tbuckley/cabot-search huggingface dataset:
The Photoproduction of 1α,25–Dihydroxyvitamin D<sub>3</sub>in Skin
Authors: Michael F. Holick, Milan Uskokovic, John W. Henley, Julia MacLaughlin, Sally Ann Holick, John T. Potts
Journal: New England Journal of Medicine (1980)

Cutaneous 7–dehydrocholesterol, exposed to ultraviolet radiation, converts to previtamin D3, which in turn converts in skin to vitamin D3 and is carried into the circulation. We investigated the feasibility of the photochemical conversion in skin of hydroxylated derivatives of 7–dehydrocholesterol — such as 1α,25–dihydroxy–7–dehydrocholesterol (1α,25(OH)2–7–DHC) — to the corresponding hydroxylated previtamin as an alternative method of delivery of 1α,25–dihydroxyvitamin D3 (1α,25–(OH)2-D3) to subjects who are deficient in the endogenous metabolite. In human volunteers and in vitamin-D-deficient rats [243H]1α,25–(OH)2-D3 appeared in blood after [243H]1α,25–(OH)2–7–DHC was applied to the skin and exposed to ultraviolet radiation. In anephric rats, intestinal calcium absorption and serum calcium levels were elevated after a topical dose of 1α,25–(OH)2–7DHC combined with ultraviolet phototherapy. Delivery of equivalent doses of 1α,25–(OH)2-D3 through the skin and orally showed that there was more prolonged stimulation in intestinal calcium absorption and serum calcium elevation after cutaneous administration. The photochemical conversion of precursors may be useful in the treatment of patients with impaired vitamin-D metabolism. (N Engl J Med. 1980; 303:349–54.)
Modeling non-uniformity in short-read rates in RNA-Seq data
Authors: Jun Li, Hui Jiang, Wing Hung Wong
Journal: Genome biology (2010)

Abstract After mapping, RNA-Seq data can be summarized by a sequence of read counts commonly modeled as Poisson variables with constant rates along each transcript, which actually fit data poorly. We suggest using variable rates for different positions, and propose two models to predict these rates based on local sequences. These models explain more than 50% of the variations and can lead to improved estimates of gene and isoform expressions for both Illumina and Applied Biosystems data.
Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study
Authors: Judith Haschka, Matthias Englbrecht, Axel J Hueber, Bernhard Manger, Arnd Kleyer, Michaela Reiser, Stephanie Finzel, Hans-Peter Tony, Stefan Kleinert, Martin Feuchtenberger, Martin Fleck, Karin Manger, Wolfgang Ochs, Matthias Schmitt-Haendle, Joerg Wendler, Florian Schuch, Monika Ronneberger, Hanns-Martin Lorenz, Hubert Nuesslein, Rieke Alten, Winfried Demary, Joerg Henes, Georg Schett, Juergen Rech
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. <h3>Methods</h3> Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)&lt;2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. <h3>Results</h3> In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). <h3>Conclusions</h3> This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. <h3>Trial registration number</h3> 2009-015740-42.
Ulcerative Endocarditis of the Pulmonic Cusps*
Authors: EDWARD WEISS
Journal: Annals of Internal Medicine (1929)

Article1 January 1929Ulcerative Endocarditis of the Pulmonic CuspsCase ReportEDWARD WEISS, M.D.EDWARD WEISS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-7-665 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptL. S., a colored woman of 34, was admitted to the Jefferson Hospital in the service of Dr. Thomas McCrae, January 24, 1928.She complained of pain in the right chest, chills, cough and expectoration. The family history was negative. The past history was unimportant. The patient had one son nine years old and had three miscarriages prior to the birth of her son.The history of the present illness was not quite clear. Apparently it began late at night on January 18, with pain in the right chest posteriorly, but there was some history of two attacks of chills... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa.*From the Department of Medicine, Jefferson Medical College Hospital, Philadelphia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1929Volume 2, Issue 7Page: 665-666KeywordsBirthEndocarditisHospital medicineMiscarriageThorax Issue Published: 1 January 1929 PDF DownloadLoading ...
A yeast screen system for aromatase inhibitors and ligands for androgen receptor: yeast cells transformed with aromatase and androgen receptor.
Authors: P Mak, F D Cruz, S Chen
Journal: Environmental Health Perspectives (1999)

