Utilizing machine learning to integrate single-cell and bulk RNA sequencing data for constructing and validating a novel cell adhesion molecules related prognostic model in gastric cancer.

BACKGROUND: Cell adhesion molecules (CAMs) play a vital role in cell-cell interactions, immune response modulation, and tumor cell migration. However, the unique role of CAMs in gastric cancer (GC) remains largely unexplored. METHODS: This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model. RESULTS: Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score. CONCLUSION: Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.

Comparison between AWGC-cachexia and GLIM-malnutrition in patients with gastric cancer.

BACKGROUND: The newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition. METHODS: Data of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival. RESULTS: A total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098-2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087-2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival. CONCLUSION: AWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment.

Development of a Predictive Nomogram for Sepsis in Patients with Urolithiasis-Related Obstructive Pyelonephritis.

Background and Objectives: In patients with urolithiasis-related obstructive pyelonephritis (UROP), sepsis represents a critical and concerning complication that can substantially increase the mortality rate. This study aimed to identify the risk factors for sepsis in UROP patients and to develop a predictive nomogram model. Materials and Methods: We analyzed data from 148 patients who met the UROP criteria and were admitted to Chang Gung Memorial Hospital between 1 January 2016 and 31 December 2021. The primary outcome evaluated was the incidence of sepsis, as defined by the most recent Sepsis-3 guidelines. To identify potential risk factors for sepsis, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, we utilized multivariable logistic regression to construct the predictive model. Results: There was a total of 102 non-sepsis cases and 46 sepsis cases. Risk factors for sepsis in multivariable analysis were a history of diabetes mellitus (DM) (OR = 4.24, p = 0.007), shock index (SI) (×10-1) (OR = 1.55, p < 0.001), C-reactive protein (CRP) (mg/dL) (OR = 1.08, p = 0.005), and neutrophil to lymphocyte ratio (NLR) (×10) (OR = 1.58, p = 0.007). The nomogram exhibited an area under the receiver operating characteristic curve of 0.890 (95% CI 0.830-0.949). Conclusions: Our study demonstrated that patients with UROP who have DM, higher SI, higher NLR, and elevated CRP levels are significantly more likely to develop sepsis. These insights may aid in risk stratification, and it is imperative that clinicians promptly initiate treatment for those identified as high risk.

Development and validation of a machine learning-based 18F-fluorodeoxyglucose PET/CT radiomics signature for predicting gastric cancer survival.

BACKGROUND: Survival prognosis of patients with gastric cancer (GC) often influences physicians' choice of their follow-up treatment. This study aimed to develop a positron emission tomography (PET)-based radiomics model combined with clinical tumor-node-metastasis (TNM) staging to predict overall survival (OS) in patients with GC. METHODS: We reviewed the clinical information of a total of 327 patients with pathological confirmation of GC undergoing 18 F-fluorodeoxyglucose (18 F-FDG) PET scans. The patients were randomly classified into training (n = 229) and validation (n = 98) cohorts. We extracted 171 PET radiomics features from the PET images and determined the PET radiomics scores (RS) using the least absolute shrinkage and selection operator (LASSO) and random survival forest (RSF). A radiomics model, including PET RS and clinical TNM staging, was constructed to predict the OS of patients with GC. This model was evaluated for discrimination, calibration, and clinical usefulness. RESULTS: On multivariate COX regression analysis, the difference between age, carcinoembryonic antigen (CEA), clinical TNM, and PET RS in GC patients was statistically significant (p < 0.05). A radiomics model was developed based on the results of COX regression. The model had the Harrell's concordance index (C-index) of 0.817 in the training cohort and 0.707 in the validation cohort and performed better than a single clinical model and a model with clinical features combined with clinical TNM staging. Further analyses showed higher PET RS in patients who were older (p < 0.001) and those who had elevated CEA (p < 0.001) and higher clinical TNM (p < 0.001). At different clinical TNM stages, a higher PET RS was associated with a worse survival prognosis. CONCLUSIONS: Radiomics models based on PET RS, clinical TNM, and clinical features may provide new tools for predicting OS in patients with GC.

