tbuckley/cabot-search huggingface dataset:
Impact of different hypopnea definitions on predictive accuracy of apnea hypopnea index for coronary artery calcification
Authors: Leong Chai Leow, Lohendran Baskaran, Swee Yaw Tan, Thun How Ong
Journal: European Respiratory Journal (2014)

Obstructive Sleep Apnea(OSA) is associated with cardiovascular disease(CVD). The change in hypopnea definition from a 4% to a 3% desaturation criteria in the 2012 American Academy of Sleep Medicine (AASM) scoring update have resulted in marked increases in Apnea Hypopnea Indices (AHI) and led to concerns about over diagnosis. It is unclear which scoring criterion is more accurate in predicting underlying cardiovascular risk.  We explored the relationship between coronary artery calcification and AHI obtained using the 2012 AASM 3% desaturation criteria(AHI 2012 ) when compared to the 2007 AASM 4% desaturation criteria(AHI 2007 ) for hypopneas.  Patients with no known CVD who were diagnosed with OSA(AHI 2007 >5) from a level 1 polysomnography (PSG) received a non-contrast cardiac CT. PSGs were scored using the 2007 AASM criteria then rescored using the 2012 AASM criteria in a blinded manner, and their association with coronary artery calcium scores (CAC) were compared.  81 patients participated with a median age of 50. Median AHI 2007  was 27.8 and median AHI 2012  was 36.9. CAC scores were less than 11, 11-400 and more than 400 in 62%, 33% and 5% of the cohort respectively. AHI 2012  correlated with high CAC score >400, (rho 0.24, p=0.03) but not AHI 2007  (rho 0.20, p=0.07). Comparison by ROC curve analysis showed no significant differences in predictive accuracy of the AHI 2007  compared to AHI 2012  for high CAC >400 (c statistic 0.77  versus  0.82, p=0.24)  In this prospective cohort study of OSA patients with no known CVD, AHI 2012  correlated better with high CAC score>400 compared to AHI 2007 , but the predictive accuracies of AHI 2007  and AHI 2012  for high CAC scores were similar.
Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey
Authors: O. N. Gill, Y. Spencer, A. Richard-Loendt, C. Kelly, R. Dabaghian, L. Boyes, J. Linehan, M. Simmons, P. Webb, P. Bellerby, N. Andrews, D. A. Hilton, J. W. Ironside, J. Beck, M. Poulter, S. Mead, S. Brandner
Journal: BMJ (2013)

<b>Objectives</b> To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments. <b>Design</b> Irreversibly unlinked and anonymised large scale survey of archived appendix samples. <b>Setting</b> Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey. <b>Sample</b> 32 441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP). <b>Results</b> Of the 32 441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million). The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled. Genetic testing of the positive specimens for the genotype at <i>PRNP</i> codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at <i>PRNP</i> codon 129. <b>Conclusions</b> This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date. These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.
ADAM15 Supports Prostate Cancer Metastasis by Modulating Tumor Cell–Endothelial Cell Interaction
Authors: Abdo J. Najy, Kathleen C. Day, Mark L. Day
Journal: Cancer Research (2008)

Abstract Using human tumor and cDNA microarray technology, we have recently shown that the ADAM15 disintegrin is significantly overexpressed during the metastatic progression of human prostate cancer. In the current study, we used lentiviral-based short hairpin RNA (shRNA) technology to down-regulate ADAM15 in the metastatic prostate cancer cell line, PC-3. ADAM15 down-regulation dramatically attenuated many of the malignant characteristics of PC-3 cells in vitro and prevented the s.c. growth of PC-3 cells in severe combined immunodeficient (SCID) mice. By inhibiting the expression of ADAM15 in PC-3 cells, we showed decreased cell migration and adhesion to specific extracellular matrix proteins. This was accompanied by a reduction in the cleavage of N-cadherin by ADAM15 at the cell surface. Fluorescence-activated cell sorting analysis revealed reduced cell surface expression of the metastasis-associated proteins αv integrin and CD44. Furthermore, matrix metalloproteinase 9 secretion and activity were abrogated in response to ADAM15 reduction. In an in vitro model of vascular invasion, loss of ADAM15 reduced PC-3 adhesion to, and migration through, vascular endothelial cell monolayers. Using an SCID mouse model of human prostate cancer metastasis, we found that the loss of ADAM15 significantly attenuated the metastatic spread of PC-3 cells to bone. Taken together, these data strongly support a functional role for ADAM15 in prostate tumor cell interaction with vascular endothelium and the metastatic progression of human prostate cancer. [Cancer Res 2008;68(4):1092–9]
Multiple Adaptive Mechanisms to Chronic Liver Disease Revealed at Early Stages of Liver Carcinogenesis in the Mdr2-Knockout Mice
Authors: Mark Katzenellenbogen, Orit Pappo, Hila Barash, Naama Klopstock, Lina Mizrahi, Devorah Olam, Jasmine Jacob-Hirsch, Ninette Amariglio, Gidi Rechavi, Leslie Ann Mitchell, Ron Kohen, Eytan Domany, Eithan Galun, Daniel Goldenberg
Journal: Cancer Research (2006)

