tbuckley/cabot-search huggingface dataset:
Brain tumor cell line authentication, an efficient alternative to capillary electrophoresis by using a microfluidics-based system
Authors: Q. An, H. L. Fillmore, M. Vouri, G. J. Pilkington
Journal: Neuro-Oncology (2013)

The current method for cell line authentication is genotyping based on short tandem repeat (STR)–PCR involving coamplification of a panel of STR loci by multiplex PCR and downstream fragment length analysis (FLA), usually performed by capillary electrophoresis. FLA by capillary electrophoresis is time-consuming and can be expensive, as the facilities are generally not accessible for many research laboratories. In the present study, a microfluidic electrophoresis system, the Agilent 2100 Bioanalyzer, was used to analyze the STR-PCR fragments from 10 human genomic loci of a number of human cell lines, including 6 gliomas, 1 astrocyte, 1 primary lung cancer, 1 lung brain metastatic cancer, and 1 rhabdomyosarcoma; and this was compared with the standard method, that is, capillary electrophoresis, using the Applied Biosystems 3130xl Genetic Analyzer. The microfluidic electrophoresis method produced highly reproducible results with good sensitivity in sizing of multiple PCR fragments, and each cell line demonstrated a unique DNA profile. Furthermore, DNA fingerprinting of samples from 5 different passage numbers of the same cell line showed excellent reproducibility when FLA was performed with the Bioanalyzer, indicating that no cross-contamination had occurred during the culture period. This novel application provides a straightforward and cost-effective alternative to STR-based cell line authentication. In addition, this application would be of great value for cell bank repositories to maintain and distribute precious cell lines.
The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma: Table 1
Authors: Padmaja Subbarao, Sonia S Anand, Allan B Becker, A Dean Befus, Michael Brauer, Jeffrey R Brook, Judah A Denburg, Kent T HayGlass, Michael S Kobor, Tobias R Kollmann, Anita L Kozyrskyj, W Y Wendy Lou, Piushkumar J Mandhane, Gregory E Miller, Theo J Moraes, Peter D Pare, James A Scott, Tim K Takaro, Stuart E Turvey, Joanne M Duncan, Diana L Lefebvre, Malcolm R Sears
Journal: Thorax (2015)

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.
Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children.
Authors: D J Keeley, P Neill, S Gallivan
Journal: Thorax (1991)

The prevalence of reversible airways obstruction has been assessed in children in three areas in Zimbabwe--northern Harare (high socioeconomic class urban children), southern Harare (low socio-economic class urban children), and Wedza Communal Land (rural children from peasant families). Peak expiratory flow (PEF) was measured before and after six minutes9 free running in 2055 Zimbabwean primary school children aged 7-9 years. Height and weight were measured and nutritional state expressed as a percentage of the 50th centile for age (Tanner-Whitehouse standards). Reversible airways obstruction was deemed to be present when peak expiratory flow was below the 2.5th centile for height before exercise and rose by more than 15% after inhalation of salbutamol and when it fell by 15% or more after exercise and rose again after salbutamol. The prevalence of reversible airways obstruction was 5.8% (95% confidence interval 4.1-7.5%) in northern Harare (n = 726); 3.1% (1.8-4.5%) in southern Harare (n = 642), and 0.1% (0.0-0.4%) in Wedza (n = 687). In northern Harare, the only study area in which white children were found, the prevalence of reversible airways obstruction was similar in white (5.3%, 10/188) and black (5.9%, 32/538) children. Indicators of nutritional state also showed no significant differences between white and black children in northern Harare but were lower in southern Harare and lower still in Wedza. Urban living and higher material standards of living appear to be associated with a higher prevalence of reversible airways obstruction in children in Zimbabwe.
Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: A mature follow-up report
Authors: S. Fetscher, W. Brugger, R. Engelhardt, L. Kanz, J. Hasse, H. Frommhold, W. Lange, R. Mertelsmann
Journal: Annals of Oncology (1999)

