tbuckley/cabot-search huggingface dataset:
Xanthomatosis and other clinical findings in patients with elevated levels of very low density lipoproteins
Authors: B.J. VERMEER, CM. GENT, B. GOSLINGS, M.K. POLANO
Journal: British Journal of Dermatology (1979)

Forty-six patients with xanthomatosis and elevated very low density lipoproteins (VLDL) levels (in different types of hyperlipoproteinaemia) were classified on the basis of the WHO criteria and the cholesterol/triglyceride ratio in VLDL. A large majority (31/46) of the patients referred to the Department of Dermatology could be classified as hyperlipoproteinaemia type III, only 8/46 as type IIB and 7/46 as type IV/V. This distinction seems to be relevant as the xanthomatous lesions differed distinctly between these three types of hyperlipoproteinaemia. Xanthochromia striata palmaris was present in 29/31 cases of hyperlipoproteinaemia type III and was not found in type IV/V patients, who had distinctive papuloeruptive xanthomas. During a follow-up in 35/46 patients all xanthomas disappeared within 2 years except the xanthelasma palpebrarum and tendinous xanthomas. All type IV/V patients (7/7) but only one type III patient (1/31) had abnormal glucose tolerance. Only 2/18 type III patients less than 45 years showed claudication and none of the young type III patients had angina pectoris. In contrast, all four type IIB patients less than 45 years had clinical signs of atherosclerosis. However, angina pectoris and/or claudication were present in 5/13 type III patients over 45 years old. The mean serum cholesterol level was equally elevated in both groups but the cholesterol was mainly present in VLDL in type III and in low density lipoproteins (LDL) in type IIB. In 9/31 type III patients the LDL level was also elevated but was easily normalized by a diet low in carbohydrate, whereas the elevated LDL level in type IIB was therapy-resistant. The recognition of xanthomatous lesions, specifically xanthochromia striata palmaris, as an early sign of type III hyperlipoproteinaemia, can lead to the early diagnosis and successful treatment of these patients, and thus possibly prevent the development of premature atherosclerosis.
Computed Tomography–Diagnosed Emphysema, Not Airway Obstruction, Is Associated with the Prognostic Outcome of Early-Stage Lung Cancer
Authors: Kazuhiro Ueda, Mitsutaka Jinbo, Tao-Sheng Li, Takaharu Yagi, Kazuyoshi Suga, Kimikazu Hamano
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Because both emphysema and lung cancer can arise from biological damage caused by cigarette smoking, we investigated if the development of emphysema is associated with the clinical features of smoker's lung cancer. Experimental Design: The subjects were a consecutive series of 100 smokers who underwent lobectomy with hilar and mediastinal dissection for clinical stage I non–small cell lung cancer. We studied the relationship between the presence or absence of emphysema at the onset of the lung cancer and clinicopathologic features. Emphysema was diagnosed by measuring the low-attenuation area using computed tomography densitometry. Results: There were no differences in clinicopathologic variables, including the degree of smoking exposure between the patients with (n = 58) and those without (n = 42) emphysema, although male gender and airflow limitation were predominant in the patients with emphysema. The presence of emphysema, but neither male gender nor airflow limitation, adversely affected both overall and disease-specific survival. According to Cox regression analysis, emphysema was an independent prognosticator among age, gender, degree of smoking exposure, tumor size, nodal status, histologic subtype, histologic grade, and microvessel invasion. These results were stabilized by a bootstrap sampling model. Conclusions: Computed tomography–diagnosed emphysema, but not airway obstruction, is associated with poor prognosis in smokers with early-stage lung cancer. Thus, routine computed tomography densitometry in smokers with lung cancer should be mandatory.
Letter: Computing muscle stiffness from ventricular pressure-volume curve.
Authors: A Fester
Journal: Circulation Research (1976)

