tbuckley/cabot-search huggingface dataset:
Novel mouse mutants with primary cellular immunodeficiencies generated by genome-wide mutagenesis
Authors: Thilo Jakob, Gabriele V. Köllisch, Maike Howaldt, Mayte Bewersdorff, Birgit Rathkolb, Marcel L. Müller, Nadja Sandholzer, Lars Nitschke, Matthias Schiemann, Martin Mempel, Markus Ollert, Antonie Neubauer, Dian A. Soewarto, Elisabeth Kremmer, Johannes Ring, Heidrun Behrendt, Heinrich Flaswinkel
Journal: Journal of Allergy and Clinical Immunology (2007)
Operational definitions of asthma in studies on its aetiology
Authors: J. Pekkanen, J. Sunyer, J. M. Anto, P. Burney
Journal: European Respiratory Journal (2005)

The most popular way to define asthma based on questionnaires is to use definitions taken from cross-sectional international studies on asthma. These definitions may not, however, be optimal for future studies focusing on risk factors of asthma. The current authors, therefore, compared the performance of different operational definitions of asthma. The European Community Respiratory Health Study I was a cross-sectional study of 21,924 subjects aged between 25–44 yrs in 18 countries. Operational definitions of asthma compared included different combinations of symptoms of asthma and bronchial hyperresponsiveness. A continuous asthma score, ranging from 0–8, was defined as the sum of positive answers to eight main symptom questions. There was no threshold in the associations of asthma symptoms with severity or risk factors of asthma, which would have suggested a dichotomous definition of asthma. Using dichotomous definitions requiring the presence of several asthma symptoms strengthened associations with studied risk factors, and also increased the estimated specificity and positive predictive value. Using a continuous asthma score also improved the power of the analyses. In conclusion, dichotomous definitions of asthma yielding higher odds ratios are achieved by requiring positive responses to several questions on symptoms. However, symptoms of asthma are possibly best analysed as a continuous asthma score.
Vertical Evolution and Horizontal Transfer of CR1 Non-LTR Retrotransposons and Tc1/mariner DNA Transposons in Lepidoptera Species
Authors: Irina Sormacheva, Georgiy Smyshlyaev, Vladimir Mayorov, Alexander Blinov, Anton Novikov, Olga Novikova
Journal: Molecular Biology and Evolution (2012)

Horizontal transfer (HT) is a complex phenomenon usually used as an explanation of phylogenetic inconsistence, which cannot be interpreted in terms of vertical evolution. Most examples of HT of eukaryotic genes involve transposable elements. An intriguing feature of HT is that its frequency differs among transposable elements classes. Although HT is well known for DNA transposons and long terminal repeat (LTR) retrotransposons, non-LTR retrotransposons rarely undergo HT, and their phylogenies are largely congruent to those of their hosts. Previously, we described HT of CR1-like non-LTR retrotransposons between butterflies (Maculinea) and moths (Bombyx), which occurred less than 5 million years ago (Novikova O, Sliwinska E, Fet V, Settele J, Blinov A, Woyciechowski M. 2007. CR1 clade of non-LTR retrotransposons from Maculinea butterflies (Lepidoptera: Lycaenidae): evidence for recent horizontal transmission. BMC Evol Biol. 7:93). In this study, we continued to explore the diversity of CR1 non-LTR retrotransposons among lepidopterans providing additional evidences to support HT hypothesis. We also hypothesized that DNA transposons could be involved in HT of non-LTR retrotransposons. Thus, we performed analysis of one of the groups of DNA transposons, mariner-like DNA elements, as potential vectors for HT of non-LTR retrotransposons. Our results demonstrate multiple HTs between Maculinea and Bombyx genera. Although we did not find strong evidence for our hypothesis of the involvement of DNA transposons in HT of non-LTR retrotransposons, we demonstrated that recurrent and/or simultaneous flow of TEs took place between distantly related moths and butterflies.
Chronic necrotising pneumonia caused by Aspergillus niger.
Authors: J Wiggins, T J Clark, B Corrin
Journal: Thorax (1989)

