tbuckley/cabot-search huggingface dataset:
Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a multicentre international study
Authors: Palak J Trivedi, Willem J Lammers, Henk R van Buuren, Albert Parés, Annarosa Floreani, Harry L A Janssen, Pietro Invernizzi, Pier Maria Battezzati, Cyriel Y Ponsioen, Christophe Corpechot, Raoul Poupon, Marlyn J Mayo, Andrew K Burroughs, Frederik Nevens, Andrew L Mason, Kris V Kowdley, Ana Lleo, Llorenç Caballeria, Keith D Lindor, Bettina E Hansen, Gideon M Hirschfield
Journal: Gut (2015)

<h3>Objective</h3> Hepatocellular carcinoma (HCC) is an infrequent yet critical event in primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined. Our objective was to identify candidate risk factors for HCC development in patients with PBC. <h3>Design</h3> Risk factor analysis was performed in over 15 centres from North America and Europe spanning &gt;40 years observation period using Cox proportional hazards assumptions, logistic regression, and Kaplan-Meier estimates. <h3>Results</h3> Of 4565 patients with PBC 123 developed HCC, yielding an incidence rate (IR) of 3.4 cases/1000 patient-years. HCC was significantly more common in men (p&lt;0.0001), and on univariate analysis factors at PBC diagnosis associated with future HCC development were male sex (unadjusted HR 2.91, p&lt;0.0001), elevated serum aspartate transaminase (HR 1.24, p&lt;0.0001), advanced disease (HR 2.72, p=0.022), thrombocytopenia (HR 1.65, p&lt;0.0001), and hepatic decompensation (HR 9.89, p&lt;0.0001). As such, non-treatment with ursodeoxycholic acid itself was not associated with cancer development; however, 12-month stratification by biochemical non-response (Paris-I criteria) associated significantly with future risk of HCC (HR 4.52, p&lt;0.0001; IR 6.6 vs 1.4, p&lt;0.0001). Non-response predicted future risk in patients with early stage disease (IR 4.7 vs 1.2, p=0.005), advanced disease (HR 2.79, p=0.02; IR 11.2 vs 4.4, p=0.033), and when restricting the analysis to only male patients (HR 4.44, p&lt;0.001; IR 18.2 vs 5.4, p&lt;0.001). On multivariable analysis biochemical non-response remained the most significant factor predictive of future HCC risk (adjusted HR 3.44, p&lt;0.0001). <h3>Conclusions</h3> This uniquely powered, internationally representative cohort robustly demonstrates that 12-month biochemical non-response is associated with increased future risk of developing HCC in PBC. Such risk stratification is relevant to patient care and development of new therapies.
Breast Cancer Patients with Progesterone Receptor PR-A-Rich Tumors Have Poorer Disease-Free Survival Rates
Authors: Torsten A. Hopp, Heidi L. Weiss, Susan G. Hilsenbeck, Yukun Cui, D. Craig Allred, Kathryn B. Horwitz, Suzanne A. W. Fuqua
Journal: Clinical Cancer Research (2004)

Abstract Purpose: No study has yet analyzed whether changes in relative expression levels of progesterone receptor (PR) isoforms A and B in human breast tumors have significance in predicting clinical outcome. Human PRs are ligand-activated nuclear transcription factors that mediate progesterone action. Their presence in breast tumors is used to predict functional estrogen receptors (ERs) and, therefore, also to predict the likelihood of response to endocrine therapies and disease prognosis. The two PR isoforms, PR-A and PR-B, possess different in vitro and in vivo activities, suggesting that in tumors, the ratio of their expression may control hormone responsiveness. In general, PR-B are strong transcriptional activators, whereas PR-A can act as dominant repressors of PR-B and ER. Thus their balance may affect tamoxifen response in breast cancers. Experimental Design: To determine whether differential expression of the PR isoforms is associated with clinical outcome and hormonal responsiveness, PR-A and PR-B were measured by immunoblot analysis of cell lysates from 297 axillary node-positive breast tumors. Results: Expression of the two isoforms correlated with each other, as well as with ER. Additional analyses revealed that patients with PR-positive tumors but high PR-A:PR-B ratios, which were often caused by high PR-A levels, were 2.76 times more likely to relapse than patients with lower ratios, indicating resistance to tamoxifen. Conclusions: This study suggests that knowledge of the PR-A:PR-B ratio may identify a subgroup of ER-positive/PR-positive patients with node-positive breast cancer that benefit poorly from endocrine therapy.
Effects of Tissue Handling on RNA Integrity and Microarray Measurements From Resected Breast Cancers
Authors: Christos Hatzis, Hongxia Sun, Hui Yao, Rebekah E. Hubbard, Funda Meric-Bernstam, Gildy V. Babiera, Yun Wu, Lajos Pusztai, W. Fraser Symmans
Journal: JNCI Journal of the National Cancer Institute (2011)

