tbuckley/cabot-search huggingface dataset:
<i>EGFR</i> Mutation Status in Japanese Lung Cancer Patients: Genotyping Analysis Using LightCycler
Authors: Hidefumi Sasaki, Katsuhiko Endo, Akimitsu Konishi, Minoru Takada, Masaaki Kawahara, Keiji Iuchi, Akihide Matsumura, Meinoshin Okumura, Hisaichi Tanaka, Tomoya Kawaguchi, Toshiki Shimizu, Hiroshi Takeuchi, Motoki Yano, Ichiro Fukai, Yoshitaka Fujii
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in ∼25% of Japanese lung cancer patients. These EGFR mutations are reported to be correlated with clinical response to gefitinib therapy. However, DNA sequencing using the PCR methods described to date is time-consuming and requires significant quantities of DNA; thus, this existing approach is not suitable for a routine pretherapeutic screening program. Experimental Design: We have genotyped EGFR mutation status in Japanese lung cancer patients, including 102 surgically treated lung cancer cases from Nagoya City University Hospital and 16 gefitinib-treated lung cancer cases from Kinki-chuo Chest Medical Center. The presence or absence of three common EGFR mutations were analyzed by real-time quantitative PCR with mutation-specific sensor and anchor probes. Results: In exon 21, EGFR mutations (CTG → CGG; L858R) were found from 8 of 102 patients from Nagoya and 1 of 16 from Kinki. We also detected the deletion mutations in exon 19 from 7 of 102 patients from Nagoya (all were deletion type 1a) and 4 of 16 patients from Kinki (one was type 1a and three were type 1b). In exon 18, one example of G719S mutation was found from both Nagoya and Kinki. The L858R mutation was significantly correlated with gender (women versus men, P &amp;lt; 0.0001), Brinkman index (600 ≤ versus 600&amp;gt;, P = 0.001), pathologic subtypes (adenocarcinoma versus nonadenocarcinoma, P = 0.007), and differentiation status of the lung cancers (well versus moderately or poorly, P = 0.0439), whereas the deletion mutants were not. EGFR gene status, including the type of EGFR somatic mutation, was correlated with sensitivity to gefitinib therapy. For example, some of our gefitinib-responsive patients had L858R or deletion type 1a mutations. On the other hand, one of our gefitinib-resistant patients had a G719S mutation. Conclusions: Using the LightCycler PCR assay, the EGFR L858R mutation status might correlate with gender, pathologic subtypes, and gefitinib sensitivity of lung cancers. However, further genotyping studies are needed to confirm the mechanisms of EGFR mutations for the sensitivity or resistance of gefitinib therapy for the lung cancer.
An estimate of the contribution of HIV infection to the recent rise in tuberculosis in England and Wales
Authors: A M C Rose
Journal: Thorax (2002)

