tbuckley/cabot-search huggingface dataset:
Genome-Wide Evidence for Efficient Positive and Purifying Selection in Capsella grandiflora, a Plant Species with a Large Effective Population Size
Authors: T. Slotte, J. P. Foxe, K. M. Hazzouri, S. I. Wright
Journal: Molecular Biology and Evolution (2010)

Recent studies comparing genome-wide polymorphism and divergence in Drosophila have found evidence for a surprisingly high proportion of adaptive amino acid fixations, but results for other taxa are mixed. In particular, few studies have found convincing evidence for adaptive amino acid substitution in plants. To assess the generality of this finding, we have sequenced 257 loci in the outcrossing crucifer Capsella grandiflora, which has a large effective population size and low population structure. Using a new method that jointly infers selective and demographic effects, we estimate that 40% of amino acid substitutions were fixed by positive selection in this species, and we also infer a low proportion of slightly deleterious amino acid mutations. We contrast these estimates with those for a similar data set from the closely related Arabidopsis thaliana and find significantly higher rates of adaptive evolution and fewer nearly neutral mutations in C. grandiflora. In agreement with results for other taxa, genes involved in reproduction show the strongest evidence for positive selection in C. grandiflora. Taken together, these results imply that both positive and purifying selection are more effective in C. grandiflora than in A. thaliana, consistent with the contrasting demographic history and effective population sizes of these species.
Frizzled 4 Regulates Stemness and Invasiveness of Migrating Glioma Cells Established by Serial Intracranial Transplantation
Authors: Xun Jin, Hee-Young Jeon, Kyeung Min Joo, Jun-Kyum Kim, Juyoun Jin, Sung Hak Kim, Bong Gu Kang, Samuel Beck, Se Jeong Lee, Joong Kyu Kim, Ae-Kyung Park, Woong-Yang Park, Yun-Jaie Choi, Do-Hyun Nam, Hyunggee Kim
Journal: Cancer Research (2011)

One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, which is considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, its nature remains poorly understood. In this study, we established highly serial intracranial transplantation. U87R4 cells were highly invasive and displayed stem cell-like properties, as compared to noninvasive but proliferative U87L4 cells. Microarray analysis during serial transplantation revealed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated whereas several cancer stem cell-relevant genes [Frizzled 4 (FZD4) and CD44] were upregulated in more invasive cells. U87R4 cells were resistant to anticancer drug-induced cell death, partly due to downregulation of caspase3 and PDCD4, and they retained activated Wnt/β-catenin signaling due to upregulation of Frizzled 4, which was sufficient to control neurosphere formation. We also found that FZD4 promoted expression of the epithelial to mesenchymal transition regulator SNAI1, along with acquisition of a mesenchymal phenotype. Taken together, our results argue that Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis.
MYO9B polymorphisms in patients with inflammatory bowel disease
Authors: C Nunez, J Oliver, J L Mendoza, M Gomez-Garcia, A Pinero, C Taxonera, M Diaz-Rubio, M A Lopez-Nevot, E G de la Concha, A Nieto, E Urcelay, A Martinez, J Martin
Journal: Gut (2007)

An abnormal function of the intestinal barrier has been found not only in patients with inflammatory bowel disease (IBD) but even in their healthy relatives, suggesting that this condition may precede disease onset by years.1 A genetic alteration in the intestinal permeability has also been proposed to exist in patients with coeliac disease. In support of this proposal, polymorphisms in the MYO9B gene (the gene for myosin IXb involved in cytoskeleton remodelling) were found to be associated with increased susceptibility to coeliac disease.2

The MYO9B gene has recently been investigated in relation to IBD and produced discordant results. No association was observed in a Norwegian population,3 but shortly afterwards an international collaboration group performed a statistically powerful study on samples collected from the UK, Netherlands, Canada and Italy in which MYO9B was found to be associated with IBD, and with ulcerative colitis and Crohn’s disease considered separately in some populations.4 In that study, a stronger effect was seen …
Food and drink industry rejects claims of irresponsibility over obesity and alcoholism
Authors: A. O'Dowd
Journal: BMJ (2011)

