tbuckley/cabot-search huggingface dataset:
1231 SVR AND PHARMACOKINETICS OF THE HCV PROTEASE INHIBITOR BI201335 WITH PEGIFN/RBV IN HCV GENOTYPE-1 PATIENTS WITH COMPENSATED LIVER CIRRHOSIS AND NON-RESPONSE TO PREVIOUS PEGIFN/RBV
Authors: S. Pol, T. Berg, M. Bonacini, M. Schuchmann, J. Lalezari, A. Erhardt, M. Bourliere, M. Manns, J.O. Stern, G. Steinmann, C.-L. Yong, J. Scherer, W. Böcher
Journal: Journal of Hepatology (2011)
Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases
Authors: Aura D Urribarri, Patricia Munoz-Garrido, María J Perugorria, Oihane Erice, Maite Merino-Azpitarte, Ander Arbelaiz, Elisa Lozano, Elizabeth Hijona, Raúl Jiménez-Agüero, Maite G Fernandez-Barrena, Juan P Jimeno, Marco Marzioni, Jose J G Marin, Tatyana V Masyuk, Nicholas F LaRusso, Jesús Prieto, Luis Bujanda, Jesús M Banales
Journal: Gut (2014)

<h3>Objective</h3> Polycystic liver diseases (PCLDs) are genetic disorders characterised by progressive bile duct dilatation and/or cyst development. Their pathogenesis is a consequence of hyperproliferation, hypersecretion and microRNA alterations in cholangiocytes. Here we evaluate the role of matrix metalloproteases (MMPs) in the hepatic cystogenesis of PCLDs. <h3>Design</h3> Metalloprotease activity was measured by microfluorimetric assays in normal and polycystic cholangiocyte cultures from humans and rats, and gene expression by real time quantitative PCR. The role of cytokines, oestrogens and growth factors present in the cystic fluid of PCLD patients was evaluated for MMP activity. The MMP inhibitor marimastat was examined for cystic expansion in vitro and in polycystic kidney (PCK) rats. <h3>Results</h3> Polycystic human and rat cholangiocytes displayed increased MMP activity, which was associated with increased mRNA levels of different MMPs. Interleukin (IL)-6 and IL-8, and 17β-oestradiol, all stimulated MMP activity in human cholangiocytes. The presence of antibodies against IL-6 and/or IL-8 receptor/s inhibited baseline MMP hyperactivity of polycystic human cholangiocytes but had no effect on normal human cholangiocytes. MMP-3 was overexpressed in cystic cholangiocytes from PCLD human and PCK rat livers by immunohistochemistry. Marimastat reduced MMP hyperactivity of polycystic human and rat cholangiocytes and blocked the cystic expansion of PCK cholangiocytes cultured in three-dimensions. Chronic treatment of 8-week-old PCK rats with marimastat inhibited hepatic cystogenesis and fibrosis. <h3>Conclusions</h3> PCLDs are associated with cholangiocyte MMP hyperactivity resulting from autocrine/paracrine stimulation by IL-6 and IL-8. Inhibition of this MMP hyperactivity with marimastat decreased hepatic cystogenesis in vitro and in an animal model of PCLD, offering a potential therapeutic tool.
MELD and serum sodium
Authors: Mark W. Russo
Journal: Hepatology (2005)

I read with interest the article by Biggins et al. evaluating serum sodium as a predictor of mortality because I was hoping their study supported my clinical intuition that hyponatremia would add predictive value to the MELD score.1 However, I was disappointed on two accounts. First, although serum sodium was independently associated with mortality in multivariate analysis, the improvement in the receiver operator curve was statistically and clinically insignificant. The area under the ROC for 3-month mortality increased from 0.88 with MELD alone to 0.917 for MELD plus sodium <126, P = .207. Results for the area under the ROC for 6-month mortality were similar. The second reason for disappointment was that the conclusion reached by the authors, "Addition of serum sodium to MELD increases the ability to predict 3- and 6-month mortality in patients with cirrhosis" was not supported by their results. A study published in the October 2004 issue of HEPATOLOGY was more encouraging and demonstrated that hyponatremia by itself may not improve upon MELD for predicting mortality, but hyponatremia in the presence of ascites is better at predicting mortality in patients with MELD scores less than 21.2 Biggins et al. may have been unaware of the results from the earlier study at the time they submitted their manuscript, but the editors should have had knowledge of both studies and asked them for an analysis of serum sodium in the subgroup of candidates with low MELD scores. Mark W. Russo M.D., M.P.H.*, * University of North Carolina at Chapel Hill, Chapel Hill, NC
APPENDICITIS FROM A PHYSICIAN'S STANDPOINT.
Authors: JAMES TYSON
Journal: JAMA (1902)

