tbuckley/cabot-search huggingface dataset:
Abstract 3607: Loss-of-function screens using haploid KBM7 and HAP1 cells to identify mechanisms of anti-cancer drug resistance
Authors: Nora M. Gerhards, Charlotte Guyader, Vincent A. Blomen, Aslı Küçükosmanoğlu, Olaf van Tellingen, Daniel J. Vis, Lodewyk F. Wessels, Thijn R. Brummelkamp, Piet Borst, Sven Rottenberg
Journal: Cancer Research (2015)

Abstract The lack of biomarkers to predict anti-cancer therapy response remains a major obstacle in the treatment of various cancers. This handicap not only affects novel targeted therapies. Also for classical chemotherapeutic drugs such as DNA cross-linking agents, topoisomerase inhibitors or microtubule-targeting compounds, which are all frequently used in the clinic, we do not understand well why some patients have a major benefit of the therapy whereas others do not. A decreased intracellular drug accumulation has been proposed as one potential mechanism, but the clinical relevance of known uptake and efflux mechanisms is still controversial for various chemotherapeutic drugs. To identify novel factors that may be relevant for the intracellular concentration of drugs, we carried out loss-of-function screens using haploid KBM7 and HAP1 cells. In particular, we used the PARP inhibitor olaparib, the topoisomerase I inhibitor topotecan, platinum drugs, and the microtubule-targeting compounds docetaxel and vinorelbine to select resistant clones. We will present results from these screens and their validation, including independent cell lines and TCGA data sets. Citation Format: Nora M. Gerhards, Charlotte Guyader, Vincent A. Blomen, Aslı Küçükosmanoğlu, Olaf van Tellingen, Daniel J. Vis, Lodewyk F. Wessels, Thijn R. Brummelkamp, Piet Borst, Sven Rottenberg. Loss-of-function screens using haploid KBM7 and HAP1 cells to identify mechanisms of anti-cancer drug resistance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3607. doi:10.1158/1538-7445.AM2015-3607
Clinical Use of the Urinary Uropepsin Determination in Medicine and Surgery
Authors: Seymour J. Gray, Colin G. Ramsey, Robert W. Reifenstein
Journal: New England Journal of Medicine (1954)

MEASUREMENT of the excretion of pepsinogen in the urine (uropepsin) has been recommended as a quantitative test for gastric secretory function by a number of investigators.1 2 3 4 5 6 7 It has been applied clinically to the study of peptic ulcer, pernicious anemia and gastric cancer and has proved of considerable value in measuring the gastric response to ACTH stimulation and conditions of stress.8 , 9 The purpose of this presentation is to evaluate the clinical use of uropepsin excretion in a variety of gastrointestinal and endocrine diseases, as well as in the postoperative stomach in which gastric aspiration presents technical difficulties.The uropepsin excretion in . . .
Tools of the Trade -- Recombinant DNA
Authors: Nadia Rosenthal
Journal: New England Journal of Medicine (1994)

When recombinant DNA -- DNA deliberately coupled from different sources -- was first produced, it was seen as a dangerous example of molecular tinkering gone wild, with potentially disastrous consequences. Two decades later, recombinant DNA, now virtually a household term, has become the most powerful tool of modern genetics. Recent progress in the application of this technique has created radically new possibilities for diagnosis and treatment and has changed the course of medical research. These advances have far-reaching consequences for the future of medicine. Yet the basic principles of recombinant DNA, like the structure of DNA itself, are surprisingly simple. . . .
Pneumoperitoneum in the Treatment of Pulmonary Emphysema
Authors: M. G. Carter, E. A. Gaensler, A. Kyllonen
Journal: New England Journal of Medicine (1950)