<h3>Objectives</h3> The objective of this 30-week randomised crossover trial was to determine whether a multi-modal realignment treatmentwould be successful in relieving pain and improving function among persons with medial tibiofemoral osteoarthritis (OA). <h3>Methods</h3> The authors conducted a double-blind randomised crossover trial of a multi-modal realignment treatment for medial tibiofemoral OA. Trial participants met American College of Rheumatology criteria for OA, with knee pain, aching or stiffness on most days of the past month and radiographic evidence of a definite osteophyte with predominant medial tibiofemoral OA. The authors tested two different treatments: (A) control treatment consisting of a neutral knee brace (no valgus angulation), flat unsupportive foot orthoses and shoes with a flexible mid-sole; and (B) active treatment consisting of a valgus knee brace, customised neutral foot orthoses and shoes designed for motion control. For each subject, the trial lasted 30 weeks, including 12 weeks each of active treatment and control treatment separated by a 6-week washout period. The primary outcome of the linear regression model was change in knee pain and function, as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). <h3>Results</h3> 80 participants with medial tibiofemoral OA were randomised. Their mean age was 62 years, their mean body mass index was 34 kg/m<sup>2</sup> and their mean WOMAC Pain score was 9.2 (0–20 scale). There was no evidence of a carryover effect. The regression model demonstrated that the mean difference in pain between the active treatment and the control treatment was −1.82 units (95% CI −3.05 to −0.60; p=0.004) on the WOMAC Pain scale, indicating a small but statistically significant decrease in pain with the multi-modal active treatment. For WOMAC Function, the realignment intervention had a non-significant effect on function, with a −2.90 unit decrease (95% CI −6.60 to 0.79) compared with the control condition (p=0.12). <h3>Conclusion</h3> Multi-modal realignment treatment decreases pain in persons with medial tibiofemoral OA.
CIRRHOSIS AND OTHER HEPATIC LESIONS PRODUCED IN DOGS BY THYROIDECTOMY AND BY COMBINED HYPOPHYSECTOMY AND THYROIDECTOMY
Authors: I. L. Chajkoff, T. Gillman, C. Entenman, J. F. Rinehart, F. L. Reichert
Journal: The Journal of Experimental Medicine (1948)

1. The reactions of the dog's liver to (a) thyroidectomy and (b) both hypophysectomy and thyroidectomy are described. 2. Fatty changes of varying severity were detected in 8 of the 9 hypophysectomized-thyroidectomized dogs, hepatic fibrosis in 7, and severe cirrhosis in 4 animals of this group. Among the thyroidectomized animals histologically demonstrable fatty livers were present in all 8, mild fibrosis was observed in 4, while early and mild cirrhosis was diagnosed in only one dog. 3. Two pathogenetically distinct forms of cirrhosis were present in the livers of dogs with the two operations, namely (a) cirrhosis initiated and developing around the radicles of the hepatic veins, and (b) periportal cirrhosis. Both forms of cirrhosis occurred in dogs that were subjected to the same experimental procedures, and both forms could be found in the same liver. The pathogenesis of these two forms of cirrhosis is described. 4. The relation between fatty change in the liver and the genesis of fibrosis is discussed, and it is suggested that, while fatty change may facilitate the evocation of cirrhosis, this reaction on the part of the supporting and vascular elements of the liver is not solely dependent on the fatty change in the liver cells. 5. The relation between the endocrines and hepatic cirrhosis is discussed. Since cirrhosis was slight in the fatty livers of thyroidectomized dogs, whereas it was often advanced in hypophysectomized-thyroidectomized dogs, it is suggested that in the absence of the pituitary cirrhogenic mechanisms are facilitated in the dog.
“Healthy Avenues of the Mind”: Psychological Theory Building and the Influence of Religion During the Era of Moral Treatment
Authors: Tanaquil Taubes
Journal: American Journal of Psychiatry (1998)

