tbuckley/cabot-search huggingface dataset:
Abstract 14: Impact of Gata4, Mef2c and Tbx5 Stoichiometry on Epigenetic Status of Direct Cardiac Reprogramming
Authors: Li Qian, Ziqing Liu, Michael Zheng, Jiandong Liu
Journal: Circulation Research (2015)

Reprogramming from fibroblasts into induced cardiomyocytes (iCMs) offers alternative strategies for cardiac disease modeling and cardiac regeneration. Cellular reprogramming is closely associated with global re-patterning of the epigenetic landscape. The reprogramming cells must overcome the epigenetic barriers to acquire the target cell-like epigenetic pattern. We have recently demonstrated that stoichiometry of iCM reprogramming factors Gata4 (G), Mef2c (M) and Tbx5 (T) has profound impact on reprogramming efficiency and quality, yet the underlying mechanism remains unclear. Here, we demonstrate that the optimal stoichiometry combination MGT resulted in a reduced binding of the repressive marker histone 3 lysine 27 trimethlytion (H3K27me3) and an enhanced binding of the active marker histone 3 lysine 4 trimethlytion (H3K4me3) on the cardiac gene loci, compared to the least optimal combination GTM. We found that this epigenetic change occurred as early as day 3 when cardiac marker genes started to be induced in the reprogramming fibroblasts. Additionally, we determined the DNA methylation status in two cardiac gene loci during MGT and GTM induced reprogramming. Subsets of the CpG islands in these promoters were significantly more demethylated in MGT than GMT-transduced cells. We thus propose these CpGs islands as the “regulatory” CpGs critical for iCM reprogramming. In conclusion, we demonstrated that stoichiometry of G, M, T influences the epigenetic status of the iCM cells, suggesting a potential mechanism of how stoichiometry of G,M,T influences reprogramming.
Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4
Authors: Adam G. Sowalsky, Haydn T. Kissick, Sean J. Gerrin, Rachel J. Schaefer, Zheng Xia, Joshua W. Russo, M. Simo Arredouani, Glenn J. Bubley, Martin G. Sanda, Wei Li, Huihui Ye, Steven P. Balk
Journal: Clinical Cancer Research (2017)

Abstract Purpose: The molecular features that account for the distinct histology and aggressive biological behavior of Gleason pattern 4 (Gp4) versus Gp3 prostate cancer, and whether Gp3 tumors progress directly to Gp4, remain to be established. Experimental Design: Whole-exome sequencing and transcriptome profiling of laser capture–microdissected adjacent Gp3 and cribiform Gp4 were used to determine the relationship between these entities. Results: Sequencing confirmed that adjacent Gp3 and Gp4 were clonal based on multiple shared genomic alterations. However, large numbers of unique mutations in the Gp3 and Gp4 tumors showed that the Gp4 were not derived directly from the Gp3. Remarkably, the Gp3 tumors retain their indolent-appearing morphology despite acquisition of multiple genomic alterations, including tumor suppressor losses. Although there were no consistent genomic alterations that distinguished Gp3 from Gp4, pairwise transcriptome analyses identified increased c-Myc and decreased p53 activity in Gp4 versus adjacent clonal Gp3 foci. Conclusions: These findings establish that at least a subset of Gp3 and aggressive Gp4 tumors have a common origin, and support a branched evolution model wherein the Gp3 and Gp4 tumors emerge early from a common precursor and subsequently undergo substantial divergence. Genomic alterations detectable in the Gp3 may distinguish these tumors from truly indolent Gp3. Screening for a panel of these genomic alterations in men who have prostate biopsies showing only Gp3 (Gleason score 6, Gs6) may allow for more precise selection of men who can be safely managed by active surveillance versus those who may benefit from further intervention. Clin Cancer Res; 23(14); 3823–33. ©2017 AACR.
The never-ending search for the perfect acute:chronic workload ratio: what role injury definition?
Authors: Billy T Hulin
Journal: British Journal of Sports Medicine (2017)

The acute:chronic workload ratio is associated with injury risk in rugby league players.1 Researchers and practitioners have discussed the most appropriate way in which acute and chronic workloads should be modelled and compared with injury. Menaspa2 suggested that when workloads do not follow weekly patterns in team sport, rolling weekly averages may disregard variations in workload within the week and as such, are not ideal. However, Drew et al 3 highlighted that evidence was required before an alternative method could be considered. Williams et al ,4 suggested an exponentially weighted moving average calculation of acute and chronic workloads. To my knowledge, all this discussion has ignored definition of injury—this could influence the findings of any workload-injury analysis.

