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Despite evidence on the interaction between cognitive individual differences (IDs) and task complexity, our knowledge of how affective IDs, such as foreign language enjoyment (FLE), interact with task complexity and other factors is limited. Since tasks and activities were found by Dewaele and MacIntyre (2014) to be most relevant to FLE, and since task complexity might interact with learners' perceptions of task difficulty, it is important to investigate how task complexity impacts FLE changes. Informed by the complex dynamic systems theory, this study employed a mixed-methods multiple case study design to study patterns and causes of high and low FLE arousals. The participants were four pairs of Taiwanese high-intermediate EFL university students who were engaged in simple or complex storytelling tasks with speech acts of refusals. The speakers' interactions were triangulated with an individual learner's rating of FLE on a per-second scale and stimulated recalls. Results revealed idiosyncratic patterns of FLE fluctuations of peer interlocutors and a high degree of overlap in sources of low and high FLE in both groups. Speakers reported high FLE as a result of interesting storylines inherent in task design and created by peers, the use of picture prompts, peer collaboration, and task performance. Performance problems, failure to retrieve appropriate vocabulary, task design, and lack of ideas led to low FLE arousals. The findings suggest that task complexity combined with other task-induced, social, and individual factors to affect the fluctuations of FLE. Implications for task design and oral communication instruction to promote FLE are discussed.

The present study aimed to examine the barriers faced by Taiwanese university English as a foreign language (EFL) instructors when incorporating mobile-assisted language learning (MALL) into their teaching, and to explore how these barriers are influenced by the instructors' background characteristics. To assess the variables, a survey questionnaire was developed and administered to a sample of 350 university instructors. Additionally, interviews were conducted with a subset of instructors to complement and clarify the quantitative data. The findings indicated that university EFL instructors encountered moderate barriers when integrating MALL into their teaching practices. Furthermore, the study identified significant differences in the barriers experienced based on the amount of time instructors dedicated to MALL on a daily basis. Both quantitative and qualitative data highlighted the importance of time as a critical factor for successful MALL integration. As a recommendation, it is advised that university administrators consider reducing instructors' workload to facilitate the seamless integration of MALL.

Abstract SPINT1, a membrane-anchored serine protease inhibitor, regulates cascades of pericellular proteolysis while its tissue-specific functions remain incompletely characterized. In this study, we generate Spint1-lacZ knock-in mice and observe Spint1 expression in embryonic pancreatic epithelium. Pancreas-specific Spint1 disruption significantly diminishes islet size and mass, causing glucose intolerance and downregulation of MAFA and insulin. Mechanistically, the serine protease HEPSIN interacts with SPINT1 in β cells, and Hepsin silencing counteracts the downregulation of Mafa and Ins1 caused by Spint1 depletion. Furthermore, we demonstrate a potential interaction between HEPSIN and GLP1R in β cells. Spint1 silencing or Hepsin overexpression reduces GLP1R-related cyclic AMP levels and Mafa expression. Spint1-disrupted mice also exhibit a significant reduction in Exendin-4-induced insulin secretion. Moreover, SPINT1 expression increases in islets of prediabetic humans compared to non-prediabetic groups. The results unveil a role for SPINT1 in β cells, modulating glucose homeostasis and insulin production via HEPSIN/MAFA signaling.

