tbuckley/cabot-search huggingface dataset:
Association between HLA-DR1 and -DR3 antigens and unexplained repeated miscarriage
Authors: O. Christiansen
Journal: Human Reproduction Update (1999)

Few, mostly small, studies have investigated the distribution of HLA class II antigens among women with unexplained recurrent miscarriage. Although some studies have reported statistically significant associations between this syndrome and certain HLA-DR antigens - especially the -DR1 and -DR3 antigens - other studies have been unable to demonstrate such associations. For the present meta-analysis, 18 cross-sectional or case-control studies (published or unpublished) reporting on frequencies of HLA-DR1 and -DR3 antigens among Caucasian women with unexplained repeated miscarriage were identified by searching literature databases (MEDLINE and EMBASE), reading the references of identified studies, and by contacting researchers within the field. The studies comprised a total of 1508 patients with only two miscarriages were included in many studies; this is defined as repeated miscarriage. The odds ratios of repeated miscarriage for the HLA-DR1 and -DR3 antigens were calculated for the individual studies and subsequently the pooled odds ratios for the studies were calculated. The combined odds ratio for HLA-DR1 was 1.29 [95% confidence interval (CI) = 1.05-1.58] (17 studies) which is statistically significant (P<0.05). The combined odds ratio for HLA-DR3 was 1.00 (95% CI 0.80-1.24) (18 studies), which is not significant. The results of the meta-analysis suggest that the HLA-DR antigen DR1 is associated with an increased susceptibility to unexplained repeated miscarriage.
Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease
Authors: Vincent Wai-Sun Wong, Julien Vergniol, Grace Lai-Hung Wong, Juliette Foucher, Henry Lik-Yuen Chan, Brigitte Le Bail, Paul Cheung-Lung Choi, Mathurin Kowo, Anthony Wing-Hung Chan, Wassil Merrouche, Joseph Jao-Yiu Sung, Victor de Lédinghen
Journal: Hepatology (2009)

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase–to–alanine aminotransferase ratio, aspartate aminotransferase–to–platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P &lt; 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance. Conclusion: Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa. (Hepatology 2010;51:454–462.)
The Multiple Risk Factor Intervention Trial (MRFIT)—Importance Then and Now
Authors: Jeremiah Stamler
Journal: JAMA (2008)

The 356 222 men aged 35 to 57 years, who were free of a history of hospitalization for myocardial infarction, screened by the Multiple Risk Factor Intervention Trial (MRFIT) in its recruitment effort, constitute the largest cohort with standardized serum cholesterol measurements and long-term mortality follow-up. For each five-year age group, the relationship between serum cholesterol and coronary heart disease (CHD) death rate was continuous, graded, and strong. For the entire group aged 35 to 57 years at entry, the age-adjusted risks of CHD death in cholesterol quintiles 2 through 5 (182 to 202, 203 to 220, 221 to 244, and ≥245 mg/dL [4.71 to 5.22, 5.25 to 5.69, 5.72 to 6.31, and ≥6.34 mmol/L]) relative to the lowest quintile were 1.29, 1.73, 2.21, and 3.42. Of all CHD deaths, 46% were estimated to be excess deaths attributable to serum cholesterol levels 180 mg/dL or greater (≥4.65 mmol/L), with almost half the excess deaths in serum cholesterol quintiles 2 through 4. The pattern of a continuous, graded, strong relationship between serum cholesterol and six-year age-adjusted CHD death rate prevailed for nonhypertensive nonsmokers, nonhypertensive smokers, hypertensive nonsmokers, and hypertensive smokers. These data of high precision show that the relationship between serum cholesterol and CHD is not a threshold one, with increased risk confined to the two highest quintiles, but rather is a continuously graded one that powerfully affects risk for the great majority of middle-aged American men.See PDF for full text of the original JAMA article.
Design a questionnaire.
Authors: D H Stone
Journal: BMJ (1993)

