Search

Background: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies., Methods: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023., Results: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention., Conclusions: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes., Competing Interests: Declaration of competing interests All authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Bacteremia is a critical condition with high mortality that requires prompt detection to prevent progression to life-threatening sepsis. Traditional diagnostic approaches, such as blood cultures, are time-consuming. This limitation has encouraged the exploration of rapid prediction methodologies. Cellular Population Data (CPD), which provides detailed insights into white blood cell morphology and functionality, is a promising technique for the early detection of bacteremia., Methods: This study applied machine learning models to analyze laboratory data from hospitalized patients at risk of bacteremia from three hospitals. Using complete blood count (CBC), differential count (DC), and CPD, collected at various time intervals, we trained two sets of artificial intelligence models: one trained using data from patients in the Emergency Department (ED) and another specifically designed for and trained using data from a hospitalized cohort. We evaluated the performance of both models by applying them to the same hospitalized population and comparing their outcomes., Results: The study encompassed analysis of over 66,000 CBC samples. The model tailored for hospitalized patients exhibited superior performance in bacteremia prediction across all cohorts compared with the ED-model, achieving an area under the receiver operating characteristic curve (AUROC) of 0.772 in the validation cohort from China Medical University Hospital and 0.808 and 0.843 in two other hospital cohorts. Notably, nearly half of the top fifteen important features identified by shapely additive explanations values were CPD parameters, underscoring the pivotal role of CPD in predictive models for bacteremia., Conclusions: Artificial intelligence models incorporating CPD data can accurately predict bacteremia in hospitalized patients. Models specifically trained on hospitalized patient data demonstrate enhanced performance over those based on ED data in predicting bacteremia occurrences. Future research must explore the clinical effects of these models, focusing on their potential to assist physicians in managing antibiotic use and patient health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

The pleiotropic and protective effects of melatonin have been demonstrated in a variety of animal models of renal injury. While coding RNAs regulated by melatonin in renal tissues are well identified, the functional involvement of long noncoding RNAs (lncRNAs) in melatonin signaling remains undefined. This study identified nuclear enriched abundant transcript 1 ( NEAT 1), a clock-controlled lncRNA that was upregulated by melatonin through the BMAL1/CLOCK heterodimer in renal tubular epithelial cells (TECs). Mechanistic studies showed that melatonin enhanced NEAT 1 expression via increasing BMAL1 stability and thereby the enrichment of BMAL 1 on NEAT 1's promoter. Further studies have revealed that NEAT 1 promotes the proliferation of TECs by increasing levels of H3K27ac and H3K4me1 at the promoter regions of the proliferation gene MKI 67. Treatment of albumin-injured TECs with melatonin promoted proliferation by transactivating NEAT 1 and restoring the expression levels of core clock genes and MKI 67. Moreover, melatonin treatment ameliorated proteinuria, hypoalbuminemia, and fibrotic lesions, which was correlated with increased levels of core clock genes, H3K27ac, Mki 67, and Neat 1 in experimental MN kidneys. Melatonin mediates a novel regulatory axis, BMAL1- NEAT 1- MKI 67, in TEC proliferation, establishing potential therapeutic targets for MN and other renal diseases., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Objectives: Altered immune and inflammatory responses resulting from alcohol abuse have been implicated in increasing the risk of autoimmune connective tissue disease (ACTD). However, limited research has been conducted on this topic in the Asian population. Therefore, this study was undertaken to investigate and address this knowledge gap., Methods: Using data from Taiwan's National Health Insurance Research Database, we identified all patients with alcohol abuse between 2000 and 2017. We selected a comparison cohort without alcohol abuse, matching them in terms of age, sex, and index date at a 3:1 ratio. We collected information on common underlying comorbidities for analysis. Both cohorts were followed up until the diagnosis of ACTD or the end of 2018., Results: A total of 57,154 patients with alcohol abuse and 171,462 patients without alcohol abuse were included in the study. The age and sex distributions were similar in both cohorts, with men accounting for 89.8% of the total. After adjusting for underlying comorbidities, patients with alcohol abuse had a higher risk of developing ACTD [adjusted hazard ratio (AHR): 1.12, 95% confidence interval (CI): 1.01-1.25]. The stratified analysis revealed that this increased risk was specific to the male population. Additionally, besides alcohol abuse, liver disease, renal disease, coronary artery disease, and chronic obstructive pulmonary disease were identified as independent predictors for ACTD., Conclusion: This study demonstrates that alcohol abuse increases the risk of developing ACTD in the Asian population, particularly among men. Therefore, it is important to implement alcohol cessation, especially in individuals with liver disease, renal disease, coronary artery disease, and chronic obstructive pulmonary disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chang, Wang, Shih, Ho, Hsu, Lin, Chiu and Huang.)

Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the SRCIN1 gene in breast cancer patients. We assessed SRCIN1 -related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the SRCIN1 pathway, we conducted cell viability assays, gene manipulation and RNA sequencing. SRCIN1 hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated SRCIN1 in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%. SRCIN1 hypermethylation was significantly correlated with increased SRCIN1 mRNA expression ( p < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells. SRCIN1 silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions. SRCIN1 hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and SRCIN1 -targeted therapies could be used in combination regimens for breast cancer patients.

