tbuckley/cabot-search huggingface dataset:
Evaluation of BCG Administered by Scarification for Immunotherapy of Metastatic Hepatocarcinoma in the Guinea Pig2
Authors: M. G. Hanna, L. C. Peters, J. U. Gutterman, E. M. Hersh
Journal: JNCI Journal of the National Cancer Institute (1976)

In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.
Birth Cohort Testing for Hepatitis C Virus — Indian Health Service 2012–2015
Authors: Brigg Reilley, Jessica Leston, Susan Hariri, Lisa Neel, Miles Rudd,, Megan Galope, John Ward, Claudia Vellozzi
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Hepatitis C virus (HCV) infection is a substantial and largely unrecognized public health problem. An estimated 3.5 million persons in the United States are currently living with HCV infection, at least half of whom are unaware of their infection (1-3). Persons born during 1945-1965 (the "baby boomer" birth cohort) have a sixfold higher prevalence (2.6%) than adults of other ages, and represent 81% of all persons chronically infected with HCV (4). Therefore, in addition to recommending testing for all persons at risk for HCV infection, CDC and the U.S. Preventive Services Task Force (USPSTF) recommend one-time HCV testing for the birth cohort (5,6). Compared with the national average, American Indian/Alaska Native (AI/AN) persons have approximately twofold the rate of acute HCV incidence and HCV associated mortality (2). In June 2012, the Indian Health Service (IHS) implemented HCV testing in the 1945-1965 birth cohort and created a nationally standardized performance measure to monitor implementation of the recommendation. As of June 2015, the proportion of the birth cohort screened for HCV increased from a baseline of 7.9% (14,402/182,503) to 32.5% (68,514/211,014) among the AI/AN population served by IHS nationwide; provider training and the use of clinical decision tools were associated with increases in HCV testing. With this fourfold increase in testing in just 3 years, IHS needs to prepare for the challenges associated with increased identification of persons living with HCV infection.
Pursuit of truly independent data monitoring committees in research
Authors: Louise Marston, David R McKenzie, Nick Freemantle
Journal: BMJ (2016)

Independent data monitoring committees aim to protect the interests of trial participants, and their duty of care towards participants should not be affected by conflicting interests. Many agencies overseeing medical research have drawn up guidance on the topic. The International Conference on Harmonisation states: “All staff involved in the conduct of the trial should remain blind to the results of [interim] analyses, because of the possibility that their attitudes to the trial will be modified and cause changes in the characteristics of patients to be recruited or biases in treatment comparisons.” 2 The US Food and Drug Administration and the European Medicines Agency provide similar regulatory guidance. 4 Neither requires the statistician performing the interim analyses to be independent or different from those involved in managing the trial and performing the final analyses. However, the FDA states: “The integrity of the trial may be best protected when the statisticians preparing unblinded data for the DMC [data monitoring committee] are external to the sponsor and uninvolved in discussions regarding potential changes in trial design while the trial is ongoing.” Industry routinely implements this FDA guidance; publicly funded trials rarely do. Inside knowledge
Agenesis of the Lung and Patent Ductus Arteriosus with Reversal of Flow
Authors: Daniel S. Lukas, Charles T. Dotter, Israel Steinberg
Journal: New England Journal of Medicine (1953)

AGENESIS of a lung is a rare developmental defect that is usually not recognized until after death. In the majority of the 57 cases reported the diagnosis was made at autopsy.1 2 3 Before 1942 the diagnosis was made correctly before death in only 3 cases; since then it has been made in 18 living patients.1 2 3 4 The increased frequency of ante-mortem recognition is probably due to the wider use of bronchoscopy, bronchography and angiocardiography in the investigation of obscure pulmonary conditions.3 Pulmonary agenesis is commonly associated with congenital anomalies of other organs, including the heart.1 2 3 Its association with a patent ductus arteriosus, . . .
Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers
Authors: Rebecca Lock, Rachel Ingraham, Ophélia Maertens, Abigail L. Miller, Nelly Weledji, Eric Legius, Bruce M. Konicek, Sau-Chi B. Yan, Jeremy R. Graff, Karen Cichowski
Journal: Journal of Clinical Investigation (2016)

Neurofibromin 1-mutant (NF1-mutant) cancers are driven by excessive Ras signaling; however, there are currently no effective therapies for these or other Ras-dependent tumors. While combined MEK and mTORC1 suppression causes regression of NF1-deficient malignancies in animal models, the potential toxicity of cotargeting these 2 major signaling pathways in humans may necessitate the identification of more refined, cancer-specific signaling nodes. Here, we have provided evidence that MAPK-interacting kinases (MNKs), which converge on the mTORC1 effector eIF4E, are therapeutic targets in NF1-deficient malignancies. Specifically, we evaluated primary human NF1-deficient peripheral nervous system tumors and found that MNKs are activated in the majority of tumors tested. Genetic and chemical suppression of MNKs in NF1-deficient murine tumor models and human cell lines potently cooperated with MEK inhibitors to kill these cancers through effects on eIF4E. We also demonstrated that MNK kinases are important and direct targets of cabozantinib. Accordingly, coadministration of cabozantinib and MEK inhibitors triggered dramatic regression in an aggressive genetically engineered tumor model. The cytotoxicity of this combination required the suppression of MNK-induced eIF4E phosphorylation and was not recapitulated by suppressing other cabozantinib targets. Collectively, these studies demonstrate that combined MNK and MEK suppression represents a promising therapeutic strategy for these incurable Ras-driven tumors and highlight the utility of developing selective MNK inhibitors for these and possibly other malignancies.
P0812 : Impact of SVRW12 in the development of complications and fibrosis regression in patients treated with triple therapy with Boceprevir and Telaprevir
Authors: C. Perelló, J. Cabezas, E. Llop, S. Menéndez, J. De La Revilla, J. Crespo, J.L. Calleja
Journal: Journal of Hepatology (2015)
Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis
Journal: New England Journal of Medicine (2006)

BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P 0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P 0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P ≤0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of inflix imab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P0.001 for both comparisons) . CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.
Dinaciclib (SCH 727965) Is a Novel Cyclin-Dependent Kinase (CDK) Inhibitor That Exhibits Activity In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: Joseph M. M. Flynn, Leslie A. Andritsos, Jeffrey A. Jones, Amy J. Johnson, Kami Maddocks, Elizabeth Wiley, Karen Small, Eun Kyung Im, Michael R. Grever, Rajat Bannerji, John C. Byrd, Honghong Zhou
Journal: Blood (2013)
Restless Legs Syndrome
Authors: Christopher J. Earley
Journal: New England Journal of Medicine (2003)

A 45-year-old woman reports having had nightly insomnia for years. On further questioning, she reports having uncomfortable sensations in her legs when she lies down at night. She has a feeling of needing to move her legs, which is relieved only by getting up and walking around. How should this patient be evaluated and treated?
Childhood Lymphoblastic Cancer: Subgroups Defined by Nonhuman Primate Antisera to Human Lymphatic Leukemia Cell Antigens2
Authors: R. Beverly Raney, T. Mohanakumar, Richard S. Metzgar, Hie-Won L. Hann, Milton H. Donaldson
Journal: JNCI Journal of the National Cancer Institute (1977)

Lymphoblasts from 23 children with acute lymphocytic leukemia (ALL) and 10 with lymphoblastic lymphoma (LBL) were studied by complement-dependent microcytoxicity tests with two nonhuman primate antisera defining leukemia-associated and lymphoma-associated antigens. Cells form 15 patients with ALL and 1 with LBL reacted only with antiserum to chronic lymphatic leukemia (CLL). These group-I patients were predominantly female. Most were pancytopenic and lacked mediastinal widening and T-cell markers; lymphoblasts from 15 were periodic acid-Schiff-positive. Cells from 8 male patients reacted only with antiserum to converted lymphosarcoma (LS). All these group-II patients expressed T-cell markers; 5 had mediastinal enlargement and 2, an abdominal mass. Six of the 8 were PAS-negative. Cells from 9 patients reacted with both antisera. The group-III patients demonstrated some characteristics of each of the above groups. Patients whose lymphoblasts reacted with CLL antiserum presented with clinical and laboratory features indicative of a good prognosis, i.e., ALL with PAS positivity and no T-cell markers or localized mass. Patients whose cells reacted with LS antiserum often had bad prognostic features: mediastinal or abdominal mass, expression of T-cell markers, and PAS negativity. These antisera appear able to differentiate childhood ALL from LBL. The distinction is important prognostically and perhaps therapeutically.
Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency
Authors: Kelly M.J. Diederen, Tom Spencer, Martin D. Vestergaard, Paul C. Fletcher, Wolfram Schultz
Journal: Neuron (2016)

Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the magnitude of upcoming reward drawn from distributions with different SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. In line with the notion of adaptive coding, BOLD response slopes in the Substantia Nigra/Ventral Tegmental Area (SN/VTA) and ventral striatum were steeper for prediction errors occurring in distributions with smaller SDs. SN/VTA adaptation was not instantaneous but developed across trials. Adaptive prediction error coding was paralleled by behavioral adaptation, as reflected by SD-dependent changes in learning rate. Crucially, increased SN/VTA and ventral striatal adaptation was related to improved task performance. These results suggest that adaptive coding facilitates behavioral adaptation and supports efficient learning.
Responsibility and trust
Journal: BMJ (1969)

Responsibility and trust, as the rational request of rational human, are the basis of social life. Human is alone in essentially and try to get rid of it at the same time. Loneliness makes people have the consciousness of responsibility and become a morality being. Avoiding loneliness bring trust to people. There is a very closed contact between responsibility、trust and others. Responsibility means being for others; Trust means being with others. As a basis of social intercourse, trust not proceeds from responsibility but accords with it, so trust has moral value.
Postoperative Radiotherapy After Breast-Conserving Surgery for Early-Stage Breast Cancer
Authors: Corey Speers, Lori J. Pierce
Journal: JAMA Oncology (2016)

Radiotherapy (RT) after breast-conserving surgery for early-stage disease has become an integral part of breast cancer treatment. This article reviews the rationale and indications for adjuvant radiotherapy to the breast and regional lymph nodes.Randomized trials have demonstrated a significant benefit in tumor control in the treated breast following whole-breast RT that, in aggregate, has resulted in an overall survival advantage compared with breast-conserving surgery alone. Recent studies have further assessed the impact of regional nodal irradiation in women with either high-risk node-negative or node-positive disease and suggest a significant benefit in regional control and breast cancer recurrence, but not in overall survival. Toxic effects, including lymphedema, were increased in the cohorts receiving comprehensive nodal RT. The benefits from regional RT should be weighed against potential radiation-associated toxic effects. Randomized trials have also demonstrated equal efficacy and toxic effects between hypofractionated and conventionally fractionated RT in appropriately selected patients. In addition, current efforts incorporating clinical, pathologic, and molecular features are under way to identify patients for whom RT to the breast can be safely omitted.Adjuvant RT in early-stage breast cancer significantly reduces in-breast tumor recurrence and improves overall survival. Although risk reductions observed in randomized trials have been relatively consistent across series, the absolute benefit of RT is not equal for all women. Efforts are under way to identify which patients benefit the most from local or locoregional RT vs those at very low risk for recurrence in whom RT can be omitted. For patients who will benefit from RT and are appropriate candidates, hypofractionated RT should be strongly considered.
Opposite roles of cannabinoid receptors 1 and 2 in hepatocarcinogenesis
Authors: Ki-Tae Suk, Ingmar Mederacke, Geum-Youn Gwak, Sung Won Cho, Adebowale Adeyemi, Richard Friedman, Robert F Schwabe
Journal: Gut (2016)

<h3>Objective</h3> The endocannabinoid system (ECS) exerts key roles in the development of liver fibrosis and fatty liver, two diseases that promote the development of hepatocellular carcinoma (HCC). Although cannabinoids exert potent antitumour effects in vitro, the contribution of the ECS to carcinogenesis in vivo remains elusive. <h3>Design</h3> Expression of key components of the ECS, including endocannanabinoids, endocannabinoid-degrading enzymes and endocannabinoid receptors, was determined in healthy liver and tumours. Diethylnitrosamine-induced hepatocarcinogenesis was determined in mice deficient in fatty acid amide hydrolase (FAAH), the main anandamide (AEA)-degrading enzyme, in cannabinoid receptor (CB)1, CB2, or transient receptor potential cation channel subfamily V member 1 (TRPV1)-deficient mice. <h3>Results</h3> Murine and human HCCs displayed activation of the ECS with strongly elevated expression of CB1 and CB2 but only moderately altered endocannabinoid levels. Contrary to the antitumour effects of cannabinoids in vitro, we observed increased hepatocarcinogenesis in FAAH-deficient mice, a mouse model with increased AEA levels. Accordingly, inactivation of CB1, the main receptor for AEA, in wild-type or FAAH-deficient mice suppressed hepatocarcinogenesis. In contrast, inactivation of CB2 increased hepatocarcinogenesis. CB1 was strongly expressed within HCC lesions and its inactivation suppressed proliferation and liver fibrosis. CB2 was predominantly expressed in macrophages. CB2 inactivation decreased the expression of T-cell-recruiting chemokines and inhibited hepatic T-cell recruitment including particular CD4+ T cells, a population with known antitumour effects in HCC. TRPV1 deletion did not alter HCC development. <h3>Conclusions</h3> Similar to their role in fibrogenesis, CB1 and CB2 exert opposite effects on hepatocarcinogenesis and may provide novel therapeutic targets.
Cutaneous Actinomycosis
Authors: Juan C Cataño, Sara Isabel Gómez Villegas
Journal: New England Journal of Medicine (2016)

