tbuckley/cabot-search huggingface dataset:
High-Resolution Rapid Diagnostic Imaging of Whole Prostate Biopsies Using Video-Rate Fluorescence Structured Illumination Microscopy
Authors: Mei Wang, Hillary Z. Kimbrell, Andrew B. Sholl, David B. Tulman, Katherine N. Elfer, Tyler C. Schlichenmeyer, Benjamin R. Lee, Michelle Lacey, J. Quincy Brown
Journal: Cancer Research (2015)

Abstract Rapid assessment of prostate core biopsy pathology at the point-of-procedure could provide benefit in a variety of clinical situations. Even with advanced transrectal ultrasound guidance and saturation biopsy protocols, prostate cancer can be missed in up to half of all initial biopsy procedures. In addition, collection of tumor specimens for downstream histologic, molecular, and genetic analysis is hindered by low tumor yield due to inability to identify prostate cancer grossly. However, current point-of-procedure pathology protocols, such as frozen section analysis (FSA), are destructive and too time- and labor-intensive to be practical or economical. Ex vivo microscopy of the excised specimens, stained with fast-acting fluorescent histology dyes, could be an attractive nondestructive alternative to FSA. In this work, we report the first demonstration of video-rate structured illumination microscopy (VR-SIM) for rapid high-resolution diagnostic imaging of prostate biopsies in realistic point-of-procedure timeframes. Large mosaic images of prostate biopsies stained with acridine orange are rendered in seconds and contain excellent contrast and detail, exhibiting close correlation with corresponding hematoxylin and eosin histology. A clinically relevant review of VR-SIM images of 34 unfixed and uncut prostate core biopsies by two independent pathologists resulted in an area under the receiver operative curve (AUC) of 0.82–0.88, with a sensitivity ranging from 63% to 88% and a specificity ranging from 78% to 89%. When biopsies contained more than 5% tumor content, the sensitivity improved to 75% to 92%. The image quality, speed, minimal complexity, and ease of use of VR-SIM could prove to be features in favor of adoption as an alternative to destructive pathology at the point-of-procedure. Cancer Res; 75(19); 4032–41. ©2015 AACR.
Acculturation and Socioeconomic Position as Predictors of Coronary Calcification in a Multiethnic Sample
Authors: Ana V. Diez Roux, Robert Detrano, Sharon Jackson, David R. Jacobs, Pamela J. Schreiner, Steven Shea, Moyses Szklo
Journal: Circulation (2005)

Background— Coronary calcium has recently emerged as a marker of subclinical coronary heart disease. Although there has been much interest in race differences in calcification, heterogeneity within race or ethnic groups has not been investigated. Methods and Results— Data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of coronary calcification, were used to investigate acculturation and socioeconomic position as predictors of coronary calcification within 2553 non-Hispanic whites, 1734 non-Hispanic blacks, 1457 Hispanics, and 797 Chinese residing in the United States. Coronary calcium was assessed by chest CT. Relative risk regression and linear regression were used to estimate adjusted associations of sociodemographic variables with the presence and amount of calcium. Not being born in the United States was associated with a lower prevalence of calcification in blacks (relative prevalence [RP], 0.75; 95% confidence limit [CL], 0.61 to 0.94) and Hispanics (RP, 0.89; 95% CL, 0.81 to 0.98) after adjustment for age, sex, income, and education. Years in the United States was positively associated with prevalence of calcification in non–US-born Chinese (adjusted RP per 10 years in United States, 1.06; 95% CL, 1.01 to 1.11) and non–US-born blacks (RP, 1.59; 95% CL, 1.22 to 2.06). Low education was associated with a higher prevalence of calcification in whites (adjusted RP for no high school versus complete college, 1.17; 95% CL, 1.05 to 1.32) but with lower prevalence of calcification in Hispanics (RP, 0.91; 95% CL, 0.77 to 1.09) ( P for interaction=0.02). US birth and time in the United States were also positively associated with the extent of calcification in persons with detectable calcium. These differences did not appear to be accounted for by smoking, body mass index, LDL and HDL cholesterol, hypertension, and diabetes. Conclusions— Acculturation and socioeconomic factors are associated with differences in the prevalence and amount of coronary calcification within whites, Chinese, blacks, and Hispanics. The presence of this heterogeneity needs to be acknowledged in the quantification and investigation of race/ethnic differences.
Response letter to ‘role of thiopurine metabolite measurement in the management of autoimmune hepatitis’
Authors: Dermot Gleeson, Michael A Heneghan
Journal: Gut (2012)

We appreciate the kind comments of Dr Al-shamma and colleagues on our guidelines.