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly performed as an adjunct to conventional cardiopulmonary resuscitation (CCPR) for refractory out-of-hospital cardiac arrest (OHCA). However, the specific benefits of ECPR concerning survival with favorable neurological outcomes remain uncertain. This study aimed to investigate the potential advantages of ECPR in the management of refractory OHCA. We conducted a retrospective cohort study involved OHCA patients between January 2016 and May 2021. Patients were categorized into ECPR or CCPR groups. The primary endpoint assessed was survival with favorable neurological outcomes, and the secondary outcome was survival rate. Multivariate logistic regression analyses, with and without 1:2 propensity score matching, were employed to assess ECPR's effect. In total, 1193 patients were included: 85underwent ECPR, and 1108 received CCPR. Compared to the CCPR group, the ECPR group exhibited notably higher survival rate (29.4% vs. 2.4%; p < 0.001). The ECPR group also exhibited a higher proportion of survival with favorable neurological outcome than CCPR group (17.6% vs. 0.7%; p < 0.001). Multivariate logistic regression analysis demonstrated that ECPR correlated with increased odds of survival with favorable neurological outcome (adjusted odds ratio: 13.57; 95% confidence interval (CI) 4.60-40.06). Following propensity score matching, the ECPR group showed significantly elevated odds of survival with favorable neurological outcomes (adjusted odds ratio: 13.31; 95% CI 1.61-109.9). This study demonstrated that in comparison to CCPR, ECPR may provide survival benefit and increase the odds of favorable neurological outcomes in selected OHCA patients., (© 2024. The Author(s).)