Effectiveness of Blended Versus Traditional Refresher Training for Cardiopulmonary Resuscitation: Prospective Observational Study.

BACKGROUND: Generally, cardiopulmonary resuscitation (CPR) skills decline substantially over time. By combining web-based self-regulated learning with hands-on practice, blended training can be a time- and resource-efficient approach enabling individuals to acquire or refresh CPR skills at their convenience. However, few studies have evaluated the effectiveness of blended CPR refresher training compared with that of the traditional method. OBJECTIVE: This study investigated and compared the effectiveness of traditional and blended CPR training through 6-month and 12-month refresher sessions with CPR ability indicators. METHODS: This study recruited participants aged ≥18 years from the Automated External Defibrillator Donation Project. The participants were divided into 4 groups based on the format of the CPR training and refresher training received: (1) initial traditional training (a 30-minute instructor-led, hands-on session) and 6-month traditional refresher training (Traditional6 group), (2) initial traditional training and 6-month blended refresher training (an 18-minute e-learning module; Mixed6 group), (3) initial traditional training and 12-month blended refresher training (Mixed12 group), and (4) initial blended training and 6-month blended refresher training (Blended6 group). CPR knowledge and performance were evaluated immediately after initial training. For each group, following initial training but before refresher training, a learning effectiveness assessment was conducted at 12 and 24 months. CPR knowledge was assessed using a written test with 15 multiple-choice questions, and CPR performance was assessed through an examiner-rated skill test and objectively through manikin feedback. A generalized estimating equation model was used to analyze changes in CPR ability indicators. RESULTS: This study recruited 1163 participants (mean age 41.82, SD 11.6 years; n=725, 62.3% female), with 332 (28.5%), 270 (23.2%), 258 (22.2%), and 303 (26.1%) participants in the Mixed6, Traditional6, Mixed12, and Blended6 groups, respectively. No significant between-group difference was observed in knowledge acquisition after initial training (P=.23). All groups met the criteria for high-quality CPR skills (ie, average compression depth: 5-6 cm; average compression rate: 100-120 beats/min; chest recoil rate: >80%); however, a higher proportion (98/303, 32.3%) of participants receiving blended training initially demonstrated high-quality CPR skills. At 12 and 24 months, CPR skills had declined in all the groups, but the decline was significantly higher in the Mixed12 group, whereas the differences were not significant between the other groups. This finding indicates that frequent retraining can maintain high-quality CPR skills and that blended refresher training is as effective as traditional refresher training. CONCLUSIONS: Our findings indicate that 6-month refresher training sessions for CPR are more effective for maintaining high-quality CPR skills, and that as refreshers, self-learning e-modules are as effective as instructor-led sessions. Although the blended learning approach is cost and resource effective, factors such as participant demographics, training environment, and level of engagement must be considered to maximize the potential of this approach. TRIAL REGISTRATION: IGOGO NCT05659108; https://www.cgmh-igogo.tw.

Novel Prediction Score for Arterial-Esophageal Fistula in Patients with Esophageal Cancer Bleeding: A Multicenter Study.

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.

Effects of Dispatcher-Assisted Public-Access Defibrillation Programs on the Outcomes of Out-of-Hospital Cardiac Arrest: A Before-and-After Study.

BACKGROUND: Public access defibrillation (PAD) programs have been implemented globally over the past decade. Although PAD can substantially increase the survival of cardiac arrest, PAD use remains low. This study aimed to evaluate whether drawing upon the successful experiences of dispatcher-assisted cardiopulmonary resuscitation programs would increase the use of PAD in dispatcher-assisted PAD programs. METHODS AND RESULTS: This study using a before-and-after design was conducted in Taoyuan City using a local out-of-hospital cardiac arrest registry system and data of dispatcher performance derived from audio recordings. The primary outcomes were the rate of bystander PAD use, sustained return of spontaneous circulation, survival to discharge, and favorable neurological outcomes. The secondary outcomes were the performance of dispatchers in terms of PAD instruction and dispatcher-assisted cardiopulmonary resuscitation administration, the time interval indicators of dispatcher-assisted cardiopulmonary resuscitation. A total of 1159 patients were included and divided into 2 groups: the before-run-in group (502 patients) and the after-run-in group (657 patients). No significant difference was observed between the 2 groups in terms of baseline characteristics. The rate of PAD use in the after-run-in group significantly increased from 5.0% to 8.7% (P=0.015). The rate of favorable neurological outcomes increased from 4.4% to 5.9%, which was not a statistically significant difference. Compared with the before-run-in group, the rate of successful automated external defibrillator acquisition was 13.5% in the after-run-in group (P<0.001). CONCLUSIONS: Implementing a dispatcher-assisted PAD protocol in a municipality setting significantly increased bystander PAD use without affecting dispatcher performance in out-of-hospital cardiac arrest recognition, cardiopulmonary resuscitation instruction, or dispatcher-assisted cardiopulmonary resuscitation time indicators.

