Tidal Versus Intermittent Peritoneal Dialysis in Chronic Peritoneal Dialysis Patients: Randomized, Open-Label, Prospective Control Study.

BACKGROUND: Tidal peritoneal dialysis (TPD) provides better fluid flow mechanics and is more comfortable for the patient, owing to fewer alarms and less pain during inflow and outflow. The long-term characteristics of patients with TPD were not evident. In this randomized controlled follow-up study, we aimed to explore the characteristics of patients with TPD, compared to IPD. METHODS: A total of 85 patients were randomized to either IPD or 70% TPD between January 2019 and December 2020, and all patients were followed up on December 2021. The characteristics of patients between the two groups were analyzed using a t-test or chi-square as appropriate. The overall survival and technical survival were analyzed using Kaplan-Meier analysis. RESULTS: Forty-two patients were assigned to IPD, and 43 patients were assigned to TPD. The basal characteristics of patients were not different between the two groups. In an average of 16 months of follow-up, 19 patients died, and 25 patients dropped out of peritoneal dialysis. The two groups had no difference in overall survival and technical survival. TPD was associated with high urine volume (p = 0.001), lower blood urea nitrogen (p = 0.002), lower phosphorus (p = 0.004), and fewer cycler alarms (p < 0.001). The chance of patients reporting abdominal fullness was higher in patients with TPD (p = 0.001). CONCLUSION: In the randomized, controlled, follow-up study, TPD may preserve residual renal function and is associated with lower urea nitrogen and phosphorus in chronic peritoneal dialysis patients. TPD is associated with fewer cycler alarms but may increase the chance of patients reporting abdominal distension.

SGLT-2 inhibitors in chronic peritoneal dialysis patients: a follow-up study.

BACKGROUND: Sodium-glucose transporter-2 inhibitors (SGLT-2i) are recommended for use in patients with type 2 diabetes comorbid atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Limited reports are currently available for their use in dialysis patients. In an observational, retrospective follow-up study, we reported the clinical characteristics of chronic peritoneal dialysis (PD) patients on SGLT-2i. METHODS: We enrolled 50 diabetic chronic PD patients, and 11 continued SGLT-2i after PD treatment. We reported the patients' ultrafiltration, HbA1c, urinary tract infection episodes, and venous CO2 during follow-up and compared the differences in these factors between patients with and without SGLT-2i. RESULTS: The mean age of the patients was 65 ± 15 years, and 16 (32%) patients were female. The age, gender, heart failure, and primary kidney disease were not different between patients with and without SGLT-2i at enrollment. In an average of 31 months follow-up, patients with SGLT-2i had higher ultrafiltration (1322 ± 200 ml/day vs. 985 ± 415 ml/day, p = 0.013), hemoglobin (11.2 ± 1.7 vs. 10.2 ± 1.7 g/dl), white blood cell count (9.2 ± 3.7 vs. 7.4 ± 2.1 109/L), and a lower venous CO2 (p = 0.036). The urine amount, the overall survival, the technical survival, and the chance of UTI were not different between patients with and without SGLT2i. CONCLUSION: SGLT-2i may increase ultrafiltration volume and hemoglobin levels in chronic PD patients. SGLT-2i did not increase urinary tract infection but was linked to subclinical metabolic acidosis. WHAT WAS KNOWN: The effect of SGLT-2i in chronic PD patients is not clear? THIS STUDY ADDS: SGLT-2i is associated with increased ultrafiltration, hemoglobin, white blood cell counts, and a decreased CO2 in PD patient. POTENTIAL IMPACT: SGLT-2i may increase ultrafiltration in PD patients.

Machine learning-based triage to identify low-severity patients with a short discharge length of stay in emergency department.

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

Association of diabetes, education level, and care dependency with use of temporary vascular access in patients with chronic kidney disease.

