tbuckley/cabot-search huggingface dataset:
Cumulative meta-analysis of randomized trials comparing gemcitabine-based chemotherapy versus gemcitabine alone in patients with advanced or metastatic pancreatic cancer (PC)
Authors: E. Banu, S. Oudard, A. Banu, A. Fodor, B. Landi, T. Lecomte, P. Laurent-Puig, P. H. Cugnenc, J. M. Andrieu
Journal: Journal of Clinical Oncology (2005)

4101 Background: Most individual trials have been to small to show clear benefit of gemcitabine (GEM) combination therapy comparing to GEM alone. Previously published meta-analysis exploring this hypothesis (Fung, ASCO 2003) included 1503 patients in 7 studies and failed to demonstrate any additional benefit of GEM combination on overall survival (OS). Methods: The end points were the effect on OS of GEM-based combination comparing to GEM alone in pts with advanced or metastatic PC and the relationship between GEM intended dose-intensity (DI) and OS. Randomized controlled trials (RTC) were included if they provided an OS assessment with presentation of the survival graph and time-to-event data. The number of pts at risk and deaths were extracted from survival curves and adjusted based on the extent of follow-up. Pooled relative risk reduction (RRR) with 95% confidence interval (CI) at 6, 12 and 18 months were calculated using a fixed effects model (EasyMa software). Heterogeneity was analyzed using Cochran method. Results: The meta-analysis was performed on an intention to treat basis. Results were based on published data of 3314 pts (1649 pts treated with GEM combinations and 1665 pts with GEM alone) included in 14 RCT. GEM was combined with platinum salt (43%), 5-FU derivates (29%) and others (28%).The follow-up range was 2.9–71.8 months. No differences of age, sex, performance status and stage of disease were found among studies. We found an OS benefit at all time points for pts treated with GEM combination [RRR of 9% (CI 3–16%), 4% (CI 0–7%) and 3% (CI 0–6%) at 6, 12 and 18 months, respectively]. Subgroup analyses suggested a benefit for pts included in RCT that tested the same planned DI of GEM in two arms at all time points and for platinum salt association (only at 6 and 18 months). Heterogeneity and rank test for publication bias were not statistically significant. Conclusions: The available evidence suggest that GEM combination therapy improves OS compared to GEM alone. Ongoing, prospectively RCT will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to GEM monotherapy. No significant financial relationships to disclose.
Altered Heterogeneity of Monocytes in Acute Myelomonocytic Leukemia&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: Barry T. Shannon, Sarah Finkelstein, Jeane P. Hester, H. Hugh Fudenberg, Ezio Merler
 8
Journal: JNCI Journal of the National Cancer Institute (1983)

Human peripheral blood monocytes isolated from normal donors and patients with acute myelomonocytic leukemia (AMML) were separated on a discontinuous density gradient of bovine serum albumin (BSA) into five fractions. Cells from each fraction were assayed for cell surface markers, prostaglandin E2 (PGE2) production, ability to affect proliferation in response to antigen by autologous peripheral blood lymphocytes previously depleted of monocytes, and ability to regulate immunoglobulin (Ig) synthesis by allogeneic B-lymphocytes. Fractions 1-5 from normal donors contained 11, 10, 23, 34, and 22%, respectively, of the total number of monocytes. In contrast, in 6 patients with AMML fraction 3 was considerably larger (52%) than any other fraction, in 1 patient comprising 87% of her monocytes. Cells from each fraction differed markedly in accessory function. In general, cells from fraction 3 were poorer as helper cells than cells from other fractions. They also produced after stimulation larger amounts of PGE2 than did cells from other fractions of the gradient. These data show that PBL contain a subpopulation of monocytes, which either helps poorly or suppresses in vitro immunologic function of T-cells (proliferation) and B-cells (lg synthesis), and that this subpopulation is increased in the blood of patients with AMML.
Painful Perianal Papules in a Middle-Aged Woman
Authors: Cristian D. Gonzalez, Catherine G. Chung, Jennie T. Clarke
Journal: JAMA Dermatology (2016)

A woman in her 50s with a history of Crohn disease was referred for evaluation of painful perianal skin growths that had been present for 1 year; physical examination revealed a tender perianal plaque with a papular, cobblestone-like surface. What is your diagnosis?
Abstract 20544: Family History Characteristics as Risk Factors for Sudden Cardiac Death Events in Hypertrophic Cardiomyopathy
Authors: Jodie Ingles, Charlotte Burns, Caroline Medi, Laura Yeates, Louise McCormack, Lauren Hunt, Julie McGaughran, John Atherton, Christopher Semsarian
Journal: Circulation (2014)

