tbuckley/cabot-search huggingface dataset:
Increased numbers of alveolar mast cells with an altered phenotype are linked to peripheral airway remodelling in patients with allergic asthma
Authors: Cecilia Andersson, Maria Weitoft Lundström, Anders Bergqvist, Michiko Mori, Leif Bjermer, Gunilla Westergren-Thorsson, Jonas Erjefält
Journal: European Respiratory Journal (2012)

BACKGROUND: A significant proportion of asthmatics have symptoms despite treatment with inhaled corticosteroids. Recent studies have revealed an expansion of highly FceRI-expressing alveolar mast cells (MCs) in asthma. The aims were to further phenotype alveolar MCs and explore their connection to peripheral tissue remodelling in different asthma cohorts.

METHODS: Bronchial and transbronchial biopsies from controls, patients with rhinitis, mild and uncontrolled asthma were processed for immunohistochemical identification of MC subtypes and expression of pro-fibrotic markers. MC alteration in relation to tissue remodelling (density of collagen, versican, decorin and biglycan) in peripheral lung was studied.

RESULTS: The alveolar parenchyma (AP) in uncontrolled asthmatics had increased densities of MCTC (p=0.05) and MCT (p=0.003). The expression of FceRI on alveolar MCs was increased in mild (p=0.01) and uncontrolled (p<0.001) asthma compared to controls. The density of collagen (p=0.01) and decorin (p=0.03) was significantly increased in AP of uncontrolled asthmatics compared to controls. The number of alveolar MCTC in the uncontrolled asthmatics was positively correlated to the density of collagen in the AP (rs=0.71, p=0.03). MCs in the AP of asthmatics expressed increased levels of pro-fibrotic markers.

CONCLUSIONS: Our data show that the alveolar region in patients with asthma is infiltrated by activated MCs that correlate to increased alveolar matrix deposition. This may reflect an important involvement of MCs in the peripheral inflammation in asthma and underscores the need to target peripheral lung inflammation in this patient group.
Lung folding simulating peripheral pulmonary neoplasm (Blesovsky's syndrome).
Authors: C R Payne, P Jaques, I H Kerr
Journal: Thorax (1980)

<b>Lloyd Davies, T. A., Doig, A. T., Fox, A. J., and Greenberg, M. (1973).</b><i>British Journal of Industrial Medicine,</i><b>30,</b> 227-231. <b>A radiographic survey of monumental masonry workers in Aberdeen.</b> A survey of radiographic appearances of the lungs of monumental masonry workers in Aberdeen was carried out to determine the present prevalence of abnormalities and to serve as a standard for future comparisons in view of changes in methods of working. No major change could be detected in the status of these granite workers in Aberdeen over the past 20 years but the different methods of survey used by Mair in 1951 and by the present study did not allow of strict comparison. Chest radiographs were reported on by three readers independently using the National Coal Board elaboration of the ILO classification and a score was given to each film using Oldham9s method. Multiple regression analysis showed that ϰ-ray changes were related to years in granite but progression was slow in comparison with foundry workers. The prevalence of radiographic appearances of category 1 or greater was 3·0% overall and 4·6% for workers in dusty jobs. Evidence of pneumoconiosis was not observed in workers exposed for less than 20 years. With the environmental control attained the threshold limit values for respirable dust were not often much exceeded.
Predictive value of automated oxygen saturation analysis for the diagnosis and treatment of obstructive sleep apnoea in a home-based setting
Authors: V Jobin, P Mayer, F Bellemare
Journal: Thorax (2007)

