independent validation datasets, the predicted models consistently surpassed a Matthews correlation coefficient (MCC) of 0.80 in host-pathogen interactions. Remarkably, the use of Eigenvector Centrality as the leading topological feature further enhanced this performance. Further, Deep-HPI-pred also offers relevant gene ontology (GO) term information for each pathogen and host protein within the system. This protein annotation data contributes an additional layer to our understanding of the intricate dynamics within host-pathogen interactions. In the additional benchmarking studies, the Deep-HPI-pred model has proven its robustness by consistently delivering reliable results across different host-pathogen systems, including plant-pathogens (accuracy of 98.4% and 97.9%), human-virus (accuracy of 94.3%), and animal-bacteria (accuracy of 96.6%) interactomes. These results not only demonstrate the model's versatility but also pave the way for gaining comprehensive insights into the molecular underpinnings of complex host-pathogen interactions. Taken together, the Deep-HPI-pred applet offers a unified web service for both identifying and illustrating interaction networks. Deep-HPI-pred applet is freely accessible at its homepage: https://cbi.gxu.edu.cn/shiny-apps/Deep-HPI-pred/ and at github: https://github.com/tahirulqamar/Deep-HPI-pred.