Introduction:  Sudden cardiac death (SCD) is a tragic outcome of hypertrophic cardiomyopathy (HCM). Risk stratification criteria to determine who would most benefit from implantable cardioverter defibrillator (ICD) therapy are imprecise. Family history of SCD in a 1st-degree relative is a known SCD risk factor (RF). This study sought to investigate family history characteristics as potential SCD RF.   HYPOTHESIS:  Those with a family history of: (1) SCD in 2nd-degree or more distant relative, and (2) resuscitated cardiac arrest or appropriate ICD therapy may also be at increased risk.   METHODS:  Patients attending 2 major HCM centres and definite diagnosis of HCM were included. Primary outcome was first SCD event (i.e. SCD, resuscitated cardiac arrest, and appropriate ICD therapy). Traditional RF included family history of SCD, severe LV wall thickness (LVWT; ≥30mm), unexplained syncope and non-sustained VT. Data were collected at earliest time point available and outcome assessed at most recent follow-up. Logistic regression analysis was performed.   RESULTS:  898 HCM patients were identified (766 probands, 132 affected relatives); mean age 53±18 years, 559 [62%] males, and mean LVWT 21±6mm). Over mean follow-up time of 4.5±4.6 years (total 3954 patient years) 60 SCD events were recorded (14 SCD, 16 resuscitated cardiac arrest, 30 appropriate ICD discharge). Compared to patients with no traditional RF (17%), ≥2 traditional RF was associated with a SCD event (OR 4.0, 95%CI 1.9-8.2, p   CONCLUSIONS:  Traditional RF remain a strong predictor of SCD events. SCD of a 2nd-degree (or more distant) relatives was the same as SCD of a 1st-degree relative. Current guidelines, which only recognise family history of SCD in a 1st-degree relative, may need to be modified
Evaluation Of IKZF1 Δ4-7 Deletion As a Suitable Marker For Minimal Residual Disease Monitoring; A Study Of 161 Consecutive Acute Lymphoblastic Leukaemia (ALL) Patients On The On-Going UKALL14 Trial
Authors: Nahid Zareian, Bella Patel, Lena Rai-Shetty, Clare Rowntree, Andrew McMillan, David I Marks, Tobias Menne, Paul Smith, Simon Purnell, Lynda Micklewright, Anthony V. Moorman, Adele Fielding
Journal: Blood (2013)
Functional cooperation of cyclin C and c-Myc in mediating homotypic cell adhesion via very late antigen-4 activation and vascular cell adhesion molecule-1 induction.
Authors: Zhao Jun Liu, Yoshiya Tanaka, Shinichiro Mine, Akio Morinobu, Hideo Yagita, Ko Okumura, Tadatsugu Taniguchi, Hirohei Yamamura, Yasuhiro Minami
Journal: Blood (1998)
The factor structure of self-report DSM-III axis II symptoms and their relationship to clinicians' ratings
Authors: S E Hyler, M Lyons, R O Rieder, L Young, J B Williams, R L Spitzer
Journal: American Journal of Psychiatry (1990)

A factor analysis of the entire item set of the DSM-III criteria was conducted to determine the extent to which the factors that emerged corresponded to the 11 personality disorders and three clusters included in DSM-III. Data were obtained from 552 patients who completed a self-report personality questionnaire and from 287 psychiatrists who rated their patients. Eleven questionnaire factors emerged that had eigenvalues greater than one, and at least three items emerged with factor loadings greater than 0.40. A correlational and multiple regression analysis of the questionnaire factors and clinicians' ratings showed few strong relationships between the factors and the 11 personality disorders but good correspondence with the three clusters.
Sodium Intake Regulates Glucose Homeostasis through the PPARδ/Adiponectin-Mediated SGLT2 Pathway
Authors: Yu Zhao, Peng Gao, Fang Sun, Qiang Li, Jing Chen, Hao Yu, Li Li, Xing Wei, Hongbo He, Zongshi Lu, Xiao Wei, Bin Wang, Yuanting Cui, Shiqiang Xiong, Qianhui Shang, Aimin Xu, Yu Huang, Daoyan Liu, Zhiming Zhu
Journal: Cell Metabolism (2016)
The Impact of Clonal Architecture of IDH1 and IDH2 Mutant Cases on the Biology of Myeloid Malignancies
Authors: Swapna Thota, Hideki Makishima, Bartlomiej P Przychodzen, Aaron D. Viny, Bhumika J Patel, Tomas Radivoyevitch, Mikkael A. Sekeres, Hetty E. Carraway, Torsten Haferlach, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2014)
Psychiatric consequences of "ethnic cleansing": clinical assessments and trauma testimonies of newly resettled Bosnian refugees
Authors: S M Weine, D F Becker, T H McGlashan, D Laub, S Lazrove, D Vojvoda, L Hyman
Journal: American Journal of Psychiatry (1995)