We conducted a phase I-II trial to assess the activity of standard-dose (SDC) and high-dose chemotherapy (HDC) with etoposide, ifosfamide, cis/carboplatin, and epirubicin (VIP-E, VIC-E) in 107 patients with limited-stage (LS, stage I-IIIB) and extensive stage (ES, stage IV) non-small-cell lung cancer (NSCLC).Updated results of a previously published trial are presented.Response rates and survival after VIP-E were comparable to those of other standard-dose combination chemotherapies in NSCLC. Treatment-related mortality (TRM) in SDC was 3% in LS-NSCLC, and 8% in ES-NSCLC. TRM was 4% in patients selected for HDC by response rate and performance score. Five-year survival in LS-NSCLC was 12% after SDC, and 18% after HDC; it was 0% for both treatment protocols in ES-NSCLC.The activity of VIP-E SDC and VIC-E HDC is not superior to that of established protocols in the treatment of NSCLC. In view of the toxicity and TRM associated with this protocol, less aggressive regimens should be preferred for most patients. Whether selected patients with chemosensitive disease could benefit from VIP-E SDC and/or VIC-E HDC in an adjuvant or neo-adjuvant setting could not be determined within the scope of this study.
High frequency of t(14;18) translocation in salivary gland lymphomas from Sjögren's syndrome patients.
Authors: E K Pisa, P Pisa, H I Kang, R I Fox
Journal: The Journal of Experimental Medicine (1991)

Sjögren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands. These patients have a markedly increased frequency of developing non-Hodgkin's lymphoma in their salivary glands and cervical lymph nodes. Translocations of proto-oncogene bcl-2 t(14;18) were observed in five of seven SS-associated lymphomas by Southern blot analysis. Using primers specific for chromosomes 14 and 18, translocation of the proto-oncogene bcl-2 was detected by polymerase chain reaction (PCR) in all five lymphomas positive by Southern blot analysis. Among SS patients lacking clinical evidence of coexistent lymphoma, no bcl-2 translocations were detected in 50 consecutive salivary gland biopsies. Of particular interest, pre-lymphoma biopsies were available from the seven SS patients who subsequently developed lymphoma and these DNA samples lacked detectable t(14;18) translocations even though they exhibited oligoclonal rearrangements of their immunoglobulin genes. We conclude that the great sensitivity of PCR can help us in detecting early onset of lymphoma in SS patients and aid in understanding the transition from autoimmunity to lymphoma.
Studies of Spondylolysis found among weightlifters
Authors: Paul T. Kotani, N. Ichikawa, W. Wakabayashi, T. Yoshii, M. Koshimune
Journal: British Journal of Sports Medicine (1971)

Lumbago will interfere with the daily activities of most people, even athletes.Low back pain is a not un- O"" S1 S 0 common complaint in those who are participating in active membership of some kind of sport, the exact lesion depending upon the type of sport.In particular almost all weightlifters have experienced or have been suffering from low back pain as they continue their athletic activities.A great number of weightlifters were found to have a complaint of low back pain, especially at the time of taking some particular position, i.e. shift- ing the motion of clean action, or before and after press action in lifting the weight.Sportsmen holding active membership in weight lifting, were examined concerning an episode of low back pain and physical and radiological examinations revealed significant abnormalities of lumbar spine.Among those cases checked clinically, 8 out of 26 weightlifters were found to have spondylolysis.Interest- ingly, most of them have not been handicapped in their activities by low back pain, regardless of whether they were demonstrating spondylolysis or not.However, this high incidence of spondylolysis, being 30.7%, among weightlifters seems to require much more exact in- vestigations.
APP-BP1 inhibits Abeta42 levels by interacting with Presenilin-1.
Authors: Yuzhi Chen, Angela M Bodles, Donna L McPhie, Rachael L Neve, Robert E Mrak, W Sue T Griffin
Journal: Molecular Neurodegeneration (2007)