A portable monitor for the automated analysis of episodic nocturnal oxygen saturation or SpO(2) (the Remmers Sleep Recorder, RSR) has been proposed for the diagnosis of obstructive sleep apnoea-hypopnoea (OSAH). A study was undertaken to compare the diagnostic performance of automated analysis with the manual scoring of polygraphic data by a more comprehensive respiratory monitor (the Suzanne recorder) used simultaneously in their intended home environment.The respiratory disturbance indexes of the two monitors were compared in 94 consecutive adult patients suspected of having OSAH and who were deemed eligible for home-based investigation.The RSR overestimated the number of respiratory events associated with a >or=4% fall in SpO(2) by 13% (p<0.005) but underestimated the number of apnoeas and hypopnoeas defined on the basis of respiratory variables alone or their association with a >or=4% fall in SpO(2) or autonomic arousals by 38-48% (p<0.0001). In addition to these significant biases, the limits of agreement in all instances were wide, indicating a poor concurrence between the two monitors.The automated analysis of SpO(2) with the RSR cannot be substituted for the manual scoring of polygraphic data with the more comprehensive respiratory monitor in the diagnosis of OSAH in an ambulatory home-based setting.
Phylogenetic analysis of slippage-like sequence variation in the V4 rRNA expansion segment in tiger beetles (Cicindelidae)
Authors: A P Vogler, A Welsh, J M Hancock
Journal: Molecular Biology and Evolution (1997)

Sequence variation in the middle part of the small-subunit rRNA was studied for representatives of the major groups in the family Cicindelidae (Coleoptera). All taxa exhibited a much expanded segment in variable region V4 compared to D. melanogaster. This expanded segment was not found in other groups of beetles, including three taxa in the closely related Carabidae. Secondary structure predictions indicate that the expanded segment folds into a single stem-loop structure in all taxa. Despite its structural conservation, the fragment differs strongly in primary sequence, even between closely related sister taxa. Several features of these sequences are consistent with slippage replication as the mechanism that has generated this sequence variation: the level of internal sequence repetition as measured by the relative simplicity factor (RSF), its variation in length between close relatives, and the strong nucleotide bias compared to the remainder of the gene. With few exceptions, there was also a correlation between sequence length and the level of sequence repetition, frequently interpreted as the result of slippage. Phylogenies inferred from the expansion segment were not consistent with existing hypotheses from other molecular data for the group. This indicates that DNA sequences in this region are not homologous throughout the entire Cicindelidae, but it leaves open the possibility that this expansion segment can be used for phylogeny reconstruction within subgroups. The implications of a phylogenetic approach to the understanding of slippage-like evolution are discussed.
Detecting somatic point mutations in cancer genome sequencing data: a comparison of mutation callers
Authors: Qingguo Wang, Peilin Jia, Fei Li, Haiquan Chen, Hongbin Ji, Donald Hucks, Kimberly Dahlman, William Pao, Zhongming Zhao
Journal: Genome Medicine (2013)

Driven by high throughput next generation sequencing technologies and the pressing need to decipher cancer genomes, computational approaches for detecting somatic single nucleotide variants (sSNVs) have undergone dramatic improvements during the past 2 years. The recently developed tools typically compare a tumor sample directly with a matched normal sample at each variant locus in order to increase the accuracy of sSNV calling. These programs also address the detection of sSNVs at low allele frequencies, allowing for the study of tumor heterogeneity, cancer subclones, and mutation evolution in cancer development.We used whole genome sequencing (Illumina Genome Analyzer IIx platform) of a melanoma sample and matched blood, whole exome sequencing (Illumina HiSeq 2000 platform) of 18 lung tumor-normal pairs and seven lung cancer cell lines to evaluate six tools for sSNV detection: EBCall, JointSNVMix, MuTect, SomaticSniper, Strelka, and VarScan 2, with a focus on MuTect and VarScan 2, two widely used publicly available software tools. Default/suggested parameters were used to run these tools. The missense sSNVs detected in these samples were validated through PCR and direct sequencing of genomic DNA from the samples. We also simulated 10 tumor-normal pairs to explore the ability of these programs to detect low allelic-frequency sSNVs.Out of the 237 sSNVs successfully validated in our cancer samples, VarScan 2 and MuTect detected the most of any tools (that is, 204 and 192, respectively). MuTect identified 11 more low-coverage validated sSNVs than VarScan 2, but missed 11 more sSNVs with alternate alleles in normal samples than VarScan 2. When examining the false calls of each tool using 169 invalidated sSNVs, we observed >63% false calls detected in the lung cancer cell lines had alternate alleles in normal samples. Additionally, from our simulation data, VarScan 2 identified more sSNVs than other tools, while MuTect characterized most low allelic-fraction sSNVs.Our study explored the typical false-positive and false-negative detections that arise from the use of sSNV-calling tools. Our results suggest that despite recent progress, these tools have significant room for improvement, especially in the discrimination of low coverage/allelic-frequency sSNVs and sSNVs with alternate alleles in normal samples.
Psychological disorders in rheumatoid arthritis: a growing consensus?
Authors: F Creed
Journal: Annals of the Rheumatic Diseases (1990)

