tbuckley/cabot-search huggingface dataset:
Re: Vasileios I. Sakalis, Markos Karavitakis, Dina Bedretdinova, et al. Medical Treatment of Nocturia in Men with Lower Urinary Tract Symptoms: Systematic Review by the European Association of Urology Guidelines Panel for Male Lower Urinary Tract Symptoms. Eur Urol 2017;72:757–69
Authors: Jae Hung Jung, Julia L. Han, Philipp Dahm
Journal: European Urology (2017)
Pooled data analysis of the safety and tolerability of intravenous pelareorep in combination with chemotherapy in 500 + cancer patients
Authors: A.A. Gutierrez, C. Reid, M. Crawford, K. Cheetham, A. Dzugalo, M. Parsi, A. Penman, N. Noronha, D. Galindez, R. O'Flynn, M. Coffey
Journal: Annals of Oncology (2017)
Sixty seconds on . . . NHS Property Services
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Yes, indeed. In April 2013 the Department of Health for England decided to set up a limited company to take on the ownership and management of roughly 3600 NHS buildings and facilities across the country, after the strategic health authorities and primary care trusts were abolished. Its portfolio includes around 1200 general practices, about 15% of the general practice estate.

It’s a fair question, and one that our good friends at the …
Listériose en Europe : besoin accru d’un réseau de surveillance européen
Authors: C Hedberg
Journal: Eurosurveillance (2006)

Il y a quatre ans, Henriette de Valk et ses collegues ont evalue le besoin ainsi que la faisabilite d’un reseau europeen dedie aux infections a Listeria chez l’homme [1]. Ce reseau etait vu comme un moyen de renforcer la surveillance a l’echelon national par une harmonisation des methodes microbiologiques et par la mise a disposition d’outils epidemiologiques pour les investigations. Les resultats de leur enquete etaient clairs : les participants reconnaissaient qu’un tel reseau faciliterait la detection et l’investigation d’epidemies et qu’il pourrait s’appuyer sur les systemes nationaux de surveillance existants [1]. Le developpement d’un reseau europeen pour Listeria a beneficie d’un soutien institutionnel important, et suite aux efforts de planification, la surveillance de la listeriose s’est amelioree dans plusieurs pays [2]. Toutefois, ce reseau reste a mettre en place.
Predicting response to chemotherapy in gastric cancer patients randomized to docetaxel: A reevaluation of the ITACA-S trial
Authors: F. Cecchi, D. Catenacci, S. Schwartz, S. Sellappan, Y. Tian, R. Miceli, F. Pietrantonio, A. Pellegrinelli, A. Martinetti, M. Di Bartolomeo, T. Hembrough
Journal: Annals of Oncology (2017)
Four study design principles for genetic investigations using next generation sequencing
Authors: Clinton C Mason
Journal: BMJ (2017)

Proper study design is crucial for obtaining meaningful results and reaching correct conclusions in scientific investigations. How to apply key study design principles to next generation sequencing (NGS) can be unclear and is sometimes overlooked by researchers who are new to this technology. A proper study design in NGS studies can be achieved with awareness of factors that can influence sequencing results and by taking the necessary steps to limit their biasing assessment. These steps include using simultaneously or similarly sequenced controls, randomising, determining the necessary sequencing depth, and performing a power calculation to determine the necessary sample size for testing hypotheses at significance levels adjusted for multiple comparisons. Applying study design principles to NGS studies will increase the likelihood of identifying genetic factors associated with human traits and diseases.
Alterations to trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (T-ADCC) in a lapatinib-resistant HER2+ breast cancer cell line model
Authors: N. Gaynor, M. Guibourdenche, B. Browne, L. O'Driscoll, N. O'Brien, N. O'Donovan, J. Crown, D. Collins
Journal: Annals of Oncology (2017)
Comprehensive characterization of BRCA1 and BRCA2 alterations in circulating tumor DNA and tumor tissue in men with prostate cancer: Implications for clinical care
Authors: P. Lara, J. McPherson, W. Heyer, R. Hartmaier, R. Devere White, J. Chung, S.M. Ali, M. Dall’Era
Journal: Annals of Oncology (2017)
Overexpression of the c-MET proto-oncogene in salivary duct carcinoma patients
Authors: C.M.L. Herpen, W. Boxtel, U.E. Flucke, E. Bloemena, E. Boon, G. Verhaegh, M.W. Aalders, M.A. Jonker, J. Schalken, Y.M.H. Versleijen-Jonkers
Journal: Annals of Oncology (2017)
PANOVA: a phase II study of TTFields (150 kHz) with concomitant standard chemotherapy for front-line advanced pancreatic adenocarcinoma: Updated efficacy results
Authors: M. Kueng, C. Guillen-Ponce, F. Rivera Herrero, J. Gallego Plazas, J.A. Lopez-Martin, M. Benavides
Journal: Annals of Oncology (2017)
The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes
Authors: Atsushi Anzai, Jennifer L. Choi, Shun He, Ashley M. Fenn, Manfred Nairz, Sara Rattik, Cameron S. McAlpine, John E. Mindur, Christopher T. Chan, Yoshiko Iwamoto, Benoit Tricot, Gregory R. Wojtkiewicz, Ralph Weissleder, Peter Libby, Matthias Nahrendorf, James R. Stone, Burkhard Becher, Filip K. Swirski
Journal: The Journal of Experimental Medicine (2017)

Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells. In the heart, fibroblast-derived GM-CSF alerts its neighboring myeloid cells to attract neutrophils and monocytes. The growth factor also reaches the bone marrow, where it stimulates a distinct myeloid-biased progenitor subset. Consequently, hearts of mice deficient in either GM-CSF or its receptor recruit fewer leukocytes and function relatively well, whereas mice producing GM-CSF can succumb from left ventricular rupture, a complication mitigated by anti–GM-CSF therapy. These results identify GM-CSF as both a key contributor to the pathogenesis of MI and a potential therapeutic target, bolstering the idea that GM-CSF is a major orchestrator of the leukocyte supply chain during inflammation.
Synergistic growth inhibition of human cancer cells with atrasentan and a Bcl-2 inhibitor
Authors: Erik Nielson, Lois Witters, Kim Leitzel, Allan Lipton
Journal: Cancer Research (2007)

4893   Endothelin-1 (ET-1), acting through its receptor ET A R, functions in normal tissue to regulate blood pressure and affect tissue differentiation and cell proliferation. It is also thought to play a role in the stimulation and metastasis of cancer cells. Atrasentan , an oral selective ET A R antagonist currently in clinical trials, inhibits ET-1 activity. Inhibitors of Bcl-2, an anti-apoptotic protein overexpressed in numerous human tumors, have been shown to induce apoptosis and sensitize cancer cells to various therapies. The purpose of this study was to assess the in vitro effects of combining Atrasentan and a  Bcl-2 inhibitor (ABT-737: Abbott Laboratories) on the growth of MCF-7 human breast cancer cells and LNCaP human prostate cancer cells. Cells were exposed to Atrasentan (5 - 30 μM) or ABT-737 ( 1-10 μM) alone or in combination for 3 days (16 different dose combinations were tested). Cell growth was determined using the colorimetric MTT tetrazolium dye assay. The Chou-Talalay method of isobologram analysis was performed to determine synergism. Dose-dependent growth inhibition was observed in both cell lines after 3 days exposure to each agent alone. Exposure to the combination of Atrasentan and the ABT-737 Bcl-2 inhibitor resulted in synergistic growth inhibition in both the MCF-7 human breast and LNCaP human prostate cancer cells. These results suggest this combination may provide a novel therapeutic strategy for treating breast and prostate cancer patients.
The 70-gene signature in node positive breast cancer: 10-year follow-up of the observational RASTER study
Authors: S.B. Vliek, V. Retel, C. Drukker, J.M. Bueno-De-Mesquita, E. Rutgers, H. van Tinteren, M.J. van de Vijver, J. Wesseling, W. van Harten, S.C. Linn
Journal: Annals of Oncology (2017)
Harvey ras (HRAS) mutations in head and neck cancer (HNC) and dependence on PI3K signaling and resistance to EGFR inhibition.
Authors: Katharina Endhardt, Arun Khattri, Michaela K. Keck, Zhixiang Zuo, Damian Rieke, Anna Lena Ress, Johannes Braegelmann, Kelley Leung, Derya Mahmutoglu, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2014)

