tbuckley/cabot-search huggingface dataset:
Murine Mammary Tumor Virus Seroepidemiology in BALB/cfC3H Mice: Correlation with Tumor Development&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: B W Altrock, R D Cardiff, P B Blair
Journal: JNCI Journal of the National Cancer Institute (1981)

Serum reactivity to murine mammary tumor virus (MuMTV) was inversely related to mammary tumor risk in 8-to 22-week-old BALB/cfC3H breeding females. Mice at low tumor risk exhibited high-titered serum reactivity to MuMTV (50% end point, greater than or equal to 1:40 by radioimmunoassay) approximately 3-6 months earlier than did the mice at high tumor risk. Maternal MuMTV antibody levels were correlated with the serum anti-MuMTV reactivity of their neonatal offspring (2 wk of age). Serologic antiviral reactivity in infected mice did not change during periods of pregnancy and lactation. All infected animals had detectable serum MuMTV reactivity by 33 weeks of age. The virus-neutralizing capabilities of some of these sera were tested, Sera from some of the young, low-tumor-risk animals that had MuMTV-precipitating antibodies also had virus-neutralizing activity. Conversely, none of the sera from the high-tumor-risk animals had detectable MuMTV-neutralizing antibodies.
A Controlled Trial of a Program for the Active Management of Labor
Authors: José A. López-Zeno, Alan M. Peaceman, Joseph A. Adashek, Michael L. Socol
Journal: New England Journal of Medicine (1992)

Over the past two decades, the rate of cesarean section in the United States has risen from 5 percent to 25 percent of deliveries, primarily because of the increased frequency of dystocia (arrest of labor). One strategy that has been proposed for increasing the rate of vaginal delivery is a program of active management of labor that encourages early amniotomy, early diagnosis of slow progress in labor, and the use of higher than usual doses of oxytocin; the efficacy and safety of this approach are uncertain, however.
Erythropoiesis-stimulating agents for cancer patients: Increasingly restrictive guidelines and policies in the United States and Europe
Authors: A. T. Samaras, S. Y. Lai, B. Kim, D. P. West, J. M. McKoy, M. Henke, S. M. Silver, C. L. Bennett
Journal: Journal of Clinical Oncology (2009)

e20725 Background: Erythropoiesis stimulating agents (ESAs) have transformed the treatment of cancer-associated anemia worldwide. However, recent reports of venous thromboembolism (VTE), tumor progression, and mortality risks associated with ESA administration to cancer patients have resulted in reassessments of the safety and appropriate usage of these agents. The present study investigated the disparate factors that contributed to the transformation of ESA policies. Methods: We reviewed meta-analyses, advisory committee recommendations, manufacturer label revisions, clinical guidelines, reimbursement policies from the Centers for Medicare and Medicaid Services (CMS), updated clinical guidelines, and ESA usage trends. Results: See Table . Conclusions: The risks and benefits of ESAs for cancer patients have been reassessed, resulting in increasingly restrictive guidelines and labels in the U.S. and Europe. In response to the 2008 ESA labeling change mandated by the U.S. Food and Drug Administration (FDA), the European advisory committee, Committee for Medicinal Products for Human Use (CHMP), convened to reassess the risk-benefit profile of ESAs and determined that for patients with reasonably long life expectancies, the benefits of ESAs do not outweigh the risks. Additionally, the U.S. National Comprehensive Cancer Network (NCCN) revised clinical guidelines in accordance with the FDA labeling change. Therefore, FDA actions combined with the CMS reimbursement policy have provided the impetus for increasingly restrictive use of ESAs. [Table: see text] [Table: see text]
Optimal correction of distinct CFTR folding mutants in rectal cystic fibrosis organoids
Authors: Johanna F. Dekkers, Ricardo A. Gogorza Gondra, Evelien Kruisselbrink, Annelotte M. Vonk, Hettie M. Janssens, Karin M. de Winter-de Groot, Cornelis K. van der Ent, Jeffrey M. Beekman
Journal: European Respiratory Journal (2016)