Radiomics based on machine learning algorithms could predict prognosis and postoperative chemotherapy benefits of patients with gastric cancer: a retrospective cohort study.

Background: Traditional clinical characteristics have certain limitations in evaluating cancer prognosis. The radiomics features provide information on tumor morphology, tissue texture, and hemodynamics, which can accurately reflect personalized predictions. This study investigated the clinical value of radiomics features on contrast-enhanced computed tomography (CT) images in predicting prognosis and postoperative chemotherapy benefits for patients with gastric cancer (GC). Methods: For this study, 171 GC patients who underwent radical gastrectomy and pathology confirmation of the malignancy at the First Affiliated Hospital of Wenzhou Medical University were retrospectively enrolled. The general information, pathological characteristics, and postoperative chemotherapy information were collected. Patients were also monitored through telephone interviews or outpatient treatment. GC patients were randomly divided into the developing cohort (n=120) and validation cohort (n=51). The intra-tumor areas of interest inside the tumors were delineated, and 1,218 radiomics features were extracted. The optimal radiomics risk score (RRS) was constructed using 8 machine learning algorithms and 29 algorithm combinations. Furthermore, a radiomics nomogram that included clinicopathological characteristics was constructed and validated through univariate and multivariate Cox analyses. Results: Eleven prognosis-related features were selected, and an RRS was constructed. Kaplan-Meier curve analysis showed that the RRS had a high prognostic ability in the developing and validation cohorts (log-rank P<0.01). The RRS was higher in patients with a larger tumor size (≥3 cm), higher Charlson score (≥2), and higher clinical stage (Stages III and IV) (all P<0.001). Furthermore, GC patients with a higher RRS significantly benefited from postoperative chemotherapy. The results of univariate and multivariate Cox regression analyses demonstrated that the RRS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) (P<0.001). A visual nomogram was established based on the significant factors in multivariate Cox analysis (P<0.05). The C-index was 0.835 (0.793-0.877) for OS and 0.733 (0.677-0.789) for DFS in the developing cohort. The calibration curve also showed that the nomogram had good agreement. Conclusions: A nomogram that combines the RRS and clinicopathological characteristics could serve as a novel noninvasive preoperative prediction model with the potential to accurately predict the prognosis and chemotherapy benefits of GC patients.

The relationship between GLIM-malnutrition, post-operative complications and long-term prognosis in elderly patients undergoing colorectal cancer surgery.

