tbuckley/cabot-search huggingface dataset:
Arrowsmith
Authors: Robert Bud
Journal: BMJ (2007)

Arrowsmith has a claim to be the greatest ever novel about medical research. Writing at the very beginning of a revolution in medicine that would yield a generation of powerful drugs, Sinclair Lewis evokes the past, present, and future of the profession, all through the career of Dr Martin Arrowsmith. Informed by Lewis's friend, the ex-Rockefeller Institute scientist Paul De Kruif, the book is based on real characters and actual institutions. It is a cutting satire, but beneath the wit is a powerful call to recognise science as the source of both truth and health. Numerous scientists maturing in the boom of biomedicine after the second world war testified to the book's allure.

Lewis was writing at a time when a drug that would fight the causes of most infection was as yet a vision without substance; penicillin still lay two decades in the future. His adviser, de Kruif, was however closely connected to the research on, and aware of the hopes for, the newly discovered phage viruses as means of destroying bacteria. The apparent success of phage treatment for plague therefore plays a key part in the novel. Indeed the book's invocation of the potential of phage straddles the line between fiction and reality.

If phage seemed to Lewis to be the alluring future, the promotion of sanitary behaviour is presented as the corrupt present. The most humorous part of the book is the description of Arrowsmith's time as assistant to the director of public health in the small town of Nautilus. His boss, Almus Pickerbaugh, is a wonderful rendition of the enthusiast in early 20th century United States. He began January with “Better Babies Week,” followed hotly by “Banish the Booze Week,” “Tougher Teeth Week,” and “Stop the Spitter Week.” This zealous promotion of sanitation is not just funny but also accurate. At the time, the real life Health and Happiness League was asking members to boycott public drinking fountains and to destroy all houseflies.

The novel's eponymous hero fails to cope with the absurdities of the public health department. Instead he escapes to the McGurk Institute, modelled on the Rockefeller Institute. Even here, he encounters managers—“men of measured merriment”—as well as his hero, the truth-seeking Max Gottlieb (modelled in part on Jacques Loeb). He is caught in the tensions between pure and applied science, yet there Arrowsmith can aspire to use fundamental knowledge to make great advances.

In the decades since the book's publication, McGurk and its real life analogues have served as the cradles of hopes for better health. Yet, at the beginning of the 21st century, the issues dealt with by that public health department in Nautilus have fresh importance. The relations between prevention, cure, and citizenship are again being renegotiated. So, although it is now more than 80 years old, Arrowsmith speaks to contemporary concerns—and fortunately this classic is still regularly reprinted.
Abstract LB-272: AXL induces epithelial to mesenchymal transition and regulates the function of breast cancer stem cells.
Authors: Michael K. Asiedu, Francis Beauchamp-Perez, James N. Ingle, Marshall D. Behrens, Derek C. Radisky, Keith Knutson
Journal: Cancer Research (2013)

Abstract Despite significant progress in the treatment of breast cancer particularly through the use of targeted therapy, relapse and chemo-resistance remain a major hindrance in the fight to minimize the burden of the disease. Accumulating evidence suggest that breast cancer stem cells (BCSCs), which show resistance to chemotherapy and radiation, drive tumor initiation and disease recurrence. It is becoming increasingly clear that a rare subpopulation of cells known as cancer stem cells (CSC), able to be generated through epithelial to mesenchymal transition (EMT) and capable of tumor initiation and self-renewal, contributes to treatment resistance and metastases. This means that a more effective therapy should target both the chemoresistant CSCs and the proliferating epithelial cells that give rise to them in order to reverse EMT and attenuate their conversion to CSCs. Here, we demonstrate a novel function of AXL in acting upstream to induce EMT in normal and immortalized human mammary epithelial cells in an apparent positive feedback loop mechanism and regulate breast CSC (BCSC) self-renewal and chemoresistance. Downregulation of AXL expression using AXL inhibitor MP470 (amuvatinib) or shRNA reversed EMT in mesenchymal normal human mammary epithelial cells and murine BCSCs attenuating self-renewal and restored chemosensitivity of the BCSCs. AXL expression was also found to be associated with expression of stem cell genes, regulation of metastases genes, increased tumorigenicity, and was important for BCSC invasion and migration. Inactivation of AXL also led to downregulation of NFκB pathway and reduced tumor formation in vivo. Together, our data suggest that targeted therapy against AXL, in combination with systemic therapies, has the potential to improve response to anti-cancer therapies and to reduce breast cancer recurrence and metastases. Citation Format: Michael K. Asiedu, Francis Beauchamp-Perez, James N. Ingle, Marshall D. Behrens, Derek C. Radisky, Keith Knutson. AXL induces epithelial to mesenchymal transition and regulates the function of breast cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-272. doi:10.1158/1538-7445.AM2013-LB-272
Shedding light on glioblastoma cellular heterogeneity
Authors: P. O. Zinn, S. K. Singh, R. R. Colen
Journal: Neuro-Oncology (2015)