6034 Background: HRAS is significantly mutated in head and neck squamous cell carcinomas (HNC) and is a putative oncogenic driver. We studied the impact of HRAS mutations and signaling, which remains poorly defined for HNSCC. Methods: We evaluated HRAS expression, copy number changes, and hotspot mutations in HNSCC tumor tissues and cell lines (Chicago HNC Genomics Cohort (CHGC) (N=120), HNC TCGA (N=279), and HNC cell lines (N=50). MAPK, PI3K-AKT pathway signaling was interrogated by immunoblotting, and viability/apoptosis were determined in HRAS mutant and control cell lines (HN4(G12D), BB49(Q61L) and H357(G13S)) in presence of EGFR, and/or PI3K inhibitors. Results: Incidence of HRAS mutations was 4% in CHGC and TCGA cohorts, and 6.1% in HNC cell lines – with almost exclusively canonical HRAS mutations. Neither HRAS expression nor copy number aberrations were associated with mutations, and no high-level CN aberrations occurred. HRAS siRNA gene knockdown was extremely effective at inducing apoptosis and decreased viability in all three HRAS mutated cell lines, but largely ineffective in control cell lines. Interestingly immunoblotting revealed that mutant HRAS signals exclusively via PI3K-AKT and not via the MAPK pathway. EGFR inhibition had no visible effect on viability or apoptosis in these cell lines, and did not impact PI3K pathway activity. By contrast PI3K inhibition was highly effective and induced apoptosis. Combinations of PI3K and EGFR inhibition showed synergy only in wild-type cell lines. Lastly we developed HRAS mutation gene expression signature that confirmed PI3K signaling dependence. By contrast HRAS wildtype co-expression modules enrich for EGFR and MAPK signaling. Conclusions: Canonical HRAS mutations are strong oncogenic drivers and in-vitro associated with high-level EGFR-resistance. Unlike KRAS in other tumor types, HRAS in HNC signals exclusively via the PI3K pathway, and PI3K inhibitors are effective at inducing apoptosis and decreased viability.
Increased attention‐deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use
Authors: J. Schmitt, A. Buske‐Kirschbaum, F. Tesch, K. Trikojat, V. Stephan, S. Abraham, A. Bauer, K. Nemat, F. Plessow, V. Roessner
Journal: Allergy (2017)

Epidemiologic evidence indicates a relevant association between atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD). Underlying mechanisms and ways to best identify subgroups of AD patients at risk for ADHD are poorly understood.To compare sociodemographic, clinical and psychosocial characteristics of children with AD, ADHD, comorbid AD/ADHD and age-matched healthy controls and to investigate aspects of AD related to ADHD symptoms.Applying a factorial design, we investigated 4 groups of children aged 6-12 years: AD-only (ie, without ADHD), ADHD-only (ie, without AD), AD + ADHD and healthy controls (HC; ie, no AD/no ADHD). Using validated instruments, ADHD symptoms and other behavioural problems, quality of life, parenting stress and sleeping problems were compared between groups. In children with AD-only, clinical signs (objective SCORAD), symptoms (POEM, VAS pruritus, VAS sleeping problems) and previous treatment of AD were assessed to investigate disease patterns related to ADHD symptoms.Compared to HC (n = 47), children with AD-only (n = 42), ADHD-only (n = 34) and comorbid AD + ADHD (n = 31) had significantly increased behavioural problems and decreased quality of life. Children with AD-only had significantly higher levels of ADHD symptoms than HC. In children with AD-only, previous use of antihistamines was significantly associated with increased ADHD symptoms (OR 1.88; 95% CI 1.04-3.39). Current clinical signs and AD symptoms were unrelated to the level of ADHD symptoms.Even if the clinical diagnosis of ADHD is excluded, children with AD show increased levels of ADHD symptoms. Further investigations need to determine whether early antihistamine exposure is a major risk factor for ADHD or a surrogate for previous AD severity and/or associated sleeping problems.
Surveillance de la borréliose de Lyme en Allemagne, 2002-2003
Authors: W H Mehnert, G Krause
Journal: Eurosurveillance (2005)

