Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.

RoBGP:A Chinese Nested Biomedical Named Entity Recognition Model Based on RoBERTa and Global Pointer

Named Entity Recognition(NER)stands as a fundamental task within the field of biomedical text mining,aiming to extract specific types of entities such as genes,proteins,and diseases from complex biomedical texts and categorize them into predefined entity types.This process can provide basic support for the automatic construction of knowledge bases.In contrast to general texts,biomedical texts frequently contain numerous nested entities and local dependencies among these entities,presenting significant challenges to prevailing NER models.To address these issues,we propose a novel Chinese nested biomedical NER model based on RoBERTa and Global Pointer(RoBGP).Our model initially utilizes the RoBERTa-wwm-ext-large pretrained language model to dynamically generate word-level initial vectors.It then incorporates a Bidirectional Long Short-Term Memory network for capturing bidirectional semantic information,effectively addressing the issue of long-distance dependencies.Furthermore,the Global Pointer model is employed to comprehensively recognize all nested entities in the text.We conduct extensive experiments on the Chinese medical dataset CMeEE and the results demonstrate the superior performance of RoBGP over several baseline models.This research confirms the effectiveness of RoBGP in Chinese biomedical NER,providing reliable technical support for biomedical information extraction and knowledge base construction.

Multi-UAV Collaborative Mission Planning Method for Self-Organized Sensor Data Acquisition

In recent years,sensor technology has been widely used in the defense and control of sensitive areas in cities,or in various scenarios such as early warning of forest fires,monitoring of forest pests and diseases,and protection of endangered animals.Deploying sensors to collect data and then utilizing unmanned aerial vehicle(UAV)to collect the data stored in the sensors has replaced traditional manual data collection as the dominant method.The current strategies for efficient data collection in above scenarios are still imperfect,and the low quality of the collected data and the excessive energy consumed by UAV flights are still the main problems faced in data collection.With regards this,this paper proposes a multi-UAV mission planning method for self-organized sensor data acquisition by comprehensively utilizing the techniques of self-organized sensor clustering,multi-UAV mission area allocation,and sub-area data acquisition scheme optimization.The improvedα-hop clustering method utilizes the average transmission distance to reduce the size of the collection sensors,and the K-Dimensional method is used to form a multi-UAV cooperative workspace,and then,the genetic algorithm is used to trade-off the speed with the age of information(AoI)of the collected information and the energy consumption to form the multi-UAV data collection operation scheme.The combined optimization scheme in paper improves the performance by 95.56%and 58.21%,respectively,compared to the traditional baseline model.In order to verify the excellent generalization and applicability of the proposed method in real scenarios,the simulation test is conducted by introducing the digital elevation model data of the real terrain,and the results show that the relative error values of the proposed method and the performance test of the actual flight of the UAV are within the error interval of±10%.Then,the advantages and disadvantages of the present method with the existing mainstream schemes are tested,and the results show that the present method has a huge advantage in terms of space and time complexity,and at the same time,the accuracy for data extraction is relatively improved by 10.46%and 12.71%.Finally,by eliminating the clustering process and the subtask assignment process,the AoI performance decreases by 3.46×and 4.45×,and the energy performance decreases by 3.52×and 4.47×.This paper presents a comprehensive and detailed proactive optimization of the existing challenges faced in the field of data acquisition by means of a series of combinatorial optimizations.

Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer

AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.

Clinical utility of the platelet-lymphocyte ratio as a predictor of postoperative complications after radical gastrectomy for clinical T2-4 gastric cancer

AIMTo identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors.METHODSThree-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy (distal gastrectomy or total gastrectomy) were included in the analysis. Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications (grade II or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage.RESULTSSixty-six patients (21.1%) experienced grade II or higher postoperative complications. The platelet-lymphocyte ratio (PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value (0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71 (sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94 (95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications (OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications.CONCLUSIONThe preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer.