OBJECTIVE: Temporary vascular access (TVA) is frequently used during the first dialysis in patients with chronic kidney disease (CKD), and it is associated with an increased risk of infection, central vein stenosis, and mortality. Here, factors associated with TVA in patients with CKD were explored. METHODS: This study included patients in a single-center CKD care program who initiated long-term renal replacement therapy. The primary outcome was TVA use at first dialysis. Factors possibly associated with TVA use were analyzed using Cox regression. RESULTS: Temporary vascular access was used in 53.2% of the patients at first dialysis. In total, 73.2% (n = 865) and 26.8% (n = 317) of the patients were on hemodialysis and peritoneal dialysis, respectively. Multivariate Cox regression analysis showed that TVA use in patients with CKD was associated with diabetes (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.28-1.81, p < 0.001), lower albumin (HR 0.82, 95% CI 0.75-0.91, p < 0.001), lower education level (HR 0.75, 95% CI 0.56-1.00, p = 0.055), and total care dependency (HR 1.92, CI 1.44-3.43, p = 0.003). CONCLUSION: Diabetes, education level, and care dependency are associated with TVA at dialysis initiation in patients with CKD.

Repeated centrifuging and washing concentrates bacterial samples in peritoneal dialysis for optimal culture: an original article.

BACKGROUND: Bacterial cultures allow the identification of infectious disease pathogens. However, obtaining the results of conventional culture methods is time-consuming, taking at least two days. A more efficient alternative is the use of concentrated bacterial samples to accelerate culture growth. Our study focuses on the development of a high-yield sample concentrating technique. RESULTS: A total of 71 paired samples were obtained from patients on peritoneal dialysis (PD). The peritoneal dialysates were repeat-centrifuged and then washed with saline, namely the centrifuging and washing method (C&W method). The concentrated samples were Gram-stained and inoculated into culture plates. The equivalent unprocessed dialysates were cultured as the reference method. The times until culture results for the two methods were compared. The reference method yielded no positive Gram stain results, but the C&W method immediately gave positive Gram stain results for 28 samples (p < 0.001). The culture-negative rate was lower in the C&W method (5/71) than in the reference method (13/71) (p = 0.044). The average time for bacterial identification achieved with the C&W method (22.0 h) was shorter compared to using the reference method (72.5 h) (p < 0.001). CONCLUSIONS: The C&W method successfully concentrated bacterial samples and superseded blood culture bottles for developing adequate bacterial cultures. The C&W method may decrease the culture report time, thus improving the treatment of infectious diseases.

Text mining in a literature review of urothelial cancer using topic model.

BACKGROUND: Urothelial cancer (UC) includes carcinomas of the bladder, ureters, and renal pelvis. New treatments and biomarkers of UC emerged in this decade. To identify the key information in a vast amount of literature can be challenging. In this study, we use text mining to explore UC publications to identify important information that may lead to new research directions. METHOD: We used topic modeling to analyze the titles and abstracts of 29,883 articles of UC from Pubmed, Web of Science, and Embase in Mar 2020. We applied latent Dirichlet allocation modeling to extract 15 topics and conducted trend analysis. Gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to identify UC related pathways. RESULTS: There was a growing trend regarding UC treatment especially immune checkpoint therapy but not the staging of UC. The risk factors of UC carried in different countries such as cigarette smoking in the United State and aristolochic acid in Taiwan and China. GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. CONCLUSIONS: The risk factors of UC may be dependent on the countries and GMCSF, IL-5, Syndecan-1, ErbB receptor, integrin, c-Met, and TRAIL signaling pathways are the most relevant biological pathway associated with UC. These findings may provide further UC research directions.

Identification of most influential co-occurring gene suites for gastrointestinal cancer using biomedical literature mining and graph-based influence maximization.

