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Purpose: To develop and internally validate a novel prediction score to predict the occurrence of arterial-esophageal fistula (AEF) in esophageal cancer bleeding., Methods: This retrospective cohort study enrolled patients with esophageal cancer bleeding in the emergency department. The primary outcome was the diagnosis of AEF. The patients were randomly divided into a derivation group and a validation group. In the derivation stage, a predictive model was developed using logistic regression analysis. Subsequently, internal validation of the model was conducted in the validation cohort during the validation stage to assess its discrimination ability., Results: A total of 257 patients were enrolled in this study. All participants were randomized to a derivation cohort ( n = 155) and a validation cohort ( n = 102). AEF occurred in 22 patients (14.2%) in the derivation group and 14 patients (13.7%) in the validation group. A predictive model (HEARTS-Score) comprising five variables (hematemesis, active bleeding, serum creatinine level >1.2 mg/dL, prothrombin time >13 s, and previous stent implantation) was established. The HEARTS-Score demonstrated a high discriminative ability in both the derivation and validation cohorts, with c-statistics of 0.90 (95% CI 0.82-0.98) and 0.82 (95% CI 0.72-0.92), respectively., Conclusions: By employing this novel prediction score, clinicians can make more objective risk assessments, optimizing diagnostic strategies and tailoring treatment approaches.

Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab., (© 2024. The Author(s).)

Objective: This study is designed to investigate the impact of body mass index (BMI) on the short-term outcomes of patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery., Methods: Data was obtained from 1006 Chinese patients who underwent isolated, primary OPCAB at a high-traffic cardiovascular center during 2020. Subjects were categorized, by BMI, into a low & normal weight (LN) group (BMI < 24 kg/m 2 ), an overweight (OVW) group (24 ≤ BMI < 28 kg/m 2 ), and an obese (OBS) group (BMI ≥ 28 kg/m 2 ). Information pertaining to patients' short-term outcomes (including incidence of mortality and morbidities; duration of postoperative mechanical ventilation; length of stay in the ICU and hospital; postoperative bleeding; etc.) were extracted, and the data from each group were compared., Results: The incidences of in-hospital mortality and morbidities were similar for all three groups. The volume of fluid infusion, postoperative bleeding within 24 h and total bleeding in LN group were higher than those in the OBS group (P < 0.001). The hemoglobin level was lower in the LN group than that in the OBS group (P < 0.001). Duration of mechanical ventilation and length of stay in the ICU in the LN group were longer than those in the OBS group (P < 0.001)., Conclusions: Our results demonstrate that BMI is not significantly related with short-term outcomes in OPCAB patients. However, we suggest that OPCAB patients with low-normal BMI are more susceptible to post-operative blood loss., (© 2024. The Author(s).)

Hair emerged as a biospecimen for long-term investigation of endogenous metabolic perturbations, reflecting the chemical composition circulating in the blood over the past months. Despite its potential, the use of human hair for metabolomics in Alzheimer's disease (AD) research remains limited. Here, we performed both untargeted and targeted metabolomic approaches to profile the key metabolic pathways in the hair of 5xFAD mice, a widely used AD mouse model. Furthermore, we applied the discovered metabolites to human subjects. Hair samples were collected from 6-month-old 5xFAD mice, a stage marked by widespread accumulation of amyloid plaques in the brain, followed by sample preparation and high-resolution mass spectrometry analysis. Forty-five discriminatory metabolites were discovered in the hair of 6-month-old 5xFAD mice compared to wild-type control mice. Enrichment analysis revealed three key metabolic pathways: arachidonic acid metabolism, sphingolipid metabolism, and alanine, aspartate, and glutamate metabolism. Among these pathways, six metabolites demonstrated significant differences in the hair of 2-month-old 5xFAD mice, a stage prior to the onset of amyloid plaque deposition. These findings suggest their potential involvement in the early stages of AD pathogenesis. When evaluating 45 discriminatory metabolites for distinguishing patients with AD from nondemented controls, a combination of l-valine and arachidonic acid significantly differentiated these two groups, achieving a 0.88 area under the curve. Taken together, these findings highlight the potential of hair metabolomics in identifying disease-specific metabolic alterations and developing biomarkers for improving disease detection and monitoring.

