tbuckley/cabot-search huggingface dataset:
Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression
Authors: Hanane Laklai, Yekaterina A Miroshnikova, Michael W Pickup, Eric A Collisson, Grace E Kim, Alex S Barrett, Ryan C Hill, Johnathon N Lakins, David D Schlaepfer, Janna K Mouw, Valerie S LeBleu, Nilotpal Roy, Sergey V Novitskiy, Julia S Johansen, Valeria Poli, Raghu Kalluri, Christine A Iacobuzio-Donahue, Laura D Wood, Matthias Hebrok, Kirk Hansen, Harold L Moses, Valerie M Weaver
Journal: Nature Medicine (2016)
Abstract B40: Autocrine and paracrine IL-6 and IL-8 drive osteosarcoma lung tropism and facilitate metastasis
Authors: Ryan D. Roberts, Amy C. Gross, Hemant K. Bid, Doris Phelps, Mary F. Wedekind, Peter J. Houghton
Journal: Cancer Research (2016)

Abstract Osteosarcoma originates in bone, but metastasizes predictably to the lungs. Patients who develop lung metastases become much more difficult to treat. Metastatic lung disease responds poorly to traditional chemotherapy. We know very little of the mechanisms that mediate this lung tropism, or predilection for spread to lung tissue. A better understanding of this process could facilitate disruption of pathways which drive the metastatic process, potentially preventing or even treating lung metastasis. We thus sought to identify tumor-lung interactions that facilitate extravasation, survival, and growth of tumor cells specifically within the lung environment. Drawing on published signatures of osteosarcoma metastasis, we curated a list of 59 candidate genes that might facilitate lung metastasis. By comparing expression in metastatic lung lesions relative to paired primary tumors, we found that metastatic tumors reliably express two cytokines, IL-6 and IL-8, at much higher levels than matched primary bone tumors. In a mouse model of osteosarcoma, we found that tumors expressing high levels of autocrine IL-6 and IL-8 established lung metastases much more readily than tumors which expressed low or no IL-6 or IL-8. Using immunohistochemistry to identify sources of these cytokines within human metastatic lesions, we found higher levels of IL-6 and IL-8 coming from non-malignant cells within the tumor, especially mononuclear infiltrates and peri-bronchiolar cells. Modelling tumor-lung interactions in vitro using a co-culture system, much higher levels of IL-6 and IL-8 were produced when osteosarcoma cells were cultured with bronchial epithelial cells, smooth muscle cells, or macrophages suggesting that paracrine interactions drive production of these cytokines upon interaction of tumor cells with resident lung cells. In murine models of osteosarcoma metastasis, blocking IL-6 and/or IL-8 production within tumor cells using inducible shRNA-expressing lentiviruses dramatically reduced metastatic efficiency. Our data suggest that IL-6 and IL-8 play a primary role in the development of osteosarcoma lung metastasis. The readily targetable nature of these pathways makes them attractive candidates for therapies designed to prevent and possibly treat osteosarcoma lung metastasis. Citation Format: Ryan D. Roberts, Amy C. Gross, Hemant K. Bid, Doris Phelps, Mary F. Wedekind, Peter J. Houghton. Autocrine and paracrine IL-6 and IL-8 drive osteosarcoma lung tropism and facilitate metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B40.
Thrombasthenia in Liver Disease
Authors: Emanuel E. Mandel, Jack Lazerson
Journal: New England Journal of Medicine (1961)

IMPAIRMENT of the hemostatic mechanism is a common experience in active disease of the liver. Several recent reports1 2 3 4 have stressed the multiplicity of plasma clotting factors that may be deficient, as well as the frequency of reduction in the number of platelets. The occurrence of a functional platelet defect in hepatic disorders has been largely ignored.5 On review of the results of the thromboplastin-generation test as applied routinely to a variety of diseases with either frank or suspected bleeding tendency, a defect in thromboplastin activity of platelets was noted to be more common than thrombocytopenia in cirrhosis. Because of the . . .
The Use of Dibenamine in Pheochromocytoma
Authors: Harold C. Spear, Dwight Griswold
Journal: New England Journal of Medicine (1948)

