Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study

IntroductionInflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients’ quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses.MethodsGenome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis.ResultsGenetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn’s disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified.DiscussionThis study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases

Knowledge mapping and research hotspots of immunotherapy in renal cell carcinoma: A text-mining study from 2002 to 2021

BackgroundRenal cell carcinoma (RCC) is one of the most lethal urological malignancies, and because early-stage RCC is asymptomatic, many patients present metastatic diseases at first diagnosis. With the development of immunotherapy, the treatment of RCC has entered a new stage and has made a series of progress. This study mainly outlines the knowledge map and detects the potential research hotspots by using bibliometric analysis.MethodsPublications concerning RCC immunotherapy from 2002 to 2021 in the Web of Science Core Collection were collected. Visualization and statistical analysis were mainly performed by freeware tools VOSviewer, CiteSpace, R software, and Microsoft Office Excel 2019.ResultsA total of 3,432 papers were collected in this study, and the annual number of papers and citations showed a steady growth trend. The United States is the leading country with the most high-quality publications and is also the country with the most international cooperation. The University of Texas MD Anderson Cancer Center is the most productive organization. The Journal of Clinical Oncology is the highest co-cited journal, and Brian I. Rini is both the most prolific author and the author with the largest centrality. The current research hotspots may be focused on “immune checkpoint inhibitors (ICIs),” “PD-1,” and “mammalian target of rapamycin.”ConclusionImmunotherapy has a bright future in the field of RCC treatment, among which ICIs are one of the most important research hotspots. The main future research directions of ICI-based immunotherapy may focus on combination therapy, ICI monotherapy, and the development of new predictive biomarkers

The Sloan Digital Sky Survey Reverberation Mapping Project: Initial C IV lag results from four years of data

K.H. acknowledges support from STFC grant ST/M001296/1.We present reverberation-mapping (RM) lags and black hole mass measurements using the C iv λ1549 broad emission line from a sample of 348 quasars monitored as a part of the Sloan Digital Sky Survey RM Project. Our data span four years of spectroscopic and photometric monitoring for a total baseline of 1300 days, allowing us to measure lags up to ~750 days in the observed frame (this corresponds to a rest-frame lag of ~300 days in a quasar at z = 1.5 and ~190 days at z = 3). We report significant time delays between the continuum and the C iv λ1549 emission line in 48 quasars, with an estimated false-positive detection rate of 10%. Our analysis of marginal lag measurements indicates that there are on the order of ~100 additional lags that should be recoverable by adding more years of data from the program. We use our measurements to calculate black hole masses and fit an updated C iv radius–luminosity relationship. Our results significantly increase the sample of quasars with C iv RM results, with the quasars spanning two orders of magnitude in luminosity toward the high-luminosity end of the C iv radius–luminosity relation. In addition, these quasars are located at some of the highest redshifts (z ≈ 1.4–2.8) of quasars with black hole masses measured with RM. This work constitutes the first large sample of C iv RM measurements in more than a dozen quasars, demonstrating the utility of multiobject RM campaigns.Publisher PDFPeer reviewe

Discovery of 16 new z ∼ 5.5 quasars: filling in the redshift gap of quasar color selection

We present initial results from the first systematic survey of luminous z ∼ 5.5 quasars. Quasars at z ∼ 5.5, the post-reionization epoch, are crucial tools to explore the evolution of intergalactic medium, quasar evolution, and the early super-massive black hole growth. However, it has been very challenging to select quasars at redshifts 5.3 ≤ z ≤ 5.7 using conventional color selections, due to their similar optical colors to late-type stars, especially M dwarfs, resulting in a glaring redshift gap in quasar redshift distributions. We develop a new selection technique for z ∼ 5.5 quasars based on optical, near-IR, and mid-IR photometric data from Sloan Digital Sky Survey (SDSS), UKIRT InfraRed Deep Sky Surveys—Large Area Survey (ULAS), VISTA Hemisphere Survey (VHS), and Wide Field Infrared Survey Explorer. From our pilot observations in the SDSS-ULAS/VHS area, we have discovered 15 new quasars at 5.3 ≤ z ≤ 5.7 and 6 new lower redshift quasars, with SDSS z band magnitude brighter than 20.5. Including other two z ∼ 5.5 quasars already published in our previous work, we now construct a uniform quasar sample at 5.3 ≤ z ≤ 5.7, with 17 quasars in a ∼4800 square degree survey area. For further application in a larger survey area, we apply our selection pipeline to do a test selection by using the new wide field J-band photometric data from a preliminary version of the UKIRT Hemisphere Survey (UHS). We successfully discover the first UHS selected z ∼ 5.5 quasar

