tbuckley/cabot-search huggingface dataset:
Early Developmental Outcome in Children With Hypoplastic Left Heart Syndrome and Related Anomalies
Authors: Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J. William Gaynor
Journal: Circulation (2012)

Background— Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass. Methods and Results— In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3±1.1 (mean±SD) months. Mean PDI (74±19) and MDI (89±18) scores were lower than normative means (each P &lt;0.001). Neither PDI nor MDI score was associated with type of Norwood shunt. Independent predictors of lower PDI score ( R 2 =26%) were clinical center ( P =0.003), birth weight &lt;2.5 kg ( P =0.023), longer Norwood hospitalization ( P &lt;0.001), and more complications between Norwood procedure discharge and age 12 months ( P &lt;0.001). Independent risk factors for lower MDI score ( R 2 =34%) included center ( P &lt;0.001), birth weight &lt;2.5 kg ( P =0.04), genetic syndrome/anomalies ( P =0.04), lower maternal education ( P =0.04), longer mechanical ventilation after the Norwood procedure ( P &lt;0.001), and more complications after Norwood discharge to age 12 months ( P &lt;0.001). We found no significant relationship of PDI or MDI score to perfusion type, other aspects of vital organ support (eg, hematocrit, pH strategy), or cardiac anatomy. Conclusions— Neurodevelopmental impairment in Norwood survivors is more highly associated with innate patient factors and overall morbidity in the first year than with intraoperative management strategies. Improved outcomes are likely to require interventions that occur outside the operating room. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00115934.
First Case of Combined Small-Cell Lung Cancer with Adenocarcinoma Harboring EML4 - ALK Fusion and an Exon 19 EGFR Mutation in Each Histological Component
Authors: Gouji Toyokawa, Kenichi Taguchi, Taro Ohba, Yosuke Morodomi, Tomoyoshi Takenaka, Fumihiko Hirai, Masafumi Yamaguchi, Takashi Seto, Mitsuhiro Takenoyama, Kenji Sugio, Yukito Ichinose
Journal: Journal of Thoracic Oncology (2012)
Surgical Diseases of the Liver
Authors: Arthur B. Voorhees
Journal: JAMA (1965)

In this text Dr. Schwartz presents an excellent summary of current knowledge about the normal and pathological function of the liver under circumstances that are of interest to the general surgeon. The division of the book is along conventional lines. The bibliography is extensive and the graphic material excellently handled.  The chapter devoted to pre- and postoperative preparation of the patient is a compendium of advocated therapy under a variety of circumstances without extensive critical comment.  Perhaps the most interesting part of the text is the chapter which deals with the multitude of special diagnostic studies which can be made on the liver. The most important recent developments have emerged as a result of the angiographic and blood pressure and flow determination techniques applied to the splanchnic circulatory system with particular reference to the liver. The author has presented concise, general descriptions of the technique and comparison of hepatic vein
Racial Differences in Paraoxonase-1 (PON1): A Factor in the Health of Southerners?
Authors: Kimberly A. Davis, J. Allen Crow, Howard W. Chambers, Edward C. Meek, Janice E. Chambers
Journal: Environmental Health Perspectives (2009)

The southern United States (excluding Florida) has the highest age-adjusted rate of cardiovascular disease (CVD) in the country, with African Americans having a higher prevalence of CVD than Caucasians. Paraoxonase-1 (PON1), an enzyme associated with high-density lipoprotein particles, participates both in the hydrolysis of oxidized lipids (thus protecting against atherosclerosis) and in the hydrolysis of organophosphates. Higher paraoxonase activity has been associated with lower risk of atherosclerosis.In this study we characterized the distribution of the functional PON1(Q192R) polymorphisms (PON status as assessed by diazoxonase to paraoxonase ratios) and the PON1 activity levels in 200 adult males and females of both races (50 in each race/sex class) from the southern United States from commercially obtained blood bank serum samples.We used spectrophotometric methods with serum to determine PON1 status, arylesterase activities (phenyl acetate hydrolysis), and levels of cotinine and C-reactive protein (CRP).African Americans had higher paraoxonase activities but lower diazoxonase activities than did Caucasians, consistent with African Americans having a lower proportion of the functional genotype QQ (QQ 15%, QR 34%, RR 44%, 7% indeterminate), than did Caucasians (QQ 60%, QR 31%, RR 7%, 2% indeterminate). Cotinine levels indicated that all samples came from non-smokers and that CRP levels were higher in African Americans than in Caucasians and higher in females than in males. CRP levels showed no association with paraoxonase activities.These data present initial observations for use in characterizing the poorer cardiovascular health status of the population in the southern United States and more specifically southern African Americans.
Apolipoprotein E in Hyperlipidemia
Authors: Cristina C. Walden
Journal: Annals of Internal Medicine (1994)

Purpose: To review DNA analysis of apolipoprotein E used to assess patients with hyperlipidemia. Data Sources and Study Selection: 44 basic science studies of molecular analysis; 42 basic science studies of the biochemical, cellular biological, and molecular biological features of apolipoprotein E; and 29 clinical investigational studies, meta-analyses, and case series of patients with mutations in apolipoprotein E. Data Extraction: Methods of DNA analysis were reviewed, using specific examples in human disease, and the role of apolipoprotein E in normal and disordered lipoprotein metabolism was reviewed. Genetic analysis of apolipoprotein E in populations and particularly in persons with type III hyperlipoproteinemia is reviewed. Data Synthesis: In the general population, common DNA variants of apolipoprotein E are consistently associated with modest differences in plasma lipids and lipoproteins. Homozygosity for the E2 isoform of apolipoprotein E predisposes some patients to the development of type III hyperlipoproteinemia, a condition that involves an additional genetic or environmental factor for full clinical expression. Rare mutations of apolipoprotein E also cause hyperlipidemia. Conclusions: DNA variation of apolipoprotein E is one of several genetic and environmental factors that interact in a complex manner to affect plasma lipoproteins. DNA analysis of apolipoprotein E can be used in persons with hyperlipidemia to identify those with type III hyperlipoproteinemia and in relatives of affected persons to identify those who are predisposed.
REACTIONS OF THE NASAL CAVITY AND POSTNASAL SPACE TO CHILLING OF THE BODY SURFACE
Authors: Stuart Mudd, Alfred Goldman, Samuel B. Grant
Journal: The Journal of Experimental Medicine (1921)

Devices are described by means of which the terminals of thermopiles may be held in stable apposition with the mucous membranes of the nasal cavity and postnasal space and local temperature variations thus followed. Chilling of the body surface has without exception caused depression of the temperature of the nasal mucosa surface, amounting in some instances to as much as 6 degrees C., and indicating marked reflex vasoconstriction and diminution of blood supply. With rewrapping, partial recovery of blood supply promptly occurs, although recovery has been incomplete within the duration of the experiments in ten of twelve instances. Application of the wires within the nasal cavity has usually caused pain and discharge of clear mucus, sometimes also lacrimation and sneezing. The rhinorrhea has occurred both on the side directly irritated and on the opposite side, although on the former more abundantly, and has apparently been little if at all affected by the diminished blood supply and shrinkage of the mucous membrane incident to chilling the body surface. Discharge from the nose has been at most a rare occurrence in experiments in which the nasal mucosa was not directly irritated. The temperature of the nasopharyngeal mucosa surface has also been depressed, typically between 1 degrees and 2 degrees C., with chilling of the body surface. This depression has also been shown to have local reflex vasoconstriction and ischemia as its basis. With rewrapping, prompt return toward normal occurs, but here also recovery of blood supply has in the majority of instances not been complete within the duration of the experiments. The thresholds of the chilling vasoconstrictor reflex to the mucous membranes of the nasal cavity and postnasal space, tonsil, oropharynx, and palate and the threshold of the reflex to the skin of the trunk have been found to be lower than the threshold of the like reflex to the skin of the forehead. Disrobing 'the warmly wrapped subject in a room a little below ordinary room temperature has been found sufficient to cause marked vasoconstriction in the sites of the former group, but only slight or no vasoconstriction in the forehead. A number of instances of cold or sore throat occurred among the subjects of the experiments, in several instances correlated with somewhat interesting bacteriologic findings which will be described elsewhere.
Oncologist criticises NICE for not recommending wider use of MRI in prostate cancer
Authors: G. Watts
Journal: BMJ (2014)

Guidance issued last week by the National Institute for Health and Care Excellence (NICE) on the diagnosis and management of prostate cancer was a “missed opportunity,” said an expert on early management of the disease, because it recommended only limited use of magnetic resonance imaging (MRI) in diagnosis.

Mark Emberton, professor of interventional oncology at University College London, told a briefing on cancer organised by the UCL School of Pharmacy on 9 January that it made good sense to image the prostate before all biopsies of the organ—and not only in the more limited circumstances suggested by NICE.1

In its guidance, …
Abstract 2733: K14-GFP-miR-31 transgenic mice confer high susceptibility to squamous cell tumorigenesis on oral tongue and esophagus.
Authors: Ssu-Hsueh Tseng, Yong-Syu Lee, Kuo-Wei Chang, Shu-Chun Lin
Journal: Cancer Research (2013)

Abstract Squamous cell carcinoma (SCC) occurring on head and neck region and esophagus causes tremendous cancer mortality around the world. Effects from tobacco and/or alcoholic carcinogens and other factors are highly associated with the prevalence of these malignancies. MiRNAs are small non-coding RNAs mediating the RNA interference on targeted mRNAs. They play important roles in the pathogenesis of malignancies. miR-31 is among the most eminently up-regulated miRNAs in SCC occurring in head and neck region and esophagus. To elucidate the molecular pathogenesis of SCC, we established miR-31 transgenic mouse lines, in which miR-31 is under the control of K14 promoter and co-expressed with GFP. GFP and miR-31 were detected in basal and suprabasal squamous cells of skin, oral cavity and esophagus in these transgenic mice. The transgenic mice exhibited higher potential for tumor induction than wild type mice on oral tongue and esophagus by 4-nitroquinoline 1-oxide (4NQO) treatment. The precancerous lesions on oral tongues and esophagus in transgenic mice were also in more advanced stages in contrast to counterparts of wild type mice. Homozygous transgenic mice had the worst prognosis than the others. 4NQO induction also up-regulated miR-31 expression in tumors of wild type mice. The tumors induced in transgenic mice expressed more abundant miR-31 and VEGF, and less abundance of factor inhibiting HIF (FIH) than tumors in wild type mice. Base excision repair genes were validated as targets of miR-31 in human SCC cell lines, and the expression of these target genes were also decreased in the squamous epithelium of transgenic mice. This study identifies the high sensitivity of K14-GFP-miR-31 transgenic mice for chemical carcinogen-induced squamous cell tumorigenesis, and this could be associated with the down-regulation of tumor suppressor genes and the impairment of repair activity to counteract carcinogenic stimuli in squamous cells. Citation Format: Ssu-Hsueh Tseng, Yong-Syu Lee, Kuo-Wei Chang, Shu-Chun Lin. K14-GFP-miR-31 transgenic mice confer high susceptibility to squamous cell tumorigenesis on oral tongue and esophagus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2733. doi:10.1158/1538-7445.AM2013-2733
EXERCISE PULSE PRESSURE AMPLIFICATION IS AN INDEPENDENT DETERMINANT OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTIONIN SUBJECTS WITH AN EXAGGERATED PERIPHERAL BLOOD PRESSURE RESPONSE TO EXERCISE
Authors: Chi Young Shim, Woo-In Yang, Sungha Park, Donghoon Choi, Hyuck-Jae Chang, Namsik Chung, Jong-Won Ha
Journal: Journal of the American College of Cardiology (2012)
Small-caliber rescue pancreatic stenting for severe post-ERCP pancreatitis: a useful tool to pull the pancreas out of the fire
Authors: Zsolt Dubravcsik, Attila Szepes, István Hritz, László Madácsy
Journal: Endoscopy (2015)

We read with great interest the recent article from the Freeman group by Kerdsirichairat et al. [1]. Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), which can be severe or even life threatening in about 10 % of cases [2]. Prophylactic pancreatic stent (PPS) placement is effective in the prevention of post-ERCP pancreatitis (PEP), as demonstrated by several randomized controlled trials and meta-analyses, including the most recent one [3].
Lipoprotein-associated estrogens
Authors: M TIKKANEN, V VIHMA, M JAUHIAINEN, A HOCKERSTEDT, H HELISTEN, M KAAMANEN
Journal: Cardiovascular Research (2002)

The discovery of a family of hormonal steroids esterified with fatty acid has raised questions concerning their physiologic role. Because of their water-insolubility these compounds are present in the circulation only as components of lipoprotein particles. Current evidence supports the hypothesis that estrogen esterification is catalyzed by lecithin:cholesterol acyltransfearse associated with HDL. In addition, recent results indicate that estradiol esters are transferred from HDL to LDL particles in a cholesteryl ester transfer protein (CETP)-associated process. The studies now focus on the various possible physiologic roles proposed for these hormone derivatives, (1) functioning as fat-soluble antioxidants incorporated in lipoproteins rendering protection against oxidation of these particles, (2) providing a mechanism for hormonal storage in lipoproteins and fat tissues, (3) providing a novel hormone transport system using lipoprotein as carriers and lipoprotein receptors for entry into cells. Quantitative methods of determination of estradiol fatty acid esters in human body fluids have been developed. Preliminary studies suggest that diet-derived plant estrogens may also form fat-soluble derivatives which become incorporated in lipoproteins.
SPECIFICITY IN THE COMBINATION OF FD FRAGMENTS WITH L CHAINS TO FORM HAPTEN-BINDING SITES
Authors: O. A. Roholt, G. Radzimski, D. Pressman
Journal: The Journal of Experimental Medicine (1966)

In the work reported here we have shown that light chains and Fd fragments can be separated completely in propionic acid and then recombined to form Fab fragments with antibody activity. This experiment indicates that in the recombination a correct alignment of the Fd fragments and the L chains occurs to give a competent antibody site, just as occurs with the recombination of separated heavy and light chains of the antibody; thus the Fc fragment is not required for correct alignment. Fd fragments of antibody alone show very low binding activity toward the specific hapten. As is the case for the combination of heavy and light chains, the combination of Fd fragments and light chains also requires that both components come from antibody from the same rabbit in order to give binding sites. When they are derived from different rabbits producing antibody against the same antigen, they still give Fab fragments as shown by immunoelectrophoresis but do not have competent binding sites. An important observation is that the subunits of the papain digest fractions, Fab(I) and Fab(II), have the capacity to cross-combine to form active Fab fragments with competent binding sites. Fd(I) from Fab(I) combines with L(II) chains from Fab(II) to give the composite (Fd(I)-L(II)) with good binding activity. Likewise, the composite (Fd(II)-L(I)) has good binding activity. The composites from the two types of antibody molecules yielding different Fab fragments have antibody activity although heretofore these molecules have appeared to be different on the bases of chromatography and amino acid analysis. There is also a preferential combination of the Fd fragments to combine with the correct L fragments to give binding sites since this combination takes preference over the combination of Fd fragments of antibody with light chains of normal globulin (or of light chains of antibody with Fd fragments of normal globulin).
Russia bans transsexuals and people with personality disorders from driving
Authors: J. Follett
Journal: BMJ (2015)

<h3>ABSTRACT</h3> Understanding how genes interact is a central challenge in biology. Experimental evolution provides a useful, but underutilized, tool for identifying genetic interactions, particularly those that involve non-loss-of-function mutations or mutations in essential genes. We previously identified a strong positive genetic interaction between specific mutations in <i>KEL1</i> (P344T) and <i>HSL7</i> (A695fs) that arose in an experimentally-evolved <i>Saccharomyces cerevisiae</i> population. Because this genetic interaction is not phenocopied by gene deletion, it was previously unknown. Using “evolutionary replay” experiments we identified additional mutations that have positive genetic interactions with the <i>kel1</i>-P344T mutation. We replayed the evolution of this population 672 times from six timepoints. We identified 30 populations where the <i>kel1</i>-P344T mutation reached high frequency. We performed whole-genome sequencing on these populations to identify genes in which mutations arose specifically in the <i>kel1</i>-P344T background. We reconstructed mutations in the ancestral and <i>kel1</i>-P344T backgrounds to validate positive genetic interactions. We identify several genetic interactors with <i>KEL1</i>, we validate these interactions by reconstruction experiments, and we show these interactions are not recapitulated by loss-of-function mutations. Our results demonstrate the power of experimental evolution to identify genetic interactions that are positive, allele specific, and not readily detected by other methods, and sheds light on a previously under-explored region of the yeast genetic interaction network.
Global initiative launches to speed up the discovery of new drugs
Authors: A. Gulland
Journal: BMJ (2011)

An Oxford University academic is spearheading a global initiative to speed up the development and discovery of new drugs.

Chas Bountra, chief scientist and head of the Structural Genomics Consortium at Oxford University, told a press briefing organised by the Science Media Centre that the global initiative, as yet unnamed, would be up and running by the end of this year to start research into diseases such as dementia, which are traditionally seen as too high risk by the drug industry.

Dr Bountra said the initiative would be a public-private partnership made up of academic institutions, drug firms, governments, regulators, and philanthropic organisations. “What we are proposing to set up is a global initiative—a public-private partnership—to work with completely novel drugs and take these to phase II [clinical trials] as quickly as we can. And we are going to …
Hemozoin: Malaria's “Built-In” Adjuvant and TLR9 Agonist
Authors: Hermann Wagner
Journal: Cell Host & Microbe (2010)

The "built-in" adjuvant in a whole-microbe vaccine potentially triggers protective immunity. Coban et al. now demonstrate that crude blood stage extract of the malaria parasite Plasmodium falciparum drives parasite-specific immune responses via Hemozoin, a byproduct of heme detoxification, functioning as a TLR9 agonist and, therefore, as a "built-in" adjuvant.
ARTICLES
Authors: Catherine Ley, Heidi M. Bauer, Arthur Reingold, Mark H. Schiffman, Janet C. Chambers, Cathy J. Tashiro, M. Michele Manos
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article ARTICLES: Determinants of Genital Human Papillomavirus Infection in Young Women Get access Catherine Ley, Catherine Ley Search for other works by this author on: Oxford Academic PubMed Google Scholar Heidi M. Bauer, Heidi M. Bauer Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur Reingold, Arthur Reingold Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark H. Schiffman, Mark H. Schiffman Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet C. Chambers, Janet C. Chambers Search for other works by this author on: Oxford Academic PubMed Google Scholar Cathy J. Tashiro, Cathy J. Tashiro Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Michele Manos M. Michele Manos Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 997–1003, https://doi.org/10.1093/jnci/83.14.997 Published: 17 July 1991 Article history Received: 22 February 1991 Revision received: 05 April 1991 Accepted: 08 April 1991 Published: 17 July 1991