PULMONARY emphysema is one of the most common, disabling and chronically progressive diseases seen in a general hospital. The usual sequence of emphysema, bronchitis, fibrosis and progressive respiratory insufficiency has defied attempts at prevention or treatment.General therapy of this disorder has included intermittent administration of oxygen and the use of bronchodilators and antibiotics — all of which increased the life span of these patients by minimizing the severity of acute bronchial infections.Attempts at specific therapy have been varied. Costal chondrectomy was used by Freund1 in 1906, with some improvement in the symptoms due to emphysema of long duration. . . .
PWE-167 The influence of a simple blood transfusion policy on over-transfusion in acute upper gastro-intestinal haemorrhage: Abstract PWE-167 Table 1
Authors: A Stokes, C Thompson, A Clegg, J Snook
Journal: Gut (2015)

<h3>Introduction</h3> Acute upper gastro-intestinal haemorrhage (AUGIH) is a common medical emergency. Whilst frequently treated with blood transfusion, RCT evidence suggests that a restrictive transfusion policy can reduce the risk of re-bleeding and death. Yet previous audits have shown a high prevalence of over-transfusion - a situation where blood is administered in excess of requirements, with the potential for deleterious effects. This study describes the impact of a simple blood transfusion policy to address over-transfusion in AUGIH. <h3>Method</h3> A cross-match policy was devised (see Table 1) to limit the number of units initially provided for patients with AUGIH according to the pre-transfusion haemoglobin concentration ([Hb]) and presence of shock and/or suspected varices. The proposed target post-transfusion [Hb] was 90–100g/l. Anonymised data was collected for all patients with suspected AUGIH during two six-month periods, before (Group 1) and after (Group 2) introduction of the policy. Over-transfusion was arbitrarily defined as a post-transfusion [Hb] exceeding 100 g/l. <h3>Results</h3> Group 1 (n = 122) and Group 2 (n = 105) were comparable in terms of age, sex, [Hb] at presentation and Rockall score. The proportion of patients over-transfused decreased from 48% in Group 1 to 28% in Group 2 (OR 0.43; 95% CI 0.19–0.98). Logistic regression analysis of combined data from the two cohorts confirmed that “initial [Hb]” and “units transfused” were the two major independent predictors of over-transfusion. The respective total blood usage figures for Groups 1 and 2 were 259 v 148 units cross-matched (a 43% reduction), and 198 v 127 units transfused in (a 36% reduction). Contributors to the latter were (1) a reduction in the proportion of patients transfused (58% v 50%; χ<sup>2</sup>=1.36, p = 0.24), and (2) a reduction in the number of units administered to each recipient (mean 2.8 v 2.4; t test 1.95, p = 0.05). <h3>Conclusion</h3> Over-transfusion in AUGIH is common and can be substantially reduced by the introduction of a simple cross-match policy. Direct benefits include a reduction in blood usage – our figures indicate a drop from 162 to 121 units per 100 patients with AUGIH. A typical DGH managing 250 cases a year could therefore potentially save £12,000 pa on blood alone – if applied across the NHS in England this equates to over £2 million pa. Further potential benefits might include reduced morbidity and mortality, and indirect cost savings from a reduction in the interventions and extended lengths of stay for rebleeding episodes. <h3>Disclosure of interest</h3> None Declared.
MO19390 (SAiL): Safety and efficacy of first-line bevacizumab (Bv)-based therapy in advanced non-small cell lung cancer (NSCLC)
Authors: L. Crino, J. Mezger, F. Griesinger, C. Zhou, M. M. Reck
Journal: Journal of Clinical Oncology (2009)