La borreliose de Lyme est une infection potentiellement grave, frequente en Allemagne, mais les donnees sur son incidence, sa dissemination et ses manifestations cliniques sont rares. La borreliose de Lyme n’est pas une maladie a declaration obligatoire en Allemagne, mais six des 16 regions allemandes - Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt et Thuringen, l’ont inclue dans leur systeme de notification. Dans ces regions, les efforts pour suivre les cas confirmes via la declaration permettent de mieux comprendre l’epidemiologie de la borreliose de Lyme en Allemagne. L’article presente un resume de l’analyse des cas de borreliose de Lyme transmis a l’institut Robert Koch en 2002-2003. 
Dans les six regions de l’est de l’Allemagne, l’incidence moyenne de la borreliose de Lyme a augmente de 31%, passant de 17,8/100 000 en 2002 a 23,3/100 000 en 2003. La repartition par âge des patients a mis en evidence une distribution bi-module avec un pic d’incidence chez les enfants de cinq a neuf ans, et un second pic chez les personnes plus âgees, de 60 a 64 ans en 2002 et de 65 a 69 en 2003. Pour les deux annees, 55% des patients etaient des femmes. Pres de 86% des cas ont ete declares entre mai et octobre. Un erytheme chronique migrant a affecte 2697 patients (89,3%) en 2002 et 3442 (86,7%) en 2003. 
Dans le cas d’une maladie transmise par un vecteur, comme la maladie de Lyme, le risque d’infection depend du degre et de la duree du contact entre les hommes et les tiques infestees par Borrelia burgdorferi. Des tiques infectees etant probablement presentes sur l’ensemble du territoire, la situation des dix autres regions allemandes est vraisemblablement comparable a celle decrite dans cette etude.
ODM-208, a novel CYP11A1-inhibitor as a therapeutic approach for the treatment of castration-resistant prostate cancer
Authors: R. Oksala, M. Karimaa, M. Ramela, R. Riikonen, R. Huhtaniemi, P. Rummakko, G. Wohlfahrt, A. Vuorela, M.V. Mustonen, P. Kallio
Journal: Annals of Oncology (2017)
The influence of body composition on the systemic exposure of paclitaxel in esophageal cancer patients
Authors: L. Van Doorn, H.N. Rier, J.L.A. van Vught, C. van Kesteren, S. Bins, R.H.J. Mathijssen, M-D. Levin, S.L.W. Koolen
Journal: Annals of Oncology (2017)
A phase 1 study of osimertinib and bevacizumab as initial treatment for patients with EGFR-mutant lung cancers.
Authors: Helena Alexandra Yu, Sara A. Hayes, Robert J. Young, Ai Ni, Christopher Rodriguez, Alex Makhnin, Gregory J. Riely, Mark G. Kris
Journal: Journal of Clinical Oncology (2017)

9033 Background: EGFR tyrosine kinase inhibitors (TKI) are the recommended first line treatment for EGFR-mutant lung cancers. Osimertinib, an EGFR TKI that inhibits both sensitizing EGFR mutations and EGFR T790M, is approved for use after progression on an EGFR TKI with evidence of EGFR T790M, and is currently being assessed as initial treatment for EGFR-mutant lung cancers. The addition of bevacizumab to erlotinib resulted in improved progression free survival (PFS) compared to erlotinib alone as initial treatment (16 vs 10 months, HR 0.41). This phase 1/2 study is assessing osimertinib and bevacizumab as initial treatment for patients with EGFR-mutant lung cancers. Methods: We evaluated toxicity and efficacy of osimertinib and bevacizumab as initial treatment for patients with advanced EGFR-mutant lung cancers. Using a 3+3 design, full doses of osimertinib (80mg PO daily) and bevacizumab (15mg/kg IV q3 weeks) were given, with a planned dose de-escalation (osimertinib 40mg PO daily) should grade 3 or greater toxicity be seen. Six patients must be treated without a dose-limiting toxicity (DLT) to determine the MTD. 43 additional patients will be treated at the MTD in the phase 2 study, with a primary endpoint of PFS at 12 months. Response was evaluated by RECIST 1.1. Results: From Sept 2016 to Jan 2017, 15 patients were enrolled. Median age: 63; Women 11; EGFR L858R = 8, Ex19del = 6, G709A/G719S = 1. After median duration of treatment of 2.7 months, no DLTs were seen in any patient. The MTD was determined to be osimertinib 80mg, bevacizumab 15mg/kg q3 weeks. In total, 15 patients are being treated at the MTD to date. Treatment-related adverse events (AE) were all grade 1-2, except for grade 3 hypertension. The most frequent treatment-related AEs (any grade) were rash (53%), diarrhea (40%), hypertension (33%), fatigue (20%), and itching (20%). All 15 patients continue on study. Conclusions: Combination osimertinib and bevacizumab is a tolerable first-line treatment for patients with EGFR-mutant lung cancers and the MTD is osimertinib 80mg and bevacizumab 15mg/kg q3 weeks. Assessment of efficacy with an endpoint of PFS at 12 months is ongoing. Supported by AstraZeneca (NCT02803203). Clinical trial information: NCT02803203.
GW28-e0736 Digoxin-induced Anemia among Patients with Atrial Fibrillation and Heart Failure: Clinical Data Analysis and Drug-gene Interaction Network
Authors: Yubi Lin, Yumei Xue, Siqi He, Ruiling Feng, Zhe Xu, Wanqun Chen, Zifeng Huang, Yang Liu, Qianhuan Zhang, Bin Zhang, Kejian Wang, Shulin Wu
Journal: Journal of the American College of Cardiology (2017)
Patterns of progression under antiPD1/PDL1 in advanced NSCLC patients allow discriminating pseudo-progression from real progression
Authors: C. Caramella, M. Tazdait, L. Mezquita, J. Lahmar, R. Ferrara, A. Marabelle, C. Balleyguier, D. Planchard, A. Gazzah, J-C. Soria, B. Besse
Journal: Annals of Oncology (2017)
Avaliação epidemiológica e virológica da actividade gripal na Europa durante a temporada 2003-2004
Authors: W J Paget, T J Meerhoff, A Meijer
Journal: Eurosurveillance (2005)