Abstract Background The World Health Organization (WHO) aims to achieve a 50% rate of exclusive breastfeeding (EBF) during the first six months of life by 2025. Continuing breastfeeding up to six months is determined by an individual woman’s choice and the availability of breastfeeding-friendly environments. Methods In this multicenter prospective longitudinal study, we identified breastfeeding-friendly environmental factors that were associated with breastfeeding practices from days 1–5 to six months postpartum. Breastfeeding-friendly environmental factors were assessed using structured questionnaires for mothers who gave birth under a Baby-Friendly Hospital Initiative (BFHI). We evaluated uptake of breastfeeding by asking mothers if they used the indicated practices, as well as their perceived level of acceptance of breastfeeding among their live-in family members and their perceived availability of lactation rooms in public settings. From 2012 to 2016, we recruited 1,870 women at 1–5 days postpartum from obstetrics medical facilities in Taiwan and followed their breastfeeding status at one, two, four, and six months postpartum. The definition of EBF was that the infant had received only breast milk since birth, with no supplemental infant formula. We categorized breastfeeding practices into two groups: continuing EBF and non-continuing EBF at six months. We used logistic regression models to identify factors associated with continuing EBF at six months postpartum. Results The prevalence of EBF and non-EBF at six months postpartum was 30.9% and 69.1%, respectively. The logistic regression analysis revealed that above university-level education, multiparity, and vaginal delivery were positively associated with continuing EBF. The Ten Step Baby-Friendly Hospital Initiative practices, perceived acceptance of breastfeeding in live-in families, and perceived availability of lactation rooms in public settings, were associated with a higher likelihood of continuing EBF. Postpartum women who returned to work at or after two months postpartum were more likely to report non-continuing EBF than women who did not return to work. Conclusion Those who promote public health should advocate for breastfeeding-friendly practices, including the adoption of breastfeeding-friendly measures in public and workplace settings and providing increased support for breastfeeding mothers during and after hospitalization.

Abstract Background Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer therapy. This study examines the cardiovascular risks of ICIs compared to non-ICI therapies. Methods Utilizing the Chang Gung Research Database (CGRD) of Taiwan, this retrospective study analyzed 188,225 cancer patients, with 1,737 undergoing ICI treatment from January 1, 2008, to June 30, 2021. Through 1:1 propensity score matching (PSM), we compared specific outcomes between patients treated with ICIs and those who were not. The analysis also accounted for the competing risk of mortality in assessing the results after PSM. The observation period spanned from this index date to whichever came first: the date of the specific outcomes, the last follow-up recorded, or the end date of the study on June 30, 2022. Results The study found no significant increase in the risk of cardiac death, non-fatal myocardial infarction, heart failure hospitalization, deep vein thrombosis, or pulmonary embolism in patients treated with ICIs as compared to those receiving non-ICI therapy. Interestingly, ICI treatment was linked to a lower risk of non-fatal stroke (0.27% per year vs. 0.46% per year; subdistribution hazard ratio = 0.59; 95% confidence interval = 0.35–0.98; P = 0.0430). Furthermore, subgroup analysis revealed that the ICI group had a decreased risk of cardiac death in patients with cancers other than head and neck cancer, and a reduced risk of stroke among diabetic patients. Conclusions ICIs do not significantly elevate the risk of cardiovascular events in cancer patients and may lower the stroke risk, underscoring the need for additional prospective studies to clarify these findings.

Abstract Plankton plays important roles in the marine ecosystems as important producers for primary production, major components in the global biogeochemical cycles, and the foundation of the marine food web. Despite their importance, long-term monitoring data about marine plankton are fairly limited, especially in the Asia-Pacific region. We fill this knowledge gap by providing a 29-year long-term monitoring data on the coastal areas of western Taiwan quarterly from 1993 to 2021. This long-term monitoring data can be used to set proper baseline for detecting human-induced impacts on the plankton, as well as modelling future scenarios under global changes.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p

ObjectivesThis study aimed to investigate the correlation of ovarian sensitivity index (OSI) and clinical parameters in IVF treatments.MethodsIVF data files between January 2011 and December 2020 in a single unit were included. The primary outcome measure was the correlation between the OSI and clinical pregnancy and live birth rates. A generalized linear model was employed to assess group differences while controlling for age. Correlations between the OSI and clinical parameters were analyzed using Pearson’s correlation test.ResultsIn total, 1,627 patient data were reviewed, comprising 1,160 patients who received GnRH antagonists and 467 who received GnRH agonists. There was no difference in the incidence of premature ovulation and LH surge in women receiving either GnRH antagonists or agonists. A higher number of mature oocytes and good embryos were obtained in the GnRH agonist cycles. No differences were observed in pregnancy and live birth rates between both groups. Regarding the correlation of the OSI with clinical parameters, serum anti-Müllerian hormone, cycle day 2 follicle-stimulating hormone, LH, and estradiol concentrations, numbers of larger follicles, fertilization rate, and the incidence of premature LH surge were positively correlated with the OSI. Whereas the body mass index, mature oocytes obtained, embryo transfer number, and dose of GnRH antagonists were negatively correlated with the OSI. In the GnRH antagonists group, an OSI of 225.75 significantly distinguished pregnancy from non-pregnancy (p < 0.001), with an AUC of 0.615, and an OSI of 208.62 significantly distinguished live births from non-live births (p < 0.001), with an AUC of 0.637. As for the GnRH agonist group, an OSI of 228 significantly distinguished live births from non-live births, (p =0.020) with an AUC of 0.569.ConclusionWe demonstrated the capability of employing OSI to distinguish the clinical pregnancy and live birth outcomes in IVF cycles.