The Sloan Digital Sky Survey Reverberation Mapping Project: Key Results

We present the final data from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project, a precursor to the SDSS-V Black Hole Mapper Reverberation Mapping program. This data set includes 11-year photometric and 7-year spectroscopic light curves for 849 broad-line quasars over a redshift range of 0.1<z<4.5 and a luminosity range of Lbol=1E44-47.5 erg/s, along with spectral and variability measurements. We report 23, 81, 125, and 110 reverberation mapping lags (relative to optical continuum variability) for broad Halpha, Hbeta, MgII and CIV using the SDSS-RM sample, spanning much of the luminosity and redshift ranges of the sample. Using 30 low-redshift RM AGNs with dynamical-modeling black hole masses, we derive a new estimate of the average virial factor of =0.62+-0.07 for the line dispersion measured from the RMS spectrum. The intrinsic scatter of individual virial factors is 0.31+-0.07 dex, indicating a factor of two systematic uncertainty in RM black hole masses. Our lag measurements reveal significant R-L relations for Hbeta and MgII at high redshift, consistent with the latest measurements based on heterogeneous samples. While we are unable to robustly constrain the slope of the R-L relation for CIV given the limited dynamical range in luminosity, we found substantially larger scatter in CIV lags at fixed L1350. Using the SDSS-RM lag sample, we derive improved single-epoch (SE) mass recipes for Hbeta, MgII and CIV, which are consistent with their respective RM masses as well as between the SE recipes from two different lines, over the luminosity range probed by our sample. The new Hbeta and MgII recipes are approximately unbiased estimators at given RM masses, but there are systematic biases in the CIV recipe. The intrinsic scatter of SE masses around RM masses is ~0.45 dex for Hbeta and MgII, increasing to ~0.58 dex for CIV.Comment: 33 pages. Data products available at ftp://quasar.astro.illinois.edu/public/sdssrm/final_result

The Sloan Digital Sky Survey Reverberation Mapping Project : improving lag detection with an extended multiyear baseline

We investigate the effects of extended multiyear light curves (9 yr photometry and 5 yr spectroscopy) on the detection of time lags between the continuum variability and broad-line response of quasars at z ≳ 1.5, and compare with the results using 4 yr photometry+spectroscopy presented in a companion paper. We demonstrate the benefits of the extended light curves in three cases: (1) lags that are too long to be detected by the shorter-duration data but can be detected with the extended data; (2) lags that are recovered by the extended light curves but are missed in the shorter-duration data due to insufficient light-curve quality; and (3) lags for different broad-line species in the same object. These examples demonstrate the importance of long-term monitoring for reverberation mapping to detect lags for luminous quasars at high redshift, and the expected performance of the final data set from the Sloan Digital Sky Survey Reverberation Mapping project that will have 11 yr photometric and 7 yr spectroscopic baselines.Publisher PDFPeer reviewe

Data_Sheet_1_Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.docx

IntroductionInflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients’ quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses.MethodsGenome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis.ResultsGenetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn’s disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified.DiscussionThis study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.</p

Development and Validation of Survival Nomograms in Patients with Primary Bladder Lymphoma

Background: The existing studies on primary bladder lymphoma (PBL) are retrospective analyses based on individual cases or small series studies, and the research on PBL is not unified and in-depth enough at present because of the scarcity of PBL and the lack of relevant literature. This study is designed to develop and validate nomograms for overall survival (OS) and cancer-specific survival (CSS) prediction in patients with PBL. Methods: According to the Surveillance, Epidemiology, and End Results (SEER) database, 405 patients diagnosed with PBL from 1975 to 2016 were collected and randomly assigned to training (n = 283) and validation (n = 122) cohort. After the multivariable Cox regression, the OS and CSS nomograms were developed. The discrimination, calibration and clinical usefulness of the nomograms were assessed and validated, respectively, by the training and validation cohort. Furthermore, all of the patients were reclassified into high- and low-risk groups and their survival were compared through Kaplan-Meier method and log-rank test. Results: Age, subtype, Ann Arbor stage, radiation and chemotherapy were identified as independent prognostic factors for OS and age, sex, and subtype for CSS, then corresponding nomograms predicting the 3- and 5-year survival were constructed. The presented nomograms demonstrated good discrimination and calibration, which the C-index in the training and validation cohort were 0.744 (95% confidence interval [CI], 0.705–0.783) and 0.675 (95% CI, 0.603–0.747) for OS nomogram and 0.692 (95% CI, 0.632–0.752) and 0.646 (95% CI, 0.549–0.743) for CSS nomogram, respectively. Furthermore, the nomograms can be used to effectively distinguish Patients with PBL at high risk of death. The clinical usefulness of the nomograms was visually displayed by decision curve analysis. Conclusion: We updated the baseline characteristics of patients with PBL and constructed OS and CSS nomograms to predict their 3- and 5-year survival. Using these nomograms, it would be convenient to individually predict the prognosis of patients with PBL and provide guidance for clinical treatment