Background: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents., Methods: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality., Results: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups., Conclusions: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Myocardial infarction (MI) is a leading cause of death worldwide, resulting in extensive loss of cardiomyocytes and subsequent heart failure. Inducing cardiac differentiation of stem cells is a potential approach for myocardial regeneration therapy to improve post-MI prognosis. Mesenchymal stem cells (MSCs) have several advantages, including immune privilege and multipotent differentiation potential. This study aimed to explore the feasibility of chemically inducing human amniotic membrane MSCs (hAMSCs) to differentiate into cardiomyocytes in vitro. Human amniotic membrane (AM) samples were obtained from routine cesarean sections at Far Eastern Memorial Hospital. The isolated cells exhibited spindle-shaped morphology and expressed surface antigens CD73, CD90, CD105, and CD44, while lacking expression of CD19, CD11b, CD19, CD45, and HLA-DR. The SSEA-1, SSEA-3, and SSEA-4 markers were also positive, and the cells displayed the ability for tri-lineage differentiation into adipocytes, chondrocytes, and osteoblasts. The expression levels of MLC2v, Nkx2.5, and MyoD were analyzed using qPCR after applying various protocols for chemical induction, including BMP4, ActivinA, 5-azacytidine, CHIR99021, and IWP2 on hAMSCs. The group treated with 5 ng/ml BMP4, 10 ng/ml Activin A, 10 μM 5-azacytidine, 7.5 μM CHIR99021, and 5 μM IWP 2 expressed the highest levels of these genes. Furthermore, immunofluorescence staining demonstrated the expression of α-actinin and Troponin T in this group. In conclusion, this study demonstrated that hAMSCs can be chemically induced to differentiate into cardiomyocyte-like cells in vitro. However, to improve the functionality of the differentiated cells, further investigation of inductive protocols and regimens is needed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shinn-Chih Wu reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are extensively branched, collagen-producing cells that closely interact with endothelial cells. This article aims to provide an overview of the recent advancements in understanding the physiological functions of pericytes and their roles in kidney diseases. In a healthy kidney, pericytes have essential physiological function in angiogenesis, erythropoietin (EPO) production, and the regulation of renal blood flow. Nevertheless, pericyte-myofibroblast transition has been identified as the primary cause of disease progression in acute kidney injury (AKI)-to-chronic kidney disease (CKD) continuum. Our recent research has demonstrated that hypoxia-inducible factor-2α (HIF-2α) regulates erythropoietin production in pericytes. However, this production is repressed by EPO gene hypermethylation and HIF-2α downregulation which were induced by transforming growth factor-β1-activated DNA methyltransferase and activin receptor-like kinase-5 signaling pathway during renal fibrosis, respectively. Additionally, AKI induces epigenetic modifications in pericytes, rendering them more prone to extracellular matrix production, cell migration and proliferation, thereby contributing to subsequent capillary rarefaction and renal fibrosis. Further investigation into the specific functions and roles of different subpopulations of pericytes may contribute for the development of targeted therapies aimed at attenuating kidney disease and mitigating their adverse effects., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the effect of administering nirmatrelvir/ritonavir and molnupiravir before hospitalisation on subsequent critical illness among patients with COVID-19 pneumonia., Methods: This retrospective cohort study included patients with COVID-19 pneumonia who required hospitalisation between 1 January 1 2022 and 31 August 2022. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 1,011 COVID-19 patients were analysed. Among them, 304 (30.1%) received molnupiravir and 131 (13.0%) received nirmatrelvir/ritonavir before hospitalisation., Results: There were significant reductions for critical illness (adjusted odds ratio 0.29, 95% confidence interval 0.21-0.39, P < 0.001) and mortality (adjusted odds ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between molnupiravir and nirmatrelvir/ritonavir. The combination of COVID-19 vaccines and oral antivirals can further reduce the risk of critical illness in high-risk populations., Conclusion: Administering molnupiravir and nirmatrelvir/ritonavir before hospitalisation reduced the risk of COVID-19 patients with moderate to severe pneumonia progressing to critical illness and mortality., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objective: Telemedicine can facilitate social distancing during an infectious disease pandemic and reduce the burden on health-care resources. Moreover, telemedicine can be utilized for medical care in remote island regions, in home health care, and during isolated major disasters such as regional earthquakes. However, the effectiveness of telemedicine for emergency consultation remains unclear. This study introduced and analyzed the national emergency medical teleconsultation (NEMTC) established in Taiwan in 2022 during the COVID-19 pandemic., Methods: In response to the COVID-19 pandemic, Taiwan's Centers for Disease Control established a temporary 24-h NEMTC contingency system. Patient information was collected from consultations through the NEMTC from April 28 to June 28, 2022. After successful consultation, physicians made recommendations for home observation, emergency department (ED) visit, or outpatient follow-up. ED visits were divided into two categories, namely self-transport and transport, by the emergency medical service system (EMSS)., Results: During the aforementioned period, 20,902 consultation requests were made through the NEMTC, and 11,804 consultations (56.5% of 20,902) were successful. Consultation success rates were significantly higher for those who had a consultation between 08:00 and 16:00, had a waiting time of less than 10 min, and were not aged between 18 and 45 years. Moreover, 8.2% of the analyzed patients were advised to visit the ED, and only 0.4% required ambulance transportation. Children and older individuals and patients with cardiovascular symptoms, shortness of breath, or neurological or abdominal symptoms had a significantly higher chance of being referred to the ED than did other individuals., Conclusions: The NEMTC response system can enhance the efficiency of the EMSS and can reduce the burden of patients with mild conditions overloading the EMSS and EDs. The NEMTC could serve as an effective rapid response system during future pandemics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Coronavirus disease 2019 (COVID-19) has been found to have a greater impact on individuals with pre-existing psychiatric disorders. However, the underlying reasons for this increased risk have yet to be determined. This study aims to investigate the potential factors contributing poor outcomes among COVID-19 patients with psychiatric disorders, including delayed diagnosis of infection, vaccination rates, immune response, and the use of psychotropic medications., Methods: This retrospective cohort study analyzed medical records of 15,783 adult patients who were diagnosed with COVID-19 infection by positive PCR tests between January and September 2022 at a single medical center. We identified psychiatric diagnoses using ICD-9 diagnostic codes from the preceding 3 years before COVID infection. Primary outcome was in-hospital mortality and secondary outcomes were severe illness requiring intensive care or mechanical ventilation, and hospitalization within 45 days after a positive COVID-19 test. We compared the rates of outcomes, viral load, vaccination status at the time of positive test, psychotropic medications prescription within 90 days prior, antiviral medication use, and blood inflammation markers between patients with and without psychiatric disorders. The Cox proportional hazard model was used to examine the association of psychiatric diagnoses, vaccination status, and psychotropic medication prescription with poor outcomes., Results: Patients with psychiatric disorders demonstrated higher rates of severe illness (10.4% v.s. 7.1%) and hospitalization (16.4% vs. 11.3%), as well as a shorter duration to in-hospital mortality (6 vs. 12.5 days) compared to non-psychiatric patients. Psychiatric patients had higher vaccination rates and lower levels of inflammatory markers than non-psychiatric patients. Antipsychotic medication use was associated with in-hospital mortality (hazard ratio [HR] = 4.79, 95% confidence interval [CI] = 1.23-18.7), while being unvaccinated was associated with hospitalization (HR = 1.81, 95% CI = 1.29 to 2.54) and severe illness (HR = 3.23, 95% CI = 1.95 to 5.34) among patients with psychiatric disorders. Sedatives prescription was associated with all poor outcomes in general patients., Conclusion: Considering the narrow time window between a positive COVID-19 test and poor outcomes, healthcare providers should undertake close monitoring of patients with preexisting psychiatric disorders during the initial days after a positive PCR test. Furthermore, caution should be taken when prescribing psychotropic medications, with special attention to antipsychotics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The poor prognosis of hepatocellular carcinoma (HCC) was ascribed to metastasis. Targeted therapy aiming at the molecules along the metastatic pathway is a promising therapeutic strategy. Among them, hydrogen peroxide inducible clone-5 (Hic-5) is highlighted. Hic-5, discovered as a reactive oxygen species (ROS)-inducible gene, was identified to be an adaptor protein in focal adhesion and a critical signaling mediator upregulated in various cancers including HCC. Moreover, Hic-5 may regulate epithelial-mesenchymal transition (EMT) transcription factor Snail and its downstream mesenchymal genes including fibronectin and matrix metalloproteinase-9 required for migration and invasion of HCC. However, the comprehensive Hic-5-mediated pathway was not established and whether Hic-5 can be a target for preventing HCC progression has not been validated in vivo . Using whole-transcriptome mRNA sequencing, we found reactive oxygen species modulator (ROMO) and ZNF395 were upregulated by Hic-5 in a patient-derived HCC cell line, HCC372. Whereas ROMO was involved in Hic-5-mediated ROS signaling, ZNF395 locates downstream of Snail for mesenchymal genes expression required for cell migration. Also, ZNF395 but not ROMO was upregulated by Hic-5 for migration in another patient-derived HCC cell line, HCC374. Further, by in vivo knock down of Hic-5 using the Stable Nucleic Acids Lipid nanoparticles (SNALP)-carried Hic-5 siRNA, progression of HCC372 and HCC374 in SCID mice was prevented, coupled with the decrease of the downstream mesenchymal genes. Our study provides the preclinical evidence that targeting Hic-5 is potentially able to prevent the progression of HCCs with Hic-5 overexpression., Competing Interests: None., (AJCR Copyright © 2023.)