Small-molecule therapies that restore defects in cystic fibrosis transmembrane conductance regulator (CFTR) gating (potentiators) or trafficking (correctors) are being developed for cystic fibrosis (CF) in a mutation-specific fashion. Options for pharmacological correction of CFTR-p.Phe508del (F508del) are being extensively studied but correction of other trafficking mutants that may also benefit from corrector treatment remains largely unknown. We studied correction of the folding mutants CFTR-p.Phe508del, -p.Ala455Glu (A455E) and -p.Asn1303Lys (N1303K) by VX-809 and 18 other correctors (C1–C18) using a functional CFTR assay in human intestinal CF organoids. Function of both CFTR-p.Phe508del and -p.Ala455Glu was enhanced by a variety of correctors but no residual or corrector-induced activity was associated with CFTR-p.Asn1303Lys. Importantly, VX-809-induced correction was most dominant for CFTR-p.Phe508del, while correction of CFTR-p.Ala455Glu was highest by a subgroup of compounds called bithiazoles (C4, C13, C14 and C17) and C5. These data support the development of mutation-specific correctors for optimal treatment of different CFTR trafficking mutants, and identify C5 and bithiazoles as the most promising compounds for correction of CFTR-p.Ala455Glu.
Giant Calculus of the Appendix
Authors: Lewis S. Pilcher
Journal: New England Journal of Medicine (1945)

THERE are few reported cases in the medical literature of the formation of large calculi in the appendix. The two largest appendiceal calculi known are the one reported by Packard1 in 1921, measuring 1.0 by 2.0 by 4.0 cm., and the one reported by Bunch and Adcock2 in 1939, measuring 2.75 cm. in each direction. The calculus in the case reported here also measured 2.75 cm. in diameter. So far as can be determined, these 3 cases are the only ones of true calculi of such large size found in the appendix.The mechanism of calculus formation in the appendix . . .
Granulocyte colony-stimulating factor (CSF), macrophage-CSF, granulocyte-macrophage CSF, interleukin-3, and interleukin-6 levels in sera from children undergoing blood stem cell autografts
Authors: Y Kawano, Y Takaue, S Saito, J Sato, T Shimizu, T Suzue, A Hirao, Y Okamoto, T Abe, T Watanabe
Journal: Blood (1993)
S88 The viral mimic polyinosinic: polycytidylic acid (Poly I:C) induces TRPA1 channel hyper-responsiveness in an adult human stem cell-derived sensory neuronal model
Authors: R Clarke, K Monaghan, I About, I El Karim, JG McGeown, SL Cosby, TM Curtis, FT Lundy, L McGarvey
Journal: Thorax (2015)

<h3>Background</h3> Changes in airway neuronal activity are likely to underpin the heightened irritant responses such as excessive cough and wheeze which accompany respiratory virus induced exacerbations of airways disease. The mechanisms responsible are unknown but we hypothesised that neurons express pathogen recognition receptors such as toll-like receptors (TLR) through which viruses may alter neural function. Investigating this is hampered by the lack of suitable human tissues with both nerve endings and cell bodies present. We have refined an adult human neural crest stem cell-derived sensory neuronal model to overcome this obstacle. <h3>Methods</h3> Human dental pulp stem cells (hDPSCs) were differentiated towards a neuronal phenotype, termed peripheral neuronal equivalents (PNEs). Using molecular and immunofluorescent techniques, together with whole cell patch clamp electrophysiology, we investigated the expression and function of TLRs and the transient receptor potential (TRP) channels TRPV1 and TRPA1 on PNEs. We then assessed the effects of exposure to a viral mimic, the synthetic TLR3 agonist (polyI:C), on cytokine release and changes in the PNE responsiveness to the TRPA1 channel agonist cinnamaldehyde (100 µM). <h3>Results</h3> hDPSCs undergo a fibroblastic to neuronal phenotypic switch to PNEs which express the sensory neuronal proteins SP and CGRP. Using qPCR we confirm that PNEs express TLR3, TLR4 and TLR7 mRNA and functional expression of TRPA1 and TRPV1 channels. PNEs pre-treated with PolyI:C (2 µg/ml) for 20 mins generated significantly larger inward (-10.8773 pA/pF; p &lt; 0.01) and outward (10.0507 pA/pF; p &lt; 0.01) currents in response to cinnamaldehyde (100 µM) compared to untreated PNEs (-2.347 pA/pF and 2.872 pA/pF respectively). The electrophysiological events elicited by PolyI:C occurred rapidly, were not sustained and appeared independent of alteration in TRP channel gene expression. PNEs incubated with PolyI:C for 24 h released significantly greater IL6 (246.504 pg/ml; p &lt; 0.01) and IL8 (2140.83 pg/ml; p &lt; 0.001) levels compared to untreated PNEs. <h3>Conclusion</h3> Using a novel human <i>in vitro</i> sensory neuronal model we observed that Poly I:C evoked sensory neuronal hyper-responsiveness with an accompanying pro-inflammatory response. Respiratory viruses may induce similar effects on sensory neurons during exacerbations of airways disease.
Use of cancer registry data for research on patterns of breast cancer care of individuals with Medicaid insurance
Authors: R. T. Anderson, F. T. Camacho, R. Balkrishnan, E. Levine, G. Kimmick, K. Long Foley, F. Torti
Journal: Journal of Clinical Oncology (2005)