THE adrenolytic drug dibenamine hydrochloride (dibenzyl-beta-chlorethyl amine hydrochloride)§ is presented as a diagnostic aid when the presence of a pheochromocytoma is suspected and as a therapeutic agent once the diagnosis is confirmed.The preoperative diagnosis of a pheochromocytoma is based on the clinical picture, retrograde pyelograms and perirenal air studies. But none of these criteria are specific. In the following case dibenamine apparently blocked the effects of a pheochromocytoma by its adrenolytic action. Thus, the drug affords a more specific test in the diagnosis of a pheochromocytoma.Method of AdministrationThe patient was given an intravenous infusion of dibenamine hydrochloride. . . .
Intermittent Severe Mitral Regurgitation
Authors: William Brody, J. Michael Criley
Journal: New England Journal of Medicine (1970)

Cardiac catheterization in a patient with episodic pulmonary edema, a systolic murmur of varying intensity and normal heart size revealed a transient precipitous elevation of left atrial and ventricular pressures. The magnitude and contour of the left atrial and diastolic left ventricular pressure tracings resembled those seen in acute severe mitral regurgitation. The pressures returned to normal, and the murmur disappeared after sublingual administration of isosorbide dinitrate. Left ventricular cineangiography, performed when the patient was asymptomatic and pressures were normal, revealed minimal mitral regurgitation, left ventricular dyskinesis and no angiographic evidence of structural derangement of the mitral valve. The patient was concluded to have intermittent severe functional mitral regurgitation (papillary-muscle dysfunction) related to ischemic heart disease. On medical management, consisting of digitalis and isosorbide dinitrate, he has remained essentially asymptomatic over the subsequent 18 months.
Prognosis of the Medically Treated Small Gastric Ulcer
Authors: Norman E. Larson, James C. Cain, Lloyd G. Bartholomew
Journal: New England Journal of Medicine (1961)

AT the Mayo Clinic, partial gastrectomy is the treatment of choice in most cases of apparently benign gastric ulcer. This is so because 10 per cent of patients whose ulcers prove cancerous are thereby given the best chances of "cure," the morbidity due to benign ulcer is terminated promptly, the results of surgical treatment of the benign ulcer are excellent, and the risk of surgical treatment is small (mortality of 1 to 2 per cent1 , 2).In the remaining cases medical management is instituted, in some with the approval of the physician, in some at the insistence of the patient, . . .
Brief psychiatric hospitalization: what are its effects?
Authors: P B Lieberman, J S Strauss
Journal: American Journal of Psychiatry (1986)

This exploratory study was undertaken to begin to identify what clinically significant changes besides symptom diminution may occur during brief psychiatric hospitalization. Intensive interviews with 20 patients at the beginning and end of a 1-month inpatient stay revealed that their cognitive abilities, self-esteem, and perceptions of the availability of other people frequently improved. The patients attributed these changes to forming relationships with others, having the opportunity to reflect, and making the decision to change. The improvements seemed to affect the patients' attitudes toward themselves and their lives, and 12 patients underwent significant life changes after discharge.
The psychological organization of depression
Authors: S Arieti, J R Bemporad
Journal: American Journal of Psychiatry (1980)

On the basis of the intensive psychotherapy of about 40 depressed patients over the course of two decades, the authors describe three premorbid types of depressive personality: 1) one based on a "dominant other" relationship, 2) one based on a "dominant goal," and 3) one that is a form of character structure or personality disorder. They also describe typical childhood experiences of depressive adults and discuss their theory of the nature of depression as a human experience. They characterize depression as a limitation of alternate ways of thinking and as self-inhibition from new experiences.
Multilobar bilateral and unilateral chest radiograph involvement: implications for prognosis in hospitalised community-acquired pneumonia
Authors: Adamantia Liapikou, Catia Cillóniz, Albert Gabarrús, Rosanel Amaro, Jorge Puig De la Bellacasa, Josep Mensa, Marcelo Sánchez, Michael Niederman, Antoni Torres
Journal: European Respiratory Journal (2016)

