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Online learning is emphasised in the 21st century curricula as one of the efficient instructional practices that improves the learning ownership of contemporary learners. A key factor in ensuring success in learners' online learning environments is the implementation of learner control. Learner control motivation is influenced by multiple interconnected beliefs and learner-directed learning practices. This study focuses on self-regulation strategies and motivational beliefs in the context of post-pandemic online tutorials. The aim of this study was to discover the influence of self-regulation strategies on learners' motivational beliefs, and the impact of learners' motivational beliefs on their learner control motivation when experiencing online tutorials. This study comprises 14 learners (age 9) from a Malaysian elementary school. Qualitative case study methodology was employed, using interviews and observations. The results of this study revealed a significant relationship between self-regulation and motivational beliefs in order to comprehend learners' motivation for learner control when experiencing online tutorials. The results drew attention on self-regulation strategies to guide online instruction that underpins learners' motivational beliefs and enhances learner control motivation.

Abstract Arctic amplification (AA), the greater Arctic surface warming compared to the global average, has been widely attributed to increasing concentrations of greenhouse gases (GHG). However, less is known about the impacts of other forcings - notably, anthropogenic aerosols (AER) - and how they may compare to the impacts of GHG. Here we analyze sets of climate model simulations, specifically designed to isolate the AER and GHG effects on global climate. Surprisingly, we find stronger AA produced by AER than by GHG during the 1955–1984 period, when the strongest global AER increase. This stronger AER-induced AA is due to a greater sensitivity of Arctic sea ice, and associated changes in ocean-to-atmosphere heat exchange, to AER forcing. Our findings highlight the asymmetric Arctic climate response to GHG and AER forcings, and show that clean air policies which have reduced aerosol emissions may have exacerbated the Arctic warming over the past few decades.

Abstract Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.

Abstract Background/purpose(s) The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. Methods We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. Results Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. Conclusion Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies. Graphical Abstract

Abstract A series of siloxane‐containing polyimide films (PIS) were prepared by copolymerising with rigid aromatic dianhydride, siloxane diamines and six different aromatic diamines. The effects of siloxane structures, fluorine and imide content, rigid or flexible segment on the heat resistance, moisture absorption, dielectric performance, mechanical and bonding properties were systematically studied. The results show that PIS films maintain good heat resistance with Tg between 292 and 420°C and 5% weight loss temperature higher than 500°C. The moisture absorption and dielectric constant can be significantly reduced due to the presence of siloxanes and fluorinated groups, with the absorption rate as low as 1.2% and dielectric constant of 2.85 at 1 MHz. When measured at 10 GHz, the dielectric constant ranges from 3.10 to 3.50, and dielectric loss varies from 0.0059 to 0.0098. The PIS‐6 film has the best comprehensive performance due to the low imide content, introduction of trifluoromethyl and ether bonds. The peeling strength of bonding PIS‐6 film with a copper foil can reach 9.2 N/cm. It is proven that siloxane‐containing PIS films with high heat resistance, low dielectric and outstanding adhesion are achieved, which can be applied for flexible integrated circuit boards, high‐frequency electronics and microelectronics fields.

Recently, a-IGZO has advanced toward the next-generation electronics system because of its compatibility with complementary metal oxide semiconductor (CMOS) and back-end-of-line (BOEL) based systems. A systematic electrical characterization of a-IGZO TFT related to reliability issues, such as positive bias temperature stress (PBTS) and negative bias temperature stress (NBTS), would entitle its integration into novel electronics systems. Unexpectedly, PBTS is characterized by the transition of positive Vth shift to negative Vth shift (ΔVth, the positive shift followed by the stress and temperature activated negative shift). This transition is attributed to charge trapping/trap-site generations and hydrogen migration to the active layer. The ΔVth shift mechanism depends on the temperature and voltage stress. On the other hand, a negative ΔVth shift has been observed during the NBTS operation and could be attributed to the hole trapping at the interface of GI/IGZO. An effective suppression of the gate leakage current has also been observed during reliability tests. Simulation results reveal a pronounced potential at the edges of source and drain regions, and considered the origin of hydrogen migration into the IGZO layer. Thermal image results also reveal the strong temperature/potential distribution at the edges of the source/drain regions, indorsing the simulation results.