A 33-year-old man presented with lesions on his left knee that had worsened over the course of several years. Five years earlier, he had been in a motor-vehicle collision that resulted in superficial soft-tissue bruises on his left knee and no associated fractures.
Thymidylate synthetase (TS) immunohistochemistry (IHC): Feasibility in a routine clinical setting for patients receiving treatment with pemetrexed for advanced nonsquamous NSCLC.
Authors: K. M. Kerr, D. A. Fennell, R. N. Shah, M. Kumar, G. Skailes, V. A. Potter, S. Moore, P. Maxwell, M. Das, M. Nicolson
Journal: Journal of Clinical Oncology (2010)

TPS293 Background: Nonsquamous (NS-) NSCLC is a predictive factor for response to pemetrexed (pem). Laboratory evidence suggests that this differential outcome may be related to low TS mRNA expression in NS-NSCLC. In this exploratory phase II trial the primary objective ( PO) is to test prospectively, the correlation between TS protein expression (TSPE) and progression free survival (PFS). This abstract reports the TS assay (TSA) protocol to measure TSPE using IHC. Methods: An open-label, single-arm, multicentric study (with appropriate UK approvals) was undertaken to test the PO in eligible patients (n=68) receiving pem/cisplatin induction followed by maintenance pem until tumour progression (PD). Key eligibility criteria included ECOG PS 0-1, histological diagnosis of stage IIIB/IV NS-NSCLC, and informed consent. The TSA protocol for this study was designed on a validated procedure developed by study sponsors. Diagnostic slides and FFPE blocks are centrally collected for diagnostic verification and TS staining. Sections of 3 μ m will be stained using primary antibody (Zymed clone 4H4B1, 1:40 dilution) in a proprietary automated system (Ventana Discovery). Positive controls used are cell lines with low/medium/high TS and archival lung carcinomas. An experienced pulmonary pathologist and a clinical scientist will independently score both the IHC stained slides and corresponding scanned digital images using previously agreed thresholds for staining intensity. Joint review will secure scores for discrepant cases. An H score will be calculated for cytoplasmic and nuclear staining-the sum of products of both staining intensity (1, 2 and 3) and distribution (0-100% of cells). An agreed final score will be established. Where possible, additional studies, at DNA and mRNA levels, of pathways related to folate metabolism will be undertaken. The aims are to i) demonstrate that routine TSPE by IHC on the usual range of diagnostic material is feasible and practical, ii) discover the range of TS protein expression in a series of NS-NSCLC, and iii) assess clinical relevance of TS IHC in predicting response to pem. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Almac Dignostics, Lilly AstraZeneca, Lilly Lilly Lilly Lilly Lilly
Molecular Basis Of (δβ)0 Thalassaemia and HPFH In Indian Population and The Role Of Non-Coding Transcripts In Increased Foetal Hemoglobin In Adults
Authors: Thiyagaraj Mayuranathan, Janakiram Rayabaram, Reena Das, Neeraj Arora, Eunice Sindhuvi Edison, Alok Srivastava, Shaji Velayudhan
Journal: Blood (2013)
Weekly G-Csf Improves the Tolerability of Weekly Paclitaxel-Carboplatin. a Phase Ii Study of the Belgian Gynaecological Oncology Group (Bgog-Ov5)
Authors: I.B. Vergote, P.R. Debruyne, F. Kridelka, P. Berteloot, F. Amant, B. Honhon, W. Lybaert, K. Leunen, K. Geldhof, D.M.E.C. Verhoeven, F. Forget, P. Vuylsteke, L. D'Hondt, M.T. Huizing, H.F.M. Van den Bulck, A. Laenen
Journal: Annals of Oncology (2014)