Feline chronic gingivostomatitis (FCGS) is a painful and severe inflammatory mucosal disease in cats that presents significant challenges in treatment. This case study describes a novel approach for a cat with FCGS that was unresponsive to antibiotics, non-steroidal anti-inflammatory drugs, and dental extraction. The cat exhibited rapid improvement after undergoing oral indocyanine green (ICG)-mediated antimicrobial photodynamic therapy (aPDT); however, treatment was discontinued due to an episode of anaphylaxis. Subsequent oral aminolevulinic acid (ALA)-mediated aPDT proved ineffective over nine sessions. The cat was then treated with a topical approach using ICG-aPDT. ICG was prepared by dissolving 5 mg of powder in 3 mL of sterile water, which was applied to the oral gingiva, followed by irradiation with an 810 nm diode laser, delivering a total fluence of 16.8 J/cm2 per session through the skin in two divided doses. The cat underwent biweekly aPDT, totaling 13 treatment sessions without any adverse events over four months. Gradual weight gain was observed from the first treatment. During the three-year follow-up, there was no recurrence of FCGS. This case report highlights the potential efficacy of topical ICG-aPDT as a treatment modality for FCGS.

Abstract Background Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. Methods We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. Results Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. Conclusions COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes.

Background: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. Methods: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. Results: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P

Abstract Although irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy. After administration of NA-iPSC cancer vaccine and radiotherapy, we found that ~60% of tumor-bearing mice achieved a complete response in microsatellite-stable CRC model. Furthermore, splenocytes from mice treated with NA-iPSC plus RT produced high levels of IFNγ secretion in response to neoantigens and had a greater cytotoxicity to cancer cells, suggesting that the NA-iPSC vaccine combined with radiotherapy elicited a superior neoantigen-specific T-cell response to eradicate cancer cells. The superior therapeutic efficacy of NA-iPSCs engineered by mouse TNBC neoantigens was also observed in the syngeneic immunocompetent TNBC mouse model. We found that the risk of spontaneous lung and liver metastasis was dramatically decreased by NA-iPSCs plus RT in the TNBC animal model. Altogether, these results indicated that autologous iPSC cancer vaccines engineered by neoantigens can elicit a high neoantigen-specific T-cell response, promote tumor regression, and reduce the risk of distant metastasis in combination with local radiotherapy.

Abstract Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration. MPS II-iPSCs were successfully differentiated into cortical neurons with characteristic biochemical and cellular phenotypes, including axonal beadings positive for phosphorylated tau, and unique electrophysiological abnormalities, which were mostly rescued in ISO-iPSC-derived neurons. RNA sequencing analysis uncovered dysregulation in three major signaling pathways, including Wnt/β-catenin, p38 MAP kinase, and calcium pathways, in mature MPS II neurons. Further mechanistic characterization indicated that the dysregulation in calcium signaling led to an elevated intracellular calcium level, which might be linked to compromised survival of neurons. Based on these dysregulated pathways, several related chemicals and drugs were tested using this mature MPS II neuron-based platform and a small-molecule glycogen synthase kinase-3β inhibitor was found to significantly rescue neuronal survival, neurite morphology, and electrophysiological abnormalities in MPS II neurons. Our results underscore that the MPS II-iPSC-based platform significantly contributes to unraveling the mechanisms underlying the degeneration and death of MPS II neurons and assessing potential drug candidates. Furthermore, the study revealed that targeting the specific dysregulation of signaling pathways downstream of GAG accumulation in MPS II neurons with a well-characterized drug could potentially ameliorate neuronal degeneration.