Endocrine disruptors are hormone mimics that modify hormonal action in humans and animals. It is thought that some endocrine disruptors modify estrogen and androgen action in humans and animals by suppressing aromatase activity. Aromatase cytochrome P450 is the key enzyme that converts C19 androgens to aromatic C18 estrogenic steroids. We have developed a novel aromatase inhibitor screening method that allows us to identify antiaromatase activity of various environmental chemicals. The screen was developed by coexpressing the human aromatase and the mouse androgen receptor in yeast cells, which carry the androgen-responsive ss-galactosidase reporter plasmid. Functional expression of aromatase in yeast has been demonstrated using the [3H]-water release assay with intact cells as well as with yeast microsomes. The aromatase activity could be blocked by known aromatase inhibitors such as aminoglutethimide (AG). Yeast-produced androgen receptors were able to transactivate a yeast basal promoter linked to an androgen-responsive element in response to androgens. The resultant triple yeast transformant responded to the treatment of testosterone, androstenedione, or 5 alpha-dihydrotestosterone (5 alpha-DHT). In the absence of the aromatase inhibitor AG, transcriptional activation was observed only for the nonaromatizable androgen 5 alpha-DHT. However, the two aromatizable androgens (testosterone and androstenedione) induced the reporter activity in the presence of AG. Using this yeast-based assay, we confirmed that two flavones, chrysin and alpha-naphtholflavone, are inhibitors of aromatase. Thus, this yeast system allows us to develop a high-throughput screening method, without using radioactive substrate, to identify aromatase inhibitors as well as new ligands (nonaromatizable androgen mimics) for the androgen receptors. In addition, this screening method also allows us to distinguish nonandrogenic aromatase inhibitors from inhibitors with androgenic activity. This yeast screening method will be useful to screen environmental chemicals for their antiaromatase activity and for their interaction with androgen receptor.
Faculty Perceptions of Gender Discrimination and Sexual Harassment in Academic Medicine
Authors: Phyllis L. Carr, Arlene S. Ash, Robert H. Friedman, Laura Szalacha, Rosalind C. Barnett, Anita Palepu, Mark M. Moskowitz
Journal: Annals of Internal Medicine (2000)

Background: Gender-based discrimination and sexual harassment are common in medical practice and may be even more prevalent in academic medicine. Objective: To examine the prevalence of gender-based discrimination and sexual harassment among medical school faculty and the associations of gender-based discrimination with number of publications, career satisfaction, and perceptions of career advancement. Design: A self-administered mailed questionnaire of U.S. medical school faculty that covered a broad range of topics relating to academic life. Setting: 24 randomly selected medical schools in the contiguous United States. Participants: A random sample of 3332 full-time faculty, stratified by specialty, graduation cohort, and sex. Measurements: Prevalence of self-reported experiences of discrimination and harassment, number of peer-reviewed publications, career satisfaction, and perception of career advancement. Results: Female faculty were more than 2.5 times more likely than male faculty to perceive gender-based discrimination in the academic environment (P < 0.001). Among women, rates of reported discrimination ranged from 47% for the youngest faculty to 70% for the oldest faculty. Women who reported experiencing negative gender bias had similar productivity but lower career satisfaction scores than did other women (P < 0.001). About half of female faculty but few male faculty experienced some form of sexual harassment. These experiences were similarly prevalent across the institutions in the sample and in all regions of the United States. Female faculty who reported being sexually harassed perceived gender-specific bias in the academic environment more often than did other women (80% compared with 61%) and more often reported experiencing gender bias in professional advancement (72% compared with 47%). Publications, career satisfaction, and professional confidence were not affected by sexual harassment, and self-assessed career advancement was only marginally lower for female faculty who had experienced sexual harassment (P = 0.06). Conclusion: Despite substantial increases in the number of female faculty, reports of gender-based discrimination and sexual harassment remain common.
87 MOLECULAR CHARACTERIZATION OF HCV RESISTANCE TO TELAPREVIR, A NOVEL, POTENT HCV PROTEASE INHIBITOR
Authors: S. Chevaliez, A. Ahmed-Belkacem, L. Barbotte, A. Soulier, D. Bartels, Y. Zhou, A. Ardzinski, N. Mani, G. Rao, C. Hezode, S. George, A. Kwong, J.-M. Pawlotsky
Journal: Journal of Hepatology (2009)
Social affordances: Is the mirror neuron system involved?
Authors: Guillaume Dezecache, Laurence Conty, Julie Grèzes
Journal: Behavioral and Brain Sciences (2013)

We question the idea that the mirror neuron system is the substrate of social affordances perception, and we suggest that most of the activity seen in the parietal and premotor cortex of the human brain is independent of mirroring activity as characterized in macaques, but rather reflects a process of one's own action specification in response to social signals.
Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921
Authors: Jean-François Bosset, Gilles Calais, Laurent Mineur, Philippe Maingon, Ljiljana Radosevic-Jelic, Alain Daban, Etienne Bardet, Alexander Beny, Antoine Briffaux, Laurence Collette
Journal: Journal of Clinical Oncology (2005)