Many adults with diabetes mellitus are unaware worldwide. The study objectives aimed to evaluate the risk of dialysis within 5 years of diagnosis between patients with newly diagnosed diabetes with and without diabetes-related complications. A retrospective longitudinal nationwide cohort study was conducted. Patients diagnosed with diabetes between 2005 and 2013 were followed up until 2018. They were categorized based on the presence or absence of complications, the number of complications, and the diabetes complications severity index (DCSI) scores. Dialysis outcomes were determined through the Registry of Catastrophic Illness from the National Health Insurance Research Database. Among the analyzed patients, 25.38% had complications at diagnosis. Patients with complications at diagnosis had a significantly higher risk of dialysis within 5 years (adjusted hazard ratio: 9.55, 95% confidence interval CI 9.02-10.11). Increasing DCSI scores and the number of complications were associated with higher dialysis risks. Patients with one complication had a 7.26-times higher risk (95% CI 6.83-7.71), while those with ≥ 3 complications had a 36.12-times higher risk (95% CI 32.28-40.41). In conclusion, newly diagnosed diabetes patients with complications face an increased risk of dialysis within 5 years. The severity and number of complications are directly linked to the risk of dialysis within this timeframe., (© 2023. Springer Nature Limited.)

Introduction: Chronic kidney disease (CKD) is a condition defined as a persistent change in kidney structure or function, or both, that compromises human health. Environmental exposure to heavy metals (e.g. cadmium, lead, arsenic and mercury) is common, and high exposure levels are known to cause nephrotoxicity. Micronutrients such as selenium and zinc are positively associated with better kidney function and renal outcomes. This study determined the associations between CKD and heavy metal exposures measured in blood or urine within a community-dwelling population, and assessed whether and how selenium and zinc modified the associations., Method: Data were extracted from 4 cycles of the US National Health and Nutrition Examination Survey (NHANES) database (2011-2012, 2013-2014, 2015-2016 and 2017-2018)., Results: Univariate analysis showed that higher quartiles of plasma lead and cadmium concentration were more likely associated with CKD than the lowest quartile, and along with folate, were linked to greater odds of CKD. Conversely, as plasma selenium and serum zinc increased, the odds of CKD decreased. Multivariate analysis had similar results after adjusting for relevant confounders. Higher plasma cadmium quartiles were associated with higher odds of CKD. Associations between higher quartiles of plasma selenium and serum zinc were significantly associated with lower odds of CKD., Conclusion: Elevated blood levels of heavy metals increase CKD, whereas elevated concentrations of plasma selenium and serum zinc decrease CKD. A high serum zinc concentration appears to interact with low-toxicity heavy metals to reduce CKD risk. This study suggests that increased selenium and zinc in the body along with avoidance of heavy metal exposures could protect against CKD.

Background: Dual antiplatelet therapy (DAPT) is a standard treatment option for acute myocardial infarction (AMI). The difference between the efficacy of ticagrelor and clopidogrel in the emergency department (ED) before percutaneous coronary intervention (PCI) remains unknown. The present study compared the in-hospital major adverse cardiovascular event (MACE) rates between patients with AMI treated with clopidogrel and those treated with ticagrelor in the ED before PCI., Methods: We retrospectively collected the data of patients diagnosed as having AMI in the ED. Patients were only included if they had successfully received complete DAPT with aspirin and ticagrelor/clopidogrel in the ED and had undergone PCI. The patients were divided into two groups according to their DAPT regimen. The primary outcome was the rate of in-hospital MACEs. The secondary outcomes included an unexpected return to the ED within 72 h, readmission within 14 d, and revascularization., Results: A total of 1836 patients were enrolled. Patients in the ticagrelor group had a lower in-hospital MACE rate (3.01% versus 7.51%, p < 0.001) and in-hospital mortality rate (2.15% versus 5.70%, p < 0.001) than those in the clopidogrel group. Multivariate logistic regression analysis revealed ticagrelor was independently associated with a lower risk of in-hospital MACEs (odds ratio [OR]: 0.53, 95% CI: 0.32-0.88, p = 0.013). After propensity score matching, the risk of in-hospital MACEs remained significantly lower in the ticagrelor group (OR 0.42, 95% CI: 0.21-0.85, p = 0.016)., Conclusion: DAPT with ticagrelor and aspirin in the ED before PCI is associated with a lower in-hospital MACE rate among patients with AMI.