A woman with asthma developed chronic necrotising semi-invasive pneumonia due to mixed Aspergillus niger and Candida albicans infection; though not severely immunosuppressed, she may have been predisposed by long term oral corticosteroid and recurrent oral antibiotic treatment. The diagnosis should be considered in patients with chronic airflow limitation who develop cavitating pneumonia.
Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase–positive anaplastic large cell lymphoma with tumor dissemination and relapse risk
Authors: Kamel Ait-Tahar, Christine Damm-Welk, Birgit Burkhardt, Martin Zimmermann, Wolfram Klapper, Alfred Reiter, Karen Pulford, Wilhelm Woessmann
Journal: Blood (2010)
Cricket fast bowling workload patterns as risk factors for tendon, muscle, bone and joint injuries
Authors: John W Orchard, Peter Blanch, Justin Paoloni, Alex Kountouris, Kevin Sims, Jessica J Orchard, Peter Brukner
Journal: British Journal of Sports Medicine (2015)

To assess workload-related risk factors for injuries to particular tissue types in cricket fast bowlers.235 fast bowlers who bowled in 14600 player innings over a period of 15 years were followed in a prospective cohort risk factor study to compare overs bowled in each match (including preceding workload patterns) and injury risk in the 3-4 weeks subsequent to the match. Injuries were categorised according to the affected tissue type as either: bone stress, tendon injuries, muscle strain or joint injuries. Workload risk factors were examined using binomial logistic regression multivariate analysis, with a forward stepwise procedure requiring a significance of <0.05.High acute match workload and high previous season workload were risk factors for tendon injuries, but high medium term (3-month workload) was protective. For bone stress injuries, high medium term workload and low career workload were risk factors. For joint injuries, high previous season and career workload were risk factors. There was little relationship between muscle injury and workload although high previous season workload was slightly protective.The level of injury risk for some tissue types varies in response to preceding fast bowling workload, with tendon injuries most affected by workload patterns. Workload planning may need to be individualised, depending on individual susceptibility to various injury types. This study supports the theory that tendons are at lowest risk with consistent workloads and susceptible to injury with sudden upgrades in workload. Gradual upgrades are recommended, particularly at the start of a bowler's career to reduce the risk of bone stress injury.
Low bone mineral density is present in newly diagnosed paediatric systemic lupus erythematosus patients
Authors: S. H. L. Lim, S. M. Benseler, P. N. Tyrrell, M. Charron, E. Harvey, D. Hebert, E. D. Silverman
Journal: Annals of the Rheumatic Diseases (2011)

The objectives of this study were to (1) determine the prevalence of low bone mineral density (BMD) in a large prospective cohort of newly diagnosed patients with paediatric systemic lupus erythematosus (pSLE) and (2) identify risk factors associated with low BMD.Single-centre cohort study of 80 children and adolescents who underwent a dual-energy x-ray absorptiometry within 3 months of diagnosis. Low lumbar spine (LS) BMD was defined as z score ≤ -2.0. BMD was correlated with baseline demographic, clinical and laboratory markers of disease activity and biochemical markers of bone health. Risk factors of BMD were evaluated with univariable and multivariable linear and logistic regression analyses.Low BMD at any site was found in 15% of newly diagnosed pSLE patients. LS BMD was associated with body mass index (BMI) z score and corrected calcium (r(2)=0.31, p<0.0001). Hip BMD was associated with BMI z score and intact parathyroid hormone (iPTH) (r(2)=0.26, p=0.002). Higher BMI z score was protective against low BMD at any site (OR 0.35).One in six newly diagnosed pSLE patients had low BMD (at any site). Low BMI z score, low calcium and high iPTH identified children at risk for low BMD at diagnosis of pSLE.
A rare diagnosis of right upper quadrant abdominal pain
Authors: C-S Chung, H-P Wang, Y-J Fang, R-H Hu, J-K Hsiao, C-H Chen
Journal: Gut (2008)

A 60-year-old woman, who had had asymptomatic chronic hepatitis C for 2 years, presented with a 6 month history of intermittent dull right upper quadrant abdominal pain. Physical examination was normal. Laboratory studies revealed elevated …
ACE Inhibition versus Angiotensin Receptor Blockade
Authors: Gozewijn D. Laverman, Giuseppe Remuzzi, Piero Ruggenenti
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Chronic renal disease is characterized by a gradual loss of renal function and an increased cardiovascular risk. Renin-angiotensin system blockade by angiotensin-converting enzyme inhibition or angiotensin receptor blockade has distinct renoprotective and cardiovascular protective effects, but which of the two drug classes confers more protection is still a matter of debate. This review highlights and compares the effects of the two drug-classes in nondiabetic renal disease and in overt or incipient nephropathy of type 1 and type 2 diabetes. Both renal and cardiovascular outcomes are considered. Regardless of their relative efficacy, both drug classes have a dose-response relationship for intermediate renal and cardiovascular parameters. Moreover, combined treatment with angiotensin-converting enzyme inhibition and angiotensin receptor blockade seems to provide better long-term renoprotection than monotherapy. Actually, in most patients, achieving maximal renal and cardiovascular protection requires a multidrug regimen, usually including several antihypertensives. Within this approach, full dose titration of either RAS blocker followed by add-on with the second drug is more important than the choice of the initial drug.
High-Throughput Screening Identifies Cardiac Glycosides as Potent Inhibitors of Human Tissue Kallikrein Expression: Implications for Cancer Therapies
Authors: Ioannis Prassas, Miltiadis Paliouras, Alessandro Datti, Eleftherios P. Diamandis
Journal: Clinical Cancer Research (2008)

