tbuckley/cabot-search huggingface dataset:
A prospective case-controlled cohort study of endothelial function in patients with moderate to severe psoriasis
Authors: C.L. Martyn-Simmons, R.R. Ranawaka, P. Chowienczyk, M.A. Crook, M.S. Marber, C.H. Smith, J.N.W.N. Barker
Journal: British Journal of Dermatology (2010)

Journal Article A prospective case‐controlled cohort study of endothelial function in patients with moderate to severe psoriasis Get access C.L. Martyn‐Simmons, C.L. Martyn‐Simmons St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.R. Ranawaka, R.R. Ranawaka St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. Chowienczyk, P. Chowienczyk Departments of Clinical Pharmacology Search for other works by this author on: Oxford Academic Google Scholar M.A. Crook, M.A. Crook Chemical Pathology and Search for other works by this author on: Oxford Academic Google Scholar M.S. Marber, M.S. Marber Cardiology, Cardiovascular Division, King's College London & Guy's and St Thomas' NHS Foundation Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.H. Smith, C.H. Smith St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.N.W.N. Barker J.N.W.N. Barker St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, Guy's Hospital, London SE1 9RT, U.K. Correspondence: J.N.W.N. Barker. E‐mail: jonathan.barker@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 26–32, https://doi.org/10.1111/j.1365-2133.2010.10031.x Published: 01 January 2011
Publication of surgeon specific outcome data: A review of implementation, controversies and the potential impact on surgical training
Authors: P.D. Radford, L.F. Derbyshire, J. Shalhoub, J.E.F. Fitzgerald
Journal: International Journal of Surgery (2014)

Government-mandated publication of named surgeon-specific outcome data (SSD) has recently been introduced across nine surgical speciality areas in England. This move is the first time that such national data has been released in any country, and it promises to provide a significant advancement in health service transparency. Data is derived from nine preexisting national surgical audit databases. However, eight of these were not originally designed for this purpose, and there is considerable controversy surrounding data quality, risk adjustment, patient use and interpretation, and surgeons' subsequent case selection. Concerns also surround the degree to which these results truly reflect the individual consultant, or the wider hospital team and accompanying resources. The potential impact on surgical training has largely been overlooked. This paper investigated the background to SSD publication and controversies surrounding this, the potential impact on surgical training and the response to these concerns from medical and surgical leaders. As SSD collection continues to be refined, the most appropriate outcomes measurements need to be established, and risk adjustment requires ongoing improvement and validation. Prospective evaluation of changes in surgical training should be undertaken, as any degradation of will have both short and long-term consequences for patients and surgeons alike. It is important that the literature supporting the safety of supervised trainee practice is also promoted in order to counterbalance any potential concerns that might detract from trainee operating opportunities. Finally, it is important that outcomes data is communicated to patients in the most meaningful way in order to facilitate their understanding and interpretation given the complexities of the data and analysis involved.
Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer
Authors: Chantal Stoepker, Najim Ameziane, Petra van der Lelij, Irsan E. Kooi, Anneke B. Oostra, Martin A. Rooimans, Saskia E. van Mil, Arjen Brink, Ralf Dietrich, Jesper A. Balk, Bauke Ylstra, Hans Joenje, Stephan M. Feller, Ruud H. Brakenhoff
Journal: Cancer Research (2015)

Abstract Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non–Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. Cancer Res; 75(17); 3543–53. ©2015 AACR.
Processes for Effective Communication in Primary Care
Authors: Saul J. Weiner, Beth Barnet, Tina L. Cheng, Timothy P. Daaleman
Journal: Annals of Internal Medicine (2005)