Eleven years have elapsed since the first operation for appendicitis was done for me by an eminent surgeon of Philadelphia. The patient was a lad eleven years of age, who had had at least two previous attacks, and the operation may be said to have been done after recovery from the second attack. It was successful and the boy recovered without a bad symptom. Since then I have lost no opportunity to study the disease from a physician's standpoint and sought to gather some information whose application might save some of the lives which are still unfortunately lost by this disease. In the course of my observation I have noted the following: First, that there occur a certain number of cases so evident and decided that no one questions the propriety of operation. These cases are all characterized by the cardinal symptoms of sudden and severe pain, great tenderness in
823 IMPACT OF PRIOR TACE/TAE ON THE EFFICACY AND SAFETY OF SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC) FROM THE ASIA-PACIFIC REGION
Authors: W.Y. Tak, S. Yu, C.J. Tsao, T.S. Yang, J.S. Kim, S. Qin, K. Burock, J. Zou, D. Voliotis, A.L. Cheng
Journal: Journal of Hepatology (2009)
The Epstein-Barr Virus and Neoplasia
Authors: George Klein
Journal: New England Journal of Medicine (1975)

Epstein–Barr virus (EBV) is a lymphotropic herpes virus in man.1 Its main target is the human B lymphocyte.2 Only B lymphocytes and most if not all B lymphocytes have specific EBV receptors.3 Recent evidence suggests that the complement receptor of the B lymphocyte is either identical or closely associated with EBV receptor (Jondal M, Klein G, Oldstone MB: unpublished data).EBV can convert normal lymphocytes, which have a limited life span in vitro, into permanently growing cell lines.4 5 6 7 8 9 Such "immortalized" lines have a diploid or near-diploid karyotype,10 carry multiple copies of the viral genome per cell11 12 13 14 and express EBV-specific nuclear . . .
Gestational diabetes: do lean young caucasian women need to be tested?
Authors: R G Moses, J Moses, W S Davis
Journal: Diabetes Care (1998)

The American Diabetes Association has recommended that pregnant women with low-risk factors need not be tested for gestational diabetes mellitus (GDM). The aim of this study was to determine the prevalence of GDM in women with low-risk factors and to see if the pregnancy outcomes of women with GDM from a low-risk group were different from the outcomes of other women with GDM. RESEARCH DESION AND METHODS: Over an 18-month period, all pregnant women were offered a test for GDM using a 75-g glucose tolerance test at the beginning of the 3rd trimester. GDM was diagnosed if the 2-h glucose level was > or =8.0 mmol/l. The prevalence of GDM was determined in women with defined low-risk factors (Caucasian ethnic origin, age <25 years, and BMI <25 kg/m2). The pregnancy outcomes of women with GDM from a low-risk group were compared with those of other women with GDM.From a tested population of 2,907 women, 573 were identified as coming from a low-risk group. The prevalence of GDM in this low-risk group was 2.8%. The pregnancy outcomes of women with GDM from a low-risk group were no different from the pregnancy outcomes of other women with GDM, with respect to frequency of insulin use, units of insulin per day, morbidity, emergency caesarian section, and the percentage of both large- and small-for-gestational-age babies. In our population, if low-risk women were excluded, 80% of women would still require testing and nearly 10% of all cases of GDM would be missed.Women from a low-risk group have a 2.8% prevalence rate of GDM. The pregnancy outcomes of women with GDM from a low-risk group are similar to the outcomes of other women with GDM. Concerning the use of the 75-g glucose tolerance test in pregnancy, the recommendation not to test women from a low-risk group requires further evaluation in different populations before it can be endorsed.
Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells.
Authors: M Bix, M Coles, D Raulet
Journal: The Journal of Experimental Medicine (1993)

