tbuckley/cabot-search huggingface dataset:
SAT0516 Influence of ethnicity on clinical pain in patients with osteoarthritis versus rheumatoid arthritis: contribution of level of education and depression
Authors: I Castrejon, J Chua, JA Block, LA Bradley, Y Yazici, N Shakoor
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The experience of pain is characterized by inter-individual and group variability, with ethnicity being one potential contributing factor. In a systematic review, it was shown how African Americans (AA) demonstrated lower pain tolerance in experimental studies<sup>1</sup>. Pain is the most common and troubling symptom in patients with osteoarthritis (OA) -maybe reflecting damage- and in patients with rheumatoid arthritis (RA) -maybe reflecting synovitis- but other pain mechanisms are important. <h3>Objectives</h3> To investigate the influence of ethnicity on clinical pain and other outcomes and to identify potential predictors of higher scores for pain in AA and Hispanic patients with OA or RA seen in routine care. <h3>Methods</h3> As part of their clinic visit, all patients complete a multidimensional health assessment questionnaire (MDHAQ) at 2 academic sites. MDHAQ includes 0–10 visual analogue scales (VAS) for pain, physical function, and a patient global evaluation (PATGL), and a depression score between others. The MDHAQ also include demographic data and patients "self-identify" their ethnicity. One random visit with complete questionnaire data for each OA (ICD-9=715.0) and RA (ICD-9=714.0) patient from each site was included in this analysis. Comparison according to patients9 self-reported ethnicity -White, African-American (AA) or Hispanics- were performed using ANOVA and chi-squared. Multiple regression models were performed to identify independent explanatory variables for clinical pain in AA and Hispanics groups versus White. <h3>Results</h3> The study included 402 OA patients and RA 373. There were no differences in age and gender between ethnicity groups in both diagnostic groups. Years of education were highest in the White followed by AA and then Hispanics in both OA and RA. AA and Hispanics showed statistically significantly higher scores for pain (6.6 vs 5.3 in OA, p&lt;0.001; 5.7 vs 4.4 in RA, p&lt;0.001) and lower physical function (3.2 vs 1.9 in OA, P&lt;0.001; 3.2 vs 1.9 in RA, p&lt;0.001) in comparison with Whites in both diagnostic groups. A lower level of education and a higher level of depression predicted greater pain on a MDHAQ in OA in separate models for AA and Hispanic patients and in RA in Hispanic patients (Table). <h3>Conclusions</h3> AA and Hispanic patients had higher level of pain than Whites, but these differences are mainly influenced by level of education and level of depression in OA and RA patients. These results support the biopsychosociocultural model of pain in which, ethnic group differences may be determined by multiple mechanisms including socio-cultural as education, and psychological as depression, in addition to biological pathways. <h3>References</h3> Rahim-Williams B, Riley JL, et al. Pain Med 2012, 13(4):522–540. <h3>Disclosure of Interest</h3> None declared
Abstract #4450: The basal body gene, RPGRIP1L, is a candidate tumor suppressor gene on chromosome 16q12.2 in human hepatocellular carcinoma
Authors: Ya-Wen Lin, Ming-De Yan, Yu-Lueng Shih
Journal: Cancer Research (2009)

