tbuckley/cabot-search huggingface dataset:
Abstract B1-44: G-DOC Plus: A cloud based next-generation systems medicine platform for precision medicine
Authors: Krithika Bhuvaneshwar, Anas Belouali, Varun Singh, Robert M. Johnson, Lei Song, Adil Alaoui, Michael Harris, Yuriy Gusev, Robert Clarke, Subha Madhavan
Journal: Cancer Research (2015)

Abstract Systems medicine leverages complex computational tools and high dimensional data offering the potential for effective individualized diagnosis, prognosis and treatment options. Our flagship web platform, the Georgetown Database of Cancer (G-DOC), was deployed with the goal of enabling translational research by integrating patient characteristics and clinical outcome data with a variety of high-throughput research data in a unified environment. With the goal of improving health outcomes through genomics research, we present G-DOC Plus, our enhanced web platform offering precision medicine, translational research and population genetics workflows. This enhanced platform takes advantage of cloud computing to handle next generation sequencing (NGS) data so that they can be analyzed in the full context of other omics and clinical information. G-DOC Plus uses cloud computing and other advanced computational tools to enable analysis of NGS and medical images in the full context of other omics and clinical information. It allows translational science researchers to explore data one sample at a time, as a sub-cohort of samples; or as a population as a whole, providing the user with a comprehensive view of the data. G-DOC Plus tools have been leveraged in cancer to support detection of prognostic markers for relapse in colorectal cancer samples, and to detect key metabolites related to disease severity; hypothesis generation; biomarker detection and multi-omic analysis, in-silico and population genetics analysis; and to explore somatic mutation and breast cancer MRI images. The long-term vision of G-DOC Plus is to extend this systems medicine platform to hospital networks to provide clinical decision support using multi-omics and relevant clinical information to support personalized patient care. G-DOC Plus was released in October 2014, and is available at: https://gdoc.georgetown.edu. Citation Format: Krithika Bhuvaneshwar, Anas Belouali, Varun Singh, Robert M. Johnson, Lei Song, Adil Alaoui, Michael Harris, Yuriy Gusev, Robert Clarke, Subha Madhavan. G-DOC Plus: A cloud based next-generation systems medicine platform for precision medicine. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-44.
Case 3-2011
Authors: James C. Cusack, Jeffrey W. Clark, Steven A. Curley, Dushyant V. Sahani, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2011)

A 58-year-old woman was seen in the multidisciplinary gastrointestinal oncology clinic because of a mass in the liver. Two weeks earlier, severe, sharp pain developed suddenly in the right upper quadrant. Imaging showed an 11-cm mass; biopsy showed neuroendocrine carcinoma.
P249 Longitudinal evaluation of physical activity impairment using the asthma control questionnaire (ACQ) in severe asthma
Authors: MJ Jeppegaard, S Veidal, V Backer, C Porsbjerg, A Menzies-Gow, J Hull
Journal: Thorax (2015)

<h3>Background and objective</h3> Patients with severe asthma remain highly symptomatic despite high dose anti-inflammatory treatment. Level of asthma control is often assessed in the clinical setting with the asthma control questionnaire (ACQ). Separate components of the ACQ focus on different aspects of control. A high score on the third question (Q3) demonstrates activity limitations and may be caused by factors other than asthma such as physical deconditioning, concomitant cardiac disease and dysfunctional breathing patterns, leading to a overestimation of the severity of asthma. This could potentially lead to overtreatment. The aim of this study was to determine whether patients with severe asthma had a continuously high ACQ score, predominated by the third question despite treatment. <h3>Methods</h3> In a group of severe asthma patients, referred to the Royal Brompton hospital in London, UK, an evaluation of ACQ as monitoring tool was performed from May to July 2015, at an index clinic (v3) and two previous attendances (v1–2). The patients suffered from severe asthma (step 4 or 5 BTS/SIGN guideline treatment) and change in ACQ score over time (total and Q3) was compared with other measures of asthma severity such as medication burden and lung function. <h3>Results</h3> Forty three patients (n = 27 females, 61.4%) of mean (SD) age: 56 (11) years were included. The total ACQ score (median (range)) at index was 2.67 (0.17–5.50), the ACQ score on Q3 was 3.00 (0.00–6.00) and mean (SD) FEV<sub>1</sub> percent of predicted was 61.9 (±23.78). The total ACQ score was lower at index visit than the first visit (-0.17 (-1.83–1.50; p = 0.041). A change in ACQ score in Q5 was found (p = 0.019), whereas Q3 was unchanged. A change in FEV<sub>1 </sub>percent predicted was -0.62 (±12.11). A correlation between FEV<sub>1</sub> percent predicted and both total ACQ score (p &lt; 0.01) and Q3 ACQ score (p &lt; 0.01) was found. There was no correlation between the changes in these three parameters. <h3>Conclusion</h3> In patients with severe asthma there is a significant improvement in total ACQ score over three visits, but no improvement in exercise induced symptoms (Q3). This can be correlated with the fact that Q3 can reflect other symptoms than asthma.
P1182 : MIR-506 is upregulated by pro-inflammatory cytokines in human cholangiocytes and inhibits cell proliferation and adhesion
Authors: O. Erice, P. Muñoz Garrido, J. Vaquero, M.J. Perugorria, M.G. Fernandez Barrena, E. Sáez, M. Merino, A. Arbelaiz, Á. Santos Laso, R. Jimenez Agüero, M. Marzioni, N.F. LaRusso, J.J. Garcia Marin, L. Bujanda, J.M. Bañales
Journal: Journal of Hepatology (2015)
Comparison of Trends in the Incidence of Multiple Myeloma in Malmö, Sweden, and Other Countries, 1950–1979
Authors: Ingemar Turesson, Olle Zettervall, Jack Cuzick, Jan G. Waldenstrom, Ramon Velez
Journal: New England Journal of Medicine (1984)

Dramatic increases in mortality from multiple myeloma have been reported in the United States and the United Kingdom over the past three decades. To assess what fraction of this increase, if any, might be attributable to a change in the incidence of this disease, we examined the incidence of multiple myeloma during 1950 to 1979 in Malmö, Sweden, a city chosen because of its medical community's longstanding interest in this disease. The average annual incidence rates per 100,000 population were 4.9 for males and 3.7 for females (adjusted to the European age-standardized population). These rates are among the highest in the world. Unlike secular trends for myeloma in the United States and the United Kingdom, where large increases in mortality rates have been reported, the rates in Malmö have increased only slightly, and the increase was restricted to males, suggesting the possibility of environmental causes. We suggest that the rates in Malmö may represent the asymptote of myeloma's incidence that will be approached in other white populations as case ascertainment among them becomes complete.
The Syndromes of Insulin Resistance and Acanthosis Nigricans
Authors: C. Ronald Kahn, Jeffrey S. Flier, Robert S. Bar, Juanita A. Archer, Phillip Gorden, Malcolm M. Martin, Jesse Roth
Journal: New England Journal of Medicine (1976)

In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found. (N Engl J Med 294:739–745, 1976)
Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection
Authors: Stephanie H. Michaels, Rebecca Clark, Patricia Kissinger
Journal: New England Journal of Medicine (1998)

To the Editor: Palella et al. (March 26 issue)1 reported that the use of more intensive antiretroviral therapies is responsible for declines in both morbidity and mortality in patients with AIDS. We conducted a study to evaluate the impact of protease inhibitors on the rates of selected opportunistic processes and mortality and found similar results. Our study population came from a public human immunodeficiency virus (HIV) outpatient clinic in New Orleans. All subjects and data were from the Adult Spectrum of Disease study, a prospective study funded by the Centers for Disease Control and Prevention examining the natural history of . . .
The Molecular Basis of Thyroid Hormone Action
Authors: Franklin H. Epstein, Gregory A. Brent
Journal: New England Journal of Medicine (1994)

Thyroid hormone exerts a broad range of effects on development, growth, and metabolism. The clinical manifestations of thyroid hormone excess and deficiency are dramatic examples of the myriad actions of the hormone. Thyroxine (T4), the primary secretory product of the thyroid, is relatively inactive and is converted to the active hormone, triiodothyronine (T3), by the enzyme thyroxine 5'-deiodinase (Figure 1)1. The actions of thyroid hormone are primarily the result of the interaction of T3 with nuclear receptors for T3 that bind to regulatory regions of genes (thyroid hormone-response elements) and modify their expression . . .
Mixed Depression in Bipolar Disorder: Prevalence Rate and Clinical Correlates During Naturalistic Follow-Up in the Stanley Bipolar Network
Authors: Shefali Miller, Trisha Suppes, Jim Mintz, Gerhard Hellemann, Mark A. Frye, Susan L. McElroy, Willem A. Nolen, Ralph Kupka, Gabriele S. Leverich, Heinz Grunze, Lori L. Altshuler, Paul E. Keck, Robert M. Post
Journal: American Journal of Psychiatry (2016)