This meta-analysis was designed to evaluate the effects of tranexamic acid (TXA) on platelets in patients undergoing cardiac surgery (CS). Relevant trials were identified by computerized searches of PUBMED, Cochrane Library, EMBASE, OVID, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP Data till Jun 4th, 2022, were searched using search terms "platelet", "Tranexamic acid", "cardiac surgery", "randomized controlled trial" database search was updated on Jan 1st 2023. Primary outcomes included platelet counts, function and platelet membrane proteins. Secondary outcome included postoperative bleeding. Search yielded 49 eligible trials, which were finally included in the current study. As compared to Control, TXA did not influence post-operative platelet counts in adult patients undergoing on- or off-pump CS, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS [(WMD = 16.72; 95% CI 6.33 to 27.10; P = 0.002)], significantly increased post-operative platelet counts in adults valvular surgery [(WMD = 14.24; 95% CI 1.36 to 27.12; P = 0.03). Additionally, TXA improved ADP-stimulated platelet aggression [(WMD = 1.88; 95% CI 0.93 to 2.83; P = 0.0001)] and improved CD63 expression on platelets [(WMD = 0.72; 95% CI 0.29 to 1.15; P = 0.001)]. The current study demonstrated that TXA administration did not affect post-operative platelet counts in adult patients undergoing either on- or off-pump CABG, but significantly increased post-operative platelet counts in pediatric patients undergoing on-pump CS and adults valvular surgery. Furthermore, TXA improved ADP-stimulated platelet aggression and improved CD63 expression on platelets. To further confirm this, more well designed and adequately powered randomized trials are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty., Methods: A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models., Results: A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly., Conclusions: Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system., (© 2024. The Author(s).)

Purpose: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE)., Materials and Methods: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test., Results: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR., Conclusion: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ethnopharmacological Relevance: Nursing home-associated pneumonia (NHAP) is a common type of infection among long-term care residents. Moreover, the mortality of NHAP is also higher than community-acquired pneumonia (CAP). In traditional Chinese medicine (TCM), the decoctions of Banxia Houpo Tang (BHT) and Ding Chuan Tang (DCT) are two formulas supporting the lungs' natural defense systems, helps to expel mucus and promote detoxification., Aim of the Study: We designed a concentrated Chinese herbal extract formula called BDT1, that combines the compounds of BHT and DCT. In this study, we evaluated the safety and efficacy of BDT1 for NHAP prevention in high-risk older residents in the nursing home., Materials and Methods: In this randomized, double-blind, placebo-controlled trial, 160 participants aged over 65 years old living in the nursing home were randomly assigned 1:1 to the BDT1 and placebo group. Besides regular medicine, participants received either BDT1 or a placebo for 12 consecutive weeks. The primary outcome was the hospitalization rate for pneumonia in the intervention period and half-year follow-up. The microscopic examination of Gram-stained sputum was also evaluated before and after the trial. Data were analyzed by using the Chi-square test and Wilcoxon Signed Ranks Test with SPSS., Results: A total of 160 participants were enrolled into two study groups in this study, which was completed with 143 participants analyzed, including 70 subjects in the BDT1 group and 73 subjects in the placebo group. After the 12-week medical treatment, the hospitalization rate for pneumonia was 10.0% and 34.2% in the BDT1 and placebo group respectively. The risk of pneumonia in half a year was lower in the BDT1 group (adjusted hazard ratio = 0.422, 95% CI = 0.226-0.791). Compared to the placebo group, the level of Gram-negative bacilli in the BDT1 group is significantly declined in sputum samples (p < 0.05)., Conclusion: In conclusion, the cumulative incidence of pneumonia and related-hospitalization rates declined significantly after 12-weeks of BDT1 treatment. Besides, Chinese herbal medicine BDT1 is a safe therapy without hepatotoxicity or nephrotoxicity., 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 B.V. All rights reserved.)