BACKGROUND: Gastrointestinal (GI) cancer including colorectal cancer, gastric cancer, pancreatic cancer, etc., are among the most frequent malignancies diagnosed annually and represent a major public health problem worldwide. METHODS: This paper reports an aided curation pipeline to identify potential influential genes for gastrointestinal cancer. The curation pipeline integrates biomedical literature to identify named entities by Bi-LSTM-CNN-CRF methods. The entities and their associations can be used to construct a graph, and from which we can compute the sets of co-occurring genes that are the most influential based on an influence maximization algorithm. RESULTS: The sets of co-occurring genes that are the most influential that we discover include RARA - CRBP1, CASP3 - BCL2, BCL2 - CASP3 - CRBP1, RARA - CASP3 - CRBP1, FOXJ1 - RASSF3 - ESR1, FOXJ1 - RASSF1A - ESR1, FOXJ1 - RASSF1A - TNFAIP8 - ESR1. With TCGA and functional and pathway enrichment analysis, we prove the proposed approach works well in the context of gastrointestinal cancer. CONCLUSIONS: Our pipeline that uses text mining to identify objects and relationships to construct a graph and uses graph-based influence maximization to discover the most influential co-occurring genes presents a viable direction to assist knowledge discovery for clinical applications.

Caffeic Acid Attenuates Multi-Drug Resistance in Cancer Cells by Inhibiting Efflux Function of Human P-glycoprotein.

: Multidrug resistance (MDR) is a complicated ever-changing problem in cancer treatment, and P-glycoprotein (P-gp), a drug efflux pump, is regarded as the major cause. In the way of developing P-gp inhibitors, natural products such as phenolic acids have gotten a lot of attention recently. The aim of the present study was to investigate the modulating effects and mechanisms of caffeic acid on human P-gp, as well as the attenuating ability on cancer MDR. Calcein-AM, rhodamine123, and doxorubicin were used to analyze the interaction between caffeic acid and P-gp, and the ATPase activity of P-gp was evaluated as well. Resistance reversing effects were revealed by SRB and cell cycle assay. The results indicated that caffeic acid uncompetitively inhibited rhodamine123 efflux and competitively inhibited doxorubicin efflux. In terms of P-gp ATPase activity, caffeic acid exhibited stimulation in both basal and verapamil-stimulated activity. The combination of chemo drugs and caffeic acid resulted in decreased IC50 in ABCB1/Flp-InTM-293 and KB/VIN, indicating that the resistance was reversed. Results of molecular docking suggested that caffeic acid bound to P-gp through GLU74 and TRY117 residues. The present study demonstrated that caffeic acid is a promising candidate for P-gp inhibition and cancer MDR attenuation.

Effects of antiepileptic drugs on lipogenic gene regulation and hyperlipidemia risk in Taiwan: a nationwide population-based cohort study and supporting in vitro studies.

To characterize the association between epilepsy, use of antiepileptic drugs (AEDs), and the risk of hyperlipidemia, we conducted a nationwide population-based cohort study with data obtained from the National Health Insurance Research Database of Taiwan. The effects of AEDs on lipogenic gene expression were also examined in vitro. We identified 3617 cases involving patients, whose epilepsy was newly diagnosed between 2000 and 2011, and selected a comparison cohort comprising 14,468 patients without epilepsy. The Cox proportional hazards model was used to evaluate the association between epilepsy, AED use, and hyperlipidemia. The incidence rate of hyperlipidemia was higher in the epilepsy cohort than in the comparison cohort, with an adjusted hazard ratio (aHR) of 1.21 [95% confidence interval (CI): 1.06-1.38] after adjusting for comorbidities and medications. Epilepsy patients not taking AEDs had a higher risk of hyperlipidemia (aHR 1.65; 95% CI 1.35-2.03). Among AEDs, only valproate treatment showed a higher risk of hyperlipidemia (aHR 1.53; 95% CI 1.01-2.33), although the dose-dependent effect did not reach statistical significance. In vitro studies with two hepatic cell lines showed that valproate may exert its effects by activating the liver X receptor alpha (LXRα) signaling pathway, inducing the expression of lipogenesis-related genes and increasing cellular lipid contents. In silico calculations concluded that valproate can bind stably with the ligand-binding domain of LXRα. Thus, valproate-induced hepatic lipogenic gene expression may occur through LXRα activation. Predicting the 'off-target' effects of valproate may prove valuable in developing antiepileptic agents with fewer adverse reactions. Monitoring blood lipid levels throughout the course of treatment is recommended.