Relating the findings from multiple injury investigations in team sport can be difficult due to the use of inconsistent definitions of injury.5 Both Hulin …
Suture endoscopique pour la prévention de la migration de prothèses dans la pathologie digestive haute bénigne: une étude comparative multicentrique
Authors: G. Lesur
Journal: Endoscopy (2016)

La pose de prothèse dans la pathologie bénigne digestive haute pose toujours le problème du risque de migration. En cas de migration de la prothèse, les résultats fonctionnels sont moins bons et très souvent d’autres interventions thérapeutiques sont nécessaires.
Dynamic Regulation of 5-Hydroxymethylcytosine At the γ-Globin Promoter During Erythroid Differentiation
Authors: Maria Armila Ruiz, Kestis Vaitkus, Aparna Vasanthakumar, Angela Rivers, Tatiana Kouznetsova, Joseph DeSimone, Lucy A. Godley, Donald Lavelle
Journal: Blood (2012)
BRAF V600 inhibitor discontinuation after complete response in advanced melanoma: a retrospective analysis of 16 patients
Authors: C. Vanhaecke, F. Deilhes, J. Chanal, E. Regnier-Rosencher, F. Boitier, S. Boulinguez, M.-F. Avril, S. Guégan, N. Dupin, S. Aractingi, N. Meyer, N. Kramkimel
Journal: British Journal of Dermatology (2017)

BRAF inhibitors (BRAFi) improve progression-free survival and overall survival in patients with advanced melanoma (1,2), with 3 to 6% of patients experiencing complete remission (CR)(1,3). Nevertheless, this efficacy comes at a cost with 90% of patients experiencing at least one adverse event and 45% grade 3 or 4 adverse events (4).

Management of long-term responders is not yet well delineated: safety argues for treatment continuation, because evolution after discontinuation is unknown.

This article is protected by copyright. All rights reserved.
The concordance between NCCTG's and NSABP's C-myc FISH assays
Authors: M. M. Reinholz, A. C. Dueck, W. L. Lingle, K. L. Allen Ziegler, A. E. Wiktor, S. Paik, R. B. Jenkins, E. A. Perez
Journal: Journal of Clinical Oncology (2008)