Communication in the delivery of health care services occurs along 2 axes: between providers and patients and among several providers. In primary care, a principle objective in the provider–patient relationship is facilitating whole-person care, which is care provided in the context of family and community. In addition, primary care emphasizes communication between the primary care physician and other providers with the goal of integrated care, or care provided in the context of a patient's overall health care needs. However, considering both the U.S. health care delivery system and medical education programs, several obstacles interfere with the necessary processes of communication. This paper addresses those obstacles with a conceptual framework for effective communication in primary care. Recommendations propose formalizing requirements for the exchange of information among providers, enhancing communication training, disseminating information technology, and mitigating external factors that disrupt communication in primary care.
Prostate Cancer Progression and Survival in BRCA2 Mutation Carriers
Authors: L. Tryggvadottir, L. Vidarsdottir, T. Thorgeirsson, J. G. Jonasson, E. J. Olafsdottir, G. H. Olafsdottir, T. Rafnar, S. Thorlacius, E. Jonsson, J. E. Eyfjord, H. Tulinius
Journal: JNCI Journal of the National Cancer Institute (2007)

Mutations in the BRCA2 gene are associated with an increased risk of prostate cancer, but it is not known whether they are associated with progression of the disease. We compared prostate cancer-specific survival, disease stage, and tumor grade between prostate cancer patients carrying the Icelandic BRCA2 999del5 founder mutation and noncarriers.Using population-based registries, we identified all 596 prostate cancer patients who were diagnosed in Iceland during 1955 through 2004 among 29603 male relatives of unselected breast cancer probands. BRCA2 mutation status could be determined for 527 patients (88.4%). Stage and grade were abstracted from original records, blindly with respect to mutation status, for a subgroup of 89 patients that included all mutation carriers and, for each carrier, two control patients without the BRCA2 999del5 mutation who were matched to the carrier on years of diagnosis and birth. Hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer-specific survival were estimated using multivariable regression models. All statistical tests were two-sided.The mutation was carried by 30 patients (5.7%). Compared with noncarriers, BRCA2 999del5 mutation carriers had a lower mean age at diagnosis (69.0 years versus 74.0 years; P = .002), more advanced tumor stage (stages 3 or 4, 79.3% versus 38.6%; P < .001), higher tumor grade (grades G3-4, 84.0% versus 52.7%, P = .007), and shorter median survival time (2.1 years, 95% CI = 1.4 to 3.6 years, versus 12.4 years, 95% CI = 9.9 to 19.7 years). Carrying the BRCA2 999del5 mutation was also associated with an increased risk of dying from prostate cancer (adjusting for year of diagnosis and birth, HR = 3.42, 95% CI = 2.12 to 5.51); the association remained after adjustment for stage and grade (HR = 2.35, 95% CI = 1.08 to 5.11). The prognosis of BRCA2 999del5 mutation carriers was not associated with period of diagnosis or with relatedness to breast cancer probands.The Icelandic BRCA2 999del5 founder mutation was strongly associated with rapidly progressing lethal prostate cancer.
HDJ-2 as a Target for Radiosensitization of Glioblastoma Multiforme Cells by the Farnesyltransferase Inhibitor R115777 and the Role of the p53/p21 Pathway
Authors: Chun-Chieh Wang, Yu-Pei Liao, Paul S. Mischel, Keisuke S. Iwamoto, Nicholas A. Cacalano, William H. McBride
Journal: Cancer Research (2006)

Abstract Resistance of glioblastoma multiforme to radiotherapy poses a major clinical challenge. Farnesyltransferase inhibitors (FTI), such as R115777, have potential to increase radiotherapeutic benefit in this disease, although their mechanism of action is unclear. In our study with eight glioblastoma multiforme cell lines, the most sensitive ones underwent cell cycle arrest in response to FTI treatment. Radiosensitization by FTIs, however, seemed to involve other pathways. If R115777 treatment was initiated &amp;lt;6 hours before irradiation, all eight glioblastoma multiforme lines were radiosensitized. However, if the time between drug and radiation was extended to 24 hours, cells harboring wild type but not mutated p53 were able to counteract drug-induced radiosensitization. The involvement of the p53/p21 pathway in the development of resistance was confirmed by showing that U87 cells transfected with human papillomavirus E6 to block p53 or interfering RNA to inhibit p21 stayed radiosensitive for 24 hours after drug treatment. The time dependency of R115777-induced radiosensitization suggested that the initial FTI target for early radiosensitization was short-lived, and that a p21-directed pathway restored resistance. Consideration of prenylated molecules that could potentially be involved led us to consider HDJ-2, a co-chaperone of heat shock protein 70. This hypothesis was strengthened by finding that cellular radiosensitivity was increased by genetic inhibition of HDJ-2, whereas overexpression conferred radioresistance. Importantly, irradiation of cells caused HDJ-2 to migrate from the cytoplasm to the nucleus, and this migration was inhibited by prior FTI treatment. These results have clinical relevance in that they help explain the variability in responses to FTIs that occurs following radiotherapy and elucidate some of the reasons for the complexity underlying FTI-induced radiosensitization. (Cancer Res 2006; 66(13): 6756-62)
Settings and artefacts relevant in colour/power Doppler ultrasound in rheumatology
Authors: S T Torp-Pedersen, L Terslev
Journal: Annals of the Rheumatic Diseases (2007)