Background: The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings., Methods: Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists., Results: A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78-7.16), mortality (OR 1.08, 95% CI 1.05-1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13-1.41), poor outcomes (OR 1.02, 95% CI 1.01-1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25-5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30., Conclusion: Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling., Systematic Review Registration: PROSPERO CRD42022359100., (© 2023. The Author(s).)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Background and Objectives: Multimorbidity increases risks, such as polypharmacy, inappropriate prescription, and functional decline. It also increases medical care utilization by older adults, placing a burden on health care systems. This study evaluated the effectiveness of an integrated ambulatory care program for health care and medication use in patients with multimorbidity and polypharmacy., Methods: We conducted a retrospective clinical review of adults with multimorbidity and polypharmacy who attended an integrated ambulatory care program at a 1193-bed university hospital between July 1 and September 30, 2019. This program involves multidisciplinary teamwork, comprehensive assessments, medication reviews, and case management. Outcomes, including the frequency of outpatient visits, emergency department visits, hospitalizations, chronic prescription medications, potentially inappropriate medications (PIMs), health care costs, and total medical expenditure, were compared before and after the program., Results: The mean age of participants (n = 134) at baseline was 74.22 ± 9.75 years. The mean number of chronic diagnoses was 9.45 ± 3.38. Participants included 72 (53.7%) women. At the 1-year follow-up, participants showed a significant decrease in the annual frequency of outpatient visits (19.78 ± 9.98 to 13.90 ± 10.22, P < .001), emergency department visits (1.04 ± 1.70 to 0.73 ± 1.40, P = .029), and chronic disease medications (10.71 ± 3.96 to 9.57 ± 3.67, P < .001) across all age groups. There was also a reduction in the annual number of PIMs (from 1.31 ± 1.01 to 1.12 ± 0.93, P = .002) among patients aged 65 years. However, no effects were observed on annual hospitalization, duration of hospital stay, or total health care expenditure, possibly due to the high disease-related treatment cost for certain participants., Conclusions: Expanding integrated ambulatory care programs in Taiwan may help patients with multimorbidity reduce their use of outpatient and emergency services, chronic prescriptions, and PIMs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Introduction: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS., Methods: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC)., Results: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p &lt; 0.001), and the binary score showed excellent correlation (r = 0.944; p &lt; 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90)., Discussion/conclusion: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards., (© 2024 S. Karger AG, Basel.)

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024., (Copyright © 2024 American Physiological Society. All rights reserved.)

A new class of fluorinated cyclopenta[2,1- b :3,4- b ']dithiophene (CPDT)-based small molecules, namely YC-oF, YC-mF, and YC-H, are demonstrated as hole-transporting materials (HTMs) for high-performance perovskite solar cells (PSCs). PSCs employing YC-oF as the HTM delivered an excellent efficiency of 22.41% with encouraging long-term stability.