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m 2 /d and leucovorin 20 mg/m 2 /d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters. Patients and Methods One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type. Results After preop RT-CT, tumors were smaller (P &lt; .0001), had less advanced pT (P &lt; .001) and pN stages (P &lt; .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P ≤ .008). Mucinous tumors increased after preop RT-CT (P &lt; .001). Conclusion In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces downsizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.
German Pelviscopic Statistics for the Years 1978-1982
Authors: H.-H. Riedel, E. Lehmann-Willenbrock, P. Conrad, K. Semm
Journal: Endoscopy (1986)

The second set of statistics on pelviscopy in Germany included information on 269,603 pelviscopies done in 322 general hospitals, and 22,859 pelviscopies done in private clinics between 1978 and 1982. In general hospitals the rate of serious complications was 1.9% and in private clinics 2.0%. Injuries to large blood vessels headed the list of complications. The main technique for tubal sterilization was the bipolar high-frequency current method with 75% in general hospitals and 73.1% in private clinics, followed by the endocoagulation technique according to Semm (36.8%). Sterilization failures were reported in 2.6%. Most failures were reported after sterilization with the bipolar electrocoagulation technique, followed by the clip technique. The rate of post-sterilization ectopic pregnancies was 1.06%. The highest rate of ectopic pregnancies was reported after using the bipolar tubal sterilization method (1.4%).
Citation Impact of NHLBI R01 Grants Funded Through the American Recovery and Reinvestment Act as Compared to R01 Grants Funded Through a Standard Payline
Authors: Narasimhan S. Danthi, Colin O. Wu, Donna M. DiMichele, W. Keith Hoots, Michael S. Lauer
Journal: Circulation Research (2015)

Rationale: The American Recovery and Reinvestment Act (ARRA) allowed National Heart, Lung, and Blood Institute to fund R01 grants that fared less well on peer review than those funded by meeting a payline threshold. It is not clear whether the sudden availability of additional funding enabled research of similar or lesser citation impact than already funded work. Objective: To compare the citation impact of ARRA-funded de novo National Heart, Lung, and Blood Institute R01 grants with concurrent de novo National Heart, Lung, and Blood Institute R01 grants funded by standard payline mechanisms. Methods and Results: We identified de novo (type 1) R01 grants funded by National Heart, Lung, and Blood Institute in fiscal year 2009: these included 458 funded by meeting Institute’s published payline and 165 funded only because of ARRA funding. Compared with payline grants, ARRA grants received fewer total funds (median values, $1.03 versus $1.87 million; P &lt;0.001) for a shorter duration (median values including no-cost extensions, 3.0 versus 4.9 years; P &lt;0.001). Through May 2014, the payline R01 grants generated 3895 publications, whereas the ARRA R01 grants generated 996. Using the InCites database from Thomson-Reuters, we calculated a normalized citation impact for each grant by weighting each article for the number of citations it received normalizing for subject, article type, and year of publication. The ARRA R01 grants had a similar normalized citation impact per $1 million spent as the payline grants (median values [interquartile range], 2.15 [0.73–4.68] versus 2.03 [0.75–4.10]; P =0.61). The similar impact of the ARRA grants persisted even after accounting for potential confounders. Conclusions: Despite shorter durations and lower budgets, ARRA R01 grants had comparable citation outcomes per $million spent to that of contemporaneously funded payline R01 grants.
Abstract 3302: CD146, a suppressor of breast cancer, is a novel target of CD44-signaling
Authors: Mohamed E. Abdraboh, Hamad Al-Riyami, Yahya Al-Farsi, Allal Ouhtit, Andrew D. Hollenbach, Ishita Gupta, Somya Shanmuganathan, Madhwa H. Raj
Journal: Cancer Research (2014)