Abstract Molecular events preceding the development of hepatocellular carcinoma were studied in the Mdr2-knockout (Mdr2-KO) mice. These mice lack the liver-specific P-glycoprotein responsible for phosphatidylcholine transport across the canalicular membrane. Portal inflammation ensues at an early age followed by hepatocellular carcinoma development after the age of 1 year. Liver tissue samples of Mdr2-KO mice in the early and late precancerous stages of liver disease were subjected to histologic, biochemical, and gene expression profiling analysis. In an early stage, multiple protective mechanisms were found, including induction of many anti-inflammatory and antioxidant genes and increase of total antioxidant capacity of liver tissue. Despite stimulation of hepatocyte DNA replication, their mitotic activity was blocked at this stage. In the late stage of the disease, although the total antioxidant capacity of liver tissue of Mdr2-KO mice was normal, and inflammation was less prominent, many protective genes remained overexpressed. Increased mitotic activity of hepatocytes resulted in multiple dysplastic nodules, some of them being steatotic. Expression of many genes regulating lipid and phospholipid metabolism was distorted, including up-regulation of choline kinase A, a known oncogene. Many other oncogenes, including cyclin D1, Jun, and some Ras homologues, were up-regulated in Mdr2-KO mice at both stages of liver disease. However, we found no increase of Ras activation. Our data suggest that some of the adaptive mechanisms induced in the early stages of hepatic disease, which protect the liver from injury, could have an effect in hepatocarcinogenesis at later stages of the disease in this hepatocellular carcinoma model. (Cancer Res 2006; 66(8): 4001-10)
IgM-PRODUCING TUMORS IN THE BALB/c MOUSE
Authors: Jan Andersson, Joel Buxbaum, Ronald Citronbaum, Steven Douglas, Luciana Forni, Fritz Melchers, Benvenuto Pernis, David Stott
Journal: The Journal of Experimental Medicine (1974)

Five adjuvant induced BALB/c tumors producing IgM-McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781-were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10-25-h stimulated normal B cells, 3469 cells resemble 20-35-h stimulated B cells, TEPC 183 cells resemble 45-65-h stimulated B cells, Y 5781 cells resemble 80-110-h stimulated B cells, and McPc 774 cells resemble 100-130-h stimulated B cells.
Ultrasound guided aspiration biopsy for pulmonary tuberculosis with unusual radiographic appearances.
Authors: A Yuan, P C Yang, D B Chang, C J Yu, L N Lee, H D Wu, S H Kuo, K T Luh
Journal: Thorax (1993)

Pulmonary tuberculosis can produce unusual radiographic appearances and negative results of sputum and bronchoscopic examinations are common. This study assessed the value of ultrasound guided aspiration biopsy in the diagnosis of pulmonary tuberculosis with unusual radiographic appearances.Thirteen patients, ultimately diagnosed as having tuberculosis, underwent a chest ultrasonographic examination between June 1984 and August 1991. All had sputum available for examination and nine were also examined by bronchoscopy. Ten patients who had a negative sputum smear and negative bronchoscopic brushing smears underwent ultrasound guided aspiration or biopsy. Percutaneous aspiration was performed with a 22 gauge needle. If the smear did not reveal acid fast bacilli, a biopsy sample was taken with a 16 gauge Tru-cut needle to obtain a histological diagnosis.The ultrasonographic examination delineated the more complex nature of the lesions better than the chest radiograph. Ultrasound guided aspiration biopsy provided the diagnosis in nine of 10 patients, while the sputum smear and culture provided diagnosis in five of 13, and bronchoscopy in four of nine. In terms of rapid diagnosis, ultrasound guided aspiration biopsy gave the diagnosis in eight of 10 cases. No patient developed a major complication.Ultrasonography can direct the needle to the most suitable part of a lesion to obtain the relevant specimens. The diagnostic yield is high and the procedure is relatively safe. It is especially helpful in patients with negative results of sputum and bronchoscopic examinations.
Geographical ancestry is a key determinant of epidermal morphology and dermal composition
Authors: A.K. Langton, M.J. Sherratt, W.I. Sellers, C.E.M. Griffiths, R.E.B. Watson
Journal: British Journal of Dermatology (2014)

Geographical ancestry plays a key role in determining the susceptibility of human skin to external insults and dermatological disease. Despite this, studies of skin from individuals of diverse geographical ancestry focus primarily on epidermal pigmentation. Few reports characterize the gross morphology and composition of the dermis and dermal-epidermal junction (DEJ).To characterize epidermal morphology and dermal composition in skin from individuals of diverse geographical ancestry.Immunohistochemical techniques were used to assess epidermal morphology and protein composition of the DEJ and dermal extracellular matrix in photoprotected skin from young African, Eurasian and Far East Asian individuals (n = 7 per group; age 18-30 years).The epidermis of African skin was thicker, with deeper rete ridges and a more convoluted DEJ than Eurasian and Far East Asian skin. Compared with Eurasians, protein composition of the DEJ was collagen VII poor in African and Far East Asian skin (P < 0·001 and P < 0·01, respectively); the dermis of African skin was enriched in fibrillar collagens (P < 0·05), but was relatively elastin poor (P < 0·05). African dermis was abundant in fibrillin-rich microfibrils and fibulin-5 (P < 0·001 and P < 0·001, respectively) compared with Eurasian and Far East Asian skin.We demonstrate that fundamental differences exist in skin structure and composition in individuals of diverse geographical ancestry. Disparate environmental pressures encountered by ancestral human populations living at different latitudes may have driven adaptations in skin structure and composition. Further research into the functional significance and clinical consequences of these differences is warranted.
Routine PET for early lung cancer
Authors: A. G Stewart
Journal: Thorax (2010)

direction of transfer of bacteria between the upper and lower airways".We therefore concluded in the abstract of our publication that "further longitudinal analyses and comparison with invasive methods are required".Such a longitudinal study is on the way with the first results being published at the recent European Cystic Fibrosis Conference. 1 However, we consider Dr Daniels' assumption that "in any patient with a 'colonised' lower airway, fomites from the lower airway will lodge within the nasopharynx" to be too simplistic.As shown in table 2 of our publication, numerous microbes preferentially resided in either the upper or the lower airways.In other words, the microbiota in these two compartments are distinct.The retrograde contamination of the nasal turbinates by expectorated bron-
Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction
Authors: Theophilus E. Owan, David O. Hodge, Regina M. Herges, Steven J. Jacobsen, Veronique L. Roger, Margaret M. Redfield
Journal: New England Journal of Medicine (2006)

The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period.
The inheritance of antibody V regions in the rabbit: linkage of an H-chain-specific idiotype to immunoglobulin allotypes.
Authors: M L Yarmush, J A Sogn, M Mudgett, T J Kindt
Journal: The Journal of Experimental Medicine (1977)

Anti-idiotype antibodies specific for the H chain of an homogeneous antistreptococcal antibody (4135 Ab) were prepared by injection of recombinant molecules consisting of the H chains from 4135 Ab and L chains isolated from the injected rabbit. The antibodies prepared in this fashion (anti-HId) were specific for the VH region of 4135 Ab. Using this preparation in an inhibition of binding assay, sera from rabbits related and unrelated to 4135 were screened for the presence of the 4135 HId. It was found that about 45% of the related rabbits, when immunized with streptococcal Group C vaccine, produced antibodies with a cross-reactive idiotype, while less than 10% of similarly immunized unrelated rabbits produced molecules bearing HId. The expression of HId was linked to the a3 allotype present in the H chain allogroup J. Antibody molecules bearing the HId determinant were isolated from heterozygous (a1a3 and a2a3) rabbits and shown to express the a3 allotype. One rabbit lacking the a3 allotype produced significant amounts of antibodies expressing HId. These antibodies were found to express both VH and CH allo-types characteristic of the J allogroup, although neither allotype was found in a preimmune IgG sample from this rabbit.
Estrogen Receptor–Binding Fragment–Associated Antigen 9 Is a Tumor-Promoting and Prognostic Factor for Renal Cell Carcinoma
Authors: Tetsuo Ogushi, Satoru Takahashi, Takumi Takeuchi, Tomohiko Urano, Kuniko Horie-Inoue, Jinpei Kumagai, Tadaichi Kitamura, Yasuyoshi Ouchi, Masami Muramatsu, Satoshi Inoue
Journal: Cancer Research (2005)