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide [1]. Studies from the USA and Europe suggest that severe CAP patients requiring admission to the intensive care unit (ICU) reach a mortality of up to 39% [2, 3]. Bilateral but not unilateral multilobar pneumonia is an independent risk factor for mortality in CAP <http://ow.ly/ZNLD4> We are indebted to all medical and nursing colleagues for their assistance and cooperation in this study.
Feasibility and efficacy of neoadjuvant chemotherapy with dose-dense methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC) in patients with high-grade urothelial cancer with muscle invasion.
Authors: M. B. Elmongy, M. Kaag, C. T. Reese, C. B. Algood
Journal: Journal of Clinical Oncology (2011)

e15189 Background: Dose dense M-VAC was compared to standard dose MVAC in EORTC study in patients with advanced metastatic baldder cancer which revealed significant improvement in complete and partial response than standard MVAC. The objective of our retrospective study was to evaluate response rate, the impact on disease-free survival, and toxicity adverse events of our patients who were treated with dose dense MVAC neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. Methods: We reviewed the clinical and pathological data of 12 patients who underwent neoadjuvant chemotherapy using dose dense MVAC q 14 days for 4-6 cycles followed by radical cystectomy and bilateral pelvic lymphadenectomy at two institution between 9/2007 and 12/2010. Dose dense MVAC therapy consisted of 30 mg/m2 methotrexate on days 1, and cisplatin 70 mg/m2, doxorubicin 30 mg/m2 and vinblastine 3 mg/m2 on day 2 and pegylated GCSF 6 mg sq on day 3. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, disease free survival, and toxicity. Results: 6 patients (50%) had a complete response rate and 6 patients (50%) had a partial response in the dose dense MVAC group. After radical cystectomy 50% of the patients had no evidence of residual cancer cells while the other 50% had stage I or II Urothelial carcinoma with no evidence of residual metastatic disease. The disease-free survival currently is 100%. Hematologic toxicities were the main adverse events. Grade 3/4 Neutropenia occurred in 5 patients (41%) and thrombocytopenia in 2 patients(16%). Conclusions: Although this is not a randomized study, the dose dense MVAC neoadjuvant therapy followed by radical cystectomy is very effective and well tolerated and may be associated with improved survival among patients with muscle-invasive bladder cancer. This data needs to be confirmed by randomized clinical trials.
P103 Inhibition of asthma-related immunological responses by cultured epithelial cell lines
Authors: W Sargent, L Stoeger, I Pavord, TJ Powell
Journal: Thorax (2015)

<h3>Background</h3> Previous studies have shown that constitutive and IgE-mediated histamine production by human lung mast cells is inhibited by a transferable factor produced by the airway epithelium. We have tested the hypothesis that a similar interaction exists between epithelial cell and mast cell lines. We have also investigated the effect of co-culture of epithelial cell lines and T<sub>H</sub>2 cells on interleukin (IL)-13 production. <h3>Methods</h3> A549 or BEAS-2B cells were grown to confluence overnight. Media was removed and LAD2, HMC1.2 or human-derived ex-vivo T-cells added for 16 h. For transwell experiments epithelial cells were added to a 24-well plate, replaced with fresh media after 16 h and mast cells media added to the insert, maintaining the mast cell/epithelium/volume ratio. Wells, and transwell insert media, were then centrifuged, supernatants harvested and mediator release quantified by histamine or IL-13 ELISA. <h3>Results</h3> Neither mast cell line consistently produced histamine in response to IgE and anti-IgE. Flow cytometry suggested that this was due to absence of the high-affinity IgE receptor FcεR1. Constitutive histamine production by HMC1.2 was reduced from 191 ± 13 ng/10<sup>6</sup> cells by 60.9% (95% CI 54.1, 67.8; p &lt; 0.0001) when co-cultured with A549 and 21% (95% CI 14.2, 28.1; p &lt; 0.0001) with BEAS-2B cells. Similar findings were seen with the LAD2 mast cell line. Constitutive IL-13 production by T<sub>H</sub>2 cells was reduced from 18000 ± 1800 pg/10<sup>6</sup> cells by 68.6% (95% CI 62.0, 75.1; P &lt; 0.0001) by A549 and 59.9% (95% CI 53.3, 66.5; p &lt; 0.0001) by BEAS-2B. Epithelial inhibition was similar when cells were separated by a transwell suggesting involvement of a transferable factor. <h3>Conclusion</h3> Epithelial cell lines inhibit a range of asthma-related immunological responses, probably by producing an inhibitory substance.
Insights into ventilation–gas exchange coupling in chronic thromboembolic pulmonary hypertension
Authors: J. Alberto Neder, Roberta P. Ramos, Jaquelina S. Ota-Arakaki, Eloara M.V. Ferreira, Daniel M. Hirai, Priscila A. Sperandio, Maria Clara N. Alencar, Flavio F. Arbex, Danilo C. Berton, Christine D'Arsigny, Denis E. O'Donnell
Journal: European Respiratory Journal (2016)