8043 Background: MO19390 (SAiL) is a single-arm, multicenter, international trial evaluating the safety and efficacy of first-line Bv in combination with a range of chemotherapy regimens in over 2,000 patients (pts). Methods: Primary endpoint was safety; secondary endpoints included time to disease progression (TTP) and overall survival (OS). Pts with untreated locally advanced, metastatic or recurrent non-squamous NSCLC (ECOG PS 0–2) received Bv (7.5 or 15mg/kg) with standard chemotherapy for up to six cycles, then non-progressors proceeded to receive Bv until disease progression. Results: This analysis (data cut-off July 2008) was based on 2,008 pts with a median age of 59. Pts (%) were: male 60.1; stage IIIB/IV 19.5/80.5 (no data 3 pts); adenocarcinoma/large cell/other 85.8/7.1/7.1; ECOG PS 0/1/2 38.1/56.1/5.8. Pts received a median of 6 Bv cycles and 4 chemotherapy cycles. 26.7% of pts experienced grade ≥3 serious adverse events (SAEs); 8.3% of pts experienced grade ≥3 SAEs related to Bv. Adverse events (AEs) of special interest (all grades) included bleeding (27.6%), hypertension (19.3%), proteinuria (14.6%), thromboembolism (8.6%), CHF (2.9%) and GI perforation (1.2%). The incidence of AEs of special interest (all grades) was comparable across the various types of chemotherapy regimens: carboplatin doublets (50.6%)/cisplatin doublets (49.9%)/non-platinum doublets (41.7%)/monotherapy (37.5%). No new safety signals were reported. Trial data were not deemed mature enough to provide efficacy results. Conclusions: SAiL confirms that Bv-based therapy has a well-established and manageable safety profile. Clinical outcomes obtained in this real-life population are consistent with those seen in the pivotal trials of bevacizumab (Avastin) in NSCLC (E4599 and AVAiL), and compare favorably with historical data. Updated efficacy results for 2,147 pts will be presented, based upon an additional 5 months’ follow-up. [Table: see text]
Impact Of Low-Grade Adverse Events (AEs) On Health-Related Quality Of Life (HRQoL) In Adult Patients With Newly Diagnosed Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia In Chronic Phase (Ph+ CML-CP) From The Enestnd Trial: 48-Month Follow-Up
Authors: Lei Chen, Annie Guerin, Maryna Marynchenko, Raluca Ionescu-Ittu, Robert Hiscock, Roy Nitulescu, Chopra Pooja, Ling-I Hsu, Christopher Keir, Eric Qiong Wu
Journal: Blood (2013)
Using a Palliative Care Framework for Seriously Ill Surgical Patients
Authors: Elizabeth J. Lilley, Christy E. Cauley, Zara Cooper
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
PAI-1, Early Life Infections and Asthma Risk, Exacerbations, and Reduced Lung Function
Authors: Kumar Rajesh, Seong Ho Cho, Jin Young Min, Joseph Kang, Wendy Chan, Dong-Young Kim, Sam Oh, Dara Torgerson, Maria del Mar Del-Pino-Yanes, Donglei Hu, Saunak Sen, Scott Huntsman, Celeste Eng, Harold J. Farber, William Rodriguez-Cintron, Jose Rodriguez-Santana, Denise Serebrisky, Shannon Thyne, Luisa Borrell, L. Keoki Williams, Max Seibold, Esteban Gonzalez Burchard, Pedro C. Avila
Journal: Journal of Allergy and Clinical Immunology (2016)
QOL-25EVALUATION OF THE UTILITY OF THE EQ-5D AND MDASI-BT IN PRIMARY BRAIN TUMOR PATIENTS
Authors: Elizabeth Vera Bolanos, Alvina Acquaye, Tito Mendoza, Mark Gilbert, Terri S. Armstrong
Journal: Neuro-Oncology (2015)