Background: Elderly people and patients with colorectal cancer (CRC) are both at high risk of malnutrition. Therefore, it is of great significance to explore suitable malnutrition screening and diagnostic indicators for elderly patients with CRC. Recently, the Global Leadership Initiative on Malnutrition (GLIM) proposed new diagnostic criteria for malnutrition. The aim of this article was to evaluate the diagnostic value of GLIM criteria for malnutrition in elderly colorectal patients. We explored the relationship between GLIM-malnutrition, post-operative complications and the long-term prognosis of elderly colorectal patients. Methods: Elderly patients (aged ≥65 years) who underwent CRC surgery from January 2015 to December 2018 were included. Malnutrition was diagnosed based on the GLIM criteria. The relationships between GLIM-malnutrition and clinical characteristics were analyzed by t-tests, Mann-Whitney U tests, and chi-squared tests. The relationships between GLIM-malnutrition and post-operative complications were analyzed by chi-squared tests, and logistic regression analyses. The relationships between GLIM-malnutrition and the long-term prognosis were analyzed by Kaplan-Meier analyses and logistic and Cox regression analyses. Results: A total of 385 elderly patients were included in this study, and 118 patients (30.65%) were diagnosed with malnutrition according to the GLIM criteria. GLIM-malnutrition was significantly associated with older age, lower body mass index (BMI), lower grip strength, tumor location, higher Nutrition Risk Screening 2002 (NRS-2002), and lower levels of albumin and hemoglobin. GLIM-malnutrition was an independent risk factor [odds ratio (OR): 1.753, 95% confidence interval (CI): 1.100-2.795, P=0.018] for post-operative complications. Cox regression analysis showed that GLIM-malnutrition was an independent risk factor for overall survival in elderly patients with CRC. Conclusions: The GLIM criteria are feasible diagnostic criteria for malnutrition of elderly patients with CRC. GLIM-malnutrition is significantly associated with post-operative complications and overall survival in elderly patients with CRC.

Clinical application of molecular residual disease detection by circulation tumor DNA in solid cancers and a comparison of technologies: review article.

Molecular residual disease (MRD), detected by circulating tumor DNA (ctDNA) can be involved in the entire process of solid tumor management, including recurrence prediction, efficacy evaluation, and risk stratification. Currently, the detection technologies are divided into two main categories, as follows: tumor-agnostic and tumor informed. Tumor-informed assay obtains mutation information by sequencing tumor tissue samples before blood MRD monitoring, followed by formulation of a personalized MRD panel. Tumor-agnostic assays are carried out using a fixed panel without the mutation information from primary tumor tissue. The choice of testing strategy may depend on the level of evidence from ongoing randomized clinical trials, investigator preference, cost-effectiveness, patient economics, and availability of tumor tissue. The review describes the difference between tumor informed and tumor agnostic detection. In addition, the clinical application of ctDNA MRD in solid tumors was introduced, with emphasis on lung cancer, colorectal cancer, Urinary system cancer, and breast cancer.

ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer.

Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation.

The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer.

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

Shoulder strap fixation of LUCAS-2 to facilitate continuous CPR during non-supine (stair) stretcher transport of OHCAs patients.

Early recognition and rapid initiation of high-quality cardiopulmonary resuscitation (CPR) are key to maximising chances of achieving successful return of spontaneous circulation in patients with out-of-hospital cardiac arrests (OHCAs), as well as improving patient outcomes both inside and outside hospital. Mechanical chest compression devices such as the LUCAS-2 have been developed to assist rescuers in providing consistent, high-quality compressions, even during transportation. However, providing uninterrupted and effective compressions with LUCAS-2 during transportation down stairwells and in tight spaces in a non-supine position is relatively impossible. In this study, we proposed adaptations to the LUCAS-2 to allow its use during transportation down stairwells and examined its effectiveness in providing high-quality CPR to simulated OHCA patients. 20 volunteer emergency medical technicians were randomised into 10 pairs, each undergoing 2 simulation runs per experimental arm (LUCAS-2 versus control) with a loaded Resusci Anne First Aid full body manikin weighing 60 kg. Quality of CPR compressions performed was measured using the CPRmeter placed on the sternum of the manikin. The respective times taken for each phase of the simulation protocol were recorded. Fisher's exact tests were used to analyse categorical variables and median test to analyse continuous variables. The LUCAS-2 group required a longer time (~ 35 s) to prepare the patient prior to transport (p < 0.0001) and arrive at the ambulance (p < 0.0001) compared to the control group. The CPR quality in terms of depth and rate for the overall resuscitation period did not differ significantly between the LUCAS-2 group and control group, though there was a reduction in both parameters when evaluating the device's automated compressions during transport. Nevertheless, the application of the LUCAS-2 device yielded a significantly higher chest compression fraction of 0.76 (p < 0.0001). Our novel adaptations to the LUCAS-2 device allow for uninterrupted compressions in patients being transported down stairwells, thus yielding better chest compression fractions for the overall resuscitation period. Whether potentially improved post-OHCA survival rates may be achieved requires confirmation in a real-world scenario study.