This article delineates the main psychological interventions used by American asylum superintendents practicing moral treatment between 1815 and 1875. Further, it explores the impact of Protestant religious ideas on specific aspects of moral treatment's theory and practice.Asylum annual reports written by superintendents (physicians dedicated to the treatment of the mentally ill) were studied along with volumes of the American Journal of Insanity from its premier issue in 1844 through the 1890s. The writings of two laymen, Thomas Gallaudet and Horace Mann, both committed advocates of moral treatment, were also examined.The superintendents espoused complex theories about individual psychology and the nature of the self based on their observations. Protestant religious thought was a major influence, helping to catalyze original psychological propositions. Interesting resonances can be found between the superintendents' concept of a central agency, a governing "I" accounting for individual behavior, and ego psychologists' concepts of the organizing functions of the ego.Moral treatment did not produce a comprehensive psychotherapeutic system. Nonetheless, the superintendents voiced surprisingly modern psychotherapeutic insights. Religious worship as well as religious notions about the inviolability of the soul greatly influenced their views of patients. Rather than being an impediment to formulating psychological ideas, religious concepts proved to be a rich framework for evolving theories about aspects of patients' internal psychological functioning.
Long-Term Effects of High-Dose Chemotherapy and Radiation for Relapsed and Refractory Hodgkin's Lymphoma
Authors: Karyn A. Goodman, Elyn Riedel, Victoria Serrano, Subhash Gulati, Craig H. Moskowitz, Joachim Yahalom
Journal: Journal of Clinical Oncology (2008)

To evaluate the risk of late morbidity and mortality, and to assess long-term health-related quality of life (QOL) among patients with relapsed/refractory Hodgkin's lymphoma (HL) after high-dose chemoradiotherapy (HDT) and autologous stem-cell rescue (ASCR).From 1985 to 1998, 218 patients with HL were treated on HDT with ASCR salvage protocols. Of these 218, 153 (70%) who survived > or = 2 years after ASCR were evaluated for late morbidity and mortality from causes other than HL. QOL information was obtained through self-administered questionnaires. Risk ratios (RR) were calculated to compare observed second malignancy (SM) rates in this cohort with expected SM rates from the Surveillance Epidemiology and End Results (SEER) registry.Median follow-up after ASCR was 11.5 years. Among 153 patients, there were 53 deaths; 33 from HL and 20 from other causes. Thirteen deaths were caused by SM, with median time from ASCR to SM diagnosis of 9 years (range, 3 to 18 years). The RR of SM was 6.5 (95% CI, 3.6 to 10.7) when compared with the general population, but 2.4 (95% CI, 1.4 to 4.05) when compared with patients with HL. Global QOL of ASCR survivors was comparable with the general population, but for specific domains, respondents' scores indicated reduced functioning and worse symptoms.HL accounts for most deaths among patients surviving HDT and ASCR. Survivors of ASCR had an elevated risk of SM compared with the cancer risk in the general population, but when compared with patients with HL in SEER, the risk was less pronounced.
The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis
Authors: Aparna Hoskote, Jia Li, Chantal Hickey, Simon Erickson, Glen Van Arsdell, Derek Stephens, Helen Holtby, Desmond Bohn, Ian Adatia
Journal: Journal of the American College of Cardiology (2004)
Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation
Authors: J Goulis, T N Chau, S Jordan, A B Mehta, A Watkinson, K Rolles, A K Burroughs
Journal: Gut (1999)