Cellular heterogeneity is one of the key contributors to poor clinical outcome in glioblastoma (GBM). In this issue Lathia and colleagues1 report on the development of a novel mouse model where the GFAP-tva mouse2 harbors a Sox2-EGFP reporter3 to enable direct visualization of intratumoral cellular heterogeneity in a RCAS-PDGFβ-driven4 GBM model. Cellular heterogeneity is associated with one of the salient features of glioblastoma stem cells (GSCs). Multiple studies have elucidated that GSCs are a unique subpopulation of cells within GBM and are responsible for hierarchical cellular organization.5 Additionally, GSCs may potentially orchestrate multiple other aspects of GBM biology, including resistance to therapy, tumor recurrence, and cellular invasion, thus contributing to dismal clinical outcomes despite aggressive therapy.6 The characterizations of GSCs isolated/enriched from surgical human GBM specimens have lent support to the cancer stem cell hypothesis and have opened avenues for understanding the complex dynamics of cancer progression, recurrence, and resistance to therapy. Thus far, marker-based enrichment of GSCs has remained controversial due to the potential dissociation from their ‘stem-cell state’ once removed from their native tumor niche (e.g. perivascular7).
GW25-e3115 Transcatheter Closure of Ruptured Sinus Valsalva Aneurysms Using Patent Ductus Arteriosus Occluders
Authors: Fang Zhenfei, Huang Yiyuan, Tang Liang, Hu Xinqun, Shen Xiangqian, Tang Jianjun, Zhou Shenghua
Journal: Journal of the American College of Cardiology (2014)
OP0194-HPR Clinical outcomes of nurse-led care for people with RA: A multicentre RCT:
Authors: M. Ndosi, M. Lewis, C. Hale, H. Bird, S. Ryan, H. Quinn, L. McIvor, J. Taylor, G. Burbage, D. Bond, J. White, D. Chagadama, S. Green, L. Kay, A.V. Pace, V. Bejarano, P. Emery, J. Hill
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Despite the development of the innovative rheumatology nurse-led clinics (NLC) in the UK, the evidence of their effectiveness is limited. <h3>Objectives</h3> To compare the outcomes of NLC to those obtained by rheumatologist-led clinics (RLC) for people with RA. The null hypothesis tested is that NLC is inferior to RLC. <h3>Methods</h3> This was a multi-centred, non-inferiority RCT. The non-inferiority margin was DAS28 change of 0.6 from baseline (primary outcome) and standardised effect size for secondary outcomes (pain, fatigue, stiffness, RAQoL, HAQ, HAD, ASES and EQ5D-VAS). Patients were assessed at baseline and at weeks 13, 26, 39 &amp; 52. Mean differences between the two groups at follow-up were estimated using linear mixed models controlling for age, gender, centre, baseline DAS28 and corresponding baseline values for secondary outcomes. This was done following per-protocol (PP) and Intention-to-treat (ITT) strategies. Level of patient satisfaction was also compared between groups. <h3>Results</h3> Patients under NLC (n=91) were comparable to those under RLC (n=90) in their demographic and baseline characteristics. Their mean (SD) age was 58.5 (11.6); disease duration 9.9 (10.7) years and 74% were female. NLC made fewer medication changes, ordered fewer X-Rays but made more conferrals, gave more patient education and psychosocial support than RLC. There was little difference in the numbers of referrals made to other health professionals. Change scores (for DAS28) at each follow-up time point and overall differences between the two groups (all outcomes) are presented in Table 1. The primary outcome demonstrated that NLC was not inferior to RLC at any follow-up time. Confidence interval estimates for all outcomes included zero; the standardized effect sizes in each case were “small”. The results were similar for the PP and ITT analyses. Levels of patient satisfaction were on average greater for the NLC group. <h3>Conclusions</h3> This was the first multicentre RCT of effectiveness of rheumatology NLC in the UK. The findings provide robust evidence against the null hypothesis; demonstrating that NLC is well-received and effective in the management of RA. <h3>Disclosure of Interest</h3> None Declared
THE ASSOCIATION OF HIGH-DENSITY LIPOPROTEIN CHOLESTEROL WITH LONG-TERM ADVERSE EVENTS AMONG PATIENTS WITH ESTABLISHED CORONARY ARTERY DISEASE: INSIGHTS FROM THE IMPROVE-IT TRIAL
Authors: Rajendra H. Mehta, Jie-Lena Sun, Yuliya Lokhnygina, Kristy Watkins, Matthew Roe, Ramón Corbalán, Michael Blazing
Journal: Journal of the American College of Cardiology (2016)
Book: Rural Healthcare
Authors: A. Savage
Journal: BMJ (1999)

