tbuckley/cabot-search huggingface dataset:
The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000–2015)
Authors: Imran Aziz, Mohammad F Peerally, Jodie-Hannah Barnes, Vigneswaran Kandasamy, Jack C Whiteley, David Partridge, Patricia Vergani, Simon S Cross, Peter H Green, David S Sanders
Journal: Gut (2016)

Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general.To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA.Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre. A diagnosis of either seronegative CD (SNCD) or seronegative non-CD (SN-non-CD) was reached. Baseline comparisons were made between the groups, with 343 seropositive CD subjects serving as controls.Of the 200 SNVA cases, SNCD represented 31% (n=62) and SN-non-CD 69% (n=138). The human leucocyte antigen (HLA)-DQ2 and/or DQ8 genotype was present in 61%, with a 51% positive predictive value for SNCD. The breakdown of identifiable causes in the SN-non-CD group comprised infections (27%, n=54), inflammatory/immune-mediated disorders (17.5%, n=35) and drugs (6.5%, n=13; two cases related to A2RBs). However, no cause was found in 18% (n=36) and of these 72% (n=26/36) spontaneously normalised duodenal histology while consuming a gluten-enriched diet. Following multivariable logistic regression analysis an independent factor associated with SN-non-CD was non-white ethnicity (OR 10.8, 95% CI 2.2 to 52.8); in fact, 66% of non-whites had GI infections. On immunohistochemistry all groups stained positive for CD8-T-cytotoxic intraepithelial lymphocytes. However, additional CD4-T helper intraepithelial lymphocytes were occasionally seen in SN-non-CD mimicking the changes associated with refractory CD.Most patients with SNVA do not have CD, in particular those who are not white. Furthermore, a subgroup with no obvious aetiology will show spontaneous histological resolution while consuming gluten. These findings suggest caution in empirically prescribing a gluten-free diet without investigation.
Single cell copy number variation analysis of circulating tumor cells in gastrointestinal cancer patients for study of intra-patient genomic heterogeneity.
Authors: Man Chun Leong, Chong Shi, Yunyun Niu, Sin Chi Ho, Lianyuan Tao, Dianrong Xiu, Haixing Wang, Andrew Wu, Sijia Lu
Journal: Journal of Clinical Oncology (2016)

e23122 Background: Tumor heterogeneity represents a key hallmark of cancer which complicates anti-cancer treatments. Presence of sub-clonal tumor population may be undetected through bulk tumor sequencing, and may emerge as dominant tumor clone in the course of therapy. This limitation may potentially be surmounted with longitudinal genomic analysis of circulating tumor cells (CTC) at single cell level. Methods: Peripheral blood samples from metastatic gastrointestinal (gastric, colorectal, and pancreatic) cancer pts were enriched for CTCs using ClearCell FX system (Clearbridge Biomedics). Enriched samples were fluorescently labelled with DAPI, EpCAM and CD45 antibodies to aid identification and recovery of single CTC/CTC clusters using micropipette. Whole genome sequencing was performed on individual cells/clusters, following MALBAC whole genome amplification (Yikon Genomics). Copy number variation (CNV) profile of CTCs were analyzed to identify chromosomal gains and losses. HeLa cells were used as positive control to verify the assay. Results: A total of 40 cells (23 CTCs and 17 leukocytes) were recovered from 5 metastatic cancer pts. Both EpCAM-expressing(10%) and EpCAM-negative(90%) CTCs were identified. 38 cells were successfully amplified and sequenced with average mapping rate of 95%. Copy number variation profile analysis revealed an elevated level of copy number alterations among putative CTCs (CD45-/DAPI+). Two distinct CNV profiles were observed in one of the colorectal patients, indicative of genomic heterogeneity or sub-clonal population. Conclusions: Individual CTCs from gastrointestinal cancer pts were successfully recovered and sequenced. Information on heterogeneity of CTCs can be harnessed to study the emergence and underlying mechanisms of drug resistance. CTC liquid biopsy presents an opportunity for longitudinal monitoring of pt mutation profile throughout treatment.
Abstract 11983: Auraptene, a Coumaric Compounds Analogous, Improved the Worsening of Systolic Function by Activating Mitochondrial Function After Myocardial Infarction in Rats
Authors: Yoichi Sunagawa, Miho Suzuki, Masafumi Funamoto, Yasufumi Katanasaka, Hidetoshi Suzuki, Akira Murakami, Hiromichi Wada, Atsushi Imaizumi, Tadashi Hashimoto, Akira Shimatsu, Takeshi Kimura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2014)

