tbuckley/cabot-search huggingface dataset:
A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method
Authors: D. A. Walker, J. Liu, M. Kieran, N. Jabado, S. Picton, R. Packer, C. St. Rose, A. S. Van Meeteren, A. Carvalho, A. Van Damme, B. Depreitere, B. Gustavsson, B. J. Due Tonnessen, A. I. Bertozzi-Salamon, A. Brentrup, C. Raybaud, C. Jones, C. Dufour, C. Dorfer, C. Sainte-Rose, C. Malluci, D. Hargrave, D. Walker, D. Van Vuurden, E. De Carli, E. Bouffet, F. Van Calenbergh, D. Frappaz, P. Frassanito, J. Goodrich, H. Baechli, J. Grill, J. Ternier, J. Cappelen, J. Caird, J. Pereira, L. Riffaud, M. Baroncini, M. Walker, M. Kieran, M. Ozek, N. Jabado, K. Nysom, P. Varlet, J. Goodden, P. Bertolini, G. Perilongo, P. Mercier, R. Grundy, R. D. Kortmann, R. Packer, S. Pfister, S. Constantini, S. Sgouros, S. Holm, T. Czech, T. Merchant, T. Stokland, V. Ridola, P. Vandertop
Journal: Neuro-Oncology (2013)

Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where <70% consensus occurred, the statement was modified and resubmitted for voting. Twenty-seven statements meeting consensus criteria are reported. For HCLGG, statements describing overall therapeutic purpose and indications for biopsy, observation, or treatment aimed at limiting the risk of visual damage and the need for on-going clinical trials were made. Primary surgical resection was not recommended. For DIPG, biopsy was recommended to ascertain biological characteristics to enhance understanding and targeting of treatments, especially in clinical trials. For HGG, biopsy is essential, the World Health Organization classification was recommended; selection of surgical strategy to achieve gross total resection in a single or multistep process should be discussed with the PNMDT and integrated with trials based drug strategies for adjuvant therapies.
Delayed progression of a murine retrovirus-induced acquired immunodeficiency syndrome in X-linked immunodeficient mice.
Authors: Y Hitoshi, Y Okada, E Sonoda, A Tominaga, M Makino, K Suzuki, J Kinoshita, K Komuro, T Mizuochi, K Takatsu
Journal: The Journal of Experimental Medicine (1993)

The murine acquired immunodeficiency syndrome (MAIDS) caused by defective LP-BM5 murine leukemia virus (MuLV) is a disease that shows severe immunodeficiency with abnormal lymphoproliferation, and hypergammaglobulinemia in susceptible C57BL/6 (B6) mice. To examine the cellular mechanisms of development of MAIDS, we injected LP-BM5 MuLV intraperitoneally into B6 mice bearing the X chromosome-linked immunodeficiency (xid). xid mice lack functionally mature B cells including Ly-1 B cells (also known as B-1 cells). All B6 mice died by 20 wk after LP-BM5 MuLV inoculation. In marked contrast, xid mice have continued to survive without any sign of MAIDS-related symptoms till at least 20 wk after the inoculation. The delayed progression of MAIDS in xid mice appears to depend on xid mutation, according to our experiments using both sexes of (B6.xid x B6)F1 and (B6 x B6.xid)F1 mice. Furthermore, Ly-1 B cells, enriched by a FACS, were shown to integrate the defective genome and appeared to be a major virus-infected B cell population. Our data corroborate that Ly-1 B cells play an important role in the induction and progression of MAIDS.
Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial
Authors: M. Weinblatt, M. Schiff, A. Goldman, J. Kremer, M. Luggen, T. Li, D. Chen, J.-C. Becker
Journal: Annals of the Rheumatic Diseases (2006)

To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE).Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE.A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections.The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.
Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries
Authors: Alexandra L Quittner, Lutz Goldbeck, Janice Abbott, Alistair Duff, Patrick Lambrecht, Amparo Solé, Marijke M Tibosch, Agneta Bergsten Brucefors, Hasan Yüksel, Paola Catastini, Laura Blackwell, Dave Barker
Journal: Thorax (2014)