Exercise intolerance due to excessive ventilation and dyspnoea are fundamental clinical features of patients with pulmonary vascular diseases [1]. Among these diseases, chronic thromboembolic pulmonary hypertension (CTEPH) is associated with the largest increase in exercise ventilation [2]. Understanding the mechanism(s) underlying excess exercise ventilation in CTEPH is clinically relevant when designing evidence-based therapeutic and rehabilitative strategies to improve patients' symptoms and quality of life. Increased "wasted" ventilation and heightened neural drive explains excess exercise ventilation in CTEPH <http://ow.ly/Z4YBc>
Recognizing symptom complex prevalence in an outpatient oncology patient population: A performance improvement project
Authors: E. McCreary, J. D'Olimpio, C. Meci
Journal: Journal of Clinical Oncology (2004)

8219 Background: Poly-symptomatology is a frequently observed problem in the treatment of cancer patients in both the outpatient and inpatient setting, frequently leading to poor compliance with therapy and diminished quality of life. Symptom complexes are not translated into routine clinical charts/data bases because patients frequently do not relate these symptoms unless prompted. Previous Performance Improvement Projects have demonstrated the need to capture relevant clinical information to enhance patient care. Methods: 8 common symptoms were formatted into a single questionnaire using a 0–10 analogue scale and given to ambulatory oncology patients to complete anonymously in the waiting room. Pain, nausea/vomiting, fatigue, depression, shortness of breath, numbness/tingling, constipation and diarrhea were rated on a scale of 0–10 in 2 domains: average and current symptom intensity. Each questionnaire was then reviewed by 3 observers who “voted” on the accuracy and completeness of the data. Questionnaires were discarded if not completed or legible. Patient confidentiality was not at risk since no identifiers were used. Results: 132 patients were screened and 401 symptoms were rated, ave 3.2 symptoms per patient.27 patients had no symptoms.27 patients had only pain/ fatigue/ depression as a complex.13 patients had only nausea/ vomiting/constipation/diarrhea as a complex.33 patients had numbness/tingling/constipation/diarrhea as a complex. Average symptom severity was 3.8/10. Conclusions: The discovery that patients have specific complexes of symptoms that are not routinely captured in normal day to day outpatient management charting indicated a need to monitor the incidence of these symptoms as they relate to quality of life. In this way, busy clinicians can utilize PI initiatives to improve patient care in vulnerable cancer populations. No significant financial relationships to disclose.
Postmortem Viability of Human Immunodeficiency Virus -- Implications for the Teaching of Anatomy
Authors: Dirk De Craemer
Journal: New England Journal of Medicine (1994)

To the Editor: I want to draw your attention to the viability of the human immunodeficiency virus (HIV) in cadavers and the implications of the presence of live HIV during embalming procedures in anatomy departments and during the dissection of embalmed cadavers by students. It is the policy of anatomy departments to keep the period between the death of a patient and the embalming of the body as short as possible to minimize degeneration. Recent findings indicate that HIV in a patient who died of AIDS is still infectious at the time of the body's arrival at the anatomy department . . .
Effect of Lithium on Neutrophil Mass and Production
Authors: Gerald Rothstein, David R. Clarkson, Wayne Larsen, Bernard I. Grosser, John W. Athens
Journal: New England Journal of Medicine (1978)

We measured the effect of lithium on the blood neutrophil mass and neutrophil production, using standard di-isopropylfluorophosphate (DF32P) methods. In 12 lithium-treated patients the total blood neutrophil pool was 105 (42 to 270) X 107 cells per kilogram (median and 95 per cent limits) as compared with 61 (27 to 138) X 107 in 71 controls (P<0.001). The neutrophil turnover rate, a measure of effective neutrophil production, was 230 (108 to 380) X 107 cells per kilogram per day in the lithium-treated group and 160 (62 to 400) X 107 in the controls (P<0.05). Neutrophil migration into skin lesions ranged from 34 to 469 X 105 cells per day in the lithium-treated patients, as compared with 1.7 to 68 X 105 in 10 controls. Lithium causes enlargement of the total circulating neutrophil mass and accelerates neutrophil production without impairing neutrophil migration into skin lesions. (N Engl J Med 298:178–180, 1978)
IMCT-17STATISTICALLY SIGNIFICANT ASSOCIATION OF GLIOBLASTOMA IMMUNOTHERAPY PHASE II CLINICAL STUDY (ICT-107) TREATMENT AND SURVIVAL TO IMMUNE RESPONSE USING A NOVEL COMPREHENSIVE ELISPOT ANALYSIS
Authors: Radleigh Santos, Anthony Gringeri, John Yu, Sylvia Janetzki, Valeria Judkowski, Clemencia Pinilla
Journal: Neuro-Oncology (2015)