6021 Background: Data from Tumor Registries are used to guide important decisions regarding cancer care and research, policy and funding. Inferences are drawn about the adequacy and timeliness of treatment and whether such treatment is disproportionately allocated by patient characteristics such as race, age, sex, insurance type and others. This study asked whether these data were adequate, and whether supplemental information from medicaid improved the overall quality and completeness of patient treatment information. Methods: To study breast cancer care of low-income insured individuals, we developed a Medicaid-Claims and tumor registry linked database using data on 851 new cases of breast cancer diagnosed in calendar years 1997–1999 who were continuously enrolled in Medicaid in the state of North Carolina for 1 year post-diagnosis. The validity of this linked database was tested using an algorithm designed to jointly use the information from registry and claims data sources. Results: Substantial and systematic gaps in the tumor registry data were found, particularly for treatments such as chemotherapy, that occur during the initial period of diagnosis of a cancer. Approximately 75 percent of cases in the claims-linked dataset had agreement with tumor registry, and an additional 4 percent showed agreement with an absence of surgery data for a total agreement rate of 79 percent. Agreement between Medicaid and tumor registry for individual components of care ranged from 65% to 89%. Conclusions: Consideration should be given to establishing automated, validated integration of Medicaid claims with state tumor registry systems to support studies on cancer care of individuals enrolled with this important form of public health insurance. No significant financial relationships to disclose.
Treatment of First Episodes of Genital Herpes Simplex Virus Infection with Oral Acyclovir
Authors: Yvonne J. Bryson, Maryanne Dillon, Michael Lovett, Guillermo Acuna, Stephen Taylor, James D. Cherry, B. Lamar Johnson, Edward Wiesmeier, William Growdon, Terri Creagh-Kirk, Ronald Keeney
Journal: New England Journal of Medicine (1983)

Original Article from The New England Journal of Medicine — Treatment of First Episodes of Genital Herpes Simplex Virus Infection with Oral Acyclovir — A Randomized Double-Blind Controlled Trial in Normal Subjects
Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: Results from the phase III AFFIRM study.
Authors: Howard I. Scher, Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N. Sternberg, Kurt Miller, Ronald De Wit, Peter Mulders, Mohammad Hirmand, Bryan Selby, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2012)

LBA1 Background: MDV3100, a novel androgen receptor signaling inhibitor (ARSI), competitively inhibits binding of androgens to the androgen receptor (AR), inhibits AR nuclear translocation, and inhibits association of the AR with DNA (Tran et al, Science. 2009;324:787). MDV3100 was selected for development based on activity in prostate cancer model systems with overexpressed AR, and was active in a phase I-II trial enrolling pre- and post-chemotherapy treated patients with progressive castration resistant disease (CRPC) (Scher et al, Lancet. 2010;375:1437). The AFFIRM trial evaluated whether MDV3100 could prolong overall survival (OS) in men with CRPC who progressed following docetaxel-based chemotherapy. Methods: In this randomized, double-blind, placebo-controlled, multinational phase III study ( NCT00974311 ), patients who had received ≤ 2 regimens of docetaxel-based chemotherapy were randomized 2:1 to MDV3100 160 mg/day or placebo. Treatment with corticosteroids was allowed but not required. Patients were stratified by baseline ECOG performance status and mean brief pain inventory score. The primary endpoint was OS. Other efficacy endpoints included radiographic progression-free survival (PFS), time to first skeletal-related event, time to prostate-specific antigen (PSA) progression, and circulating tumor cell count conversion rate. Results: 1,199 patients were randomized between Sep 2009 and Nov 2010. Based on a planned interim analysis at 520 death events, the Independent Data Monitoring Committee (IDMC) recommended the study be unblinded and placebo patients offered MDV3100 due to a significant OS benefit (p&lt;0.0001; hazard ratio 0.631). The estimated median OS was 18.4 months for MDV3100 treated compared to 13.6 months for placebo treated men, a median OS difference of 4.8 months. Data to be available include PFS, time to PSA progression, and safety. Conclusions: MDV3100, a novel ARSI, significantly improves OS in men with postdocetaxel-treated CRPC reducing the risk of death by 37% relative to placebo. The IDMC determined the risk:benefit of MDV3100 was favorable and recommended the phase III AFFIRM trial be unblinded.
Immune Complexes in Hepatocytic Nuclei of Hb Ag-Positive Chronic Hepatitis
Authors: Michael A. Gerber, Euzenir Sarno, Salvatore J. Vernace
Journal: New England Journal of Medicine (1976)