Loss of heterozygosity (LOH) on chromosome 16q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC). Our previous data showed that the smallest common deleted region was between  D16S415  and  D16S419 , encompassed approximately by a 0.75-cM region on 16q12.2 and suggested that the putative tumor suppressor genes (TSGs) at this locus might be involved in the development of HCC. Of the 4 genes ( CHD9 ,  RBL2 ,  AKTIP  and  RPGRIP1L)  located in this region, only  RPGRIP1L  was downregulated in HCCs. Downregulation of  RPGRIP1L  was found in 91% (10/11) HCC cell lines and 35% (14/40) HCCs, respectively. One nonsense mutation was found in one HCC and this mutation resulted in premature stop codon. To investigate the role of  RPGRIP1L  in HCCs, we used overexpression of  RPGRIP1L  in four HCC cell lines (HepG2, Huh6, Huh7, and Hep3B). Overexpression of  RPGRIP1L  suppressed colony formation of tumor cells. Conversely, expression of  RPGRIP1L M  (nonsense mutant form) in HCC cells enhanced colony formation. Furthermore, knockdown  RPGRIP1L  by RNA interference in SK-HepI cells promoted cell transformation. Taken together, these data strongly suggest the  RPGRIP1L  might be the putative TSG at chromosome 16q12.2 in HCC. Moreover, we showed that that Mad2, Survivin, and Securin were elevated in  RPGRIP1L   M   - HepG2 transfectants and  RPGRIP1L -shRNA-SK-HepI transfectants. After knockdown  MAD2 in   RPGRIP1L -shRNA-SK-HepI transfectants partly reverse cellular transformation capability. These data suggest that  RPGRIP1L  suppress cellular transformation partly through mitotic checkpoint protein Mad2.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4450.
Adherent-Invasive <i>E. coli</i> enhances colonic hypersensitivity and P2X receptors expression during post-infectious period
Authors: Amandine Lashermes, Ludivine Boudieu, Julie Barbier, Benoit Sion, Agathe Gelot, Nicolas Barnich, Denis Ardid, Frédéric Antonio Carvalho
Journal: Gut Microbes (2017)

Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are related gastrointestinal disorders characterized by abdominal pain associated with colonic hypersensitivity (CHS). Studies in humans have reported an abnormal colonization of Adherent-Invasive E. coli (AIEC) in the ileum of Crohn's disease (CD) patients associated with overexpression of the bacterial colonizing receptor CEACAM6. The aim of the present study was to investigate whether AIEC reference strain LF82 could induce intestinal impairment during infectious and/or post-infectious periods and subsequently the development of CHS. Transgenic mice overexpressing human CEACAM6 protein (TG) and their wild-type littermates were gavaged by CD-associated AIEC bacteria (reference strain LF82) or PBS for 3 d. Colonic hypersensitivity was assessed by colorectal distension (CRD) test during infectious (D4) and post-infectious periods (D21). Several markers of intestinal inflammation were monitored and the colonic expression of purinergic P2X receptors was quantified. At D4, an increased visceromotor response (VMR) to the CRD test was observed in TG mice infected with CD-associated AIEC LF82 in comparison with non-infected TG mice and persisted in a subgroup of infected animals at D21 after bacteria clearance. Increased VMR was associated with low-grade intestinal inflammation, increased intestinal permeability and expression of P2X 3, 4 and 7. This study shows that certain susceptible hosts infected with CD-associated AIEC bacteria can develop persistent CHS associated with low-grade inflammation and increased P2X receptors expression. Thus, CD-associated AIEC infection in CEACAM6 transgenic mice could be used as a novel post-infectious mouse model mimicking quiescent IBD with IBS-like symptoms such as visceral pain.
Predicting real-world effectiveness using overall survival and progression-free survival-based clinical trial efficacy measures.
Authors: Jason Shafrin, Ningqi Hou, Ron Brookmeyer, Desi Peneva, Seanna Vine, Jinhee Park, Jie Zhang, Robert A. Figlin, Darius N. Lakdawalla
Journal: Journal of Clinical Oncology (2016)