The paper explains the most important parameters for the use of colour and power Doppler in rheumatology. Recommendations for machine settings are given. The commonly encountered artefacts and their importance for image interpretation are explained.
Selectively Enhanced Cellular Signaling by G <sub>i</sub> Proteins in Essential Hypertension
Authors: Frank Pietruck, Albrecht Moritz, Michael Montemurro, Alexandra Sell, Stefan Busch, Dieter Rosskopf, Sebastian Virchow, Helmut Esche, Norbert Brockmeyer, Karl H. Jakobs, Winfried Siffert
Journal: Circulation Research (1996)

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)–sensitive guanine nucleotide–binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein–mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca 2+ ] i rises induced by lyso -phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [ 3 H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of G s with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of Gα i2 , Gα i3 , Gβ 2 , and Gβ 4 . Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits Gα i2 , Gα i3 , Gβ 1 , and Gβ 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.
Transfer of microRNAs by extracellular membrane microvesicles: a nascent crosstalk model in tumor pathogenesis, especially tumor cell-microenvironment interactions
Authors: Li Zhang, C Alexander Valencia, Biao Dong, Meng Chen, Pu-Jun Guan, Ling Pan
Journal: Journal of Hematology & Oncology (2015)

Anticancer treatments aiming at killing malignant cells have been applied for decades but have been unsuccessful at curing the disease. The modern concept of tumor microenvironment, especially angiogenesis, suggests that the tumor is not only composed of malignant cells, but also consists of other groups of cells that work together. Recently, genetic message transfer has been revealed between tumor cells and their microenvironment. The latest cell-derived vector, extracellular membrane microvesicles (EMVs), has been found to provide membrane protection and allowed to deliver genetic information beyond the cells. Additionally, EMV-associated microRNAs are involved in a variety of cellular pathways for tumor initiation and progression. Previous published reviews have focused on miRNA that included EMVs as a sensitive marker for tumor monitoring in clinical applications that are based on the alteration of their expression levels in conjunction with disease occurrence and progression. From the aspect of cellular crosstalk, this article will review the role of EMV-mediated microRNA transfer in tumor pathogenesis, including tumor treatment obstacles, history and features, and current research in inflammatory/immune pathologies, as well as in solid tumors and hematological malignancies. This nascent crosstalk model will provide a novel insight into complementing the classic mechanisms of intercellular communication and contribute to the potential therapeutic strategy via small RNA molecule-carrying EMVs for multimodality treatment of cancer.
Screening and Diagnosis of Gestational Diabetes Mellitus
Authors: Ofra Kalter-Leibovici, Laurence S. Freedman, Liraz Olmer, Nicky Liebermann, Anthony Heymann, Orna Tal, Liat Lerner-Geva, Nir Melamed, Moshe Hod
Journal: Diabetes Care (2012)