Thrombocytopenia in cirrhotic patients may be due to deficient production of thrombopoietin.To determine the relation between thrombopoietin and thrombocytopenia in cirrhotic patients before and after orthotopic liver transplantation.Thrombopoietin concentrations and platelet counts were measured in 43 cirrhotic patients and 21 normal controls and serially for 14 days after transplantation in 23/43 patients.27 of the 43 patients had thrombocytopenia (platelet count less than 120 x 10(9)/l; group 1) whereas 16 patients had normal platelet count (group 2). Thrombopoietin concentrations were lower in group 1 than in group 2 (92.5 (20.3-286.3) v 226.6 (30.1-848.3) pg/ml, p=0.003) and normal controls (92.5 (20.3-286.3) v 158.3 (22.5-232.9) pg/ml, p=0.028). Post-transplantation thrombopoietin concentrations increased with a peak at day 5. The rise was significant in patients with low pretransplantation platelet count (89.1 (21.29-247.6) to 545.1 (66.2-2569) pg/ml; n=16, p=0.001) but not in those with normal platelet count (262.8 (30.1-848.3) to 315.1 (114-954.6) pg/ml; n=7, p=0.47). No correlation was found pretransplantation between spleen volume and platelet count (r=-0.11, p=0.6) or thrombopoietin concentrations (r=-0.04, p=0.8). However, pretransplantation thrombopoietin concentrations correlated with platelet count (r=0.47, p=0.0015), whereas an inverse correlation was found between peak thrombopoietin concentrations and nadir platelet count (r=-0.41 p=0. 049) post-transplantation.Inadequate thrombopoietin production may contribute to cirrhotic thrombocytopenia. Thrombopoietin production is restored after liver transplantation leading to the resolution of thrombocytopenia.
Effects of procainamide on the dispersion of recovery of excitability during coronary occlusion.
Authors: R Levites, J I Haft, J Calderon, None Venkatachalapathy
Journal: Circulation (1976)

In 14 mongrel dogs, refractory periods were determined in nonischemic and acutely ischemic zones of myocardium during control conditions, 15 minutes after coronary ligation, and 10 and 20 minutes after a procainamide infusion. Following coronary ligation, refractory periods in the nonischemic area remained unchanged (100.8% of control) while in the ischemia area they decreased to 88.6% of control (P less than 0.02) causing a dispersion of refractoriness of 12.2%. After the administration of procainamide, refractory periods lengthened in the nonischemic as well as in the ischemic areas but the changes were such that the temporal dispersion caused by the coronary ligation was reduced from 12.2% to 5.5% (P less than 0.01) after 10 minutes, and to 5.0% (P less than 0.02) after 20 minutes of drug infusion. It is concluded that procainamide exerts different overall effects on the nonischemic and acutely ischemic canine myocardium. It is postulated that this action may play a role in the suppression of re-entrant arrhythmias.
Disability assessment doctors come under GMC scrutiny
Authors: A. O'Dowd
Journal: BMJ (2011)

Seven doctors working for a company hired by the government to assess people for eligibility for disability benefit are being investigated by the General Medical Council, it has emerged.

Doctors working for Atos Healthcare, the UK company paid by the Department for Work and Pensions to carry out work capability assessments on people claiming incapacity benefit, are being investigated by the GMC over complaints about their conduct.

Although the GMC will not give precise details, it has confirmed to the BMJ that 30 complaints made against doctors employed by Atos were investigated in 2010. Fourteen more cases concerning doctors working for Atos were opened in 2011.

Of all these cases 10 are still active and involve seven doctors, some of whom have …
Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver
Authors: Carl A. Goresky, K. Sandy Pang, Andreas J. Schwab, Ford Barker Iii, Wendy F. Cherry, Glen G. Bach
Journal: Hepatology (1992)