<h3>Background</h3> Individuals with chronic diseases and parent caregivers are at increased risk for symptoms of depression and anxiety. Prevalence of psychological symptoms was evaluated in adolescents and adults with cystic fibrosis (CF) and parent caregivers across nine countries. <h3>Methods</h3> Patients with CF, ages 12 years and older, and caregivers of children with CF, birth to18 years of age, completed measures of depression and anxiety across 154 CF centres in Europe and the USA. Psychological symptoms were compared across countries using χ<sup>2</sup>. Logistic regression examined extent of comorbid symptoms, predictors of depression and anxiety, and concordance between parent and adolescent symptomatology. <h3>Results</h3> Psychological symptoms were reported by 6088 patients with CF and 4102 parents. Elevated symptoms of <i>depression</i> were found in 10% of adolescents, 19% of adults, 37% of mothers and 31% of fathers. Elevations in <i>anxiety</i> were found in 22% of adolescents, 32% of adults, 48% of mothers and 36% of fathers. Overall, elevations were 2–3 times those of community samples. Participants reporting elevated anxiety were more likely to report depression (ORs: adolescents=14.97, adults=13.64, mothers=15.52, fathers=9.20). Significant differences in reports of depression and anxiety were found by patient age and parent respondent. Concordance between 1122 parent–teen dyads indicated that adolescents whose parents reported depression were more likely to be elevated on depression (OR=2.32). Similarly, adolescents whose parents reported anxiety were more likely to score in the elevated range on the anxiety measure (OR=2.22). <h3>Conclusions</h3> Symptoms of depression and anxiety were elevated in both patients with CF and parents across several European countries and the USA. Annual screening of psychological symptoms is recommended for both patients and parents.
Cost effectiveness and cost utility analysis of multidisciplinary care in patients with rheumatoid arthritis: a randomised comparison of clinical nurse specialist care, inpatient team care, and day patient team care
Authors: W B van den Hout
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To assess the relative cost effectiveness of clinical nurse specialist care, inpatient team care, and day patient team care. <b>Methods:</b> Incremental cost effectiveness analysis and cost utility analysis, alongside a prospective randomised controlled trial with two year follow up. Included were patients with rheumatoid arthritis (RA) with increasing difficulty in performing activities of daily living over the previous six weeks. Quality of life and utility were assessed by the Rheumatoid Arthritis Quality of Life questionnaire, the Short Form-6D, a transformed rating scale, and the time tradeoff. A cost-price analysis was conducted to estimate the costs of inpatient and day patient hospitalisations. Other healthcare and non-healthcare costs were estimated from cost questionnaires. <b>Results:</b> 210 patients with RA (75% female, median age 59 years) were included. Aggregated over the two year follow up period, no significant differences were found on the quality of life and utility instruments. The costs of the initial treatment were estimated at €200 for clinical nurse specialist care, €5000 for inpatient team care, and €4100 for day patient team care. Other healthcare costs and non-healthcare costs were not significantly different. The total societal costs did not differ significantly between inpatients and day patients, but were significantly lower for the clinical nurse specialist patients by at least €5400. <b>Conclusions:</b> Compared with inpatient and day patient team care, clinical nurse specialist care was shown to provide equivalent quality of life and utility, at lower costs. Therefore, for patients with health conditions that allow for any of the three types of care, the preferred treatment from a health-economic perspective is the care provided by the clinical nurse specialist.
Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation
Authors: Daqing Ma, Ta Lim, Jing Xu, Haidy Tang, Yanjie Wan, Hailin Zhao, Mahmuda Hossain, Patrick H. Maxwell, Mervyn Maze
Journal: Journal of the American Society of Nephrology (2009)

