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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

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.

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.

Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE.From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE.2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08-4.87, p0.0001). Their offspring tended to have lower Apgar scores (7) at both 1 min (10.7% vs. 2.58%, p0.0001) and 5 min (4.25% vs. 1.17%, p0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85-2.71, p0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61-3.45, p0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54-5.06, p0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks.Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. Intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. The combination of Intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of Intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.

Herein, Ni is for the first time put forward as a promising dopant to promote the photoelectrochemical property of cuprous oxide (Cu2O) with particularly n-type conduction. An electrochemical route...

Anisotropic growth of Cu2 O crystals deposited on an indium-doped tin oxide-coated glass substrate through facile electrodeposition and low-temperature calcination results in favorable solar photoelectrochemical water splitting. XRD, TEM, and SEM reveal that appreciable oxygen vacancies are populated in the Cu2 O crystals with a highly branched dendritic thin film morphology, which are further substituted by Cu atoms to form Cu antisite defects exclusively along the [111] direction. The post-thermal treatment presumably accelerates such migration of the lattice imperfections, favoring the exposure of the catalytically active (111) facets. The Cu2 O thin film derived in this way shows n-type conduction with a donor concentration in the order of 1017 cm-3 and a flat-band potential of -1.19 V vs. Ag/AgCl, which is also confirmed by Mott-Schottky analysis. The material is employed as a photoanode and delivers a photocurrent density of 2.2 mA cm-2 at a potential of 0.3 V vs. Ag/AgCl, surpassing reported values more than twofold. Such superiority mostly originates from the synergism of the selective facet exposure within the Cu2 O crystals, which have decent crystallinity, as shown by Raman and photoluminescence spectroscopy, and a favorable bandgap of 2.1 eV, as confirmed by UV/Vis spectroscopy. The n-type Cu2 O thin film reported herein holds excellent promise for solar-related applications.

Key Points Question Is statin use during pregnancy associated with adverse perinatal outcomes? Findings In this cohort study of 1 443 657 pregnancies, in which 469 women were dispensed prescription statins during pregnancy, maternal statin exposure during pregnancy was not associated with increased risk of congenital anomalies among offspring but was associated with low birth weight (, Importance Statins are the drug class most commonly used to treat hyperlipidemia. Recently, they have been used during pregnancy for the prevention or treatment of preeclampsia. However, the safety of statin use during pregnancy has been questioned, and the sample sizes of most previous studies have been small. Objective To examine the perinatal outcomes among offspring associated with maternal use of statins during pregnancy. Design, Setting, and Participants This retrospective cohort study included 1 443 657 pregnant women 18 years of age or older with their first infant born during the period from January 1, 2004, to December 31, 2014. Data for this study were taken from the Taiwan National Health Insurance Research Database. Statistical analysis was performed from April 7, 2020, to July 31, 2021. Exposures Maternal statin use during pregnancy. Main Outcomes and Measures Women who have received a diagnosis of hyperlipidemia before pregnancy and who were receiving prescription statins during pregnancy were the statin-exposed group. Data on congenital anomalies, birth weight, gestational age, preterm birth, low birth weight, very low birth weight, fetal distress, and Apgar score were compared between participants with and partcipants without statin exposure during pregnancy. Risk ratios (RRs) were calculated by multivariable analyses using Poisson regression models to adjust for potential confounders. Subgroup analysis was performed to compare offspring of women who used statins for more than 3 months prior to pregnancy and maintained or stopped statin use after pregnancy. Results A total of 469 women (mean [SD] age, 32.6 [5.4] years; mean [SD] gestational age, 38.4 [1.6] weeks) who used statins during pregnancy and 4690 age-matched controls (mean [SD] age, 32.0 [4.9] years; mean [SD] gestational age, 37.3 [2.4] weeks) with no statin exposure during pregnancy were enrolled. After controlling for maternal comorbidities and age, low birth weight was more common among offspring in the statin-exposed group (RR, 1.51 [95% CI, 1.05-2.16]), with a greater chance of preterm birth (RR, 1.99 [95% CI, 1.46-2.71]), and a lower 1-minute Apgar score (RR, 1.83 [95% CI, 1.04-3.20]). Congenital anomalies were not associated with statin exposure during pregnancy. In addition, multivariable analysis showed that there was no association between statin use for periconceptual hyperlipidemia and adverse perinatal outcomes among women who had used statins prior to pregnancy. Conclusions and Relevance This study suggests that statins may be safe when used during pregnancy because there was no association with congenital anomalies, but caution is needed because of an increased risk of low birth weight and preterm labor. The data also suggest that statins could be safely used during pregnancy for women with long-term use of statins before pregnancy., This cohort study uses data from the Taiwan National Health Insurance Research Database to examine perinatal outcomes among offspring associated with maternal use of statins during pregnancy.

