tbuckley/cabot-search huggingface dataset:
Fully Automated Identification of Dysplastic Neutrophil in Peripheral Blood Using the Positional Parameters Provided by the Coulter LH750 Analyzer.
Authors: Gina Zini, Mariagrazia Garzia, Antonella Di Mario, Bianca Maria Ricerca, Paola Piccioni, Michela Tarnani, Giuseppe d’Onofrio
Journal: Blood (2005)
Wearable Recording Devices for Surgical Training
Authors: George Shorten, Eugene Dempsey, Karthikeyan Kallidaikurichi Srinivasan
Journal: JAMA Surgery (2017)

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Humoral Immune Response after a Four-Site Intradermal Rabies Booster Vaccination in Previously Rabies Immunized HIV-Infected Adults
Authors: Suda Punrin, Jettanong Klaewsongkram, Terapong Tantawichien, Natchaya Ratananpinit, Wachiraporn Saengseesom, Rattana Suttisri
Journal: Journal of Allergy and Clinical Immunology (2017)
Combining web-based educational tools and mobile apps.
Authors: Vishal Kukreti, Ken Sutcliffe, Angela Dosis, Sherrie Hertz
Journal: Journal of Clinical Oncology (2012)

315 Background: Mobile apps (MA) can be useful resources to provide point of care information. Over 50% of patients use a smartphone (SP), 75% of North American physicians own a SP, and 58% of SP users have downloaded mobile MA. MA are more readily accessible than web-based tools and usable without network connectivity. Methods: Cancer Care Ontario (CCO) has developed MA for patients and providers using the principles of end user satisfaction, simplicity and intuitiveness. These MA are taken from established web based, validated educational modules. Designed to ensure a rich native experience for each platform (WP7 and iOS), CCO’s process includes proof of concept, information design, and user interface design supported by user acceptance testing. Results: Two MA have been created: “CCO Drug Formulary” and “CCO Symptom Management Guidelines Application”. The first MA provides information on both drugs and regimens used in cancer treatment for patients and providers through alternate navigation in the same MA. From launch in October 2011 until June 2012, the Drug Formulary app had 4,280 downloads, including 39% from Asia and 14% from Europe, suggesting a global market. The second app provides symptom management guidelines for providers, hence supporting clinical decision making at point of care. From January 2011 to June 2012, the Symptom Management Guidelines MA had 4,050 downloads, in a mainly North American market. Both patient and provider feedback on preliminary evaluation has been positive. Conclusions: Patients and providers are receptive to MA as a tool to deliver real-time information at point of care. MA are another interface to existing technology solutions and other rich data sources. Further research into patient outcomes from adoption of such technology is needed.
394TiP KEYNOTE-122: Phase 2 study of pembrolizumab versus standard-of-care chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal carcinoma
Authors: A.T.C. Chan, V. Lee, R. Ngan, M.-J. Ahn, Q.S. Ng, R.-L. Hong, J.-C. Lin, R.F. Swaby, C. Gause, S. Saraf, A. Spreafico
Journal: Annals of Oncology (2016)
Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations
Authors: Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A. Newton, Cindy Barba, Nicolai S.C. van Oers, Richard C. Wang, Christine Kim Garcia
Journal: Journal of Clinical Investigation (2017)

Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function. While these promoter mutations were initially identified as oncogenic drivers of cancer, individuals expressing the mutations have no history of cancer. Neither promoter mutation was found in population-based cohorts of similar or advanced age. The TERT promoter mutations were found more frequently in cis with the WT allele than the TERT coding sequence mutation. EBV-transformed lymphoblastoid B cell lines (LCLs) derived from subjects with TERT promoter mutations showed increased telomerase expression and activity compared with cell lines from family members with identical coding mutations. TERT promoter mutations resulted in an increased proliferation of LCLs and demonstrated positive selection over time. The persistence and recurrence of noncoding gain-of-function mutations in these cases suggests that telomerase activation is not only safely tolerated but also advantageous for clonal expansion.
Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassemia
Authors: Ampaiwan Chuansumrit, Pimprae Pengpis, Pat Mahachoklertwattana, Nongnuch Sirachainan, Preamrudee Poomthavorn, Witaya Sungkarat, Praguywan Kadegasem, Patcharin Khlairit, Pakawan Wongwerawattanakoon
Journal: Blood (2015)
Epigenomic Inactivation of RasGAPs Activates RAS Signaling in a Subset of Luminal B Breast Cancers
Authors: Rosalie Sears, Joe W. Gray
Journal: Cancer Discovery (2017)