Introduction: Heart failure is associated with pathological growth and mitochondrial dysfunction of constituent cardiomyocytes. To achieve effective oral pharmacological therapy for heart failure, we screened compounds isolated from natural products and found that auraptene derived from the peel of Citrus Hassaku may be applicable to pharmacological therapy for heart failure. Hypothesis: We assessed the hypothesis that auraptene could improve the deterioration of mitochondrial function and the development of heart failure in rats with myocardial infarction (MI). Methods and Results: In cultured cardiomyocytes, auraptene (2.5-10 μM) dose-dependently repressed phenylephrine-induced hypertrophic responses such as increase in cell size and ANF and ET-1 promoter activations. Auraptene also activated mitochondrial- and lipid metabolism-related gene transcriptions, such as PGC1α, PPARα/γ, mCPT1, UCP3, and PDK4. One week after operation, 22 rats with a moderate size of MI (Fractional shortening (FS) &lt; 40%) were then randomly assigned to vehicle (n=8), auraptene low-dose (5 mg/kg/day, n=7), or high-dose (50 mg/kg/day, n=7). Oral daily treatments with these agents were continued for 6 weeks. There were no differences in left ventricle (LV) geometric and functional data among the 3 MI groups before treatment. After treatment, LVFS was significantly higher in the auraptene low-dose (21%, p &lt; 0.0001) and high-dose (26%, p &lt; 0.0001) groups than the vehicle group (16%). LV wall thickness in the remote non-infarct area was significantly thinner in the auraptene low-dose (1.4 mm, p &lt; 0.01) and high-dose (1.2 mm, p &lt; 0.0001) groups than the vehicle group (2.5 mm). Histological analysis demonstrated that auraptene treatment significantly suppressed MI-induced increases in myocardial cell diameter and perivascular fibrosis compared with vehicle treatment. Moreover, auraptene also prevented the activations of ANF and MCP-1 mRNA levels and up-regulated mitochondrial- and lipid metabolism-related gene transcriptions in LV. Conclusions: Auraptene treatment prevents the worsening of LV systolic function and represses hypertrophy after MI in adult rats. A natural compound, auraptene is expected as a novel useful agent for heart failure therapy in humans.
N‐terminal fragment of the type‐B natriuretic peptide (NT‐proBNP) contributes to a simple new frailty score in patients with newly diagnosed multiple myeloma
Authors: Paolo Milani, S. Vincent Rajkumar, Giampaolo Merlini, Shaji Kumar, Morie A. Gertz, Giovanni Palladini, Martha Q. Lacy, Francis K. Buadi, Suzanne R. Hayman, Nelson Leung, David Dingli, John A. Lust, Yi Lin, Prashant Kapoor, Ronald S. Go, Yi L. Hwa, Wilson I. Gonsalves, Steven R. Zeldenrust, Robert A. Kyle, Angela Dispenzieri
Journal: American Journal of Hematology (2016)

Multiple myeloma (MM) patient frailty has been delineated primarily by age and ECOG performance score (PS) and recently by the IMWG frailty score based on functional status [Activity of Daily Living (ADL) and Instrumental-ADL scores], comorbidities [Charlson-comorbidity-index (CCI)] and age. It was hypothesized that N-terminal natriuretic peptide type B (NT-proBNP) might be both a more convenient measure of frailty and a predictor of overall survival (OS). Three-hundred and fifty-one consecutive symptomatic MM patients who were seen at Mayo Clinic within 30 days of diagnosis and who had blood stored were eligible. Data from the first visit was abstracted and used to calculate an ADL, CCI, and measure the NT-proBNP level. The best cutoff of NT-proBNP predicting OS was 300 ng/L. Variables predictive for OS were ECOG-PS, age, CCI, ADL, ISS, revised-ISS, and NT-proBNP. On multivariate analysis age ≥70, PS ≥2, and NT-proBNP ≥300 were independent predictors of survival. Patients were assigned a score of 1 for each of these variables, creating stages I-IV with scores of 0-3 points, respectively. The median OS from diagnosis was not reached, 58, 28, and 18 months (P < 0.0001), respectively. This frailty risk schema was independent of initial therapy and the revised-ISS. NT-proBNP is a useful predictor of survival independent of age and PS. It is a widely available biomarker that could be added to the panel of laboratory tests of newly diagnosed MM patients and serve as a simple and objective tool of determining frailty in clinical practice. Am. J. Hematol. 91:1129-1134, 2016. © 2016 Wiley Periodicals, Inc.
Abstract 17308: Leukoaraiosis is Associated With Atrial Fibrillation and Greater Disability at 90-days in Patients Hospitalized With a Cardioembolic Stroke
Authors: Ameeta Karmarkar, Johanna Helenius, Nils Henninger, David D McManus
Journal: Circulation (2015)