Abstract Background This study aims to investigate the relationship between gestational metabolic syndrome (GMS) and the Chinese Healthy Eating Index (CHEI) in mid-pregnancy, and to identify potentially beneficial or high-risk dietary habits. We have developed a mid-pregnancy version of CHEI-2022, adapting the Chinese Healthy Eating Index to align with the food quantity recommendations outlined in the 2022 Dietary Guidelines for Chinese Residents for mid-pregnancy. Methods Using the inclusion and exclusion criteria, data from 2411 mid-pregnant individuals were collected through interviews. The Total CHEI score and its component scores were determined through analysis of responses from the food frequency questionnaire. GMS diagnosis involved conducting physical examinations and performing blood biochemical tests. A logistic regression model was employed to analyze the relationship between GMS or related indices and both the total CHEI score and its component scores. Results The study identified an overall GMS prevalence of 21.65% (522 out of 2411 participants). During mid-pregnancy, participants diagnosed with GMS exhibited higher BMI, FBG, 1hPBG, 2hPBG, TC, TG, HDL, SBP, as well as higher educational levels and daily activity, compared to those without GMS (P

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10-25 , odds ratio (OR) = 21.7, 95% confidence interval (95% CI) = 12.1-38.8) and NUDT15 rs746071566 (P = 4.2 × 10-9 , OR = 7.1, 95% CI = 3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate = from 7.6% decreased to 0.4%; P = 9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

Study region: The island of Taiwan. Study focus: This study presents long-term and high-resolution modeling of flood occurrence, interdecadal patterns of river-floodplain dynamics, and analysis of flooding during two typhoon events—Nari and Morakot over Taiwan. The modeling system combines a hydrological model (HiGW-MAT) and a river hydrodynamics model (CaMa-Flood), simulating hydrologic-hydrodynamic processes at ∼ 5 km resolution with flood occurrences downscaled to ∼ 90 m. New hydrological insights for the region: As the first investigation to conduct spatially comprehensive and temporally continuous modeling in Taiwan, this study presents important advances on the application of large-scale hydrological-hydrodynamic models in settings like that of Taiwan with important implications on flood prediction under climate change. The assessment of interdecadal changes in streamflow indicates no consistent trends over the past four decades; however, the variabilities in monthly-scale streamflow are significant and regionally diverse across Taiwan. Decadal changes in flood occurrence are also minimal at the island-scale, but the changes vary substantially across different regions and exhibit an increased variability over time. Furthermore, the simulated flood patterns in response to Typhoons Nari and Morakot suggest that the modeling framework can be used to reproduce the spatial dynamics and temporal progression of flooding under extreme events in relatively small regions like Taiwan.

Abstract Heterozygous deletions in the ANKS1B gene cause ANKS1B neurodevelopmental syndrome (ANDS), a rare genetic disease characterized by autism spectrum disorder (ASD), attention deficit/hyperactivity disorder, and speech and motor deficits. The ANKS1B gene encodes for AIDA-1, a protein that is enriched at neuronal synapses and regulates synaptic plasticity. Here we report an unexpected role for oligodendroglial deficits in ANDS pathophysiology. We show that Anks1b-deficient mouse models display deficits in oligodendrocyte maturation, myelination, and Rac1 function, and recapitulate white matter abnormalities observed in ANDS patients. Selective loss of Anks1b from the oligodendrocyte lineage, but not from neuronal populations, leads to deficits in social preference and sensory reactivity previously observed in a brain-wide Anks1b haploinsufficiency model. Furthermore, we find that clemastine, an antihistamine shown to increase oligodendrocyte precursor cell maturation and central nervous system myelination, rescues deficits in social preference in 7-month-old Anks1b-deficient mice. Our work shows that deficits in social behaviors present in ANDS may originate from abnormal Rac1 activity within oligodendrocytes.

Summary: Purpose: Heart failure (HF) is a highly recurrent disease with a high sudden death rate and a substantial influence on disease-related quality of life (QOL). Social support, symptom distress, care needs, and meaning in life all have significant impacts on QOL. We hypothesized that meaning in life plays a mediating role in the relationship of social support, symptom distress, and care needs with QOL among patients with chronic HF. Methods: Based on cross-sectional analysis, we recruited 186 HF outpatients who completed structured questionnaires for social support, symptom distress, care needs, meaning in life, and QOL. Structural equation modeling was used to analyze the mediating role of meaning in life in the relationship of social support, symptom distress, and care needs with QOL. Results: The final model showed good model fit. Meaning in life was associated with global QOL (β = 0.18, p = .032). Although symptom distress (β = −0.26, p = .005) and care needs (β = −0.36, p = .021) were negatively associated with global QOL, meaning in life played a partial mediating role between symptom distress and global QOL (β = −0.02, p = .023) and between care needs and global QOL (β = −0.07, p = .030). However, meaning in life played a complete mediating role between social support and global QOL (β = 0.08, p = .047). The model showed that meaning in life, symptom distress, and care needs explained 50% of global QOL. Conclusions: In patients with chronic HF, meaning in life played a mediating role in the relationship of social support, symptom distress, and care needs with QOL. Implementing an intervention to enrich meaning in life may help patients manage the issues caused by symptoms and alleviate their unmet needs.

