tbuckley/cabot-search huggingface dataset:
52 The effect of paracetamol legislation on admissions from paracetamol overdose in ireland
Authors: Ismail, B Christopher, C Kiat, E Tatro, R MacNicholas, AP McCormick, D Houlihan
Journal: Gut (2017)

Background  Paracetamol overdose (POD) is a prevalent issue worldwide and ease of access has been described as a principal factor for the drug so commonly used. In 2001, Ireland introduced a pack size legislation limiting access to 24-tablets in a pharmacy and 12-tablets in a non-pharmacy setting within a single transaction. To date no study has been published to assess the impact of the legislation at a national level.  Aim  The aim of this study is to assess whether the 2001-legislation has reduced hospital admissions from POD in Ireland.  Method  Data for POD from 1997 to 2011 was obtained from Healthcare Pricing Office, HSE, which collects data for inpatient admissions to hospitals in Ireland. The data from the five years before and after the legislation was compared (1997-2001vs.2002-2006). Data from 2002–2006 was then compared to a further five years (2007-2011) to assess whether the changes were maintained.  Results  There were a total of 14 225 patients admitted from 1997-2006. 7647 patients were admitted from 1997-2001 and 6414 from 2002-2006. There was a statistically significant difference between the mean number of admission during these periods (1529±72.7 vs 1315.6±140.78;p-value 0.0166).  From the year 2007-2011, 5719 patients were admitted. When comparing 2002-2006 with 2007-2011, a statistically significant difference was again noted (1315.6±140.78 vs 1143.80±85.73;p-value 0.0481).  Conclusions  This study has demonstrated that the 2001-legislation has significantly reduced POD admissions in Ireland. Results of this study can potentially be used as a basis for legislation on other potential harmful substances for example minimum pricing for alcohol which the Irish government is currently reviewing.
Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma
Authors: Michail S. Lionakis, Kieron Dunleavy, Mark Roschewski, Brigitte C. Widemann, John A. Butman, Roland Schmitz, Yandan Yang, Diane E. Cole, Christopher Melani, Christine S. Higham, Jigar V. Desai, Michele Ceribelli, Lu Chen, Craig J. Thomas, Richard F. Little, Juan Gea-Banacloche, Sucharita Bhaumik, Maryalice Stetler-Stevenson, Stefania Pittaluga, Elaine S. Jaffe, John Heiss, Nicole Lucas, Seth M. Steinberg, Louis M. Staudt, Wyndham H. Wilson
Journal: Cancer Cell (2017)
Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study
Authors: Tom van der Hulle, Whitney Y Cheung, Stephanie Kooij, Ludo F M Beenen, Thomas van Bemmel, Josien van Es, Laura M Faber, Germa M Hazelaar, Christian Heringhaus, Herman Hofstee, Marcel M C Hovens, Karin A H Kaasjager, Rick C J van Klink, Marieke J H A Kruip, Rinske F Loeffen, Albert T A Mairuhu, Saskia Middeldorp, Mathilde Nijkeuter, Liselotte M van der Pol, Suzanne Schol-Gelok, Marije ten Wolde, Frederikus A Klok, Menno V Huisman, Anne J Fogteloo, Lucia J M Kroft, Marjolein P Brekelmans, René M J Vermaire, Hanny Bastiaansen-Bergsma, Jossi S Biedermann, Adinda Klijn, Sanne van der Voort, Arthur W E Lieveld, Peter Y de Jong, Cees G Schaar, Antonio Iglesias del Sol
Journal: The Lancet (2017)
Abstract 380: Resident Cardiac Fibroblasts Give Rise to Periostin+ Myofibroblasts Which are the Primary Mediators of Cardiac Fibrosis
Authors: Onur Kanisicak, Hadi Khalil, Jason Karch, Matthew Brody, Suh-Chin Lin, Michelle Sargent, Jeffery D Molkentin
Journal: Circulation Research (2015)