Reliable stability and yield of RNA from breast cancer tissues are important for biobanking, clinical trials, and diagnostic testing. Aliquots of fresh primary tumor tissue from 17 surgically resected invasive breast cancers were placed into RNAlater at room temperature after tumor removal (baseline) and up to 3 hours thereafter or were snap frozen at baseline and 40 minutes thereafter. Samples were stored at −80°C until gene expression profiling with Affymetrix Human Gene U133A microarrays. We evaluated the effects of cold ischemic time (the time from tumor specimen removal to sample preservation) and sample preservation method on RNA yield, Bioanalyzer-based RNA integrity number, microarray-based 3′/5′ expression ratios for assessing transcript integrity, and microarray-based measurement of single-gene and multigene expression signatures. The statistical significance of the effects was assessed using linear mixed effects regression models. All statistical tests were two-sided. Sample preservation in RNAlater statistically significantly improved RNA integrity compared with snap freezing as assessed by the RNA integrity number, which increased from 7.31 to 8.13 units (difference = 0.82 units, 95% confidence interval [CI] = 0.53 to 1.11 units, P < .001), and RNA yield, which increased threefold from 8.9 to 28.6 μg (difference = 19.7 μg, 95% CI = 14.1 to 25.3 μg, P < .001). Prolonged cold ischemic delay at room temperature before sample stabilization decreased the RNA integrity number by 0.12 units/h (95% CI = 0.02 to 0.23 units/h) compared with a projected average RNA integrity number of 7.39 if no delays were present (P = .008) and decreased the RNA yield by 1.5 μg/h (95% CI = 0 to 4 μg/h) from a baseline mean RNA yield of 33.5 μg if no delays were present (P = .019). Prolonged cold ischemia statistically significantly increased the 3′/5′ ratio of control gene transcripts, particularly of STAT1 (P < .001). Snap freezing statistically significantly increased the 3′/5′ ratio of three control transcripts (ACTB, GAPDH, and 18S rRNA). Expression levels of single genes and multigene signatures for breast cancer were largely unaffected by sample preservation method or cold ischemia. Sample preservation in RNAlater improves RNA yield and quality, whereas cold ischemia increases RNA fragmentation as measured by the 3′/5′ expression ratio of control genes. However, expression levels of single genes and multigene signatures that are of diagnostic relevance in breast cancer were mostly unaffected by sample preservation method or prolonged cold ischemic duration.
Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis
Authors: Luciano Ottonello, Paola Gnerre, Maria Bertolotto, Marina Mancini, Patrizia Dapino, Rodolfo Russo, Giacomo Garibotto, Tommaso Barreca, Franco Dallegri
Journal: Journal of the American Society of Nephrology (2004)

Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD.
Chronic urticaria in Chinese population: a hospital-based multicenter epidemiological study
Authors: H. Zhong, Z. Song, W. Chen, H. Li, L. He, T. Gao, H. Fang, Z. Guo, J. Xv, B. Yu, X. Gao, H. Xie, H. Gu, D. Luo, X. Chen, T. Lei, J. Gu, B. Cheng, Y. Duan, A. Xv, X. Zhu, F. Hao
Journal: Allergy (2013)