Abstract Summary: Invasion and metastasis of a subset of aggressive luminal B breast cancers is driven by the concomitant inactivation of the RasGAPs DAB2IP and RASAL2. Inactivation of both proteins increases RAS activity and drives invasion, whereas inactivation of DAB2IP specifically promotes NF-κB–mediated epithelial–mesenchymal transition. Cancer Discov; 7(2); 131–3. ©2017 AACR. See related article by Olsen et al., p. 202.
Increased Bone Marrow Plasma Cell Infiltration Pre-Transplant Is Associated with Worse Outcomes in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation for Multiple Myeloma,
Authors: Nina Shah, Qaiser Bashir, Simrit Parmar, Yvonne T Dinh, Sofia Qureshi, Gabriela Rondon, Uday R Popat, Yago Nieto, Roy Jones, Richard Champlin, Muzaffar H. Qazilbash
Journal: Blood (2011)
A Novel Strategy for the Treatment of Acute Graft-Versus-Host Disease Using the Adsorbent To Remove Excessive Inflammatory Cytokines.
Authors: Akiyoshi Takami, Takanori Teshima, Koshin Ushizaki, Takumi Taniguchi, Tohru Endo, Hiroshi Sakurai, Yukio Kondo, Hirohito Yamazaki, Shigeru Shimadoi, Hirokazu Okumura, Shinji Nakao
Journal: Blood (2007)
Mir-29b Negatively Regulates Osteoclastic Cell Differentiation and Function: Implications for the Treatment of Multiple Myeloma-Related Bone Disease
Authors: Marco Rossi, Maria Rita Pitari, Nicola Amodio, Maria Teresa Di Martino, Emanuela Leone, Francesco Conforti, Francesco Maria Paolino, Cirino Botta, Teresa Del Giudice, Eleonora Iuliano, Manlio Ferrarini, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Blood (2012)
CSIG-18. miRNA/mRNA NETWORKS IN NEOPLASTIC VERSUS NORMAL GLIAL PRECURSOR CELLS WITHIN HUMAN GLIOMAS
Authors: Romane Auvergne, Adam Cornwell, Mikhail Osipovitch, Fraser Sim, Devin Chandler-Militello, Christopher Wu, Abdellatif Benraiss, Steven Goldman
Journal: Neuro-Oncology (2016)

Glioma and particularly glioblastoma (GBM) remains one of the most deadly cancers. The existence of tumor stem/progenitor cells, also called tumor precursor cells (TPCs), has been associated with both glioma initiation and aggressiveness. In this study, we suggest that glioma TPC result from the transformation of normal glial progenitor cells (GPC), and then, capable of dynamic interconversion between different sub-phenotypes. To identify the regulatory circuits specifying these states and enabling transitions between them, we compared the microRNA expression profiles of A2B5-defined human TPCs derived from both low- and high-grade gliomas, to normal adult and fetal GPCs; as well as with one another. Endogenous miRNA targets were identified by integrated analysis of miRNA/mRNA expression and interactions. We identified a discrete subset of miRNA substantially dysregulated in A2B5+ TPC at every stage of glioma development, and as a function of tumor grade and phenotype. More than forty percent of the differentially expressed miRNAs in A2B5+TPC were commonly dysregulated in normal human fetal versus adult GPCs. MiRNAs/mRNA pairs were collectively associated with cell movement, epithelial-mesenchymal transition, as well as with PI3/AKT, ILK and TGF-B signaling pathways. Taken together, our data shed light on the transcriptional dynamics of glial precursors over glioma initiation and malignant progression, and demonstrate how regulation of miRNA expression variation relates directly to neurodevelopmental stages. In addition, by establishing the miRNA/mRNA signatures of neoplastic versus normal glial precursors, our study provides a set of specific TPCs networks of potential therapeutic utility.
NTOX-08. SAFETY OF INTRA-ARTERIAL CHEMOTHERAPY IN THE TREATMENT OF BRAIN TUMOURS
Authors: David Fortin, Samuel Caux, Gerald Gahide
Journal: Neuro-Oncology (2016)

