tbuckley/cabot-search huggingface dataset:
Primary lymphoma of the stomach: Three-year results of a prospective multicenter study
Authors: P. Koch, B. Grothaus-Pinke, W. Hiddemann, N. Willich, B. Reers, F. del Valle, H. Bodenstein, M. Pfreundschuh, E. Möller, J. Kocik, R. Parwaresch, M. Tiemann
Journal: Annals of Oncology (1997)
Health-related quality of life (HRQoL) results from the AURELIA trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum-resistant recurrent ovarian cancer (OC).
Authors: Martin R. Stockler, Felix Hilpert, Michael Friedlander, Madeleine King, Lari B. Wenzel, Chee Lee, Florence Joly, Nikolaus De Gregorio, Jose Angel Arranz Arija, Mansoor Raza Mirza, Roberto Sorio, Ulrich Freudensprung, Vesna Sneller, Gill Hales, Eric Pujade Lauraine
Journal: Journal of Clinical Oncology (2013)

5542 Background: Adding BEV to CT significantly improved PFS in platinum-resistant OC in the open-label phase III AURELIA trial. As symptom improvement is a major goal of treatment, determining effects on HRQoL was a key secondary aim of AURELIA. Methods: After investigator selection of single-agent CT (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel), patients (pts) with measurable/assessable platinum-resistant OC were randomized to CT ± BEV. HRQoL and symptoms were assessed at baseline and every 2 or 3 cycles (8/9 wks) until PD using the EORTC OC Module (OV28) and FOSI. The primary HRQoL endpoint was an absolute improvement of ≥15% (≥15 points) on the 100-point OV28 subscale for abdominal (abdo)/GI symptoms (items 1–6) at wk 8/9. Pts with missing questionnaires (Qs) were included and considered not to have improved. A sensitivity analysis excluded pts with Qs missing for reasons other than PD/death or switch from CT to BEV. Subgroup analyses of symptomatic pts included only those with a baseline score ≥15 (sufficient to show ≥15-point improvement). Mixed-model repeated measures (MMRM) analysis was used to compare Qs from all time points until PD/death, not just wk 8/9. The FOSI was analyzed similarly. Results: Baseline Qs were available from 89% of 361 randomized pts. At wk 8/9, 81% of BEV–CT vs 68% of CT pts who were alive and PD-free returned OV28 Qs. For the primary HRQoL endpoint, more BEV–CT than CT pts had a ≥15% improvement in the OV28 abdo/GI symptom subscale at wk 8/9 (21.9% vs 9.3%, 12.7% difference [95% CI 4.4–20.9]; p = 0.002). The sensitivity analysis described above showed a 13.3% difference [95% CI 4.5–22.1]. In the subgroup of 233 pts with a baseline score ≥15, there was a 16.9% difference (95% CI 6.1–27.6) favoring BEV–CT (29.6% vs 12.7%). MMRM analysis of OV28 abdo/GI symptom subscale scores also favored BEV–CT (6.4-point difference [95% CI 1.28–11.6]). More BEV–CT than CT pts had a ≥15% improvement in FOSI score at wk 8/9 (12.2% vs 3.1%, 9.0% difference [95% CI 2.9–15.2]). Conclusions: Adding BEV to CT resulted in more frequent ≥15% improvements in patient-reported abdo/GI symptoms in platinum-resistant OC. Clinical trial information: NCT00976911.
The effect of variation in donor platelet function on transfusion outcome: a semirandomized controlled trial
Authors: Anne M. Kelly, Stephen F. Garner, Theodora Foukaneli, Thomas R. Godec, Nina Herbert, Brennan C. Kahan, Alison Deary, Lekha Bakrania, Charlotte Llewelyn, Willem H. Ouwehand, Lorna M. Williamson, Rebecca A. Cardigan
Journal: Blood (2017)
CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes
Authors: Limin Xia, Wenjie Huang, Marina Bellani, Michael M. Seidman, Kaichun Wu, Daiming Fan, Yongzhan Nie, Yi Cai, Yang W. Zhang, Li-Rong Yu, Huili Li, Cynthia A. Zahnow, Wenbing Xie, Ray-Whay Chiu Yen, Feyruz V. Rassool, Stephen B. Baylin
Journal: Cancer Cell (2017)
Abstract 247: Dose-dependent Role of Inwardly Rectifying Potassium Current on Cardiac Automaticity of Human Embryonic Stem Cell-derived Cardiomyocytes
Authors: Jidong Fu, Adrienne Dennis
Journal: Circulation Research (2015)