Resident cardiac fibroblasts (CFs) are potential therapeutic targets in treating or preventing heart failure since they play a critical role in cardiac remodeling and fibrosis after injury or with prolonged stress stimulation. Heterogeneity among activated fibroblasts within the heart has been noted by a number of previous studies in the literature. In addition to resident CFs, many cell types such as endothelial, perivascular and bone marrow cells have been suggested to go through a mesenchymal transition and acquire a myofibroblast-like phenotype during disease conditions. Hence, the cellular origin of the activated myofibroblast within the heart remains uncertain, in part because of a lack in reliable genetic strategies to define cellular lineage. Recent studies suggest that epicardial precursor cells expressing transcription factor 21 (Tcf21) give rise to resident CFs in the adult heart. In addition, the secreted matricellular protein periostin (Postn), appears to be expressed only within activated fibroblasts (myofibroblasts) within the heart. Here we used Tcf21-MerCreMer (Tcf21MCM) knockin mice and Postn-MerCreMer (PostnMCM) knock-in (KI) mice to lineage trace resident CFs and myofibroblasts with injury stimulation. To account for other potential cellular lineages giving rise to fibroblasts in the heart we also performed lineage tracing with the mouse genetic models including LysM-Cre (macrophage), ckit-Cre (bone marrow), Tie2CreERT2 (endothelial) and Myh11-CreERT2 (smooth muscle) in conjunction ROSA26 (R26) locus based loxP inactivated reporter alleles. Results of this study indicate that the Tcf21+ resident CFs are the predominant source for the activated periostin+ MFs which are the key mediators of extracellular matrix (ECM) production and ECM stability in heart whereas the contribution of other lineages to MFs are minimal. Additionally, we have performed single cell RNA sequencing on TCF21+ and Postn+ isolated CFs pre and post myocardial injury in order to define the fibroblast lineage itself at greater molecular depth.
Influence of platinum-based chemotherapy on disseminated tumor cells in patients with primary ovarian cancer
Authors: P. Wimberger, R. Kimmig, A. Schulte, M. E. Scheulen, S. Kasimir-Bauer
Journal: Journal of Clinical Oncology (2006)

5067 Background: Recent studies in patients (pts) with breast cancer have demonstrated the prognostic significance of disseminated tumor cells (DTC) in the bone marrow (BM) which even can survive high-dose chemotherapy. For ovarian cancer, the impact of chemotherapy on DTC is unknown. Here we evaluated whether first-line chemotherapy with carboplatinum and paclitaxel can eliminate DTC in BM and peripheral blood (PB) of pts with primary ovarian cancer (OC, FIGO IC-IIIC). Methods: PB of 28 pts with OC and bilateral BM aspirates of 18/28 pts were assessed for DTC before and after chemotherapy using density gradient centrifugation and an immunocytochemical cytokeratin (CK) assay with the anti-CK antibody A45-B/B3. Results: We identified CK+ cells in 7/28 blood samples (25%) before therapy with a mean number of 2 cells/20 ml (range 1–3). After chemotherapy, CK+ cells were detected in 3/28 blood samples (11%) with a mean number of 9 cells/20 ml (range 1–18). In 5 out of these 7 CK+ patients prior to therapy, no CK+ cells were found after therapy, a no change and a reduction of DTC could be demonstrated in one patient each. CK+ cells were found in 10/18 BM samples (56%) before therapy with a mean number of 2 cells/9x10E6 BM cells (range 1–7) and in 8/18 BM samples (44%) after therapy with a mean number of 10 cells/9x10E6 BM cells (range 2–35). After chemotherapy, no CK+ cells were found in 6 pts, no change in DTC counts was documented in 2 pts and a significant enhancement of DTC was shown in 6 pts, including 4 pts who had no CK+ cells before chemotherapy. Conclusions: DTC are frequently present in the BM and PB of pts with OC and are not always successfully eliminated after platinum-based chemotherapy. It has to be considered, whether these pts might profit from an additive immunotherapy as already shown by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells (Proc Am Assoc Cancer Res 46: 4260, 2005). No significant financial relationships to disclose.
A First-in-Human Study of Autologous T Lymphocytes with Antibody-Dependent Cell Cytotoxicity (ADCC) in Patients with B-Cell Non-Hodgkin Lymphoma (NHL)
Authors: Michelle Poon, Yeh Ching Linn, Noriko Shimasaki, Lip Kun Tan, Liang Piu Koh, Elaine Coustan-Smith, Dario Campana
Journal: Blood (2016)
GENE-05. EVALUATION OF CLINICAL AND MOLECULAR FEATURES IN INFANTS AGED LESS THAN 12 MONTHS TREATED FOR AGGRESSIVE BRAIN TUMORS
Authors: Ludovica Facchini, Milena Guidi, Maurizio Lucchesi, Anna Maria Buccoliero, Laura Giunti, Carla Mocheo, Lorenzo Genitori, Iacopo Sardi
Journal: Neuro-Oncology (2017)

