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Physiological stress represents a drastic change of internal state and can drive avoidance behavior, but the neural circuits are incompletely defined. Here, we characterize a sensory-interneuron circuit for mitochondrial stress-induced avoidance behavior in C. elegans. The olfactory sensory neurons and the AIY interneuron are essential, with the olfactory neurons acting upstream of AIY. Unlike pathogen avoidance, stress-induced avoidance does not require AIB, AIZ or RIA interneurons. Ablation or inhibition of the head motor neurons SMDD/V alters the worm's locomotion and reduces avoidance. These findings substantiate our understanding of the circuit mechanisms that underlie learned avoidance behavior triggered by mitochondrial stress.

In this study, risk factors were identified to assess the impact of burnout on the health and daytime function of 412 female flight attendants from an international airline from 2017 to 2018 with convenience sampling. Data were obtained from self-administered questionnaires. Analysis of variance, Pearson's correlation analysis, and independent t-tests were used to assess the relationships between burnout and demographic and work-related factors. A structural equation model analysis was performed to assess the effect of burnout impact factors on mental health using the Brief Symptom Rating Scale, six common physical symptoms, and daytime dysfunction (a subscale of the Athens Insomnia Scale). The results showed a moderate level of burnout, as reported by 19.2 percent of the participants. Personal and work-related characteristics, including marital status and working hours, were not significantly associated with burnout. Smoking behavior was the only significant risk factor (

為維護孕產兒安全，國立成功大學醫學院附設醫院根據衛生福利部公告的111-112年度醫療品質及病人安全工作目標之執行策略、一般原則、參考做法，制訂「醫療品質及病人安全工作目標與策略工作計畫表」， 對於生產六大高風險「妊娠高血壓／子癇前症、植入性胎盤／前置胎盤、胎盤早期剝離、羊水栓塞／靜脈栓塞、胎兒窘迫、產後大出血」均訂有適當處置流程，醫護團隊具備有評估辨識高風險狀況的能力，能即時判別生產時機及採取適當處置，且能啟動跨團隊之緊急應變措施。我們在每項執行計畫中亦詳列出作法及頻率，並訂有相對應之管考指標／預期效益及目標，以期能真正落實並維護孕產兒安全。 To promote safe maternal and newborn care, National Cheng Kung University Hospital has formulated "Healthcare Quality and Patient Safety Work Goals and Strategic Work Plans" in accordance with general principles and reference practices recommended by the Ministry of Health and Welfare. Appropriate procedures have been developed for major obstetric complications, including gestational hypertension/preeclampsia, abnormally invasive placenta/placenta previa, placental abruption, amniotic fluid embolism/venous thrombosis, fetal distress, and postpartum hemorrhage. With such plans, the medical team can efficiently identify high-risk conditions and delivery timing and implement appropriate measures accordingly. Team resource management for pregnancy-related emergency complications is crucial. Herein report our promoting experience; we included effective strategies and set corresponding management indicators or goals to ensure maternal and newborn safety. &nbsp

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Previous studies indicated that the expression of the KDM1 genes (KDM1s), members of the amine oxidase superfamily, has prognostic value for breast and prostate cancer and malignant neuroblastoma. This study aimed to investigate the expression of KDM1s, their prognostic value, and their correlation with immune infiltration in patients with HCC.Multiomics analyses were utilized to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of KDM1s in patients with HCC.The high expression of KDM1A indicated poor overall survival (OS) and disease-free survival, whereas the high expression of KDM1B was significantly associated with poor OS. The genetic alterations and biological interaction network of KDM1s may provide detailed information for the dysregulated function of KDM1s in patients with HCC. KDM1-related signaling pathways and miRNA targets were explored and may provide value as therapeutic targets or tumor progression markers. The increased mRNA expression of KDM1s was significantly correlated with the infiltration of diverse immune cells in HCC.This data-driven study indicates that KDM1s are promising prognostic biomarkers for survival and have the potential to become novel molecular targets in HCC treatments.