Jim Cox, Iain Mungall Radcliffe Medical Press; £22.50, pp 184 ISBN 1 85775 267 8 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> For half my working life I was a general practitioner in inner London. Then I worked partly in Africa and partly “locuming” round Britain, from St Austell to Papa Westray. I found myself in a different world, one that this book powerfully reminds me of. The distances; the loneliness, sometimes welcome, sometimes not; the independence and self sufficiency of the people “What about the rota?” I asked my first employer … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
PWE-124 Understanding The Mechanisms Underpinning Treatment Non-response In Primary Biliary Cirrhosis: A Tool For Treatment Stratification
Authors: AC Pitts, JM Palmer, DE Jones, JK Dyson, L Griffiths, S Ducker, JA Kirby
Journal: Gut (2014)

<h3>Introduction</h3> The pathogenesis of Primary Biliary Cirrhosis (PBC) is poorly understood. The Th1 CD4<sup>+</sup> cell subset has known involvement, however, the Th17 subset demonstrated in autoimmune disease requires further investigation. Ursodeoxycholic acid (UDCA) is the primary treatment and response is measured by liver biochemistry change; suboptimal improvement (non-response) has a poorer prognosis and there remains a lack of effective second-line therapies. This study aimed to pilot transcriptional investigation of T-cells in PBC, including UDCA response stratification and Th17 polarisation, following recent revelation of demographic associations with non-response. <h3>Methods</h3> Affymetrix® GeneChip® Microarray analysis examined the gene expression differences of CD4<sup>+</sup> T-cells isolated from PBC responders (n = 3), non-responders (n = 4) and healthy controls (n = 3). The samples studied were taken at baseline and after culture with anti-CD3/28 beads +/- Th17 polarising cytokines. <h3>Results</h3> 900 genes were significantly differentially expressed with &gt;2 fold change in patients versus healthy controls and 113 genes in responsive versus non-responsive groups at baseline. Study of CD3/28 activated cells +/-Th17 polarisation revealed no significant differences. In PBC patients, features up-regulated included CD69 (adjusted p &lt; 0.00005) and those down-regulated HLA class II transcripts (p &lt; 0.05). <h3>Conclusion</h3> Despite a small cohort, for the first time using microarray, this project demonstrated differences between PBC patients and healthy individuals and, importantly, between UDCA response groups. This substantiates the view that UDCA non-responsive disease represents a distinct biological entity requiring different clinical management. Up-regulation of the activation marker CD69 implies ongoing T-cell stimulation in PBC. HLA class II transcript down-regulation may imply a role in T cell anergy or regulation. <h3>Disclosure of Interest</h3> None Declared.
PWE-130 Phenotype And Localisation Of Liver Infiltrating B Cell Subsets In Autoimmune And Inflammatory Liver Diseases
Authors: D Geh, H Jeffery, DH Adams, YH Oo
Journal: Gut (2014)