The inwardly rectifying potassium current (IK1), encode by Kir2 family, is responsible for maintaining the negative resting potential, and contributes to phase 3 repolarization of the cardiac action potential. IK1 was generally thought to suppress cardiac automaticity, while the suppression of IK1 in adult ventricular cardiomyocytes (CMs) could engineer bio-artificial pacemaker-like cells to spontaneously fire action potential. Our studies also showed that overexpressed the gene of Kir2.1 could facilitate the electrophysiological maturing of mouse and human embryonic stem cell-differentiated CMs (ESC-CMs), which have the high degree of automaticity with nearly 50% of cells that can spontaneously fire action potential. In this study, we extensively analyzed the electrophysiology of mouse and human ESC-CMs, and found that the maximum diastolic potential in spontaneously firing ESC-CMs, -72.1±1.3 mV in atrial cells and -75.0±2.1 mV in ventricular cells, were significantly more hyperpolarized than that in quiescent ESC-CMs (-64.4±2.1 mV in atrial cells and -67.1±3.2 mV in ventricular cells). Applying a small amount of IK1 to hyperpolarize the membrane potential could enable those quiescent ESC-CMs to spontaneously fire action potential, indicating the enhancement of cardiac automaticity, while a large amount of IK1 could quiet those spontaneously firing cells down. By combining computational and experimental analyses, we confirmed that the synergistic interaction of IK1 and pacemaker current (If) could efficiently regulate cardiac automaticity during the differentiation. Our studies disclosed a dose-dependent role of IK1 on cardiac automaticity that a small amount of IK1 enhances and a large amount of IK1 suppresses cardiac automaticity in ESC-CMs during differentiation.
Hepatitis B virus quasispecies complexity is lower in hepatitis B virus–hepatitis D virus infection than in hepatitis B virus monoinfection
Authors: C. Godoy, S. Sopena, J. Gregori, D. Tabernero, M. Homs, R. Casillas, A. Ruiz, M. Riveiro-Barcela, J. Quer, R. Esteban, F. Rodriguez, M. Buti
Journal: Journal of Hepatology (2017)
Validation of response assessment according to international consortium for MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating agents
Authors: M Duchmann, T Braun, J-B Micol, U Platzbecker, S Park, S Pilorge, O Beyne-Rauzy, N Vey, M Sébert, B Gruson, P-Y Dumas, R Guieze, M-L Chretien, K Laribi, Y Chait, L Legros, L Sahnes, P Hirsch, C Salanoubat, E Solary, P Fenaux, R Itzykson
Journal: Blood Cancer Journal (2017)