Background: ABCG2 rs2231142 is an important genetic factor that contributes to the development of gout and hyperuricemia (HUA). Epidemiologic studies have demonstrated that lifestyle risk factors of HUA (e.g., alcohol consumption) and genetic predisposition (e.g., ABCG2 gene) together, contribute to enhanced serum uric acid levels. However, the interaction between ABCG2 rs2231142, alcohol consumption, and HUA in the Taiwanese population is still unclear. Therefore, this study investigated whether the risk of HUA is associated with ABCG2 rs2231142 variants and how this is affected by alcohol consumption. Method: study subjects were selected from the participants of the Taiwan Biobank database. Overall, 114,540 participants aged 30 to 70 years were enrolled in this study. The interaction between ABCG2 rs2231142, alcohol consumption, and serum uric acid (sUA) levels was analyzed by multiple logistic regression models. Results: the prevalence of HUA was 32.7% and 4.4 % in the male and female populations, respectively. In the whole study population, the minor T allele of ABCG2 rs2231142 was significantly associated with HUA risk, and the occurrence of HUA was high in TT genotype and TG genotype. The risk of HUA was significantly increased by the combined association of ABCG2 rs2231142 and alcohol consumption for TG/TT genotype compared to the GG genotype (wild-type genotype), especially among women. Conclusion: the ABCG2 rs2231142 is a crucial genetic locus for sUA levels in the Taiwanese population and our findings revealed that alcohol consumption combined with the ABCG2 rs2231142 risk allele contributes to increased HUA risk.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Physiological stress triggers aversive learning that profoundly alters animal behavior. Systemic mitochondrial disruption induces avoidance of C. elegans to non-pathogenic food bacteria. Mutations in cat-2 and dat-1, which control dopamine synthesis and reuptake, respectively, impair this learned bacterial avoidance, suggesting that dopaminergic modulation is essential. Cell-specific rescue experiments indicate that dopamine likely acts from the CEP and ADE neurons to regulate learned bacterial avoidance. We find that mutations in multiple dopamine receptor genes, including dop-1, dop-2 and dop-3, reduced learned bacterial avoidance. Our work reveals a role for dopamine signaling in C. elegans learned avoidance behavior induced by mitochondrial stress.

Simple Summary β-escin, a component of horse chestnut seed extract, was first identified as an inhibitor of ovarian cancer (OvCa) adhesion/invasion in our high-throughput screening program using a three-dimensional organotypic model assembled from primary human cells and extracellular matrix. The goal of the study presented here is to determine if β-escin and structurally-similar compounds have a therapeutic potential against OvCa metastasis. β-escin and cardiac glycosides inhibit ovarian cancer adhesion/invasion to the omental microenvironment in vivo, and β-escin inhibits ovarian cancer metastasis in the prevention and intervention setting. Additionally, β-escin was found to decrease the stemness of ovarian cancer cells, inhibit extracellular matrix production in the tumor microenvironment, and inhibit HIF1α stability in ovarian cancer cells and the tumor microenvironment. This study reveals that the natural compound β-escin has therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment. Abstract The high mortality of OvCa is caused by the wide dissemination of cancer within the abdominal cavity. OvCa cells metastasize to the peritoneum, which is covered by mesothelial cells, and invade into the underlying stroma, composed of extracellular matrices (ECM) and stromal cells. In a study using a three-dimensional quantitative high-throughput screening platform (3D-qHTS), we found that β-escin, a component of horse chestnut seed extract, inhibited OvCa adhesion/invasion. Here, we determine whether β-escin and structurally similar compounds have a therapeutic potential against OvCa metastasis. Different sources of β-escin and horse chestnut seed extract inhibited OvCa cell adhesion/invasion, both in vitro and in vivo. From a collection of 160 structurally similar compounds to β-escin, we found that cardiac glycosides inhibited OvCa cell adhesion/invasion and proliferation in vitro, and inhibited adhesion/invasion and metastasis in vivo. Mechanistically, β-escin and the cardiac glycosides inhibited ECM production in mesothelial cells and fibroblasts. The oral administration of β-escin inhibited metastasis in both OvCa prevention and intervention mouse models. Specifically, β-escin inhibited ECM production in the omental tumors. Additionally, the production of HIF1α-targeted proteins, lactate dehydrogenase A, and hexokinase 2 in omental tumors was blocked by β-escin. This study reveals that the natural compound β-escin has a therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment.