The beta-amyloid precursor protein (APP) is sequentially cleaved by the beta- and then gamma-secretase to generate the amyloid beta-peptides Abeta40 and Abeta42. Increased Abeta42/Abeta40 ratios trigger amyloid plaque formations in Alzheimer's disease (AD). APP binds to APP-BP1, but the biological consequence is not well understood. We report that when the endogenous APP-BP1 was suppressed by small interfering RNAs (siRNAs), cell-associated Abeta42 was dramatically increased in APP695 expressing primary neurons. The accumulation of Abeta42 was accompanied by significant increases in APP and APP-CTF in APP-BP1 siRNA expressing neurons. In contrast, APP-BP1 overexpression in primary neurons significantly decreased the levels of Abeta and endogenous APP but not APLPs. We also investigated the potential mechanism of APP-BP1-mediated APP processing. APP-BP1 co-precipitated with Presenilin-1 (PS1) in native rat brain extracts, co-migrated with the gamma-secretase components in brain membrane extracts in glycerol gradient centrifugation, and colocalized in primary neurons. Further, the endogenous PS1-CTF was significantly downregulated by APP-BP1 expression. Our data suggest that APP-BP1 may inhibit Abeta42 production by interacting with PS1 under physiological conditions.
Use of caffeinated substances and risk of crashes in long distance drivers of commercial vehicles: case-control study
Authors: L. N. Sharwood, J. Elkington, L. Meuleners, R. Ivers, S. Boufous, M. Stevenson
Journal: BMJ (2013)

<b>Objective</b> To determine whether there is an association between use of substances that contain caffeine and the risk of crash in long distance commercial vehicle drivers. <b>Design</b> Case-control study. <b>Setting</b> New South Wales (NSW) and Western Australia (WA), Australia. <b>Participants</b> 530 long distance drivers of commercial vehicles who were recently involved in a crash attended by police (cases) and 517 control drivers who had not had a crash while driving a commercial vehicle in the past 12 months. <b>Main outcome measure</b> The likelihood of a crash associated with the use of substances containing caffeine after adjustment for factors including age, health disorders, sleep patterns, and symptoms of sleep disorders as well as exposures such as kilometres driven, hours slept, breaks taken, and night driving schedules. <b>Results</b> Forty three percent of drivers reported consuming substances containing caffeine, such as tea, coffee, caffeine tablets, or energy drinks for the express purpose of staying awake. Only 3% reported using illegal stimulants such as amphetamine (“speed”); 3,4 methylenedioxymethamphetamine (ecstasy); and cocaine. After adjustment for potential confounders, drivers who consumed caffeinated substances for this purpose had a 63% reduced likelihood of crashing (odds ratio 0.37, 95% confidence interval 0.27 to 0.50) compared with drivers who did not take caffeinated substances. <b>Conclusions</b> Caffeinated substances are associated with a reduced risk of crashing for long distance commercial motor vehicle drivers. While comprehensive mandated strategies for fatigue management remain a priority, the use of caffeinated substances could be a useful adjunct strategy in the maintenance of alertness while driving.
Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease
Authors: P W Lowry
Journal: Gut (2001)

<h3>BACKGROUND</h3> Measurement of 6-thioguanine nucleotide concentrations may be useful for optimising treatment with azathioprine and 6-mercaptopurine. <h3>METHODS</h3> We conducted a study of 170 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between 6-thioguanine nucleotide concentrations and both disease activity, as measured by the inflammatory bowel disease questionnaire (active disease &lt;170, remission ⩾170) and leucopenia. Blood was submitted for whole blood 6-thioguanine nucleotide concentration and leucocyte count. <h3>RESULTS</h3> Mean (SD) inflammatory bowel disease questionnaire score was 176 (32). There was no correlation between inflammatory bowel disease questionnaire scores and 6-thioguanine nucleotide concentrations (<i>r</i><sub>s</sub>=−0.09, p=0.24). Median 6-thioguanine nucleotide concentrations in 56 patients with active disease and 114 patients in remission were similar (139<i>v </i>131 pmol/8×10<sup>8</sup> red blood cells; p=0.26). There was no correlation between 6-thioguanine nucleotide concentrations and leucocyte counts. <h3>CONCLUSIONS</h3> In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, 6-thioguanine nucleotide concentrations did not correlate with disease activity, as measured by the inflammatory bowel disease questionnaire, or leucocyte count. These findings are discrepant with most previous studies, possibly due to selection of responding patients who tolerated the medications. A prospective, randomised, dose optimisation trial using 6-thioguanine nucleotide concentrations is warranted.
Epidemiologists and Diabetologists
Authors: Harry R Keen
Journal: Diabetes Care (1981)

