Biomedical subjects

Ronghui Xu

Publications and source records attributed to Ronghui Xu.

13 recordsLinked to original sources

PubMed2025

Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBDs). METHODS: Using an administrative claims database, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016 and 2023 and had insurance coverage for at least 1 year before and after treatment initiation. We compared the risk of infections (overall and serious infections requiring hospitalization), venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) through stabilized inverse probability of treatment weighted Cox proportional hazards model accounting for disease characteristics, health care utilization, comorbidities, prior and concomitant medications, and competing risk of mortality. RESULTS: We included 856 patients treated with JAK inhibitors (age, 47 ± 17 years; 82% with ulcerative colitis [UC]) and 9422 patients treated with TNF antagonists (age, 45 ± 18 years; 44% with UC). JAK inhibitors were associated with higher risk of overall infections (incidence rate, 62.4 per 100 person-years [PY] vs 37.4 per 100 PY; hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.33-1.93), but not serious infections (4.9 vs 5.4; HR, 0.97; 95% CI, 0.66-1.44) compared with TNF antagonists. There was no difference in the risk of VTE (1.3 vs 1.2; HR, 0.66; 95% CI, 0.28-1.57) and MACE (0.4 vs 0.7; HR, 0.50; 95% CI, 0.19-1.30). Findings were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitors, age, prior biologic exposure, concomitant use of corticosteroids, and baseline risk of adverse events. CONCLUSIONS: In an observational study of patients with IBD, JAK inhibitors were not associated with an increased risk of serious infections, VTE, or MACE compared with TNF antagonists, although the overall risk of infections was higher.

Humans↗

PubMed2005

Explained randomness in proportional hazards models.

A coefficient of explained randomness, analogous to explained variation but for non-linear models, was presented by Kent. The construct hinges upon the notion of Kullback-Leibler information gain. Kent and O'Quigley developed these ideas, obtaining simple, multiple and partial coefficients for the situation of proportional hazards regression. Their approach was based upon the idea of transforming a general proportional hazards model to a specific one of Weibull form. Xu and O'Quigley developed a more direct approach, more in harmony with the semi-parametric nature of the proportional hazards model thereby simplifying inference and allowing, for instance, the use of time dependent covariates. A potential drawback to the coefficient of Xu and O'Quigley is its interpretation as explained randomness in the covariate given time. An investigator might feel that the interpretation of the Kent and O'Quigley coefficient, as a proportion of explained randomness of time given the covariate, is preferable. One purpose of this note is to indicate that, under an independent censoring assumption, the two population coefficients coincide. Thus the simpler inferential setting for Xu and O'Quigley can also be applied to the coefficient of Kent and O'Quigley. Our second purpose is to point out that a sample-based coefficient in common use in the SAS statistical package can be interpreted as an estimate of explained randomness when there is no censoring. When there is censoring the SAS coefficient would not seem satisfactory in that its population counterpart depends on an independent censoring mechanism. However there is a quick fix and we argue in favour of its use.

Antimetabolites, Antineoplastic↗

PubMed2004

Adjuvant chemotherapy for resected adenocarcinoma of the esophagus, gastro-esophageal junction, and cardia: phase II trial (E8296) of the Eastern Cooperative Oncology Group.

PURPOSE: To evaluate the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected adenocarcinoma of the distal esophagus, gastro-esophageal (GE) junction, and cardia. PATIENTS AND METHODS: We conducted a multicenter phase II trial. Patients had pathologically staged T2 node-positive to T3-4, any node status adenocarcinoma of the distal esophagus, GE junction, or gastric cardia with negative margins (R0). Treatment consisted of four cycles of paclitaxel 175 mg/m2 intravenously (i.v.) over 3 hours followed by cisplatin 75 mg/m2 i.v. every 21 days. A positive outcome was considered to be an improvement in 2-year survival rate by > or = 20% compared to historic controls. RESULTS: Fifty-nine patients were recruited from 20 centers. Of 55 eligible patients, 49 (89%) had lymph node involvement. Forty-six patients (84%) completed all four cycles. Of the total 59 patients, 31 (56%) developed grade 3 or 4 toxicity with leukopenia/neutropenia, nausea/vomiting, and metabolic toxicities were most common. The median follow-up for surviving patients was 4 years. At 2 years, 33 patients were alive and 22 were dead, with a survival rate of 60% (95% CI, 46% to 73%; one-sided P = .0008 compared with the historic controls). CONCLUSION: Our data suggest that adjuvant paclitaxel and cisplatin may improve survival in R0 resected patients with locally advanced adenocarcinoma of the distal esophagus, GE junction, and cardia. These results warrant further testing in randomized trials.