The mortality rate from acute kidney injury after major cardiovascular operations can be as high as 60%, and no therapies have been proved to prevent acute kidney injury in this setting. Here, we show that preconditioning with the anesthetic gas xenon activates hypoxia-inducible factor 1alpha (HIF-1alpha) and its downstream effectors erythropoietin and vascular endothelial growth factor in a time-dependent manner in the kidneys of adult mice. Xenon increased the efficiency of HIF-1alpha translation via modulation of the mammalian target of rapamycin pathway. In a model of renal ischemia-reperfusion injury, xenon provided morphologic and functional renoprotection; hydrodynamic injection of HIF-1alpha small interfering RNA demonstrated that this protection is HIF-1alpha dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1alpha and that administration of xenon before renal ischemia can prevent acute renal failure. If these data are confirmed in the clinical setting, then preconditioning with xenon may be beneficial before procedures that temporarily interrupt renal perfusion.
THE RELATIONSHIP BETWEEN THE GROWTH CAPACITY OF PRIMARY TUMORS AND THE DISTRIBUTION OF METASTASES OF A TRANSPLANTED TUMOR OF THE RABBIT
Authors: Chester M. Van Allen
Journal: The Journal of Experimental Medicine (1925)

As an adjunct to the study of a transplantable malignant tumor of the rabbit an index of malignancy has been developed which has proven useful in evaluating the severity of the disease for the purpose of statistical investigations. The index consists of two figures, one of which expresses the growth capacity of the primary lesion on a volume basis, and the other the extent of the metastatic lesions according to the distribution of peripheral tumors. In the present communication these two values for each animal are utilized for the study of the relationship existing between the size of the primary tumor and the distribution of metastases in this experimental tumor. The data from a group of 128 rabbits form the basis of the analysis. These animals represent three entire series that had been used for the purposes of other experiments at various times, all, however, conducted under carefully controlled uniform conditions. The indices of malignancy of these animals were analyzed by means of graphs, in which individual values are preserved while at the same time investigation of mass behavior is permitted. From this analysis it is concluded (1) that the severity of the disease as a whole is very irregular among individuals of a series and from series to series, and (2) that the relationship between the extent of the primary lesions and that of the secondary lesions is inconstant among individuals but assumes definite proportions when the data are viewed in the mass. For the mass proportion between the two phases of the disease is predominatingly a direct one, but in certain small groups of seriously affected rabbits the proportion shows a tendency to reversal, while, in addition, there occurs a reduction in the rate of growth of the primary tumor, which reduction, together with the reversal in relationship, appears to be more pronounced from series to series as malignancy increases. An attempt has been made to account for these results in the light of what has been ascertained of the modes of defense of the rabbit host against the inroads of the cells of this transplanted tumor.
Ethical issues raised by common copy number variants and single nucleotide polymorphisms of certain and uncertain significance in general medical practice
Authors: Arthur L Beaudet
Journal: Genome Medicine (2010)

The ethical issues surrounding genotyping for single nucleotide polymorphisms (SNPs) or for copy number variation (CNV) are very different. SNP genotyping can focus on ancestry, risk probability, single gene diagnosis, pharmacogenetics, and carrier testing, and the combination of these in a single test can present difficulties. The interpretation of such tests, inconsistencies between laboratories, and access to genotype information for future reference need to be considered, as well as the value of genotypes of known clinical significance compared with those that provide modest risk modifications with limited potential to take medically useful steps. For CNV genotyping, the major concerns relate to CNVs of uncertain significance and to those with incomplete penetrance. Such CNVs present acute difficulties in counseling symptomatic and asymptomatic individuals and have substantial potential for stigmatization of both groups, as well as raising difficulties when detected in prenatal diagnosis. Improved prenatal diagnosis of many disorders provided by array tests compared with the traditional karyotype probably outweighs the uncertainties for families who would terminate pregnancies with findings associated with severe disabilities. There are substantive concerns about offering SNP or CNV genotyping direct to consumers without a physician or counselor to provide guidance for interpretation of the results.
“The wise, for cure, on exercise depend”: physical activity interventions in primary care in Wales
Authors: N H Williams
Journal: British Journal of Sports Medicine (2008)