The diverse roles of circular RNAs in pancreatic cancer.

Pancreatic cancer is one of the malignant tumors with poor prognosis. The molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Several key signaling pathways, such as Notch, Wnt and hedgehog pathways, are important to drive pancreatic carcinogenesis. Recently, noncoding RNAs, especially circular RNAs (circRNAs), have been characterized to participate into pancreatic cancer development. Therefore, in this review article, we describe the association between circRNAs and pancreatic cancer prognosis. Moreover, we discuss how circRNAs are involved in regulation of cellular processes in pancreatic cancer, including proliferation, apoptosis, cell cycle, migration, invasion, EMT, metastasis, angiogenesis, drug resistance and immune escape. Furthermore, we mention that several compounds could regulate the expression of circRNAs, indicating that targeting circRNAs by compounds might be helpful for treating pancreatic cancer patients.

Impact of the Coronavirus Disease 2019 Pandemic on an Emergency Department Service: Experience at the Largest Tertiary Center in Taiwan.

PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is an emerging contagious pathogen that has caused community and nosocomial infections in many countries. This study aimed to evaluate the impact of Coronavirus disease 2019 (COVID-19) on emergency services of the largest medical center in Taiwan by comparing emergency department (ED) usage, turnover, and admission rates before the COVID-19 outbreak with those during the outbreak. MATERIALS AND METHODS: A retrospective cohort study was conducted in the ED of the largest tertiary medical center in Taiwan. Trends of adult, non-trauma patients who visited the ED during February-April 2019 were compared with those during February-April 2020. The number of visits, their dispositions, crowding parameters, and turnover rates were analyzed. The primary outcome was the change in ED attendance between the two periods. The secondary outcomes were changes in hospital admission rates, crowding parameters, and turnover rates. RESULTS: During the outbreak, there were decreased non-trauma ED visits by 33.45% (p < 0.001) and proportion of Taiwan Triage and Acuity Scale (TTAS) 3 patients (p=0.02), with increased admission rates by 4.7% (p < 0.001). Crowding parameters and turnover rate showed significant improvements. CONCLUSION: Comparison of periods before and during the COVID-19 outbreak showed an obvious decline in adult, non-trauma ED visits. The reduction in TTAS 3 patient visits and the increased hospital admission rates provide references for future public-health policy-making to optimise emergency medical resource allocations globally.

Learning Effectiveness Assessment between Primary School Students and Adults in Basic Life Support Education.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a big issue of critical care. It is well known that bystander cardiopulmonary resuscitation (CPR) with an automated external defibrillator (AED) used did improve the survival rate. Therefore, CPR education including basic life support (BLS) and AED has been advocated for years. It showed significant improvement of knowledge and willingness to perform CPR through adolescents after the course. However, little is known regarding the ability and learning effectiveness of school students who attend such courses. Therefore, this study aimed to evaluate the CPR effectiveness of both adolescents (12 years old) and adults who undergo the same course of BLS and AED. METHODS: This is a retrospective study. Sixth-grade elementary school students in Northern Taiwan were selected to compare with the adult group. Both took 90 minutes of the BLS and AED course by the doctor with BLS instructor qualification. The primary outcomes were CPR quality and passing or failing the skill examination parameters. The secondary outcome was the posttraining written test and questionnaire of CPR willingness. RESULTS: In the written test, there was a statistical difference in the pretest score except AED knowledge, but no difference was revealed in the posttest score. No statistical difference in CPR quality was noted. In the skill examination, only checking breathing status had statistical difference (elementary group (71%) vs. adult group (86%) (p=0.003)). CONCLUSION: We revealed that sixth-grade elementary students' performance in CPR and AED was similar to that of adults after completing the current 90-minute course. Therefore, we strongly advocate offering CPR and AED courses to 12-year-old children, and these courses should emphasize checking the victim's breathing status.

Opposing biological functions of the cytoplasm and nucleus DAXX modified by SUMO-2/3 in gastric cancer.

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.