Abstract More than 80% of cancer related deaths are caused by cancer cell metastasis, a crucial step in the onset of tumor development. Among the molecules involved in promoting cancer metastasis is the cell adhesion molecule CD44, whose role in promoting cancer cell motility and metastasis is well known. Despite this knowledge, the molecular mechanism through which CD44 promotes tumor development and cell metastasis is still unclear. CD146 (MUC 18) is another member of the cell adhesion molecule family, first identified in highly metastatic melanomas. The absence of CD146 in normal melanocytes and its high expression in melanomas suggests its tumor promoting actions. Despite the association between CD146 expression and development of melanoma, the expression patterns and the role of CD146 in normal and metastatic breast tissues are still controversial. In this paper we provided evidence clarifying some of these discrepancies by presenting CD146 as a negative downstream target for CD44. Finally, this study demonstrates a new role of CD44 in regulating neovascularization and in promoting cancer cell transmigration of blood vessels via regulation of its downstream target CD146. Citation Format: Mohamed E. Abdraboh, Hamad Al-Riyami, Yahya Al-Farsi, Allal Ouhtit, Andrew D. Hollenbach, Ishita Gupta, Somya Shanmuganathan, Madhwa Hg Raj. CD146, a suppressor of breast cancer, is a novel target of CD44-signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3302. doi:10.1158/1538-7445.AM2014-3302
The power of placebo
Authors: E Ernst, A Herxheimer
Journal: BMJ (1996)

Links are revealed this week between the colour of a pill, its name, and its pharmacological action (pp 1624, 1627).1 2 This news will come as no surprise to many. Pink pills and tonics were the mainstay of many physicians—perhaps their main resource—before the era of antibiotics. But what are the active ingredients of the placebo effect and how can we make the best use of it?

Many non-specific concomitants of treatments help to determine the direction and size of the placebo effect. These can be placed on a continuum ranging from the tangible to the intangible.3 The form of medications, touch, words, gestures, and the ambience of the consultation can all play a part in conveying a doctor's confidence in a treatment, empathy with the patient, and professional status.4 5 6 Non-specific aspects of …
Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPARγ
Authors: Yau-Sheng Tsai, Hyo-Jeong Kim, Nobuyuki Takahashi, Hyung-Suk Kim, John R. Hagaman, Jason K. Kim, Nobuyo Maeda
Journal: Journal of Clinical Investigation (2004)

Peroxisome proliferator–activated receptor γ (PPARγ), the molecular target of a class of insulin sensitizers, regulates adipocyte differentiation and lipid metabolism. A dominant negative P467L mutation in the ligand-binding domain of PPARγ in humans is associated with severe insulin resistance and hypertension. Homozygous mice with the equivalent P465L mutation die in utero. Heterozygous mice grow normally and have normal total adipose tissue weight. However, they have reduced interscapular brown adipose tissue and intra-abdominal fat mass, and increased extra-abdominal subcutaneous fat, compared with wild-type mice. They have normal plasma glucose levels and insulin sensitivity, and increased glucose tolerance. However, during high-fat feeding, their plasma insulin levels are mildly elevated in association with a significant increase in pancreatic islet mass. They are hypertensive, and expression of the angiotensinogen gene is increased in their subcutaneous adipose tissues. The effects of P465L on blood pressure, fat distribution, and insulin sensitivity are the same in both male and female mice regardless of diet and age. Thus the P465L mutation alone is sufficient to cause abnormal fat distribution and hypertension but not insulin resistance in mice. These results provide genetic evidence for a critical role for PPARγ in blood pressure regulation that is not dependent on altered insulin sensitivity.
Cytomegalovirus Infections in Homosexual Men
Authors: LAWRENCE MINTZ
Journal: Annals of Internal Medicine (1983)

Levels of cytomegalovirus antibody (IgG and IgM) were measured and urine viral cultures were done in 237 homosexual men over a mean period of 14.1 months. The initial prevalence of cytomegalovirus IgG antibody was 86.9%. By the 9th month of follow-up, 71% of serosusceptible men had become infected with cytomegalovirus. During the study period cytomegaloviruria was noted in 32% of seropositive men. Cytomegalovirus IgM antibody was intermittently present in the serum of 95% of IgG-seropositive men, suggesting that frequent reactivation of latent infection or reexposure to exogenous virus had occurred. Of seven sexual practices investigated, only passive anal-genital intercourse correlated with the acquisition of cytomegalovirus infection (p =0.008).
The Anti-Tuberculosis Work in Missouri.
Authors: William Porter
Journal: JAMA (1905)

St. Louis, Sept. 18, 1905. <h3>To the Editor:</h3> —The best way to fight tuberculosis is to fight it; the best agency in the fight is education. During the past year Missouri has made a great advance in the warfare against consumption, and the work has been taken up earnestly and intelligently both by the physicians and the laity. Two lines of action have been followed—one, the organization of local associations for the study and prevention of tuberculosis; the other, the providing for private and public sanatoria, which in themselves are object-lessons teaching the great principles of limitation. At the last meeting of the state association, a resolution was passed asking each county society to appoint a committee on local organization, and this is to be acted on throughout the state this winter. In the larger towns action is already being taken in the formation of societies and the appointing of