Physical inactivity is an important public health problem, which could be addressed by health promotion initiatives in primary care. The interventions most widely available to primary care clinicians are advice/counselling and exercise referral. A review of four systematic reviews found that brief advice from a general practitioner, supported by written materials, has a modest short-term effect on physical activity lasting 6-12 months. Exercise referral schemes have been introduced throughout Wales and the rest of the UK. A systematic review and meta-analysis found that such schemes resulted in a statistically significant increase in the proportion of sedentary people becoming moderately active, but the absolute risk reduction was small, with 17 sedentary people needing to be referred for one to become moderately active. This small effect size could partly be explained by poor rates of uptake and adherence and was not likely to be an efficient use of resources. These findings were in concordance with the guidance from the National Institute for Health and Clinical Excellence, which states that schemes should only be recommended if they are part of a properly designed and controlled research study. Since 2007, a national exercise referral scheme is being rolled out throughout Wales in three phases, and is being evaluated in a pragmatic randomised controlled trial comparing exercise referral with an advice booklet.
Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma
Authors: Antonio Palumbo, Francesca Gay, Federica Cavallo, Francesco Di Raimondo, Alessandra Larocca, Izhar Hardan, Arnon Nagler, Maria T. Petrucci, Roman Hajek, Sara Pezzatti, Michel Delforge, Francesca Patriarca, Francesca Donato, Chiara Cerrato, Chiara Nozzoli, Zhinuan Yu, Luana Boccadifuoco, Tommaso Caravita, Giulia Benevolo, Tommasina Guglielmelli, Donatella Vincelli, Christian Jacques, Meletios A. Dimopoulos, Giovannino Ciccone, Pellegrino Musto, Paolo Corradini, Michele Cavo, Mario Boccadoro
Journal: Journal of Clinical Oncology (2015)

Purpose Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent–based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. Methods We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent–based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. Results In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P &lt; .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P &lt; .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). Conclusion In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials.
NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations
Authors: Yi-Ping Fu, Hege Edvardsen, Alpana Kaushiva, Juan P Arhancet, Tiffany M Howe, Indu Kohaar, Patricia Porter-Gill, Anushi Shah, Hege Landmark-Høyvik, Sophie D Fosså, Stefan Ambs, Bjørn Naume, Anne-Lise Børresen-Dale, Vessela N Kristensen, Ludmila Prokunina-Olsson
Journal: Molecular Cancer (2010)

Abstract Background A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER) + versus ER - cancer. Results We found association between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of NOTCH2 was found to be lowest in tumors with TP53 mutations and highest in TP53 wild-type/ER + tumors (p = 0.0059). In the latter group, the NOTCH2 expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between NOTCH2 expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of NOTCH2 , a truncated version of NOTCH2 consisting of only the extracellular domain. Conclusion This is the first study to show that the expression of NOTCH2 differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER + luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER + luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development.
Changes of serum 7S fragment of type IV collagen andN-terminal propeptide of type III procollagen after transcatheter arterial embolization as a model of acute liver injury
Authors: Takeaki Suou, Sadako Yamada, Junko Kobayashi, Ushio Hoshino, Eiji Nishimuki, Hironaka Kawasaki
Journal: Hepatology (1993)

To evaluate the mechanism of increased serum concentrations of the N-terminal propeptide of type III procollagen and the 7S fragment of type IV collagen in acute liver injury, we serially measured serum levels of these substances after transcatheter arterial embolization in patients with hepatocellular carcinoma. The results demonstrated marked increases in serum levels of the 7S fragment of type IV collagen in accordance with increased serum levels of transaminase after transcatheter arterial embolization. In contrast, a transient decrease in serum levels of the N-terminal propeptide of type III procollagen was found after transcatheter arterial embolization and transcatheter arterial infusion, although no significant changes in serum levels of the N-terminal propeptide and 7S fragment were seen after hepatic arteriography alone. The absolute change in serum levels of the 7S fragment after treatment showed positive correlation with serum transaminase levels and negative correlation with the decrease in serum levels of alpha-fetoprotein, although serum levels of N-terminal peptide did not demonstrate such a correlation. The results suggest that in acute liver injury induced by transcatheter arterial embolization, at least in part, increased in serum levels of the 7S fragment of type IV collagen reflect accelerated liberation of type IV collagen from the destroyed surrounding nontumorous tissues and that decreased serum N-terminal propeptide of type III procollagen reflects diminished synthesis of type III collagen caused by anticancer drugs.