The design of questionnaires is a craft which has been badly neglected by the medical profession. A questionnaire should be appropriate, intelligible, unambiguous, unbiased, capable of coping with all possible responses, satisfactorily coded, piloted, and ethical. The key steps in designing a questionnaire are to: decide what data you need, select items for inclusion, design the individual questions, compose the wording, design the layout and presentation, think about coding, prepare the first draft and pretest, pilot, and evaluate the form, and perform the survey. Despite the apparently complicated nature of the task, theoretical knowledge is no substitute for practical experience.
Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young
Authors: Jan Skupien, Sylwia Gorczynska-Kosiorz, Tomasz Klupa, Krzysztof Wanic, Eric A. Button, Jacek Sieradzki, Maciej T. Malecki
Journal: Diabetes Care (2008)

1,5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in a lowered plasma concentration. As a low renal threshold for glucose has been described in hepatocyte nuclear factor-1alpha (HNF-1alpha) maturity-onset diabetes of the young (MODY), the 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in patients with HNF-1alpha MODY and in type 2 diabetic subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1alpha MODY.We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 type 2 diabetic patients and 47 nondiabetic control subjects. The 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). Receiver operating characteristic (ROC) curve analysis was used to evaluate 1,5-AG as a screening marker for HNF-1alpha MODY.The mean 1,5-AG plasma concentration in diabetic HNF-1alpha mutation carriers was 5.9 microg/ml, and it was lower than that in type 2 diabetic patients (11.0 microg/ml, P = 0.003) and in nondiabetic control subjects (23.9 microg/ml, P < 0.00005). The ROC curve analysis revealed 85.7% sensitivity and 80.0% specificity of 1,5-AG in screening for HNF-1alpha MODY at the criterion of <6.5 microg/ml in patients with an A1C level between 6.5 and 9.0%.1,5-AG may be a useful biomarker for differential diagnosis of patients with HNF-1alpha MODY with a specific range of A1C, although this requires further investigation. However, the clinical use of this particle in diabetic HNF-1alpha mutation carriers for metabolic control has substantial limitations.
The Firstborn Phenomenon Among Psychiatric Residents
Authors: SHELDON H. KARDENER, MARIELLE FULLER
Journal: American Journal of Psychiatry (1972)

There has been a reawakening of interest in the study of birth order. Investigations have shown a significant preponderance of firstborn children in such areas as medical school. They have also shown that firstborns have a greater achievement level and different personality characteristics than other children. In support of this, the authors present their findings of residents' responses to a questionnaire regarding their training; of 160 subjects who responded, 92 were firstborn children.
Trajectories of Psychological Distress in Adolescent and Young Adult Patients With Cancer: A 1-Year Longitudinal Study
Authors: Minyoung Kwak, Brad J. Zebrack, Kathleen A. Meeske, Leanne Embry, Christine Aguilar, Rebecca Block, Brandon Hayes-Lattin, Yun Li, Melissa Butler, Steven Cole
Journal: Journal of Clinical Oncology (2013)

Purpose To examine prevalence and changes in symptoms of psychological distress over 1 year after initial cancer diagnosis in adolescent and young adult (AYA) patients with cancer. Sociodemographic and clinical predictors of changes in distress were examined. Patients and Methods In this multisite, longitudinal, prospective study of an ethnically diverse sample, 215 patients age 14 to 39 years were assessed for psychological distress within the first 4 months of diagnosis and again 6 and 12 months later. Linear mixed models with random intercept and slope estimated changes in distress, as measured by the Brief Symptom Inventory-18 (BSI-18). Results Within the first 4 months of diagnosis, 60 respondents (28%) had BSI-18 scores suggesting caseness for distress. On average, distress symptoms exceeded population norms at the time of diagnosis, dipped at the 6-month follow-up, but increased to a level exceeding population norms at the 12-month follow-up. A statistically significant decline in distress over 1 year was observed; however, the gradient of change was not clinically significant. Multivariate analyses revealed that the reduction in distress over time was primarily a function of being off treatment and involved in school or work. Notably, cancer type or severity was not associated with distress. Conclusion Findings emphasize the importance of early psychosocial intervention for distress in AYAs as well as the need to manage treatment-related symptoms and facilitate AYAs' involvement in work or school to the extent possible. Continued research is needed to understand how distress relates to quality of life, functional outcomes, treatment, and symptom burden throughout the continuum of care.
Peripheral Blood Flow in Normal Pregnancy
Authors: J. Ginsburg, S. L. B. Duncan
Journal: Cardiovascular Research (1967)