Beneficial management practices (BMPs), including nutrient management plans and reduced tillage, have been assessed at a subwatershed and watershed level to examine their impacts on nutrient export, economic opportunity cost, and producer incomes. In assessing nutrient effects on crop production, a crop-specific yield function was estimated. The linear and quadratic nitrogen (N) fertilizer terms were found to have correct signs, with a positive linear relationship, and were significant for major crops grown in the South Tobacco Creek (STC) Watershed. Crop response to phosphorus (P) occurred only for wheat (<i>Triticum aestivum</i> L.). Nutrient application rates within the STC Watershed were generally within provincial recommended rates; however, data shows an increasing trend in the application of N in wheat, canola (<i>Brassica napus</i> L.), barley (<i>Hordeum vulgare</i> L.), and oat (<i>Avena sativa</i> L.) production over course of the study. Nutrient export parameters at the field scale (4 to 5 ha [10 to 12 ac]), subwatershed scale (210 ha [519 ac]), and watershed scale (7,700 ha [19,000 ac]) were compared to production inputs. At the field scale, in a paired watershed study, N exported was not significantly related to the N applied. The relationships between P exported and P applied and conservation tillage management practices were statistically significant. At a larger subwatershed, the export of P from the subwatershed was significantly influenced by the volume of flow of water runoff and previous year P application. The export of N was only influenced by volume of flow but not by N application. For the STC Watershed, applied N did not affect N export. Assessment of P export found that the conversion to conservation tillage practices increased the P export. The opportunity value of the lost nutrients for the 210 ha (519 ac) subwatershed averaged about C$5.50 ha<sup>−1</sup> y<sup>−1</sup> (C$2.23 ac<sup>−1</sup> yr<sup>−1</sup>), while on the paired subwatershed, the average loss was C$4.50 ha<sup>−1</sup> y<sup>−1</sup> (C$1.82 ac<sup>−1</sup> yr<sup>−1</sup>) on a conventionally managed field and C$2.75 ha<sup>−1</sup> y<sup>−1</sup> (C$1.11 ac<sup>−1</sup> yr<sup>−1</sup>) on a field under reduced tillage. For the entire STC Watershed, the export of nutrients represented a loss of opportunity of C$6.80 ha<sup>−1</sup> y<sup>−1</sup> (C$2.75 ac<sup>−1</sup> yr<sup>−1</sup>) or about 7% of annual fertilizer cost. Assessment of STC manure-applied data on an annual basis shows that the hauling and application of hog manure from 1998 to 2006 was generally more expensive than the nutrient value of the manure; however, in recent years, due to the increase in the value of commercial nutrients, the nutrient value of hog manure exceeds the cost.
Treating stroke within 90 minutes improves outcome significantly, researchers find
Authors: A. O'Dowd
Journal: BMJ (2013)

Patients are much less likely to have lasting disability after a stroke if they are treated much sooner than the period recommended in current official guidelines, concludes a new European study.

The study, published online in Stroke ,1 the journal of the American Heart Association, found that patients who received thrombolysis within 90 minutes of experiencing mild or moderate stroke symptoms had a 37% better improvement rate than patients who were treated later (odds ratio 1.37 (95% confidence interval 1.11 to 1.7); P=0.004). These patients had little or no disability three months later in comparison with those who were treated between 90 and 270 minutes.