Abstract The estrogen receptor–binding fragment–associated antigen 9 (EBAG9) has been identified as a primary estrogen-responsive gene in human breast cancer MCF7 cells. A high expression of EBAG9 has been observed in invasive breast cancer and advanced prostate cancer, suggesting a tumor-promoting role of the protein in malignancies. Here we show that intratumoral (i.t.) administration of small interfering RNA against EBAG9 exerted overt regression of tumors following s.c. implantation of murine renal cell carcinoma (RCC) Renca cells. Overexpression of EBAG9 did not promote the proliferation of culture Renca cells; however, the inoculated Renca cells harboring EBAG9 (Renca-EBAG9) in BALB/c mice grew faster and developed larger tumors compared with Renca cells expressing vector alone (Renca-vector). After renal subcapsular implantation, Renca-EBAG9 tumors significantly enlarged compared with Renca-vector tumors in BALB/c mice, whereas both Renca-EBAG9 and Renca-vector tumors were developed with similar volumes in BALB/c nude mice. No apparent difference was observed in specific cytotoxic T-cell responses against Renca-EBAG9 and Renca-vector cells; nonetheless, the number of infiltrating CD8+ T lymphocytes was decreased in Renca-EBAG9 subcapsular tumors. Furthermore, immunohistochemical study of EBAG9 in 78 human RCC specimens showed that intense and diffuse cytoplasmic immunostaining was observed in 87% of the cases and positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients. Multivariate analysis revealed that high EBAG9 expression was an independent prognostic predictor for disease-specific survival (P = 0.0485). Our results suggest that EBAG9 is a crucial regulator of tumor progression and a potential prognostic marker for RCC.
Antidepressant Pharmacotherapy in the Treatment of Depression in the Very Old: A Randomized, Placebo-Controlled Trial
Authors: Steven P. Roose, Harold A. Sackeim, K. Ranga Rama Krishnan, Bruce G. Pollock, George Alexopoulos, Helen Lavretsky, Ira R. Katz, Heikki Hakkarainen
Journal: American Journal of Psychiatry (2004)

This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old."This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression.A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%).In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.
Is raised breath hydrogen related to the pathogenesis of pneumatosis coli?
Authors: N W Read, M N Al-Janabi, P A Cann
Journal: Gut (1984)

Clinical and physiological studies were carried out in five patients with pneumatosis coli in order to investigate the origin of the high fasting breath hydrogen concentration in this condition and to determine its possible significance in the pathogenesis of the disease. All five patients excreted abnormally high fasting concentrations of hydrogen in their breath (69 +/- 9 ppm, mean +/- SEM). Moreover, analysis of the contents of the gas filled cysts revealed between 2% and 8% of hydrogen gas. Colonic washout significantly reduced breath hydrogen concentrations to 9 +/- 6 ppm, but did not abolish the cysts. Conversely, deflation of the cysts was achieved with oxygen or antibiotics, though this only reduced breath hydrogen concentrations to about 66% of their original value. After feeding a radiolabelled meal, breath hydrogen concentrations rose before the meal appeared to reach the colon, suggesting overgrowth of anaerobic bacteria in the small intestine. Despite this, 14C glycocholate breath tests were within normal limits. An alternative possibility is that the high levels of hydrogen excreted in the breath may be produced in the intestinal lumen possibly from the fermentation of copious amounts of colonic mucus. Finally, measurement of whole gut transit time and stool weight suggested that patients were constipated despite passing mucus and blood. The relevance of our observations to the pathogenesis of submucosal cysts is unclear, but the data favour the hypothesis that these are produced by invasion of the colonic submucosa with anaerobic bacteria.
Phylogenetic relationships of bolitoglossine salamanders: a demonstration of the effects of combining morphological and molecular data sets
Authors: T. R. Jackman, G. Applebaum, D. B. Wake
Journal: Molecular Biology and Evolution (1997)

We analyzed sequence data for 555 bp of the mitochondrial gene cytochrome b in plethodontid salamanders, taken from 18 ingroup (tribe Bolitoglossini) and 4 outgroup (tribe Plethodontini) taxa. There were 257 variable sites, of which 219 were phylogenetically informative. Sequence differences among taxa exceeded 20%, and there were up to 15% amino acid differences among the sequences. We also analyzed 37 morphological (including karyological) characters, taken from the literature. Data were analyzed separately and then combined using parsimony and likelihood approaches. There is little conflict between the morphological and DNA data, and that which occurs is at nodes that are weakly supported by one or both of the data sets. Treated separately, the morphological and DNA data provide strong support for some nodes but not for others. The combined data act synergistically so that good support is obtained for nearly all of the nodes in the tree. Recent divergences are supported by silent transitions, and older divergences are supported by a combination of morphological, karyological, DNA transversion, and amino acid changes. Eliminating silent changes from the DNA data improves the consistency index and improves some bootstrap and decay index values for several deeper branches in the tree. However, the combined data set with all characters included provides a better supported tree overall. Maximum likelihood and parsimony with all of the data give not only the same topology but also remarkably similar branch lengths. Results of this analysis support the monopoly of the supergenera Hydromantes and Batrachoseps, and of a sister group relationship of Batrachoseps and the supergenus Bolitoglossa (represented in this study one species of the genus Bolitoglossa).
Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study
Authors: David W Dodick, Peter J Goadsby, Egilius L H Spierings, Joel C Scherer, Steven P Sweeney, David S Grayzel
Journal: The Lancet Neurology (2014)