A small subset of T cells of mature phenotype express the alpha/beta T cell receptor, but not CD4 and CD8 coreceptors (alpha/beta double-negative [DN] cells). The repertoire of V beta usage of alpha/beta DN cells is strongly biased towards V beta 8 expression, suggesting that the formation of the population is subject to selection. We now report that deficiency of class I expression leads to a strongly depressed frequency of V beta 8+ DN cells, but has little effect on V beta 8- DN cells. Studies of hematopoietic chimeras between class I+ and class I- mice demonstrated that expression of class I molecules by hematopoietic cells is necessary and sufficient for selection of most V beta 8 DN cells. The lack of a role for class I expression by thymic epithelial cells suggests that the mechanism of selection of these cells by class I differs significantly from the mechanism of selection of conventional T cells. Models to explain the selection of these cells as well as their possible function in vivo are discussed.
Abstract S4-07: Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomised trials
Authors: R Coleman, M Gnant, A Paterson, T Powles, G von Minckwitz, K Pritchard, J Bergh, J Bliss, J Gralow, S Anderson, V Evans, H Pan, R Bradley, C Davies, R Gray
Journal: Cancer Research (2013)

Abstract Background: Disseminated tumour cells can remain dormant in the bone marrow for years prior to subsequent activation and the development of overt metastases. Bisphosphonates (BP) have profound effects on bone physiology and could potentially modify the metastatic disease process. Variable outcomes in terms of disease recurrence have been reported, with efficacy apparently influenced by menopausal status. Methods: We sought individual patient data for meta-analysis from 41 randomised trials that compared BP to no BP (placebo or open control). Primary outcomes were time to recurrence, time to first distant recurrence and breast cancer mortality. Predefined subgroup comparisons were of type of BP (amino-/non-amino), duration and schedule of BP treatment, menopausal status, age, ER status, concomitant chemotherapy and site of distant recurrence (bone/other). Results: Data on 17,751 women (75% of 23,573 randomised in relevant trials) have so far been received, with around 3,300 breast cancer recurrences and 2,500 deaths. Effects on breast cancer mortality, recurrence and bone metastases for 17,016 women in the locked database and for 10,540 who were postmenopausal are shown below. No. eventsRate Ratio (SE)10 year gain2p valueAll women (n = 17,016)Breast cancer mortality2,0490.91 (0.04)1.7%0.04Breast cancer recurrence3,2840.94 (0.04)1.0%0.13Distant recurrence2,7510.92 (0.04)1.3%0.05Bone recurrence8250.79 (0.07)1.4%0.002Other distant recurrence1,9260.99 (0.05)0.1%0.8Postmenopausal women (n = 10,540)Breast cancer mortality1,1070.83 (0.06)3.1%0.004Breast cancer recurrence1,8090.86 (0.05)3.0%0.002Distant recurrence1,5030.83 (0.05)3.3%0.0007Bone recurrence4450.65 (0.08)2.9%0.00001Other distant recurrence1,0580.93 (0.06)0.7%0.26 Reductions in bone recurrence for postmenopausal women were similar irrespective of bisphosphonate type, treatment schedule, ER status, nodal involvement or use of concomitant chemotherapy. There were no improvements in bone (RR = 1.00, 2p = 0.97) or other recurrence for premenopausal women. Adjuvant bisphosphonates also reduced bone fractures (RR = 0.83, 2p = 0.009). Conclusion: Adjuvant bisphosphonates reduce bone recurrences and improve breast cancer survival in postmenopausal but not premenopausal women. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S4-07.
The false dichotomy of imagery
Authors: Nigel J. T. Thomas
Journal: Behavioral and Brain Sciences (2002)

Pylyshyn's critique is powerful. Pictorial theories of imagery fail. On the other hand, the symbolic description theory he manifestly still favors also fails, lacking the semantic foundation necessary to ground imagery's intentionality and consciousness. However, contrary to popular belief, these two theory types do not exhaust available options. Recent work on embodied, active perception supports the alternative perceptual activity theory of imagery.
Anxiety and Hope during the Course of Three Different Medical Illnesses: A Longitudinal Study
Authors: Irena Heszen-Niejodek, Louis A. Gottschalk, Maciej Januszek
Journal: Psychotherapy and Psychosomatics (1999)