The authors describe the psychiatric assessments and trauma testimonies of 20 Bosnian refugees of "ethnic cleansing" who have recently resettled in the United States.Refugees referred from agencies managing refugee resettlement underwent systematic, trauma-focused, clinical interviews that included standardized assessment scales.The traumatic experiences of ethnic cleansing in these Bosnian refugees were genocidal in nature. The number of types of traumatic experiences correlated positively with age. Posttraumatic stress disorder (PTSD) was diagnosed in 65% of the refugees, and depressive disorders in 35%. PTSD severity scores were correlated with the number of types of traumatic events experienced.Ethnic cleansing has caused high rates of PTSD and depression, as well as other forms of psychological morbidity, in this group of resettled Bosnian refugees. The longitudinal sequelae of ethnic cleansing as a form of massive psychic trauma remain to be studied.
A Novel Phase Ii Trial of Ipilimumab, Carboplatin and Etoposide (Ice) for the First Line Treatment of Extensive Stage Small Cell Lung Cancer (Sclc)
Authors: C. Ottensmeier, I. Galea, N. Cross, T. Maishman, D. Hamid, J. Cave, M. Wheater, T. Geldart, C. Mulatero, V. Potter, S. Danson, P. Woll, R. Griffiths, L. Nolan
Journal: Annals of Oncology (2014)
PTU-015 Incidence of polyp recurrence after endoscopic mucosal resection of flat and sessile colonic polyps
Authors: J Mannath, V Subramanian, R Singh, K Ragunath
Journal: Gut (2010)

<h3>Introduction</h3> Endoscopic mucosal resection (EMR) is now widely used for treatment of sessile and flat colonic adenomas. En-bloc resection is believed to have many theoretical advantages including better histological assessment and lower recurrence rates. There are limited data directly comparing the polyp recurrence rates following endoscopically complete resection by either piecemeal or en-bloc resection techniques. <h3>Methods</h3> The aim of the study was to evaluate the incidence density (polyp recurrence) after piecemeal or en-bloc resection and to calculate the adjusted incidence rate ratio between these two methods. All patients undergoing EMR of flat or sessile colonic polyps &gt;10 mm were prospectively audited in a single tertiary centre hospital. Duration of follow-up was calculated from the time of EMR to the date of the last follow-up colonoscopy. Follow-up colonoscopies were determined by the British Society of Gastroenterology guidelines. Incidence density of polyp recurrence was calculated in patients undergoing either piecemeal or en-bloc resection and a Poisson distribution was assumed for the purposes of calculation. Analysis for incidence rate ratio was adjusted for the site and size of lesion, use of argon plasma coagulation (APC), morphology of the lesion and histology of lesion. Stata V.9.1 was used for the analysis. <h3>Results</h3> EMR was performed on 154 polyps &gt;10 mm in size in 130 patients (69 males, mean age 68). 79 polyps with a mean size of 22.6±9 mm were resected piecemeal and 75 polyps with a mean size of 14.6±5.5 mm were resected en-bloc. There were nine recurrences in the piecemeal group and one recurrence in the en-bloc group. The incidence density (ID) of polyp recurrence in the piecemeal group was 80.2 per 1000 person years of follow-up (95% CI 36.7 to 152.2). The ID of polyp recurrence in the en-bloc group was 10.7 per 1000 person years of follow-up (95% CI 0.3 to 59.6). The adjusted incidence rate ratio (IRR) for recurrence in the en-bloc compared to piecemeal group was 0.42 (95% CI 0.22 to 0.78). Among patients undergoing piecemeal resection, the adjusted IRR for additional use of APC was 0.7 (95% CI 0.38 to 1.27), for histologically less advanced lesions was 0.3 (95% CI 0.14 to 0.61) and for sessile but not flat lesions was 0.13 (95% CI 0.19 to 0.75). <h3>Conclusion</h3> The adjusted recurrence rates after en-bloc resection of colonic polyps are 60% less than that after piecemeal resection. The use of APC did not significantly change the recurrence rates after piecemeal resection, but flat lesions and histologically advanced lesions made recurrences more likely.
The Drosophila ribosomal protein S6 gene includes a 3' triplication that arose by unequal crossing-over.
Authors: M J Stewart, R Denell
Journal: Molecular Biology and Evolution (1993)