Each year in the United Kingdom around 150 000 people have …
Optimal Chemotherapy for High-Risk Early-Stage Breast Cancer
Authors: Carl D. Atkins
Journal: Journal of Clinical Oncology (2010)

Burnell et al 1 show that doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) is significantly inferior to cyclophosphamide, epirubicin, and fluorouracil (CEF) or dose-dense epirubicin and cyclophosphamide followed by paclitaxel (EC/T) in terms of relapse-free survival in node-positive and high-risk node-negative breast cancer.However, the toxicities of the regimens are quite different: AC/T had a febrile neutropenia rate of only 4.8%, whereas the rates for CEF and EC/T were 22.3% and 16.4%, respectively.Using the lower limits of the CIs calculated by the authors, we may determine that that the absolute improvement in relapse-free survival with the more aggressive regimens may be no more than 1% to 2% (the maximum benefit being 10% to 12%).To determine whether the excess toxicity is worthwhile, it would be helpful to know if it is modifiable.Of course, all patients treated with dose-dense EC/T received filgrastim, but the authors note that filgrastim use was permitted, not mandated, with CEF.Could the authors provide information on the percentage of patients treated with CEF who received filgrastim, as well as its effect on febrile neutropenia?If this was relatively low, the abrogation of febrile neutropenia by the routine addition of filgrastim or pegfilgrastim could make CEF the optimal regimen in this patient population.
Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin
Authors: E.G.V. EVANS, I.G.V. JAMES, R.A.J. SEAMAN, M.D. RICHARDSON
Journal: British Journal of Dermatology (1993)

In a multicentre, double-blind, randomized, parallel group study in general practice, 269 patients with clinically diagnosed fungal infection of the skin were treated with either naftifine (Exoderil) or 1% clotrimazole plus 1% hydrocortisone (CHC; Canesten HC) applied twice daily for 4 weeks. Only 115 patients were shown subsequently to have a fungal infection by laboratory tests; the others had inflammatory disease of unknown aetiology. In those with fungal disease, both treatments were equally effective in terms of mycological cure (negative microscopy and culture). Clinical results for all 265 patients showed no clinically identifiable difference between the two preparations in terms of resolution of the disease, indicating that naftifine does have anti-inflammatory activity at least equal to CHC. This study suggests that there is no clinical advantage in treating patients with clinically diagnosed fungal infection of the skin with an antimycotic/corticosteroid combination as opposed to naftifine alone.
Inhibition of the Notch-Hey1 Axis Blocks Embryonal Rhabdomyosarcoma Tumorigenesis
Authors: Brian C. Belyea, Sarasija Naini, Rex C. Bentley, Corinne M. Linardic
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role in other human cancers, we hypothesized that aberrant Notch signaling may contribute to RMS tumorigenesis and present novel therapeutic opportunities. Experimental Design: Human RMS cell lines and tumors were evaluated by immunoblot, IHC, and RT-PCR to measure Notch ligand, receptor, and target gene expression. Manipulation of Notch signaling was accomplished using genetic and pharmacologic approaches. In vitro cell growth, proliferation, and differentiation were assessed using colorimetric MTT and BrdU assays, and biochemical/morphologic changes after incubation in differentiation-promoting media, respectively. In vivo tumorigenesis was assessed using xenograft formation in SCID/beige mice. Results: Notch signaling is upregulated in human RMS cell lines and tumors compared with primary skeletal muscle, especially in the embryonal (eRMS) subtype. Inhibition of Notch signaling using Notch1 RNAi or γ-secretase inhibitors reduced eRMS cell proliferation in vitro. Hey1 RNAi phenocopied Notch1 loss and permitted modest myogenic differentiation, while overexpression of an activated Notch moiety, ICN1, promoted eRMS cell proliferation and rescued pharmacologic inhibition. Finally, Notch inhibition using RNAi or γ-secretase inhibitors blocked tumorigenesis in vivo. Conclusions: Aberrant Notch-Hey1 signaling contributes to eRMS by impeding differentiation and promoting proliferation. The efficacy of Notch pathway inhibition in vivo supports the development of Notch-Hey1 axis inhibitors in the treatment of eRMS. Clin Cancer Res; 17(23); 7324–36. ©2011 AACR.
Structure of a gene encoding a murine thymus leukemia antigen, and organization of Tla genes in the BALB/c mouse.
Authors: D A Fisher, S W Hunt, L Hood
Journal: The Journal of Experimental Medicine (1985)