The main objective of active cancer immunotherapy is the activation of a patient's own T cells to attack tumor cells. The accurate measurement of the expansion and functionality of these T cells upon treatment is a key element in establishing the association between treatment and treatment outcomes or survival. While much research and clinical work has been focused on establishing and optimizing immunomonitoring during clinical trials, direct association of patient immune response to patient clinical endpoints remains difficult. IFN-g ELISPOT has been used extensively to monitor the immune response in immunotherapy trials. While there have been significant efforts to harmonize ELISPOT procedures and analysis, a standard methodology for classifying a positive immune response in an immunotherapy context has not emerged. Past studies have used techniques ranging from simple quantification of spot counts to published laboratory ELISPOT statistical analysis on single samples, but these studies lack consensus on establishing response to treatment with pre- and post- treatment samples. Here, novel statistical methods are presented for the direct generation of p-values comparing pre- and post- treatment ELISPOT responses evaluated ex-vivo in patients treated with a multi-peptide loaded dendritic cell-based immunotherapy. Then, a comprehensive scoring system is introduced which incorporates these novel methods, along with previously used metrics, into a single numerical scale. Using an analysis of score distribution, this scoring system is shown to distinguish response from non-response even in the context of low levels of T cell response detection sometimes associated with ex-vivo evaluation. Consequently, binary classification of patients as responders and non-responders is performed. Finally, this classification system is shown to compare favorably to other methodologies with respect to its ability to find statistically significant associations between the immune response detected ex-vivo and treatment group, IL-12 production of dendritic cells, and both overall and progression-free patient survival.
Megakaryocyte Abnormalities Occur In The Absence Of Cell-Mediated Immunity In a Murine Model Of Passive Immune Thrombocytopenia (ITP)
Authors: John W. Semple, Kristin Hunt, Yu Hou, Rukhsana Aslam, Edwin R. Speck, Heyu Ni, Alan H Lazarus
Journal: Blood (2013)
A Vaccine Consisting of Recombinant<i>Borrelia burgdorferi</i>Outer-Surface Protein A to Prevent Lyme Disease
Authors: Leonard H. Sigal, John M. Zahradnik, Philip Lavin, Sondra J. Patella, Gary Bryant, Ray Haselby, Eileen Hilton, Mark Kunkel, Debra Adler-Klein, Terrence Doherty, Janine Evans, Stephen E. Malawista, Philip J. Molloy, Adam L. Seidner, James R. Sabetta, Henry J. Simon, Mark S. Klempner, John Mays, Donald Marks
Journal: New England Journal of Medicine (1998)

Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease.
Exercise in the Disposition of Dietary Calories
Authors: George V. Mann, Katherine Teel, Olive Hayes, Ann McNally, Dorothy Bruno
Journal: New England Journal of Medicine (1955)

THE evidence relating the level of the serum lipids to the etiology of human atherosclerosis is indirect.1 The association of atherosclerosis or its clinical consequences with a record of persistent hypercholesteremia has been observed on many occasions and in both natural and experimental conditions. The relation exists in several species although the degree of association appears to be species specific.2 , 3 The development of refined biophysical methods for the characterization of serum lipids has not greatly clarified this relation of serum lipids to disease although the new methods have emphasized a lack of correlation between the serum cholesterol and lipoprotein quantities . . .
Mortality and Late Results of Infectious Hepatitis in Pregnant Women
Authors: Howard Lawrence Frucht, James Metcalfe
Journal: New England Journal of Medicine (1954)

The immediate mortality from infectious hepatitis, especially in its nonepidemic form, is extremely low. Previous work has suggested a higher mortality in pregnant women, at least in areas where undernutrition is common.It was the purpose of the study reported here to investigate the immediate mortality of infectious hepatitis in pregnant women and also to evaluate liver function a year or more after the acute episode in women who survived.All cases diagnosed as nonobstructive jaundice at the Boston Lying-in Hospital in the past eighteen years were reviewed to select patients for this study. No case occurring more recently than . . .