Abstract Engineering asymmetric transmission between left-handed and right-handed circularly polarized light in planar Fabry–Pérot (FP) microcavities would enable a variety of chiral light-matter phenomena, with applications in spintronics, polaritonics, and chiral lasing. Such symmetry breaking, however, generally requires Faraday rotators or nanofabricated polarization-preserving mirrors. We present a simple solution requiring no nanofabrication to induce asymmetric transmission in FP microcavities, preserving low mode volumes by embedding organic thin films exhibiting apparent circular dichroism (ACD); an optical phenomenon based on 2D chirality. Importantly, ACD interactions are opposite for counter-propagating light. Consequently, we demonstrated asymmetric transmission of cavity modes over an order of magnitude larger than that of the isolated thin film. Through circular dichroism spectroscopy, Mueller matrix ellipsometry, and simulation using theoretical scattering matrix methods, we characterize the spatial, spectral, and angular chiroptical responses of this 2D chiral microcavity.

Previous studies have suggested a possible association between carbon monoxide poisoning (COP) and hypothyroidism, but the evidence is limited. Therefore, the aim of this study was to further investigate this relationship. Using data from the Taiwan National Health Research Database, we identified 32,162 COP patients and matched with 96,486 non-COP patients by age and index date for an epidemiological study. The risk of hypothyroidism was compared between the two cohorts until 2018. Independent predictors of hypothyroidism were analyzed using competing risk analysis. An animal study was also conducted to support the findings. COP patients had an increased risk of hypothyroidism compared to non-COP patients in the overall analysis (adjusted hazard ratio [AHR]= 3.88; 95 % confidence interval [CI]: 3.27−4.60) and in stratified analyses by age, sex, and comorbidities. The increase in the overall risk persisted even after more than six years of follow-up (AHR= 4.19; 95 % CI: 3.18−5.53). Independent predictors of hypothyroidism, in addition to COP, included age ≥65 years, female sex, hyperlipidemia, and mental disorder. The animal study showed damages in the hypothalamus, pituitary gland, and thyroid, as well as altered hormone levels 28 days after COP exposure. The epidemiological results showed an increased risk of hypothyroidism in COP patients, which was further supported by the animal study. These findings suggest the need for close monitoring of thyroid function in COP patients, especially in those who are age ≥65 years, female, and have hyperlipidemia or mental disorder.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = −0.021, p = 0.011), Pb (coefficients = −0.060, p < 0.001), and Zn (coefficients = −0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p

Abstract It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low‐density sEV subpopulation. This low‐density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell‐derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles.

Abstract From eukaryotes to prokaryotes, all cells secrete extracellular vesicles (EVs) as part of their regular homeostasis, intercellular communication, and cargo disposal. Accumulating evidence suggests that small EVs carry functional small RNAs, potentially serving as extracellular messengers and liquid‐biopsy markers. Yet, the complete transcriptomic landscape of EV‐associated small RNAs during disease progression is poorly delineated due to critical limitations including the protocols used for sequencing, suboptimal alignment of short reads (20–50 nt), and uncharacterized genome annotations—often denoted as the ‘dark matter’ of the genome. In this study, we investigate the EV‐associated small unannotated RNAs that arise from endogenous genes and are part of the genomic ‘dark matter’, which may play a key emerging role in regulating gene expression and translational mechanisms. To address this, we created a distinct small RNAseq dataset from human prostate cancer & benign tissues, and EVs derived from blood (pre‐ & post‐prostatectomy), urine, and human prostate carcinoma epithelial cell line. We then developed an unsupervised data‐based bioinformatic pipeline that recognizes biologically relevant transcriptional signals irrespective of their genomic annotation. Using this approach, we discovered distinct EV‐RNA expression patterns emerging from the un‐annotated genomic regions (UGRs) of the transcriptomes associated with tissue‐specific phenotypes. We have named these novel EV‐associated small RNAs as ‘EV‐UGRsʼ or “EV‐dark matter”. Here, we demonstrate that EV‐UGR gene expressions are downregulated by ∼100 fold (FDR

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = −0.89, 95% Confidence Interval [CI]: −1.48 to −0.30). In contrast, listening to music alone showed a smaller effect (SMD = −0.26, 95% CI: −0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.