We have determined the DNA sequence of a gene encoding a thymus leukemia (TL) antigen in the BALB/c mouse, and have more definitively mapped the cloned BALB/c Tla-region class I gene clusters. Analysis of the sequence shows that the Tla gene is less closely related to the H-2 genes than H-2 genes are to one another or to a Qa-2,3-region genes. The Tla gene, 17.3A, contains an apparent gene conversion. Comparison of the BALB/c Tla genes with those from C57BL shows that BALB/c has more Tla-region class I genes, and that one of the genes absent in C57BL is gene 17.3A.
Randomized Phase III Evaluation of Cisplatin Plus Fluorouracil Versus Cisplatin Plus Paclitaxel in Advanced Head and Neck Cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group
Authors: Michael K. Gibson, Yi Li, Barbara Murphy, Maha H.A. Hussain, Ronald C. DeConti, John Ensley, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2005)

Purpose To determine the response rate, survival and toxicity of infusional cisplatin plus fluorouracil (CF) versus cisplatin plus paclitaxel (CP) in patients with incurable squamous cell cancer of the head and neck, with the hypothesis that CP is superior. Patients and Methods Two hundred eighteen patients with locally advanced, recurrent, or metastatic disease were randomly assigned to CF (cisplatin 100 mg/m 2 day 1 and fluorouracil 1,000 mg/m 2 /24 hours by continuous intravenous infusion day 1 through 4) or CP (cisplatin 75 mg/m 2 day 1 and paclitaxel 175 mg/m 2 over 3 hours on day 1). Cycles were repeated every 3 weeks until progression or a minimum of 6 cycles with complete response or stable disease. The primary outcome was overall survival. Secondary outcomes included response rate and toxicity. Results No significant difference in overall survival or response rate was seen. Estimated median survival was 8.7 months in the CF group and 8.1 month in the CP group. Objective response rate (complete response plus partial response) was 27% in the CF group and 26% in the CP group. Toxicity was similar between groups, with the most frequent including myelosuppression, thrombocytopenia, anemia, nausea, vomiting, and stomatitis. A total of 12 deaths occurred (CF, seven; CP, five) during treatment; eight from infection, two from hemorrhage, one from cardiac causes and one from unknown causes. Gastrointestinal and hematologic toxicities were more common in the CF group, whereas neurotoxicity was equivalent between groups. Conclusion This phase III, randomized, multicenter trial showed no difference in survival between patients treated with CF or CP.
Local adipose tissue depots as cardiovascular risk factors
Authors: S THALMANN, C MEIER
Journal: Cardiovascular Research (2007)

Obesity is associated with increased cardiovascular morbidity and mortality. Although obesity-associated hypertension, dyslipidemia and insulin resistance account in part for this association, it becomes increasingly apparent that a systemic and local pro-inflammatory response of adipose tissue might also be a contributing factor. White adipose tissue (WAT) is a highly active organ secreting various peptides such as cytokines, chemokines and hormone-like proteins. Besides the visceral and subcutaneous depots, WAT is also found in the close vicinity of blood vessels (perivascular adipose tissue), where it secretes cytokines such as interleukin-1, tumor necrosis factor alpha, pro-atherogenic chemokines, and pro-angiogenic peptides. These factors appear to contribute directly to alterations of the function and structure of the vascular wall, including chronic inflammation, alterations of vascular tone, proliferation of smooth muscle cells, neo-angiogenesis and hence to the development of atherosclerosis and cardiovascular complications.
Association of HL-A 5 and immune responsiveness in vitro to streptococcal antigens.
Authors: L J Greenberg, E D Gray, E J Yunis
Journal: The Journal of Experimental Medicine (1975)

Lymphocytes, from randomly selected individuals having normal immune function, when incubated in vitro with varying concentrations of streptococcal antigens, responded in three ways: (a) response over the entire antigen concentration range, i.e., responders; (b) low response to only the highest antigen concentrations; and (c) no response at any antigen concentration. Frequency distribution analysis of these groups indicated that a significant association occurred between the ability to respond and HL-A 5.