The hepatocytic entry of acetaminophen sulfate conjugate was examined in the rat liver, perfused with red cells with and without albumin, by use of the multiple-indicator dilution technique. [3H]acetaminophen sulfate was injected into the portal vein in a bolus of blood containing51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or125I-labeled albumin (a high-molecular-weight interstitial reference, included when albumin was present), and the time courses of their outflow into the hepatic venous blood were observed. The [3H]acetaminophen sulfate, which binds partially to albumin, emerged between albumin and sucrose in the presence of albumin, precessed the upslope of the sucrose curve and showed a late low-in-magnitude tailing; the precession disappeared in the absence of albumin. Biliary excretion of [3H]acetaminophen sulfate was less than 1% of the dose. Quantitative evaluation with a barrier-limited, spacedistributed variable transit time model (including rapidly equilibrating albumin binding) accounted for the albumin effect on [3H]acetaminophen sulfate behavior and demonstrated a low liver cell permeability for the acetaminophen sulfate and a small interstitial binding space for its nonalbumin-bound fraction in excess of that for sucrose, which in the absence of albumin was of similar dimensions. (HEPATOLOGY 1992;16:173–190.)
Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome
Authors: Michael L. Nickerson, Michelle B. Warren, Jorge R. Toro, Vera Matrosova, Gladys Glenn, Maria L. Turner, Paul Duray, Maria Merino, Peter Choyke, Christian P. Pavlovich, Nirmala Sharma, McClellan Walther, David Munroe, Rob Hill, Eamonn Maher, Cheryl Greenberg, Michael I. Lerman, W.Marston Linehan, Berton Zbar, Laura S. Schmidt
Journal: Cancer Cell (2002)
Recent Changes in Breast Cancer Incidence in Spain, 1980–2004
Authors: Marina Pollán, Roberto Pastor-Barriuso, Eva Ardanaz, Marcial Argüelles, Carmen Martos, Jaume Galcerán, María-José Sánchez-Pérez, María-Dolores Chirlaque, Nerea Larrañaga, Ruth Martínez-Cobo, María-Cres Tobalina, Enrique Vidal, Rafael Marcos-Gragera, Antonio Mateos, Isabel Garau, María-Dolores Rojas-Martín, Rosario Jiménez, Ana Torrella-Ramos, Josefina Perucha, Maria-Eugenia Pérez-de-Rada, Susana González, María-José Rabanaque, Joan Borràs, Carmen Navarro, Esther Hernández, Ángel Izquierdo, Gonzalo López-Abente, Carmen Martínez
Journal: JNCI Journal of the National Cancer Institute (2009)

Since the 1980s, Spain experienced two decades of sharply increasing breast cancer incidence. Declines in breast cancer incidence have recently been reported in many developed countries. We examined whether a similar downturn might have taken place in Spain in recent years.
Environmental Adaptation Contributes to Gene Polymorphism across the Arabidopsis thaliana Genome
Authors: Cheng-Ruei Lee, Thomas Mitchell-Olds
Journal: Molecular Biology and Evolution (2012)

The level of within-species polymorphism differs greatly among genes in a genome. Many genomic studies have investigated the relationship between gene polymorphism and factors such as recombination rate or expression pattern. However, the polymorphism of a gene is affected not only by its physical properties or functional constraints but also by natural selection on organisms in their environments. Specifically, if functionally divergent alleles enable adaptation to different environments, locus-specific polymorphism may be maintained by spatially heterogeneous natural selection. To test this hypothesis and estimate the extent to which environmental selection shapes the pattern of genome-wide polymorphism, we define the "environmental relevance" of a gene as the proportion of genetic variation explained by environmental factors, after controlling for population structure. We found substantial effects of environmental relevance on patterns of polymorphism among genes. In addition, the correlation between environmental relevance and gene polymorphism is positive, consistent with the expectation that balancing selection among heterogeneous environments maintains genetic variation at ecologically important genes. Comparison of the gene ontology annotations shows that genes with high environmental relevance are enriched in unknown function categories. These results suggest an important role for environmental factors in shaping genome-wide patterns of polymorphism and indicate another direction of genomic study.
Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.
Authors: C H Tseng, T Y Tai, C K Chong, C P Tseng, M S Lai, B J Lin, H Y Chiou, Y M Hsueh, K H Hsu, C J Chen
Journal: Environmental Health Perspectives (2000)

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.