Abstract The interannual variation of evapotranspiration in tropical rainforests is thought to be small, despite the variability of precipitation. Here we investigated the cause of this phenomenon in the Maritime Continent using observations, reanalysis data and model simulations. We find that evapotranspiration’s interannual variation is dampened by the self-compensating mechanism of canopy evaporation and transpiration. During El Niño, when precipitation is lower than climatology, canopy evaporation decreases due to less interception, while canopy transpiration increases in response to increased incoming solar radiation, resulting in a compensating effect and a small interannual variation of evapotranspiration. Deforestation, however, eliminates transpiration’s dampening effect and, thus, amplifies the interannual variation of evapotranspiration significantly. This increase in evapotranspiration’s interannual variation due to deforestation further affect the local hydrological cycle, resulting in decreased interannual variation of precipitation. The results highlight the impacts of deforestation and emphasize the critical role of tropical rainforests in the hydroclimatological cycle.

Abstract Background Coronary heart disease (CHD) is a cardiovascular disease with high mortality. At present, percutaneous coronary intervention (PCI) is considered as the main effective treatment for CHD due to less trauma, shorter course of treatment, and better curative effect. However, PCI alone is not a permanent cure, so cardiac rehabilitation (CR) is needed for a supplement. Nowadays, the evaluation of the nursing-sensitive quality of CR after PCI focuses on the outcomes of patients, lacks a complete evaluation indicator system, and is prone to problems such as nursing management imbalance. Objective A scientific, sensitive, comprehensive and practical nursing-sensitive quality indicator system based on the structure-process-outcome model was constructed to provide a reference for evaluating nursing-sensitive quality of CR after PCI. Methods Firstly, through literature analysis and semi-structured interview, the indicator system was collected, screened and determined. Then, the framework of the indicator system was established, and the draft of nursing-sensitive quality indicator system of CR after PCI was formed. Subsequently, the nursing-sensitive quality indicator system of CR after PCI was initially established using Delphi method. Finally, the specific weight was determined by analytic hierarchy process (AHP), and the nursing-sensitive quality indicator system of CR after PCI was established and perfected. Results Two rounds of expert consultations were separately given 15 questionnaires, and all these questionnaires were returned, with a questionnaire response rate of 100%. Such result indicated that experts were highly motivated. Besides, the authoritative coefficients for two rounds of expert consultations were 0.865 and 0.888, and the coordination coefficients were 0.491 and 0.522, respectively. Hence, the experts’ authority and coordination were high and the results were reliable. After the second round of expert consultation, the nursing-sensitive quality indicator system of CR after PCI was established, eventually. This system consisted of 3 first-level indicators (structural indicator, process indicator and outcome indicator), 11 s-level indicators and 29 third-level indicators. Conclusion A relatively complete and reliable nursing-sensitive quality indicator system of CR after PCI has been established in this study. Such system is scientific and reliable and can provide a reference for the evaluation of clinical teaching quality of CR after PCI.

Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

s u m m a r y: Purpose: The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. Methods: This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. Results: Seven themes were identified: “being reborn at the end of the road but having difficulty recovering”, “living with a disease with an ineffable feeling”, “feeling like being drained: physical weakness and a dysfunctional body”, “struggling with impaired physical mobility and facing unexpected events”, “suffering from mental exhaustion”, “receiving care from loved ones”, and “turning over a new leaf”. Conclusions: Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible.

Background: Heart failure (HF) remains a leading cause of morbidity and mortality globally, necessitating the identification of reliable prognostic biomarkers to guide therapeutic interventions. Recent clinical observations have underscored phenylalanine (PHE) as a prognostic marker in HF, although the mechanisms involving inter-organ crosstalk remain understood. Methods: This study adopted a dull approach, with a retrospective analysis of 550 HF patients to establish the prognostic value of pre-discharge PHE levels and a study on the inter-organ crosstalk of PHE among 24 patients. We analyzed the correlations between PHE concentrations and clinical outcomes, alongside a comprehensive examination of PHE metabolism across the skeletal muscle, liver, heart, kidney, and lung. Results: In the clinical prognostic analysis of 550 patients hospitalized for acute decompensated HF, elevated PHE levels (≥65.6 μM) were significantly and independently associated with increased all-cause mortality during a median follow-up of 4.5 years (log rank = 36.7, p < 0.001), underscoring its value as a prognostic marker in HF. The inter-organic crosstalk study elucidated the mechanism associated with PHE elevation in patients with HF, characterized by an increase in PHE output in skeletal muscle and a decrease in hepatic and cardiac PHE uptakes. Notably, PHE concentration gradients across these organs were correlated with HF severity, such as the NYHA functional class, B-type natriuretic peptide levels, and the presence of acute HF. Conclusions: Our findings confirm the prognostic significance of PHE in patients with HF and unveil the complex metabolic interplay among key organs that contribute to PHE dysregulation. These insights not only reinforce the importance of metabolic monitoring in HF management but also open avenues for therapeutic targets.