tbuckley/cabot-search huggingface dataset:
Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers
Authors: Deanna Alexis Carere, Mick P Couper, Scott D Crawford, Sarah S Kalia, Jake R Duggan, Tanya A Moreno, Joanna L Mountain, J Scott Roberts, Robert C Green
Journal: Genome Medicine (2014)

Abstract Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research.
Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial
Authors: H. Heinrich, O. Goetze, D. Menne, P. X. Iten, H. Fruehauf, S. R. Vavricka, W. Schwizer, M. Fried, M. Fox
Journal: BMJ (2010)

To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms.Randomised controlled crossover study.20 healthy adults (14 men) aged 23-58.Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium (13)Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order.Cumulative percentage dose of (13)C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales).Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of (13)C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, -0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference -0.40, -0.01 to -0.79; P<0.046). No difference in dyspeptic symptoms was present.Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms.ClinicalTrials.gov NCT00943696.
NADPH Oxidase Mediates Tissue Factor–Dependent Surface Procoagulant Activity by Thrombin in Human Vascular Smooth Muscle Cells
Authors: Olaf Herkert, Isabel Diebold, Ralf P. Brandes, John Hess, Rudi Busse, Agnes Görlach
Journal: Circulation (2002)

Tissue factor (TF) initiates the extrinsic coagulation cascade leading to thrombin formation. Thrombin induces TF mRNA in vascular smooth muscle cells (VSMCs), thereby contributing to the prolonged procoagulant activity and enhanced thrombogenicity at sites of vascular injury. However, the signaling mechanisms mediating this thrombogenic cycle are unclear. Characteristically, vascular injury promotes the generation of reactive oxygen species (ROS). Because ROS exert signaling functions, we investigated whether the NADPH oxidase, an important source of ROS in VSMCs, contributes to upregulation of TF by thrombin.Thrombin not only stimulated TF mRNA expression, but also TF-dependent surface procoagulant activity in cultured human VSMCs. This response was attenuated by antioxidants; the flavin inhibitor diphenylene-iodonium, Clostridium difficile toxin B, which inhibits Rho GTPases, p22phox antisense oligonucleotides, or the dominant-negative RacT17N mutant. Inhibitors of p38 MAP kinase and phosphatidylinositol (PI) 3-kinase also prevented thrombin-stimulated TF mRNA expression. Furthermore, thrombin stimulated the phosphorylation of the PI 3-kinase target protein kinase B/Akt in a redox-sensitive and NADPH oxidase-dependent manner.These findings indicate that the NADPH oxidase is essentially involved in the redox-sensitive induction of TF mRNA expression and surface procoagulant activity by thrombin. This response is mediated by NADPH oxidase-dependent activation of p38 MAP kinase and the PI 3-kinase/protein kinase B/Akt pathway. Given that active TF promotes thrombin formation, the NADPH oxidase may play a crucial role in perpetuating the thrombogenic cycle in the injured vessel wall.
Cartilage macromolecules in knee joint synovial fluid. Markers of the disease course in patients with acute oligoarthritis
Authors: E. Lindqvist, T. Saxne
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To investigate the development of chronic joint symptoms in patients presenting with acute oligoarthritis including knee joint synovitis with effusion and explore whether prognostic information can be derived from initial synovial fluid concentrations of aggrecan and cartilage oligomeric matrix protein (COMP) for development of chronic joint symptoms. <h3>METHODS</h3> Retrospective follow up of 25 patients identified in a bank of knee joint synovial fluids collected consecutively from patients presenting with knee joint synovitis and symptoms from at most three additional joints and in whom no diagnosis could be established at presentation. <h3>RESULTS</h3> The 10 patients who developed chronic joint symptoms were characterised by lower knee joint synovial fluid concentrations of aggrecan as well as lower aggrecan/COMP ratios (p&lt;0.001) than the 15 patients who had a transient arthritis. No other clinical or laboratory differences between the groups were apparent at the time of presentation. <h3>CONCLUSIONS</h3> The synovial fluid content of aggrecan is a potential tool in acute arthritis for distinguishing patients with a benign disease course from those who will develop a chronic joint disorder.
Sodium homeostasis with chronic sodium loading in preascitic cirrhosis
Authors: F Wong
Journal: Gut (2001)