We agree that azathioprine (AZA) plus prednisolone is the best initial regime for autoimmune hepatitis (AIH), and like them, we would encourage perseverance with AZA in patients with minor adverse reactions, which may improve with time.

AZA-induced hepatotoxicity in patients with inflammatory bowel disease (IBD) is usually defined as rises in serum transaminases; most cases have not had histological confirmation. We …
Use of Beef Ultralente for Basal Insulin Delivery: Plasma Insulin Concentrations After Chronic Ultralente Administration in Patients with IDDM
Authors: R A Rizza, P C O'Brien, F J Service
Journal: Diabetes Care (1986)

Ultralente has been used as the basal component of intensive insulin therapy programs. To determine the degree to which a single daily subcutaneous injection of beef ultralente provides stable basal insulin concentrations, plasma free insulin concentrations were measured in six insulin-dependent diabetic patients over a 40-h period. All short-acting insulin was withheld during this interval. Each patient had been maintained on a chronic ultralente based program before study. Little if any evidence of a temporal peak in plasma insulin concentrations was observed. Although considerable variation in plasma insulin concentrations was observed in one individual, beef ultralente provided relatively stable plasma insulin concentrations in the group as a whole. Beef ultralente appears to be a reasonable insulin preparation to use as the basal component in an intensive insulin therapy program.
Creativity or mental illness: Possible errors of relational priming in neural networks of the brain
Authors: James E. Swain, John D. Swain
Journal: Behavioral and Brain Sciences (2008)

Abstract If connectionist computational models explain the acquisition of complex cognitive skills, errors in such models would also help explain unusual brain activity such as in creativity – as well as in mental illness, including childhood onset problems with social behaviors in autism, the inability to maintain focus in attention deficit and hyperactivity disorder (ADHD), and the lack of motivation of depression disorders.
Development and application of MLVA methods as a tool for inter-laboratory surveillance
Authors: C A Nadon, E Trees, L K Ng, E Møller Nielsen, A Reimer, N Maxwell, K A Kubota, P Gerner-Smidt, Collective the MLVA Harmonization Working Group
Journal: Eurosurveillance (2013)

Multiple-locus variable-number of tandem-repeats analysis (MLVA) has emerged as a valuable method for subtyping bacterial pathogens and has been adopted in many countries as a critical component of their laboratory-based surveillance. Lack of harmonisation and standardisation of the method, however, has made comparison of results generated in different laboratories difficult, if not impossible, and has therefore hampered its use in international surveillance. This paper proposes an international consensus on the development, validation, nomenclature and quality control for MLVA used for molecular surveillance and outbreak detection based on a review of the current state of knowledge.
Linifanib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: Results of a Randomized Phase III Trial
Authors: Calin Cainap, Shukui Qin, Wen-Tsung Huang, Ik Joo Chung, Hongming Pan, Ying Cheng, Masatoshi Kudo, Yoon-Koo Kang, Pei-Jer Chen, Han-Chong Toh, Vera Gorbunova, Ferry A.L.M. Eskens, Jiang Qian, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, Saied El-Nowiem
Journal: Journal of Clinical Oncology (2014)

This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy.Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1.We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P < .001).Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib.
Thrombin Stimulates Human Endothelial Arginase Enzymatic Activity via RhoA/ROCK Pathway
Authors: Xiu-Fen Ming, Christine Barandier, Hema Viswambharan, Brenda R. Kwak, François Mach, Lucia Mazzolai, Daniel Hayoz, Jean Ruffieux, Sandro Rusconi, Jean-Pierre Montani, Zhihong Yang
Journal: Circulation (2004)