The treatment of brain tumors is greatly limited the delivery impediment caused by the blood-brain barrier and blood-tumor barrier. To circumvent this limitation, different approaches have been studied, including intra-arterial delivery. Because of a significant local increase in plasma-peak concentration, this strategy increases the local area under the curve, and translates into a 3 to 5.5 fold increase in intra-tumoral chemotherapy concentration. However, intra-arterial chemotherapy in the treatment of brain tumors has a notoriously bad name, thanks to prior trials led in past decades showing significant neurotoxicities. This toxicity was related to the choice of therapeutics. Different agents are now available devoid of such toxicity, and we believe it is now time to revisit this approach. In this paper, we present our experience regarding the safety of this intra-arterial chemotherapy. For 15 uninterrupted years now, we have been using intra-arterial chemotherapy in the treatment glioma, lymphomas and metastatic disease, using a varied array of agents: carboplatin, etoposide phosphate, melphalan, methotrexate and doxil. As each patient enrolled in our trials undergo an MR scan prior to each cycle on monthly basis, and all these reports are archived in a centralized medical informatics system (Ariane) we used a database search of keywords associated to vascular complications: stroke, lacuna, lacunar stroke, bleeding, hematoma, dissection, ischemia, ischemic, etc. Once a keyword was identified in a report, the chart was reviewed and the MR scan was pulled and also reviewed by a radiologist (GG). On a total of 3583 intra-arterial treatments in 722 patients, we found a total of 55 vascular complications, 28 of which were symptomatic (20 lacuna, 5 strokes). Asymptomatic findings were mostly small lacuna (n=21) and 4 small hematomas. In this paper, we provide a full breakdown of the data. We conclude that intraarterial chemotherapy is reasonably safe.
Longitudinal assessment of childhood optic gliomas: Relationship between brain imaging and optic pathway function
Authors: B. Falsini, I. Lazzareschi, A. Ruggiero, L. Ziccardi, L. Placentino, C. Colosimo, C. Di Rocco, R. Riccardi
Journal: Journal of Clinical Oncology (2007)

2087 Background: To evaluate longitudinally the relationship between brain imaging and functional findings in childhood optic gliomas (OG) by comparing over time magnetic resonance imaging (MRI) with flicker visual evoked potential (FVEP) changes. Methods: Fourteen children (median age 3 yrs, range: 2–7) suffering from OGs involving chiasm and retro-chiasmatic visual pathways underwent serial MRI and FVEP examinations over a median follow-up time of 38 months (range 12–76). FVEPs were monocularly recorded in response to 8 Hz sine-wave flicker stimuli presented in a mini-Ganzfeld according to a published technique (Trisciuzzi et al., Clin. Neurophysiol., 2004). MRI examinations were performed according to standard procedures. Longitudinal results of both tests were examined in a blind fashion by independent evaluators. FVEPs were judged to be improved, stable or worsened if changes in the amplitude and/or phase of the fundamental response component exceeded the limits of test-retest variability (±90th percentile) established in the same patients. MRI results were judged to show regression, stabilization or progression of OG based on its changes in size (±20%) or extension. Two to seven pairs (&lt; one month apart) of FVEP/MRI examinations per patient (median: 4, range 2–7) were collected. Agreement between test changes over time were evaluated by K-statistics. Results: Based on a total of 38 pairs of longitudinal FVEP/MRI examinations, both tests agreeed in showing worsening (progression), stabilization and improvement (regression) in 5, 10 and 15 cases, respectively. In 3 cases, FVEPs showed a worsening and MRI a stabilization, while in 5 cases FVEPs showed an improvement and MRI a stabilization. Agreement between FVEP and MRI changes was 78.9% (95% CI: ± 37%, K = 0.67, p &lt; 0.001). Conclusions: The results indicate that changes over time in FVEPs, an objective and non-invasive test of visual function, can accurately predict associated changes in OG size and extension as assessed by MRI, and suggest that the latter changes may have a significant impact on visual function during developmental age. No significant financial relationships to disclose.
320P Adjuvant chemotherapy comprising a paclitaxel and carboplatin regimen or paclitaxel and ifosfamide regimen for uterine carcinosarcoma, a single institutional retrospective study
Authors: Y. Ohtake, T. Nishikawa, H. Yoshida, M. Ishikawa, S. Ikeda, T. Kato, A. Shimomura, T. Shimoi, E. Noguchi, K. Yonemori, C. Shimizu, M. Yunokawa, K. Tamura
Journal: Annals of Oncology (2016)
Venous Thromboembolism Prophylaxis Practices in Acutely Ill Medical Patients with Heart Failure (NYHA Class III or IV): Findings from IMPROVE.
Authors: Ricardo Pavanello, James B. Froehlich, Victor Tapson, Jean-Francois Bergmann, Mashio Nakamura, Geno Merli, Mario Pini, Franco Piovella, Frederick A. Spencer, Gordon FitzGerald, Frederick A. Anderson
Journal: Blood (2005)
A Two-Part Study of Givinostat in Patients with Polycythemia Vera: Maximum Tolerated Dose Definition and Preliminary Efficacy Results
Authors: Guido Finazzi, Bruno Martino, Antonio Pezzuto, Andrzej Hellmann, Mary Frances McMullin, Richard Noble, Nikolas von Bubnoff, Nathalie Cambier, Jean-Pierre Marolleau, Marco Ruggeri, Alessandro M. Vannucchi, Ruben Mesa, Raoul Tibes, Paolo Bettica, Silvia DI Tollo, Alessandro Rambaldi
Journal: Blood (2016)
Phase 2 study of lenvatinib (LN) in patients (Pts) with RET fusion-positive adenocarcinoma of the lung
Authors: V. Velcheti, T. Hida, K.L. Reckamp, J.C. Yang, H. Nokihara, P. Sachdev, K. Feit, T. Kubota, T. Nakada, C.E. Dutcus, M. Ren, T. Tamura
Journal: Annals of Oncology (2016)
ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4
Authors: Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J. Koh, Evgenii Boriushkin, Anne Hamik, Alex K. Wong, Young-Kwon Hong
Journal: Circulation Research (2017)