Summary: Background: The effect of positron emission tomography (PET) on the surgical treatment of locoregionally recurrent colorectal cancer (LRRCRC) remains unclear and warrants further investigation. Material and methods: A total of 193 patients with LRRCRC were identified from a prospectively maintained institutional database, of whom 134 LRRCRCs were deemed resectable and underwent resection with curative intent, whereas the remaining 59 LRRCRCs were unresectable. Patients with resectable LRRCRC were further classified according to whether recurrence was detected solely by PET (n = 35, PET-only group) or by a combination of computed tomography (CT)/magnetic resonance imaging (MRI) and PET (n = 99, CT/MRI/PET group). Clinicopathologic features, operative morbidity/mortality, and overall survival were compared between the patient groups based on long-term follow-up for at least 5 years. Results: Patients in the PET-only group tended to have less extensive organ resection (p = 0.0074), less blood loss (p 0.05) compared with the CT/MRI/PET group. Although the PET-only group had significantly higher R0 resection rate (80 % vs. 54.55 %, p = 0.0079), they also had a higher risk (17.14 % vs. 2.02 %, p = 0.0011) of sham operation. The estimated 5-year and 10-year survival rates significantly decreased in order (p

Abstract ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Blockade of the ATP receptor P2RX7 by the systemic administration of small molecules significantly attenuated the therapeutic efficacy of chemotherapy and decreased the infiltration of immune cells. In contrast, administration of an ATP mimic markedly increased the therapeutic efficacy of chemotherapy and enhanced the infiltration of immune cells in vivo. High PANX1 expression was positively correlated with the recruitment of DCs and T cells within the tumor microenvironment and was associated with favorable survival outcomes in CRC patients who received adjuvant chemotherapy. Furthermore, a loss-of-function P2RX7 mutation was associated with reduced infiltration of CD8+ immune cells and poor survival outcomes in patients. Taken together, these results reveal that TNFα-mediated PANX1 cleavage promotes ATP-P2RX7 signaling and is a key determinant of chemotherapy-induced antitumor immunity.

Background/Aims Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg

Fibromyalgia is a chronic illness usually accompanied by long-lasting, general pain throughout the body, often accompanied by anxiety, depression, fatigue, and sleep disruption. Meanwhile, doctors and scientists have not entirely discovered detailed mechanisms; patients always have an exaggerated sensation to pervasive pain without satisfied medical service. Given the lack of knowledge on its underlying mechanism, current treatments aim to provide pain and/or symptom relief. The present study aimed to clarify the role of cannabinoid receptor 1 (CB1) signaling in a mouse fibromyalgia pain model. To develop the mouse fibromyalgia model, mice were subjected to intermittent cold stress (ICS). Our results indicated that mechanical (2.09 ± 0.09 g) and thermal hyperalgesia (4.77 ± 0.29 s), which were evaluated by von Frey and Hargraves’ tests, were induced by ICS, suggesting successful modeling. The hurting replies were then provoked by electroacupuncture (EA) but not for sham EA mice. Further, in a Western blot analysis, we found significantly decreased CB1 protein levels in the thalamus, somatosensory cortex, and anterior cingulate cortex. In addition, the levels of pain-related protein kinases and transcription factor were increased. Treatment with EA reliably increased CB1 expression in various brain regions sequentially alleviated by nociceptive mediators. Furthermore, the administration of a CB1 agonist significantly attenuated fibromyalgia pain, reversed EA analgesia by the CB1 antagonist, and further reversed the chemogenetic inhibition of SSC. Our innovative findings evidence the role of CB1 signaling in the interaction of EA and fibromyalgia, suggesting its potential for clinical trials and as a treatment target.