The number of patients with tuberculosis has been increasing slowly in England and Wales since the late 1980s. HIV infection has been a contributory factor to increases in tuberculosis in a number of comparable industrialised countries. This study investigated the extent of tuberculosis and HIV co-infection in England and Wales in 1993 and 1998, and estimated its contribution to the increase in tuberculosis observed during this period.Patients aged 16-54 years old at diagnosis on the 1993 and 1998 National Tuberculosis Survey databases were matched with those on the HIV/AIDS patient database. A coded process maintained patient confidentiality. Primary outcome measures were the increase between 1993 and 1998 in the numbers with both infections reported and an estimate of the proportion of the increase in tuberculosis during this period attributable to HIV co-infection.In 1993 61 (2.2%) tuberculosis patients aged 16-54 years matched with patients reported to the HIV database, increasing to 112 (3.3%) in 1998 (p=0.08; OR 1.35; 95% CI 0.97 to 1.87). Patients co-infected with HIV contributed an estimated 8.5% of the increase in number of tuberculosis patients between 1993 and 1998 nationwide (11% in London). In both years prevalence of co-infection was greatest in London and in patients of white and black African ethnic groups.In 1998 the number of tuberculosis patients co-infected with HIV in England and Wales, though still small, had nearly doubled since 1993, with most of the increase occurring in London. As HIV infection may be undiagnosed in patients with tuberculosis, and tuberculosis may be unreported in patients with diagnosed HIV infection, the true extent of co-infection will have been underestimated by this study. In addition, constraints in coded matching make it inevitable that some reported co-infections are missed. Routine HIV testing of all patients with tuberculosis should now be considered, particularly in patients of white or black African ethnic origin under 55 years of age.
NMDA Receptors Control Cue-Outcome Selectivity and Plasticity of Orbitofrontal Firing Patterns during Associative Stimulus-Reward Learning
Authors: Marijn van Wingerden, Martin Vinck, Vincent Tijms, Irene R.S. Ferreira, Allert J. Jonker, Cyriel M.A. Pennartz
Journal: Neuron (2012)
Peroxidasin-like protein: expanding the horizons of matrix biology
Authors: A.-P. Papageorgiou, S. Heymans
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Peroxidasin-like protein: a novel peroxidase homolog in the human heart’ by Z. Peterfi et al ., doi:10.1093/cvr/cvt256. 

The extracellular matrix (ECM) is an intertwining network of proteins that provides support to the surrounding cells within a given organ. The ECM consists of collagens, elastins, glycoproteins, proteoglycans, and glycosaminoglycans, and performs a critical function not only during cardiac development and homoeostasis, but also during disease. On the one hand, this function can be structural, allowing for maintained strength and stability. Excessive matrix deposition induces cardiac stiffening, whereas abnormal collagen degradation causes cardiac dilatation.1 On the other hand, this vast entity also acts as a biochemical reservoir for intra- and extracellular communication between the different cardiac cells making the ECM extremely diverse in its function.2

Peterfi et al. 3 describe for the first time a novel peroxidase homologue, peroxidasin-like protein (PXDNL), whose expression is exclusive to the heart. This work follows their previous research describing the role of peroxidasin (PXDN) in matrix deposition following a fibrotic stimulus in the kidney.4 Intriguingly, both these proteins are derived from peroxidase-ancestors and have structural domains characteristic of ‘classical’ ECM proteins ( Figure 1 ). They include leucine-rich repeats similar to a subgroup of proteoglycans, such as decorin, mimecan, biglycan, and lumican, and which …
Endothelial Cx40 limits myocardial ischaemia/reperfusion injury in mice
Authors: Sandrine Morel, Vincent Braunersreuther, Marc Chanson, Diane Bouis, Viviane Rochemont, Bernard Foglia, Graziano Pelli, Esther Sutter, David J. Pinsky, François Mach, Brenda R. Kwak
Journal: Cardiovascular Research (2014)

AimsGap junctions are indispensable for the function of heart and blood vessels by providing electrical coupling and direct cell-to-cell transfer of small signalling molecules. Gap junction channels between neighbouring cells are composed of 12 connexins (Cx). Changes in Cx43 expression, localization, and channel properties in cardiomyocytes contribute to infarction and reperfusion injury of the heart. It is increasingly recognized that deleterious consequences of ischaemia/reperfusion (IR) are modulated by the inflammatory response and endothelial function. The role of the endothelial connexins, i.e. Cx40 and Cx37, in cardiac IR injury is, however, not known.
PHYSIOLOGICAL ONTOGENY
Authors: Alfred E. Cohn
Journal: The Journal of Experimental Medicine (1925)

These experiments show, then, that there are changes in rate which take place during the incubation period and that the direction of the curve expressing them changes in an orderly fashion. No attempt has yet been made to ascertain the influences operative in bringing about these alterations. It is our intention, however, to attempt to correlate them with such processes as changes in the rate of the general metabolism of the body, changes in structure of the heart muscle, and if possible with changes in the inherent dynamics of the muscle. It will be seen that the number of experiments at a given age is relatively speaking small. The temperature in spite of the precaution mentioned has likewise not been uniform, the range in the greatest number (38) of experiments having been 38°C. ± 1°. A few (four) counts have been made when the temperature was as low as 33.6°C. and a few (two) also at a temperature as high as 40°C. Although a curve as smooth as the one which has been drawn in all probability represents the general course of heart rate change, an explanation of the deviations which have been found is desirable. At least two influences which may be operative suggest themselves. First may be considered the effect of the unavoidable injury incident to cutting a window in the shell and removing so much of the shell membrane as to make the object visible. It has been a uniform practise to discard those eggs in which hemorrhage took place, so that if opening the egg has a share in the difficulty, this operation may be thought of as exerting a mechanical stimulus on a nervous or other controlling mechanism. But whether, especially at the early ages, a mechanism of such a nature exists within the embryo, we do not know. The search for one lies for the present beyond the range of our interest. A second influence responsible for the relatively large deviation in rate from the average may be that of fluctuations in temperature. The air of the room in which the observations were made was, in a given situation, fairly uniform at 38°C. ± 1.0°. as the temperature records show. In the earlier experiments the temperature was read at a distance about 1 foot away from the egg. Between this point and the egg a difference unknown to us may well have existed. It is improbable, however, that it can have been more than 2°C., that is to say, 38° ± 2°. Roughly if the change in rate is approximately 15 beats per degree a maximum deviation of 30 beats may be expected. In point of fact a deviation as great as this did not take place. In later experiments the temperature was read in the immediate vicinity of the eggs, so that a correction can be made more accurately. There is in all probability a high degree of uniformity in the rate of the heart of the chicken embryo at each stage of development, although variation is also found. What the extent of the deviation is that may properly be encountered we do not yet know. It is desirable to pursue this subject further. Observations will accordingly be made and will be reported later.
Natural selection of protein structural and functional properties: a SNP perspective
Authors: Jinfeng Liu, Yan Zhang, Xingye Lei, Zemin Zhang
Journal: Genome biology (2008)

The rates of molecular evolution for protein-coding genes depend on the stringency of functional or structural constraints. The Ka/Ks ratio has been commonly used as an indicator of selective constraints and is typically calculated from interspecies alignments. Recent accumulation of single nucleotide polymorphism (SNP) data has enabled the derivation of Ka/Ks ratios for polymorphism (SNP A/S ratios).Using data from the dbSNP database, we conducted the first large-scale survey of SNP A/S ratios for different structural and functional properties. We confirmed that the SNP A/S ratio is largely correlated with Ka/Ks for divergence. We observed stronger selective constraints for proteins that have high mRNA expression levels or broad expression patterns, have no paralogs, arose earlier in evolution, have natively disordered regions, are located in cytoplasm and nucleus, or are related to human diseases. On the residue level, we found higher degrees of variation for residues that are exposed to solvent, are in a loop conformation, natively disordered regions or low complexity regions, or are in the signal peptides of secreted proteins. Our analysis also revealed that histones and protein kinases are among the protein families that are under the strongest selective constraints, whereas olfactory and taste receptors are among the most variable groups.Our study suggests that the SNP A/S ratio is a robust measure for selective constraints. The correlations between SNP A/S ratios and other variables provide valuable insights into the natural selection of various structural or functional properties, particularly for human-specific genes and constraints within the human lineage.
Sensitivity and Specificity of a Rapid Whole-Blood Assay for D-Dimer in the Diagnosis of Pulmonary Embolism
Authors: Jeffrey S. Ginsberg
Journal: Annals of Internal Medicine (1998)