BACKGROUND: Patients with malignant glioma are highly symptomatic and often have functional limitations beginning from the time of diagnosis. The utility of measuring general health status may have value in determining impact of disease. This study provided a description of health status and utility scores in glioma patients throughout the illness trajectory using the EQ-5D. Furthermore, it evaluated the additive information provided by MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) in describing health-related quality of life as assessed by the EQ-5D. METHODS: Malignant glioma patients completed the EQ-5D and MDASI-BT self-reports. The MDASI-BT is a measure of symptom burden and interference whereas the EQ-5D is a functional measure of general health status. Linear regression evaluated whether MDASI-BT scores adequately predict patient health outcomes measured by the EQ-5D. RESULTS: The sample included 100 patients [65% male, 75% with a GBM, median age 52 (range 20-75), 56% in active treatment]. Thirty percent of patients reported no problems on any of the 5 areas measured by the EQ-5D. The remaining 70% reported some/moderate problems in at least 1 area. The most extreme cases reported inability to perform usual activities (8%) and significant anxiety/depression (5%). The MDASI-BT neurologic factor score and the WAW (Walking/Activity/Work) interference score explained 52% of the variability in the EQ-5D in this patient population while adjusting for the effect of tumor grade, recurrence status, and Karnofsky Performance Status (KPS). Residual diagnostics confirmed the adequacy of model fit. CONCLUSIONS: The majority of brain tumor patients reported at least one functional limitation on the EQ-5D. Over half of the variance in the EQ-5D was explained by the MDASI-BT, KPS, tumor grade, and recurrence status underscoring the benefit of using this information for planning patient care. The resultant model demonstrates the significant contribution symptom burden has on determining health status in this patient population.
Hepatitis B Virus RNA Transcripts and DNA in Chronic Liver Disease
Authors: Osamu Yokosuka, Masao Omata, Fumio Imazeki, Yoshimi Ito, Kunio Okuda
Journal: New England Journal of Medicine (1986)

To study the relation between gene expression of hepatitis B virus (HBV) and liver disease, we studied HBV RNA transcripts and DNA in liver-biopsy specimens from 30 patients with chronic liver disease (17 seropositive for hepatitis B surface antigen and 13 seronegative). HBV-specific RNA was found in all the seropositive patients and in none of the seronegative patients. Two major RNAs, sizes 29S (long) and 21S (short), were found in nine seropositive patients, of whom seven had free HBV DNA and eight were seropositive for hepatitis B e antigen. Six of the nine patients had hepatitis B core antigen in hepatocytes and active liver disease. In contrast, Inactive liver disease was noted in the remaining eight seropositive patients, who had only one (21S) RNA. None of these patients had free HBV DNA (five of eight had integrated DNA) or hepatitis B core antigen in hepatocytes. Hybridization analysis suggested that 29S and 21S RNAs are messenger RNAs of hepatitis B core antigen and hepatitis B surface antigen, respectively. These data indicate that the free DNA and its products are causally related to the activity of liver disease and that once HBV DNA has been integrated, the disease will become quiescent. None of the determinants were identified in patients seronegative for hepatitis B surface antigen. (N Engl J Med 1986; 315:1187–92.)
Antibody Induction of Lymphocyte-Mediated Cytotoxicity against Human Transitional-Cell Carcinomas of the Urinary Tract
Authors: Thomas R. Hakala, Paul H. Lange, Anthony E. Castro, Arthur Y. Elliott, Elwin E. Fraley
Journal: New England Journal of Medicine (1974)

Serum from a patient with transitional-cell carcinoma of the urinary tract, which induced lymphocyte-mediated cytotoxicity against the carcinoma, was studied to determine the active factor and characterize its mode of action. The active serum factor was an IgG immunoglobulin that induced cytotoxicity only in the presence of effector cells (lymphocytes) and did not require the presence of complement. Contact between the IgG and a tumor-associated antigen appeared to be required before cytotoxicity could be induced in the lymphocyte. The IgG induced lymphocytes from donors with and without transitional-cell carcinoma to become cytotoxic against cells derived from transitional-cell carcinoma of the renal pelvis, ureter, and bladder but not against normal adult or embryonic cells or against renal-cell-carcinoma cells. These characteristics indicate that the active serum factor is a lymphocyte-dependent antibody that is directed against an antigen associated with transitional-cell carcinoma. (N Engl J Med 291:637–641, 1974)
Immediate Hypersensitivity to Hog Trypsin Resulting from Industrial Exposure
Authors: Harvey R. Colten, Phillip L. Polakoff, Steven F. Weinstein, Denise J. Strieder
Journal: New England Journal of Medicine (1975)