Gastric polyps: Association with Helicobacter pylori status and the pathology of the surrounding mucosa, a cross sectional study

aim:To assess the endoscopic characteristics of gastric polyps and their association with Helicobacter pylori(H.pylori)status in a predominantly Hispanic population.m ETHODS:We conducted a retrospective study of all esophagogastroduodenoscopies performed at our institution.Demographic,endoscopic and histopathological data were reviewed.Categorization of patients into Hispanic and Non-Hispanic was based on selfidentification.Patients without resection/biopsy were not included in the analysis.Identification of polyps type was based on histological examination.One way analysis of variance was used to compare continuousvariables among different polyp types and Fisher’s exact test was used compare categorical variables among polyp types.Unadjusted and adjusted comparisons of demographic and clinical characteristics were performed according to the H.pylori status and polyp type using logistic regressions.RESULTS:Of 7090 patients who had upper endoscopy,335 patients had gastric polyps(4.7%).Resection or biopsy of gastric polyps was performed in 296 patients(88.4%)with a total of 442 polyps removed or biopsied.Of 296 patients,87(29%)had hyperplastic polyps,82(28%)had fundic gland polyps and 5(1.7%)had adenomatous polyps.Hyperplastic polyps were significantly associated with positive H.pylori status compared with fundic gland polyps(OR=4.621;95%CI:1.92-11.13,P=0.001).Hyperplastic polyps were also found to be significantly associated with portal hypertensive gastropathy compared with fundic gland polyps(OR=6.903;95%CI:1.41-33.93,P=0.0174).Out of 296 patients,30(10.1%)had a followup endoscopy with a mean duration of 26±16.3 mo.Interval development of cancer was not noted in any of the patients during follow up period.CONCLUSi ON:Gastric hyperplastic polyps were significantly associated with positive H.pylori status and portal hypertensive gastropathy as compared with fundic gland polyps.

Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence

AIM: To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy. METHODS: Eighty-seven patients, 36 patients with resected colon cancer and 51 patients after polypectomy, were divided into 2 groups: one group was treated with a flavonoid mixture (daily standard dose 20 mg apigenin and 20 mg epigallocathechin-gallat, n = 31) and compared with a matched control group (n = 56). Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire. RESULTS: Of 87 patients enrolled in this study, 36 had resected colon cancer and 29 of these patients had surveillance colonoscopy. Among the flavonoid-treated patients with resected colon cancer (n = 14), there was no cancer recurrence and one adenoma developed. In contrast the cancer recurrence rate of the 15 matched untreated controls was 20% (3 of 15) and adenomas evolved in 4 of those patients (27%). The combined recurrence rate for neoplasia was 7% (1 of 14) in the treated patients and 47% (7 of 15) in the controls (P = 0.027). CONCLUSION: Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer.

Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma.METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection.RESULTS: One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off &#x02265; 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off &#x02265; 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS.CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients

BACKGROUND: Portal vein thrombosis (PVT) is due to many risk factors, but its pathogenesis is still not clearly understood. To identify the risk factors for PVT, we analyzed the clinical characteristics and complications associated with PVT in cir-rhotic patients. METHODS: We studied patients with liver cirrhosis who were admitted to our unit from April 2009 to December 2014. The patients were divided into the PVT and non-PVT groups, and were compared by variables including gender, age, the etiology of cirrhosis, stage of cirrhosis, complications, imaging, and treatment. RESULTS: PVT was found in 45 (9.8%) of 461 cirrhotic pa-tients admitted to our hospital. Most patients (45.9%) had hepatitis B virus (HBV)-related cirrhosis, with a similar dis-tribution of etiologies between the groups. However, there was no positive relationship between PVT and etiologies of cirrhosis. Most patients (71.5%) were in the stage of hepatic decompensation. No statistically signiifcant differences were found in complications including esophageal varices, ascites, and hepatic encephalopathy between the groups. However, there was a signiifcant positive correlation between hepatocel-lular carcinoma (HCC) and PVT (P<0.01). In 30 patients with PVT, thrombosis occurred in the portal vein and/or portal branches, 37.8% were diagnosed on ultrasound. CONCLUSIONS: The incidence of PVT was 9.8%, mainly in patients with HBV-related cirrhosis. The development of PVT was associated with the severity of liver disease and HCC.

Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

Marked elevations of B-type natriuretic peptide （BNP） are not generally seen in patients with heart failure and preserved ejection fraction （HFpEF）. The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic data in 4 groups of patients with levels of BNP ≤ 100 pg/mL, 100-400 pg/mL, 400-1,000 pg/mL and 〉 1,000 pg/mL were compared. Patients with HFpEF and BNP 〉 1,000 pg/mL （28% of the population） were characterized by impaired renal function and greater use of anti-hypertensive medications. A subset of these patients with BNP 〉 1,000 pg/mL had normal renal function （21%） and were significantly older, more frequently female, and tended to have lower ejection fractions. Conversely, patients with HFpEF and BNP ≤100 pg/mL were younger and had preserved renal function. BNP was inversely related to the likelihood of subsequent admission for heart failure, but not to myocardial infarction or death. In conclusion： BNP 〉 1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This elevation of BNP often reflects impaired renal function, but can also be seen in patients with preserved renal function but relatively impaired systolic function.

Disparities of conjugating protective enzyme activities in the colon of patients with adenomas and carcinomas

AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.

More synergetic cooperation of Yamanaka factors in induced pluripotent stem cells than in embryonic stem cells

The role of Yamanaka factors as the core regulators in the induction of pluripotency during somatic cell reprogramming has been discovered recently. Our previous study found that Yamanaka factors regulate a developmental signaling network in maintaining embryonic stem （ES） cell pluripotency. Here, we established completely reprogrammed induced pluripotent stem （iPS） cells and analyzed the global promoter occupancy of Yamanaka factors in these cells by ChiP-chip assays. We found that promoters of 565 genes were co-bound by four Yamanaka factors in iPS cells, a 10-fold increase when compared with their binding in ES cells. The promoters occupied by a single Yamanaka factor distributed equally in activated and repressed genes in iPS cells, while in ES cells Oct4, Sox2, or KIf4 distributed mostly in repressed genes and c-Myc in activated ones. Pathway analysis of the ChiP-chip data revealed that Yamanaka factors regulated 16 developmental signaling pathways in iPS cells, among which 12 were common and 4 were unique compared to pathways regulated in ES ChiP-chip dataset in iPS cells and observed similar results, cells. We further analyzed another recently published showing the power of ChiP-chip plus pathway analysis for revealing the nature of pluripotency maintenance and regeneration. Next, we experimentally tested one of the repressive signaling pathways and found that its inhibition indeed improved efficiency of cell reprogramming. Taken together, we proposed that there is a core developmental signaling network necessary for pluripotency, with TGF-β, Hedgehog, Wnt, p53 as repressive （Yin） regulators and Jak-STAT, cell cycle, focal adhesion, adherens junction as active （Yang） ones; and Yamanaka factors synergistically regulate them in a Yin-Yang balanced way to induce pluripotency.

Measuring episodic abdominal pain and disability in suspected sphincter of Oddi dysfunction

AIM:To evaluate the reliability of an instrument that measures disability arising from episodic abdominal pain in patients with suspected sphincter of Oddi dysfunction(SOD).METHODS:Although several treatments have been utilized to reduce pain and associated disability,measurement tools have not been developed to reliably track outcomes.Two pilot studies were conducted to assess test-retest reliability of a newly developed instrument,the recurrent abdominal pain intensity and disability(RAPID) instrument.The RAPID score is a 90-d summation of days where productivity for various daily activities is reduced as a result of abdominal pain episodes,and is modeled after the migraine disability assessment instrument used to measure headache-related disability.RAPID was administered by telephone on 2 consecutive occasions in 2 consenting populations with suspected SOD:a pre-sphincterotomy population(Pilot Ⅰ,n = 55) and a post-sphincterotomy population(Pilot Ⅱ,n = 70).RESULTS:The average RAPID scores for Pilots Ⅰ and Ⅱ were:82 d(median:81.5 d,SD:64 d) and 48 d(median:0 d,SD:91 d),respectively.The concordance between the 2 assessments for both populations was very good:0.81 for the pre-sphincterotomy population and 0.95 for the post-sphincterotomy population.CONCLUSION:The described pilot studies suggest that RAPID is a reliable instrument for measuring disability resulting from abdominal pain in suspected SOD patients.

Trends and outcomes of transarterial chemoembolization in hepatocellular carcinoma:a national survey

BACKGROUND:Transarterial chemoembolization(TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma(HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last decade.METHODS:We utilized the National Inpatient Sample(2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients(age >18 years). Multivariate analyses for the outcomes of in-hospital "procedure-related complications"(PRCs) and "post-procedure complications"(PPCs) were performed. We also compared early(2002 to 2006) and late(2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and mortality.RESULTS:Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE(P<0.001) and associated PRCs(P=0.006) were observed to be increasing. There was less mortality [adjusted Odds ratio(a OR):0.58; 95% CI:0.41, 0.82], reduced length of hospital stay(-1.87 days; 95% CI:-2.77,-0.97) and increased hospital charges($19232; 95% CI:11013, 27451) in the late era. Additionally, there was increased mortality(a OR:4.07; 95% CI:2.96, 5.59), PRCs(a OR:3.21; 95% CI:2.56, 4.02), and PPCs(a OR:2.70; 95% CI:2.11, 3.46) among patients with coagulopathy.CONCLUSIONS:There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC.

Convergence of Invariant Measures of Truncation Approximations to Markov Processes

Let Q be the Q-matrix of an irreducible, positive recurrent Markov process on a countable state space. We show that, under a number of conditions, the stationary distributions of the n × n north-west corner augmentations of Q converge in total variation to the stationary distribution of the process. Two conditions guaranteeing such convergence include exponential ergodicity and stochastic monotonicity of the process. The same also holds for processes dominated by a stochastically monotone Markov process. In addition, we shall show that finite perturbations of stochastically monotone processes may be viewed as being dominated by a stochastically monotone process, thus extending the scope of these results to a larger class of processes. Consequently, the augmentation method provides an attractive, intuitive method for approximating the stationary distributions of a large class of Markov processes on countably infinite state spaces from a finite amount of known information.

Gastric food retention at endoscopy is associated with severity of liver cirrhosis

BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing factors have not been fully elucidated.Retained gastric food on esophagogastroduodenoscopy(EGD)has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity.Therefore,we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease.Additionally,we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.METHODSWe performed a retrospective case-control study of cirrhotic subjects whounderwent EGD at an academic medical center between 2000 and 2015. Threehundred sixty-four patients with confirmed cirrhosis, who underwent a total of1044 EGDs for the indication of esophageal variceal screening or surveillance,were identified. During the same period, 519 control patients without liverdisease, who underwent a total of 881 EGDs for the indication of anemia, wereidentified. The presence of retained food on EGD was used as a surrogate fordelayed gastric emptying. The relative frequency of delayed gastric emptyingamong cirrhotics was compared to non-cirrhotics. Characteristics of patients withand without retained food on EGD were compared using univariable andmultivariable logistic regression analysis to identify associated factors.RESULTSOverall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics weremore likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P <0.001). Characteristics associated with retained food on univariable analysisincluded age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004),Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P =0.007), and lower platelet count (P = 0.027). On multivariate logistic regressionanalysis, in addition to the presence of cirrhosis (adjusted OR = 5.83;95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34;95%CI:1.08-5.06, P = 0.031), opioid use (OR = 3.08;95%CI: 1.29-7.34, P = 0.011), andChild-Pugh class C (OR = 4.29;95%CI: 1.43-12.9, P = 0.01) were also associatedwith a higher likelihood of food retention on EGD.CONCLUSIONCirrhotics have a higher frequency of retained food at EGD than non-cirrhotics.Decompensated cirrhosis, defined by Child-Pugh class C, is associated with ahigher likelihood of delayed gastric emptying.