Human tissue kallikreins (KLK) comprise a subgroup of 15 homologous secreted serine proteases. Primarily known for their clinical use as cancer biomarkers (e.g., PSA), KLKs have recently been directly implicated in cancer-related processes, including invasion, angiogenesis, and tumor growth regulation. Therefore, the identification of compounds that would modulate expression of KLKs might be of considerable therapeutic value.A cell-based high-throughput screening (HTS) of three small molecule libraries ( approximately 4,500 compounds) was undertaken; KLK expression in the breast cancer cell line MDA-MB-468 was assessed with sensitive ELISAs.The initial screening resulted in 66 "putative hits" that decreased KLK5 expression by at least 50% over control. Secondary screening and mini-dose-response assays resulted in 21 "validated hits." These 21 compounds were clustered in only three distinct functional families and were further analyzed in vitro to determine their effectiveness (IC(50)s). Hits that failed to show dose-responsiveness or interfered with the viability of the cells were excluded. Multiple members of the cardiac glycoside family were found to be novel inhibitors of KLK expression, acting at low concentrations (10-50 nmol/L). Furthermore, members of the same family induced marked decreases in c-MYC and c-FOS expression, in a dose-dependent manner that correlated the KLK inhibition, suggesting a transcriptional mechanism of regulation of KLK expression.We conclude that cardiac glycosides can dramatically suppress the transcription of KLKs and that these effects may be linked to proto-oncogene (c-myc/fos) expression. These findings may partially explain the recently realized antineoplastic actions of cardiac glycosides.
Colour categorization and the space between perception and language
Authors: Don Dedrick
Journal: Behavioral and Brain Sciences (1997)

We need to reconsider and reconceive the path that will take us from innate perceptual saliencies to basic (and perhaps other) colour language. There is a space between the perceptual and the linguistic levels that needs to be filled by an account of the rules that people use to generate relatively stable reference classes in a social context.
Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus
Authors: Gundula Min-Oo, Anny Fortin, Giuseppina Pitari, Mifong Tam, Mary M. Stevenson, Philippe Gros
Journal: The Journal of Experimental Medicine (2007)