The hypomethylating agents (HMA) azacitidine (AZA) 1,2 and decitabine (DAC) 3,4 are active in Chronic Myelomonocytic Leukemia (CMML) with overall response rates (ORR) of 40-70%, translating into median overall survivals (OS) of 12-22 months.Response to HMA in these CMML cohorts was mostly evaluated according to IWG-2006 criteria, 5 which do not assess improvement of myeloproliferative features nor quality of life.In myelodysplastic syndroms (MDS) patients treated with HMA, these criteria have limited impact in predicting OS. 6,7 Normalization of WBC and monocyte counts, regression of splenomegaly or other extramedullary disease, and improvement of quality of life have been reported in CMML patients treated with HMA 1,8 and studies in MDS and primary myelofibrosis have shown that symptom improvement could be correlated to a prolonged OS. 9,10 To capture both MDS and myeloproliferative neoplasm (MPN) features in a singly response scale in CMML, an international expert panel, the MDS/MPN International Working Group, proposed new response criteria for MDS/MPN, hereafter referred to as overlap-MDS/MPN criteria. 11These new criteria take in consideration bone marrow and peripheral blood blast reduction and improvement of cytopenias, but also account for correction of WBC, monocyte and peripheral immature myeloid cell counts
Lung Cancer Heterogeneity and New Strategies for Drug Therapy
Authors: Diane C. Wang,, William Wang,, Bijun Zhu,, Xiangdong Wang
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patient-derived xenografts using their own cancer cells isolated during surgery or biopsies. These results will be more precise if the drugs used in the strategies are selected through protein structure-guided compound screening or a DNA-encoded chemical library before validation in the patient's own cancer cells. Thus, a deeper understanding of heterogeneity mechanisms and improved validation of the therapeutic strategy will result in more precise treatments for patients.
Prevalence of osteoporosis and bone fracture was 2-fold higher in chronic hepatitis B compared to non-chronic hepatitis B patients and continued to increase in the last decade: results of a United States population-based cohort study
Authors: S.C. Gordon, J. Lim, I. Liou, A.B. Ozbay, L. Moore-Schiltz, G. Dusheiko, M.H. Nguyen
Journal: Journal of Hepatology (2017)
Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls, whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy
Authors: Athanasios D. Anastasilakis, Dimitrios Koulaxis, Nikoleta Kefala, Stergios A. Polyzos, Jagriti Upadhyay, Eirini Pagkalidou, Fotios Economou, Chrysostomos D. Anastasilakis, Christos S. Mantzoros
Journal: Metabolism (2017)
Abstract IA08: Therapeutic resistance and feedback loops
Authors: Jean J. Zhao
Journal: Clinical Cancer Research (2017)

Abstract Therapeutic resistance is a major obstacle in the clinic. Utilizing our novel genetically engineered mouse models (GEMMs) of breast cancer driven by inducible expression of PIK3CAH1047R or a wildtype HER2, coupled with pharmacological approaches, we identified a number of significant resistance mechanisms to PI3K- or HER2-targeted therapy. For example, we found spontaneous focal amplification of Met and Myc, recurrent mutations in Ras and β-catenin, and compensatory activation of the MAPK pathway render resistance to PI3K inhibition. We recently identified Cyclin D1-CDK4 mediated resistance to HER2-targeted therapy through a signaling feedback loop. More importantly, our results led to the design of a randomized phase II trial examining a CDK4/6 inhibitor plus trastuzumab as a regimen for patients with metastatic, refractory HER2+ breast cancer. In addition to GEMMs, we have led the efforts at DFCI to establish and characterize novel breast cancer patient-derived xenograft (PDX) models, with an emphasis on brain metastases, an emerging clinical challenge. I will discuss how we have used these models to discover a therapeutic strategy that overcomes resistance and yields durable remission of brain metastases of HER2+ breast cancer in animals. Citation Format: Jean J. Zhao. Therapeutic resistance and feedback loops. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA08.
Erratum: Recognition of the nonclassical MHC class I molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells
Authors: Daniel M Andrews, Lucy C Sullivan, Nikola Baschuk, Christopher J Chan, Richard Berry, Claire L Cotterell, Jie Lin, Heloise Halse, Sally V Watt, Jennifer Poursine-Laurent, Chyung-Ru Wang, Anthony A Scalzo, Wayne M Yokoyama, Jamie Rossjohn, Andrew G Brooks, Mark J Smyth
Journal: Nature Immunology (2013)
Real world efficacy of 12 weeks sofosbuvir, daclastivir with ribavirin among cirrhotic pre and post-transplant genotype 3 hepatitis C infected patients
Authors: D. Schmidt-Martin, S. Bufton, M. Roberts, K. Rye, S. Singhal, S. Eldred, I. Perry, C. Corbett, E. Unitt, V. Wood, H. Dillon, G.H. Haydon, D. Mutimer, A.M. Elsharkawy
Journal: Journal of Hepatology (2017)
History of Asthma is Associated with Albuminuria within an International Pediatric Cohort of Sickle Cell Disease Patients: A Casire Group Analysis
Authors: Immacolata Tartaglione, Baba PD Inusa, Raffaella Colombatti, Deepa Manwani, Silverio Perrotta, Eugenia Vicky Naa Kwarley Asare, Connie M. Piccone, Fredericka Sey, Charles Antwi-Boasiako, Laura Sainati, Adetola A. Kassim, Donna Boruchov, Angela Rivers, William Zempsky, Crawford John Strunk, Biree Andemariam, Andrew D. Campbell
Journal: Blood (2016)
MAD2gamma, a novel MAD2 isoform, expression in multiple cancer cell lines, mitotic arrest effects, and association with cisplatin-resistance in testicular germ cell tumors.
Authors: Alejandro Lopez-Saavedra, Irwin Alejandro Hernandez Cruz, Fernando Luna-Maldonado, Luis Alonso Herrera
Journal: Journal of Clinical Oncology (2015)