To sustain normal growth and allow rapid responses to environmental cues, plants alter the plasma membrane protein composition under different conditions presumably by regulation of delivery, stability, and internalization. Exocytosis is a conserved cellular process that delivers proteins and lipids to the plasma membrane or extracellular space in eukaryotes. The octameric exocyst complex contributes to exocytosis by tethering secretory vesicles to the correct site for membrane fusion; however, whether the exocyst complex acts universally for all secretory vesicle cargo or just for specialized subsets used during polarized growth and trafficking is currently unknown. In addition to its role in exocytosis, the exocyst complex is also known to participate in membrane recycling and autophagy. Using a previously identified small molecule inhibitor of the plant exocyst complex subunit EXO70A1, Endosidin2 (ES2), combined with a plasma membrane enrichment method and quantitative proteomic analysis, we examined the composition of plasma membrane proteins in the root of Arabidopsis seedlings, after inhibition of the ES2-targetted exocyst complex, and verified our findings by live imaging of GFP-tagged plasma membrane proteins in root epidermal cells. The abundance of 145 plasma membrane proteins was significantly reduced following short-term ES2 treatments and these likely represent candidate cargo proteins of exocyst-mediated trafficking. Gene Ontology analysis showed that these proteins play diverse functions in cell growth, cell wall biosynthesis, hormone signaling, stress response, membrane transport, and nutrient uptake. Additionally, we quantified the effect of ES2 on the spatial distribution of EXO70A1 with live-cell imaging. Our results indicate that the plant exocyst complex mediates constitutive dynamic transport of subsets of plasma membrane proteins during normal root growth.

Supplementary Figure S4 shows the activity of non-lead compounds in secondary biological assays.

Supplementary Figure S1 shows the primary screen, protocol, layout and performance.

Supplementary Figure S7 shows the effect of Milciclib and NCGC00117362 on mTOR, and PP-121 and NCGC00117362 on retinoblastoma.

Supplementary Table S1 shows the gene and pathway analysis of genes regulated by NCGC00117362 in Kuramochi ovarian cancer cells.

The tumor microenvironment (TME) is a key determinant of metastatic efficiency. We performed a quantitative high-throughput screen (qHTS) of diverse medicinal chemistry tractable scaffolds (44,420 compounds) and pharmacologically active small molecules (386 compounds) using a layered organotypic, robust assay representing the ovarian cancer metastatic TME. This 3D model contains primary human mesothelial cells, fibroblasts, and extracellular matrix, to which fluorescently labeled ovarian cancer cells are added. Initially, 100 compounds inhibiting ovarian cancer adhesion/invasion to the 3D model in a dose-dependent manner were identified. Of those, eight compounds were confirmed active in five high-grade serous ovarian cancer cell lines and were further validated in secondary in vitro and in vivo biological assays. Two tyrosine kinase inhibitors, PP-121 and milciclib, and a previously unreported compound, NCGC00117362, were selected because they had potency at 1 μmol/L in vitro. Specifically, NCGC00117362 and PP-121 inhibited ovarian cancer adhesion, invasion, and proliferation, whereas milciclib inhibited ovarian cancer invasion and proliferation. Using in situ kinase profiling and immunoblotting, we found that milciclib targeted Cdk2 and Cdk6, and PP-121 targeted mTOR. In vivo, all three compounds prevented ovarian cancer adhesion/invasion and metastasis, prolonged survival, and reduced omental tumor growth in an intervention study. To evaluate the clinical potential of NCGC00117362, structure–activity relationship studies were performed. Four close analogues of NCGC00117362 efficiently inhibited cancer aggressiveness in vitro and metastasis in vivo. Collectively, these data show that a complex 3D culture of the TME is effective in qHTS. The three compounds identified have promise as therapeutics for prevention and treatment of ovarian cancer metastasis.

Supplementary Methods describes the Proteomics and Gene Expression Analysis Methods and References.

Supplementary Figure S9 shows the testing of SAR analogs of NCGC00117362 in secondary confirmatory assays.