Introduction: Atrial fibrillation (AF) has been associated with a poor post-stroke prognosis. AF has been linked to increased leukoaraiosis (LA) burden, which is associated with greater functional impairment after stroke. Hypothesis: We hypothesized that AF is associated with the severity of LA burden and thus impacts 90-day outcomes in patients hospitalized with acute cardioembolic ischemic stroke. Methods: We retrospectively analyzed 317 consecutive patients with acute cardioembolic ischemic stroke enrolled in the University of Massachusetts Medical Center’s Stroke Registry between 2010 and 2014. Stroke mechanism was determined according to the Causative Classification System. LA burden was graded on MRI using the Fazekas scale. Infarct volume was quantified on diffusion weighted images. Neurological deficit severity was assessed at admission according to the National Institutes of Health Stroke Scale (NIHSS). We evaluated the degree of disability using the modified Rankin score (mRS) at 90 days. Participants were categorized as having excellent (mRS 0-1), or poor (mRS 2-6) status. Results: A total of 132 patients were classified as having a definite (n=81) or probable (n=51) cardioembolic stroke. Of these, 54 (41%) had AF (previously known or newly documented). Compared to patients without AF, patients with AF were older (p=0.001), more likely to be receiving antihypertensives(p=0.008) and anticoagulants (p&lt;0.05 each), were associated with a poor outcome at 90 days. Conclusions: We observed that AF was related to severity of LA and that LA burden was an independent predictor of significant disability 90-days post-discharge. Further study is needed to investigate the links between AF, LA, and outcomes after cardioembolic stroke.
Encore - a Randomized, Controlled, Open-Label Non-Inferiority Study Comparing Eliglustat to Imiglucerase in Gaucher Disease Type 1 Patients Stabilized on Enzyme Replacement Therapy: 24-Month Results
Authors: Barry E. Rosenbloom, Timothy M. Cox, Guillermo I. Drelichman, Renata Cravo, Manisha Balwani, Thomas Andrew Burrow, Ana Maria Martins, Elena Lukina, Leorah H. Ross, Jennifer Angell, Judith Peterschmitt
Journal: Blood (2014)
Insulin vs Sulfonylureas for Second-Line Diabetes Treatment
Authors: Ilker Tasci, Umut Safer
Journal: JAMA (2014)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The clinical spectrum of mycosis fungoides in Tanzania, East Africa
Authors: M.L. Grijsen, R.G. Mtayangulwa, B. Naafs, P. Jansen, M.H. Vermeer, D. Mavura, E.J. Masenga, R. Willemze
Journal: British Journal of Dermatology (2016)

Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphomas and presents with cutaneous patches, plaques and/or tumours1. To date, few studies have reported on MF in Sub-Saharan Africa. In this case-series we illustrate the clinical spectrum of MF by presenting five patients who presented at the RDTC in Moshi, Tanzania, and were diagnosed based on clinical findings and routine histology performed on multiple skin biopsies. Additional immunohistochemistry was performed at LUMC, the Netherlands. A LUMC-expert panel comprising dermatologists and pathologists revised all histology samples. All patients were HIV-negative, and treated with topical potent steroids and antiparasitic treatment (single dose albendazole 400 mg) prior to the initiation of immunosuppressive therapy.

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Colonic biogeography in health and ulcerative colitis
Authors: Aonghus Lavelle, Grainne Lennon, Desmond C. Winter, P. Ronan O'Connell
Journal: Gut Microbes (2016)

The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.
P0858 : Early HCV RNA decline by baseline characteristics in HCV infected patients receiving sofosbuvir-based treatment: An Italian single center experience
Authors: A. Mangia, V. Piazzolla, R. Santoro, L. Mottola, D. Petruzzellis, M. Ripoli, F. Leone, D. Facciorusso
Journal: Journal of Hepatology (2015)
Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts
Authors: Nina Iszatt, Hein Stigum, Marc-André Verner, Richard A. White, Eva Govarts, Lubica Palkovicova Murinova, Greet Schoeters, Tomas Trnovec, Juliette Legler, Fabienne Pelé, Jérémie Botton, Cécile Chevrier, Jürgen Wittsiepe, Ulrich Ranft, Stéphanie Vandentorren, Monika Kasper-Sonnenberg, Claudia Klümper, Nynke Weisglas-Kuperus, Anuschka Polder, Merete Eggesbø
Journal: Environmental Health Perspectives (2015)