Preascitic cirrhotic patients receiving 200 mmol of sodium daily for seven days remain in positive sodium balance. Thereafter, sodium handling is unknown.To assess renal sodium handling in preascitic cirrhosis on a high sodium diet for five weeks.Sixteen biopsy proven preascitic cirrhotics were assessed at weekly intervals for five weeks on a diet of 200 mmol sodium/day using a daily weight diary and weekly 24 hour urinary sodium estimations. Fasting supine neurohormone levels were measured at baseline and weekly for five weeks while haemodynamics were measured at baseline and at five weeks.The daily diet of 200 mmol of sodium resulted in weight gain and a positive sodium balance for three weeks, associated with significant suppression of plasma renin activity and aldosterone levels, and a significant rise in plasma atrial natriuretic peptide levels (p<0.05). Patients' weights plateaued during week 4, associated with complete sodium balance and significant suppression of plasma noradrenaline levels (p<0.05). This was followed by a negative sodium balance and weight loss, and finally complete sodium balance, again despite a mean net gain of 2.3 (0.3) kg, associated with a return of plasma renin activity and aldosterone levels to within normal ranges. The lack of increase in central blood volume in addition to the persistent increase in plasma atrial natriuretic peptide levels indicated that residual volume expansion, consequent to persistent weight gain, was distributed on the venous side of the circulation. No free fluid was seen on repeat abdominal ultrasound after five weeks.Preascitic cirrhotics have a natriuretic "escape" after three weeks on high sodium dietary intake, associated with elevated plasma atrial natriuretic peptide levels and suppression of the renin-angiotensin-aldosterone system. With continued suppressed sympathetic activity, preascitics re-establish complete sodium balance but with a net weight gain and presumed increased intravascular volume, but without ascites. This further elucidates the compensated sodium retaining abnormality that characterises preascitic cirrhosis.
Iatrogenic Aortic Dissection … or Intramural Hematoma?
Authors: Terrence D. Welch, Thomas Foley, Gregory W. Barsness, Peter C. Spittell, R. Thomas Tilbury, Maurice Enriquez-Sarano, Artur Evangelista, Soon J. Park, Hector I. Michelena
Journal: Circulation (2012)
A statistical test for detecting geographic subdivision.
Authors: R R Hudson, D D Boos, N L Kaplan
Journal: Molecular Biology and Evolution (1992)

A statistical test for detecting genetic differentiation of subpopulations is described that uses molecular variation in samples of DNA sequences from two or more localities. The statistical significance of the test is determined with Monte Carlo simulations. The power of the test to detect genetic differentiation in a selectively neutral Wright-Fisher island model depends on both sample size and the rates of migration, mutation, and recombination. It is found that the power of the test is substantial with samples of size 50, when 4Nm less than 10, where N is the subpopulation size and m is the fraction of migrants in each subpopulation each generation. More powerful tests are obtained with genes with recombination than with genes without recombination.
THE RELATIONSHIP OF PSYCHIATRIC ILLNESS WITH GASTROINTESTINAL DISEASE
Authors: Andrew Fullwood, M.D, Douglas A. Drossman, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Higher rates of psychiatric comorbidity as well as more impaired psychosocial adjustment occur with the functional bowel disorders and are particularly high in self-selected referral patients compared with community populations. Reciprocally, some studies show higher rates of functional bowel disturbances in patients with psychiatric diagnoses. Remaining alert for and addressing coexisting psychiatric illness will enhance treatment outcome (increased patient compliance, functioning, and satisfaction). Additionally, psychological factors affect the clinical expression of structural disease. Resetting treatment goals from cure to coping with chronic illness and setting personal limits are important.
Glucose-Independent Ethnic Differences in HbA1c in People Without Known Diabetes
Authors: Matthew J.L. Hare, Dianna J. Magliano, Paul Z. Zimmet, Stefan Söderberg, Noorjehan Joonas, Vassen Pauvaday, José Larhubarbe, Jaakko Tuomilehto, Sudhir Kowlessur, K. George M.M. Alberti, Jonathan E. Shaw
Journal: Diabetes Care (2012)