The treatment for childhood brain tumors are well defined for older children but are not as well defined for infants younger than twelve months of age. Although they generally have a poor prognosis, it is related to several factors such as malignant histological type, size and location of the tumor, immature stage of fetal development, and treatment-related complications. We retrospectively reviewed data about these patients at our institution. We identified 10 infants aged less than 12 months, 3 females and 7 males. The median age at diagnosis was 56 days (range: 1–279 days; mean: 80,9 days). Tumor resection was followed by adjuvant chemotherapy including two cycles of high-dose thiotepa with autologous stem cells rescue. No patient had radiation therapy as first line program treatment. Pathological diagnosis was available in all cases: 3 anaplastic astocytoma (AA), 2 glioblastoma multiforme (GBM), 2 primitive neuroectodermal tumor (PNET), 2 atypical teratoid/rhabdoid tumors (AT/RT) and one glioneuronal tumor with neuropil-like islands (GTNI). In three cases diagnosis was prenatal. Two AT/RT cases had germline mutations of INI-1 gene (rhabdoid tumor predisposition syndrome) and GTNI patient had a somatic trisomy 8 mosaicism. About our series, at the time of survival analysis, median overall survival (OS) was not reached. Seven patients are still alive. No statistically significant differences were detected in subgroups analysis. This is probably due to the small number of patients for each subgroups. However, a worse survival was seen in children with tumor that harboring germline mutations. The median OS for these patients was 18 months compared to a not reached median OS for patients with sporadic tumors (p: 0,06 with Mantel-Cox test). High-dose chemotherapy after surgery can be afforded in front-line therapy of infants aged less than 12 months without excessive morbidity and rather encouraging results.
FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal Cancer
Authors: Gianluca Tomasello, Fausto Petrelli, Michele Ghidini, Alessandro Russo, Rodolfo Passalacqua, Sandro Barni
Journal: JAMA Oncology (2017)

The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial.
Стан мікробіоти порожнини товстої кишки дітей, хворих на гострий ентероколіт, які перебувають на природному вигодовуванні, при інфікованості грудного молока
Authors: L.I. Sydorchuk, D.V. Rotar, A.S. Sydorchuk, A.V. Gumenna, O.O. Blinder, I.Y.  Sydorchuk
Journal: GASTROENTEROLOGY (2017)

Актуальність. Проблема гострого ентероколіту є надзвичайно актуальною внаслідок їх знач­ного поширення й порівняно низької ефективності етіотропного та патогенетичного лікування. Метою дослідження було вивчення таксономічного складу і популяційного рівня мікробіоти вмісту порожнини товстої кишки дітей, хворих на гострий ентероколіт, при природному вигодовуванні молоком, інфікованим Staphylococcus aureus, а також розкрити механізми колонізації досліджуваного біотопу мікроорганізмами. Матеріали та методи. Бактеріологічному й мікологічному дослідженню підлягав вміст порожнини товстої кишки 53 дітей віком від одного до шести місяців, хворих на ентероколіт, які перебували на грудному вигодовуванні інфікованим молоком, контрольну групу становили 35 зразків вмісту порожнини товстої кишки здорових дітей, також досліджувалось грудне молоко матерів-годувальниць обох груп. Результати. Дослідження грудного молока показали, що в 49 (92,45 %) пробах виділено та ідентифіковано Staphylococcus aureus, а в 4 (7,55 %) — Staphylococcus epidermidis (3,0–7,0 lg КУО/мл (М ± m = (4,37 ± 0,38) lg КУО/мл)). S.аureus та S.еpidermidis виділяли зі зразків випорожнень усіх хворих дітей у 2,92 раза частіше, ніж у практично здорових дітей. На фоні вигодовування дитини інфікованим молоком із досліджуваного біотопу елімінують еубактерії, пептокок, а E.coli Hly+, протеї, цитробактер і стафілококи контамінують порожнину товстої кишки. Популяційний рівень Bifidobacterium знижується на 43,03 % (на 3 порядки), Lactobacillus — на 32,24 % (на 2 порядки). Спостерігається заселення товстої кишки E.coli Hly+ у 16,48 %, протеями — у 22,53 %, цитробактерами — у 3,77 %, пептококами — у 15,09 %, пептострептококами — у 55,42 % і стафілококами — у 91,43 %. Висновки. Доведено, що сформований дисбактеріоз товстокишкового мікробіоценозу в дітей грудного віку, хворих на гострий ентероколіт, характеризується зменшенням кількості біфідобактерій і лактобактерій та зростанням кількості й значення в мікробіоценозі грамнегативних умовно-патогенних ентеробактерій, бактероїдів та грампозитивних умовно-патогенних бактерій роду Staphylococcus, Peptostreptococcus і Peptococcus.
Precision Medicine: Functional Advancements
Authors: Thomas Caskey
Journal: Annual Review of Medicine (2017)