Background The epidemiologic profiles of chronic urticaria (CU) vary considerably among regions, and few such data are available from China. Methods We performed a multicenter open questionnaire investigation about the clinical and laboratory features of CU, defined as recurrent wheals with/without angioedema lasting for ≥6 weeks, among 3027 patients. Results Female preponderance was observed (female/male ratio, 1.46 : 1). The mean age at diagnosis was 34.7 ± 13.8 years, and the mean disease duration was 18.5 ± 46.1 months (range, 1.5–127 months). Patients were classified as having chronic spontaneous urticaria (CSU, 61.0% of patients), physical urticaria (PU, 26.2%), or other urticaria types (OU, 2.3%). Nocturnal attacks were reported by 60% of cases. The Urticaria Activity Score (UAS) in patients with CSU was 3.8 ± 1.4. The mean Dermatology Life Quality Index was 7.3 ± 3.4 (range 0–30). Induction or exacerbation of wheals with alcohol drinking was reported by 55.7% of patients. Chronic hepatitis B was less prevalent in our CU patients compared with the general Chinese population (2.7% vs 7%). Positive autologous serum skin tests (ASSTs) were observed in 66.9% of patients. Patients with positive ASST had higher UAS, greater angioedema frequencies, longer disease durations, and poorer QoL compared with patients with negative ASST (P < 0.05). Conclusion In this Chinese population, CU usually affected youth, and CSU was the most common subtype. Autoreactivity and alcohol consumption were the top two triggers for CU, whereas latent infectious and chronic inflammatory diseases were not as common as in previous reports.
MALDI-TOF MS Andromas strategy for the routine identification of bacteria, mycobacteria, yeasts, Aspergillus spp. and positive blood cultures
Authors: E. Bille, B. Dauphin, J. Leto, M.-E. Bougnoux, J.-L. Beretti, A. Lotz, S. Suarez, J. Meyer, O. Join-Lambert, P. Descamps, N. Grall, F. Mory, L. Dubreuil, P. Berche, X. Nassif, A. Ferroni
Journal: Clinical Microbiology and Infection (2011)
Sjogren's syndrome criteria
Authors: R Manthorpe
Journal: Annals of the Rheumatic Diseases (2002)

lassification criteria are necessary to identify diseases for which no diagnostic or specific tests yet exist.They are especially of value within the systemic rheumatic diseases.Their main purpose is to organise crude data and information into useful information which will improve clinical care, treatment, and follow up.Classification criteria need to be foolproof so that it is unlikely that changes will be needed in the immediate future.
Increased OXPHOS activity precedes rise in glycolytic rate in H-RasV12/E1A transformed fibroblasts that develop a Warburg phenotype
Authors: Ad JC de Groof, Mariska M te Lindert, Michiel MT van Dommelen, Min Wu, Marieke Willemse, Amy L Smift, Mike Winer, Frank Oerlemans, Helma Pluk, Jack AM Fransen, Bé Wieringa
Journal: Molecular Cancer (2009)

The Warburg phenotype in cancer cells has been long recognized, but there is still limited insight in the consecutive metabolic alterations that characterize its establishment. We obtained better understanding of the coupling between metabolism and malignant transformation by studying mouse embryonic fibroblast-derived cells with loss-of-senescence or H-RasV12/E1A-transformed phenotypes at different stages of oncogenic progression.Spontaneous immortalization or induction of senescence-bypass had only marginal effects on metabolic profiles and viability. In contrast, H-RasV12/E1A transformation initially caused a steep increase in oxygen consumption and superoxide production, accompanied by massive cell death. During prolonged culture in vitro, cell growth rate increased gradually, along with tumor forming potential in in vitro anchorage-independent growth assays and in vivo tumor formation assays in immuno-deficient mice. Notably, glucose-to-lactic acid flux increased with passage number, while cellular oxygen consumption decreased. This conversion in metabolic properties was associated with a change in mitochondrial NAD+/NADH redox, indicative of decreased mitochondrial tricarboxic acid cycle and OXPHOS activity.The high rate of oxidative metabolism in newly transformed cells is in marked contrast with the high glycolytic rate in cells in the later tumor stage. In our experimental system, with cells growing under ambient oxygen conditions in nutrient-rich media, the shift towards this Warburg phenotype occurred as a step-wise adaptation process associated with augmented tumorigenic capacity and improved survival characteristics of the transformed cells. We hypothesize that early-transformed cells, which potentially serve as founders for new tumor masses may escape therapies aimed at metabolic inhibition of tumors with a fully developed Warburg phenotype.
Appraisal of the Double Two-Step Exercise Test
Authors: George P. Robb
Journal: JAMA (1975)