To localize immune complexes in viral hepatitis Type B and to assess their pathogenic role, we examined by the direct fluorescent-antibody technic 21 liver specimens with hepatitis B core antigen (HBc Ag) in hepatocytic nuclei from 10 patients with HBs Ag-seropositive acute viral hepatitis and from 11 patients with HBs Ag-seropositive chronic active hepatitis. IgG with in vitro fixation of complement was demonstrated in HBc Ag-containing hepatocytic nuclei of all patients with chronic active, but not in those with acute viral hepatitis. All patients except for one had antibody to HBc Ag in the serum as determined by indirect immunofluorescence. The evidence suggests that intranuclear IgG in chronic active hepatitis has anti-HBc specificity and forms immune complexes with HBc Ag. The binding of IgG to intranuclear HBc Ag might have pathogenic importance in chronic active hepatitis. (N Engl J Med 294:922–925, 1976)
CBM-06IMMUNE BIOMARKER RESULTS FROM A TRIAL OF NIVOLUMAB ± IPILIMUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: CHECKMATE-143
Authors: Daniel E. Lowther, Kent Weinhold, Elizabeth Reap, Gordana Vlahovic, Antonio Omuro, Solmaz Sahebjam, Joachim Baehring, Alfredo Voloschin, Timothy Cloughesy, Michael Lim, Vlad Coric, Robert Latek, Jason Simon, Benjamin Lerner, Khadir Raddassi, David A. Hafler, John Sampson
Journal: Neuro-Oncology (2015)

BACKGROUND: The prognosis for patients with glioblastoma (GBM) remains poor despite the availability of first-line therapies including surgery and chemoradiation. Recent evidence suggests that there are varying degrees of lymphocyte infiltration in GBM, and the composition may have prognostic significance. Expansion of regulatory T cells (CD4+FoxP3+, Treg) at the tumor site has been observed and is implicated in cancer-associated immunity in GBM. Immune checkpoint inhibitors, such as the fully human anti-PD-1 monoclonal antibody nivolumab, have shown promising antitumor activity in both solid tumors and preclinical glioma models. The CHECKMATE-143 study is evaluating nivolumab as monotherapy and in combination with ipilimumab (anti-CTLA-4) in patients with recurrent GBM (Cohorts 1 and 1b). As part of the initial phase of this study, T-cell maturation, activation, exhaustion, and effector function, as well as Treg frequencies and function and myeloid-derived suppressor cell frequencies were examined. METHODS: Analyses were performed on peripheral blood drawn from patients at pre-determined time points and upon tumor tissue samples obtained if resection was performed at the time of progression or suspected progression. Baseline and on-treatment samples were obtained from patients (n = 20) randomized 1:1 to receive either nivolumab 3 mg/kg Q2W or nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W followed by nivolumab 3 mg/kg Q2W. Phenotypic analysis was determined by CyTOF and flow cytometry; Treg suppressive function by thymidine incorporation; cytokine release by multiplex immunoassay; and gene expression by RNAseq. RESULTS: Treatment-related changes in lymphocyte populations (including but not limited to T, B, and NK cells, granulocytes, and memory and effector T-cell subsets) in peripheral blood and resected tumor will be reported. CONCLUSIONS: Peripheral and tumor biomarker analyses of GBM subjects treated with checkpoint inhibitors will provide insights into treatment-related changes versus tumor progression.
Cyanocobalamin-Dependent Depression of the Serum Alkaline Phosphatase Level in Patients with Pernicious Anemia
Authors: C. K. V. van Dommelen, C. H. L. Klaassen
Journal: New England Journal of Medicine (1964)