During pregnancy the mean blood flow through the hands, measured under standard conditions with the subjects supine, rose progressively from 2·7 ml./100 ml.min. to 18·1 ml. at term. The flow subsided during the puerperium, but by the sixth week it was still, at 9·1 ml., significantly elevated above the level of early pregnancy. The blood flow through the feet showed similar, though less striking, changes. The flows were somewhat higher in twin-pregnancies than in singleones. The blood flow through the forearm and calf of the leg remained little changed throughout.
Inhibition of Growth and Transformation of Human Cells by Interferon 2
Authors: Edwin V. Gaffney, Paul T. Picciano, Carol A. Grant
Journal: JNCI Journal of the National Cancer Institute (1973)

Interferon (IF) produced in amnion cell cultures inhibited the growth of a line of simian virus 40-transformed human cells. IF was not effective in FL, HeLa, WI-38, untransformed amnion, or L-929 cells. Growth inhibition was short term and could be continued, provided IF-containing medium was renewed. The incomplete inhibition of growth at high IF concentrations implied that only a portion of the cell cycle issensitive. The time interval between exposure to IF and growth reduction was 6 hours. The factor responsible for an inhibition of cell growth appears to be related to the factor responsible for antiviral activity.
Saliva Polymerase-Chain-Reaction Assay for Cytomegalovirus Screening in Newborns
Authors: Suresh B. Boppana, Shannon A. Ross, Masako Shimamura, April L. Palmer, Amina Ahmed, Marian G. Michaels, Pablo J. Sánchez, David I. Bernstein, Robert W. Tolan, Zdenek Novak, Nazma Chowdhury, William J. Britt, Karen B. Fowler
Journal: New England Journal of Medicine (2011)

Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives--real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth--have been developed.In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth.A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively.Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.).
Snake α-Neurotoxin Binding Site on the Egyptian Cobra (Naja haje) Nicotinic Acetylcholine Receptor Is Conserved
Authors: Zoltan Takacs, Kirk C. Wilhelmsen, Steve Sorota
Journal: Molecular Biology and Evolution (2001)

Evolutionary success requires that animal venoms are targeted against phylogenetically conserved molecular structures of fundamental physiological processes. Species producing venoms must be resistant to their action. Venoms of Elapidae snakes (e.g., cobras, kraits) contain alpha-neurotoxins, represented by alpha-bungarotoxin (alpha-BTX) targeted against the nicotinic acetylcholine receptor (nAChR) of the neuromuscular junction. The model which presumes that cobras (Naja spp., Elapidae) have lost their binding site for conspecific alpha-neurotoxins because of the unique amino acid substitutions in their nAChR polypeptide backbone per se is incompatible with the evolutionary theory that (1) the molecular motifs forming the alpha-neurotoxin target site on the nAChR are fundamental for receptor structure and/or function, and (2) the alpha-neurotoxin target site is conserved among Chordata lineages. To test the hypothesis that the alpha-neurotoxin binding site is conserved in Elapidae snakes and to identify the mechanism of resistance against conspecific alpha-neurotoxins, we cloned the ligand binding domain of the Egyptian cobra (Naja haje) nAChR alpha subunit. When expressed as part of a functional Naja/mouse chimeric nAChR in Xenopus oocytes, this domain confers resistance against alpha-BTX but does not alter responses induced by the natural ligand acetylcholine. Further mutational analysis of the Naja/mouse nAChR demonstrated that an N-glycosylation signal in the ligand binding domain that is unique to N. haje is responsible for alpha-BTX resistance. However, when the N-glycosylation signal is eliminated, the nAChR containing the N. haje sequence is inhibited by alpha-BTX with a potency that is comparable to that in mammals. We conclude that the binding site for conspecific alpha-neurotoxin in Elapidae snakes is conserved in the nAChR ligand binding domain polypeptide backbone per se. This conclusion supports the hypothesis that animal toxins are targeted against evolutionarily conserved molecular motifs. Such conservation also calls for a revision of the present model of the alpha-BTX binding site. The approach described here can be used to identify the mechanism of resistance against conspecific venoms in other species and to characterize toxin-receptor coevolution.
Association of Left Atrial Fibrosis Detected by Delayed-Enhancement Magnetic Resonance Imaging and the Risk of Stroke in Patients With Atrial Fibrillation
Authors: Marcos Daccarett, Troy J. Badger, Nazem Akoum, Nathan S. Burgon, Christian Mahnkopf, Gaston Vergara, Eugene Kholmovski, Christopher J. McGann, Dennis Parker, Johannes Brachmann, Rob S. MacLeod, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2011)
Impaired activity of the bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat
Authors: Nynke R. Koopen, Henk Wolters, Rick Havinga, Roel J. Vonk, Peter L. Jansen, Michael Müller, Folkert Kuipers
Journal: Hepatology (1998)