This study assesses the feasibility, safety, and effectiveness of noninvasive stereotactic body radiotherapy (SBRT) as an approach for pulmonary artery denervation in canine models. SBRT with CyberKnife resulted in reduced mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, and insignificantly increased cardiac output. In comparison to the control group, serum norepinephrine levels at 1 month and 6 months were significantly lower in the CyberKnife group. Computed tomography, pulmonary angiography, and histology analysis revealed that SBRT was associated with minimal collateral damage., Competing Interests: Supported by grants from the State Key Program of National Natural Science Foundation of China (No.81830012, No82330014 to Dr Y. Li); National Natural Science Foundation of China (No.82070336 to Dr Y. Li); National Natural Science Foundation of China (No. 81974024 to Dr Gong)Youth Foundation of National Natural Science Foundation of China (No. 82100507 to Dr Zhang). This study was approved by the Animal Use and Management Ethics Committee of the First Affiliated Hospital of Harbin Medical University. The use of animals and all procedures were in agreement with the Guide for the Care and Use of Laboratory Animals (NIH Publication 2011; eighth edition). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Imidacloprid is a neonicotinoid insecticide that efficiently controls piercing-sucking mouthparts pests. However, the impact of low lethal concentration of imidacloprid on key demographic parameters of wheat aphids, Schizaphis graminum (R.) and Rhopalosiphum padi (L.) has been scarcely studied. In this study, we used the age stage, two-sex life table approach to investigate the sublethal effects of imidacloprid on the biological traits of S. graminum and R. padi. Bioassays showed that imidacloprid possesses high toxicity to adult S. graminum and R. padi, with LC50 of 3.59 and 13.78 mg L-1 following 24 h exposure. A low lethal concentration of imidacloprid (LC25) significantly decreased adult longevity and total longevity of progeny generation aphids (F1) of S. graminum. Nevertheless, imidacloprid (LC25) had no significant effects on the fecundity and longevity of directly exposed parental parental S. graminum and R. padi (F0). Our results showed that the low lethal concentration of imidacloprid affected the demographic parameters that ultimately impact on the population of S. graminum. This study provides detailed information about the overall effects of imidacloprid on S. graminum and R. padi that might help to manage these two key pests., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the proliferation of research on anesthesiology training at all stages of medical education, there is relatively little published literature surveying the perspectives and concerns of anesthesiologists regarding cardiovascular anesthesia training. Therefore, we conducted a survey to investigate the attitudes, barriers, expectations, stress experiences, satisfaction, and future aspirations of anesthesiologists trained at a tertiary cardiovascular specialty hospital in China. A questionnaire survey was conducted among 260 anesthesiologists who received cardiovascular anesthesia training at departments of anesthesiology in a tertiary cardiovascular specialty hospital in China. After the study protocol was approved, electronic questionnaires were distributed to the target group through the online survey software "Wen Juan Xing." Respondents were asked to complete an anonymous questionnaire on their smartphones through WeChat, with the restriction of one response per device enabled. Of the 260 trainees, 240 (98%) completed the questionnaire. The majority of the trainees were 31 years of age or above. A large majority had approximately 10 years of clinical anesthesia practice, and nearly one-third had never undertaken cardiovascular specialty anesthesia practice before. The most common reasons for attending the refresher training were the need to learn basic specialty theory and improve clinical skills. The barriers were mainly time constraints or staff shortages in the department. Sixty-one (93.8%) trainees described the experience as "stressful or highly stressful" and identified poor teacher interaction as the highest-ranking stressor. Anesthesiologists were most dissatisfied with job rewards, with a satisfaction rate of only 15%. Anesthesiologists are highly stressed during the refresher training. Poor teacher interaction and low job rewards were identified as the highest-ranking stressors during cardiovascular anesthesia training. Training providers need to pay more attention to these stressors to enhance the quality of cardiovascular anesthesia training., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aqueous rechargeable battery has been an intense topic of research recently due to the significant safety issues of conventional Li-ion batteries (LIBs). Amongst the various candidates of aqueous batteries, aqueous zinc ion batteries (AZIBs) hold great promise as a next generation safe energy storage device due to its low cost, abundance in nature, low toxicity, environmental friendliness, low redox potential, and high theoretical capacity. Yet, the promise has not been realized due to their limitations, such as lower capacity compared to traditional LIB, dendrite growth, detrimental degradation of electrode materials structure as ions intercalate/de-intercalate, and gas evolution/corrosion at the electrodes, which remains a significant challenge. To address the challenges, various 2D materials with different physiochemical characteristics have been utilized. This review explores fundamental physiochemical characteristics of widely used 2D materials in AZIBs, including graphene, MoS 2 , MXenes, 2D metal organic framework, 2D covalent organic framework, and 2D transition metal oxides, and how their characteristics have been utilized or modified to address the challenges in AZIBs. The review also provides insights and perspectives on how 2D materials can help to realize the full potential of AZIBs for next-generation safe and reliable energy storage devices.

Background: The impact of meeting leisure-time physical activity (LTPA) recommendations and household physical activity (HPA) on all-cause mortality in the Taiwanese population is unclear. We aimed to investigate the relationship between sufficient LTPA and all-cause mortality in middle-aged and older Taiwanese adults and the role of HPA in those with insufficient LTPA., Methods: This nationwide prospective cohort study included 4,960 participants aged ≥50 years from the Taiwan Longitudinal Study in Aging (TLSA) survey. Physical activity patterns were assessed in 2003 and then followed up until 2015 for mortality through the National Death Registration Record. Cox proportional hazards regression was conducted to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality., Results: Of the 4,960 participants, 1,712 died of all-cause mortality. Compared to those who had insufficient LTPA, participants who engaged in sufficient LTPA showed a significantly lower risk of all-cause mortality (HR = 0.84, 95% CI, 0.73-0.97). For those with insufficient LTPA, HPA also had a significantly reduced risk of all-cause mortality (HR = 0.85, 95% CI, 0.75-0.96) among general population. Similar associations were observed in subsequent sensitivity analyses. The subgroup analysis showed that the relationship between HPA and reduced mortality risk was only found in the women with insufficient LTPA group., Conclusion: This study confirmed that sufficient LTPA is associated with a lower risk of all-cause mortality. If sufficient LTPA cannot be performed, additional HPA is related to lower mortality.