OBJECTIVE To determine whether glucose-independent differences in HbA1c exist between people of African, South Asian, and Chinese ethnicities. RESEARCH DESIGN AND METHODS Data from 6,701 people aged 19–78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA1c, plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history. RESULTS Mean HbA1c, after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA1c, was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P &amp;lt; 0.001), Chinese (5.7%, P &amp;lt; 0.001), or Africans from the main island of Mauritius (5.7%, P &amp;lt; 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8–10.0); HbA1c 17.3% (15.3–19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups. CONCLUSIONS People of African ethnicity from Rodrigues have higher HbA1c than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.
Insights into the Demographic History of African Pygmies from Complete Mitochondrial Genomes
Authors: C. Batini, J. Lopes, D. M. Behar, F. Calafell, L. B. Jorde, L. van der Veen, L. Quintana-Murci, G. Spedini, G. Destro-Bisol, D. Comas
Journal: Molecular Biology and Evolution (2010)

Pygmy populations are among the few hunter-gatherers currently living in sub-Saharan Africa and are mainly represented by two groups, Eastern and Western, according to their current geographical distribution. They are scattered across the Central African belt and surrounded by Bantu-speaking farmers, with whom they have complex social and economic interactions. To investigate the demographic history of Pygmy groups, a population approach was applied to the analysis of 205 complete mitochondrial DNA (mtDNA) sequences from ten central African populations. No sharing of maternal lineages was observed between the two Pygmy groups, with haplogroup L1c being characteristic of the Western group but most of Eastern Pygmy lineages falling into subclades of L0a, L2a, and L5. Demographic inferences based on Bayesian coalescent simulations point to an early split among the maternal ancestors of Pygmies and those of Bantu-speaking farmers (∼70,000 years ago [ya]). Evidence for population growth in the ancestors of Bantu-speaking farmers has been observed, starting ∼65,000 ya, well before the diffusion of Bantu languages. Subsequently, the effective population size of the ancestors of Pygmies remained constant over time and ∼27,000 ya, coincident with the Last Glacial Maximum, Eastern and Western Pygmies diverged, with evidence of subsequent migration only among the Western group and the Bantu-speaking farmers. Western Pygmies show signs of a recent bottleneck 4,000–650 ya, coincident with the diffusion of Bantu languages, whereas Eastern Pygmies seem to have experienced a more ancient decrease in population size (20,000–4,000 ya). In conclusion, the results of this first attempt at analyzing complete mtDNA sequences at the population level in sub-Saharan Africa not only support previous findings but also offer new insights into the demographic history of Pygmy populations, shedding new light on the ancient peopling of the African continent.
Effect of high and low density lipoproteins on proliferation of cultured bovine vascular endothelial cells.
Authors: J P Tauber, J Cheng, D Gospodarowicz
Journal: Journal of Clinical Investigation (1980)