Taxifolin Resensitizes Multidrug Resistance Cancer Cells via Uncompetitive Inhibition of P-Glycoprotein Function.

P-glycoprotein (P-gp) effluxes lots of chemotherapeutic agents and leads to multidrug resistance (MDR) in cancer treatments. The development of P-gp inhibitors from natural products provide a potential strategy for the beneficial clinical outcomes. This study aimed to evaluate the effects of the natural flavonoid taxifolin, luteolin, (-)-gallocatechin, and (-)-catechin on human P-gp activity. The kinetic interactions and underlying mechanisms of taxifolin-mediated transporter inhibition were further investigated. The transporter inhibition ability was evaluated in human P-gp stable expression cells (ABCB1/Flp-InTM-293) by calcein-AM uptake assays. The kinetics study for P-gp inhibition was evaluated by doxorubicin and rhodamine123 efflux assays. The MDR reversal ability of taxifolin were performed by SRB assays to detect the cell viability in sensitive cancer cell line (HeLaS3), and resistant cancer cell line (KB-vin). Cell cycle analysis and ABCB1 real-time RT-PCR were used for mechanical exploration. The results demonstrated that taxifolin decreased ABCB1 expression in a concentration-dependent manner. The function of P-gp was inhibited by taxifolin through uncompetitive inhibition of rhodamine 123 and doxorubicin efflux. The combination of taxifolin significantly resensitized MDR cancer cells to chemotherapeutic agents. These results suggested that taxifolin may be considered as a potential P-gp modulator for synergistic treatment of MDR cancers.

Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo.

Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation. Our study demonstrated that 1 markedly inhibited the growth and migration of VSMCs (A7r5 cells). A cytometric analysis suggested that 1 induced growth inhibition by arresting VSMCs at the G1 phase of the cell cycle. A rat carotid artery balloon injury model indicated that neointima formation of the balloon-injured vessel was markedly reduced after extravascular administration of 1. Compound 1 decreased the expression levels of ADAM15 (a disintegrin and metalloprotease 15) and its downstream signaling pathways in the VSMCs. Moreover, the expressions and activities of matrix metalloproteinases (MMP-2 and MMP-9) were also suppressed by 1 in a concentration-dependent manner. Additionally, the molecular mechanisms appear to be mediated, in part, through the downregulation of ADAM15, FAK, ERK, and PI3K/Akt.

Association of epilepsy, anti-epileptic drugs (AEDs), and type 2 diabetes mellitus (T2DM): a population-based cohort retrospective study, impact of AEDs on T2DM-related molecular pathway, and via peroxisome proliferator-activated receptor γ transactivation.