Precision medicine was conceptualized on the strength of genomic sequence analysis. High-throughput functional metrics have enhanced sequence interpretation and clinical precision. These technologies include metabolomics, magnetic resonance imaging, and I rhythm (cardiac monitoring), among others. These technologies are discussed and placed in clinical context for the medical specialties of internal medicine, pediatrics, obstetrics, and gynecology. Publications in these fields support the concept of a higher level of precision in identifying disease risk. Precise disease risk identification has the potential to enable intervention with greater specificity, resulting in disease prevention-an important goal of precision medicine.
Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study
Authors: A B Halpern, M Othus, E M Huebner, S A Buckley, E L Pogosova-Agadjanyan, K F Orlowski, B L Scott, P S Becker, P C Hendrie, T L Chen, M-E M Percival, E H Estey, D L Stirewalt, R B Walter
Journal: Leukemia (2017)
EXTH-27. VALIDATION OF BMI-1 AS A THERAPEUTIC TARGET IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Shiva Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Rachid Drissi
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is overexpressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is overexpressed in DIPG patient tissue samples and in patient-derived cancer stem cells independent of H3K27 mutation status. BMI-1 downregulation leads to the inhibition of DIPG patient-derived stem cell proliferation, cell cycle signaling, self-renewal, telomerase expression and activity, causes increased apoptosis, and suppresses DIPG cell invasion. Moreover, targeted inhibition of BMI-1 sensitizes DIPG cells to radiomimetic drug-induced DNA damage. Together, our data validate BMI-1 as a potential therapeutic target to treat children with DIPG regardless of H3 mutation status.
Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement From the American Heart Association
Authors: Jennifer L. Cook, Monica Colvin, Gary S. Francis, Kathleen L. Grady, Timothy M. Hoffman, Mariell Jessup, Ranjit John, Michael S. Kiernan, Judith E. Mitchell, Francis D. Pagani, Michael Petty, Pasala Ravichandran, Joseph G. Rogers, Marc J. Semigran, J. Matthew Toole
Journal: Circulation (2017)
Concurrent use of long-acting bronchodilators in COPD and the risk of adverse cardiovascular events
Authors: Samy Suissa, Sophie Dell'Aniello, Pierre Ernst
Journal: European Respiratory Journal (2017)

The cardiovascular risk of concurrently using long-acting β 2 -agonists (LABAs) and anticholinergics (LAMAs) in COPD is uncertain. We assessed the comparative cardiovascular and cerebrovascular safety of adding a second long-acting bronchodilator in patients with COPD. We identified a cohort of COPD patients, new users of LABA or the LAMA tiotropium during 2002–2012, from the UK Clinical Practice Research Datalink. Using high-dimensional propensity scores, each patient adding a second bronchodilator was matched with a patient who remained on monotherapy. Patients were followed for 1 year for the occurrence of acute myocardial infarction (AMI), stroke, heart failure and arrhythmia. The cohorts included up to 31 174 patients adding a bronchodilator matched to 31 174 patients remaining on bronchodilator monotherapy. Adding a long-acting bronchodilator, compared to remaining on monotherapy, was not associated with an increased risk of AMI (hazard ratio (HR) 1.12, 95% CI 0.92–1.36), stroke (HR 0.87, 95% CI 0.69–1.10) or arrhythmia (HR 1.05, 95% CI 0.81–1.36), but the risk was elevated for heart failure (HR 1.16, 95% CI 1.03–1.30). Adding a second long-acting bronchodilator in the real-world-setting treatment of COPD does not increase the risk of most cardiovascular events. The modest increase for heart failure warrants further investigation.
Don't admit defeat: A new dawn for the item in visual search
Authors: Stefan Van der Stigchel, Sebastiaan Mathôt
Journal: Behavioral and Brain Sciences (2017)