We deeply appreciate their contributions, and will continue to call on them as ad hoc reviewers.As we begin our fourth year of publication, we do so with the knowledge that losses during conception, gestation, and the neonatal period occur at higher rates than in later life.Yet, as we move through childhood, we recognize that we still lack the maturity of more established publications.Still in the growth phase, we remain open to molding.We are willing to be flexible and experiment with ideas and features that older journals will not try.Your critiques are essential to our knowing whether these experiments are worthwhile.More important, however, is the continuing support of you, our readership, and of our advertisers, which combine to make possible this venture we call DIABETES CARE.
Unrelated Donor Bone Marrow Transplantation for Children With Acute Myeloid Leukemia Beyond First Remission or Refractory to Chemotherapy
Authors: Nancy J. Bunin, Stella M. Davies, Richard Aplenc, Bruce M. Camitta, Kenneth B. DeSantes, Rakesh K. Goyal, Neena Kapoor, Nancy A. Kernan, Joseph Rosenthal, Franklin O. Smith, Mary Eapen
Journal: Journal of Clinical Oncology (2008)

Purpose Identify prognostic factors that influence outcome after unrelated donor bone marrow transplantation in children with acute myeloid leukemia (AML). Patients and Methods Included are 268 patients (age ≤ 18 years) with AML in second complete remission (n = 142), relapse (n = 90), or primary induction failure (n = 36) at transplantation. All patients received bone marrow grafts from an unrelated donor and a myeloablative conditioning regimen. Cox regression models were constructed to identify risk factors that influence outcome after transplantation. Results In this analysis, the only risk factor that predicted leukemia recurrence and overall and leukemia-free survival was disease status at transplantation. The 5-year probabilities of leukemia-free survival were 45%, 20%, and 12% for patients who underwent transplantation at second complete remission, relapse, and primary induction failure, respectively. As expected, risk of acute but not chronic graft-versus-host disease (GVHD) was lower with T-cell–depleted bone marrow grafts; T-cell–depleted grafts were not associated with higher risks of leukemia recurrence. We observed similar risks of leukemia relapse in patients with and without acute and chronic GVHD. Conclusion Children who underwent transplantation in remission had a superior outcome compared with children who underwent transplantation during relapse or persistent disease. Nevertheless, 20% of children who underwent transplantation in relapse are long-term survivors, suggesting that unrelated donor bone marrow transplantation is an effective therapy in a significant proportion of children with recurrent or primary refractory AML.
SOX9 Is Expressed in Human Fetal Prostate Epithelium and Enhances Prostate Cancer Invasion
Authors: Hongyun Wang, Irwin Leav, Soichiro Ibaragi, Michael Wegner, Guo-fu Hu, Michael L. Lu, Steven P. Balk, Xin Yuan
Journal: Cancer Research (2008)

Abstract SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and was β-catenin regulated. Here we report additional in vivo results showing that SOX9 is highly expressed during fetal prostate development by epithelial cells expanding into the mesenchyme, suggesting it may contribute to invasive growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced growth, angiogenesis, and invasion. Conversely, short hairpin RNA–mediated SOX9 suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results support important functions of SOX9 in both the development and maintenance of normal prostate, and indicate that these functions contribute to PCa tumor growth and invasion. [Cancer Res 2008;68(6):1625–30]
An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study
Authors: G. S. Collins, D. G. Altman
Journal: BMJ (2010)