BackgroundInfant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects.ObjectivesWe investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity).MethodsWe pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure.ResultsWe found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01).ConclusionTo our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels.CitationIszatt N, Stigum H, Verner MA, White RA, Govarts E, Palkovicova Murinova L, Schoeters G, Trnovec T, Legler J, Pelé F, Botton J, Chevrier C, Wittsiepe J, Ranft U, Vandentorren S, Kasper-Sonnenberg M, Klümper C, Weisglas-Kuperus N, Polder A, Eggesbø M, OBELIX. 2015. Prenatal and postnatal exposure to persistent organic pollutants and infant growth: a pooled analysis of seven European birth cohorts. Environ Health Perspect 123:730–736; http://dx.doi.org/10.1289/ehp.1308005
Partial Characterization and In Vitro Expansion of Putative CLL Precursor/Stem Cells Which Are Dependent on Bone Marrow Microenvironment for Survival
Authors: Medhat Shehata, Rainer Hubmann, Martin Hilgarth, Susanne Schnabl, Dita Demirtas, Elina Ponath, Ekaterina Brynzak, Sabine Strommer, Volker Wachek, Alexander Hauswirth, Berthold Streubel, Katrina Vanura, Josef Schwarzmeier, Alexander Gaiger, Christoph Zielinski, Peter Valent, Ulrich Jaeger
Journal: Blood (2010)
PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma
Authors: Tian Luo, Cristina Loira-Pastoriza, Harshad P. Patil, Bernard Ucakar, Giulio G. Muccioli, Cynthia Bosquillon, Rita Vanbever
Journal: Journal of Controlled Release (2016)
Assessing the reproducibility of exome copy number variations predictions
Authors: Celine S. Hong, Larry N. Singh, James C. Mullikin, Leslie G. Biesecker
Journal: Genome Medicine (2016)

Reproducibility is receiving increased attention across many domains of science and genomics is no exception. Efforts to identify copy number variations (CNVs) from exome sequence (ES) data have been increasing. Many algorithms have been published to discover CNVs from exomes and a major challenge is the reproducibility in other datasets. Here we test exome CNV calling reproducibility under three conditions: data generated by different sequencing centers; varying sample sizes; and varying capture methodology.Four CNV tools were tested: eXome Hidden Markov Model (XHMM), Copy Number Inference From Exome Reads (CoNIFER), EXCAVATOR, and Copy Number Analysis for Targeted Resequencing (CONTRA). To examine the reproducibility, we ran the callers on four datasets, varying sample sizes of N = 10, 30, 75, 100, 300, and data with different capture methodology. We examined the false negative (FN) calls and false positive (FP) calls for potential limitations of the CNV callers. The positive predictive value (PPV) was measured by checking the CNV call concordance against single nucleotide polymorphism array.Using independently generated datasets, we examined the PPV for each dataset and observed wide range of PPVs. The PPV values were highly data dependent (p <0.001). For the sample sizes and capture method analyses, we tested the callers in triplicates. Both analyses resulted in wide ranges of PPVs, even for the same test. Interestingly, negative correlations between the PPV and the sample sizes were observed for CoNIFER (ρ = -0.80). Further examination of FN calls showed that 44 % of these were missed by all callers and were attributed to the CNV size (46 % spanned ≤3 exons). Overlap of the FP calls showed that FPs were unique to each caller, indicative of algorithm dependency.Our results demonstrate that further improvements in CNV callers are necessary to improve reproducibility and to include wider spectrum of CNVs (including the small CNVs). These CNV callers should be evaluated on multiple independent, heterogeneously generated datasets of varying size to increase robustness and utility. These approaches to the evaluation of exome CNV are essential to support wide utility and applicability of CNV discovery in exome studies.
A Key Commitment Step In Erythropoiesis Is Synchronized with the Cell Cycle Clock through Mutual Inhibition Between PU.1 and S-Phase Progression
Authors: Ramona Pop, Jeffrey R Shearstone, Qichang Shen, Ying Liu, Kelly Hallstrom, Miro Koulnis, Joost Gribnau, Merav Socolovsky
Journal: Blood (2010)
Relapse of Central Nervous System Lymphoma after systemic Lymphoma (SCNSL): Clinical Features and Outcome as compared to Primary CNS Lymphoma (PCNSL) Patients
Authors: Ingo Schmidt-Wolf, Hendrik Pels, Annika Jürgens, Katrin Patrij, Luise Wätzel, Ulrich Herrlinger, Holger Schulz, Andreas Engert, Michael Linnebank, Gabriele Schackert, Heinz Reichmann, Frank Kroschinsky, Marlies Vogt-Schaden, Gertlinde Egerer, Carlo Schaller, Monika Lamprecht, Peter Hau, Martina Deckert, Rolf Fimmers, Christoph Bangard, Marcel Reiser
Journal: Blood (2008)