Background Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC.Methods Cytosolic dsRNA level and its sensors were evaluated via cell-based assays (co-culture assay, confocal microscopy, pharmacological inhibition and immunofluorescent staining) and in vivo experiments. Biopsies and surgical tissues from patients with CRC who received preoperative chemoradiotherapy (neoCRT) were collected for multiplex cytokine assays, immunohistochemical analysis and SNP genotyping. We also generated a cancer-specific adenovirus-associated virus (AAV)-IFNβ1 construct to evaluate its therapeutic efficacy in combination with RT, and the immune profiles were analyzed by flow cytometry and RNA-seq.Results Our studies revealed that RT stimulates the autonomous release of dsRNA from cancer cells to activate TLR3-mediated IFN-I signatures to facilitate antitumor immune responses. Patients harboring a dysfunctional TLR3 variant had reduced serum levels of IFN-I-related cytokines and intratumoral CD8+ immune cells and shorter disease-free survival following neoCRT treatment. The engineered cancer-targeted construct AAV-IFNβ1 significantly improved the response to RT, leading to systematic eradication of distant tumors and prolonged survival in defective TLR3 preclinical models.Conclusion Our results support that increasing cancer-intrinsic IFNβ1 expression is an immunotherapeutic strategy that enhances the RT-induced antitumor immune response in locally patients with advanced CRC with dysfunctional TLR3.

BackgroundPhysical frailty is an important issue in aging societies. Three models of physical frailty assessment, the 5-Item fatigue, resistance, ambulation, illness and loss of weight (FRAIL); Cardiovascular Health Study (CHS); and Study of Osteoporotic Fractures (SOF) indices, have been regularly used in clinical and research studies. However, no previous studies have investigated the predictive ability of machine learning (ML) for physical frailty assessment. The aim was to use two ML algorithms, random forest (RF) and extreme gradient boosting (XGBoost), to predict these three physical frailty assessment models.Materials and methodsQuestionnaires regarding demographic characteristics, lifestyle habits, living environment, and physical frailty assessment were answered by 445 participants aged 60 years and above. The RF and XGBoost algorithms were used to assess their scores for the three physical frailty indices. Furthermore, feature importance and Shapley additive explanations (SHAP) were used to determine the important physical frailty factors.ResultsThe XGBoost algorithm obtained higher accuracy for predicting the three physical frailty indices; the areas under the curve obtained by the XGBoost algorithm for the 5-Item FRAIL, CHS, and SOF indices were 0.84. 0.79, and 0.69, respectively. The feature importance and SHAP of the XGBoost algorithm revealed that systolic blood pressure, diastolic blood pressure, age, and body mass index play important roles in all three physical frailty models.ConclusionThe XGBoost algorithm has a more accurate predictive rate than RF across all three physical frailty assessments. Thus, ML can be a useful tool for the early detection of physical frailty.

BackgroundThe adoption of mobile health (mHealth) apps among older adults (>65 years) is rapidly increasing. However, use of such apps has not been fully effective in supporting people with dementia and their caregivers in their daily lives. This is mainly attributed to the heterogeneous quality of mHealth apps, highlighting the need for improved app quality in the development of dementia-related mHealth apps. ObjectiveThe aims of this study were (1) to assess the quality and content of mobile apps for dementia management and (2) to investigate the relationship between app quality and download numbers. MethodsWe reviewed dementia-related mHealth apps available in the Google Play Store and Apple App Store in Taiwan. The identified mobile apps were stratified according to a random sampling approach and evaluated by five independent reviewers with sufficient training and proficiency in the field of mHealth and the related health care sector. App quality was scored according to the user version of the Mobile Application Rating Scale. A correlation analysis was then performed between the app quality score and number of app downloads. ResultsAmong the 17 apps that were evaluated, only one was specifically designed to provide dementia-related education. The mean score for the overall app quality was 3.35 (SD 0.56), with the engagement (mean 3.04, SD 0.82) and information (mean 3.14, SD 0.88) sections of the scale receiving the lowest ratings. Our analyses showed clear differences between the top three– and bottom three–rated apps, particularly in the entertainment and interest subsections of the engagement category where the ratings ranged from 1.4 to 5. The top three apps had a common feature in their interface, which included memory, attention, focus, calculation, and speed-training games, whereas the apps that received lower ratings were found to be deficient in providing adequate information. Although there was a correlation between the number of downloads (5000 or more) and app quality (t15=4.087, P