Supplementary Figure S2 shows the activity outcomes from confirmatory and counter screens.

Supplementary Figure S8 shows the validation of gene regulation by NCGC00117362 in ovarian cancer cell lines and effect of PP-121 and Milciclib on these genes.

Supplementary Figure S5 shows the activity of inert compounds and mTOR inhibitors in secondary biological in vivo adhesion/invasion assay.

Supplementary Figure S6 shows the effect of Milciclib on cyclin E low- and high-expressing ovarian cancer cell lines.

Supplementary Figure S3 shows the activity of non-lead compounds in secondary confirmatory assays.

BackgroundHyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population.MethodsA total of 120,267 adults aged 30–70 years were enrolled from the Taiwan Biobank data-base in this retrospective case–control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored.ResultsThe frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09–1.28) and 1.12 (1.06–1.18) for TT and GT genotypes, respectively, compared with the GG genotype (pConclusionsABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p p = 0.073), especially among patients whose with an inactive disease activity was p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Bronchopulmonary dysplasia (BPD) has been a critical morbidity in preterm infants. To improve our definition and prediction of BPD is challenging yet indispensable. We aimed to apply machine learning (ML) to investigate effective models by using the recently-proposed and data-driven definition to predict late respiratory support modalities at 36 weeks’ post menstrual age (PMA). We collected data on very-low-birth-weight infants born between 2016 and 2019 from the Taiwan Neonatal Network database. Twenty-four attributes associated with their early life and seven ML algorithms were used in our analysis. The target outcomes were overall mortality, death before 36 weeks’ PMA, and severity of BPD under the new definition, which served as a proxy for respiratory support modalities. Of the 4103 infants initially considered, 3200 were deemed eligible. The logistic regression algorithm yielded the highest area under the receiver operating characteristic curve (AUROC). After attribute selection, the AUROC of the simplified models remain favorable (e.g., 0.801 when predicting no BPD, 0.850 when predicting grade 3 BPD or death before 36 weeks’ PMA, and 0.881 when predicting overall mortality). By using ML, we developed models to predict late respiratory support. Estimators were developed for clinical application after being simplified through attribute selection.

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs;100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs [bEVs];200 nm, microvesicles) are less well explored. Here, we identify bEVs and sEVs as distinct EV populations, and determine that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence resonance energy transfer (BRET)-based EV reporter, reveals dose-dependent EV biodistribution at non-lethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, et individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass spectrometry (MS)-identified tumor progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include SLC29A1, CD9 and CD44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications. This article is protected by copyright. All rights reserved.

Most advanced non-small-cell lung cancer (NSCLC) patients received targeted therapies of epidermal growth factor receptor tyrosine kinase inhibitors. However, few studies reported the relationships between adverse events (AEs) and psychological distress.The aims of this study were to (1) examine the differences in the incidence of AEs, fear of progression (FoP), anxiety, and depression among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors (first, gefitinib and erlotinib; second, afatinib; third, osimertinib) and (2) examine the difference in levels of FoP, anxiety, and depression between the presence and absence of AEs in NSCLC patients.This study used a cross-sectional study design. Patients with NSCLC (N = 120) were recruited from a medical center in northern Taiwan. Adverse events, FoP, anxiety, and depression were assessed by questionnaires.The incidence rates of photosensitivity, mouth and throat sores, and diarrhea were significantly high in the gefitinib, erlotinib, and afatinib groups, respectively. A lesser proportion of patients experienced AEs in the osimertinib group, compared with those in the gefitinib and erlotinib, and afatinib groups. The incidence rates of FoP, anxiety, and depression were 13.8% to 26.0%, 24.1% to 40.4%, and 17.6% to 40.0%, respectively. Patients with photosensitivity, paronychia, and alopecia had significantly higher levels of FoP, anxiety, and depression.This study confirmed the priorities of care among 3 generations of epidermal growth factor receptor tyrosine kinase inhibitors in NSCLC patients, using both the Common Terminology Criteria for Adverse Events (CTCAE 4.03) and PRO-CTCAE 1.0. Photosensitivity, paronychia, and alopecia were associated with higher levels of FoP, anxiety, and depression. Therefore, these AEs require further management.Our study suggests a follow-up to address AEs and psychological distress.