Adenocarcinoma↗

PubMed2004

Differential stability of beta-catenin along the animal-vegetal axis of the sea urchin embryo mediated by dishevelled.

beta-Catenin has a central role in the early axial patterning of metazoan embryos. In the sea urchin, beta-catenin accumulates in the nuclei of vegetal blastomeres and controls endomesoderm specification. Here, we use in-vivo measurements of the half-life of fluorescently tagged beta-catenin in specific blastomeres to demonstrate a gradient in beta-catenin stability along the animal-vegetal axis during early cleavage. This gradient is dependent on GSK3beta-mediated phosphorylation of beta-catenin. Calculations show that the difference in beta-catenin half-life at the animal and vegetal poles of the early embryo is sufficient to produce a difference of more than 100-fold in levels of the protein in less than 2 hours. We show that dishevelled (Dsh), a key signaling protein, is required for the stabilization of beta-catenin in vegetal cells and provide evidence that Dsh undergoes a local activation in the vegetal region of the embryo. Finally, we report that GFP-tagged Dsh is targeted specifically to the vegetal cortex of the fertilized egg. During cleavage, Dsh-GFP is partitioned predominantly into vegetal blastomeres. An extensive mutational analysis of Dsh identifies several regions of the protein that are required for vegetal cortical targeting, including a phospholipid-binding motif near the N-terminus.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Genetic and environmental contributions to the development of alcohol dependence in male twins.

BACKGROUND: Information on the heritability of the development of alcohol dependence could provide a better understanding of the importance of genetic components in disease transition. OBJECTIVE: To examine the genetic and nongenetic contributions to the age at onset of regular alcohol use, the age at diagnosis of alcohol dependence, and the transition from regular alcohol use to alcohol dependence. DESIGN: Classic twin study. SETTING: General community. PARTICIPANTS: This study included 3372 twin pairs of known zygosity from the Vietnam Era Twin Registry. The diagnosis of DSM-III-R-defined alcohol dependence and related information were obtained through telephone-administered interviews conducted in 1992. MAIN OUTCOME MEASURES: Standardized proportions due to genetic vs nongenetic factors of the total variation in twin resemblance on the age at onset of regular alcohol use, the age at meeting criteria for a diagnosis of alcohol dependence, and the transition period from regular alcohol use to a diagnosis of alcohol dependence. RESULTS: Genetic influence accounted for 49% of the variation in the age at diagnosis of alcohol dependence. After adjusting for co-occurring psychiatric diseases, additive genetic factors still explained more than 37% of the variance in age at onset of alcohol dependence and at least 25% of the variance in the transition period between regular drinking and the diagnosis of alcohol dependence. Additionally, after grouping participants as early and late regular users of alcohol, the genetic effects on the transition period for early regular users were statistically significantly greater than those for late regular users. CONCLUSION: Our results demonstrate a substantial heritable basis for alcohol dependence according to its developmental sequence, including age at onset of regular use, age at diagnosis, and the transition period between regular use and diagnosis.

Adult↗

PubMed2004

Inhibitory effects of phaseolotoxin on proliferation of leukemia cells HL-60, K-562 and L1210 and pancreatic cells RIN-m5F.

Phaseolotoxin (PT) is a non-host specific phytotoxin produced by the plant pathogenic bacterium Pseudomonas syringae (P.s.) pv. phaseolicola. In the present study, the inhibitory effect of PT on the proliferation of leukemia cells was studied. After 4 days of treatment, PT decreased cell growth of leukemia cell lines HL-60, K-562 and L1210 in a dose-dependent manner. In addition, PT also reduced cell growth of the insulinoma pancreatic cell line RIN-m5F. IC50 values were 2.1 +/- 1.0 microM (HL-60), 13.3 +/- 3.7 microM (K-562), 2.5 +/- 0.4 microM (L1210) and 5.5 +/- 0.3 microM (RIN-m5F). Although the exact mechanism by which PT inhibits cell growth in these cells is currently not known, we present first evidence that PT may in part be active via inhibition of ornithine decarboxylase (ODC). Based on our findings, PT presents a lead compound with potential for further development into a new anti-cancer agent.

Animals↗

PubMed2004

Genetic and environmental contributions to age of onset of alcohol dependence symptoms in male twins.

AIMS: To investigate genetic and environmental influences on the development of specific alcohol dependence symptoms. DESIGN AND PARTICIPANTS: A classical twin study of 3372 male-male twin pairs in the Vietnam Era Twin (VET) Registry based on telephone interviews about alcohol use. MEASUREMENTS: The nine diagnostic symptoms according to the Diagnostic and Statistical Manual of Mental Disorder, version III (revised) (DSM-III-R) definition of alcohol dependence. Symptoms were grouped into those based on impaired control, biological effects and social consequences (Beresford's classification) or early versus late symptoms (Nelson's classification). Survival models with random effects were used to examine the age of onset of each symptom. FINDINGS: Approximately 38% of the variation in age of onset of each symptom group based on Beresford's classification is due to additive genetic factors. The age of onset of late symptoms from Nelson's classification appears to be most affected by genetic factors. Estimates of genetic effects for impaired control symptoms are greatly decreased when twins with comorbid psychiatric disorders are excluded. CONCLUSIONS: Our results support the heritability of age of onset of DSM-III-R-defined symptoms for alcohol dependence. However, no symptom group in Beresford's classification could be identified as more heritable than other symptom groups. A strong association between genetic vulnerability and co-occurring diseases for symptoms indicative of impaired control could be found. In addition, our findings show that the late symptom group could be a good candidate for subsequent genetic research.