Mouse strains AcB55 and AcB61 are resistant to malaria by virtue of a mutation in erythrocyte pyruvate kinase (PklrI90N). Linkage analysis in [AcB55 × A/J] F2 mice detected a second locus (Char9; logarithm of odds = 4.74) that regulates the blood-stage replication of Plasmodium chabaudi AS independently of Pklr. We characterized the 77 genes of the Char9 locus for tissue-specific expression, strain-specific alterations in gene expression, and polymorphic variants that are possibly associated with differential susceptibility. We identified Vnn1/Vnn3 as the likely candidates responsible for Char9. Vnn3/Vnn1 map within a conserved haplotype block and show expression levels that are strictly cis-regulated by this haplotype. The absence of Vnn messenger RNA expression and lack of pantetheinase protein activity in tissues are associated with susceptibility to malaria and are linked to a complex rearrangement in the Vnn3 promoter region. The A/J strain also carries a unique nonsense mutation that leads to a truncated protein. Vanin genes code for a pantetheinase involved in the production of cysteamine, a key regulator of host responses to inflammatory stimuli. Administration of cystamine in vivo partially corrects susceptibility to malaria in A/J mice, as measured by reduced blood parasitemia and decreased mortality. These studies suggest that pantetheinase is critical for the host response to malaria.
Increased carbon monoxide in exhaled air of patients with cystic fibrosis
Authors: P Paredi, P L Shah, P Montuschi, P Sullivan, M E Hodson, S A Kharitonov, P J Barnes
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Inflammation, oxidative stress, and recurrent pulmonary infections are major aggravating factors in cystic fibrosis. Nitric oxide (NO), a marker of inflammation, is not increased, however, probably because it is metabolised to peroxynitrite. Exhaled carbon monoxide (CO), a product of heme degradation by heme oxygenase 1 (HO-1) which is induced by inflammatory cytokines and oxidants, was therefore tested as a non-invasive marker of airway inflammation and oxidative stress. <h3>METHODS</h3> Exhaled CO and NO concentrations were measured in 29 patients (15 men) with cystic fibrosis of mean (SD) age 25 (1) years, forced expiratory volume in one second (FEV<sub>1</sub>) 43 (6)%, 14 of whom were receiving steroid treatment. <h3>RESULTS</h3> The concentration of exhaled CO was higher in patients with cystic fibrosis (6.7 (0.6) ppm) than in 15 healthy subjects (eight men) aged 31 (3) years (2.4 (0.4) ppm, mean difference 4.3 (95% CI 2.3 to 6.1), p&lt;0.001). Patients not receiving steroid treatment had higher CO levels (8.4 (1.0) ppm) than treated patients (5.1 (0.5) ppm, mean difference 3.3 (95% CI –5.7 to -0.9), p&lt;0.01). Normal subjects had higher NO levels (6.8 (0.4) ppb) than patients with cystic fibrosis (3.2 (0.2) ppb, mean difference 3.8 (95% CI 2.6 to 4.9), p&lt;0.05) and were not influenced by steroid treatment (3.8 (0.4) ppb and 2.7 (0.3) ppb for treated and untreated patients, respectively, mean difference 0.8 (95% CI –0.6 to 2.3), p&gt;0.05). Patients homozygous for the ΔF508 CFTR mutation had higher CO and NO concentrations than heterozygous patients (CO: 7.7 (1.8) ppm and 4.0 (0.6) ppm, respectively, mean difference 3.7 (95% CI –7.1 to –0.3), p&lt;0.05; NO: 4.1 (0.5) ppb and 1.9 (0.7) ppb, respectively, mean difference 2.2 (95% CI –3.7 to –0.6), p&lt;0.05). <h3>CONCLUSIONS</h3> High exhaled CO concentrations in patients with cystic fibrosis may reflect induction of HO-1. Measurement of exhaled CO concentrations may be clinically useful in the management and monitoring of oxidation and inflammatory mediated lung injury.
C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction
Authors: Paul M Ridker, Nina P. Paynter, Nader Rifai, J. Michael Gaziano, Nancy R. Cook
Journal: Circulation (2008)

Background— High-sensitivity C-reactive protein and family history are independently associated with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women); however, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men. Methods and Results— Among 10 724 initially healthy American nondiabetic men who were followed up prospectively over a median period of 10.8 years, we compared the test characteristics of global model fit, discrimination, calibration, and reclassification in 2 prediction models for incident cardiovascular events, one based on age, blood pressure, smoking status, total cholesterol, and high-density lipoprotein cholesterol (traditional model) and the other based on these risk factors plus high-sensitivity C-reactive protein and parental history of myocardial infarction before age 60 years (Reynolds Risk Score for men). A total of 1294 cardiovascular events accrued during study follow-up. Compared with the traditional model, the Reynolds Risk Score had better global fit (likelihood ratio test P &lt;0.001), a superior (lower) Bayes information criterion, and a larger C-index ( P &lt;0.001). For the end point of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8% (1904/10 724) of the study population (and 20.2% [1392/6884] of those at 5% to 20% 10-year risk) into higher- or lower-risk categories, with markedly improved accuracy among those reclassified. For this model comparison, the net reclassification index was 5.3%, and the clinical net reclassification index was 14.2% (both P &lt;0.001). In models based on the Adult Treatment Panel III preferred end point of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7% of the study population (and 20.1% of those at 5% to 20% 10-year risk) were reclassified to higher- or lower-risk groups, again with significantly improved global fit, larger C-index ( P &lt;0.001), and markedly improved accuracy among those reclassified. For this model, the net reclassification index was 8.4% and the clinical net reclassification index was 15.8% (both P &lt;0.001). Conclusions— As previously shown in women, a prediction model in men that incorporates high-sensitivity C-reactive protein and parental history significantly improves global cardiovascular risk prediction.
What Is the Most Cost-Effective Population-Based Cancer Screening Program for Chinese Women?
Authors: Pauline P.S. Woo, Jane J. Kim, Gabriel M. Leung
Journal: Journal of Clinical Oncology (2007)