Synchrotron radiation can be used as a light source in X-ray microscopy to acquire a high-resolution image of a microscale object for tomography. However, numerous projections must be captured for a high-quality tomographic image to be reconstructed; thus, image acquisition is time consuming. Such dense imaging is not only expensive and time consuming but also results in the target receiving a large dose of radiation. To resolve these problems, sparse acquisition techniques have been proposed; however, the generated images often have many artefacts and are noisy. In this study, a deep-learning-based approach is proposed for the tomographic reconstruction of sparse-view projections that are acquired with a synchrotron light source; this approach proceeds as follows. A convolutional neural network (CNN) is used to first interpolate sparse X-ray projections and then synthesize a sufficiently large set of images to produce a sinogram. After the sinogram is constructed, a second CNN is used for error correction. In experiments, this method successfully produced high-quality tomography images from sparse-view projections for two data sets comprising Drosophila and mouse tomography images. However, the initial results for the smaller mouse data set were poor; therefore, transfer learning was used to apply the Drosophila model to the mouse data set, greatly improving the quality of the reconstructed sinogram. The method could be used to achieve high-quality tomography while reducing the radiation dose to imaging subjects and the imaging time and cost., (open access.)

Background: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC)., Aim: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD)., Methods: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010., Results: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 ( P < 0.001) than in those who underwent surgery before 2010., Conclusion: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact., Competing Interests: Conflict-of-interest statement: None of the authors have conflicts of interest related to the manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Previous studies have shown an association between hyperuricemia and microvascular diseases, but the association between uric acid and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to determine the relationship between gout and AAA., Methods: A population-based cohort study was conducted to validate the association between gout and AAA formation. The outcome in this study was the cumulative incidence of AAA in patients with or without gout during the 14-year follow-up period., Results: Our analysis included 121,236 patients with gout and 121,236 propensity score-matched controls from the National Health Insurance Research Database in Taiwan. Compared to the controls, patients who had gout exhibited a significantly increased incidence of AAA development [adjusted hazard ratio (HR) = 2.465, p < 0.001]. We also found that patients who were treated with anti-gout medications had a significantly lower risk of being diagnosed with an AAA than patients who were not treated with anti-gout medications (adjusted HR = 0.489, p < 0.001)., Conclusions: We have provided clinical evidence that gout is associated with the development of AAA., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

UTX/KDM6A, a histone H3K27 demethylase and a key component of the COMPASS complex, is frequently lost or mutated in cancer; however, its tumor suppressor function remains largely uncharacterized in multiple myeloma (MM). Here, we show that the conditional deletion of the X-linked Utx in germinal center (GC) derived cells collaborates with the activating Braf V600E mutation and promotes induction of lethal GC/post-GC B cell malignancies with MM-like plasma cell neoplasms being the most frequent. Mice that developed MM-like neoplasms showed expansion of clonal plasma cells in the bone marrow and extramedullary organs, serum M proteins, and anemia. Add-back of either wild-type UTX or a series of mutants revealed that cIDR domain, that forms phase-separated liquid condensates, is largely responsible for the catalytic activity-independent tumor suppressor function of UTX in MM cells. Utx loss in concert with Braf V600E only slightly induced MM-like profiles of transcriptome, chromatin accessibility, and H3K27 acetylation, however, it allowed plasma cells to gradually undergo full transformation through activation of transcriptional networks specific to MM that induce high levels of Myc expression. Our results reveal a tumor suppressor function of UTX in MM and implicate its insufficiency in the transcriptional reprogramming of plasma cells in the pathogenesis of MM., (© 2023. The Author(s).)