Adult↗

PubMed2003

Measuring explained variation in linear mixed effects models.

We generalize the well-known R(2) measure for linear regression to linear mixed effects models. Our work was motivated by a cluster-randomized study conducted by the Eastern Cooperative Oncology Group, to compare two different versions of informed consent document. We quantify the variation in the response that is explained by the covariates under the linear mixed model, and study three types of measures to estimate such quantities. The first type of measures make direct use of the estimated variances; the second type of measures use residual sums of squares in analogy to the linear regression; the third type of measures are based on the Kullback-Leibler information gain. All the measures can be easily obtained from software programs that fit linear mixed models. We study the performance of the measures through Monte Carlo simulations, and illustrate the usefulness of the measures on data sets.

Antipsychotic Agents↗

PubMed2003

An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation.

The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in 'pre-bilaterians', we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

Active Transport, Cell Nucleus↗

PubMed2003

A comparison of parametric versus permutation methods with applications to general and temporal microarray gene expression data.

MOTIVATION: In analyses of microarray data with a design of different biological conditions, ranking genes by their differential 'importance' is often desired so that biologists can focus research on a small subset of genes that are most likely related to the experiment conditions. Permutation methods are often recommended and used, in place of their parametric counterparts, due to the small sample sizes of microarray experiments and possible non-normality of the data. The recommendations, however, are based on classical knowledge in the hypothesis test setting. RESULTS: We explore the relationship between hypothesis testing and gene ranking. We indicate that the permutation method does not provide a metric for the distance between two underlying distributions. In our simulation studies permutation methods tend to be equally or less accurate than parametric methods in ranking genes. This is partially due to the discreteness of the permutation distributions, as well as the non-metric property. In data analysis the variability in ranking genes can be assessed by bootstrap. It turns out that the variability is much lower for permutation than parametric methods, which agrees with the known robustness of permutation methods to individual outliers in the data.

Algorithms↗

PubMed2003

Randomized, controlled trial of an easy-to-read informed consent statement for clinical trial participation: a study of the Eastern Cooperative Oncology Group.

PURPOSE: Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual. METHODS: A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes. RESULTS: Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups. CONCLUSION: Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade.

Clinical Protocols↗

PubMed2002

Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival.

The physical interactions between B cells and stromal cells from the lymphoid tissue microenvironment are critical to the survival of normal and malignant B cells. They are principally mediated by integrins expressed on B cells and counterreceptors on stromal cells. Specifically, alpha4beta1 integrin engagement rescues B cells from physiological or drug-induced apoptosis. Therefore, in order to understand the mechanisms by which integrins prevent apoptosis in leukemia B cells, we compared the temporal gene expression profiles induced by beta1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells. Among the 38 selected differentially expressed genes, 6 genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4), and intercellular communication (GJB3) were validated by real-time quantitative polymerase chain reaction (RT-Q-PCR). Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis. We further demonstrate that Fn stimulation also inhibits caspase 3 activation but increases XIAP and survivin expression. Moreover, integrin stimulation also prevents caspase activation induced by doxorubicin. Therefore, we identified genes modulated by adhesion of human precursor B leukemia cells that regulate proliferation and apoptosis, highlighting new pathways that might provide insights into future therapy aiming at targeting apoptosis of leukemia cells.

Apoptosis↗

PubMed2002

Survival analysis with time-varying regression effects using a tree-based approach.

Nonproportional hazards often arise in survival analysis, as is evident in the data from the International Non-Hodgkin's Lymphoma Prognostic Factors Project. A tree-based method to handle such survival data is developed for the assessment and estimation of time-dependent regression effects under a Cox-type model. The tree method approximates the time-varying regression effects as piecewise constants and is designed to estimate change points in the regression parameters. A fast algorithm that relies on maximized score statistics is used in recursive segmentation of the time axis. Following the segmentation, a pruning algorithm with optimal properties similar to those of classification and regression trees (CART) is used to determine a sparse segmentation. Bootstrap resampling is used in correcting for overoptimism due to split point optimization. The piecewise constant model is often more suitable for clinical interpretation of the regression parameters than the more flexible spline models. The utility of the algorithm is shown on the lymphoma data, where we further develop the published International Risk Index into a time-varying risk index for non-Hodgkin's lymphoma.

Algorithms↗