tbuckley/cabot-search huggingface dataset:
Does History Repeat Itself? Wavelets and the Phylodynamics of Influenza A
Authors: J. A. Tom, J. S. Sinsheimer, M. A. Suchard
Journal: Molecular Biology and Evolution (2011)

Unprecedented global surveillance of viruses will result in massive sequence data sets that require new statistical methods. These data sets press the limits of Bayesian phylogenetics as the high-dimensional parameters that comprise a phylogenetic tree increase the already sizable computational burden of these techniques. This burden often results in partitioning the data set, for example, by gene, and inferring the evolutionary dynamics of each partition independently, a compromise that results in stratified analyses that depend only on data within a given partition. However, parameter estimates inferred from these stratified models are likely strongly correlated, considering they rely on data from a single data set. To overcome this shortfall, we exploit the existing Monte Carlo realizations from stratified Bayesian analyses to efficiently estimate a nonparametric hierarchical wavelet-based model and learn about the time-varying parameters of effective population size that reflect levels of genetic diversity across all partitions simultaneously. Our methods are applied to complete genome influenza A sequences that span 13 years. We find that broad peaks and trends, as opposed to seasonal spikes, in the effective population size history distinguish individual segments from the complete genome. We also address hypotheses regarding intersegment dynamics within a formal statistical framework that accounts for correlation between segment-specific parameters.
Overexpression of Akt converts radial growth melanoma to vertical growth melanoma
Authors: Baskaran Govindarajan, James E. Sligh, Bethaney J. Vincent, Meiling Li, Jeffrey A. Canter, Brian J. Nickoloff, Richard J. Rodenburg, Jan A. Smeitink, Larry Oberley, Yuping Zhang, Joyce Slingerland, Rebecca S. Arnold, J. David Lambeth, Cynthia Cohen, Lu Hilenski, Kathy Griendling, Marta Martínez-Diez, José M. Cuezva, Jack L. Arbiser
Journal: Journal of Clinical Investigation (2007)

Melanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma.
Elevation of Multiple Serum Markers in Patients With Stage I Ovarian Cancer
Authors: R. P. Woolas, F.-J. Xu, I. J. Jacabs, Y.-H. Yu, L. Daly, A. Brechuck, J. T. Soper, D. L. Clarke-pearson, D. H. Oram, R. C. Bast
Journal: JNCI Journal of the National Cancer Institute (1993)

The high overall mortality from ovarian cancer (> 60%) relates, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics staging), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a less expensive and more convenient initial screening test, the sensitivity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity but detects only about one half of early stage ovarian carcinomas.The purpose of this retrospective study was to determine whether assays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone.Using immunoradiometric assays, we measured preoperative serum levels of CA 125 tumor-associated antigen, macrophage colony-stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovarian cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who had participated in a screening trial and remained free from cancer at 1 year of followup. All specimens were obtained from cryopreserved aliquots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/mL, or OVX1 levels were greater than 12.1 U/mL.At least one of the serum markers was elevated in 98% of patients with stage I ovarian cancer; CA 125 levels were elevated in 67%. By the same criteria, 11% of healthy individuals and 51% of patients with benign pelvic masses had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly greater than the sensitivity of the CA 125 assay (P < .0005) and specificity was moderate.A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity and moderate specificity.Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substantially reduce the expense and improve the specificity of screening compared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.
Asthma in children exposed to nitrogen dioxide in ice arenas
Authors: P. Thunqvist, G. Lilja, M. Wickman, G. Pershagen
Journal: European Respiratory Journal (2002)

Very high concentrations of nitrogen dioxide (NO 2 ) have been measured in arenas using combustion engine-powered resurfacing machines. This study was performed to compare the occurrence of asthma in children playing ice hockey in arenas using propane-powered machines and in children attending arenas using electric machines. Children regularly playing hockey in the arenas (nine propane, six electric) were sent a questionnaire, including questions on allergic disease and risk factors. Measurements of NO 2 were performed with passive diffusion samplers during 3 consecutive days. The mean NO 2 concentration in the propane arenas was 276 µg·m −3 (range 28–1015 µg·m −3 ) and 11 µg·m −3 (2–30) in the electric arenas. Questionnaires were answered by 1,536 children (78%), with an overall prevalence of asthma of 16%. The odds ratio (OR) for asthma was 0.9 (95% confidence interval (CI) 0.7–1.2) comparing propane arenas to electric. However, children in propane arenas with higher than median concentration of NO 2 reported more wheezing (OR 1.4, 95% CI 1.0–1.9) and nasal symptoms (OR 1.7, 95% CI 1.3–2.3) than children in propane arenas with lower concentrations. In conclusion, children playing ice hockey in indoor arenas have a high prevalence of asthma, but it appears unlikely that increased exposure to combustion products, including nitrogen dioxide, is a major contributor to this excess risk.
Why do children have chronic abdominal pain, and what happens to them when they grow up? Population based cohort study
Authors: M. Hotopf, S. Carr, R. Mayou, M. Wadsworth, S. Wessely
Journal: BMJ (1998)