Objectives: Given the substantial disease burden, appropriate and effective management of migraine is a public health priority. To gain insights into real-world migraine management practices in Taiwan, current treatment patterns, costs, and health care resource use were assessed., Methods: This was a retrospective, longitudinal study using the Taiwan National Health Insurance Research Database. Included patients had an initial diagnosis of migraine (defined using International Classification of Diseases codes) between 1 January 2013 and 31 December 2017. Data analyzed included demographics; the use, number, and type of acute and preventive medications; and drug and medical services costs. Data were stratified according to migraine type (chronic [CM] or episodic [EM] migraine)., Results: A total of 312,718 patients were included in the analyses: 53,992 (17.3%) had CM and 258,726 (82.7%) had EM. Most patients (81.7%) had used acute and/or preventive medications; acute medications used more frequently than preventive medications (78.0% vs. 20.2%). Acute medications were used by 81.6 and 77.3% of patients with CM and EM, respectively. Commonly used acute medications were acetaminophen (68.8%), ergots (49.4%), and non-steroidal anti-inflammatory drugs (38.4%); the use of triptans (6.0%), tramadol (3.1%), and other opioids (0.2%) was less common. A total of 28.6 and 18.5% of patients with CM and EM, respectively, used preventive medications. Flunarizine (68.9%), propranolol (40.7%), and topiramate (16.0%) were the most commonly used preventive medications. Most patients had used 1-2 acute or preventive medications, with the use of ≥3 acute or preventive medications more common in patients with CM than EM. Average total medical cost per annum was 4,169 New Taiwan Dollars (NTDs) per CM patient and 2,928 NTDs per EM patient, with CM patients having higher costs associated with medical service utilization and acute medication use., Conclusion: These real-world data suggest unmet needs for Taiwanese patients with migraine, including under-utilization of preventive medications and greater costs and health care resource use for patients with CM versus EM. These findings provide important information on treatment patterns, cost, and health care resource use for patients with migraine in Taiwan., Competing Interests: H-FC, TP, YH, and GD are full-time employees of Eli Lilly and Co. Y-FW has received honoraria as a speaker from Taiwan branches of Allergan/AbbVie, Eli Lilly, Novartis, Pfizer, Sanofi, UCB, Viatris, Orient EuroPharma, Chugai, and Teva. He has received research grants from the Taiwan Ministry of Science and Technology, and Taipei Veterans General Hospital. S-JW has served on the advisory boards of Daiichi-Sankyo, Eli Lilly and Novartis; has received honoraria as a moderator from Allergan/AbbVie, Pfizer, Eli Lilly, Biogen and Eisai and has been the PI in trials sponsored by Eli Lilly, Novartis, and Allergan/AbbVie. He has received research grants from the Taiwan Minister of Technology and Science (MOST), Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Veterans General Hospital, Taiwan Headache Society and Taiwan branches of Eli Lilly, Novartis, and Pfizer. The remaining 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 © 2023 Wang, Wang, Huang, Chen, Yen, Shia, Tsai, Chan, Panni and Dell’Agnello.)