Clinical, immunologic and psysiologic studies were undertaken to establish the role of hog trypsin dust in four cases of occupational asthma and to define the mechanism of this respiratory disease. Objective evidence was obtained that these patients, but not their asymptomatic co-workers, were allergic to trypsin, and that this fact accounted for their respiratory symptoms. Direct skin testing, passive transfer of IgE antibodies, antigen-mediated histamine release from peripheral blood leukocytes and airway obstruction in response to inhalation challenge indicated IgE-mediated, Type I hypersensitivity. These effects were induced by inactivated trypsin and were therefore independent of tryptic enzymatic activity. The data suggested that periodic skin testing for immediate sensitivity to organic dust would be an inexpensive and convenient screening procedure for early detection and prevention of some types of occupational asthma.
Survival with the Acquired Immunodeficiency Syndrome
Authors: R Rothenberg, M Woelfel, R Stoneburner, J Milberg, R Parker, B Truman
Journal: New England Journal of Medicine (1987)

In a cohort of 5833 subjects in whom the acquired immunodeficiency syndrome (AIDS) was diagnosed in New York City before 1986, the cumulative probability of survival (mean +/- SE) was 48.8 +/- 0.7 percent at one year and 15.2 +/- 1.8 percent at five years. The group with the most favorable survival rate--white homosexual men 30 to 34 years old who presented with Kaposi's sarcoma only--had a one-year cumulative probability of survival of 80.5 percent; that group was used as the reference group in assessing the effect of five variables: sex, race or ethnic background, age, probable route of acquiring AIDS (risk group), and manifestations of AIDS at diagnosis. The range in the mortality rate was greater than threefold, depending on these variables. Black women who acquired the disease through intravenous drug abuse, for example, had a particularly poor prognosis. The manifestations of disease at diagnosis had the most influence on survival, accounting on average for 56.3 percent of the excess risk. This variable was followed in importance by age (12.2 percent), race or ethnicity (10.6 percent), risk group (8.4 percent), and sex (8.0 percent), with 4.5 percent of the risk attributable to interactions between variables. When we compared subcohorts based on the year of diagnosis (1981 through 1985), we found a significant improvement in the one-year cumulative probability of survival among subjects with Pneumocystis carinii pneumonia, but not among subjects without P. carinii pneumonia.
Pretransplantation Blood Transfusion Revisited
Authors: Esther van Twuyver, Rob J.D. Mooijaart, Ineke J.M. ten Berge, Anneke R. van der Horst, Joep M. Wilmink, W. Martin Kast, Cornelis J.M. Melief, Leo P. de Waal
Journal: New England Journal of Medicine (1991)

Blood transfusion before organ transplantation has a beneficial effect on allograft survival; the mechanism of this effect has remained a mystery. In murine models, the presence of common histocompatibility antigens in the blood donor and the recipient favors the induction of allograft tolerance.
Case 26-1998
Authors: Edwin L. Zalneraitis, Jean-Paul Vonsattel
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 15-year-old right-handed girl was admitted to the hospital because of hemiparesis, slurred speech, and urinary retention.The patient had been in excellent health until two and a half weeks earlier, when she began to have urinary urgency but found it difficult to empty her bladder. A few days later she felt unsteady and fell several times. Her handwriting slowed, and she had difficulty articulating her thoughts. Several days before admission, weakness and numbness developed in the right arm and leg, accompanied by right facial droop and slurred speech. On the evening before admission, she was found . . .
A Clinical Trial of Antioxidant Vitamins to Prevent Colorectal Adenoma
Authors: E. Robert Greenberg, John A. Baron, Tor D. Tosteson, Daniel H. Freeman, Gerald J. Beck, John H. Bond, Thomas A. Colacchio, John A. Coller, Harold D. Frankl, Robert W. Haile, Jack S. Mandel, David W. Nierenberg, Richard Rothstein, Dale C. Snover, Marguerite M. Stevens, Robert W. Summers, Rosalind U. van Stolk
Journal: New England Journal of Medicine (1994)

People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer.