tbuckley/cabot-search huggingface dataset:
Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy
Authors: Peter G. Rose, James Java, Charles W. Whitney, Frederick B. Stehman, Rachelle Lanciano, Gillian M. Thomas, Paul A. DiSilvestro
Journal: Journal of Clinical Oncology (2015)

To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes.
OBSERVATIONS ON THE SUCCUS ENTERICUS
Authors: Herman O. Mosenthal
Journal: The Journal of Experimental Medicine (1911)

Nitrogen equivalent to about 35 per cent of the nitrogen intake, though not necessarily derived directly from it, is daily secreted in the succus entericus in dogs on a mixed diet; about 10 per cent is excreted in the feces. and about 25 per cent is reabsorbed. The amount of reabsorbed nitrogen-containing material is considerably larger if the bile and pancreatic secretion are included. The metabolic significance of this reabsorption can only be surmised. That it is probably of great importance is indicated by the fact that in the experiments here recorded the amount of nitrogen reabsorbed equaled approximately 25 per cent of the nitrogen intake.
Neutrophilic Urticaria With Systemic Inflammation
Authors: Hrishikesh Belani, Lianne Gensler, Urmila Bajpai, Eric Meinhardt, Jonathan Graf, Laura Pincus, Kieron S. Leslie
Journal: JAMA Dermatology (2013)

Predominantly neutrophilic infiltrates are seen in a subset of patients with urticaria. The lesions tend to be less itchy and poorly responsive to standard therapy, including antihistamines. We describe 2 patients having neutrophilic urticaria with systemic inflammation (NUSI) without known connective tissue disorder or malignancy. We propose the term NUSI to help classify a previously undefined multisystemic inflammatory entity likely mediated by interleukin 1 (IL-1).Patient 1, a 47-year-old woman, was seen with urticaria and associated night sweats, fevers, and polyarticular arthritis. Acute-phase reactants were elevated with worsening of symptoms. Initial treatment with a combination of topical and systemic corticosteroids, antihistamines, and immunosuppressants was unsuccessful. A 100% clinical resolution was achieved with anakinra, an IL-1 receptor antagonist. Patient 2, a 24-year-old woman, was seen with urticaria and associated joint pain and swelling. Initial treatment included a combination of antihistamines, colchicine, and dapsone. Only colchicine provided moderate benefit but was stopped because of significant gastrointestinal tract discomfort. Anakinra was initiated; the patient achieved 100% control while receiving daily therapy.The diagnosis of NUSI is important to consider in patients who are seen with antihistamine-resistant urticaria in combination with systemic inflammatory symptoms. Interleukin 1 blockade is a viable option for therapy.
Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine
Authors: D H Schwartz, G Gorse, M L Clements, R Belshe, A Izu, A M Duliege, P Berman, T Twaddell, D Stablein, R Sposto
Journal: The Lancet (1993)

A recombinant human immunodeficiency virus 1 IIIB (HIV-1IIIB) gp120 subunit vaccine (IIIB-rgp120/HIV-1, Genentech) was tested for safety and immunogenicity in a randomised, double-blind, placebo-controlled phase-I trial. HIV-1-seronegative adult volunteers received three 100 micrograms or 300 micrograms doses of IIIB-rgp120/HIV-1 in alum adjuvant (10 vaccinees in each group), or alum adjuvant alone (8 vaccinees), at 0, 4, and 32 weeks by intramuscular injection. The three injections were well tolerated in both vaccine groups. Antibodies that neutralised homologous HIV-1IIIB were induced in 9 of 10 recipients after three 300 micrograms doses, and 6 of these 9 sera also neutralised heterologous HIV-1SF2. A dose response was evident, since three 100 micrograms injections induced lower titres of HIV-1IIIB neutralising antibodies and in fewer recipients (5 of 9) than the higher dose, with no neutralisation of HIV-1SF2. Similarly, syncytia-inhibiting, CD4-rgp120-blocking, and HIV-1IIIB V3-binding antibodies were induced in a dose dependent manner. Response to the 300 micrograms per dose vaccination occurred in a larger proportion of volunteers and at higher mean titres than seen in previous human trials with other recombinant envelope subunit vaccines or live vaccinia-env priming followed by envelope subunit boosting.
Diabetes Enhances Vulnerability to Particulate Air Pollution–Associated Impairment in Vascular Reactivity and Endothelial Function
Authors: Marie S. O’Neill, Aristidis Veves, Antonella Zanobetti, Jeremy A. Sarnat, Diane R. Gold, Panayiotis A. Economides, Edward S. Horton, Joel Schwartz
Journal: Circulation (2005)

Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes.Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution (fine particles [PM2.5], particle number, black carbon, and sulfates [SO4(2-)]) approximately 500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO4(2-) were associated with decreased flow-mediated (-10.7%; 95% CI, -17.3 to -3.5) and nitroglycerin-mediated (-5.4%; 95% CI, -10.5 to -0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity (-12.6%; 95% CI, -21.7 to -2.4), and PM2.5 was associated with nitroglycerin-mediated reactivity (-7.6%; 95% CI, -12.8 to -2.1). Effects were stronger in type II than type I diabetes.Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic.
Alpha-1-antitrypsin regulates IL-8 release and CXCR2 expression in human neutrophils
Authors: Nupur Aggarwal, Jan Hegermann, Veronica Grau, Matthias Ochs, Tobias Welte, Sabina Janciauskiene
Journal: European Respiratory Journal (2014)

The modulation of the neutrophil CXC chemokine receptor-2 (CXCR2) is an important mechanism controlling neutrophil responsiveness. The expression of CXCR2 is rapidly down-modulated by lipopolysaccharide (LPS) via tyrosine kinase-dependent mechanism whereas IL-8 accounts for the similar down-modulation of surface CXCR2 expression through rapid receptor internalization. Acute phase protein, α1-antitrypsin (A1AT), is a know regulator of neutrophil responses to LPS, however AAT9s effect on the CXCR2 expression has not been investigated. Priming of human neutrophils with LPS (10ng/3x10 6  cells) caused a time-dependent decrease of surface CXCR2 levels and reduction in mRNA CXCR2 (80%, p=0.027) by 4 hours. At 1h, A1AT (1mg/3x10 6 cells) enhanced whereas at 4 h abolished effect of LPS on CXCR2 expression. Similarly, when compared to IL-8 (50 ng/3x10 6  cells) primed cells, addition of AAT caused an enhanced internalization (for up to 1h) and a subsequent re-expression (at 4h) of the surface CXCR2 without effecting mRNA of CXCR2. Remarkably, within a short-term (1h) A1AT enters into the neutrophil, induces transient ERK1/2 activation and localizes into plasma membranes, cytosol and secretary vesicles pushing out IL-8 from these compartments. Pretreatment with U0126, a highly specific MEK1/2 inhibitor, abolished A1AT ability to induce ERK1/2 activation and IL-8 release, and attenuated effect of A1AT on CXCR2 expression in LPS or IL-8-primed neutrophils. Our data show that A1AT modulates surface CXCR2 expression via activation of ERK1/2 pathway and concomitant modulation of IL-8 release. These findings help us to understand the therapeutic role of A1AT in combating neutrophil mediated inflammation.
The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection
Authors: P B Jeppesen, P B Mortensen
Journal: Gut (1998)

Background —Medium chain C8–C10 triglycerides (MCTs) improve fat absorption in short bowel patients. Effects on overall energy absorption remain unknown. Aims —To determine whether MCTs and medium chain fatty acids (MCFAs) are absorbed in the colon like the short chain fatty acids (SCFAs) or are lost in faeces similarly to long chain fatty acids (LCFAs). Methods— Nine small bowel resected patients without and 10 with a colon in continuity excreted 2–6 MJ/day and were randomised and crossed over between two high fat diets (10 MJ/day, 50% as fat), based on either long chain triglycerides (LCT) alone or equal quantities of LCT and MCT. Results —Patients with a colon absorbed C8–C10 fatty acids considerably better than patients without a colon at similar and extreme levels of LCFA malabsorption; the colonic impact on absorption of C14–18 fatty acids was negligible. MCT redoubled fat (MCT+LCT) absorption from 23% to 58% in patients with a colon, and increased overall bomb calorimetric energy absorption from 46% to 58%. The increase in fat absorption from 37% to 46% in patients without a colon did not improve overall energy absorption because malabsorption of carbohydrate and protein increased. Conclusion— In small bowel resected patients, the colon seems to serve as a digestive organ for medium chain fat, probably absorbed as MCFAs, perhaps because like the SCFAs, they are water soluble. Only patients with a colon gained from MCT treatment.
Controlled relaxation. I. Quantitation of electromyogram with abdominal relaxation
Authors: R. H. De Jong
Journal: JAMA (1966)

Twenty-five surgical patients anesthetized with halothane received succinylcholine, curare, or gallamine for abdominal muscle relaxation. Twitch amplitude of the action potential from small muscles of the hand or foot to supramaximal motor nerve stimulation was measured while the surgeon estimated abdominal muscle tone. Minimal neuromuscular block (76% to 100% transmission) never produced excellent abdominal relaxation. Major neuromuscular block (1% to 25% transmission) by any of the relaxants produced excellent relaxation in 21 (84%) subjects. With profound block (5% to 10% transmission), evidenced by only a faint muscle contraction, excellent relaxation was uniformly produced. Depth of neuromuscular block can be clinically monitored with a simple peripheral nerve stimulator. Adjusting muscle relaxant dosage to maintain a faint but perceptible muscle contraction assures maximal operating conditions while avoiding excessive drug administration.
Diabetes Prevalence and Care in the Métis Population of Ontario, Canada
Authors: Baiju R. Shah, Karen Cauch-Dudek, Lisa Pigeau
Journal: Diabetes Care (2011)