Background: Bacteremia is a life-threatening complication of infectious diseases. Bacteremia can be predicted using machine learning (ML) models, but these models have not utilized cell population data (CPD)., Methods: The derivation cohort from emergency department (ED) of China Medical University Hospital (CMUH) was used to develop the model and was prospectively validated in the same hospital. External validation was performed using cohorts from ED of Wei-Gong Memorial Hospital (WMH) and Tainan Municipal An-Nan Hospital (ANH). Adult patients who underwent complete blood count (CBC), differential count (DC), and blood culture tests were enrolled in the present study. The ML model was developed using CBC, DC, and CPD to predict bacteremia from positive blood cultures obtained within 4 h before or after the acquisition of CBC/DC blood samples., Results: This study included 20,636 patients from CMUH, 664 from WMH, and 1622 patients from ANH. Another 3143 patients were included in the prospective validation cohort of CMUH. The CatBoost model achieved an area under the receiver operating characteristic curve of 0.844 in the derivation cross-validation, 0.812 in the prospective validation, 0.844 in the WMH external validation, and 0.847 in the ANH external validation. The most valuable predictors of bacteremia in the CatBoost model were the mean conductivity of lymphocytes, nucleated red blood cell count, mean conductivity of monocytes, and neutrophil-to-lymphocyte ratio., Conclusions: ML model that incorporated CBC, DC, and CPD showed excellent performance in predicting bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

The molecular mechanisms contributing to the regulation of Th17-mediated inflammation remain underexplored. We here report a SUMO-specific protease (SENP)2-mediated pathway induced in pathogenic Th17 cells that restricts the pathogenesis of inflammatory colitis. SENP2 regulates the maturation of small ubiquitin-like modifiers (SUMO) and recycles SUMO from the substrate proteins. We find higher levels of SENP2 in pathogenic Th17 cells. By deleting Senp2 in T-cell lineages in mice, we demonstrate that the lack of Senp2 exacerbates the severity of experimental colitis, which is linked to elevated levels of GM-CSF + IL-17A + pathogenic Th17 cells and more severe dysbiosis of the intestinal microbiome. Adoptive transfer experiments demonstrate the cell-autonomous effect of Senp2 in restraining Th17 differentiation and colitis. The enzymatic activity of SENP2 is important for deSUMOylation of Smad4, which reduces Smad4 nuclear entry and Rorc expression. Our findings reveal a SENP2-mediated regulatory axis in the pathogenicity of Th17 cells., (© 2023. The Author(s).)

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t -test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD ( p < 0.001) and a decrease in FPCS ( p = 0.012) and TIS ( p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

Objectives: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity., Methods: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade., Results: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay., Conclusions: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis., Methods: This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher's exact test. The Mann-Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases., Results: Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784-0.956); CRP, 0.800 (95% CI, 0.707-0.892); NLR, 0.724 (95% CI, 0.616-0.832); PLR, 0.662 (95% CI, 0.525-0.798); and WBC, 0.679 (95% CI, 0.563-0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively., Conclusions: A large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department., (© 2023. The Author(s).)

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene-deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin-like modifier (SUMO)-specific ubiquitin-like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1-related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene-deleted meiotic cells. The Top2-12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin-binding proteins is regulated by the NPC-bound SUMO-specific protease and is important for the progression of meiosis., (© 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Developing new electron transport layers has been an effective way to fabricate high-performance bulk-heterojunction organic solar cells (OSCs). Resolving the longstanding problems associated with commonly used zinc oxide (ZnO), such as electron traps and light-induced device deterioration, however, is still a great challenge. In this study, glycerol diglycidyl ether (GDE) and 1,4-butanesultone (BS) are blended with polyethyleneimine (PEI) to produce cross-linkable PEI-based materials, PEI-GDE and PEI-GDE-BS, which can function as alternative electron transport layers to replace conventional ZnO cathode-modifying layers in inverted OSCs. PEI-GDE and PEI-GDE-BS are amendable to low-temperature annealing processes to produce cross-linked films. The inverted device structure of ITO/ETL/PM6:BTP-BO-4F:PC 71 BM/MoO 3 /Ag was used to evaluate the effects of incorporating PEI-GDE and PEI-GDE-BS as electron transport materials. Compared with ZnO-based devices, the PEI-GDE- and PEI-GDE-BS-based devices exhibit significant improvements in photovoltaic performances due to smoother surface roughness, higher charge collection and exciton dissociation efficiencies, higher electron mobilities, and stronger π-π interactions. In particular, a PEI-GDE-BS-based device shows an outstanding power conversion efficiency (PCE) of 17.55% with a V OC of 0.83 V, a J SC of 27.88 mA/cm 2 , and an FF of 75.96%, which offers great possibilities in the applications of flexible solar cells.