Objective: DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression. Method: In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit. Results: Mixed depression, defined as an IDS-C score ≥15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring ≥3 nonoverlapping YMRS items concurrent with an IDS-C score ≥15, to broader definitions requiring ≥2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity. Conclusions: Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression.
Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)
Authors: T. Hamaguchi, K. Shirao, Y. Moriya, S. Yoshida, S. Kodaira, Y. Ohashi
Journal: Journal of Clinical Oncology (2007)

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m 2 /day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.
Absence of Parathyroid Hormone Messenger RNA in Nonparathyroid Tumors Associated with Hypercalcemia
Authors: Ellen L. Simpson, Gregory R. Mundy, Sharyn M. D'Souza, Kenneth J. Ibbotson, Richard Bockman, John W. Jacobs
Journal: New England Journal of Medicine (1983)

We used a sensitive and specific hybridization assay that detects evidence of parathyroid hormone synthesis in tumors to investigate whether this hormone mediates the hypercalcemia of malignant disease. The assay uses Radio-labeled, cloned parathyroid hormone DNA to hybridize selectively with parathyroid hormone messenger RNA. We assayed 13 human and 3 animal tumors of diverse cell origins that are frequently associated with the hypercalcemia of cancer. Five of the human tumors were obtained from patients known to be hypercalcemic at the time of tumor excision, two were from normocalcemic patients, and six were from patients with breast cancer whose serum calcium levels were unknown. Messenger RNA was prepared from cultured cell lines or tumors; active RNA fractions were hybridized with either human or bovine cloned parathyroid hormone DNA that had been labeled to a high specific activity with [32P]nucleotide. We were unable to detect parathyroid hormone RNA transcripts in any of the tumors. Our results indicate that parathyroid hormone rarely, if ever, causes hypercalcemia in malignant disease. (N Engl J Med 1983; 309: 325–30.)
Time is ripe for a "pregnancy based system" of data collection
Authors: A. Saha
Journal: BMJ (1995)

approach.Case finding, notification of cases, enhanced surveillance, and modification of the environment in which the disease exists are strategies that can usefully be applied to bullying.Doctors are perhaps better placed than parents to push this approach.We need also to recruit the vast majority of children who are neither bullies nor victims.In my survey of a secondary school in Nottingham the response of three quarters of children to the bully- ing of another child was that of a bystander who does not want to get involved; a fifth said they could be persuaded to join in (unpublished data).Whitney and Smith found that most children did nothing to help victims either because they did not know how to help or because they thought it was not their business.2Perhaps this statistic would make a good indicator of the success of an anti- bullying programme.Children should be taught not only not to bully others but also not to tolerate bullying of others.Health care staff working with children in the primary care setting have a vested interest in working in concert with school authorities towards this ideal: they will have less morbidity related to bullying to deal with.One approach would be to regard the detection of a case of bullying as an indication of serious problems in the interrelation- ships of children in the school.As in established child protection procedures, a case conference should be called of all professionals concerned and a strategy agreed for the prevention of future cases.
Management of Severe Ulcer Rebleeding
Authors: Dennis M. Jensen
Journal: New England Journal of Medicine (1999)

The number of patients hospitalized for upper gastrointestinal bleeding from ulcers has decreased substantially in recent years. The decrease reflects a variety of factors: the widespread use of histamine H2–receptor blockers and proton-pump inhibitors, the eradication of Helicobacter pylori in patients with ulcers, and increased awareness among patients with ulcers of the potential dangers of taking nonsteroidal antiinflammatory drugs. Nonetheless, severe upper gastrointestinal bleeding remains a common medical emergency.1 In the past two decades, the responsibility for the initial diagnosis and treatment of gastrointestinal bleeding has shifted in most medical centers from general surgeons and radiologists to gastrointestinal . . .
P10 Effect of Pirfenidone on gas transfer in patients with idiopathic pulmonary fibrosis
Authors: PM George, L Richardson, EA Renzoni, M Kokosi, TM Maher, AU Wells, F Chua
Journal: Thorax (2015)