LOWERING of the serum alkaline phosphatase activity has received little attention.1 It is known in scurvy and hypophosphatasemia and after exposure to radioactive substances that are deposited in bone. In children the serum alkaline phosphatase falls to adult levels when the skeletal growth is disturbed (as in achondroplasia or cretinism).2 We observed a patient suffering from both pernicious anemia and Paget's disease. The serum phosphatase level was normal and increased to abnormal height only after administration of vitamin B12.One possible explanation of these facts was that osteoblastic activity had been depressed by vitamin B12 deficiency. If . . .
Managing atypical and typical herpetic central nervous system infections: results of a multinational study
Authors: Y. Cag, H. Erdem, S. Leib, S. Defres, S. Kaya, L. Larsen, M. Poljak, D. Ozturk-Engin, B. Barsic, X. Argemi, S.M. Sørensen, A.L. Bohr, P. Tattevin, J.D. Gunst, L. Baštáková, M. Jereb, I.S. Johansen, O. Karabay, A.U. Pekok, O.R. Sipahi, M. Chehri, G. Beraud, G. Shehata, R. Fontana, M. Maresca, H. Karsen, G. Sengoz, M. Sunbul, G. Yilmaz, H. Yilmaz, A. Sharif-Yakan, S. Kanj, E. Parlak, F. Pehlivanoglu, F. Korkmaz, S. Komur, S. Kose, M. Ulug, S. Bolukcu, S.A. Coskuner, J.P. Stahl, N. Ince, Y. Akkoyunlu, G. Halac, E. Sahin-Horasan, H. Tireli, G. Kilicoglu, A. Al-Mahdawi, S.A. Nemli, A. Inan, S. Senbayrak, H. Vahaboglu, N. Elaldi
Journal: Clinical Microbiology and Infection (2016)
Particle-Associated RNA-Dependent DNA Polymerase and High-Molecular-Weight RNA in a Human Cell Line Derived From Polycythemia Vera Bone Marrow
Authors: B. J. Weimann, N. Kluge, S. K. Dube, G. von Ehrenstein, J. C. Krieg, J. Kind, W. Ostertag
Journal: JNCI Journal of the National Cancer Institute (1975)

A particle fraction with a density of 1.15-1.19 g/cm3 was isolated from the cytoplasm of a human cell line established in culture from the bone marrow of an untreated patient with polycythemia vera. Electron micrographs of cross sections of cells and cell homogenates revealed virus-like particles on which DNA could be synthesized. An RNA-dependent DNA polymerase, isolated from the particles, preferred poly(rA)-oligo(dT) over poly(dA)-oligo(dT) and was able to polymerize deoxyguanosine monophosphate in a reaction stimulated by poly(rC)-oligo(dG).
Abstract 2296: An isoform of BARD1, associated with many types of cancer, is a driver of oncogenesis by inducing telomere aberrations in vitro and in vivo
Authors: Maxim Pilyugin, Pierre-Alain Andre, Magdalena Ratajska, Irmgard Irminger-Finger
Journal: Cancer Research (2015)

Abstract BARD1 has tumor suppressor functions by binding to BRCA1 and to p53 via RING finger and ankyrin repeats, respectively. The BARD1-BRCA1 heterodimer has E3 ligase activity, and the BARD1-p53 interaction promotes apoptosis. The expression of N-terminally truncated RING-less BARD1 isoforms, however, was correlated with poor prognosis in various cancers. We performed overexpression experiments with various isoforms of BARD1 and found that BARD1δ, lacking RING and ANK regions, induces cell cycle arrest, multipolar mitotic spindles, genomic instability, and telomere aberrations. Co-localization studies and interaction assays in HeLa, MCF7, or HEK 293 cells, using tagged BARD1δ and full length (FL) BARD1, showed that the BRCT domains, present in BARD1δ and FL BARD1, interact with centrosome binding proteins and telomere binding proteins. BARD1δ overexpressing cells showed multipolar spindles and telomere alterations. Similar telomere alterations were observed in cells with reduced expression of FL BARD1 by siRNA. This is consistent with the observed distinct telomeric abnormalities in blood cells of patients with a BARD1 germline mutation that causes translation of a truncated protein lacking the BRCT domains. CRE-inducible BARD1δ transgenic mice showed dose-dependent growth arrest and tumor formation in various organs. These in vitro and in vivo observations suggest that BARD1δ plays a significant role in tumorigenesis by inducing genomic and telomere instability. Citation Format: Maxim Pilyugin, Pierre-Alain Andre, Magdalena Ratajska, Irmgard Irminger-Finger. An isoform of BARD1, associated with many types of cancer, is a driver of oncogenesis by inducing telomere aberrations in vitro and in vivo. [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 2296. doi:10.1158/1538-7445.AM2015-2296