Na Europa, a temporada da gripe 2003-2004 foi marcada pela disseminacao de uma nova variante, o virus A/Fujian/411/2002 (H3N2), um pouco differente do componente da estirpe A(H3N2) utilizada na vacina antigripal. Na Europa, foram detectados casos esporadicos no fim da temporada 2003-2004 e a actividade gripal associada com este virus occorreu no principio da temporada 2003-2004. Geralmente, a actividade gripal manifestou-se primeiro na Europa occidental (Irlanda, Reino Unido e peninsula iberica) nos meses de outobro e novembro, pois foi se deslocando em direcao do leste a traves da Europa, afectando a Letonia, a Lituania e a Polonia em janeiro e fevereiro de 2004. Em geral, a intensidade da actividade clinica foi superior a aquela da temporada 2002-2003 (segundo 13 redes das 20). Alem disso, nos paises que declarem dados por grupos etarios as taxas de consultas mais altas foram observadas em criancas de 0 a 14 anos. No entanto, apesar da emergencia desta nova variante A(H3N2), as incidencias clinicas nao aumentaram especialmente, comparadas com os dados historicos. A composicao da vacina antigripal 2004-2005 foi modificada comparada com a temporada 2003-2004, e inclui uma estirpe semelhante ao virus A/Fujian/411/2002 (H3N2) e uma nova estirpe de tipo B (B/Shanghai/361/2002).
OCTOVA: A randomised phase II trial of olaparib, chemotherapy, or olaparib and cediranib in patients with BRCA-mutated platinum-resistant ovarian cancer
Authors: S. Nicum, V.Y. Strauss, N. McGregor, I. McNeish, R. Roux, M. Hall, A. Michael, C. Roberts
Journal: Annals of Oncology (2017)
Revealing potential immune responses (IRs) in patients with advanced colorectal cancer (aCRC) on first line chemotherapy: A prospective study of neutrophil to lymphocyte ratio, immune function and outcome
Authors: S. Turnbull, E. West, K. Scott, E. Tidswell, A. Melcher, M. Seymour, C. Ralph, J. Seligmann
Journal: Annals of Oncology (2017)
Young endothelial cells revive aging blood
Authors: Vivian Y. Chang, Christina M. Termini, John P. Chute
Journal: Journal of Clinical Investigation (2017)

The hematopoietic system declines with age, resulting in decreased hematopoietic stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell depletion. Aging of the hematopoietic system is associated with an increased incidence of myeloid malignancies and a decline in adaptive immunity. Therefore, strategies to rejuvenate the hematopoietic system have important clinical implications. In this issue of the JCI, Poulos and colleagues demonstrate that infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted HSC self-renewal and restored immune cell content in aged mice. Additionally, delivery of young BM ECs along with HSCs following total body irradiation improved HSC engraftment and enhanced survival. These results suggest an important role for BM endothelial cells (ECs) in regulating hematopoietic aging and support further research to identify the rejuvenating factors elaborated by BM ECs that restore HSC function and the immune repertoire in aged mice.
Proteomics of triple negative breast cancer developing metastases to central nervous system
Authors: K. Rojas, L. Trilla-Fuertes, A. Gámez, J. Sepulveda Sanchez, L. Manso Sánchez, G. Prado-Vásquez, C. Chiva, A. Zapater-Moros, S. Llorente-Armijo, D.C. Mendiola, E. Sabidó, J.A. Fresno, E.M. Ciruelos Gil, L. Paz-Ares
Journal: Annals of Oncology (2017)
Tumor hyaluronan (HA) is a novel biomarker: Results of the randomized phase 2 HALO 202 study of PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) vs AG in previously untreated, metastatic pancreatic ductal adenocarcinoma (mPDA)
Authors: A. Hendifar, A. Bullock, T. Seery, L. Zheng, D. Sigal, P.S. Ritch, F.S. Braiteh, M. Zalupski, N. Bahary, W. Harris, J. Pu, F. Lian, J. Zhu, W. Wu, D. Chondros, P. Jiang, S.R. Hingorani
Journal: Annals of Oncology (2017)