Arginase competes with endothelial nitric oxide synthase (eNOS) for the substrate l-arginine and decreases NO production. This study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis.In human endothelial cells isolated from umbilical veins, thrombin concentration- and time-dependently stimulated arginase enzymatic activity, reaching a 1.9-fold increase (P<0.001) at 1 U/mL for 24 hours. The effect of thrombin was prevented by C3 exoenzyme or the HMG-CoA reductase inhibitor fluvastatin, which inhibit RhoA, or by the ROCK inhibitors Y-27632 and HA-1077. Adenoviral expression of constitutively active RhoA or ROCK mutants enhanced arginase activity (approximately 3-fold, P<0.001), and the effect of active RhoA mutant was inhibited by the ROCK inhibitors. Neither thrombin nor the active RhoA/ROCK mutants affected arginase II protein level, the only isozyme detectable in the cells. Moreover, a significantly higher arginase II activity (1.5-fold, not the protein level) and RhoA protein level (4-fold) were observed in atherosclerotic aortas of apoE-/- compared with wild-type mice. Interestingly, l-arginine (1 mmol/L), despite a significantly higher eNOS expression in aortas of apoE-/- mice, evoked a more pronounced contraction, which was reverted to a greater vasodilation by the arginase inhibitor l-norvaline (20 mmol/L) compared with the wild-type animals (n=5, P<0.001).Thrombin enhances arginase activity via RhoA/ROCK in human endothelial cells. Higher arginase enzymatic activity is involved in atherosclerotic endothelial dysfunction in apoE-/- mice. Targeting vascular arginase may represent a novel therapeutic possibility for atherosclerosis.
The Natural History of LDL Control in Type 2 Diabetes
Authors: Diana Rucker, Jeffrey A. Johnson, T.K. Lee, Dean T. Eurich, Richard Z. Lewanczuk, Scot H. Simpson, Ellen L. Toth, Sumit R. Majumdar
Journal: Diabetes Care (2006)

Despite randomized trials repeatedly showing the benefits of lowering LDL cholesterol with hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statins) (1–3), these medications are suboptimally used in type 2 diabetes (4–10). Although this care gap in type 2 diabetes has been frequently described in cross-sectional studies (6–11), it may be as informative to understand LDL control over time. In particular, there is growing recognition of care gaps in diabetes when comparing urban and academic settings with rural settings (11,12). Therefore, we examined changes over an 18-month period for adherence to guideline-recommended LDL cholesterol targets in a rural cohort with type 2 diabetes and determined the rates and correlates of 1 ) losing control of LDL cholesterol in those who were initially at target and 2 ) achieving control of LDL cholesterol in those who were not initially at target.

The Diabetes Outreach Van Enhancement (DOVE) study was a controlled trial of a multifaceted intervention directed at health care providers to improve the quality of care for rural patients with type 2 diabetes in northern Alberta, Canada. The intervention consisted of an educational outreach (“academic detailing”) service, whereby specialist physicians promoted aggressive cardiovascular risk reduction for diabetes to primary care physicians. The study rationale, design, and outcomes have been previously published (12–16). All subjects provided written consent, and the study was approved by the University of Alberta.

All patients had universal health care coverage and fee-for-service primary care physicians, with the nearest specialists being ∼6 …
2-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking
Authors: G. Zhang, C. M. Hayden, S-K. Khoo, P. Candelaria, I. A. Laing, S. Turner, P. Franklin, S. Stick, L. Landau, J. Goldblatt, P. N. Le Souëf
Journal: European Respiratory Journal (2007)