e15629 Background: The mitotic spindle assembly checkpoint (SAC) signaling pathway has recently been identified as a promising target for cancer therapy. A weak or disrupted SAC signaling may contribute to resistance to spindle inhibitors and DNA-damaging agents in human cancers. Mitotic arrest deficient 2 (MAD2α) has been implicated in the association between SAC signaling failures and the response to chemotherapy. In this study, we identified a novel splice variant of MAD2, which we have designated MAD2γ, and investigated its association with DNA-damage response. Methods: Endogenous expression of MAD2γ and MAD2α was measured through semiquantitative RT-PCR in distinct cancer cell lines and primary normal foreskin fibroblasts, and through quantitative RT-PCR in primary tumor samples from patients with testicular germ cell tumors. A plasmid construct expressing MAD2γ was transfected in HCT116, and its intracellular localization, and SAC function were evaluted through immunofluorescence and mitotic index. Results: MAD2γ is expressed in several cancer cell lines and non-cancerous primary foreskin fibroblasts. Ectopically expressed MAD2γ localized in the nucleus, and its overexpression in a SAC-competent cancer cell line, HCT116, reduced the mitotic index, suggesting that SAC signaling was impaired. Furthermore, overexpression of endogenous MAD2γ in patients with testicular germ cell tumors was associated with resistance to cisplatin-based chemotherapy, whereas expression of MAD2α was not significantly different betwee resistant and sensitive patients. In addition, treatment with cisplatin significantly increased the expression of MAD2γ, but not MAD2α, in HCT116 cells. Conclusions: Our data suggest that MAD2γmay play an opposing role to MAD2α in the activation of the SAC signaling and that MAD2γ expression is associated with resistance to DNA-damaging agents, such as cisplatin-based chemotherapy. Our results highlight the importance of identifying alternative splicing events that may compromise SAC signaling, which is a promising target for cancer therapy.
Abstract P158: MicroRNA-22 Modulates Cardiac Gene Expression and Controls Compensation to Hemodynamic Stress in Mice
Authors: Priyatansh Gurha, Robert Kelm, Mark Entman, George Taffet, Allan Bradley, Antony Rodriguez
Journal: Circulation Research (2011)