6564 Background: Efficacy measured in cancer medication randomized controlled trials (RCTs) may not accurately predict real-world effectiveness. We measured the relationship between RCT efficacy and real-world effectiveness in two cases: first using RCT overall survival (OS) endpoints and next using RCT progression-free survival (PFS) or time to progression (TTP) endpoints from RCTs evaluating the same therapies. Methods: We measured cancer treatment efficacy relative to control using 28 phase III RCTs that reported both OS and either PFS or TTP endpoints in five tumor sites (breast, colorectal, lung, ovary, and pancreas). We estimated real-world OS benefit as the mortality hazard ratio (MHR) among real-world patients meeting RCT exclusion/inclusion criteria and using one of the relevant treatment or control therapies in Surveillance and Epidemiology End Results (SEER)-Medicare data (1991-2010). MHRs were calculated by fitting a Cox proportional hazard model to the SEER-Medicare data adjusting for patient age, gender, and cancer stage. We then predicted real-world MHRs as the product of the MHR or PFS/TTP surrogate hazard ratio (SHR) from the corresponding trial, and a multiplicative adjustment factor relating real-world MHRs to the corresponding trial hazard ratios. Results: 19,470 patients used one of the RCT treatment or control arm medications and met the RCT inclusion criteria. In the RCTs, treatment arm therapies on average decreased mortality over controls by 15% (average MHR = 0.85, range: 0.56 – 1.10, OS endpoints) and decreased progression by 26% (average SHR = 0.74, range: 0.43 – 1.03, PFS/TTP endpoints). Real-world MHRs were equal (HR = 1.00, 95% CI: 0.96 – 1.05) to RCT MHRs, and real-world MHRs were 16% higher (HR = 1.16, 95% CI: 1.11 – 1.20) than RCT SHRs. Conclusions: Across a range of cancer sites, real-world treatment effectiveness measured by OS is close to that measured by OS in RCTs, but surrogate endpoints (PFS/TTP) in RCTs somewhat over-predicted OS benefits observed in the real world. Physicians and payers relying on RCT SHRs alone might consider discounting them by 16% in order to project likely real-world OS improvements for these five tumors.
Arsenic trioxide: Pharmacokinetics in acute promyelocytic leukemia (APL) patients.
Authors: Cristina Maria Ghiuzeli, Anthony Calabro, Randall Jesse Saunders, Daniel R. Budman, Miroslav Styblo, Craig E. Devoe, Steven L. Allen
Journal: Journal of Clinical Oncology (2013)

7055 Background: Arsenic (As) has significantly increased survival for APL patients. As and its metabolites’ effects on cell proliferation, apoptosis, and methylation, especially long term, remain largely unknown. It is imperative to study the pharmacokinetics of As at therapeutic doses in order to limit untoward effects resulting from treatment. Arsenic trioxide (ATO), available as arsenous acid (iAs III ), is readily metabolized through sequential methyl group additions and electron reduction steps: iAs III →MAs V →MAs III →DMAs V →DMAs III →TMAs V O →TMAs III . iAs III , MAs III and DMAs III are more biologically active and more toxic than pentavalent forms. The key enzyme involved is arsenic methyltransferase, and polymorphisms contribute to metabolic differences between individuals. Methods: Cancer patients not treated with ATO (controls) had one collection of blood and urine samples, while APL patients receiving therapeutic doses of ATO had collections immediately prior to and at 1, 2, 4, 6, and 24 hours, days 4, 8, 15, and 4 weeks after ATO-free interval. Total iAs (iAs III +iAs V ), MAs (MAs III +MAs V ) and DMAs (DMAs III +DMAs V ) were measured in plasma using hydride generation cryotrapping atomic absorption spectrometry, a sensitive automated method of arsine detection. The same As species were measured in urine and in exfoliated bladder cells isolated from urine. Results: We report data on ten control patients and six treated patients (ATO 0.15 mg/kg/day). Initial average As concentrations in treated patients (0.051 ng/ml) were similar at baseline to the controls (0.046 ng/ml). We observed that iAs is quickly metabolized from a peak average plasma concentration of 32 ng As/ml to a trough of 10 ng As/ml within six hours from infusion, remaining unchanged for at least 24 hours. MAs and DMAs concentrations begin to increase at six hours, and continue to rise by day 4 to an average concentration of 8.5 and 10.4 ng As/ml respectively, followed by decline to baseline 4 weeks after final ATO infusion. Conclusions: Treatment with ATO leads to the formation of MAs and DMAs whose long term toxicity in APL patients is poorly understood. Studies involving analysis of As metabolites are needed to assess possible long term toxicities on non-targeted organs.
Cover Image: Invasion of a cutaneous melanoma tumour
Authors: D. Hill, P. Lovat
Journal: British Journal of Dermatology (2017)