&lt;i&gt;Background:&lt;/i&gt; Somatic illness and its consequences evoke strong emotions of various kinds. They may affect the course of illness and the treatment results through their physiological components. The purpose of the study was to explore emotional reactions to different kinds of illnesses and changes of these emotions over time. &lt;i&gt;Methods:&lt;/i&gt; Subjects were 259 medical patients suffering from: primary hypertension, myocardial infarction and cancer of the lungs or pharynx. The study was longitudinal and consisted of three phases. The first was performed immediately after the patient was diagnosed, the second was done 5 weeks later and the third about half a year after the onset of illness. The patients’ emotional state was evaluated with the Gottschalk-Gleser Content Analysis Scales: the Anxiety and the Hope Scales. &lt;i&gt;Results:&lt;/i&gt; Significant effects of the kind of illness and of its interaction with the phase of the study were found. In the hypertension group, both anxiety and hope were slightly elevated immediately after diagnosis, then slightly lowered. The myocardial infarction group exhibited a low level of these emotions in the first phase, an increase in the second and then a little decrease. Cancer patients manifested high anxiety and relatively low hope in the initial phase, then a decrease in anxiety and an increase in hope. &lt;i&gt;Conclusions:&lt;/i&gt; Both anxiety and hope accompany the illness in its consecutive phases, reflecting properties of illness as a source of psychological stress and the coping process.
Ethicists find no justification for UK ban on sex selection of embryos
Authors: C. Dyer
Journal: BMJ (2013)

<h3>OBJECTIVES:</h3> To differentiate methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) and methicillin-sensitive S. aureus (MSSA) strains and detect the source of epidemic strains and prevent their access to patients. <h3>METHODS:</h3> All the procedures were carried out in the Department of Microbiology, Medical Faculty Hospital, Dokuz Eylul University, Izmir, Turkey from 1996-1998, and antibiotic susceptibility tests continued in the laboratory of King Fahad Hospital, Al-Baha, Kingdom of Saudi Arabia (KSA), from 2001-2004. A total of 81 S. aureus strains (71 MRSA, 10 MSSA) from Turkey were isolated from different sites of patients in Intensive Care Unit9s (ICU9s), evaluated by plasmid profile, Restriction Endonuclease Analysis of Plasmids (REAP), and antibiotic sensitivity tests. A total of 117 S. aureus strains (24 MRSA, 93 MSSA) from KSA were isolated from different sites of patients in ICU9s, evaluated by antibiotic sensitivity tests as recommended by National Committee for Clinical Laboratory Standards (NCCLS). <h3>RESULTS:</h3> Seventy-one MRSA from Turkey were divided into 13 groups by antibiotic sensitivity tests and into 4 groups by plasmid profiles, in which 3rd and 4th groups subdivided into 2 subgroups, and into 5 groups by REAP. The 1st, 2nd, 3rd and 5th groups were subdivided into 2 subgroups. Ten MSSA were divided into 4 groups by antibiotic sensitivity tests, 3 in plasmid profiles and 2 in REAP tests. Twenty-four MRSA strains from KSA were divided into 9 groups by antibiotic sensitivity tests while 93 MSSA strains were divided into 7 groups. <h3>CONCLUSIONS:</h3> In respect to epidemiological survey, plasmids profiles and REAP seems to discriminate more respect to antibiotic sensitivity tests but at the same time neither of them were 100% accurately differential. According to the plasmid profile of the 3rd MSSA (Turkey) group, a multi-drug resistance by antibiotic susceptibility tests were noticed and showed the same plasmid profile in MRSA first subgroup of the 3rd group, but the same groups were different in REAP tests. In order to distinguish the discriminatory power of the strains, where REAP is better than plasmid profile and antibiotic sensitivity tests, we may formulate the statement into the following; REAP &gt; plasmid profile &gt; antibiotic sensitivity tests. For typing and gathering of epidemiological data, it is suggested that all 3 methods should be employed in clinical laboratories as they are cheap, practical and easily interpreted.
Beware the influence of the "SIF" (single issue fanatic) in clinical guidelines
Authors: K. Barraclough
Journal: BMJ (2013)

The start of science was arguably Descartes’ formulation of systematic doubt. Yet today the sceptic seems under-represented on expert committees.