In 2019, the coronavirus pandemic was caused by severe acute respiratory syndrome coronavirus 2. In Taiwan, an inflatable negative pressure isolation chamber (INPIC) was applied into the emergency air medical transport (EAMT) in 2020. The standard operating procedure of the INPIC as infection control was developed and practiced in the UH-60M helicopter. There were five cases moved by the EAMT from the Lanyu Township and Ludao Township to Taiwan's mainland. After they were screened positive for coronavirus disease 2019 (COVID-19) with a rapid test, the medical staff completed the INPIC preparation and loaded the patients into it before the EAMT. This study reported that none of the crewmembers were infected with COVID-19 during the transfers. However, some restrictions of the INPIC could be improved in the future, e.g. limited space, thermal stress, equipment immobilization, and communication barrier. The medical team should assess the efficiency and safety using the INPIC based on each patient's condition before the flight.

Abstract Due to the rise of renewable energy/green energy issues in recent years, many countries have agreed to adopt the forms of environmental protection, cleanliness, and no impact on the environment for the sources and composition of energy. They have also drawn up relevant international agreements (i.e., Kyoto Protocol, Paris Agreement) to strictly limit and manage CO2 emissions. The newly advocated electric vehicles have gradually been regarded as a method to improve the environment by all countries. Through the introduction of new electric transport modes, the innovation and reform of the energy structure are promoted, and traditional transportation has also changed. In recent years, Taiwan has promoted the policy of replacing traditional fuel two-wheeled vehicles with electric two-wheeled vehicles (ETWVs), and gradually increased the number of ETWVs in Taiwan by replacing old fuel vehicles and subsidizing the purchase of ETWVs. This study is aimed at college students to explore the important factors that affect their willingness to buy ETWVs. As college students are the first group to buy ETWVs, if their willingness to buy ETWVs can be increased, environmental sustainability may be enhanced. Through a questionnaire designed to investigate the two-wheeled vehicle use preferences of college students in Taiwan, this paper explores the significant factors affecting college students’ purchase of ETWVs. This study applies Logistic Regression and Ordered Logit models, and the results of model estimation show that household income, gender, environmental awareness, recognition of ETWVs, the fuel costs of existing vehicles, number of people in each household, operational efficiency of ETWVs, and subsidy and incentive measures will all positively affect the purchase intention of college students.

Abstract Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient’s prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

Abstract Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011–3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.

Abstract Regional lymph node metastasis is an important predictor for survival outcome and an indicator for postoperative adjuvant chemotherapy in patients with colorectal cancer. Even with advances in adjuvant chemotherapeutic regimens, 5-year distant metastasis and survival rates are still unsatisfactory. Here, we evaluate the clinical significance of polymorphisms in receptors for HMGB1, which is the hallmark of chemotherapy-induced immunogenic cell death, in patients with stage II–III colon carcinoma (COAD). We found that high cytosolic HMGB1 is elicited in stage III COAD patients who received adjuvant chemotherapy. Patients with the TLR1-N248S polymorphism (rs4833095), which causes loss-of-function in HMGB1-mediated TLR1–TLR2 signaling, may influence the therapeutic efficacy of adjuvant chemotherapy, leading to a high risk of distant metastasis within 5 years [HR = 1.694, 95% CI = 1.063–2.698, p = 0.027], suggesting that TLR1-N248S is an independent prognostic factor for locally advanced colon carcinoma patients. We found that defective TLR1 impaired TLR1/2 signaling during dendritic cell (DC) maturation for the antitumor immune response under immunogenic chemotherapy oxaliplatin (OXP) treatment. Defective TLR1 on DCs impaired their maturation ability by HMGB1 and reduced the secretion of IFNγ from T cells to eradicate tumor cells in vitro. Moreover, systemic inhibition of TLR1/2 dramatically reduced the tumor-infiltrating immune cells by OXP treatment, leading to poor therapeutic response to OXP. In contrast, administration of a TLR1/2 agonist synergistically increased the benefit of OXP treatment and triggered a high density of tumor-infiltrating immune cells. We also observed that fewer tumor-infiltrating cytotoxic T lymphocytes were located within the tumor microenvironment in patients bearing the TLR1-N248S polymorphism. Overall, our results suggest that dysfunctional TLR1 may reduce the therapeutic response to adjuvant chemotherapy by impairing HMGB1-mediated DC maturation and attenuating the antitumor immune response in locally advanced colon carcinoma patients.