To study the implications of implementing the International Association of Diabetes in Pregnancy Study Group (IADPSG) recommendations for screening and diagnosis of gestational diabetes mellitus (GDM) in Israel and explore alternative methods for identifying women at risk for adverse pregnancy outcomes.We analyzed data of the Israeli Hyperglycemia and Adverse Pregnancy Outcomes study participants (N = 3,345). Adverse outcome rates were calculated and compared for women who were positive according to 1) IADPSG criteria, 2) IADPSG criteria with risk stratification, or 3) screening with BMI or fasting plasma glucose (FPG).Adopting IADPSG recommendations would increase GDM diagnosis by ∼50%. One-third of IADPSG-positive women were at low risk for adverse outcomes and could be managed less intensively. FPG ≥89 mg/dL or BMI ≥33.5 kg/m(2) at 28-32 weeks of gestation detected proportions of adverse outcomes similar to IADPSG criteria.Implementing IADPSG recommendations will substantially increase GDM diagnosis. Risk stratification in IADPSG-positive women may reduce over-treatment. Screening with FPG or BMI may be a practical alternative.
Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome)
Authors: Pia Ostergaard, Michael A Simpson, Fiona C Connell, Colin G Steward, Glen Brice, Wesley J Woollard, Dimitra Dafou, Tatjana Kilo, Sarah Smithson, Peter Lunt, Victoria A Murday, Shirley Hodgson, Russell Keenan, Daniela T Pilz, Ines Martinez-Corral, Taija Makinen, Peter S Mortimer, Steve Jeffery, Richard C Trembath, Sahar Mansour
Journal: Nature Genetics (2011)
Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo
Authors: Anna K Walduck, Matthias Weber, Christian Wunder, Stefan Juettner, Manfred Stolte, Michael Vieth, Bertram Wiedenmann, Thomas F Meyer, Michael Naumann, Michael Hoecker
Journal: Molecular Cancer (2009)

Abstract Background Helicobacter pylori is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the Cox-2 gene is up-regulated in the gastric mucosa during H. pylori infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an in vivo model, thereby identifying potential targets for the study of the role of Cox- 2 in H. pylori pathogenesis and the initiation of pre- cancerous changes. Results Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after H. pylori infection. H. pylori infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of H. pylori infection. The Cox-2 dependent subset included those influencing gastric physiology ( Gastrin, Galr1 ), epithelial barrier function ( Tjp1, connexin45, Aqp5 ), inflammation ( Icam1 ), apoptosis ( Clu ) and proliferation ( Gdf3, Igf2 ). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression. Conclusion This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by H. pylori infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.
Repeatability of breathlessness measurements in cancer patients
Authors: A WILCOCK, V CROSBY, D CLARKE, A TATTERSFIELD
Journal: Thorax (1999)

The case history is described of a young woman who presented with primary pulmonary hypertension and non-specific inflammatory signs.The patient received prolonged immunosuppressive treatment with low dose methotrexate and prednisone without any vasodilator agent.After one year the pulmonary artery pressure fell from a mean value of 47 mm Hg to 30 mm Hg and there was a corresponding clinical response.This case suggests that, in patients with pulmonary hypertension of unknown origin, immunopathogenetic factors should be sought in order to consider the utility of immunosuppressive therapy.
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial
Authors: Rafael Rosell, Enric Carcereny, Radj Gervais, Alain Vergnenegre, Bartomeu Massuti, Enriqueta Felip, Ramon Palmero, Ramon Garcia-Gomez, Cinta Pallares, Jose Miguel Sanchez, Rut Porta, Manuel Cobo, Pilar Garrido, Flavia Longo, Teresa Moran, Amelia Insa, Filippo De Marinis, Romain Corre, Isabel Bover, Alfonso Illiano, Eric Dansin, Javier de Castro, Michele Milella, Noemi Reguart, Giuseppe Altavilla, Ulpiano Jimenez, Mariano Provencio, Miguel Angel Moreno, Josefa Terrasa, Jose Muñoz-Langa, Javier Valdivia, Dolores Isla, Manuel Domine, Olivier Molinier, Julien Mazieres, Nathalie Baize, Rosario Garcia-Campelo, Gilles Robinet, Delvys Rodriguez-Abreu, Guillermo Lopez-Vivanco, Vittorio Gebbia, Lioba Ferrera-Delgado, Pierre Bombaron, Reyes Bernabe, Alessandra Bearz, Angel Artal, Enrico Cortesi, Christian Rolfo, Maria Sanchez-Ronco, Ana Drozdowskyj, Cristina Queralt, Itziar de Aguirre, Jose Luis Ramirez, Jose Javier Sanchez, Miguel Angel Molina, Miquel Taron, Luis Paz-Ares
Journal: The Lancet Oncology (2012)