Computing Muscle Stiffness from VentricularPressure-Volume CurveIn their recent study of muscle stiffness, Glantz and Kernoff 1 stated that equations used by Mirsky and Parmley 2 and by Fester and Samet 3 (among others), lack experimental validation and are not logically derived equations.While statements of this nature, naturally have to be supported by reasonable scientific arguments, these were notably absent.Furthermore, in so stating, one would at least show that his own derived equations are indeed a progressive forward solution to the problem that other authors so "illogically" failed to solve.Yet, for reasons given below, the opposite is observed:A. From experimental observations, 4 ' s including their own 1 !! (see Fig. 3, dog 6, curves 2, 3, and Fig. 4, dogs 5, 4), and studies of others, 3 ' • it was clearly demonstrated that the PV (pressure volume) or the stress strain (<?-t) curves of the ventricular muscle are not exponential at low levels of pressure and stress and that the portion of the curve that may be approximated by an exponential mode, yields a stress asymptote which in most of the cases studied, is above zero level, especially in diseased hearts; i.e., the exponent does not pass through the origin (coordinate a = 0, e = 0).Rather, the muscle may behave as a Hookean material early in the stretch and as non-Hookean material (exponential or other polynomial) when further stretched. 4Hence, the researcher is obliged to fit an equation to an observation and not an observation to an equation.B. Unfortunately the choice of Equations 1 and 4 in the study of Glantz and Kernoff 1 is, by mathematical definition, an attempt to fit muscle behavior, neither observed experimentally nor clinically to rigid equations of special case.According to these equations, 1 the exponent must pass through the origin.This is the reason for their observed "worst fits" in some of the hearts and these "fits" would be even worse if their equations were to be applied to diseased hearts.Thus, it appears to be more logical to use general equations of an exponent (three constants instead of two) as utilized by Diamond et al. 4 and normalized in a logical fashion by Equations 6 and 9 in the study of Fester and Samet. 3These equations are mathematically free to fit the suitable "experimentally validated" portion of the curve that is indeed exponential.For example, the fits in Figure 4 of the Glantz and Kernoff study 1 would be much better if coordinates from V = 44 ml and above in dog 5 and V = 47 ml and above in dog 4, were fed into the computer, utilizing, however, a = Ae Bf + C and not a = A(eB< -1)! C. Their choice of strain is also limiting, especially for in vivo studies as it is almost impossible to find the unstrained dimension (X*).Hence, it would be more logical to choose the natural strain definition of « = log.(L/L0 ) since de = dL/L, i.e., the unstrained dimension, L o , is eliminated. 2 ' 3
Targeting Multiple Signaling Pathways by Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate
Authors: Naghma Khan, Farrukh Afaq, Mohammad Saleem, Nihal Ahmad, Hasan Mukhtar
Journal: Cancer Research (2006)

Abstract Cell signaling pathways, responsible for maintaining a balance between cell proliferation and death, have emerged as rational targets for the management of cancer. Emerging data amassed from various laboratories around the world suggests that green tea, particularly its major polyphenolic constituent (−)-epigallocatechin-3-gallate (EGCG), possesses remarkable cancer chemopreventive and therapeutic potential against various cancer sites in animal tumor bioassay systems and in some human epidemiologic studies. EGCG has been shown to modulate multiple signal transduction pathways in a fashion that controls the unwanted proliferation of cells, thereby imparting strong cancer chemopreventive as well as therapeutic effects. This review discusses the modulations of important signaling events by EGCG and their implications in cancer management.(Cancer Res 2006;66(5):2500–5)
Ductus Arteriosus and the Mechanism of Closure
Authors: P. Yngve Hörnblad
Journal: New England Journal of Medicine (1970)