Objectives: To investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA). Methods: We conducted a nationwide, population-based, case-control study using Taiwan’s National Health Insurance Research Database for 2003–2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses. Results: Using multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd’s ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02–0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64–0.81), cyclosporin (OR, 1.43; 95% CI, 1.07–1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27–1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities. Conclusions: This population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.

Multipartite entanglement is indispensable in the implementation of quantum technologies and the fundamental test of quantum mechanics. Here we study how the W state and W-like state may be generated in a quantum-dot array by controlling the coupling between an incident photon and the quantum dots on a waveguide. We also discuss how the coupling may be controlled to observe the sudden death of entanglement. Our work can find potential applications in quantum information processing.

BACKGROUND/PURPOSE The in-hospital length of stay (LOS) among very-low-birth-weight (VLBW, BW

Objective: To examine the difference in levels of fear of cancer progression (FoP), anxiety, depression between presence/absence of the target-adverse events (AEs); and to examine the differences in incidence rate of AEs and FoP, anxiety, and depression among three generations of EGFR-TKIs therapy (first, gefitinib and erlotinib [G1]; second, afatinib [G2]; third, osimertinib [G3]) in non-small-cell lung cancer (NSCLC) patients.Methods: A cross-sectional study design. NSCLC patients (n=128) were recruited from a medical center in Taiwan. A set of structured questionnaires assessing AEs, FoP, anxiety and depression. Results: Parts of AEs, such as photosensitivity, paronychia, and alopecia, exhibited significantly higher levels of FoP, anxiety, and depression. Less patients experienced AEs in the G3 group than those in the G1 or G2 group but still reported experiencing itching, dry skin with grade 3 severity. The incidence rates of mouth/throat sores, and cheilosis/cheilitis in the G2 group was significantly higher than those in the G1 or G3 group. The incidence rate of FoP, anxiety and depression were 13.8-26.3%, 23.8-40.4% and 16.7-42.1%, respectively.Conclusions: The priorities of care among three generations of EGFR-TKIs in patients with NSCLC were established. FoP, anxiety and depression were present among different targeted therapies and require further attention.

Invasive interventions have been conducted in preterm infants with significant patent ductus arteriosus (PDA) when medical treatment has failed, and methods of invasive intervention have been reported. Surgical ligation via lateral thoracotomy has been a well-established procedure for decades. Recently, transcatheter occlusion has been safely and feasibly applied to the premature population. However, little research has been conducted on the benefits of transcatheter occlusion in very-low-birth-weight (VLBW) infants compared to surgical ligation. This study compared transcatheter and surgical techniques in VLBW infants in terms of short-term respiratory outcomes. The medical records of 401 VLBW infants admitted to a tertiary hospital between September 2014 and January 2019 were retrospectively reviewed. Patients who were diagnosed with a congenital anomaly, a chromosomal anomaly, or congenital heart disease, except for an inter-atrial shunt, were excluded. The perinatal conditions, neonatal morbidities, periprocedural vital signs, and respiratory support trajectories were compared between the transcatheter-treated and surgically ligated group. A total of 31 eligible VLBW infants received invasive intervention: 14 were treated with transcatheter occlusion (Group A), and 17 infants were treated with surgical ligation (Group B). Respiratory outcomes were not statistically significant between the two groups, despite Group A showing a trend toward early improvement in post-intervention respiratory trajectory. In this small case study, a different trend in post-intervention respiratory trajectories was observed. Future research with larger case numbers should be conducted to address our preliminary observations in more detail.