The Métis are a distinct Aboriginal people in Canada with a unique history, culture, and language. This study examined diabetes prevalence and care in the Métis of Ontario.The 14,480 people in the citizenship registry of the Métis Nation of Ontario were linked with provincial health care databases to determine diabetes prevalence and processes of care. Rates were compared between the Métis and the general Ontario population.The age/sex standardized prevalence of diabetes for the Métis was 11.2%, nearly 25% higher than that of the general Ontario population. Métis were more likely to be hospitalized (12.7 vs. 10.7%) or require emergency room visits (36.1 vs. 27.7%).Métis people have an increased burden of diabetes that puts them at risk for complications and morbidity. Ensuring adequate access to and quality of care for diabetes is essential to maintain the health of the Métis people.
Development of Teratomas From the Ectoderm of Mouse Egg Cylinders2
Authors: Sanjivani B. Diwan, Leroy C. Stevens
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Development of Teratomas From the Ectoderm of Mouse Egg Cylinders Get access Sanjivani B. Diwan, Sanjivani B. Diwan Search for other works by this author on: Oxford Academic PubMed Google Scholar Leroy C. Stevens Leroy C. Stevens 4 4Address reprint requests to Dr. L. C. Stevens. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 4, October 1976, Pages 937–942, https://doi.org/10.1093/jnci/57.4.937 Published: 01 October 1976 Article history Received: 01 March 1976 Accepted: 12 July 1976 Published: 01 October 1976
Functional Analysis of Genes in Regions Commonly Amplified in High-Grade Serous and Endometrioid Ovarian Cancer
Authors: Sally J. Davis, Karen E. Sheppard, Richard B. Pearson, Ian G. Campbell, Kylie L. Gorringe, Kaylene J. Simpson
Journal: Clinical Cancer Research (2013)

Ovarian cancer has the highest mortality rate of all the gynecologic malignancies and is responsible for approximately 140,000 deaths annually worldwide. Copy number amplification is frequently associated with the activation of oncogenic drivers in this tumor type, but their cytogenetic complexity and heterogeneity has made it difficult to determine which gene(s) within an amplicon represent(s) the genuine oncogenic driver. We sought to identify amplicon targets by conducting a comprehensive functional analysis of genes located in the regions of amplification in high-grade serous and endometrioid ovarian tumors.High-throughput siRNA screening technology was used to systematically assess all genes within regions commonly amplified in high-grade serous and endometrioid cancer. We describe the results from a boutique siRNA screen of 272 genes in a panel of 18 ovarian cell lines. Hits identified by the functional viability screen were further interrogated in primary tumor cohorts to determine the clinical outcomes associated with amplification and gene overexpression.We identified a number of genes as critical for cellular viability when amplified, including URI1, PAK4, GAB2, and DYRK1B. Integration of primary tumor gene expression and outcome data provided further evidence for the therapeutic use of such genes, particularly URI1 and GAB2, which were significantly associated with survival in 2 independent tumor cohorts.By taking this integrative approach to target discovery, we have streamlined the translation of high-resolution genomic data into preclinical in vitro studies, resulting in the identification of a number of genes that may be specifically targeted for the treatment of advanced ovarian tumors.
Relationship Between Cyclophilin A Levels and Matrix Metalloproteinase 9 Activity in Cerebrospinal Fluid of Cognitively Normal Apolipoprotein E4 Carriers and Blood-Brain Barrier Breakdown
Authors: Matthew R. Halliday, Nunzio Pomara, Abhay P. Sagare, Wendy J. Mack, Blas Frangione, Berislav V. Zlokovic
Journal: JAMA Neurology (2013)