Perovskite CsPbI

BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; 200 nm, microvesicles) are less well explored. Here, we identify bEVs and sEVs as distinct EV populations, and determine that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence resonance energy transfer (BRET)-based EV reporter, reveals dose- dependent EV biodistribution at non-lethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, et individually promotein vivotumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass spectrometry (MS)- identified tumor progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include SLC29A1, CD9 and CD44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinctin vivoproperty and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.

Return to work (RTW) is important for survivors of head and neck cancer (HNC). The purposes of the study were to investigate the RTW ratio among HNC survivors and identify factors significantly affecting RTW in this population.A cross-sectional study with consecutive sampling was conducted in a medical center in Taiwan, with 111 patients with HNC who had completed major treatments within 5 years and were employed before their cancer diagnosis enrolled as participants. Cervical range of motion (CROM) functionality, handgrip and hip flexor strength, maximal mouth opening (MMO), selected symptoms, depression, and disease/treatment-related factors were assessed. All of the factors were analyzed using t-test, chi-square test, and multiple logistic regression.Less than half (44.1%, n = 49) of the participants had returned to work. The t-test/chi-square test results showed the RTW group to be younger in age and better educated; have better handgrip/hip flexor strength, MMO, and CROM; have less speech difficulty and pain; and have less-advanced cancer than the non-RTW group. Further analysis of the above significant variables by logistic regression revealed early cancer stage, dominant handgrip strength, and less speech difficulty were the robust factors related to RTW.The RTW ratio is low in HNC survivors. RTW in HNC survivors is a multifactorial and complicated issue and needs to be further examined.Assessing the factors related to RTW systematically and developing comprehensive interventions and rehabilitation programs to reduce related dysfunctions are necessary to enhance RTW ability in HNC survivors.

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancy globally with a pessimistic prognosis. Previous studies have demonstrated that abnormal expression of genes in the lysine-specific histone demethylase 3 (KDM3) family with epigenetic changes and dysregulation of enzymes promotes cancer progression. In this study, multiomics analyses were utilized to analyze differential expression, prognostic value, genetic alteration, protein-protein interaction, associated biological pathways and immune cell infiltration of KDM3s in patients with HCC. KDM3A-C were significantly upregulated to different extents based on pathologic and tumor grades in patients with HCC compared to normal tissue. Of note, higher KDM3A expression was associated with poor survival in HCC patients, whereas KDM3B and KDM3C were not associated with survival. Furthermore, KDM3A-B genetic alterations had significant effects on survival in patients with HCC. Analyses of the KEGG pathway and miRNAs targets of KDM3A and KDM3B in HCC may provide potential value in tumor behaviors and treatment. The differential expression of the KDM3 family has a strongly significant correlation with the infiltration of the abundance of immune cells, including B cells, CD8

This study uses near-field electrospinning (NFES) technology to make a novel self-powered strain sensor and applies it to the real-time monitoring of a bending structure, so that the measurement equipment can be reduced in volume. A self-powered strain sensor consists of polyvinylidene difluoride (PVDF) fibers, a PDMS fixed substrate, and an aluminum electrode. PVDF fibers are spun with DMSO and acetone using NFES technology, with a diameter of about 8 μm, Young’s modulus of 1.1 GPa, and piezoelectric effect of up to 230 mV. The fixed substrate is a film made of PDMS by thermal curing, then adhered to the PDMS film surface of the sheet Al metal as an Al electrode, and then combined with PVDF fiber film, to become a self-powered strain sensor. As a result, the XRD β value of the self-powered strain sensor reaches 2112 and the sensitivity is increased by 20% over a traditional strain sensor. The cumulative angle algorithm can be applied to measure the angular change of the object over a unit of time or the cumulative displacement of the object over the entire period of motion. The experimental results demonstrate that the self-powered strain sensor combined with the angle accumulation algorithm may be applied to monitor the bending structure, thereby achieving continuous measurements of bending structure changes, and improving on traditional piezoelectric sensors, which can only be sensed once. In the future, self-powered strain sensors will have the ability to continuously measure in real-time, enabling the use of piezoelectric sensors for long-term monitoring of structural techniques.