To test the hypotheses that children with abdominal pain have anxious parents and come from families with high rates of physical illness and that they grow up to suffer from high rates of medically unexplained symptoms and psychiatric disorders.Population based birth cohort study.General population.Participants in the Medical Research Council (MRC) national survey of health and development, a population based birth cohort study established in 1946.Abdominal pain present throughout childhood in the absence of defined organic disease, and measures of physical symptoms and psychiatric disorder at age 36 years.There were high rates of complaints about physical health among the parents of children with persistent abdominal pain, and the mothers had higher neuroticism scores. Children with persistent abdominal pain were more likely to suffer from psychiatric disorders in adulthood (odds ratio 2.72 (95% confidence interval 1.65 to 4.49)) but were not especially prone to physical symptoms once psychiatric disorder was controlled for (odds ratio 1. 39 (0.83 to 2.36)).Persistent abdominal pain is associated with poor health and emotional disorder in the parents. Children with abdominal pain do not necessarily continue to experience physical symptoms into adulthood but are at increased risk of adult psychiatric disorders.
Hepatitis C virus–induced reduction in miR‐181a impairs CD4+ T‐cell responses through overexpression of DUSP6
Authors: Guang Y. Li, Yun Zhou, Ruo S. Ying, Lei Shi, Yong Q. Cheng, Jun P. Ren, Jeddidiah W.D. Griffin, Zhan S. Jia, Chuan F. Li, Jonathan P. Moorman, Zhi Q. Yao
Journal: Hepatology (2014)

T cells play a crucial role in viral clearance or persistence; however, the precise mechanisms that control their responses during viral infection remain incompletely understood. MicroRNA (miR) has been implicated as a key regulator controlling diverse biological processes through posttranscriptional repression. Here, we demonstrate that hepatitis C virus (HCV)–mediated decline of miR‐181a expression impairs CD4 + T‐cell responses through overexpression of dual specific phosphatase 6 (DUSP6). Specifically, a significant decline of miR‐181a expression along with overexpression of DUSP6 was observed in CD4 + T cells from chronically HCV‐infected individuals compared to healthy subjects, and the levels of miR‐181a loss were found to be negatively associated with the levels of DUSP6 overexpression in these cells. Importantly, reconstitution of miR‐181a or blockade of DUSP6 expression in CD4 + T cells led to improved T‐cell responses including enhanced CD25 and CD69 expression, increased interleukin‐2 expression, and improved proliferation of CD4 + T cells derived from chronically HCV‐infected individuals. Conclusion : Since a decline of miR‐181a concomitant with DUSP6 overexpression is the signature marker for age‐associated T‐cell senescence, these findings provide novel mechanistic insights into HCV‐mediated premature T‐cell aging through miR‐181a‐regulated DUSP6 signaling and reveal new targets for therapeutic rejuvenation of impaired T‐cell responses during chronic viral infection. (H epatology 2015;61:1163–1173)
Elevated C-Reactive Protein Values and Atherosclerosis in Sudden Coronary Death
Authors: Allen P. Burke, Russell P. Tracy, Frank Kolodgie, Gray T. Malcom, Arthur Zieske, Robert Kutys, Joseph Pestaner, John Smialek, Renu Virmani
Journal: Circulation (2002)