We made an evaulation of the double two-step exercise test in the diagnosis and prognosis of coronary artery disease, on the basis of the findings among 3,325 male applicants for life insurance who were given the test and observed for an average of nine years. The results suggest that (1) ischemic ST segment depression of any amount after exercise is pathognomonic of coronary insufficiency, for all practical purposes; (2) the amount of ischemic depression is related to the severity of the coronary insufficiency and the prognosis; (3) ischemic depression in multiple leads denotes widespread coronary insufficiency; (4) a nonischemic response practically excludes coronary disease of a type that will cause premature death; and (5) the exercise test is more reliable than the medical history in the diagnosis of silent coronary disease.
Extended Efficacy and Safety of Denosumab in Breast Cancer Patients with Bone Metastases Not Receiving Prior Bisphosphonate Therapy
Authors: Allan Lipton, Guenther G. Steger, Jazmin Figueroa, Cristina Alvarado, Philippe Solal-Celigny, Jean Jacques Body, Richard de Boer, Rossana Berardi, Pere Gascon, Katia S. Tonkin, Robert E. Coleman, Alexander H.G. Paterson, Guozhi M. Gao, Amy C. Kinsey, Mark C. Peterson, Susie Jun
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)–naïve patients with breast cancer-related bone metastases. Experimental Design: Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks). Results: At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were −73% and −75% for the pooled denosumab groups and −79% and −71% for the IV BP group. Among patients with ≥1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP–treated patients achieved &amp;gt;65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP–treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred. Conclusions: In IV BP–naïve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.
TRIM Proteins in Therapeutic Membrane Repair of Muscular Dystrophy
Authors: Jenna Alloush, Noah Weisleder
Journal: JAMA Neurology (2013)

Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases.One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.
Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer
Authors: Gypsyamber D'Souza, Aimee R. Kreimer, Raphael Viscidi, Michael Pawlita, Carole Fakhry, Wayne M. Koch, William H. Westra, Maura L. Gillison
Journal: New England Journal of Medicine (2007)

Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.We performed a hospital-based, case-control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case-control comparisons.A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16.Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.
Combined Surface Micropatterning and Reactive Chemistry Maximizes Tissue Adhesion with Minimal Inflammation
Authors: Maria J. N. Pereira, Cathryn A. Sundback, Nora Lang, Woo Kyung Cho, Irina Pomerantseva, Ben Ouyang, Sarah L. Tao, Kevin McHugh, Olive Mwizerwa, Praveen K. Vemula, Mark C. Mochel, David J. Carter, Jeffrey T. Borenstein, Robert Langer, Lino S. Ferreira, Jeffrey M. Karp, Peter T. Masiakos
Journal: Advanced Healthcare Materials (2013)

The use of tissue adhesives for internal clinical applications is limited due to a lack of materials that balance strong adhesion with biocompatibility. The use of substrate topography is explored to reduce the volume of a highly reactive and toxic glue without compromising adhesive strength. Micro‐textured patches coated with a thin layer of cyanoacrylate glue achieve similar adhesion levels to patches employing large amounts of adhesive, and is superior to the level of adhesion achieved when a thin coating is applied to a non‐textured patch. In vivo studies demonstrate reduced tissue inflammation and necrosis for patterned patches with a thinly coated layer of reactive glue, thus overcoming a significant challenge with existing tissue adhesives such as cyanoacrylate. Closure of surgical stomach and colon defects in a rat model is achieved without abdominal adhesions. Harnessing the synergy between surface topography and reactive chemistry enables controlled tissue adhesion with an improved biocompatibility profile without requiring changes in the chemical composition of reactive tissue glues.
THE ACTION OF ENZYMES FROM CLOSTRIDIUM TERTIUM ON THE I ANTIGENIC DETERMINANT OF HUMAN ERYTHROCYTES
Authors: Donald M. Marcus, Elvin A. Kabat, Richard E. Rosenfield
Journal: The Journal of Experimental Medicine (1963)

A method was described for the partial purification of beta galactosidase and beta glucosaminidase from Clostridium tertium culture supernatants. Treatment of erythrocytes with preparations containing both enzymes decreases their ability to react with anti-I cold agglutinins, and with Type XIV antipneumococcal horse serum. Erythrocytes of blood group A1 are altered more rapidly and extensively than are group O cells. The enzymatic treatment of stroma results in a decrease in ability to absorb anti-I agglutinins and the release of galactose and N-acetylglucosamine as monosaccharides. The data suggest that these two sugars may be structural units of the erythrocyte I determinant, but no direct evidence is available.