Objectives To determine the bidirectional relationship between macrophage activation syndrome (MAS) and SLE. Methods Using the 1997–2013 Taiwan National Health Insurance Research Database, we identified patients with newly diagnosed SLE from 2001 to 2013 and selected individuals without SLE from a 1 million representative population. Propensity score (PS) matching was performed to balance incident SLE patients and individuals without SLE according to age, sex, comorbidities and medical utilization. The association between a history of MAS and SLE was studied using conditional logistic regression analysis shown as an adjusted odds ratio (aOR). The risk of MAS associated with SLE was analysed using Cox proportional regression analysis, shown as an adjusted hazard ratio (aHR), and we conducted a sensitivity analysis using various definitions of MAS. Results We included 10 481 SLE patients and 20 962 PS-matched (1:2) non-SLE individuals. The correlation between a history of MAS and SLE did not reach statistical significance after adjustment for potential confounders [aOR 1.18 (95% CI, 0.80, 1.75)] in the age-/sex-matched populations. In the 1:2 PS-matched populations, the risk of MAS markedly increased in patients with SLE [aHR 7.18 (95% CI 4.97, 10.36)]. Other risk factors for MAS included female gender, age ≥65 years, low income, a history of inflammatory bowel disease and a history of MAS. Conclusion This nationwide, population-based study revealed that a history of MAS was not significantly associated with SLE risk. However, the risk of MAS was markedly associated with SLE and a history of MAS.

The purposes of the study were (1) to assess the physical activity (PA) status, muscle strength (MS), and flexibility of survivors of head and neck cancer (HNC) and compare these findings with normative data from national labor fitness measures; (2) to examine the differences among PA subgroups, as categorized using Godin’s scores; and (3) to examine the association between stretching exercises and cervical range of motion (CROM). A cross-sectional study with consecutive sampling was used to recruit HNC survivors from a medical center in Northern Taiwan who had completed either radiation therapy (RT) or multimodality treatments including RT within the current 5 years. The level of PA, daily function, fatigue, quality of life (QOL), MS (handgrip and hip flexor), BMI, and flexibility (CROM and fingertip-to-floor tests) of the participants were assessed. A total of 108 participants completed the assessments from 135 eligible patients (80% response rate). Although 60.2% reported engaging in PA, only 16.7% met WHO guidelines. Compared to subjects in the normative data, the survivors of HNC in this study had poorer handgrip strength, BMI, and CROM, but better forward flexion. The participants who were consistent with WHO PA guidelines reported less fatigue, better right hip flexor MS, and better QOL than those who did not engage in any PA. Lack of sufficient PA and generally poorer fitness were found in study subjects. Longitudinal research to explore changes in fitness and barriers to PA compliance is strongly suggested to better enhance HNC patients’ PA and fitness.

Cytoadherence and consequential migration are crucial for pathogens to establish colonization in the host. In contrast to the nonadherent isolate of Trichomonas vaginalis, the adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (TvFACPα) was identified from the actin-centric interactome, with an atypically greater binding preference to G-actin than F-actin. TvFACPα partially colocalized with F-actin at the parasite pseudopodia protrusion and formed the protein complexes with α-actin through its c-terminal domain. Meanwhile, TvFACPα overexpression suppresses F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACPα enriched in the amoeboid stage of adhered trophozoites was reduced by a CKII inhibitor. The site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACPα actin-binding activity and consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACPα also controls the conversion of adherent trophozoite from amoeboid migration to flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACPα binding actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization of T. vaginalis.