<h3>Background</h3> Idiopathic pulmonary fibrosis (IPF) is a severe and progressive interstitial lung disease (ILD). Treatment with the anti-fibrotic agent Pirfenidone slows decline in forced vital capacity (FVC). Pulmonary vasculopathy is a relatively common and life-limiting complication of IPF and is frequently associated with a reduction in the diffusing capacity of the lung for carbon monoxide (DLco). However, it is not known what effect Pirfenidone may have on DLco. <h3>Methods</h3> We performed a retrospective analysis of patients with diagnoses of IPF on long term Pirfenidone treatment. Lung function data were collected at treatment initiation and then at 12 months, (6–18 months). To assess for a treatment effect, similar data were also collected from an untreated control cohort of biopsy proven IPF patients from the pre-Pirfenidone era managed at the same centre. Data were analysed using Stata. <h3>Results</h3> 138 patients were studied; n = 66 patients in the untreated control group and n = 72 patients in the Pirfenidone treated group. The control group had a higher baseline predicted FVC (74.8% v 67.5%) (p &lt; 0.05) but baseline predicted DLco measurements were similar (44% v 40%) (p = 0.19). 12 month relative FVC change was greater in the untreated group; 9.9% (273 mL) (±11.4%) versus 3.9% (123 mL) (±11.9%) (p &lt; 0.005). 12 month relative DLco decline was also greater in the untreated group; 16.4% (±20.5%) versus 7.5% (±17.6%) (p &lt; 0.01). In multivariate analyses, the effect of Pirfenidone treatment had a 6.7% impact on FVC change (2.7–10.6) (p &lt; 0.001) and a 9.0% impact on DLco change (2.5–15.5) (p &lt; 0.01). Right ventricular systolic pressure correlated with baseline predicted DLco (p &lt; 0.005, r<sup>2</sup> = -0.14). <h3>Discussion</h3> In this study we have demonstrated that over 12 months, Pirfenidone confers a reduction in gas transfer decline paralleling that seen for FVC. This treatment effect on DLco may be due to a combination of deceleration in ILD progression as well as attendant effects at the level of the pulmonary vasculature. This may have particularly relevance given the correlation between DLco and echocardiographic parameters of pulmonary vascular disease. <h3>Conclusion</h3> Treatment of IPF with Pirfenidone markedly attenuates declines in gas transfer. This is of interest as it may provide insights into mechanisms underpinning disease stabilisation.
Case 13-2007
Authors: Michael V. Seiden, Devanshi Patel, Mary Jane O'Neill, Esther Oliva
Journal: New England Journal of Medicine (2007)

A 46-year-old woman was evaluated at the Center for Cancer Risk Analysis because of her recent diagnoses of endometrial, ovarian, and colon cancers. A routine Papanicolaou smear had disclosed an atypical glandular cell; endometrial curettage disclosed endometrioid carcinoma; and at hysterectomy, small bilateral ovarian tumors and a colon cancer were found. There was a maternal history of endometrial, breast, and colon cancers and colonic polyps.
Ectopic Pregnancy
Authors: Kurt T. Barnhart
Journal: New England Journal of Medicine (2009)

A healthy 29-year-old woman who has been trying to conceive presents with vaginal spotting for the past 5 days and intermittent crampy abdominal pain in her left lower quadrant for the past 3 days. Her last menstrual period was 6 weeks and 2 days before presentation. She has had a spontaneous vaginal delivery and an anembryonic gestation treated by dilation and curettage. How should this patient be evaluated and treated?
Congenital Heart Disease in Twins
Authors: James J. Nora, J. Campbell Gilliland, Robert J. Sommerville, Dan G. McNamara
Journal: New England Journal of Medicine (1967)

THE familial nature of congenital heart disease has become increasingly apparent.1 2 3 However, a major obstacle to the acceptance of a significant genetic role in the etiology of congenital heart defects has been the failure to demonstrate that when 1 member of a set of identical twins is affected with a congenital heart lesion, the co-twin is also affected.Uchida and Rowe4 found no concordance for congenital heart disease in 13 monozygotic twin pairs nor in 13 sets of dizygotic twins in which 1 member had a congenital heart defect. A similar lack of concordance was discovered by Campbell,5 who reported . . .