Introduction: Cardiovascular (CV) events are the major cause of morbidity and mortality associated with blood pressure (BP) in hemodialysis (HD) patients. BP varies significantly during HD treatment, and the dramatic variation in BP is a well-recognized risk factor for increased mortality. The development of an intelligent system capable of predicting BP profiles for real-time monitoring is important. Our aim was to build a web-based system to predict changes in systolic BP (SBP) during HD., Methods: In this study, dialysis equipment connected to the Vital Info Portal gateway collected HD parameters that were linked to demographic data stored in the hospital information system. There were 3 types of patients: training, test, and new. A multiple linear regression model was built using the training group with SBP change as the dependent variable and dialysis parameters as the independent variables. We tested the model's performance on test and new patient groups using coverage rates with different thresholds. The model's performance was visualized using a web-based interactive system., Results: A total of 542,424 BP records were used for model building. The accuracy was greater than 80% in the prediction error range of 15%, and 20 mm Hg of true SBP in the test and new patient groups for the model of SBP changes suggested the good performance of our prediction model. In the analysis of absolute SBP values (5, 10, 15, 20, and 25 mm Hg), the accuracy of the SBP prediction increased as the threshold value increased., Discussion: This databae supported our prediction model in reducing the frequency of intradialytic SBP variability, which may help in clinical decision-making when a new patient receives HD treatment. Further investigations are needed to determine whether the introduction of the intelligent SBP prediction system decreases the incidence of CV events in HD patients., (© 2023 S. Karger AG, Basel.)

Background: The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm., Methods: This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients <18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital., Results: A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively)., Conclusion: In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion., Competing Interests: Declaration of Competing Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sudden cardiac arrest (SCA) is a critical complication of acute myocardial infarction, especially ST-segment elevation myocardial infarction (STEMI). This study identified the risk factors for SCA in patients with STEMI before receiving catheterization., Methods: We retrospectively analyzed the data of patients with STEMI and cardiac arrest who presented to a tertiary care center in Taiwan between January 1, 2016, and December 31, 2019. Only patients with coronary artery disease (CAD) confirmed by coronary angiography were included in this study. We collected the patients' demographic and clinical data, such as age, sex, medical history, estimated glomerular filtration rate (eGFR), and coronary angiographic findings. The primary outcome of this study was SCA in patients with STEMI. Continuous and nominal variables were compared using the two-sample Student's t-test and chi-squared test, respectively. The results of logistic regression were subjected to multivariate analysis with adjustment for possible confounders., Results: A total of 920 patients with STEMI and coronary angiography-documented CAD and 108 patients with SCA who presented between January 1, 2016, and December 31, 2019, were included. The bivariate logistic regression analysis of patients' demographic data revealed that patients with STEMI and SCA were slightly younger, were more likely to have diabetes mellitus, and had a lower eGFR than did the patients without SCA. The coronary angiographic findings indicated a higher prevalence of left main CAD and three-vessel disease in patients with SCA than in patients without SCA. Multivariate logistic regression revealed that left main CAD (odds ratio [OR]: 3.77; 95% confidence interval [CI], 1.84 to 7.72), a lower eGFR (OR: 0.97; 95% CI, 0.96 to 0.98), and younger age (OR: 0.98; 95% CI, 0.96 to 0.99) were the risk factors for SCA in patients with STEMI., Conclusions: Left main CAD, lower eGFR, and younger age are the risk factors for cardiac arrest in patients with acute myocardial infarction., (© 2022. The Author(s).)