Current guidance requires referral of every patient with a raised prostate specific antigen concentration (10% of men over 50), pigmented lesions that score 3 on the 7 point score (50% of pigmented lesions1), microscopic haematuria in the over 50s (up to 16.1% of …
The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model
Authors: Thomas Mercher, Glen D. Raffel, Sandra A. Moore, Melanie G. Cornejo, Dominique Baudry-Bluteau, Nicolas Cagnard, Jonathan L. Jesneck, Yana Pikman, Dana Cullen, Ifor R. Williams, Koichi Akashi, Hirokazu Shigematsu, Jean-Pierre Bourquin, Marco Giovannini, William Vainchenker, Ross L. Levine, Benjamin H. Lee, Olivier A. Bernard, D. Gary Gilliland
Journal: Journal of Clinical Investigation (2009)

Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two–megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin κ J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus oncogene (MPL) efficiently induced a short-latency AMKL that recapitulated all the features of human AMKL, including megakaryoblast hyperproliferation and maturation block, thrombocytopenia, organomegaly, and extensive fibrosis. Our results establish that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL.
Clinical Investigation of the Value of Synthetic Hyaluronidase Inhibitors in Rheumatoid Arthritis
Authors: L. Hahn, S. Thune, E. Truedsson
Journal: Annals of the Rheumatic Diseases (1952)

<h3>Introduction</h3> Schistosomiasis is still a major public health problem in Brazil, where it is assumed that there 2 500 000 to 8 000 000 cases of the disease, despite the development of control activities. The North-eastern region, where is situated the state of Maranhão, is the most affected area. This study analyses trends of the percentage of positive cases of Schistosomiasis in Maranhao, between 1997 and 2003. <h3>Methods</h3> We analysed a time series of percentages of positive cases, grouped according to 15 Regional Health Authorities in the state, available in the information system of the Schistosomiasis Control Program (SISPCE). Trend analysis was performed through polynomial regression models. Statistical significance, coefficients of determination (R<sup>2</sup>) and residuals were used to define the best model. <h3>Results</h3> The percentage of positive cases of schistosomiasis amounted to 7.42% in the study period. Two Regional Health Authorities showed constant downward trends with an average annual percentage of positive cases of 1.72 and 0.66, respectively. Meanwhile, the others showed upward trends. <h3>Conclusions</h3> The declining trends suggest the possibility of underreporting. It is believed that data registration in the Regional Health Authorities has been affected by changes in the activities of the SISPCE, due to decentralisation of the Program to municipalities. In some cases, best living conditions could have contributed to the observed declines. However, deficit of environmental sanitation and poverty are significant in the majority of the state and certainly are related to the increments observed in the other regionals.
MEDICAL EDUCATION AND THE MEDICAL PROFESSION
Authors: John W. Cline
Journal: JAMA (1952)

The American Medical Association and the Federation of State Licensing Boards have had a long and fruitful partnership in the efforts to raise medical standards throughout the United States. The Association values highly and is appreciative of the support that the state boards have given to its recommendations. If it had not been for this continuing support, much of the improvement in the quality of medical education, and thus in the quality of medical practice, that we have witnessed in the last 50 years would have been impossible. The state boards, as official governmental bodies, have final decision with respect to the standards physicians must meet to be eligible for licensure. It is also the state boards that have final discretion as to who shall and shall not receive a license. We look forward to continued cooperation in the public interest in the years to come. Last October, I was
ApoB-100–Related Peptide Vaccine Protects Against Angiotensin II–Induced Aortic Aneurysm Formation and Rupture
Authors: Tomoyuki Honjo, Kuang-Yuh Chyu, Paul C. Dimayuga, Juliana Yano, Wai Man Lio, Portia Trinidad, Xiaoning Zhao, Jianchang Zhou, Shuang Chen, Bojan Cercek, Moshe Arditi, Prediman K. Shah
Journal: Journal of the American College of Cardiology (2015)
Quality of Life Analyses from the Randomized, Open-Label, Phase III PointBreak Study of Pemetrexed-Carboplatin-Bevacizumab followed by Maintenance Pemetrexed-Bevacizumab Versus Paclitaxel-Carboplatin-Bevacizumab followed by Maintenance Bevacizumab in Patients with Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer
Authors: David R. Spigel, Jyoti D. Patel, Craig H. Reynolds, Edward B. Garon, Robert C. Hermann, Ramaswamy Govindan, Mark R. Olsen, Katherine B. Winfree, Jian Chen, Jingyi Liu, Susan C. Guba, Mark A. Socinski, Philip Bonomi
Journal: Journal of Thoracic Oncology (2015)