<h3>Introduction</h3> B cells classically provide humoral immunity in the form of antibody production as part of the adaptive immune response. Regulatory and antigen presenting functions of B cells have been reported before and autoantibodies are associated with autoimmune liver diseases. B cell depletion in animal models of PBC has highlighted the regulatory roles of B cells in ameliorating disease. Some evidence of efficacy of anti-B cell therapy using rituximab in human autoimmune liver diseases further supports a role for B cells. Mature B cells (Bm) subpopulations had been described in Sjogren’s syndrome. However, little is known about the localisation, subsets, phenotype and function of B cells in human liver diseases. <h3>Methods</h3> In this study we characterised the frequencies of B cell subsets in the blood and liver of patients with inflammatory and autoimmune liver diseases. <h3>Results</h3> Frequencies of naïve mature BM1 cells were reduced in the liver compared to blood (7.5% ± 2.3 vs. 20.2% ±2.8 p = 0.0022) and IgD<sup>neg</sup>CD27<sup>neg</sup> subset was increased in diseased livers compared to diseased blood (22.9% ± 6.8 vs. 6.0% ± 1.1 p = 0.0013). B cells localise close to the bile ducts in PBC and reside around hepatocytes in AIH. Frequencies of regulatory B cells (CD19<sup>pos</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>) were significantly reduced in diseased blood vs. control blood (1.8% ± 0.4 vs. 3.6% ± 0.5 p = 0.01) similar to recent observation in acute rheumatoid arthritis. However this population is increased in the diseased liver compared with blood (6.2% ± 0.07 vs. 1.8% ± 0.4 p = 0.007), suggesting enrichment of regulatory B cells within the inflamed liver. Liver infiltrating B cells were capable of IL-10 production. <h3>Conclusion</h3> We have characterised for the first time the heterogeneity of B cell subsets and presence of regulatory B cells and IL-10 secreting B cells in human diseased livers. We showed that B cells reside close to bile ducts along with other immune cells; thus B cells may play a role in biliary pathology. <h3>Disclosure of Interest</h3> None Declared.
Screening for gastric cancer in Western countries
Authors: Iris Lansdorp-Vogelaar, Ernst J Kuipers
Journal: Gut (2015)

Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide.1 In 2013, 841 000 people worldwide died due to gastric cancer.2 Eastern Asia, Eastern Europe and some regions in Central and South America have the highest incidence of stomach cancer, whereas Western Europe and North America have lower rates. The majority of gastric malignancies are intestinal type adenocarcinomas.3 These cancers develop according to a multistep process, in strong association with Helicobacter pylori infection. This bacterium causes chronic gastritis, which can slowly progress via atrophy, intestinal metaplasia and dysplasia to gastric adenocarcinoma.4 This process takes decades3 and provides an excellent window of opportunity for early detection and prevention of gastric cancer.