Pipeline installation is a time-consuming and expensive process in the oil sector. Because of this, a pipe is often utilized to carry diverse petroleum products; hence, it is crucial to use a precise and dependable control system to identify the kind and quantity of oil products being transported. This study attempts to identify four petroleum products by using an X-ray tube-based system, feature extraction in the frequency and temporal domains, and feature selection using Particle Swarm Optimization (PSO) in conjunction with a Group Method of Data Handling (GMDH) neural network. A sodium iodide detector, a test pipe that simulates petroleum compounds, and an X-ray source make up the implemented system. The detector's output signals were transmitted to the frequency domain, where the amplitudes of the top five dominant frequencies could be determined. Furthermore, the received signals were analyzed to extract five temporal characteristics-MSR, 4th order moment, skewness, WL, and kurtosis. The PSO system takes into account the extracted time and frequency features as input in order to introduce the optimal combination. Four different GMDH neural networks were constructed, and the chosen characteristics were used as inputs for those networks. Finding the volume ratio of each product was the responsibility of each neural network. The four designed neural networks were able to predict the amount of ethylene glycol, crude oil, gasoil, and gasoline with RMSE of 0.26, 0.17, 0.19, and 0.23, respectively. One compelling argument for using the proposed approach in the oil industry is that it can calculate the volume ratio of products with a root mean square error of no more than 0.26. The adoption of a feature selection method to choose the best ones is credited with this remarkable degree of precision. By providing appropriate inputs to neural networks, the control system has significantly outperformed its predecessors in terms of precision and efficiency.

Abstract Background This study aims to analyze the impact of Framework of Convention of Tobacco Control (FCTC) on regulatory contents of trade agreements from 2001 to 2019. Methods A search of trade agreements from‘WTO Regional Free Trade Agreement Database’ using keywords including “tobacco”, “cigarette”, “smoking” and “FCTC” from May to August 2020 resulted in a total sample of 268 trade agreements, from which 69 trade agreements were coded and analyzed. Provisions in trade agreements, identified via the aforementioned keywords, were categorized into 6 trade measures. The word counts of the provisions containing; FCTC; were calculated. Chi-square tests were applied to analyze the differences of regulatory patterns between different time frames. The import and export values (USD) of tobacco products under trade agreements containing the term “FCTC” were further collected from the “International Trade Statistics 2001–2020” for understanding the impact of the provision on the trade flow. Results Among 69 agreements, the percentage of trade agreements containing keyword as “FCTC” increased significantly from 0% to 2011 to 12% after 2011. A significant decrease of using trade measures as “the exclusion list” was found after 2011 (from 10% to 0). The word counts of provisions containing; FCTC; increased from 24 words in 2011 to 164 words in 2018, and the content of the provisions became more concrete over time. There are six trade agreements containing “FCTC”, and all these 6 agreements were ratified by European Union (EU). Despite EU ratified trade agreements with “FCTC”, the import and export values of tobacco products between EU and the other party countries increased with time. But the gap of average trade values between trade agreements with and without “FCTC” being widened with time. Conclusions As a first study evaluated the impact of FCTC on regulatory contents of trade agreements, our study results showed that after countries signed trade agreements containing keyword FCTC, the regulatory contents changed significantly. Further studies are recommended to understand the reason and criteria for incorporating FCTC provisions into trade agreements, especially in the EU.

Abstract Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p

Photon-number-resolving detectors are in high demand for applications in photonic quantum technology. In this study, we demonstrate the photon-number-resolving capabilities of our self-developed, highly efficient InGaAs/InAlAs single-photon avalanche diode. We achieved intrinsic photon number resolving by harnessing the high multiplication gain generated through an avalanche process in the InAlAs multiplication layer. With a maximum single-photon detection efficiency of 46%, we were able to distinguish photon number states up to 5 from the signal probability distribution without encountering avalanche saturation that could otherwise limit the capability of photon number resolving. We reasonably anticipate that the photon-number-resolving accuracy and capability can be further improved once the noise issue in such InGaAs/InAlAs SPADs is carefully managed.