22110 Background: Preliminary results from the National Surgical Adjuvant Breast and Bowel (NSABP) adjuvant trastuzumab breast cancer (BC) trial, B-31, suggested that HER2-positive BC patients with primary tumor C-myc (MYC) amplification derived more benefit from trastuzumab than those patients without MYC amplification. The purpose of this pilot study was to establish the concordance between NSABP's and North Central Cancer Treatment Group's (NCCTG) fluorescence in situ hybridization (FISH) assays so that a MYC biomarker validation study can be performed. Methods: Whole sections (WS) of 85 independent HER2-positive (IHC 3+ or FISH amplified) breast tumors and sections from tissue microarrays (TMAs) containing three cores from each of these tumors were sent to NCCTG's research base (Mayo Clinic Rochester, MN) and NSABP's research base (University of Pittsburg, PA) and analyzed with probes from Abbott Molecular (Des Plaines, IL). NSABP's assay uses a single probe for the MYC gene, and a gene copy number score was provided for each WS and TMA spot. NCCTG's assay uses probes for both MYC and centromere 8 (CEP 8), and the MYC:CEP8 ratio, a calculated gene copy number score, and overall interpretation were provided for each WS and TMA spot. Results: The concordance between WS and maximum TMA score was 94% and 90% for NSABP and NCCTG, respectively; and between WS and maximum TMA MYC:CEP8 ratio was 96% for NCCTG. The WS concordance between NSABP's gene copy number score and NCCTG's MYC:CEP8 ratio, calculated gene copy number score, and overall interpretation were 80%, 93%, and 76%, respectively. Conclusions: We obtained acceptable assay concordance, which allows for cross-validation and even potential pooled analyses of NCCTG's and NSABP's MYC FISH data. These types of assay validation and concordance studies are vital to the ability to properly conduct correlative translational studies, which will be reported independently in the context of N9831, a similar adjuvant trastuzumab trial to B31. No significant financial relationships to disclose.
Six, Not Eight Cycles of Bi-Weekly CHOP with Rituximab (R-CHOP-14) Is the Preferred Treatment for Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Results of the RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
Authors: Michael Pfreundschuh, Marita Kloess, Rudolf Schmits, Samira Zeynalova, Eva Lengfelder, Astrid Franke, Hans Steinhauer, Marcel Reiser, Michael Clemens, Christine Nickenig, Martha de Wit, Martin Hoffmann, Roland Mertelsmann, Bernd Metzner, Anthony Ho, Lorenz Truemper, Hans Eimermacher, Hans Mergenthaler, Ruediger Liersch, Ulrich Duehrsen, Leopold Balleisen, Frank Hartmann, Viola Poeschel, Norbert Schmitz, Markus Loeffler
Journal: Blood (2005)
Fifth Ovarian Cancer Consensus Conference: individualized therapy and patient factors
Authors: J. McGee, M. Bookman, P. Harter, C. Marth, I. McNeish, K.N. Moore, A. Poveda, F. Hilpert, K. Hasegawa, M. Bacon, C. Gatsonis, A. Brand, F. Kridelka, J. Berek, N. Ottevanger, T. Levy, S. Silverberg, B.-G. Kim, H. Hirte, A. Okamoto, G. Stuart, K. Ochiai
Journal: Annals of Oncology (2017)
Matched Case Control Analysis Comparing Long Term Survival of Multiple Myeloma Patients Who Received Stem Cell Transplant with and without Idiotype-Pulsed Dendritic Cell Vaccine
Authors: Yi Lin, Morie A Gertz, Robert B. Sims, Sumithra Mandrekar, Kristina Laumann, Betsy LaPlant, Angela Dispenzieri, Suzanne R Hayman, Francis K Buadi, David Dingli, Douglas Padley, Dennis A. Gastineau, Shaji Kumar, Vincent Rajkumar, Martha Q Lacy
Journal: Blood (2011)
FDG-PET for Staging and Follow-up of HIV-Infected Patients with Non Hodgkin Lymphoma and Hodgkin Lymphoma: A Single Center Experience.
Authors: Silvia Cantoni, Erika Ravelli, Maria Cristina Moioli, Chiara Rusconi, Vittorio Ruggero Zilioli, Claudia Maria Basilico, Livio Gargantini, Annamaria Nosari, Alberto Volonterio, Claudio Rossetti, Enrica Morra
Journal: Blood (2009)
In Vitro and In Vivo Activity of the Src/Abl Kinase Inhibitor AP23464 and Analogs Against Activation Loop Mutants of KIT.
Authors: Amie S. Corbin, Shadmehr Demehri, Ian J. Griswold, Chester A. Metcalf, William C. Shakespeare, Joseph Snodgrass, Scott Wardwell, David C. Dalgarno, John Iuliucci, Tomi K. Sawyer, Brian J. Druker, Michael W. Deininger
Journal: Blood (2004)
Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Patients (pts) with Advanced Chronic Myeloid Leukemia (CML) Post Imatinib Failure.
Authors: Elias Jabbour, Marcos De Lima, Leandro de Padua Silva, Sergio Giralt, Jorge Cortes, Muzaffar Qazilbash, Gabriela Rondon, Stefan Ciurea, Roy Jones, Yago Nieto, Martin Korbling, Daniel Couriel, Hagop Kantarjian, Richard Champlin
Journal: Blood (2008)
Tetra-Arsenic Tetra-Sulfide Containing Triple-Agent Regimen as the First Line Therapy for Acute Promyelocytic Leukemia: Expeditiously Consecutive Complete Remission and Improved Disease-Free Survival.
Authors: Tong Wu, Jie Zhao, Bin Jiang, Shu-Lan Wu, Ping-Di Yang, Fu-Xiang Shan, Chun-Rong Tong, Dao-Pei Lu
Journal: Blood (2007)
Lyn Kinase Is Constitutively Activated, Controls the mTOR/p70S6K/4E-BP1 Pathway and Regulates Cell Proliferation in Acute Myeloid Leukemia.
Authors: Christian Recher, Cedric Dos Santos, Cecile Demur, Valerie Bardet, Nais Prade-Houdellier, Guy Laurent, Bernard Payrastre
Journal: Blood (2006)
Gain with no pain? Pain management in dermatological photodynamic therapy
Authors: B. Wang, L. Shi, Y.F. Zhang, Q. Zhou, J. Zheng, R.M. Szeimies, X.L. Wang
Journal: British Journal of Dermatology (2017)