<b>Objective</b> To evaluate the performance of the QRISK2 score for predicting 10-year cardiovascular disease in an independent UK cohort of patients from general practice records and to compare it with the NICE version of the Framingham equation and QRISK1. <b>Design</b> Prospective cohort study to validate a cardiovascular risk score. <b>Setting</b> 365 practices from United Kingdom contributing to The Health Improvement Network (THIN) database. <b>Participants</b> 1.58 million patients registered with a general practice between 1 January 1993 and 20 June 2008, aged 35-74 years (9.4 million person years) with 71 465 cardiovascular events. <b>Main outcome measures</b> First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic stroke) recorded in general practice records. <b>Results</b> QRISK2 offered improved prediction of a patient's 10-year risk of cardiovascular disease over the NICE version of the Framingham equation. Discrimination and calibration statistics were better with QRISK2. QRISK2 explained 33% of the variation in men and 40% for women, compared with 29% and 34% respectively for the NICE Framingham and 32% and 38% respectively for QRISK1. The incidence rate of cardiovascular events (per 1000 person years) among men in the high risk group was 27.8 (95% CI 27.4 to 28.2) with QRISK2, 21.9 (21.6 to 22.2) with NICE Framingham, and 24.8 (22.8 to 26.9) with QRISK1. Similarly, the incidence rate of cardiovascular events (per 1000 person years) among women in the high risk group was 24.3 (23.8 to 24.9) with QRISK2, 20.6 (20.1 to 21.0) with NICE Framingham, and 21.8 (18.9 to 24.6) with QRISK1. <b>Conclusions</b> QRISK2 is more accurate in identifying a high risk population for cardiovascular disease in the United Kingdom than the NICE version of the Framingham equation. Differences in performance between QRISK2 and QRISK1 were marginal.
Primary Cutaneous B-Cell Lymphoma
Authors: Lynn D. Wilson, Benjamin D. Smith
Journal: Journal of Clinical Oncology (2006)

proliferating endothelial cells were considered more sensitive to this agent than resting endothelial cells.We therefore selected a panendothelial marker, CD146, and used magnetic beads conjugated to an anti-CD146 antibody as the assay of choice to quantify the CEC. 2 In contrast to what Shaked et al suggest in their letter, this assay allowed us to select for viable cells and to exclude dead or apoptotic cells. 3This method makes it likely that these cells were recently released into the circulation.Moreover, the size assessment allowed an additional discrimination with other circulating mononuclear cells.The purpose of our exploratory analysis was to correlate treatment of ZD6126 with an increase in CD146 positive cells.We found that there was a temporal relationship between peak levels of ZD6126 and the subsequent increase in CEC.This finding suggests that ZD6126 has a direct effect on the vasculature.The observed cardiovascular adverse effects are in line with this assumption.However, using this assay we cannot exclude the contribution of other cell types or EPC to the observed increase in cell numbers.Our exploratory analysis provides a basis to study the increase in CEC during treatment with vascular targeting agents in more detail.We agree with Shaked et al that in future studies specific attention should be given to the origin of these cells.Because the magnetic bead assay is laborious, flow cytometry may be the preferred assay to measure CEC/EPC.Finally, it is important to realize that the value of CEC or EPC as a prognostic marker can only be determined in randomized controlled trials.
Disruption of Protein Kinase A Regulation Causes Immortalization and Dysregulation of D-Type Cyclins
Authors: Kiran S. Nadella, Lawrence S. Kirschner
Journal: Cancer Research (2005)

Abstract Phosphorylation is a key event in cell cycle control, and dysregulation of this process is observed in many tumors, including those associated with specific inherited neoplasia syndromes. We have shown previously that patients with the autosomal dominant tumor predisposition Carney complex carry inactivating mutations in the PRKAR1A gene, which encodes the type 1A regulatory subunit of protein kinase A (PKA), the cyclic AMP–dependent protein kinase. This defect was associated with dysregulation of PKA signaling, and genetic analysis has suggested that complete loss of the gene may be required for tumorigenesis. To determine the mechanism by which dysregulation of PKA causes tumor formation, we generated in vitro primary mouse cells lacking the Prkar1a protein. We report that this genetic disruption of PKA regulation causes constitutive PKA activation and immortalization of primary mouse embryonic fibroblasts (MEFs). At the molecular level, knockout of Prkar1a leads to up-regulation of D-type cyclins, and this increase occurs independently of other pathways known to increase cyclin D levels. Despite the immortalized phenotype, known mediators of cellular senescence (e.g., p53 and p19ARF) seem to remain intact in Prkar1a−/− MEFs. Mechanistically, cyclin D1 mRNA levels are not altered in the knockout cells, but protein half-life is markedly increased. Using this model, we provide the first direct genetic evidence that dysregulation of PKA promotes important steps in tumorigenesis, and that cyclin D1 is an essential target of PKA.