Ribosomal protein S6 (rpS6) is the major phosphoprotein of the small ribosomal subunit of eukaryotes and is phosphorylated in response to treatment with mitogens and other stimuli. We have examined the organization of the rpS6 gene of Drosophila melanogaster. Comparisons of a cDNA with genomic DNA identify a transcription unit including three exons. Two tandem repeats downstream of this transcription unit reiterate divergent copies of the third exon and flanking regions. Comparisons of these three repeats with respect to nucleotide base substitutions and deletions or insertions show clearly that they arose via a duplication and subsequent crossing-over between misaligned copies. Although no direct evidence exists that the downstream exons are transcribed, the maintenance of open reading frames in spite of extensive genetic changes is consistent with a protein-coding function.
GLP-1 based therapies: clinical implications for gastroenterologists
Authors: Mark M Smits, Daniel H van Raalte, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Djuna L Cahen
Journal: Gut (2016)

The gut-derived incretin hormone, glucagon-like peptide 1 (GLP-1) lowers postprandial blood glucose levels by stimulating insulin and inhibiting glucagon secretion. Two novel antihyperglycaemic drug classes augment these effects; GLP-1 receptor agonists and inhibitors of the GLP-1 degrading enzyme dipeptidyl peptidase 4. These so called GLP-1 based or incretin based drugs are increasingly used to treat type 2 diabetes, because of a low risk of hypoglycaemia and favourable effect on body weight, blood pressure and lipid profiles. Besides glucose control, GLP-1 functions as an enterogastrone, causing a wide range of GI responses. Studies have shown that endogenous GLP-1 and its derived therapies slow down digestion by affecting the stomach, intestines, exocrine pancreas, gallbladder and liver. Understanding the GI actions of GLP-1 based therapies is clinically relevant; because GI side effects are common and need to be recognised, and because these drugs may be used to treat GI disease.
Hepatic gene transfer of human aquaporin‐1 improves bile salt secretory failure in rats with estrogen‐induced cholestasis
Authors: Julieta Marrone, Leandro R. Soria, Mauro Danielli, Guillermo L. Lehmann, Maria Cecilia Larocca, Raúl A. Marinelli
Journal: Hepatology (2016)

The adenoviral gene transfer of human aquaporin-1 (hAQP1) water channels to the liver of 17α-ethinylestradiol-induced cholestatic rats improves bile flow, in part by enhancing canalicular hAQP1-mediated osmotic water secretion. To gain insight into the mechanisms of 17α-ethinylestradiol cholestasis improvement, we studied the biliary output of bile salts (BS) and the functional expression of the canalicular BS export pump (BSEP; ABCB11). Adenovector encoding hAQP1 (AdhAQP1) or control vector was administered by retrograde intrabiliary infusion. AdhAQP1-transduced cholestatic rats increased the biliary output of major endogenous BS (50%-80%, P < 0.05) as well as that of taurocholate administered in choleretic or trace radiolabel amounts (around 60%, P < 0.05). Moreover, liver transduction with AdhAQP1 normalized serum BS levels, otherwise markedly elevated in cholestatic animals. AdhAQP1 treatment was unable to improve BSEP protein expression in cholestasis; however, its transport activity, assessed by adenosine triphosphate-dependent taurocholate transport in canalicular membrane vesicles, was induced by 90% (P < 0.05). AdhAQP1 administration in noncholestatic rats induced no significant changes in either biliary BS output or BSEP activity. Canalicular BSEP, mostly present in raft (high cholesterol) microdomains in control rats, was largely found in nonraft (low cholesterol) microdomains in cholestasis. Considering that BSEP activity directly depends on canalicular membrane cholesterol content, decreased BSEP presence in rafts may contribute to BSEP activity decline in 17α-ethinylestradiol cholestasis. In AdhAQP1-transduced cholestatic rats, BSEP showed a canalicular microdomain distribution similar to that of control rats, which provides an explanation for the improved BSEP activity.Hepatocyte canalicular expression of hAQP1 through adenoviral gene transfer promotes biliary BS output by modulating BSEP activity in estrogen-induced cholestasis, a novel finding that might help us to better understand and treat cholestatic disorders. (Hepatology 2016;64:535-548).
Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder
Authors: Michael D. Keller, Rahul Pandey, Dong Li, Joseph Glessner, Lifeng Tian, Sarah E. Henrickson, Ivan K. Chinn, Linda Monaco-Shawver, Jennifer Heimall, Cuiping Hou, Frederick G. Otieno, Soma Jyonouchi, Leonard Calabrese, Joris van Montfrans, Jordan S. Orange, Hakon Hakonarson
Journal: Journal of Allergy and Clinical Immunology (2016)
Validation of Modeled Early Longitudinal Ca-125 Kinetics for Predicting Survival in Ovarian Cancer (Oc) Phase III Trials: Could the Failure of Adding Gemcitabine to Carboplatin-Paclitaxel (Ago-Ovar 9) Have Been Foreseen Earlier in the Trial?
Authors: M. Wilbaux, B. You, E. Hénin, A. Hardy-Bessard, A. Lortholary, E. Pujade-Lauraine, G. Freyer, M. Tod, A. Reuss, A. Du Bois, J. Sehouli, U. Wagner, J. Pfisterer
Journal: Annals of Oncology (2014)
Test for Malignant Transformation of Rat Liver Cells in Culture: Cytology, Growth in Soft Agar, and Production of Plasminogen Activator
Authors: R. Montesano, C. Drevon, T. Kuroki, L. Saint Vincent, S. Handleman, K. K. Sanford, Deborah DeFeo, I. Bernard Weinstein
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Test for Malignant Transformation of Rat Liver Cells in Culture: Cytology, Growth in Soft Agar, and Production of Plasminogen Activator Get access R. Montesano, R. Montesano Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Drevon, C. Drevon Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Kuroki, T. Kuroki Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Saint Vincent, L. Saint Vincent Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Handleman, S. Handleman Search for other works by this author on: Oxford Academic PubMed Google Scholar K. K. Sanford, K. K. Sanford Search for other works by this author on: Oxford Academic PubMed Google Scholar Deborah DeFeo, Deborah DeFeo Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Bernard Weinstein I. Bernard Weinstein Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 6, December 1977, Pages 1651–1658, https://doi.org/10.1093/jnci/59.6.1651 Published: 01 December 1977 Article history Received: 18 February 1977 Accepted: 21 July 1977 Published: 01 December 1977
Chronic Stable Angina
Authors: Maria M Wanitschek, Jakob Dörler, Hannes F Alber
Journal: New England Journal of Medicine (2016)