Background: Patients with suspected pulmonary embolism often have nondiagnostic lung scans and may present in circumstances where lung scanning is unavailable. Levels of d-dimer, a fibrin-specific product, are increased in patients with acute thrombosis; this may simplify the diagnosis of pulmonary embolism. Objective: To determine the sensitivity and specificity of a whole-blood d-dimer assay in patients with suspected pulmonary embolism and in subgroups of patients with low pretest probability of pulmonary embolism or nondiagnostic lung scans. Design: Prospective cohort. Setting: Four tertiary care hospitals. Patients: 1177 consecutive patients with suspected pulmonary embolism. Measurements: All patients underwent an assessment of pretest probability by use of a standardized clinical model, a d-dimer assay, ventilation-perfusion lung scanning, and bilateral compression ultrasonography. Patients in whom pulmonary embolism was not initially diagnosed were followed for 3 months. Accordingly, patients were categorized as positive or negative for pulmonary embolism. Results: Of the 1177 patients, 197 (17%) were classified as positive for pulmonary embolism. Overall, the d-dimer assay showed a sensitivity of 84.8% and a specificity of 68.4%. In 703 patients (3.4%) with a low pretest probability of pulmonary embolism, the likelihood ratio associated with a negative d-dimer test result was 0.27, resulting in a posterior probability of 1.0% (95% CI, 0.3% to 2.2%). In 698 patients with nondiagnostic lung scans (previous probability, 7.4%), the likelihood ratio associated with a negative d-dimer test result was 0.36, resulting in a posterior probability of 2.8% (CI, 1.4% to 4.8%). Conclusions: A normal d-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan.
Improving the Quality of Adult Mortality Data Collected in Demographic Surveys: Validation Study of a New Siblings' Survival Questionnaire in Niakhar, Senegal
Authors: Stéphane Helleringer, Gilles Pison, Bruno Masquelier, Almamy Malick Kanté, Laetitia Douillot, Géraldine Duthé, Cheikh Sokhna, Valérie Delaunay
Journal: PLoS Medicine (2014)

Stéphane Helleringer and colleagues conducted a validation study in Niakhar, Senegal to investigate whether a new approach, sibling survival calendars, improves the quality of adult mortality data collected in demographic surveys. Please see later in the article for the Editors' Summary
Irritable Spine as an Idiopathic Affection
Authors: J. G. S. Coghill
Journal: BMJ (1879)

THE BRITISH MEDICAL 7OURNAL.fluid, are requisite.Friction and elastic compression are also essential elements in the treatment of these diseases in certain stages.If the effused fluid have undergone degenerative metamorphosis, it should be evacuated by means of the aspirator, if possible.If, however, the contents cannot escape by the aspirator, then the joint should be freely incised under the antiseptic spray, and carefully washed out and dressed according to the principles so admirably described by Mr. Lister.If the disease have progressed to caries or necrosis before it comes under observation, it is frequently accompanied with one or more tor- tuous sinuses which afford but an insufficient exit to the morbid materials, and hence it is possible, by means of a free incision in the right direction, to facilitate the exit of the discharges, and then by fol- lowing out the general instructions above given, repair may take place with more or less deformity and partial or complete ankylosis.But in this latter condition of caries or necrosis, after having given the patient the benefit of the treatment just recommended, and the disease still goes on progressively, showing the extent of disease to be so great, or, that the constitution of the patient is so bad that he will probably succumb before the escape of the diseased bone could be effected by the slow process of exfoliation; then, exsection and complete removal of the diseased parts is our only remedy.This, when done properly, and with proper after-treatment, will frequently yield the most satisfac- tory results.In the knee, we have a splendid limb with ankylosis ; in the ankle, hip, elbow, and wrist, we frequently have fine results with but slight deformity and very nearly complete motion.
Early vs. late worsening heart failure during acute heart failure hospitalization: insights from the PROTECT trial
Authors: Robert J. Mentz, Marco Metra, Gad Cotter, Olga Milo, Colleen McKendry, Karen Chiswell, Beth A. Davison, John G.F. Cleland, Daniel M. Bloomfield, Howard C. Dittrich, Mona Fiuzat, Piotr Ponikowski, Michael M. Givertz, Adriaan A. Voors, John R. Teerlink, Christopher M. O'Connor
Journal: European Journal of Heart Failure (2015)
Human Immunodeficiency Virus-1 Induces Loss of Contact Inhibition in Podocytes
Authors: ELISSA J. SCHWARTZ, ANDREA CARA, HANS SNOECK, MICHAEL D. ROSS, MASAAKI SUNAMOTO, JOCHEN REISER, PETER MUNDEL, PAUL E. KLOTMAN
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Human immunodeficiency virus—associated nephropathy (HIVAN) affects up to 10% of HIV-positive black adults and children and is the leading cause of renal disease in infected individuals. The disease is characterized by proliferation of renal epithelial cells, both glomerular and tubular. Diseased kidneys are enlarged, and glomerular visceral epithelial cells (podocytes) express proliferation markers. In a transgenic murine model of HIVAN expressing a deletion construct of HIV-1, the identical pathologic features are observed. It was demonstrated that HIV-1 mRNA is expressed in renal epithelium of the transgenic mouse and in patients with HIVAN, suggesting a direct role for HIV-1 in disease pathogenesis in both humans and the murine model. For investigating the mechanisms responsible for proliferative changes in podocytes, the HIV-1 transgenic mouse was bred onto the immortomouse background, and conditionally immortalized transgenic and nontransgenic podocyte cell lines were established. Transgenic podocytes demonstrated increased spontaneous proliferation, compared with nontransgenic podocytes at confluence, and they were found to have a greater percentage of cells in the proliferative phase of the cell cycle. It is striking that transgenic podocytes were not contact inhibited and formed aggregates in soft agar. Aggregates also formed when nontransgenic podocytes were infected with the identical HIV-1 construct used to generate the transgenic model. This demonstrates that the loss of contact inhibition is due to a direct effect of HIV-1. Therefore, proliferation induced by HIV-1 gene expression is likely to play a key role in the pathogenesis of HIVAN.
Asymmetric Male and Female Genetic Histories among Native Americans from Eastern North America
Authors: Deborah A Bolnick, Daniel I Bolnick, David Glenn Smith
Journal: Molecular Biology and Evolution (2006)