Introduction: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains controversial. We aimed to conduct a nationwide, population-based, retrospective, cohort study to evaluate this relationship. Methods: We extracted data from the Taiwan Longitudinal Generation Tracking Database of patients with new-onset epilepsy and compared it with that of a comparison cohort of patients without epilepsy. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing T2DM between the two cohorts. Next-generation RNA sequencing was used to characterize T2DM-related molecularchanges induced by AEDs and the T2DM-associated pathways they alter. The potential of AEDs to induce peroxisome proliferator-activated receptor γ (PPARγ) transactivation was also evaluated. Results: After adjusting for comorbidities and confounding factors, the case group (N = 14,089) had a higher risk for T2DM than the control group (N = 14,089) [adjusted hazards ratio (aHR), 1.27]. Patients with epilepsy not treated with AEDs exhibited a significantly higher risk of T2DM (aHR, 1.70) than non-epileptic controls. In those treated with AEDs, the risk of developing T2DM was significantly lower than in those not treated (all aHR ≤ 0.60). However, an increase in the defined daily dose of phenytoin (PHE), but not of valproate (VPA), increased the risk of T2DM development (aHR, 2.28). Functional enrichment analysis of differentially expressed genes showed that compared to PHE, VPA induced multiple beneficial genes associated with glucose homeostasis. Among AEDs, VPA induced the specific transactivation of PPARγ. Discussion: Our study shows epilepsy increases the risk of T2DM development, however, some AEDs such as VPA might yield a protective effect against it. Thus, screening blood glucose levels in patients with epilepsy is required to explore the specific role and impact of AEDs in the development of T2DM. Future in depth research on the possibility to repurpose VPA for the treatment of T2DM, will offer valuable insight regarding the relationship between epilepsy and T2DM.

Cardiothoracic ratio values and trajectories are associated with risk of requiring dialysis and mortality in chronic kidney disease.

BACKGROUND: The prognostic role of the cardiothoracic ratio (CTR) in chronic kidney disease (CKD) remains undetermined. METHODS: We conducted a retrospective cohort study of 3117 patients with CKD aged 18-89 years who participated in an Advanced CKD Care Program in Taiwan between 2003 and 2017 with a median follow up of 1.3(0.7-2.5) and 3.3(1.8-5.3) (IQR) years for outcome of end-stage renal disease (ESRD) and overall death, respectively. We developed a machine learning (ML)-based algorithm to calculate the baseline and serial CTRs, which were then used to classify patients into trajectory groups based on latent class mixed modelling. Association and discrimination were evaluated using multivariable Cox proportional hazards regression analyses and C-statistics, respectively. RESULTS: The median (interquartile range) age of 3117 patients is 69.5 (59.2-77.4) years. We create 3 CTR trajectory groups (low [30.1%], medium [48.1%], and high [21.8%]) for the 2474 patients with at least 2 CTR measurements. The adjusted hazard ratios for ESRD, cardiovascular mortality, and all-cause mortality in patients with baseline CTRs ≥0.57 (vs CTRs <0.47) are 1.35 (95% confidence interval, 1.06-1.72), 2.89 (1.78-4.71), and 1.50 (1.22-1.83), respectively. Similarly, greater effect sizes, particularly for cardiovascular mortality, are observed for high (vs low) CTR trajectories. Compared with a reference model, one with CTR as a continuous variable yields significantly higher C-statistics of 0.719 (vs 0.698, P = 0.04) for cardiovascular mortality and 0.697 (vs 0.693, P < 0.001) for all-cause mortality. CONCLUSIONS: Our findings support the real-world prognostic value of the CTR, as calculated by a ML annotation tool, in CKD. Our research presents a methodological foundation for using machine learning to improve cardioprotection among patients with CKD.

An enlarged heart occurs during various medical conditions and can result in early death. However, it is unclear whether this is also the case in patients with chronic kidney disease (CKD). Although the size of the heart can be measured on chest X-rays, this process is time consuming. We used artificial intelligence to quantify the heart size of 3117 CKD patients based on their chest X-rays within hours. We found that CKD patients with an enlarged heart were more likely to develop end-stage kidney disease or die. This could improve monitoring of CKD patients with an enlarged heart and improve their care.

Identification of Key Prognostic Genes of Triple Negative Breast Cancer by LASSO-Based Machine Learning and Bioinformatics Analysis.