The aim of the present study was to assess the effects of possible interactions between beta(2)-adrenoceptor gene polymorphisms and passive smoking on forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC) and exhaled nitric oxide (eNO) in children aged 11 yrs. A cross-sectional analysis of the longitudinal cohort was conducted for associations between beta(2)-adrenoceptor gene polymorphisms and lung function and eNO with regard to passive smoking. Among children exposed to tobacco smoke, those with Arg16 (at least one Arg allele) exhibited lower adjusted mean FEV(1) (2.19 versus 2.38 L) and FVC (2.43 versus 2.64 L) than Gly16 homozygotes. Those with Gln27 (at least one Gln allele) also exhibited a lower adjusted mean FEV(1) relative to Glu27 homozygotes (2.24 versus 2.39 L). Among children with no exposure to smoking, those with Arg16 or Gln27 showed lower adjusted geometric mean eNO levels compared with Gly16 homozygotes (15.4 versus 30.9 ppb) and Glu27 homozygotes (18.0 versus 49.7 ppb). In conclusion, passive smoking had a significant effect on associations between beta(2)-adrenoceptor gene polymorphisms and asthma-related phenotypes, enhancing the relationship between Arg16 and lung function and removing the relationship between Arg16 or Gln27 and exhaled nitric oxide levels.
Intake of Potassium, Magnesium, Calcium, and Fiber and Risk of Stroke Among US Men
Authors: A. Ascherio, E. B. Rimm, M. A. Hernán, E. L. Giovannucci, I. Kawachi, M. J. Stampfer, W. C. Willett
Journal: Circulation (1998)

Animal experiments and epidemiological studies have suggested that high potassium intake may reduce the risk of stroke, but the evidence is inconclusive, and the role of other nutrients in potassium-rich foods remains unknown.We examined the association of potassium and related nutrients with risk of stroke among 43 738 US men, 40 to 75 years old, without diagnosed cardiovascular diseases or diabetes, who completed a semiquantitative food frequency questionnaire in 1986. During 8 years of follow-up, 328 strokes (210 ischemic, 70 hemorrhagic, 48 unspecified) were documented. The multivariate relative risk of stroke of any type for men in the top fifth of potassium intake (median intake, 4.3 g/d) versus those in the bottom (median, 2.4 g/d) was 0.62 (95% CI, 0.43, 0.88; P for trend=0.007). Results for ischemic stroke alone were similar. Intakes of cereal fiber and magnesium, but not of calcium, were also inversely associated with risk of total stroke. These inverse associations were all stronger in hypertensive than normotensive men and were not materially altered by adjustment for blood pressure levels. Use of potassium supplements was also inversely related to risk of stroke, particularly among men taking diuretics (relative risk, 0.36; 95% CI, 0.18, 0.72).Although these data do not prove a causal relationship, they are consistent with the hypothesis that diets rich in potassium, magnesium, and cereal fiber reduce the risk of stroke, particularly among hypertensive men. Potassium supplements may also be beneficial, but because of potential risks, use should be carefully monitored and restricted to men taking potassium-losing diuretics.
The human natural anti-Gal IgG. III. The subtlety of immune tolerance in man as demonstrated by crossreactivity between natural anti-Gal and anti-B antibodies.
Authors: U Galili, J Buehler, S B Shohet, B A Macher
Journal: The Journal of Experimental Medicine (1987)

A well-defined antigen/antibody system was used to evaluate the effect of immune tolerance on the spectrum of specificities of natural antibodies. The antibody used in this study, anti-Gal, is a naturally occurring, polyclonal IgG that constitutes 1% of the circulating IgG in humans. We have previously shown that anti-Gal, purified from AB sera, specifically interacts with glycosphingolipids bearing a Gal alpha 1----3Gal epitope, but not with the closely related B antigen in which the penultimate galactose of the Gal alpha 1----3Gal epitope is fucosylated Gal alpha 1----3(Fuc alpha 1----2)Gal. This narrow specificity was assumed to be the result of an effective immune tolerance mechanism that prevents the expression of antibody clones that can recognize both the Gal alpha 1----3Gal and the self B epitopes. If the assumption that immune tolerance determines the range of anti-Gal specificity is correct, then anti-Gal from individuals lacking the B antigen (A and O blood types) would be expected to interact with both Gal alpha 1----3Gal and Gal alpha 1----3(Fuc alpha 1----2)Gal epitopes. In this study, anti-Gal from the serum of individuals of various blood types was purified by affinity chromatography on Gal alpha 1----3Gal adsorbent and tested for its reaction with the B antigen. Whereas anti-Gal from AB and B individuals only reacted with Gal alpha 1----3Gal epitopes, anti-Gal from A and O individuals reacted with both Gal alpha 1----3Gal and B epitopes. Furthermore, it was determined that the majority of anti-B reactivity in A and O individuals is in fact anti-Gal antibodies capable of recognizing both Gal alpha 1----3Gal and B epitopes. It can be concluded from these results that immune tolerance accurately controls the spectrum of natural antibody specificities by preventing the production of antibody clones that can interact with self antigens.
Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung.
Authors: D Bucens, M C Pain
Journal: Circulation Research (1975)