Key Clinical PointsChronic Stable Angina In patients with suspected angina, it is important not only to make a diagnosis, but also to assess the prognosis. Management of angina should include lifestyle changes and pharmacotherapy to reduce cardiovascular risks, including those associated with high blood pressure and elevated lipid levels. Standard antianginal medications include beta-blockers, long-acting nitrates, and calcium-channel blockers; ranolazine is a new agent approved by the Food and Drug Administration for angina. Relief of angina should be assessed again within 2 weeks after the initiation of therapy. An invasive strategy is a reasonable option in patients who do not have a response to medical therapy. Physiological assessment of the target lesion is useful to guide decisions regarding revascularization.
Clinical nonrecognition of neuroleptic-induced movement disorders: a cautionary study
Authors: P J Weiden, J J Mann, G Haas, M Mattson, A Frances
Journal: American Journal of Psychiatry (1987)

Extrapyramidal side effects are a major limitation in the use of neuroleptics, and tardive dyskinesia is a special public health problem. Accurate clinical diagnosis of extrapyramidal syndromes is necessary for effective management. The authors compared clinicians' recognition of the major extrapyramidal syndromes in 48 psychotic inpatients with independent blind diagnoses by clinical researchers using standardized ratings. The major finding was a high rate of clinical underrecognition of all major extrapyramidal syndromes, especially tardive dyskinesia. The authors discuss the clinical predictors of nonrecognition of extrapyramidal side effects and recommend improved training in their detection.
A Comparative Analysis of Radiation Lethality in Mammals Exposed at Constant Average Intensity for the Duration of Life
Authors: George A. Sacher
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article A Comparative Analysis of Radiation Lethality in Mammals Exposed at Constant Average Intensity for the Duration of Life Get access George A. Sacher George A. Sacher Division of Biological and Medical Research, Argonne National Laboratory, Lemont, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 1125–1144, https://doi.org/10.1093/jnci/15.4.1125 Published: 01 February 1955 Article history Received: 08 November 1954 Published: 01 February 1955
Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure
Authors: Simone Frea, Stefano Pidello, Virginia Bovolo, Cristina Iacovino, Erica Franco, Francesco Pinneri, Alessandro Galluzzo, Alessandra Volpe, Massimiliano Visconti, Andrea Peirone, Mara Morello, Serena Bergerone, Fiorenzo Gaita
Journal: European Journal of Heart Failure (2016)