Funding sources: DH: National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) David Sainsbury Fellow. Conflicts of interest: none declared. Dear Editor, This image illustrates the vertical cutaneous invasion of an early‐stage melanoma tumour. Human melanoma cells were identified by immunofluorescent staining of Melan‐A, a marker of melanocytic lineage (red), within the cutaneous microenvironment. These are invading from the epidermis – highlighted by immunofluorescent staining for cytokeratin 14 (white) – into the dermis (nuclei stained with 4ʹ,6‐diamidino‐2‐phenylindole, blue). Immunofluorescent staining of type IV collagen (green), a basement membrane marker, is evident below the basal‐layer keratinocytes of intact epidermis, but is disrupted in areas of skin adjacent to melanoma, indicating its breakdown by invading melanoma cells. ...
Cardiac Resynchronization Therapy—Does One Size Fit All?
Authors: Megan Baker, David Weidendorf, Lakshmi Swaminathan
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Cardiac-Specific Conversion Factors to Estimate Radiation Effective Dose From Dose-Length Product in Computed Tomography
Authors: Sigal Trattner, Sandra Halliburton, Carla M. Thompson, Yanping Xu, Anjali Chelliah, Sachin R. Jambawalikar, Boyu Peng, M. Robert Peters, Jill E. Jacobs, Munir Ghesani, James J. Jang, Hussein Al-Khalidi, Andrew J. Einstein
Journal: JACC. Cardiovascular imaging (2017)

This study sought to determine updated conversion factors (k-factors) that would enable accurate estimation of radiation effective dose (ED) for coronary computed tomography angiography (CTA) and calcium scoring performed on 12 contemporary scanner models and current clinical cardiac protocols and to compare these methods to the standard chest k-factor of 0.014 mSv·mGy−1cm−1. Accurate estimation of ED from cardiac CT scans is essential to meaningfully compare the benefits and risks of different cardiac imaging strategies and optimize test and protocol selection. Presently, ED from cardiac CT is generally estimated by multiplying a scanner-reported parameter, the dose-length product, by a k-factor which was determined for noncardiac chest CT, using single-slice scanners and a superseded definition of ED. Metal-oxide-semiconductor field-effect transistor radiation detectors were positioned in organs of anthropomorphic phantoms, which were scanned using all cardiac protocols, 120 clinical protocols in total, on 12 CT scanners representing the spectrum of scanners from 5 manufacturers (GE, Hitachi, Philips, Siemens, Toshiba). Organ doses were determined for each protocol, and ED was calculated as defined in International Commission on Radiological Protection Publication 103. Effective doses and scanner-reported dose-length products were used to determine k-factors for each scanner model and protocol. k-Factors averaged 0.026 mSv·mGy−1cm−1 (95% confidence interval: 0.0258 to 0.0266) and ranged between 0.020 and 0.035 mSv·mGy−1cm−1. The standard chest k-factor underestimates ED by an average of 46%, ranging from 30% to 60%, depending on scanner, mode, and tube potential. Factors were higher for prospective axial versus retrospective helical scan modes, calcium scoring versus coronary CTA, and higher (100 to 120 kV) versus lower (80 kV) tube potential and varied among scanner models (range of average k-factors: 0.0229 to 0.0277 mSv·mGy−1cm−1). Cardiac k-factors for all scanners and protocols are considerably higher than the k-factor currently used to estimate ED of cardiac CT studies, suggesting that radiation doses from cardiac CT have been significantly and systematically underestimated. Using cardiac-specific factors can more accurately inform the benefit-risk calculus of cardiac-imaging strategies.
Redefining thymus medulla specialization for central tolerance
Authors: Emilie J. Cosway, Beth Lucas, Kieran D. James, Sonia M. Parnell, Manuela Carvalho-Gaspar, Andrea J. White, Alexei V. Tumanov, William E. Jenkinson, Graham Anderson
Journal: The Journal of Experimental Medicine (2017)