Several strategies have been proposed for gastric cancer screening. These include H. pylori screening and treatment, endoscopy with random or targeted biopsy sampling, serological testing for pepsinogens, gastrin and H. pylori antibodies and breath testing for volatile organic compounds.5 A test-and-treat approach for H. pylori has been proposed as the preferred strategy for population screening in high gastric cancer-risk populations in the Asia–Pacific region.6 ,7 This test-and-treat approach benefits from availability of non-invasive tests (serology, breath and stool tests) and is a single screen and treat strategy without the need for further surveillance. This is based on the low risk of recurrent H. pylori infection after successful eradication, and the low risk of gastric cancer in H. pylori negatives without premalignant lesions. Disadvantages include the risk of increased antibiotic resistance in the …
AB0940 The Prevalence of Achalasia among Patients with Autoimmune Diseases
Authors: Y. Katada, Y. Harada, A. Yura, M. Yoshimura, M. Katayama, S. Teshigawara, E.K. Tanaka, A. Watanabe, S. Oshima, S. Tsuji, Y. Saeki, J. Murata, F. Nakanishi, E. Masuda, T. Hijioka, N. Yamaguchi, J. Hashimoto, M. Matsushita
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Esophageal achalasia is a rare disease characterized by degeneration of Auerbach9s plexus. Although its presumed etiologies include autoimmune process, its precise mechanisms remain uncertain. Recently, it has reported that patients with achalasia are more likely to have autoimmune diseases. <h3>Objectives</h3> To elucidate the significance of achalasia in patients with autoimmune diseases <h3>Methods</h3> The computerized medical records system of our medical center were screened for patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM), and achalasia for recent 30 years (between 1982 and 2012). Then the details of picked up patients were investigated. <h3>Results</h3> Twelve patients with achalasia were identified. Among them, 1 patient was also with SLE and 2 patients with SSc (table). All of them experienced nocturnal coughing with regurgitation of ingested food without gastric acid and suffered from aspiration pneumonia. Interestingly, all these 3 patients had autoantibodies relating to SSc (scl-70 or centromere), although patient 1 had no sign indicating SSc. The prevalence of such autoimmune diseases in achalasia patients was 25% (3/12). Inversely, the prevalence of achalasia in SLE patients was estimated at 0.19% (1/539), while that in SSc patients 0.67% (2/297). These patients are 19 times and 67 times more likely to suffer from achalasia compared with general population (1/10000), respectively. None of the 98 patients with PM and of 55 patients with DM had achalasia. The onset of achalasia could be before, at the same time as, or after that of autoimmune diseases. <h3>Conclusions</h3> The prevalence of achalasia among patients with autoimmune diseases (especially SSc) is much higher than that in general population. When patients with autoimmune diseases present recurrent regurgitation of food without gastric acid, esophageal achalasia must be ruled out, considering it might be underdiagnosed. Patients with SSc can exhibit similar symptoms, having reflux esophagitis.However, their regurgitations are usually with gastric acid. This is an important point for differential diagnosis. Further study is required to reveal its nature and clinical significance. <h3>References</h3> Booy JD. Et al. Dis Esophagus. 2012;25:209-13. Katada N. et al. Ann Thorac Cardiovasc Surg 2012; 18: 420–428. Gockel I. et al. Dtsch Arztebl Int. 2012;109:209-14. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4910
CÁPSULA ENDOSCÓPICA DE COLON VERSUS COLONOSCOPIA EN EL CRIBADO FAMILIAR DE CANCER COLORRECTAL
Authors: C Alvarez, JM Dedeu, X Bessa, I Ibáñez, M Andreu, H Córdova, M Pellisé, A Ginès, G Fernández, A Castells, B Gonzalez-Suarez
Journal: Endoscopy (2011)

Objetivos: Los pacientes con historia familiar de cáncer colorectal (CCR) presentan un riesgo aumentado de presentar CCR. Los objetivos fueron evaluar la capacidad diagnóstica de la cápsula endoscópica respecto a la colonoscopia en pacientes con historia familiar de CCR, así como evaluar la limpieza colónica con preparación mediante Moviprep.
Abstract 3439: Sarcomatoid renal cell carcinoma as a biological example of epithelial to mesenchymal transition (EMT)
Authors: Anna-Karin Boström, Christina Möller, Elise Nilsson, Håkan Axelson, Martin E. Johansson
Journal: Cancer Research (2011)

Abstract About 8% of clear cell renal cell carcinoma (CCRCC) cases contain areas of a radically different morphology, demonstrating spindle shaped cells and a histological resemblance to sarcomas. These biphasic neoplasms are called sarcomatoid CCRCC (sCCRCC). Patients diagnosed with sCCRCC face a considerably worse prognosis due to an increased propensity for metastasis. Using a set of biphasic CCRCC cases, we showed that sCCRCC has a higher proliferative index and more prononced vimentin expression as compared to the CCRCC counterpart. We selected a CCRCC/sCCRCC case demonstrating overgrowth as well as metastatic spread for extended immunohistochemical characterization. Using mouse xenografts we evaluated a $$$$CCRCC cell-line and put forward the hypothesis that some CCRCC cell-lines may be derived from the sarcomatoid component rather than from the clear cell part, with obvious implications for the validity of in vitro models of CCRCC. We confirm that sCCRCC is derived from the clear cell component and show that sCCRCC morphologically and immunohistochemically may represent a completed epithelial mesenchymal transition (EMT). Furthermore we suggest that TGF-β1 may be the driving force behind sarcomatoid transdifferentiation i.e. EMT in CCRCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3439. doi:10.1158/1538-7445.AM2011-3439
Polychondritis with Auricular and Ocular Involvement
Authors: Gabriela Rodríguez-Colón, Alan G Palestine
Journal: New England Journal of Medicine (2015)

A 46-year-old man presented with a 1-month history of auricular pain and swelling of the pinnae, followed by bilateral eye redness, pain, and photophobia. Examination revealed bilateral erythema and tenderness of the auricles and thickening and deformity of the pinnae.