Improved insight into the molecular mechanisms of triple negative breast cancer (TNBC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify key genes which may affect the prognosis of TNBC patients by bioinformatic analysis. In our study, the RNA sequencing (RNA-seq) expression data of 116 breast cancer lacking ER, PR, and HER2 expression and 113 normal tissues were downloaded from The Cancer Genome Atlas (TCGA). We screened out 147 differentially co-expressed genes in TNBC compared to non-cancerous tissue samples by using weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were constructed, revealing that 147 genes were mainly enriched in nuclear division, chromosomal region, ATPase activity, and cell cycle signaling. After using Cytoscape software for protein-protein interaction (PPI) network analysis and LASSO feature selection, a total of fifteen key genes were identified. Among them, BUB1 and CENPF were significantly correlated with the overall survival rate (OS) difference of TNBC patients (p value < 0.05). In addition, BUB1, CCNA2, and PACC1 showed significant poor disease-free survival (DFS) in TNBC patients (p value < 0.05), and may serve as candidate biomarkers in TNBC diagnosis. Thus, our results collectively suggest that BUB1, CCNA2, and PACC1 genes could play important roles in the progression of TNBC and provide attractive therapeutic targets.

Cross-Platform in-silico Analyses Exploring Tumor Immune Microenvironment with Prognostic Value in Triple-Negative Breast Cancer.

Introduction: Only a proportion of triple-negative breast cancer (TNBC) is immunotherapy-responsive. We hypothesized that the tumor microenvironment (TME) influences the outcomes of TNBC and investigated the relevant signaling pathways. Materials and Methods: Immune score (IS) and stromal score (SS) were calculated using the ESTIMATE and correlated with the overall survival (OS) in TNBC. RNA-seq data from 115 TNBC samples and 112 normal adjacent tissues were retrieved. Validations in the methylation levels in 10 TNBC and five non-TNBC cell lines were obtained. Cox model overall survival (OS) validated the derived transcription factor (TF) genes in cBioPortal breast cancer patients. Results: SS-low predicts a higher OS compared with SS-high patients (P = 0.0081 IS-high/SS-low patients had better OS (P = 0.045) than IS-low/SS-high patients. More macrophages were polarized to the M2 state in patients with IS-low/SS-high patients (P < 0.001). Moreover, CIBERSORTx showed more CD8+ cytotoxic T-cells in IS-high/SS-low patients (p = 0.0286) and more resting NK cells in the IS-low/SS-high TME (P = 0.0108). KEGG pathway analysis revealed that overexpressed genes were enriched in the IL-17 and cytokine-cytokine receptor interaction pathways. The lncRNA DRAIC, a tumor suppressor, was consistently deactivated in the 10 TNBC cell lines. On the cBioPortal platform, we validated that 13% of ER-negative, HER2-unamplified BC harbored IL17RA deep deletion and 25% harbored TRAF3IP2 amplification. On cBioPortal datasets, the nine altered TF genes derived from the X2K analysis showed significantly worse relapse-free survival in 2377 patients and OS in 4819 invasive BC patients than in the unaltered cohort. Conclusion: Of note, the results of this integrated in silico study can only be generalized to approximately 17% of patients with TNBC, in which infiltrating stromal cells and immune cells play a determinant prognostic role.

Prediction of All-Cause Mortality Based on Stress/Rest Myocardial Perfusion Imaging (MPI) Using Deep Learning: A Comparison between Image and Frequency Spectra as Input.

BACKGROUND: Cardiovascular management and risk stratification of patients is an important issue in clinics. Patients who have experienced an adverse cardiac event are concerned for their future and want to know the survival probability. METHODS: We trained eight state-of-the-art CNN models using polar maps of myocardial perfusion imaging (MPI), gender, lung/heart ratio, and patient age for 5-year survival prediction after an adverse cardiac event based on a cohort of 862 patients who had experienced adverse cardiac events and stress/rest MPIs. The CNN model outcome is to predict a patient's survival 5 years after a cardiac event, i.e., two classes, either yes or no. RESULTS: The best accuracy of all the CNN prediction models was 0.70 (median value), which resulted from ResNet-50V2, using image as the input in the baseline experiment. All the CNN models had better performance after using frequency spectra as the input. The accuracy increment was about 7~9%. CONCLUSIONS: This is the first trial to use pure rest/stress MPI polar maps and limited clinical data to predict patients' 5-year survival based on CNN models and deep learning. The study shows the feasibility of using frequency spectra rather than images, which might increase the performance of CNNs.