Thoracic endovascular aortic repair (TEVAR) is a new alternative surgical treatment for aortic pathologies, which is more minimally invasive. The aim of current study was to summarize the single-center experience of general anesthesia for patients undergoing TEVAR. In adult patients undergoing surgery for congenital heart disease, the strategy of "fast-track" anesthesia with early extubation in theater is associated with a shorter intensive care unit (ICU) stay, and lower health-care-related costs. Fast-track anesthesia has not been assessed in patients under TEVAR. Adult patients who received general anesthesia for TEVAR in our center from January 2020 to December 2020 were included. Baseline characteristics, airway management, anesthetic techniques and major complications were collected. A total of 204 (171 male, mean age 58.1 ± 11.5 years) patients met inclusion criteria for this study. The distribution of pathologies included 29 descending thoracic aneurysms, 87 type B dissections, and 88 intramural hematoma/perforating aortic ulcer. Etomidate was the induction agent in 190 (93.1%) patients, compared with propofol in 16 (7.8%). Cisatracurium was the muscle relaxant in 201 (98.5%), compared with rocuronium in 3 (1.5%). Midazolam (benzodiazepines) was given to 124 (60.8%) patients during anesthesia induction. General anesthesia was maintained with sevoflurane in 85.3% (174) patients, dexmedetomidine in 201 (98.5%) and propofol in 204 (100%). Postoperative length of stay (LOS) in the hospital was 6.0 (5.0-7.8) days. LOS in the ICU was 23.0 (20.0-27.8) hours. Overall neurologic event rate was 2.0% (n = 4) (spinal cord ischemia 1.5% [n = 3]; stroke 0.5% [n = 1]). After matching, patients who received "fast-track" anesthesia had a shorter LOS in ICUs (21.0 [18.0-24.0] vs 24.0 [20.0-44.0] hours; P = .005), and a shorter postoperative LOS in hospital (5.0 [4.0-7.0] vs 6.0 [5.0-8.0] days; P = .001). There were no in-hospital deaths. Fast-track anesthesia is feasible and safe in patients underwent TEVAR. This management strategy is associated with shorter LOS of ICU and total postoperative hospital stays. An early extubation strategy should be implemented for hemodynamically stable patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported., Methods: This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded., Results: In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4-76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1-8; IQR:1-2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis. In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS., Conclusions: We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death., Competing Interests: Declaration of competing interest Yung Tai Chen, Hsin-Chih Yeh, Hsiang-Ying Lee, Po-Fan Hsieh, Eric Chieh-lung Chou, Yao-Chou Tsai, Ting-En Tai, Jian-Hua Hong, Chao-Yuan Huang, Yuan-Hong Jiang, Yu-Khun Lee, Jen-Shu Tseng, Chih-Chin Yu, Bing-Juin Chiang, Thomas Y. Hsueh, Chia-Chang Wu, and Chung-You Tsai have no conflicts of interest or financial ties to disclose., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The purpose of this study was to identify drivers of genomic evolution in esophageal adenocarcinoma (EAC) and other solid tumors., Methods: An integrated genomics strategy was used to identify deoxyribonucleases correlating with genomic instability (as assessed from total copy number events in each patient) in 6 cancers. Apurinic/apyrimidinic nuclease 1 (APE1), identified as the top gene in functional screens, was either suppressed in cancer cell lines or overexpressed in normal esophageal cells and the impact on genome stability and growth was monitored in vitro and in vivo. The impact on DNA and chromosomal instability was monitored using multiple approaches, including investigation of micronuclei, acquisition of single nucleotide polymorphisms, whole genome sequencing, and/or multicolor fluorescence in situ hybridization., Results: Expression of 4 deoxyribonucleases correlated with genomic instability in 6 human cancers. Functional screens of these genes identified APE1 as the top candidate for further evaluation. APE1 suppression in EAC, breast, lung, and prostate cancer cell lines caused cell cycle arrest; impaired growth and increased cytotoxicity of cisplatin in all cell lines and types and in a mouse model of EAC; and inhibition of homologous recombination and spontaneous and chemotherapy-induced genomic instability. APE1 overexpression in normal cells caused a massive chromosomal instability, leading to their oncogenic transformation. Evaluation of these cells by means of whole genome sequencing demonstrated the acquisition of changes throughout the genome and identified homologous recombination as the top mutational process., Conclusions: Elevated APE1 dysregulates homologous recombination and cell cycle, contributing to genomic instability, tumorigenesis, and chemoresistance, and its inhibitors have the potential to target these processes in EAC and possibly other cancers., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Jimusaria is the first reported Chinese dicynodont, previously only known from Xinjiang. Here we refer two specimens from the Naobaogou Formation, Nei Mongol, China to Jimusaria based on the following features: squamosal separated from supraoccipital by tabular, tabular contacting opisthotic, sharp and thin lateral dentary shelf expanding anteriorly into a thick swelling, nasals fused as single element, rod-like medial bar formed by footplate of epipterygoid connecting to the parabasisphenoid and periotic medially. A new species, J. monanensis , is named based on the diagnostic characters on these two specimens such as distinct caniniform buttress lacking posteroventral furrow, naso-frontal suture forming an anterior directed sharp angle, and converging ventral ridges on posterior portion of anterior pterygoid rami. In Jimusaria , the epipterygoid posteromedially contacts the parabasisphenoid and the periotic as a rod-like bar, a unique morphology unknown in any other dicynodonts. This structure probably increases the stability of the palatal complex. A similar structure might also appear in other dicynodonts as a cartilage connection. The new occurrence of Jimusaria increases the diversity of the tetrapod assemblage from the Naobaogou Formation, and further strengthens the connection between the tetrapod faunas from Nei Mongol and Xinjiang. Based on the current record, Jimusaria is one of the few tetrapod genera which survived in the end-Permian mass extinction., Competing Interests: The authors declare that they have no competing interests., (© 2023 Shi and Liu.)