Introduction: This study compared the casualties and types of rescues conducted on the main climbing route (MCR) and accessory climbing routes (ACRs) in Yushan National Park (YSNP) between 2008 and 2019., Methods: We collected the following information for all documented mountain rescue operations conducted on the MCRs and ACRs in YSNP between 2008 and 2019: accident location, casualty type, victim number, and type of rescue. The victims were categorized as to injury, illness, mortality, or no medical problem (NMP) groups according to their condition at the time of rescue., Results: Two-hundred forty-four rescue operations involving 329 victims were conducted during the 12-y study period. Among them, 105 (32%) did not require medical treatment, 102 (31%) were injured, 82 (25%) were ill, and 40 (12%) were deceased. Of the 82 individuals with illness, 69 (84%) had acute altitude sickness. The accident and mortality rates on the ACRs were significantly higher than those on the MCR (P<0.001; χ 2 ). The ACR incidents involved significantly higher percentages of helicopter-based rescues and victims in the NMP group (P<0.001)., Conclusions: Acute altitude sickness accounted for most of the rescues. ACRs had higher injury and mortality rates and required more helicopter-based rescues for patients who did not have medical problems. This study may serve as a reference to reduce casualties and overuse of helicopters by educating tourists on the appropriate use of maps and the evaluation of trails in relation to weather conditions., (Copyright © 2022 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Upregulation of death-domain-associated protein (Daxx) is strongly associated with diverse cancer types. Among these, the clinicopathological significance and molecular mechanisms of Daxx overexpression in colorectal cancer (CRC) remain unknown. Here, we showed that Daxx expression was increased in both clinical CRC samples and CRC cell lines. Daxx knockdown significantly reduced proliferation activity in CRC cells and tumor growth in a xenograft model. Further studies revealed that Daxx expression could be attenuated by either treatment with the PIK3CA inhibitor PIK-75 or PIK3CA depletion in CRC cells. Conversely, expression of PIK3CA constitutively active mutants could increase Daxx expression. These data suggest that PIK3CA positively regulates Daxx expression. Consistently, the expression levels of PIK3CA and Daxx were positively correlated in sporadic CRC samples. Interestingly, Daxx knockdown or overexpression yielded decreased or increased levels of PIK3CA, respectively, in CRC cells. We further demonstrated that Daxx activates the promoter activity and expression of PIK3CA. Altogether, our results identify a mechanistic pathway of Daxx overexpression in CRC and suggest a reciprocal regulation between Daxx and PIK3CA for CRC cell growth., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Overcrowding in emergency departments (ED) is a critical problem worldwide, and streaming can alleviate crowding to improve patient flows. Among triage scales, patients labeled as "triage level 3" or "urgent" generally comprise the majority, but there is no uniform criterion for classifying low-severity patients in this diverse population. Our aim is to establish a machine learning model for prediction of low-severity patients with short discharge length of stay (DLOS) in ED., Methods: This was a retrospective study in the ED of China Medical University Hospital (CMUH) and Asia University Hospital (AUH) in Taiwan. Adult patients (aged over 20 years) with Taiwan Triage Acuity Scale level 3 were enrolled between 2018 and 2019. We used available information during triage to establish a machine learning model that can predict low-severity patients with short DLOS. To achieve this goal, we trained five models-CatBoost, XGBoost, decision tree, random forest, and logistic regression-by using large ED visit data and examined their performance in internal and external validation., Results: For internal validation in CMUH, 33,986 patients (75.9%) had a short DLOS (shorter than 4 h), and for external validation in AUH, there were 13,269 (82.7%) patients with short DLOS. The best prediction model was CatBoost in internal validation, and area under the receiver operating cha racteristic curve (AUC) was 0.755 (95% confidence interval (CI): 0.743-0.767). Under the same threshold, XGBoost yielded the best performance, with an AUC value of 0.761 (95% CI: 0.742- 0.765) in external validation., Conclusions: This is the first study to establish a machine learning model by applying triage information alone for prediction of short DLOS in ED with both internal and external validation. In future work, the models could be developed as an assisting tool in real-time triage to identify low-severity patients as fast track candidates., (© 2022. The Author(s).)