Does Weekends Effect Exist in Asia? Analysis of Endovascular Thrombectomy for Acute Ischemic Stroke in A Medical Center.

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

Prediction of non-responsiveness to pre-dialysis care program in patients with chronic kidney disease: a retrospective cohort analysis.

The responsiveness of patients with chronic kidney disease (CKD) to nephrologists' care is unpredictable. We defined the longitudinal stages (LSs) 1-5 of estimated glomerular filtration rate (eGFR) by group-based trajectory modeling for repeated eGFR measurements of 7135 patients with CKD aged 20-90 years from a 13-year pre-end-stage renal disease (ESRD) care registry. Patients were considered nonresponsive to the pre-dialysis care if they had a more advanced eGFR LS compared with the baseline. Conversely, those with improved or stable eGFR LS were considered responsive. The proportion of patients with CKD stage progression increased with the increase in the baseline CKD stage (stages 1-2: 29.2%; stage 4: 45.8%). The adjusted times to ESRD and all-cause mortality in patients with eGFR LS-5 were 92% (95% confidence interval [CI] 86-96%) and 57% (95% CI 48-65%) shorter, respectively, than in patients with eGFR LS-3A. Among patients with baseline CKD stages 3 and 4, the adjusted times to ESRD and all-cause death in the nonresponsive patients were 39% (95% CI 33-44%) and 20% (95% CI 14-26%) shorter, respectively, than in the responsive patients. Our proposed Renal Care Responsiveness Prediction (RCRP) model performed significantly better than the conventional Kidney Failure Risk Equation in discrimination, calibration, and net benefit according to decision curve analysis. Non-responsiveness to nephrologists' care is associated with rapid progression to ESRD and all-cause mortality. The RCRP model improves early identification of responsiveness based on variables collected during enrollment in a pre-ESRD program. Urgent attention should be given to characterize the underlying heterogeneous responsiveness to pre-dialysis care.

LASSO and Bioinformatics Analysis in the Identification of Key Genes for Prognostic Genes of Gynecologic Cancer.

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium-calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.

Identification of Hub Genes Associated With Development of Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.

Improved insight into the molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify significant genes associated with HNSCC and to further analyze its prognostic significance. In our study, the cancer genome atlas (TCGA) HNSCC database and the gene expression profiles of GSE6631 from the Gene Expression Omnibus (GEO) were used to explore the differential co-expression genes in HNSCC compared with normal tissues. A total of 29 differential co-expression genes were screened out by Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods. As suggested in functional annotation analysis using the R clusterProfiler package, these genes were mainly enriched in epidermis development and differentiation (biological process), apical plasma membrane and cell-cell junction (cellular component), and enzyme inhibitor activity (molecular function). Furthermore, in a protein-protein interaction (PPI) network containing 21 nodes and 25 edges, the ten hub genes (S100A8, S100A9, IL1RN, CSTA, ANXA1, KRT4, TGM3, SCEL, PPL, and PSCA) were identified using the CytoHubba plugin of Cytoscape. The expression of the ten hub genes were all downregulated in HNSCC tissues compared with normal tissues. Based on survival analysis, the lower expression of CSTA was associated with worse overall survival (OS) in patients with HNSCC. Finally, the protein level of CSTA, which was validated by the Human Protein Atlas (HPA) database, was down-regulated consistently with mRNA levels in head and neck cancer samples. In summary, our study demonstrated that a survival-related gene is highly correlated with head and neck cancer development. Thus, CSTA may play important roles in the progression of head and neck cancer and serve as a potential biomarker for future diagnosis and treatment.