Background — Elevations in serum C-reactive protein measured by high-sensitivity assay (hs-CRP) have been associated with unstable coronary syndromes. There have been no autopsy studies correlating hs-CRP to fatal coronary artery disease. Methods and Results — Postmortem sera from 302 autopsies of men and women without inflammatory conditions other than atherosclerosis were assayed for hs-CRP. There were 73 sudden deaths attributable to atherothrombi, 71 sudden coronary deaths with stable plaque, and 158 control cases (unnatural sudden deaths and noncardiac natural deaths without conditions known to elevate CRP). Atherothrombi were classified as plaque ruptures (n=55) and plaque erosion (n=18); plaque burden was estimated in each heart. Total cholesterol, high-density lipoprotein cholesterol, diabetes, smoking history, and body mass index were also determined. Immunohistochemical stains for CRP and numbers of thin cap atheromas per heart were quantitated in coronary deaths with hs-CRP in the highest and lowest quintiles. The median hs-CRP was 3.2 μg/mL in acute rupture, 2.9 μg/mL in plaque erosion, 2.5 μg/mL in stable plaque, and 1.4 μg/mL in controls. Mean log hs-CRP was higher in rupture ( P &lt;0.0001), erosion ( P =0.005), and stable plaque ( P =0.0003) versus controls. By multivariate analysis, atherothrombi ( P =0.02), stable plaque ( P =0.003), and plaque burden ( P =0.03) were associated with log hs-CRP independent of age, sex, smoking, and body mass index. Mean staining intensity for CRP of macrophages and lipid core in plaques was significantly greater in cases with high hs-CRP than those with low CRP ( P =0.0001), as were mean numbers of thin cap atheromas ( P &lt;0.0001). Conclusions — hs-CRP is significantly elevated in patients dying suddenly with severe coronary artery disease, both with and without acute coronary thrombosis, and correlates with immunohistochemical staining intensity and numbers of thin cap atheroma.
Calculated Low-Density Lipoprotein Cholesterol Should Not Be Used for Management of Lipoprotein Abnormalities in Patients With Diabetes Mellitus
Authors: Juan Rubiés-Prat, Jordi L Reverter, Mariano Sentí, Juan Pedro-Botet, Isabel Salinas, Anna Lucas, Xavier Nogués, Anna Sanmartí
Journal: Diabetes Care (1993)

OBJECTIVE To assess the validity of calculated low-density lipoprotein cholesterol by the Friedewald formula for management of lipoprotein abnormalities in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 61 patients with type I diabetes, 50 patients with type II diabetes, and 116 healthy control subjects. RESULTS Calculated LDL cholesterol coincided with measured LDL cholesterol, with &amp;lt; 10% error, in 54 (49%) patients with diabetes mellitus, and 85 (73%) control subjects. Calculated LDL cholesterol was overestimated, with an error of &amp;gt; or = 10% of measured LDL cholesterol in 39% of patients and 26% of control subjects, and underestimated in 13 and 1%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrated a poor concordance between calculated and measured LDL cholesterol, both in patients and control subjects. When comparing the mean differences of calculated and measured LDL cholesterol for diabetic subjects versus control subjects, significantly greater differences in type II (but not type I) diabetic subjects were seen. CONCLUSIONS Calculation of LDL cholesterol by the Friedewald formula may be inaccurate for assessment of cardiovascular risk in patients with type II diabetes and may not be appropriate for management of lipoprotein abnormalities in those diabetic patients.
Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli
Authors: T H J Florin
Journal: Gut (1997)

Background and aims —The colons of patients with pneumatosis cystoides coli produce excessive H 2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1–5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chloral hydrate treatment. One produced methane, the other did not. (Pneumatosis cystoides coli patients are non-methanogenic according to the literature.) Both had overnight fasting breath H 2 of less than 10 ppm. A literature review disclosed just one patient who was using chloral at the time of diagnosed pneumatosis cystoides coli, but an epidemic of the disease in workers exposed to trichloroethylene. Methods —(i) In vitro experiments with human faeces: chloral or closely related alkyl halides were added to anaerobic faecal cultures derived from four methane-producing and three non-methanogenic human subjects. H 2 and CH 4 gases were measured. (ii) In vivo animal experiment: chloral hydrate was added to drinking water of four Wistar rats, and faecal H 2 compared with control rats. Results —Alkyl halides increased H 2 up to 900 times in methanogenic and 10 times in non-methanogenic faecal cultures. The K i of chloral was 0.2 mM. Methanogenesis was inhibited in concert with the increase in net H 2 . In the rat experiment, chloral hydrate increased H 2 10 times, but did not cause pneumatosis. Conclusions —Chloral and trichloroethylene are alkyl halides chemically similar to chloroform, a potent inhibitor of H 2 consumption by methanogens and acetogens. These bacteria are the most important H 2 -consuming species in the colon. It is postulated that exposure to these alkyl halides increases net H 2 production, which sets the scene for “counterperfusion supersaturation” and the formation of gas cysts. In recent times, very low prescribing rates for chloral have caused primary pneumatosis cystoides to become extremely rare. As with primary pneumatosis, secondary pneumatosis cystoides, which occurs if there is small bowel bacterial overgrowth distal to a proximally located gut obstruction, is predicted by counterperfusion supersaturation. “Inherent unsaturation” due to metabolism of O 2 is a safety factor, which could explain why gas bubbles do not form more often in tissue with high H 2 tension.
Plasma Osteopontin Is an Independent Prognostic Marker for Head and Neck Cancers
Authors: David Petrik, Philip W. Lavori, Hongbin Cao, Yonghua Zhu, Priscilla Wong, Erin Christofferson, Michael J. Kaplan, Harlan A. Pinto, Patrick Sutphin, Albert C. Koong, Amato J. Giaccia, Quynh-Thu Le
Journal: Journal of Clinical Oncology (2006)