Background: Polyglutamine (polyQ) diseases are dominant neurodegenerative diseases caused by an expansion of the polyQ-encoding CAG repeats in the disease-causing gene. The length of the CAG repeats is the major determiner of the age at onset (AO) of polyQ diseases, including Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3)., Objective: We set out to identify common genetic variant(s) that may affect the AO of polyQ diseases., Methods: Three hundred thirty-seven patients with HD or SCA3 were enrolled for targeted sequencing of 583 genes implicated in proteinopathies. In total, 16 genes were identified as containing variants that are associated with late AO of polyQ diseases. For validation, we further investigate the variants of PIAS1 because PIAS1 is an E3 SUMO (small ubiquitin-like modifier) ligase for huntingtin (HTT), the protein linked to HD., Results: Biochemical analyses revealed that the ability of PIAS1 S510G to interact with mutant huntingtin (mHTT) was less than that of PIAS1 WT , resulting in lower SUMOylation of mHTT and lower accumulation of insoluble mHTT. Genetic knock-in of PIAS1 S510G in a HD mouse model (R6/2) ameliorated several HD-like deficits (including shortened life spans, poor grip strength and motor coordination) and reduced neuronal accumulation of mHTT., Conclusions: Our findings suggest that PIAS1 is a genetic modifier of polyQ diseases. The naturally occurring variant, PIAS1 S510G , is associated with late AO in polyQ disease patients and milder disease severity in HD mice. Our study highlights the possibility of targeting PIAS1 or pathways governing protein homeostasis as a disease-modifying approach for treating patients with HD. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Abstract: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and liver is one of the most commonly injured organs after blunt abdominal trauma. The traumatic liver injury-HCC risk relationship remains unclear.We extracted data of patients with traumatic liver injury between 2000 and 2013 from Taiwan National Health Insurance Research Database (n = 15,966) and those of age-, gender-, occupation-, and index year-matched individuals without traumatic liver injury from the general population (n = 63,864). Cox proportional hazard models were employed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC occurrence in the traumatic liver injury cohort compared with that in the comparison cohort.Patients with traumatic liver injury had an increased HCC risk (adjusted HR 2.13, 95% CI 1.59-2.85); this increased risk was more pronounced within 1 year after injury (adjusted HR 8.84, 95% CI 4.29-18.2). After >1 year of injury, HCC risk remained 1.53-fold higher in patients with traumatic liver injury than in those without traumatic liver injury (95% CI 1.08-2.15).People with traumatic liver injury demonstrate a high HCC risk, particularly within the first year of the injury., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Discussing the quality measurements based on interrupted time series in ischemic stroke, delays are often attributed to weekends effect. This study compared the metrics and outcomes of emergent endovascular thrombectomy (EST) during working hours versus non-working hours in the emergency department of an Asian medical center., Methods: A total of 297 patients who underwent EST between January 2015 and December 2018 were retrospectively included, with 52.5% of patients presenting during working hours and 47.5% presenting during nights, weekends, or holidays., Results: Patients with diabetes were more in non-working hours than in working hours (53.9% vs. 41.0%; p=0.026). It took longer during nonworking hours than working hours in door-to -image times (13 min vs. 12 min; p=0.04) and door-to-groin puncture times (median: 112 min vs. 104 min; p=0.042). Significant statistical differences were not observed between the two groups in neurological outcomes, including successful reperfusion and complications such as intracranial hemorrhage and mortality. However, the change in National Institute of Health Stroke Scale (NIHSS) scores in 24 hours was better in the working-hour group than in the nonworking-hour group (4 vs. 2; p=0.058)., Conclusion: This study revealed that nonworking-hour effects truly exist in patients who received EST. Although delays in door-to-groin puncture times were noticed during nonworking hours, significant differences in neurological functions and mortality were not observed between working and non-working hours. Nevertheless, methods to improve the process during non-working hours should be explored in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Melatonin is a hormone majorly secreted by the pineal gland and contributes to a various type of physiological functions in mammals. The melatonin production is tightly limited to the AANAT level, yet the most known molecular mechanisms underlying AANAT gene transcription is limited in the pinealocyte. Here, we find that c-Fos and cAMP-response element-binding protein (CREB) decreases and increases the AANAT transcriptional activity in renal tubular epithelial cell, respectively. Notably, c-Fos knockdown significantly upregulates melatonin levels in renal tubular cells. Functional results indicate that AANAT expression is decreased by c-Fos and resulted in enhancement of cell damage in albumin-injury cell model. We further find an inverse correlation between c-Fos and AANAT levels in renal tubular cells from experimental membranous nephropathy (MN) samples and clinical MN specimens. Our finding provides the molecular basis of c-Fos in transcriptionally downregulating expression of AANAT and melatonin, and elucidate the protective role of AANAT in preventing renal tubular cells death in albumin-injury cell model and MN progression., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chia-Chao Wu reports financial support was provided by Tri-Service General Hospital. Chia-Chao Wu reports financial support was provided by Ministry of Science and Technology. Nil reports a relationship with nil that includes:. Nil has patent nil pending to nil. nil, (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this work, two asymmetric non-fullerene acceptors (NFAs), BTP-EHBO-4F and BTP-PHD-4F, are designed to be applied in green-solvent-processable organic photovoltaics (OPVs). BTP-EHBO-4F and BTP-PHD-4F show good solubilities in green solvent o -xylene. As a result, PM6:BTP-EHBO-4F-based devices exhibit outstanding photovoltaic performances using o -xylene as a solvent. By comparison, due to the poor solubility of Y6 in o -xylene, PM6:Y6-based devices show poor performances. Owing to the favorable phase separation, molecule packing, and orientation observed from atomic force microscopy (AFM) and grazing-incidence wide-angle X-ray scattering (GIWAXS) measurements, PM6:BTP-PHD-4F-based devices demonstrate a PCE of 15.91% with a V OC of 0.87 V, a J SC of 25.64 mA/cm 2 , and an FF of 71.34%. Moreover, PM6:BTP-EHBO-4F-based devices exhibit an impressive PCE of 16.82% with a V OC of 0.85 V, a J SC of 26.12 mA/cm 2 , and an FF of 75.78%, which is outstanding for OPVs using o -xylene as a solvent.

Promyelocytic leukemia protein (PML) is a tumor suppressor possessing multiple modes of action, including induction of apoptosis. We unexpectedly find that PML promotes necroptosis in addition to apoptosis, with Pml -/- macrophages being more resistant to TNF-mediated necroptosis than wild-type counterparts and PML-deficient mice displaying resistance to TNF-induced systemic inflammatory response syndrome. Reduced necroptosis in PML-deficient cells is associated with attenuated receptor-interacting protein kinase 1 (RIPK1) activation, as revealed by reduced RIPK1[S166] phosphorylation, and attenuated RIPK1-RIPK3-MLKL necrosome complex formation. We show that PML deficiency leads to enhanced TNF-induced MAPK-activated kinase 2 (MK2) activation and elevated RIPK1[S321] phosphorylation, which suppresses necrosome formation. MK2 inhibitor treatment or MK2 knockout abrogates resistance to cell death induction in PML-null cells and mice. PML binds MK2 and p38 MAPK, thereby inhibiting p38-MK2 interaction and MK2 activation. Moreover, PML participates in autocrine production of TNF induced by cellular inhibitors of apoptosis 1 (cIAP1)/cIAP2 degradation, since PML-knockout attenuates autocrine TNF. Thus, by targeting MK2 activation and autocrine TNF, PML promotes necroptosis and apoptosis, representing a novel tumor-suppressive activity for PML., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)