Bovine vascular endothelial cells maintained on dishes coated with an extracellular matrix and exposedto medium supplemented with lipoprotein-deficient serum (LPDS) require the presence of lipoprotein to proliferate optimally. High density lipoprotein (HDL) seems to be the major factor involved in the proliferation of vascular endothelial cells. This is mostly due to its lack of toxicity when added at high concentration, as well as to its nondependence on LPDS to exhibit its mitogenic properties. Therefore, HDL at physiological concentrations (1,000--1,500 microgram protein/ml) can fully replace serum. Low density lipoprotein, unlike HDL, has a biphasic effect. Although mitogenic for vascular endothelial cells when added at low concentration, once physiological concentrations are reached it becomes toxic for the cells. Moreover, and in contrast with HDL, the mitogenic effect of low density lipoprotein was found to be a function of the LPDS concentration to which cultures were exposed. The substrate upon which cultures are maintained has been found to be an important factor if a mitogenic effect of HDL is to be observed. When maintained on plastic, cells proliferate poorly in response to HDL unless fibroblast growth factor is added to the medium. In contrast, when maintained on extracellular matrix, an optimal growth rate is induced by HDL, even in the absence of fibroblast growth factor. This suggests that, in vivo, the integrity of the basement membrane upon which endothelial cells rest and migrate is an important factor in determining the cells response to lipoproteins present in plasma.
Association study of the <i>RANK</i> locus in white European rheumatoid arthritis families: Table 1
Authors: V Hugo Teixeira, P Dieudé, L Michou, P Migliorini, A Balsa, R Westhovens, P Barrera, H Alves, C Vaz, M Fernandes, D Pascual-Salcedo, S Bombardieri, J Dequeker, T R Radstake, P Van Riel, L van de Putte, A Lopes-Vaz, T Bardin, F Cornélis, E Petit-Teixeira
Journal: Annals of the Rheumatic Diseases (2009)

Rheumatoid arthritis (RA) linkage has been observed on the 18q chromosome in the white population.1 The 18q locus has also shown evidence of linkage with type I insulin-dependent diabetes mellitus, systemic lupus erythematosus and Grave’s disease.2 A candidate gene on chromosome 18q, the TNFRSF11A ( RANK ) gene, which encodes the receptor activator of nuclear factor kappa B, has been shown to be involved in the osteoclast differentiation playing a pivotal role in bone resorption.3 A single RANK haplotype was reported to be associated with RA in a case–control association study.4 Furthermore, activating mutations in the RANK gene cause bone disorders such as early-onset Paget’s disease,5 expansile skeletal hyperphosphatasia6 and familial expansile osteolysis.7 The aim of this …
Regulation of the Na+/H+ Exchanger (NHE1) in Breast Cancer Metastasis
Authors: Schammim R. Amith, Larry Fliegel
Journal: Cancer Research (2013)

Abstract The pH gradient in normal cells is tightly controlled by the activity of various pH-regulatory membrane proteins including the isoform protein of the Na+/H+ exchanger (NHE1). NHE1 is constitutively active in a neoplastic microenvironment, dysregulating pH homeostasis and altering the survival, differentiation, and proliferation of cancer cells, thereby causing them to become tumorigenic. Cytoplasmic alkalinization in breast cancer cells occurs as a result of increased NHE1 activity and, while much is known about the pathophysiologic role of NHE1 in tumor progression with regard to ion flux, the regulation of its activity on a molecular level is only recently becoming evident. The membrane domain of NHE1 is sufficient for ion exchange. However, its activity is regulated through the phosphorylation of key amino acids in the cytosolic domain as well as by its interaction with other intracellular proteins and lipids. Here, we review the importance of these regulatory sites and what role they may play in the disrupted functionality of NHE1 in breast cancer metastasis. Cancer Res; 73(4); 1259–64. ©2013 AACR.
Pulmonary embolism guidelines: will they work?
Authors: A C Miller
Journal: Thorax (2003)

<h3>ABSTRACT</h3> Previous studies have attempted to characterize the antibody response of individuals to the SARS-CoV-2 virus on a linear peptide level by utilizing peptide microarrays. These studies have helped to identify epitopes that have potential to be used for diagnostic tests to identify infected individuals, however, the immunological responses of individuals who have received the currently available Moderna mRNA-1273 or Pfizer BNT162b2 mRNA vaccines have not been characterized. We aimed to identify linear peptides of the SARS-CoV-2 spike protein that elicited high IgG or IgA binding activity and to compare the immunoreactivity of infected individuals to those who received both doses of either vaccines by utilizing peptide microarrays. Our results revealed peptide epitopes of significant IgG binding among recently infected individuals. Some of these peptides are located near functional domains implicated in the high infectivity of SARS-CoV-2. Vaccinated individuals lacked these distinct markers despite overall binding activity being similar.
Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: a cross-sectional survey
Authors: I. Muraki, T. Tanigawa, K. Yamagishi, S. Sakurai, T. Ohira, H. Imano, A. Kitamura, M. Kiyama, S. Sato, T. Shimamoto, M. Konishi, H. Iso
Journal: Thorax (2010)