Purpose To confirm the relationship between plasma osteopontin (OPN) levels and treatment outcomes in head and neck squamous cell carcinoma (HNSCC) patients in an expanded study. Patients and Methods One hundred forty patients with newly diagnosed HNSCC were enrolled onto this study, 54 previously reported and 86 new patients. Pretreatment plasma OPN levels were assessed in all patients by an enzyme-linked immunosorbent assay method. OPN levels were correlated to treatment outcomes in the new group of patients. Detailed analyses were also performed on the relationship between OPN and tumor control rate, event-free survival (EFS), and postrelapse survival for the entire group. Results Using a previously defined cut off point of 450 ng/mL, there was a significant correlation between OPN and freedom-from-relapse (P = .047), overall survival (P = .019), and EFS (P = .023) in the new, independent patient cohort (n = 86). Sequence of event analyses using the entire group (N = 140) revealed that OPN was an independent prognostic factor for initial tumor control, EFS in those who have achieved tumor control, and postrelapse survival. Conclusion In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.
Prognosis of Anti-Hepatitis C Virus Antibody-Positive Patients on Regular Hemodialysis Therapy
Authors: EIJUN NAKAYAMA, TAKASHI AKIBA, FUMIAKI MARUMO, CHIFUMI SATO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The prevalence of hepatitis C virus (HCV) infection is high in patients who are on chronic hemodialysis, but the role of HCV infection and HCV-related liver disease in the mortality of these patients has not been shown. Therefore, we conducted a prospective cohort study of 1470 patients who were on chronic hemodialysis (17 to 89 yr old) from 16 dialysis centers in Japan. Among them, 276 patients (18.8%) were positive for anti-HCV antibodies and 1194 patients were negative. The patients were followed for 6 yr from 1993 to 1999. Only one case, a patient from the anti-HCV-antibody-positive group, was lost to the follow-up during this period. The mortality was higher in the anti-HCV-antibody-positive group (91 of 276 patients died) than in the anti-HCV-antibody-negative group (277 of 1193 died) (33.0% versus 23.2%, P &lt; 0.01). A Cox proportional hazard examination showed that positivity for anti-HCV antibodies was one of the risk factors for death with an adjusted relative risk of 1.57 (95% confidence interval, 1.23 to 2.00). As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent in the anti-HCV-antibody-positive patients than in the anti-HCV-antibody-negative patients (5.5% versus 0.0%, P &lt; 0.001; 8.8% versus 0.4%, P &lt; 0.001, respectively). These findings show that the mortality is increased in anti-HCV-antibody-positive patients who are on chronic hemodialysis. Hepatocellular carcinoma and liver cirrhosis are factors that may influence the mortality.
Oesophageal motor function before and after healing of oesophagitis.
Authors: P Singh, A Adamopoulos, R H Taylor, D G Colin-Jones
Journal: Gut (1992)

Forty three patients with reflux oesophagitis were studied to investigate the effect of healing on oesophageal function. All patients underwent oesophageal manometry and transit studies before and after complete healing of oesophagitis. Oesophagitis was treated with omeprazole 40 mg/day for a median duration of 12 weeks. Twenty three patients also had an acid clearance test before and after healing. Thirty eight of the 43 patients had 24 hour oesophageal pH monitoring before treatment and this was repeated after healing (while on omeprazole) in 31 of them. Thirty four volunteers served as controls. All volunteers underwent manometry, 33 had oesophageal transit studies, and 23 had acid clearance test. Patients had significantly reduced lower oesophageal sphincter pressures and distal and middle oesophageal amplitudes, longer durations of contraction, and slower velocity of propagation than the controls (16.5 v 22.5 mm Hg; 52 v 92 mm Hg; 46 v 79 mm Hg; 3.1 v 2.7 seconds; and 3.3 v 4.1 cm/second respectively with the corresponding p values = 0.017; 0.0001; 0.0001; 0.017; and 0.006). Patients had significantly longer transit times (9 v 7 and 17 v 11 seconds: p = 0.027 and 0.002 for erect and supine postures respectively). They also had longer acid clearance times (350 v 288 and 536 v 405 seconds: p = 0.044 and 0.016 for sitting and supine postures respectively). There was no significant change in any of the indices of oesophageal function after healing of oesophagitis (lower oesophageal sphincter pressure = 16.5 v 20; distal amplitude = 52 v 60; middle amplitude = 46 v 49; duration of contraction = 3.1 v 3.1; velocity = 3.3 v 3.3; erect transit time = 9 v 9; supine transit time = 17 v 24; acid clearance test (sitting) = 350 v 371; acid clearance test (supine) = 536 v 645). These results indicate that oesophageal motor dysfunction in reflux oesophagitis is a primary phenomenon.