Pain during photodynamic therapy (PDT) is the main limiting adverse effect in its use in dermatology. Given its multifactorial nature, we reviewed both intrinsic and extrinsic factors that are involved in PDT pain. We propose a threshold theory for pain experience in PDT: it correlates positively with fluence rate and dose below a certain threshold (rate of ~60 mW cm-2 , dose of ~50 J cm-2 ); when the threshold is surpassed, pain intensity saturates. Additionally, we carefully compared recent updates on pain management strategies and we suggest that cold-air analgesia and low-irradiance light sources (such as variable pulsed light and daylight PDT) represent the current best analgesic options. Finally, we discuss the possible mechanisms of pain experience during PDT. Reactive oxygen species, transient receptor potential channels and inflammatory responses are key mediators in pain. Further investigation into these pathways should help with the development of more effective analgesic strategies. Taking these points together, for pain management in PDT, an individualized plan of analgesia is possible.
Lack of WNT Pathway Co-Receptors as a Possible Reason for Chronic Lymphoctic Leukemia (CLL) Cells Resistance to Dickkopf-1 (DKK1).
Authors: Alexandra Filipovich, Rajesh Kumar Gandhirajan, Iris Gehrke, Julian Paesler, Simon Jonas Poll-Wolbeck, Sabrina Uhrmacher, Magdalena Hertweck, Felix Erdfelder, Regina Razavi, Michael Hallek, Karl Anton Kreuzer
Journal: Blood (2009)
A retrospective comparison of contrast enhanced spectral mammography (CESM) to breast MRI in breast cancer detection: An initial study for sensitivity analysis.
Authors: Luna Li, Kristin Brill, Pauline Germaine, Elizabeth Tinney, Karen Hendershott, Lydia Liao
Journal: Journal of Clinical Oncology (2014)

7 Background: CESM is a new study using contrast and dual energy digital mammographic technology to detect contrast enhanced cancer that may be invisible on conventional mammogram. Limited studies have shown that adding CESM to diagnostic workup adjunct with mammogram and breast ultrasound does increase sensitivity for breast cancer detection. More studies are needed to compare the sensitivity of CESM to BMRI to further define the role of CESM in breast cancer diagnosis. Methods: This study involved 50 malignant breasts in 48 women retrospectively chosen from of 960 patients in our institution during the period of October 2012 to March 2014. Both CESM and BMRI were done for each patient within 30 days. The cancer diagnoses were confirmed by tissue diagnoses. The size of lesions was classified into three categories based on standard of breast cancer stages: 1 (0.2cm - &lt; = 2 cm), 2 (2 cm &lt; lesion &lt; = 5 cm), 3 (&gt; 5 cm). The enhancement intensity of both lesions and background has been quantified based on a scale of 0-3. Statistical significance was analyzed using T test for mean size of index cancer and mean score of enhancement intensity of background and lesions on CESM and BMRI. Sensitivity and positive predictive value (PPV) were calculated for both CESM and BMRI. Morphology consistence was calculated on both studies. Results: Both CESM and BMRI have sensitivity of 100% for breast cancer detection. CESM has a PPV of 98% versus 93% for BMRI. No statistical significance was identified on mean size of index cancer. The enhancement intensity of background and lesions is significantly higher on CESM than on BMRI (p &lt; 0.01). The smallest cancer can be detected by both CESM and BMRI is less than 0.5 cm. Morphology consistence was 46/50 (92%). Conclusions: Our study indicates that CESM and BMRI have comparable high sensitivity on breast cancer detection. CESM has a higher PPV than BMRI that may indicate a better specificity (no significant difference due to the small sample size). Significantly less background enhancement intensity on CESM than on BMRI reflect an increased specificity. More studies need to be conducted for further evaluation.
La sévérité endoscopique de l’atteinte oesophagienne est corrélée à la réduction de la distensibilité dans l’œsophagite à éosinophiles
Authors: G. Lesur
Journal: Endoscopy (2016)

Le but de ce travail américain émanant d’une équipe de référence était de rechercher une éventuelle corrélation entre l’aspect endoscopique au cours de l’œsophagite à éosinophiles et ses conséquences motrices évaluées par la technique de l’endo-FLIP (Endoluminal functional luminal imaging probe).
ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans
Authors: J.J. Lyons, Y. Liu, C.A. Ma, X. Yu, M.P. O’Connell, M.G. Lawrence, Y. Zhang, K. Karpe, M. Zhao, A.M. Siegel, K.D. Stone, C. Nelson, N. Jones, T. DiMaggio, D.N. Darnell, E. Mendoza-Caamal, L. Orozco, J.D. Hughes, J. McElwee, R.J. Hohman, P.A. Frischmeyer-Guerrerio, M.E. Rothenberg, A.F. Freeman, S.M. Holland, J.D. Milner
Journal: The Journal of Experimental Medicine (2017)

Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these congenital disorders have been associated with either increased TGF-β activity or impaired STAT3 activation, suggesting that these pathways might intersect and that their disruption may contribute to atopy. In this study, we show that STAT3 negatively regulates TGF-β signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation and SMAD2/3 binding protein. Individuals with dominant-negative
Are all RET fusions NSCLC alike? Clinical pitfalls and response to targeted therapy: KIF5B vs. CCDC6.
Authors: Michal Sarfaty, Assaf Moore, Maya Gottfried, Rivka Katzenelson, Hovav Nechushtan, Mira Wollner, Victoria Neiman, Lior Soussan-Gutman, Addie Dvir, Maya Ilouze, Nir Peled
Journal: Journal of Clinical Oncology (2015)

e19005 Background: Rearranged during Transfection (RET) fusions have been reported in 1-2% of lung adenocarcinomas (LADC), KIF5B-RET fusion being the common variant, and less commonly CCDC6-RET, TRIM33-RET and NCOA4–RET. The natural history and the management of RET fusion NSCLC are still unclear. We hereby present a series depicting the clinical course of nine RET-fusions NSCLC patients. Methods: A multicenter, retrospective, descriptive report of NSCLC patients who harbored RET fusions, diagnosed and treated between May 2009 and October 2014. Results: Nine patients were included in this study, 4 male patients and 5 female patients. The mean age at diagnosis was 55 years (range 28-72). Five were never smokers and four light smokers. Six harbored the KIF5B-RET variant and three the CCDC6-RET. Six cases had hyper-acute presentation and/or recurrence. Five of them harbored the KIF5B variant. Unique characteristics include bilateral miliary lung metastasis on presentation and early abdominal, pelvic and bone involvement. One patient who harbored the CCDC6-RET mutation displayed a profound and durable response to a cisplatin/pemetrexed/bevacizumab regimen for 8 months. One patient who harbored the KIF5B-RET variant was treated with cabozantinib and showed a rapid and durable complete response by Response Evaluation Criteria in Solid Tumors for 8 months. To our knowledge, this is the first study to report a complete response to cabozantinib for this indication. Conclusions: RET-fusion LADC patients may have an abrupt and acute presentation; in our series, tend to be associated with KIF5B fusion variant. While some RET-fusion positive LADC patients might benefit from combination chemotherapy, it may also be advocated that the most effective targeted therapy is cabozantinib with a potential long standing complete response. The dose, as well as rate and duration of response need to be further assessed in large randomized control trials.
Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline
Authors: Catherine John, María Soler Artigas, Jennie Hui, Sune Fallgaard Nielsen, Nicholas Rafaels, Peter D Paré, Nadia N Hansel, Nick Shrine, Iain Kilty, Anders Malarstig, Scott A Jelinsky, Signe Vedel-Krogh, Kathleen Barnes, Ian P Hall, John Beilby, Arthur W Musk, Børge G Nordestgaard, Alan James, Louise V Wain, Martin D Tobin
Journal: Thorax (2017)

<h3>Background</h3> Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. <h3>Objectives</h3> We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. <h3>Methods</h3> We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV<sub>1</sub> and FEV<sub>1</sub>/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. <h3>Results</h3> The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10<sup>−16</sup> for FEV<sub>1</sub>/FVC) but no effect on longitudinal decline (p=0.160 for FEV<sub>1</sub>/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts. <h3>Conclusions</h3> Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.
Genome-Wide 500K SNP Array Analyses Reveal High Frequencies of Cryptic Genetic Abnormalities and Identify Recurrent Microdeletions Targeting Novel Genes in Adult Acute Lymphoblastic Leukemia.
Authors: Kajsa Paulsson, Jean-Baptiste Cazier, Jane Stevens, Tracy Chaplin, Finlay MacDougall, Debra Lillington, T. Andrew Lister, Bryan D. Young
Journal: Blood (2007)
Secondary Monoclonal Gammopathy of Undetermined Significance after Allogeneic Stem Cell Transplantation in Multiple Myeloma
Authors: Marian Schmitz, Henny Otten, Laurens Franssen, Suzanne van Dorp, Theo Strooisma, Henk M. Lokhorst, Niels W.C.J. van de Donk
Journal: Blood (2014)
Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and HIF-2α Are Independent Prognostic Factors for Normal Karyotype Acute Myeloid Leukemia (NK AML)
Authors: Kellie M. Demock, Joseph Marinaro, Ian McInnis, Laurie Ann Ford, Meir Wetzler, Lili Tian, George Deeb, Eunice S. Wang
Journal: Blood (2008)