IN the recent studies on closure of the ductus arteriosus, whole-body freezing and sectioning have made the ductus available for morphologic studies in a state that can be considered to reflect its state in vivo1 , 2 rather than distorted by artifacts.In newborn infants the ductus arteriosus has a circular lumen with a smooth inner surface, and a thin wall composed mainly of the media, which has straight elastic lamellas and slender interposed muscle cells.3 During closure, which begins after birth,4 the ductus of all species displays similar morphologic changes, which conclusively indicate that the narrowing is brought about by contraction . . .
Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell–stimulating programs in basophils
Authors: Kang Chen, Weifeng Xu, Melanie Wilson, Bing He, Norman W Miller, Eva Bengtén, Eva-Stina Edholm, Paul A Santini, Poonam Rath, April Chiu, Marco Cattalini, Jiri Litzman, James B Bussel, Bihui Huang, Antonella Meini, Kristian Riesbeck, Charlotte Cunningham-Rundles, Alessandro Plebani, Andrea Cerutti
Journal: Nature Immunology (2009)
Age-Specific Incidence, Outcome, Cost, and Projected Future Burden of Atrial Fibrillation–Related Embolic Vascular Events
Authors: Gabriel S.C. Yiin, Dominic P.J. Howard, Nicola L.M. Paul, Linxin Li, Ramon Luengo-Fernandez, Linda M. Bull, Sarah J.V. Welch, Sergei A. Gutnikov, Ziyah Mehta, Peter M. Rothwell
Journal: Circulation (2014)

Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain.We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981-1986 to 2002-2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P=0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group.Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.
Trends in treatment and outcomes of rheumatoid arthritis in Germany 1997-2007: results from the National Database of the German Collaborative Arthritis Centres
Authors: S. Ziegler, D. Huscher, K. Karberg, A. Krause, S. Wassenberg, A. Zink
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> New strategies and options for the treatment of rheumatoid arthritis (RA) have evolved during the past decade. A study was undertaken to investigate to what extent this influenced daily rheumatological care and how this translates into clinical and patient-reported outcomes. <h3>Methods</h3> Data from a total of 38 723 outpatients with RA enrolled in the National Database of the German Collaborative Arthritis Centres in the years 1997–2007 were analysed. The cross-sectional annual data were compared to detect time trends. <h3>Results</h3> Between 1997 and 2007 the prescription of combinations of traditional disease-modifying antirheumatic drugs (DMARDs) increased from 8% of all patients to 23%; biological agents were prescribed to 16% of patients with RA in 2007. The mean disease activity (DAS28) fell from 4.5 to 3.4 (median 4.5–3.2). The percentage of patients with low disease activity (DAS28 &lt;3.2) increased significantly from 23% to 49%. The proportion of patients with ≥6 swollen joints fell from 43.1% in 1997 to 8.1% in 2007 and, in those with ≥6 tender joints, from 46.3% to 15.8%. There was a large decrease in the total annual number of days of sick leave due to the rheumatic condition from 27.2 to 8.8 days per gainfully employed person. This reduction is far beyond the decline in the general population. There was also a tendency to higher participation in the work force, specifically in older patients, reflecting the trend seen in the general population. <h3>Conclusions</h3> The intensity of drug treatment in patients with RA has increased during the past 7 years. This has been accompanied by not only a decrease in disease activity but also a considerable reduction of economic losses due to sick leave and permanent work disability.
CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION
Authors: Michael Heidelberger, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1936)

1. The absolute, quantitative agglutinin method has been used for the determination of the presence or absence of small amounts of specific polysaccharide in pneumococcus variants. 2. A technique is described for the removal of group specific antibody from antipneumococcus horse serum. 3. The type specific anticarbohydrate agglutinin and precipitin are not only present in identical amounts in Type I antipneumococcus horse serum, but a reduction in one is also accompanied by a quantitatively identical reduction in the other, providing evidence for their actual identity. In purified antibody solutions somewhat more agglutinin than precipitin is found, possibly owing to alteration of a portion of the antibody in the process of purification.
Receptivity to Internet-Delivered Interventions to Promote Skin Self-examination and Sun Protection Behaviors in Patients With Melanoma
Authors: Ashley K. Day, Jerod L. Stapleton, Sharon L. Manne, Kristina L. Tatum, James S. Goydos, Elliot J. Coups
Journal: JAMA Dermatology (2015)

This survey of adults with a diagnosis of melanoma assessed patient characteristics associated with a willingness to receive Internet-delivered interventions to promote skin self-examination and sun protection behaviors.
Mammalian Sperm Proteins Are Rapidly Evolving: Evidence of Positive Selection in Functionally Diverse Genes
Authors: Dara G. Torgerson, Rob J. Kulathinal, Rama S. Singh
Journal: Molecular Biology and Evolution (2002)

A growing number of genes involved in sex and reproduction have been demonstrated to be rapidly evolving. Here, we show that genes expressed solely in spermatozoa represent a highly diverged subset among mouse and human tissue-specific orthologs. The average rate of nonsynonymous substitutions per site (Ka) is significantly higher in sperm proteins (mean Ka = 0.18; N = 35) than in proteins expressed specifically in all other tissues (mean Ka = 0.074; N = 473). No differences, however, are found in the synonymous substitution rate (Ks) between tissues, suggesting that selective forces, and not mutation rate, explain the high rate of replacement substitutions in sperm proteins. Four out of 19 sperm-specific genes with characterized function demonstrated evidence of strong positive Darwinian selection, including a protein involved in gene regulation, Protamine-1 (PRM1), a protein involved in glycolysis, GAPDS, and two egg-binding proteins, Adam-2 precursor (ADAM2) and sperm-adhesion molecule-1 (SAM1). These results demonstrate the rapid evolution of sperm-specific genes and highlight the molecular action of sexual selection on a variety of characters involved in mammalian sperm function.
A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity
Authors: Asuka Terashima, Hiroshi Watarai, Sayo Inoue, Etsuko Sekine, Ryusuke Nakagawa, Koji Hase, Chiaki Iwamura, Hiroshi Nakajima, Toshinori Nakayama, Masaru Taniguchi
Journal: The Journal of Experimental Medicine (2008)

Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4+ NKT cells but not on other splenic leukocyte populations tested. IL-17RB+ CD4+ NKT cells produce predominantly IL-13 and Th2 chemokines upon stimulation with IL-25 in vitro. IL-17RB+ NKT cells were detected in the lung, and depletion of IL-17RB+ NKT cells by IL-17RB–specific monoclonal antibodies or NKT cell–deficient Jα18−/− mice failed to develop IL-25–dependent AHR. Cell transfer of IL-17RB+ but not IL-17RB− NKT cells into Jα18−/− mice also successfully reconstituted AHR induction. These results strongly suggest that IL-17RB+ CD4+ NKT cells play a crucial role in the pathogenesis of asthma.
Abstract 2095: A virtual pyrogram generator to resolve ambiguity of pyrosequencing results
Authors: Guoli Chen, Matthew T. Olson, Alan O'Neill, Alexis Norris-Kirby, Katie Beierl, Shuko Harada, Marija Debeljak, Keila Rivera-Roman, Samantha Finley, Amanda Stafford, Christopher D. Gocke, Ming-Tseh Lin, James R. Eshleman
Journal: Cancer Research (2012)

Abstract We report a freely available software program, Pyromaker, which generates simulated pyrosequencing traces based on user inputs and aids in analysis of complex pyrosequencing results. To achieve this goal, simulated pyrograms are generated based on the hypothesized mutations and matched with the actual pyrogram. We validated the software testing common KRAS gene mutations and several mutations in the BRAF, GNAS and, p53 genes. We demonstrate that all eighteen possible single base mutations within codons 12 and 13 of KRAS gene generate unique simulated pyrosequencing traces and highlight the distinctions between them. We further verify that all reported codon 12 and 13 complex mutations produce unique pyrograms. However, some complex pyrograms are indistinguishable from single base mutations, using a standard dispensation order. Pyromaker was used in two strategies, one in which hypothesis-based simulated pyrograms were pattern-matched with the actual pyrograms. In a second mode, with only the pyrogram, Pyromaker was used to identify the underlying mutation by iteratively reconstructing the mutant pyrogram. Either strategy was able to successfully identify the complex mutations, which were confirmed by cloning and subsequent sequencing. With two examples of KRAS codon 12 mutations, (GGTαTTT, G12F and GGTαGAG, G12E), we report optimal combinations of the five analysis approaches that permit unambiguous mutation identification. The most efficient one is pyrosequencing with Pyromaker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2095. doi:1538-7445.AM2012-2095
Lung function and bronchodilator response in 4-year-old children with different wheezing phenotypes
Authors: E. Oostveen, S. Dom, K. Desager, M. Hagendorens, W. De Backer, J. Weyler
Journal: European Respiratory Journal (2009)

Persistent wheeze is a common chronic disease in early childhood and later may progress to asthma. However, the association between pre- and post-bronchodilator lung function and the wheezing phenotype in preschool children is not known. Children 4 yrs of age involved in a prospective birth cohort study (in Antwerp, Belgium) concerning perinatal factors and the occurrence of asthma and allergies, were invited to participate in lung function measurements with the forced oscillation technique. The wheezing phenotype was assessed via (bi)annual questionnaires. Wheezing phenotype and baseline respiratory impedance data were available for 325 children, 96% of whom underwent bronchodilation tests. The baseline resistance at 4 Hz was higher in children with early transient (11.0 hPa·s·L −1 , n = 127) or persistent wheeze (11.9 hPa·s·L −1 , n = 54) than in children who never wheezed (10.3 hPa·s·L −1 , n = 144). After bronchodilation, the resistance decreased on average by 22%. The decrease was greater among the persistent wheezers than among those who never wheezed (3.4 versus 2.3 hPa·s·L −1 ). The baseline lung function was poorer and the bronchodilator response was greater in 4-yr-old children with persistent wheeze than in those who never wheeze or who had early transient wheeze, implying a higher bronchomotor tone in the former group.
Intestinal epithelial spheroids: new tools for studying gastrointestinal diseases
Authors: Maria Rescigno
Journal: Gut (2014)

The intestinal tract is one of the most complex organs of our body because it has to perform several functions, including digestion and absorption of nutrients. Being exposed to a continuous insult by the local microbiota, the intestinal epithelium is constantly renewed from Lgr5+ stem cell progenitors located in the crypts of Lieberkuhn.1 These progenitors have been recently exploited to regenerate ‘mini-guts’ (organoids) in vitro.2 An appropriate cocktail of small molecules and growth factors has been identified that preserves stemness but also favours the differentiation of enterocytes and Paneth cells thus forming the organotypic structure of a crypt-villous organoid (for a review, see ref. 3).

In this issue of Gut , VanDussen et al 4 show a powerful method of growing human epithelial cells in culture from biopsies of several intestinal segments of either healthy individuals or patients with several pathologies. 

The authors established a very simple methodology starting from biopsies collected during routine endoscopy. Crypts were isolated with collagenase digestion and embedded in matrigel with 50% conditioned medium obtained from fibroblasts engineered to secrete Wnt3a, R-spondin and Noggin.5 These three factors were previously shown by the same authors among others to be sufficient to propagate and maintain intestinal epithelial cells in the mouse system.3 

In the current manuscript, …
Missing Data and Measurement Variability in Assessing Progression-Free Survival Endpoint in Randomized Clinical Trials
Authors: Rajeshwari Sridhara, Sumithra J. Mandrekar, Lori E. Dodd
Journal: Clinical Cancer Research (2013)

Abstract Progression-free survival (PFS) is frequently used as the primary efficacy endpoint in the evaluation of cancer treatment that is considered for marketing approval. Missing or incomplete data problems become more acute with a PFS endpoint (compared with overall survival). In a given clinical trial, it is common to observe incomplete data due to premature treatment discontinuation, missed or flawed assessments, change of treatment, lack of follow-up, and unevaluable data. When incomplete data issues are substantial, interpretation of the data becomes tenuous. Plans to prevent, minimize, or properly analyze incomplete data are critical for generalizability of results from the clinical trial. Variability in progressive disease measurement between radiologists further contributes to data problems with a PFS endpoint. The repercussions of this on phase III clinical trials are complex and depend on several factors, including the magnitude of the variability and whether there is a systematic reader evaluation bias favoring one treatment arm particularly in open-label trials. Clin Cancer Res; 19(10); 2613–20. ©2013 AACR.