Previous studies have investigated the human population history of eastern North America by examining mitochondrial DNA (mtDNA) variation among Native Americans, but these studies could only reconstruct maternal population history. To evaluate similarities and differences in the maternal and paternal population histories of this region, we obtained DNA samples from 605 individuals, representing 16 indigenous populations. After amplifying the amelogenin locus to identify males, we genotyped 8 binary polymorphisms and 10 microsatellites in the male-specific region of the Y chromosome. This analysis identified 6 haplogroups and 175 haplotypes. We found that sociocultural factors have played a more important role than language or geography in shaping the patterns of Y chromosome variation in eastern North America. Comparisons with previous mtDNA studies of the same samples demonstrate that male and female demographic histories differ substantially in this region. Postmarital residence patterns have strongly influenced genetic structure, with patrilocal and matrilocal populations showing different patterns of male and female gene flow. European contact also had a significant but sex-specific impact due to a high level of male-mediated European admixture. Finally, this study addresses long-standing questions about the history of Iroquoian populations by suggesting that the ancestral Iroquoian population lived in southeastern North America.
Lung function in adolescents after uncomplicated whooping cough in childhood
Authors: DB Teculescu, C Aubry, QT Pham, J Locuty, JP Deschamps, M Manciaux
Journal: European Respiratory Journal (1989)

Ventilatory function (forced vital capacity, forced expiratory volume in one second, forced expiratory flows), static lung volumes, phase III slope and closing volume (single-breath nitrogen washout test) were measured in 499 children and adolescents aged 10-16 yrs from a general population sample in North-East France. A history of whooping cough was given by 44 children (22 of each sex); their results were compared to those of the 455 children (215 girls) with a negative history. The only difference between the two groups was a minimal increase in the residual volume/total lung capacity ratio in cases (19.2 +/- 3.1 vs 18.0 +/- 2.9%). We conclude that uncomplicated whooping cough in early childhood did not lead to significant pulmonary function abnormality in this population of children born after 1967.