An isolated perfused canine lung preparation in which determinants of vascular caliber could be individually controlled was developed. The relation of pulmonary arterial (Pa), venous (PV), and alveolar (PA) pressures was such that Pa greater than PA greater than PV throughout the whole lung. The addition of isoprenaline to the perfusate abolished vascular reactivity. Once stability was reached, vascular cross-sectional area remained acceptably constant for 2.25 hours as judged by normalized conductance. The influence of perfusate hematocrit, blood gas tensions, and pH on pressure-flow relations was then studied in 15 isolated canine lungs. The hematocrit-vascular conductance relation was derived at constant perfusion pressure. Conductance varied linearly with hematocrit over a range of 16.5 to 89.5%. Mean pulmonary arterial blood gas tensions were: PO2 = 121 mm Hg, PCO2 = 28 mm Hg, and pH = 7.46. Acute respiratory acidosis (PO2 = 30 mm Hg, PCO2 = 81 mm Hg, pH = 7.17) and lactic acidosis and hypoxemia (PO2 = 32 mm Hg, PCO2 = 21 mm Hg, pH = 6.96) did not significantly alter this relation. Transformation of the conductance-hematocrit data indicated that hematocrit was the most important determinant of relative apparent viscosity of the blood. Both acute respiratory and lactic acidosis failed to significantly increase relative viscosity within the range of hematocrit usually found in secondary polycythemia.
Metastatic ovarian carcinoma-associated subepidermal blistering disease with autoantibodies to both the p200 dermal antigen and the γ2 subunit of laminin 5 showing unusual clinical features
Authors: J. Mitsuya, H. Hara, K. Ito, N. Ishii, T. Hashimoto, T. Terui
Journal: British Journal of Dermatology (2008)

Anti-p200 pemphigoid is an autoimmune subepidermal blistering disease characterized by autoantibodies to an unknown 200-kDa acidic noncollagenous glycoprotein of the lower lamina lucida, whereas antilaminin 5 mucous membrane pemphigoid is characterized by autoantibodies to a major basement membrane extracellular matrix, laminin 5. We report a 64-year-old Japanese woman with a subepidermal blistering disease associated with lymph node metastasis of ovarian clear cell carcinoma 10 years after its surgical treatment. Clinical features showed severe blisters and erosions on multiple mucous membranes (i.e. lip, oral cavity, nose, eye, genitalia and anus) and on both the periungual and subungual regions. This is the first report in which an immunoblot analysis revealed the unusual combination of autoantibodies to both the p200 antigen and the gamma 2 subunit of laminin 5.
Mathematical correlation between villus height and the nutritional state in Sprague-Dawley rats.
Authors: J L Zambonino Infante, J M Rouanet, P Besancon
Journal: Gut (1993)

Three different experiments were carried out on growing male Sprague-Dawley rats. In the first experiment, dietary nitrogen was given in casein at four different protein values ranging from 5 to 16%. Rats were fed ad libitum for 21 days. In the second experiment, which lasted 17 days, animals were given three diets that differed in the molecular form of the nitrogen supply - that is, proteins or peptides. The protein value (N x 6.25) was 10% in each diet. In the third experiment, malnourished rats were refed diets with a protein value of 15% (N x 6.25) for eight days. The dietary nitrogen was either in the form of protein, peptide, or amino acid. Body weight was recorded daily. At the end of each experiment the intestinal villus height was measured by light microscopy. Data were statistically analysed by Exner's coefficient. The results assessed the validity of the correlation between villus height and gain in body weight.