<h3>Background</h3> There are conflicting results for the association between obstructive sleep apnoea and raised C reactive protein (CRP) levels. A study was undertaken to investigate whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnoea, was associated with CRP levels among a community-dwelling Japanese population. <h3>Methods</h3> Among participants in the Circulatory Risk in Communities Study (CIRCS), 1422 male and 2466 female community residents aged 40–69 years were tested during sleep. No nocturnal intermittent hypoxia, mild nocturnal intermittent hypoxia and moderate to severe nocturnal intermittent hypoxia were defined using 3% oxygen desaturation index cut-off points at 5 and 15 events/h, respectively. High-sensitivity CRP levels were measured using a latex particle-enhanced immunonephelometric assay. Multivariate analysis was adjusted for age, sex, body mass index, smoking status, current alcohol intake, hypertension, hypercholesterolaemia, diabetes mellitus and menopausal status for women. <h3>Results</h3> Multivariable-adjusted mean CRP levels among men were 0.70 mg/l (95% CI 0.65 to 0.75) for no nocturnal intermittent hypoxia, 0.82 mg/l (95% CI 0.74 to 0.89) for mild nocturnal intermittent hypoxia and 0.84 mg/l (95% CI 0.70 to 1.00) for moderate to severe nocturnal intermittent hypoxia (p for trend=0.03). The values for women were 0.59 mg/l (95% CI 0.57 to 0.62), 0.66 mg/l (95% CI 0.59 to 0.73) and 0.82 mg/l (95% CI 0.62 to 1.03), respectively (p for trend=0.008). Compared with no nocturnal intermittent hypoxia, the prevalence of a high CRP level (≥1.0 mg/l) was 1.4–1.7-fold higher for mild to severe nocturnal intermittent hypoxia in both sexes. <h3>Conclusions</h3> Nocturnal intermittent hypoxia is associated with raised serum CRP levels among middle-aged Japanese subjects.
Sinus and atrioventricular nodal distribution of sympathetic fibers that contain neuropeptide Y.
Authors: M R Warner, M N Levy
Journal: Circulation Research (1990)

Neuropeptide Y and norepinephrine are localized in sympathetic nerve terminals throughout the heart. We sought to determine the functional distribution of the neuropeptide Y-containing sympathetic fibers to the sinus and atrioventricular (AV) nodal regions. We recorded cycle length, AV interval, and arterial pressure in 14 anesthetized dogs. We assessed the release of neuropeptide Y from sympathetic nerve terminals by measuring the attenuation of the vagal effects on cycle length and AV interval that occurred after unilateral ansa subclavia stimulation. Three-minute trains of right or left ansa stimulation, each applied at frequencies of 2, 5, and 10 Hz, produced a frequency-dependent inhibition of the vagal effects on cycle length and AV interval. After right ansa stimulation (10 Hz), however, the percent inhibition of the vagal effects on cycle length was 21 +/- 5% greater (p less than 0.001) than the percent inhibition of the vagal effects on AV interval. Conversely, after left ansa stimulation (10 Hz), the percent inhibition of the vagal effects on AV interval was 54 +/- 7% greater (p less than 0.001) than the percent inhibition of the vagal effects on cycle length. The vagal stimulus characteristics (frequency or voltage) did not significantly alter the percent inhibition, nor did the percent inhibition depend on the vagus stimulated (right or left vagus). We conclude that most of the neuropeptide Y-containing sympathetic fibers at the sinus node originate in right-sided ganglia, whereas most of those at the AV node originate in left-sided ganglia.