Rationale: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. Objective: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. Methods and Results: Primary endothelial cells from dermal blood and lymphatic vessels (blood vascular endothelial cells and lymphatic endothelial cells [LECs]) were exposed to low-rate steady laminar flow. Shear stress–induced molecular and cellular responses were defined and verified using various mutant mouse models. Steady laminar flow induced the classic shear stress responses commonly in blood vascular endothelial cells and LECs. Surprisingly, however, only LECs showed enhanced cell proliferation by regulating the vascular endothelial growth factor (VEGF)-A, VEGF-C, FGFR3, and p57/CDKN1C genes. As an early signal mediator, ORAI1, a pore subunit of the calcium release–activated calcium channel, was identified to induce the shear stress phenotypes and cell proliferation in LECs responding to the fluid flow. Mechanistically, ORAI1 induced upregulation of Krüppel-like factor (KLF)-2 and KLF4 in the flow-activated LECs, and the 2 KLF proteins cooperate to regulate VEGF-A, VEGF-C, FGFR3, and p57 by binding to the regulatory regions of the genes. Consistently, freshly isolated LECs from Orai1 knockout embryos displayed reduced expression of KLF2, KLF4, VEGF-A, VEGF-C, and FGFR3 and elevated expression of p57. Accordingly, mouse embryos deficient in Orai1 , Klf2 , or Klf4 showed a significantly reduced lymphatic density and impaired lymphatic development. Conclusions: Our study identified a molecular mechanism for laminar flow–activated LEC proliferation.
Pharmacokinetic interaction study evaluating the effect of BMS-275291 on the pharmacokinetics of paclitaxel and carboplatin in patients with advanced or metastatic non-small cell lung cancer (NSCLC)
Authors: S. M. Malik, J. J. Hwang, C. P. Belani, S. Galbraith, S. Bai, N. A. Rizvi
Journal: Journal of Clinical Oncology (2004)

7309 Background: BMS-275291 is an inhibitor of matrix metalloproteinases. A large randomized, placebo controlled Phase II/III clinical study has been conducted to examine whether adding BMS-275291 to carboplatin plus paclitaxel therapy would improve survival in advanced NSCLC. Objective: This study was conducted to examine the effect of BMS-275291 on the plasma pharmacokinetics (PK) of paclitaxel and carboplatin when administered together to patients with advanced NSCLC. Methods/Results: Treatment with intravenous infusion of paclitaxel (200 mg/m2) and carboplatin (AUC=6) was commenced on Day 1 and repeated q 21 days. BMS-275291 1200 mg was given orally daily starting on Day 2. PK sampling for paclitaxel and carboplatin were obtained on Day 1 and 22, and for BMS-275291 on Day 22. 18 patients (11 male, 7 female) with Stage IIIB or IV NSCLC were enrolled. The median age was 61.5 yrs. 2 patients had grade 4 hypersensitivity reactions to paclitaxel including 1 patient who had a cardiac arrest. Both patients recovered. Grade 3 or 4 neutropenia was seen in 7 and 3 patients respectively and grade 3 thrombocytopenia in 4 patients. 3 patients had grade 3 arthralgia or myalgia. 6 patients developed grade 1 or 2 rash. PK samples were obtained on both Day 1 and Day 22 from 11 patients for BMS-275291, 10 patients for paclitaxel, and 9 patients for carboplatin. The peak concentration (Cmax) and exposure (AUCT) of paclitaxel and carboplatin on Day 1 was not significantly different on Day 1 compared with Day 22 (see Table). The mean (±SD) steady state parameters for BMS-275291 on Day 22 were Cmax 6.2 (±3.4) μg/mL, AUCT 23.1 (±8.9) μg.h/mL and T1/2 5.3 (±1.9) h. Conclusion: Administration of BMS-275291 1200 mg qd does not significantly affect the pharmacokinetic profile of paclitaxel or carboplatin and the combination was generally well tolerable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Leflunomide Overcomes CD40L/IL-4-Mediated Resistance to Fludarabine-Induced Apoptosis and Effectively Blocks Proliferation of CLL Cells
Authors: Sascha Dietrich, Annika Zota, Michael Hess, Michael Rieger, Christof Schweizer, Anthony D. Ho, Peter Dreger, Thomas Luft
Journal: Blood (2010)
Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease
Authors: Alexa R. Weingarden, Byron P. Vaughn
Journal: Gut Microbes (2017)

Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.