To test the hypothesis that impaired activity of the bile canalicular organic anion transporting system mrp2 (cmoat) is a key event in the etiology of 17α-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats, EE (5 mg/kg subcutaneously daily) was administered to male normal Wistar (NW) and mrp2-deficient Groningen Yellow/Transport-deficient Wistar (GY/TR − ) rats. Elevated plasma bilirubin levels in GY/TR − rats increased upon EE-treatment from 65 ± 8.4 μmol/L to 183 ± 22.7 μmol/L within 3 days, whereas bilirubin levels remained unaffected in NW rats. Biliary bilirubin secretion was 1.5-fold increased in NW rats but remained unaltered in GY/TR − rats. Plasma bile salt concentrations remained unchanged in both strains, although hepatic levels of the sinusoidal Na + -taurocholate cotransporting protein (ntcp) were markedly reduced. Biliary secretion of endogenous bile salt was not affected in either strain. A clear reduction of mrp2 levels in liver plasma membranes of NW rats was found after 3 days of treatment. The bile salt-independent fraction of bile flow (BSIF) was reduced from 2.6 to 2.0 μL/min/100 g body weight in NW rats with a concomitant 62% reduction of biliary glutathione secretion. The absence of mrp2 and biliary glutathione in GY/TR − rats did not prevent induction of EE-cholestasis; a similar absolute reduction of BSIF, i.e., from 1.1 to 0.6 μL/min/100 g body weight, was found in these animals. EE treatment caused a reduction of the maximal biliary secretory rate (S RM ) of the mrp2 substrate, dibromosulphthalein (DBSP), from 1,040 to 695 nmol/min/100 g body weight (−38%) in NW rats and from 615 to 327 nmol/min/100 g body weight (−46%) in GY/TR − rats. These results demonstrate that inhibition of mrp2 activity and/or biliary glutathione secretion is not the main cause of EE-induced cholestasis in rats. The data indicate that alternative pathways exist for the biliary secretion of bilirubin and related organic anions that are also affected by EE.
The Role of BPTF in Melanoma Progression and in Response to BRAF-Targeted Therapy
Authors: Altaf A. Dar, Mehdi Nosrati, Vladimir Bezrookove, David de Semir, Shahana Majid, Suresh Thummala, Vera Sun, Schuyler Tong, Stanley P. L. Leong, David Minor, Paul R. Billings, Liliana Soroceanu, Robert Debs, James R. Miller, Richard W. Sagebiel, Mohammed Kashani-Sabet
Journal: JNCI Journal of the National Cancer Institute (2015)

Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma. The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided. shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents. These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF.
1364 THE HOMA INDEX IS A USEFUL TOOL FOR RISK STRATIFICATION OF ADVANCED FIBROTIC DISEASE IN A LARGE COHORT OF EUROPEAN NAFLD PATIENTS
Authors: V. Ratziu, G. Marchesini, M. Romero-Gomez, E. Bugianesi, C. Day, S. Bellentani, C. de Oliveira, M. Trauner, J.-F. Dufour, T. Sorensen, L. Fedchuk, C. Holst
Journal: Journal of Hepatology (2013)
The Oxford years — The last of the Quarto!
Authors: P SLEIGHT
Journal: Cardiovascular Research (2007)

The following is an account of my tenure as Editor-in-Chief of Cardiovascular Research , which began in 1983. I took over from Ron Linden, who followed the first editor, Jack Shillingford; I quit after almost 10 years on the 25th anniversary, in 1991. That was 16 years ago and with the passage of time (incredibly rapid) it is hard to come up with very good recollections! ’ Particularly since I had handed over all the journal files and correspondence to the new team. My only aide-memoire is the nicely bound copy of the 25th volume which was presented to me by the publisher, … 

* Tel.: +44 186 576 0564; fax: +44 186 576 8844. peter.sleight{at}attglobal.net