In humans, apolipoprotein E (apoE) has 3 isoforms: apoE2, apoE3, and apoE4.APOE4 is a major genetic risk factor for Alzheimer disease (AD). 1 Apolipoprotein E4 has direct effects on the cerebrovascular system, resulting in microvascular lesions and blood-brain barrier (BBB) damage, as recently reviewed. 25][6] Our recent studies in transgenic mice have demonstrated that apoE4 leads to BBB breakdown by activating the proinflammatory cyclophilin A (CypA)-matrix metalloproteinase 9 (MMP-9) pathway in brain pericytes, which in turn results in degradation of the BBB tight junctions and basement membrane proteins. 7It has also been shown that apoE4-mediated BBB breakdown leads to secondary neuronal injury and cognitive decline in transgenic mice. 7Apolipoprotein E2 and apoE3 maintained normal BBB integrity in transgenic mice by suppressing the CypA-MMP-9 pathway. 7Here, we studied the cerebrospinal fluid (CSF)/plasma albumin quotient (Q Alb ), an established marker of BBB breakdown, 8 and CypA and active MMP-9 levels in the CSF of cognitively normal individuals with different APOE genotypes to determine whether apoE4dependent changes in BBB permeability and CypA-MMP-9 pathway as shown in APOE4, but not APOE3 and APOE2 transgenic mice, also occur in humans.
Dystroglycan Matrix Receptor Function in Cardiac Myocytes Is Important for Limiting Activity-Induced Myocardial Damage
Authors: Daniel E. Michele, Zhyldyz Kabaeva, Sarah L. Davis, Robert M. Weiss, Kevin P. Campbell
Journal: Circulation Research (2009)

Genetic mutations in a number of putative glycosyltransferases lead to the loss of glycosylation of dystroglycan and loss of its laminin-binding activity in genetic forms of human muscular dystrophy. Human patients and glycosylation defective myd mice develop cardiomyopathy with loss of dystroglycan matrix receptor function in both striated and smooth muscle.To determine the functional role of dystroglycan in cardiac muscle and smooth muscle in the development of cardiomyopathy in muscular dystrophies.Using cre/lox-mediated gene targeting, we show here that loss of dystroglycan function in ventricular cardiac myocytes is sufficient to induce a progressive cardiomyopathy in mice characterized by focal cardiac fibrosis, increase in cardiac mass, and dilatation ultimately leading to heart failure. In contrast, disruption of dystroglycan in smooth muscle is not sufficient to induce cardiomyopathy. The specific loss of dystroglycan function in cardiac myocytes causes the accumulation of large, clustered patches of myocytes with membrane damage, which increase in number in response to exercise-induced cardiac stress, whereas exercised mice with normal dystroglycan expression accumulate membrane damage limited to individual myocytes.Our findings suggest dystroglycan function as an extracellular matrix receptor in cardiac myocytes plays a primary role in limiting myocardial damage from spreading to neighboring cardiac myocytes, and loss of dystroglycan matrix receptor function in cardiac muscle cells is likely important in the development of cardiomyopathy in glycosylation-deficient muscular dystrophies.
Acute respiratory distress syndrome due to methicillin-resistant Staphylococcus aureus sepsis in hyper-IgE syndrome
Authors: E Sato, H Yamamoto, T Honda, S Koyama, K Kubo, M Sediguchi
Journal: European Respiratory Journal (1996)

We report the case of a 34 year old woman with acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) due to methicillin-resistant Staphylococcus aureus (MRSA) sepsis with hyperimmunoglobulin E syndrome (HIES). Although chemotactic activity of neutrophils was impaired in this patient, neutrophils accumulated in the lungs as assessed by bronchoalveolar lavage fluid (BALF) counts. In addition to antibiotics and oxygen therapy, the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) resulted in a remarkable recovery.
THE CD1 SYSTEM: Antigen-Presenting Molecules for T Cell Recognition of Lipids and Glycolipids
Authors: Steven A. Porcelli, Robert L. Modlin
Journal: Annual Review of Immunology (1999)

▪ Abstract Recent studies have identified the CD1 family of proteins as novel antigen-presenting molecules encoded by genes located outside of the major histocompatibility complex. CD1 proteins are conserved in all mammalian species so far examined and are prominently expressed on cells involved in antigen presentation, which suggests a role in activation of cell-mediated immunity. This has now been confirmed by functional studies demonstrating the ability of CD1 proteins to restrict the antigen-specific responses of T cells in humans and mice. Identification of naturally occurring antigens presented by CD1 has revealed the surprising finding that these are predominantly a variety of foreign lipids and glycolipids, including several found prominently in the cell walls and membranes of pathogenic mycobacteria. Structural, biochemical, and biophysical studies support the view that CD1 proteins bind the hydrophobic alkyl portions of these antigens directly and position the polar or hydrophilic head groups of bound lipids and glycolipids for highly specific interactions with T cell antigen receptors. Presentation of antigens by CD1 proteins requires uptake and intracellular processing by antigen presenting cells, and evidence exists for cellular pathways leading to the presentation of both exogenous and endogenous lipid antigens. T cells recognizing antigens presented by CD1 have a range of functional activities that suggest they are likely to mediate an important component of antimicrobial immunity and may also contribute to autoimmunity and host responses against neoplastic cells.