Abstract Even though we lack a precise definition of “item,” it is clear that people do parse their visual environment into objects (the real-world equivalent of items). We will review evidence that items are essential in visual search, and argue that computer vision – especially deep learning – may offer a solution for the lack of a solid definition of “item.”
Development of a histology-guided gene expression tumor classifier for cancer of unknown primary (CUP).
Authors: Linda R. Mileshkin, Keith Byron, Richard Tothill, Fan Shi, Lisa Paiman, Justin Bedo, Adam Kowalczyk, Evangeline Buela, Robert Klupacs, David Bowtell
Journal: Journal of Clinical Oncology (2014)

11108 Background: Accurate identification of the primary tumor in cases of cancer of unknown primary (CUP) is required for effective treatment selection and improved patient outcomes. Here we present the development and clinical validation of a histology-guided gene expression classifier. Methods: RNA from 450 formalin-fixed paraffin embedded tissue samples of known origin comprising 18 tumor groups were used to train and develop the classifier. Whole-genome expression data was collected from each sample using Illumina DASL bead-based arrays. A hierarchical tumor classifier utilizing both conventional histopathology and gene expression data was developed using a binary support vector machine, together with recursive feature elimination. The classifier was then validated on an independent cohort of 94 tumors of known origin and 58 CUP samples. Results: Based on the validation set of tumors, the classifier demonstrated an accuracy of 89% for the highest predicted tumor class, increasing to 98% for the correct prediction within the two highest similarity scores. When applied to CUP samples having a presumed final clinical diagnosis of a primary site six months following gene expression analysis (n=49), the classifier was found to improve the accuracy of histology alone from 33% to 78% for a single prediction and from 73% to 90% within the two highest predicted tumor class scores. Conclusions: This study demonstrates that combining gene expression data and conventional histopathology improves the accuracy of determining the primary site of origin in cases of CUP.
Genotypes are related to neurocognitive performance but not concussion history in collegiate student-athletes
Authors: Eric E Hall, Graham D. Cochrane, Mark Sundman, Matthew C Kostek, Kirtida Patel, Kenneth P Barnes, Caroline J Ketcham
Journal: British Journal of Sports Medicine (2017)

Background Single-nucleotide polymorphisms (SNPs) of neurologically relevant genes play a role in concussions from increasing susceptibility or hampering cognitive performance. Objective The purpose of this study was to investigate the effects of polymorphisms of APOE, APOE promoter, COMT and DRD2 on baseline neurocognitive function and concussion history in collegiate student-athletes. Design Cross-sectional. Setting Collegiate campus in North Carolina. Participants 262 (194 males, 68 females) collegiate student-athletes. Assessment of risk factors Buccal mucosa swabs were collected from participants. SNP genotyping was run on all samples to determine APOE, APOE promoter, COMT, and DRD2 genotypes. Participants were split into three groups based on their genotypes for each gene. Outcome measures Participants completed the Immediate Post-Concussion Assessment and Cognitive Testing neurocognitive assessment which generated composite scores on Verbal Memory, Visual Memory, Visuomotor Speed, and Reaction Time as well as Impulse Control Results None of the genotype variables influenced number of concussions (p&gt;0.05). MANOVA analysis determined no differences for APOE promoter and DRD2 genotypes (p&gt;0.05). There were statistical differences for APOE for Visuomotor composite (APOE-e3 (m=41.2, %95 CI [40.8, 42.1]) vs e4 (m=39.1, %95 CI [37.8, 40.5], p=0.017) and Reaction Time (APOE-e4 (m=0.62, %95 CI [0.60, 0.64]) was different than both e2 (m=0.57, %95 CI [0.54, 0.60] and e3(m=0.58, %95 CI [0.56, 0.59], p&lt;0.005). There were also differences for COMT for Impulse Control (Val/Val (m=6.2 %95 CI [5.4, 7.1]) was different Val/Met (m=4.7, %95 CI [4.1, 5.2] and Met/Met (m=4.7, %95 CI [3.8, 5.6], p&lt;0.02). Conclusions APOE and COMT single nucleotide polymorphisms lead to significant differences in neurocognitive performance at baseline but not concussion history. Competing interests None.