Tumor relapse and drug resistance are major factors that limit the curability of multiple myeloma (MM). New regimens have improved overall MM survival rates, but patients with high-risk features continue to have inferior outcomes. Chromosome 17p13 deletion (del17p) that includes the loss of the TP53 gene is a high-risk cytogenetic abnormality and is associated with poor clinical outcomes owing to relatively short remissions and the development of pan-drug resistant disease. Increased relapse rates suggest that del17p enhances clonogenic growth, and we found that the loss of p53 increased both the frequency and drug resistance of tumor-initiating MM cells (TICs). Subsequent RNA sequencing (RNA-seq) studies demonstrated significant activation of the Notch signaling pathway and upregulation of inhibitor of DNA binding (ID1/ID2) genes in p53-knock out (p53-KO) cells. We found that the loss of ID1 or HES-1 expression or treatment with a gamma-secretase inhibitor (GSI) significantly decreased the clonogenic growth of p53-KO but not p53 wild-type cells. GSI treatment in a small set of MM specimens also reduced the clonogenic growth in del17p samples but not in non-del17p samples. This effect was specific as overexpression of the Notch intracellular domain (NICD) rescued the effects of GSI treatment. Our study demonstrates that the Notch signaling and ID1 expression are required for TIC expansion in p53-KO MM cells. These findings also suggest that GSI may be specifically active in patients with p53 mutant MM., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi-substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report a low-valent CoH-catalyzed facial-selective cyclopropene hydroalkylation to access multi-substituted cyclopropanes. This reaction exhibits a broad substrate scope of alkyl halides and cyclopropenes and tolerates many functional groups. Moderate-to-good facial-selectivity is obtained without any directing groups. Mechanism studies provide evidence that alkyl radicals are generated from alkyl halides and irreversible CoH insertion is responsible for the facial-selectivity. Our preliminary exploration demonstrates that asymmetric cyclopropene hydroalkylation can be realized without conspicuous auxiliary groups., (© 2023 Wiley-VCH GmbH.)

Background: The benefit of inpatient comprehensive geriatric assessment on patient survival and function has been demonstrated among frail older patients. However, the influence of outpatient geriatric evaluation and management (GEM) on clinical outcomes remains debated. This study aimed to update the research evidence detailing the effect of outpatient GEM on survival and nursing-home admission through a comparison with conventional care., Methods: Cochrane Library, EMBASE, and MEDLINE databases were searched up to January 29th, 2022, to identify randomized controlled trials (RCTs) including older people over age 55 that compared outpatient GEM with conventional care on mortality (primary outcome) and nursing-home admission (secondary outcome) during a follow-up period of 12 to 36 months., Results: Nineteen reports from 11 studies that recruited 7,993 participants (mean age 70-83) were included. Overall, outpatient GEM significantly reduced mortality (risk ratio (RR) = 0.87, 95% confidence interval (CI) = 0.77-0.99, I 2  = 12%). For the subgroup analysis categorized by different follow-up periods, its prognostic benefit was only disclosed for 24-month mortality (RR = 0.68, 95% CI = 0.51-0.91, I 2  = 0%), but not for 12- or 15 to 18-month mortality. Furthermore, outpatient GEM had significantly trivial effects on nursing-home admission during the follow-up period of 12 or 24 months (RR = 0.91, 95% CI = 0.74-1.12, I 2  = 0%)., Conclusions: Outpatient GEM led by a geriatrician with a multidisciplinary team improved overall survival, specifically during the 24-month follow-up period. This trivial effect was demonstrated in rates of nursing-home admission. Future research on outpatient GEM involving a larger cohort is warranted to corroborate our findings., (© 2023. The Author(s).)

This study explored the application of healthcare failure mode and effect analysis (HFMEA) to identify and evaluate risk-associated factors in the intensive care unit (ICU) through a clinical-based expert knowledge (decision) for the physiological monitor operational maintenance process., Methods and Intervention: A mixed qualitative and quantitative proactive approach to explore the HFMEA process by analyzing 20 units of physiological monitors in the ICU. An HFMEA expert team of six people was formed to perform a risk-based analysis and evaluate the potential hazard index, mitigating the hazard scores and risks., Results: From the main processes and possible failure reasons, one high-risk hazard index greater than or equal to 8 of the standard score was found. This standard score indicates the signed manufacturer's contract for maintenance was the hazard index failure mode on the parts not regularly replaced according to the contract. This systematic hazard index failure mode shows the highest hazard scores in the possible failure reason category, established as a standard maintenance procedure. In addition, the HFMEA expert analysis of the 20 units of physiological monitors within 6 months of the original and remanufactured part maintenance results in operational availability from 90.9% for self-repair to 99.2% for contract manufacturer repair., Conclusions: This study concludes a systematic reference in malpractices caused by maintenance negligence. The HFMEA expert team agrees that hazard failure scores greater than or equal to 8 are vital assessments and evaluations for decision-making, especially in maintaining healthcare intensive unit care physiological monitors., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: The authors have no conflicts of interest relevant to this article.