Recent evidence suggests that miRNAs play an important role in cardiac morphogenesis and pathophyiology of heart failure. To explore the role of miR-22 in the mouse heart physiology, we generated miR-22 null (KO) mice. Although, miR-22 KO mice showed normal cardiac structure and function at baseline, these mice are sensitized to maladaptive remodeling (cardiac dilation) and decompensation in response to pressure overload by transverse aortic constrictions (TAC) stimulation. Genome-wide molecular analysis of KO hearts revealed attenuated expression of numerous CarG-dependent genes encoding proteins that reside at the sarcomeric Z-disc (including Myh7, Acta1, Mlp, Melusin, MyoZ2) indicating that miR-22 is required for optimum muscle gene expression. Alterations in sarcomeric gene expression is especially interesting as this suggests a primary role of miR-22 in controlling cardiac contractility and adaptation to stress. Targetomics analysis revealed that mechanistically this effect could be modulated in part by miR-22 target PURB (Purine Rich element binding protein B), a transcriptional/translational repressor. In conclusion we define a critical role of miR-22 in cardiac adaptation to hemodynamic stress. Furthermore, these data provides a previously unseen essential molecular mechanism that underlies homeostatic control of sarcomeric protein expression in the heart.
A reduction in the hepatic venous pressure gradient (HVPG) prevents clinical outcomes in compensated and decompensated cirrhosis: a meta-analysis
Authors: L. Turco, C. Villanueva, V. La Mura, J.C. Garcia-Pagan, T. Reiberger, J. Genesca, R.J. Groszmann, B.C. Sharma, C. Merkel, C. Bureau, E. Alvarado, J.G. Abraldes, A. Albillos, R. Banares, M. Peck-Radosavljevic, S. Augustin, S. Sarin, J. Bosch, G. Garcia-Tsao
Journal: Journal of Hepatology (2017)
Phacomatosis pigmentokeratotica and precocious puberty associated with <i> <scp>HRAS</scp> </i> mutation
Authors: R.J. Martin, M. Arefi, M. Splitt, L. Redford, C. Moss, N. Rajan
Journal: British Journal of Dermatology (2017)

Germline mutations in the oncogene HRAS cause syndromes with systemic and cutaneous features, notably Costello syndrome (CS).1 Postzygotic activating mutations in HRAS are increasingly recognised as a cause of epidermal naevi which are sometimes associated with the extracutaneous features of germline rasopathies. Epidermal naevi caused by HRAS mutations present with varied morphology including sebaceous naevus, woolly hair naevus and phacomatosis pigmentokeratotica (PPK)2.

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Establishing and maintaining the National Vaccination Register in Finland
Authors: Ulrike Baum, Jonas Sundman, Susanna Jääskeläinen, Hanna Nohynek, Taneli Puumalainen, Jukka Jokinen
Journal: Eurosurveillance (2017)