Physiological stress induces aversive memory formation and profoundly impacts animal behavior. In C. elegans, concurrent mitochondrial disruption induces aversion to the bacteria that the animal inherently prefers, offering an experimental paradigm for studying the neural basis of aversive memory. We find that, under mitochondrial stress, octopamine secreted from the RIC modulatory neuron targets the AIY interneuron through the SER-6 receptor to trigger learned bacterial aversion. RIC responds to systemic mitochondrial stress by increasing octopamine synthesis and acts in the formation of aversive memory. AIY integrates sensory information, acts downstream of RIC, and is important for the retrieval of aversive memory. Systemic mitochondrial dysfunction induces RIC responses to bacterial cues that parallel stress induction, suggesting that physiological stress activates latent communication between RIC and the sensory neurons. These findings provide insights into the circuit and neuromodulatory mechanisms underlying stress-induced aversive memory.

Background To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). Methods We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. Results The number of annual outpatient visits increased after ASDAS assessment (5.8 ± 3.4 vs. 5.4 ± 3.4, p

BackgroundTo investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS).MethodsWe identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first.ResultsThe number of annual outpatient visits increased after ASDAS assessment (5.8 ± 3.4 vs. 5.4 ± 3.4, p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (8.7 ± 3.8 vs. 9.2 ± 4.4 min, p = 0.030), especially among patients whose ASDAS-C-reactive protein (CRP) was ConclusionThe use of an EMRMS increased the frequency of ambulatory visits among AS patients with high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.Trial registrationInstitutional Review Board (IRB) of Taichung Veterans General Hospital (TCVGH-IRB No.: CE20145B)

Although colloidal lead halide perovskite quantum dots (PQDs) exhibit desirable emitter characteristics with high quantum yields and narrow bandwidths, instability has limited their applications in devices. In this paper, we describe spray-synthesized CsPbI3 PQD quantum emitters displaying strong photon antibunching and high brightness at room temperature and stable performance under continuous excitation with a high-intensity laser for more than 24 h. Our PQDs provided high single-photon emission rates, exceeding 9 × 106 count/s, after excluding multiexciton emissions and strong photon antibunching, as confirmed by low values of the second-order correlation function g(2)(0) (reaching 0.021 and 0.061 for the best and average PQD performance, respectively). With such high brightness and stability, we applied our PQDs as quantum random number generators, which demonstrably passed all of the National Institute of Standards and Technology's randomness tests. Intriguingly, all of the PQDs exhibited self-healing behavior and restored their PL intensities to greater than half of their initial values after excitation at extremely high intensity. Half of the PQDs even recovered almost all of their initial PL intensity. The robust properties of these spray-synthesized PQDs resulted from high crystallinity and good ligand encapsulation. Our results suggest that spray-synthesized PQDs have great potential for use in future quantum technologies (e.g., quantum communication, quantum cryptography, and quantum computing).

To synthesise and evaluate the effectiveness of virtual reality interventions in preoperative children.Children consider operations as a predictable threat and stressful event. Children's anxiety before an operation increases as the time draws closer. Children could understand the operating room environment and process before the operation using virtual reality, which may reduce their anxiety before an operation.A systematic review and meta-analysis of randomised controlled trials following the Cochrane method were conducted.CINAHL, Cochrane Library, Embase, Joanna Briggs Institute, MEDLINE and PubMed databases were searched for randomised controlled trials published before February 2021. A random-effects model meta-analysis to calculate pooled prevalence and 95% confidence intervals was performed. Conduction of the review adheres to the PRISMA checklist.Of 257 articles screened, six interventions involving 529 participants aged 4-12 years were included in the analysis. All study evidence levels were B2/Level 2, the quality was medium to high on the modified Jadad scale, with a low risk of bias. The results revealed that virtual reality significantly reduced preoperative anxiety in children (SMD: -0.91, 95% CI: -1.43 to -0.39, p = .0006). Furthermore, virtual reality significantly improved children's compliance with anaesthesia (SMD: 3.49, 95% CI: 1.32 to 9.21, p = .01).Children who used virtual reality before an operation felt more familiar with the operating room environment and understood the preoperative preparation procedures. Virtual reality effectively reduced children's anxiety and improved their compliance with anaesthesia.This systematic review and meta-analysis investigated the effect of virtual reality on preoperative anxiety in children and the findings supported its positive effects. The results could provide a reference for incorporating virtual reality into preoperative preparation guidelines.