During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3+ T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.
Klebsiella pneumoniae (ST1519) producing KPC-19 carbapenemase in a patient undergoing selective digestive decontamination before liver transplantation
Authors: A.R. Centonze, A.M. Azzini, R. Mazzi, M. Merighi, E. Concia, A. Mazzariol
Journal: Clinical Microbiology and Infection (2017)
Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling
Authors: Mari Tenno, Katsuyuki Shiroguchi, Sawako Muroi, Eiryo Kawakami, Keita Koseki, Kirill Kryukov, Tadashi Imanishi, Florent Ginhoux, Ichiro Taniuchi
Journal: The Journal of Experimental Medicine (2017)

The mouse Langerhans cell (LC) network is established through the differentiation of embryonic LC precursors. BMP7 and TGFβ1 initiate cellular signaling that is essential for inducing LC differentiation and preserving LCs in a quiescent state, respectively. Here we show that loss of Cbfβ2, one of two RNA splice variants of the Cbfb gene, results in long-term persistence of embryonic LC precursors after their developmental arrest at the transition into the EpCAM+ stage. This phenotype is caused by selective loss of BMP7-mediated signaling essential for LC differentiation, whereas TGFβR signaling is intact, maintaining cells in a quiescent state. Transgenic Cbfβ2 expression at the neonatal stage, but not at the adult stage, restored differentiation from Cbfβ2-deficient LC precursors. Loss of developmental potential in skin-residential precursor cells was accompanied by diminished BMP7–BMPR1A signaling. Collectively, our results reveal an essential requirement for the Cbfβ2 variant in LC differentiation and provide novel insight into how the establishment and homeostasis of the LC network is regulated.
Sofosbuvir‐velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct‐acting antiviral regimen
Authors: Edward J. Gane, Mitchell L. Shiffman, Kyle Etzkorn, Giuseppe Morelli, Catherine A.M. Stedman, Mitchell N. Davis, Federico Hinestrosa, Hadas Dvory‐Sobol, K.C. Huang, Anu Osinusi, John McNally, Diana M. Brainard, John G. McHutchison, Alex J. Thompson, Mark S. Sulkowski
Journal: Hepatology (2017)

The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct‐acting antiviral–based therapies remains unclear. In this multicenter, open‐label, phase 2 study, we evaluated the efficacy and safety of a fixed‐dose combination of sofosbuvir‐velpatasvir (400 mg/100 mg) plus weight‐adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct‐acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment. In total, 63 of 69 (91%; 95% confidence interval, 82%‐97%) patients achieved sustained virologic response at 12 weeks, including 36 of 37 (97%; 95% confidence interval, 86%‐100%) patients with hepatitis C virus genotype 1 infection, 13 of 14 (93%; 95% confidence interval, 66%‐100%) patients with genotype 2 infection, and 14 of 18 (78%; 95% confidence interval, 52%‐94%) patients with genotype 3 infection. Most adverse events were of mild or moderate severity. The most frequently reported adverse events were fatigue, nausea, headache, insomnia, and rash. One patient (1%) with genotype 1a infection discontinued all study drugs due to an adverse event (irritability). Conclusion: Retreatment of patients who previously failed direct‐acting antiviral–based therapies with sofosbuvir‐velpatasvir plus ribavirin for 24 weeks was well tolerated and effective, particularly those with hepatitis C virus genotype 1 or 2 infection. (H epatology 2017;66:1083‐1089).
Fetal Alcohol Spectrum Disorder—High Rates, High Needs, High Time for Action
Authors: Albert E. Chudley
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal