tbuckley/cabot-search huggingface dataset:
Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration
Authors: Michael H Schiff, Jonathan S Jaffe, Bruce Freundlich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>ABSTRACT</h3> With the growing amount and diversity of intermediate omics data complementary to genomics (e.g., DNA methylation, gene expression, and protein abundance), there is a need to develop methods to incorporate intermediate omics data into conventional genomic evaluation. The omics data helps decode the multiple layers of regulation from genotypes to phenotypes, thus forms a connected multi-layer network naturally. We developed a new method named NN-LMM to model the multiple layers of regulation from genotypes to intermediate omics features, then to phenotypes, by extending conventional linear mixed models (“LMM”) to multi-layer artificial neural networks (“NN”). NN-LMM incorporates intermediate omics features by adding middle layers between genotypes and phenotypes. Linear mixed models (e.g., pedigree-based BLUP, GBLUP, Bayesian Alphabet, single-step GBLUP, or single-step Bayesian Alphabet) can be used to sample marker effects or genetic values on intermediate omics features, and activation functions in neural networks are used to capture the nonlinear relationships between intermediate omics features and phenotypes. NN-LMM had significantly better prediction performance than the recently proposed single-step approach for genomic prediction with intermediate omics data. Compared to the single-step approach, NN-LMM can handle various patterns of missing omics measures, and allows nonlinear relationships between intermediate omics features and phenotypes. NN-LMM has been implemented in an open-source package called “JWAS”.
AMPHOTERICIN B IN BILATERAL CAVITARY HISTOPLASMOSIS
Authors: Charles M. Sinn
Journal: JAMA (1960)

Most cases of pulmonary histoplasmosis seem to have an acute but benign course, and the infection usually subsides without the necessity of specific therapy. Many acute pulmonic Histoplasma infections are probably never specifically recognized. The chronic pulmonary form of the disease has received much recognition during recent years.<sup>1</sup>It has been shown that the clinical and roentgenographic findings may closely simulate pulmonary tuberculosis.<sup>2</sup>Furcolow and Brasher<sup>3</sup>found a surprising incidence of patients with unrecognized chronic pulmonary histoplasmosis languishing in tuberculosis sanitoriums throughout the central part of the United States. Unfortunately, once cavitation has occurred in histoplasmosis the natural clinical course is slow dissemination of the infection and deterioration of the patient's condition until he dies.<sup>4</sup> Until the development of amphotericin B there was no specific therapy of value for these patients. Amphotericin B is an antifungal antibiotic isolated from the species of Streptomyces, which has been
CONTACT DERMATITIS DUE TO GOLD.
Authors: M. A. COWAN
Journal: British Journal of Dermatology (1960)

Journal Article CONTACT DERMATITIS DUE TO GOLD. Get access M. A. COWAN, M.B., M.R.C.P. M. A. COWAN, M.B., M.R.C.P. Late Registrar, Rupert Hallam Department of Dermatology, The Royal Infirmary, Sheffield, 6 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 10, 1 October 1960, Pages 348–349, https://doi.org/10.1111/j.1365-2133.1960.tb13816.x Published: 01 October 1960
SUPPRESSION OF MEMORY BY PASSIVE IMMUNIZATION LATE IN THE PRIMARY RESPONSE
Authors: Michael A. Axelrad
Journal: The Journal of Experimental Medicine (1971)

The acquisition of a capacity to respond well to sheep erythrocytes in the presence of anti-SRBC antibody was taken as an indication of the presence of immunological memory. By the use of passive immunization, both the primary IgG plaque-forming cell response and the establishment of memory were abolished, despite occurrence of a full peak IgM PFC response. Evidence for regarding the aquisition of memory and the IgM PFC and IgG PFC responses as three separate processes was presented. Antibody on day 3 of the response to 1.5 x 10(8) SRBC abolished formation of memory; this effect was less if passive immunization was further delayed and absent by day 10.
A study in cocaine. Sherlock Holmes and Sigmund Freud
Authors: D. F. Musto
Journal: JAMA (1968)

Cocaine stimulated the early careers of two brilliant investigators, Sigmund Freud and Sherlock Holmes. In fact, their common attraction to the euphoric properties of the coca leaf may be more than a coincidence. But whatever the Freud-Holmes relationship, the cocaine episodes in each of their lives reflect the impact of a new psychic drug on literature and science. Some of their admirers may deny or overlook this aspect of their careers, thinking that any association with such a drug can only be an embarrassment. But the international enthusiasm for cocaine which antedated and extended beyond their periods of endorsement makes it unlikely that any fair-minded person will censure them. The cocaine episode illustrates how easily objective evaluation may be submerged by personal enthusiasm and how remarkably difficult it may be, in spite of vast amounts of evidence, to judge correctly a widely used drug. Perhaps a reason for delay in
Effect of digoxin on atioventricular conduction. Studies in patients with and without cardiac autonomic innervation.
Authors: D J Goodman, R M Rossen, D S Cannom, A K Rider, D C Harrison
Journal: Circulation (1975)

The effect of digoxin on atrioventricular (a-v) conduction was compared in five patients with an intact cardiac autonomic nervous system (Group I) and seven patients who had undergone cardiac transplantation (Group II), in whom we have previously shown the transplanted heart to be completely denervated. Small decreases in the atrial effective refractory period (ERP) (from 262 plus or minus 12 to 254 plus or minus 11 msec) and atrial functional refractory period (FRP) (from 304 plus or minus 12 msec) were observed in Group I patients after digoxin, but these changes were not significant. However, significant increases in the A-V nodal ERP (from 315 plus or minus 18 msec to 351 plus or minus 17 msec, P less than 0.05), and A-V nodal FRP (from 426 plus or minus 42 to 460 plus or minus 46 msec, P less than 0.01) were produced by digoxin and were unrelated to changes in cycle length. In Group II patients with denervated hearts, changes in atrial ERP (from 246 plus or minus 4 to 243 plus or minus 6 during spontaneous sinus rhythm; from 204 plus or minus 10 to 216 plus or minus 8 msec during atrial pacing) and atrial FRP (from 311 plus or minus 12 to 316 plus or minus 11 msec during spontaneous sinus rhythm; from 254 plus or minus 12 to 260 plus or minus 10 msec during atrial pacing) were not significant. However, in contrast to the Group I patients, the digoxin-induced changes in A-V nodal ERP (from 280 plus or minus 22 to 297 plus or minus 18 msec during atrial pacing) and FRP (from 368 plus or minus 18 to 377 plus or minus 18 msec during spontaneous sinus rhythm; from 334 plus or minus 13 to 346 plus or minus 16 msec during atrial pacing) were also statistically insignificant. Our results demonstrate that the electrophysiologic effects of digoxin on atrioventricular conduction in man are most marked in the atrioventricular node and are dependent on cardiac innervation
Epidemiology of Type 2 Diabetes: Risk Factors
Authors: Steven M. Haffner
Journal: Diabetes Care (1998)

A number of cross-sectional and prospective studies that compared the insulin sensitivity of various national and ethnic populations within the U.S. to the total U.S. population were analyzed to find possible risk factors for the development of type 2 diabetes. It was found that the risks for diabetes in African-Americans, Hispanics, and Native Americans are approximately 2, 2.5, and 5 times greater, respectively, than in Caucasians. Studies of the prevalence of type 2 diabetes in Mexican Americans and non-Hispanic whites in San Antonio showed that there is an inverse relationship between socioeconomic status and the prevalence of diabetes. It also appears that cultural effects lead to an increased incidence of obesity in these populations, which may lead to insulin resistance. Genetic factors may also be a contributing factor. A 5-year, prospective study of insulin resistance in Pima Indians showed a relationship between impaired glucose tolerance and subsequent development of type 2 diabetes. In a 7-year study in Mexican Americans, those subjects who had both high insulin secretion and impaired insulin sensitivity had a 14-fold increased risk of developing type 2 diabetes. Regardless of cultural and ethnic factors, the San Antonio Heart Study, which compared Mexican Americans and non-Hispanic whites, showed that in both groups, the strongest predictors of developing type 2 diabetes are elevated fasting insulin concentrations and low insulin secretion.
Twelve-minute walking test for assessing disability in chronic bronchitis.
Authors: C R McGavin, S P Gupta, G J McHardy
Journal: BMJ (1976)

The distance covered in 12 minutes' walking was used to test exercise tolerance in chronic bronchitis. The distance covered bore a poor relation to the forced expiratory volume in 1 second but a significant relation to the forced vital capacity and the maximum oxygen consumption and ventilation on a bicycle ergometer. The test may be a simple practical guide to everyday disability in chronic bronchitis.
When To Discuss Advance Directives
Authors: Richard Neubauer
Journal: Annals of Internal Medicine (1993)

Letters15 March 1993When To Discuss Advance DirectivesRichard Neubauer, MDRichard Neubauer, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-6-199303150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I enjoyed reading Dr. Litwin's description of his first encounter with the sudden, unexpected death of a patient during his internship [1]. He describes how, in an early morning meeting with the family of a deceased patient, he finally became a physician. Such encounters capture the essence of our craft; we not only heal the sick but we also guide and give comfort to those who are left behind. We in private practice have the privilege of getting to know patients over decades, which makes such moments even more poignant.There was also a disturbing side to ...REFERENCE1. Litwin MS. Ode to joy. Ann Intern Med. 1992; 117:337. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1993Volume 118, Issue 6Page: 475-476KeywordsHeartNursing homesSleepStroke ePublished: 15 August 2000 Issue Published: 15 March 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Management of female prisoners with abnormal cervical cytology
Authors: G P Downey, G Gabriel, A R S Deery, J Crow, P G Walker
Journal: BMJ (1994)

t=-3 9, df=184, P=0-001).The distribution of feeding was the same whether data were provided by the mothers or by the patients.Stratified analysis showed that no factor among those we analysed (birth weight, type of delivery, social class, sex, age group, number ofother children in the household) confounded or modified the association between feeding and illness.
Squamous cell carcinoma of skin involving the median nerve
Authors: D.J. DANDY, D.D. MUNRO
Journal: British Journal of Dermatology (1973)

Journal Article Squamous cell carcinoma of skin involving the median nerve Get access D.J. DANDY, D.J. DANDY Orthopaedic and Dermatology Departments, St Bartholomew's Hospital, London, E.C.I, and Edgware General Hospital, Middlesex Search for other works by this author on: Oxford Academic Google Scholar D.D. MUNRO D.D. MUNRO Orthopaedic and Dermatology Departments, St Bartholomew's Hospital, London, E.C.I, and Edgware General Hospital, Middlesex Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 5, 1 November 1973, Pages 527–531, https://doi.org/10.1111/j.1365-2133.1973.tb03017.x Published: 01 November 1973 Article history Accepted: 09 April 1973 Published: 01 November 1973
Increase in the blood pressure of rats chronically fed low levels of lead.
Authors: H M Perry, M W Erlanger, E F Perry
Journal: Environmental Health Perspectives (1988)

Groups of 15 to 18 female weanling Long-Evans rats fed a rye-based diet low in lead (0.25 ppm) were exposed to 0.1, 1.0, and 5.0 ppm lead in drinking water. No suggestion of clinical lead toxicity was recognized. Systolic pressures were measured at 3-month intervals after weaning. The groups of lead-exposed animals had consistently and significantly higher average pressures than control animals, the increase approximating 15 mm Hg. With the lowest lead exposure (0.1 ppm), the increase in average pressure was gradual, being half minimal at 3 months and requiring 1 year to become maximal. After 1 year, half of these rats had pressures from 0 to 10 mm Hg above the control average; 40, 20, and 10% had pressures that were 20, 30, and 40 mm Hg, respectively, above the control average. Thus, rats exposed to lead in amounts comparable to the environmental exposure of many Americans had an average elevation in systolic pressure comparable to that of human beings with essential hypertension.
Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line.
Authors: A Weiss, J D Stobo
Journal: The Journal of Experimental Medicine (1984)

The association between T3 and the T cell antigen receptor was examined using the T3 bearing T cell leukemic line Jurkat. A monoclonal antibody, C305, was produced, which reacted with idiotypic-like determinants expressed on Jurkat. The molecule with which this antibody reacted was a disulfide-linked heterodimer of 90 kD, composed of polypeptides of 42 and 54 kD. Thus, C305 reacted with a molecule with characteristics of the putative T cell antigen receptor described by others. A series of mutants of Jurkat, induced with ethyl methane sulfonate or radiation, was selected for T3 or antigen receptor negativity. In every instance, there was a concomitant loss of both T3 and the antigen receptor as assessed by quantitative absorption, indirect immunofluorescence, and antibody plus complement-mediated cytotoxicity. The absence of antigen receptor molecules was confirmed on diagonal gels, excluding the possibility that conformational changes of the antigen receptor on such T3-negative mutants were responsible for the failure of such mutants to react with C305. Moreover, in a mutant that expressed a marked decrease in the level of T3 expression, there was a comparable decrease in the expression of antigen receptor determinants. These results suggest that there is an obligate requirement for the coexpression of T3 and the T cell antigen receptor. Furthermore, attempts to activate such mutants with the lectin phytohemagglutinin suggested that the expression of T3 and/or the antigen receptor was required for activation of these cells.
Long term culture of human embryonic stem cells on recombinant vitronectin in ascorbate free media
Authors: Andrew B.J. Prowse, Michael R. Doran, Justin J. Cooper-White, Fenny Chong, Trent P. Munro, Jane Fitzpatrick, Tung-Liang Chung, David N. Haylock, Peter P. Gray, Ernst J. Wolvetang
Journal: Biomaterials (2010)
Ventricular Fibrillation Due to Digitalis Preparations
Authors: CHARLES D. ENSELBERG, JAMES P. CROCE, BERNARD LOWN
Journal: Circulation (1951)

Contrary to expectations, there are very few substantiated clinical case reports of ventricular fibrillation attributable to digitalis preparations. Two cases, one of them fatal, are here described. The nature of ventricular fibrillation due to digitalis is different from that due to other agents. Hence it may not respond to present methods of treatment in the rare cases when opportunity for treatment exists. It is vital therefore to prevent ventricular fibrillation by the avoidance of digitalis when certain premonitory signs are present.
Use of Blood Groups in Cases of Disputed Paternity
Authors: William C. Boyd
Journal: New England Journal of Medicine (1949)

USE OF BLOOD GROUPS IN CASES OF DISPUTED PATERNITYThe application of blood groups in cases of disputed paternity depends upon the fact that the laws of their inheritance are accurately known. Thus, neither antigen A nor antigen B will appear in the blood of a child unless it was present in the blood of at least one of the child's parents. In addition, 2 persons of Group O will never produce a child of Group AB. Conversely, 2 persons of Group AB will never produce a child of Group O. Table 1 shows the possible outcome of the various types of . . .
Wassermann Test in Pregnancy
Authors: M. W. Blackwood
Journal: BMJ (1961)

<h3>Summary</h3> Chromosomal instability (CIN), characterized by frequent missegregation of chromosomes during mitosis, is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that comprise the mitotic spindle<sup>1–3</sup>. Thus, CIN tumor cells may respond differently than normal diploid cells to treatments that target mitotic spindle regulation. We tested this idea by inhibiting a subset of kinesin motor proteins that control spindle microtubule dynamics and mechanics but are not required for the proliferation of near-diploid cells. Our results indicated that KIF18A was required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but was not required in near-diploid cells. CIN tumor cells exhibited mitotic delays, multipolar spindles due to centrosome fragmentation, and increased cell death following inhibition of KIF18A. Sensitivity to KIF18A knockdown was strongly correlated with centrosome fragmentation, which required dynamic microtubules but did not depend on bipolar spindle formation or mitotic arrest. Our results indicate the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce the proliferative capacity of CIN cells.
Evolution of the indoor biome
Authors: Laura J. Martin, Rachel I. Adams, Ashley Bateman, Holly M. Bik, John Hawks, Sarah M. Hird, David Hughes, Steven W. Kembel, Kerry Kinney, Sergios-Orestis Kolokotronis, Gabriel Levy, Craig McClain, James F. Meadow, Raul F. Medina, Gwynne Mhuireach, Corrie S. Moreau, Jason Munshi-South, Lauren M. Nichols, Clare Palmer, Laura Popova, Coby Schal, Martin Täubel, Michelle Trautwein, Juan A. Ugalde, Robert R. Dunn
Journal: Trends in Ecology & Evolution (2015)
A truncating mutation in the laminin-332α chain highlights the role of the LG45 proteolytic domain in regulating keratinocyte adhesion and migration
Authors: G. Di Zenzo, M. El Hachem, A. Diociaiuti, R. Boldrini, V. Calabresi, F. Cianfarani, P. Fortugno, E. Piccinni, G. Zambruno, D. Castiglia
Journal: British Journal of Dermatology (2014)

Altered function of laminin-332 (α3β3γ2) consequent to mutations in the LAMA3, LAMB3 and LAMC2 genes causes junctional epidermolysis bullosa non-Herlitz (JEB-nH). JEB-nH patients suffer from skin blistering and have an increased risk of developing aggressive skin carcinomas in adulthood. Laminin-332 is proteolytically processed and its extracellular mature form lacks the α3 chain C-terminal globules 4 and 5 (LG45). The LG45 tandem has cell adhesion and protumorigenic properties. However, mutations that affect this domain are very rare and their functional effects in patients have not been explored to date.To characterize molecularly an adult patient with JEB-nH and altered laminin-332 expression presenting multiple skin carcinomas, and to analyse LG45-mediated biological functions using keratinocytes from the patient.A mutational search in laminin-332 genes was performed by hetero-duplex analysis. LAMA3 mRNA and laminin-332 protein levels in patient keratinocytes were investigated by real-time reverse transcriptase polymerase chain reaction and radioimmunoprecipitation assay, respectively. Keratinocyte migration was examined by scratch and Boyden chamber assays.We identified a homozygous LAMA3 mutation, p.Leu1648TrpfsX32, which truncates the last 45 amino acids of the carboxyl terminal LG5 subdomain. Gene expression studies revealed that the mutant transcripts were stable and even increased, precursor laminin-332 molecules were retained intracellularly and the amount of mature extracellular heterotrimers was reduced to about 50%. Finally, the patient's keratinocytes migrated faster than normal keratinocytes.Structural disruption of LG5 highlights the critical functions of the LG45 proteolytic region in precursor laminin-332 secretion and keratinocyte adhesion and migration. Perturbation of LG45 function might explain the non-aggressive behaviour of carcinomas in this patient.
Effect of tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis
Authors: M. E. Dodd, J. Abbott, J. Maddison, A. J. Moorcroft, A. K. Webb
Journal: Thorax (1997)

BACKGROUND: Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment. This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients9 preference. METHODS: Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second (FEV1) of 54% predicted (range 24-98) were studied. They inhaled a nebulised solution of hypertonic, isotonic, and hypotonic colistin over three consecutive days in random order in a double blind fashion. Measurements of chest tightness, using a visual analogue scale (VAS), and FEV1 were recorded before and 0, 15, 30, 60, and 90 minutes following inhalation. The solution preferred by each patient was determined at the end of the three days. RESULTS: All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness, with no differences between the solutions. However, the mean (SE) time to the maximum fall in FEV1 % predicted was significantly different between the solutions (hypertonic 7.8 (2.1) min, isotonic 19.2 (5.5) min, and hypotonic 34.2 (5.9) min) with a mean difference (95% CI) between hypotonic and hypertonic solutions of 28.04 (14.6 to 41.5) min, between isotonic and hypertonic solutions of 12.0 (-0.1 to 24.1) min, and between hypotonic and isotonic solutions of 15.6 (1.8 to 29.4) min. Positive correlations existed for the maximum fall in FEV1 % predicted between the hypertonic and isotonic solutions (r = 0.62, p &lt; 0.001) and between the hypotonic and isotonic solutions (r = 0.64, p &lt; 0.001). There was no correlation between the objective and subjective measurements for any solution. The patients9 preference varied. CONCLUSIONS: All tonicities of colistin caused equal symptoms of chest tightness and reduction in pulmonary function. It is recommended that the patient is challenged with nebulised colistin before prescription of the drug and that the challenge is preceded by an inhaled bronchodilator. Most of the patients preferred the isotonic or hypotonic solutions. The isotonic solution reflects a fall in FEV1 representative of all the solutions. The fall in FEV1 to the hypotonic solution occurred over a longer period and may be better tolerated by some patients.
Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis
Authors: Tetsuhiro Tanaka, Makiko Matsumoto, Reiko Inagi, Toshio Miyata, Ichiro Kojima, Takamoto Ohse, Toshiro Fujita, Masaomi Nangaku
Journal: Kidney International (2005)