Computerised, population-based vaccination registers are valuable tools for assessing the vaccine uptake and impact in populations. However, reliable impact assessment is only possible if the data quality can be reviewed and monitored continuously. This report describes the establishment and maintenance of the National Vaccination Register (NVR) in Finland. Currently, the NVR covers nationwide records of vaccinations given within the frame of the National Vaccination Programme since 2009. All vaccinations registered in the NVR contain a record of the personal identity code, the administered vaccine, and the date of vaccination. The vaccine lot number is the key component for recording and identifying vaccinations, because of its broad availability across patient information systems and its importance in vaccine safety monitoring. Vaccination records are accumulated and updated daily into the NVR, and their completeness is monitored monthly to assess deficiencies in data entry and data collection. Additionally, an alert system reports unexpected changes in data accumulation prompting the validation of observed changes in vaccination coverage. The presented process documentation may serve as basis to improve the design and quality of other vaccination or healthcare registers and aims to inspire the set-up of vaccination registers in those countries which still do not have one.
Multicenter randomized trial comparing short-term stenting versus balloon dilatation for dominant strictures in primary sclerosing cholangitis
Authors: C. Ponsioen, U. Arnelo, A. Bergquist, E. Rauws, V. Paulsen, P. Cantu, I. Parzanese, E. de Vries, K. Said, O. Chazouilleres, A. Kemgang, B. Desaint, M. Farkkila, S. Van der Merwe, W. Van Steenbergen, H.-U. Marschall, P.-O. Stotzer, D. Thorburn, S. Pereira, L. Aabakken
Journal: Journal of Hepatology (2017)
Tenofovir, entecariv and lamivudine in patients with severe acute exacerbation and hepatic decompensation of chronic hepatitis B
Authors: J.G. Park, Y.R. Lee, S.Y. Park, H.J. Lee, W.Y. Tak, Y.O. Kweon, S.Y. Jang, H. Keun, M.K. Kang
Journal: Journal of Hepatology (2017)
Knee extensor strength and body weight in adolescent men and the risk of knee osteoarthritis by middle age
Authors: Aleksandra Turkiewicz, Simon Timpka, Jonas Bloch Thorlund, Eva Ageberg, Martin Englund
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To assess the extent to which knee extensor strength and weight in adolescence are associated with knee osteoarthritis (OA) by middle age. <h3>Methods</h3> We studied a cohort of 40 121 men who at age 18 years in 1969/1970 underwent mandatory conscription in Sweden. We retrieved data on isometric knee extensor strength, weight, height, smoking, alcohol consumption, parental education and adult occupation from Swedish registries. We identified participants diagnosed with knee OA or knee injury from 1987 to 2010 through the National Patient Register. We estimated the HR of knee OA using multivariable-adjusted Cox proportional regression model. To assess the influence of adult knee injury and occupation, we performed a formal mediation analysis. <h3>Results</h3> The mean (SD) knee extensor strength was 234 (47) Nm, the mean (SD) weight was 66 (9.3) kg. During 24 years (median) of follow-up starting at the age of 35 years, 2049 persons were diagnosed with knee OA. The adjusted HR (95% CI) of incident knee OA was 1.12 (1.06 to 1.18) for each SD of knee extensor strength and 1.18 (1.15 to 1.21) per 5 kg of body weight. Fifteen per cent of the increase in OA risk due to higher knee extensor strength could be attributed to knee injury and adult occupation. <h3>Conclusion</h3> Higher knee extensor strength in adolescent men was associated with increased risk of knee OA by middle age, challenging the current tenet of low muscle strength being a risk factor for OA. We confirmed higher weight to be a strong risk factor for knee OA.
Analysis of 98 Relapses of Localized Aggressive NHL Initially Treated by the GOELAMS 02 03 Trials
Authors: J. Fernandes, S. Tabuteau, Ph Colombat, M. Hunault, A. Le Mevel, M. Escoffre, Th Lamy, Ch Le Maignan, V. Delwail, B. Desablens
Journal: Blood (2002)
UK plan to improve air quality is too weak, say campaigners
Authors: Susan Mayor
Journal: BMJ (2017)

Campaigners have criticised the UK government’s draft plan to improve air quality, published on 5 May,1 as being too weak to improve public health.

“The plan looks much weaker than we had hoped for,” said James Thornton, of Client Earth, the environmental law charity that took ministers to court, arguing that their failure to take measures to reduce air pollution put them in breach of EU law and domestic regulations.

Thornton continued, “The court ordered the government to take this public health issue seriously, and while the government says that pollution is the largest environmental risk to public health, …
CASPASE ACTIVATION IN ACETAMINOPHEN-INDUCED ACUTE LIVER FAILURE: IMPORTANCE OF MULTIPLE ORGAN FAILURE
Authors: Charalambos G. Antoniades, Ragai Mitry, Robin Hughes, Matthew J. Bruce, Mark McPhail, Philip A. Berry, William Bernal, Georg Auzinger, Parthi Srinivasan, Hector Vilca-Melendez, Wayel Jassem, Nigel Heaton, Julia Wendon
Journal: Hepatology (2010)