To develop a policy-relevant generalized cost-effectiveness (CE) model of population-based cancer screening for Chinese women.Disability-adjusted life-years (DALYs) averted and associated screening and treatment costs under population-based screening using cervical cytology (cervical cancer), mammography (breast cancer), and fecal occult blood testing (FOBT), sigmoidoscopy, FOBT plus sigmoidoscopy, or colonoscopy (colorectal cancer) were estimated, from which average and incremental CE ratios were generated. Probabilistic sensitivity analysis was undertaken to assess stochasticity, parameter uncertainty, and model assumptions.Cervical, breast, and colorectal cancers were together responsible for 13,556 DALYs (in a 1:4:3 ratio, respectively) in Hong Kong's 3.4 million female population annually. All status quo strategies were dominated, thus confirming the suboptimal efficiency of opportunistic screening. Current patterns of screening averted 471 DALYs every year, which could potentially be more than doubled to 1,161 DALYs under the same screening and treatment budgetary threshold of US $50 million with 100% Pap coverage every 4 years and 30% coverage of colonoscopy every 10 years. With higher budgetary caps, biennial mammographic screening starting at age 50 years can be introduced.Our findings have informed how best to achieve allocative efficiency in deploying scarce cancer care dollars but must be coupled with better integrated care planning, improved intersectoral coordination, increased resources, and stronger political will to realize the potential health and economic gains as demonstrated.
Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?
Authors: Francesca Ingegnoli, Roberta Gualtierotti, Tommaso Schioppo, Annalisa Orenti, Patrizia Boracchi, Chiara Lubatti, Claudio Mastaglio, Valentina Galbiati, Antonella Murgo, Silvana Zeni, Claudia Grossi, Orietta Borghi, William Rosenberg, Laura Castelnovo, Luigi Meroni Pier
Journal: Annals of the Rheumatic Diseases (2013)

Raynaud's phenomenon (RP) can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc).1 

Enhanced liver fibrosis (ELF) test, an algorithm combining tissue inhibitors of matrix metalloproteinases (TIMP-1), hyaluronic acid (HA) and aminoterminal propeptide of type III procollagen (PIIINP), has been related to several measures of fibrosis in SSc patients.2–⇓4

We evaluated whether these biomarkers could discriminate between primary and secondary RP.

Consecutive adult patients with RP at the first rheumatologic evaluation were recruited from February 2011 to May 2012 with ethics committee approval. Exclusion criteria were history of any fibrosing disorder, organ transplantation, hepatocellular carcinoma or treatment with interferon. One patient was excluded for interferon treatment. Fifteen limited cutaneous SSc and 15 diffuse …
Tumor-Specific Effector CD8+ T Cells That Can Establish Immunological Memory in Humans after Adoptive Transfer Are Marked by Expression of IL7 Receptor and <i>c-myc</i>
Authors: Smita S. Chandran, Biman C. Paria, Abhishek K. Srivastava, Luke D. Rothermel, Daniel J. Stephens, Udai S. Kammula
Journal: Cancer Research (2015)

Abstract The optimal T-cell attributes for adoptive cancer immunotherapy are unclear. Recent clinical trials of ex vivo–expanded tumor-infiltrating lymphocytes indicated that differentiated T effector cells can elicit durable antitumor responses in some patients with cancer, with their antitumor activity tightly correlated with their persistence in the host. Thus, there is great interest in the definition of intrinsic biomarkers that can predict the conversion of short-lived tumor antigen–specific T effector cells into long-lived T memory cells. Long-term persistence of ex vivo–expanded tumor-specific CD8+ T effector clones has been reported in refractory metastatic melanoma patients after adoptive T-cell transfer. By using highly homogeneous clone populations from these preparations, we performed a comparative transcriptional profiling to define preinfusion molecular attributes that can be ascribed to an effector-to-memory transition. Through this route, we discovered that preinfusion T-cell clones that expressed the IL7 receptor (IL7R) and c-myc were more likely to persist longer after adoptive transfer to patients. The predictive value of these two biomarkers was strengthened by using IL7R protein, IL7-induced pSTAT5, and c-myc mRNA expression to prospectively identify human tumor-specific T effector clones capable of engraftment into immunodeficient mice. Overall, our findings reveal IL7R and c-myc expression as intrinsic biomarkers that can predict the fate of CD8+ T effector cells after adoptive transfer. Cancer Res; 75(16); 3216–26. ©2015 AACR.