The influence of nonalcoholic fatty liver disease (NAFLD) on the long-term risk of cirrhosis and hepatocellular carcinoma (HCC) in Asian populations has not been widely investigated.We enrolled 129,374 adults aged 30 years and older, all of whom participated in a health screening program from 2008 through 2013, were seronegative for hepatitis B surface antigen and anti-hepatitis C virus antibodies, and had limited daily alcohol consumption (20 g/d for men and10 g/d for women). Abdominal ultrasonography was performed to determine the presence of NAFLD. The participants were divided into the following groups: NAFLD with increased or normal liver enzyme levels, and non-NAFLD with normal liver enzyme levels. The incidences of cirrhosis and HCC were determined through computerized data linkage with nationwide registries. Cox proportional hazard models were used to estimate the hazard ratios of NAFLD on the risks of cirrhosis and HCC.The incidence rates of cirrhosis and HCC increased as follows: non-NAFLD with normal liver enzyme levels (n = 66,801; 51%), NAFLD with normal liver enzyme levels (n = 41,461; 32%), and NAFLD with increased liver enzyme levels (n = 21,112; 16%). In the NAFLD group with increased liver enzyme levels and the NAFLD group with normal liver enzyme levels, the corresponding multivariate-adjusted hazard ratios for cirrhosis were 3.51 (95% confidence interval [CI]: 2.36-5.22) and 0.73 (95% CI: 0.46-1.16), and for HCC were 1.91 (95% CI: 1.08-3.38) and 0.57 (95% CI: 0.31-1.04), respectively, compared with the non-NAFLD group (P for trend.001). The findings were consistent after restricting the analysis to nonobese individuals (body mass index,25 kg/mIndividuals with NAFLD and increased liver enzyme levels showed significantly higher risks for cirrhosis and HCC and should be monitored.

ObjectivesThe Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort.MethodsFrom November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5).ResultsIn our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively.ConclusionWe propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.

ObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.ConclusionsmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

Gallbladder disease is very common in obese patients. Concomitant cholecystectomy with laparoscopic sleeve gastrectomy (CC-LSG) may be necessary in such cases, and it has been proven safe when indicated. Herein, we presented an experience of our practical four-port-sharing technique for CC-LSG that can substitute the conventional trocar placement. A cohort study was conducted between January 2017 and March 2022 using a prospective database. Out of 238 patients with obesity who underwent bariatric surgery, 45 patients with gallbladder disease received CC-LSG using our four-port-sharing technique. The patients' demographic characteristics, intraoperative outcomes, and postoperative outcomes were examined. Of 45 obese patients with gallbladder disease undergoing CC-LSG, 18 patients with symptomatic cholelithiasis, 25 patients with asymptomatic cholelithiasis, and 2 patients with gallbladder polyps were identified. The mean age of these 45 patients (26 men and 19 women) was 38.3 years, and the mean body mass index was 41.8 kg/m2. There was no case of conversion to laparotomy. The mean operative time of LC and following LSG, the volume of blood loss, and hospital stay were 52.7 minutes and 95.2 minutes, 13.3 mL, and 3.8 days, respectively. No postoperative complications, including hemorrhage, bile leakage, staple leakage, pulmonary embolism, incisional hernia, and wound infection were noted. In CC-LSG, the application of our four-port-sharing technique is safe and feasible for obese patients with gallbladder diseases.

We experimentally study the manipulation of the biphoton wave packets by engineering the loss in the parametric down-conversion. We demonstrate a tailored biphoton wave packet shortened by one order of magnitude as compared to the lossless process.