tbuckley/cabot-search huggingface dataset:
Testing whether Metazoan Tyrosine Loss Was Driven by Selection against Promiscuous Phosphorylation
Authors: Siddharth Pandya, Travis J. Struck, Brian K. Mannakee, Mary Paniscus, Ryan N. Gutenkunst
Journal: Molecular Biology and Evolution (2014)

Protein tyrosine phosphorylation is a key regulatory modification in metazoans, and the corresponding kinase enzymes have diversified dramatically. This diversification is correlated with a genome-wide reduction in protein tyrosine content, and it was recently suggested that this reduction was driven by selection to avoid promiscuous phosphorylation that might be deleterious. We tested three predictions of this intriguing hypothesis. 1) Selection should be stronger on residues that are more likely to be phosphorylated due to local solvent accessibility or structural disorder. 2) Selection should be stronger on proteins that are more likely to be promiscuously phosphorylated because they are abundant. We tested these predictions by comparing distributions of tyrosine within and among human and yeast orthologous proteins. 3) Selection should be stronger against mutations that create tyrosine versus remove tyrosine. We tested this prediction using human population genomic variation data. We found that all three predicted effects are modest for tyrosine when compared with the other amino acids, suggesting that selection against deleterious phosphorylation was not dominant in driving metazoan tyrosine loss.
Patients Have a Right to Privacy and Anonymity in Medical Publication
Authors: Povl Riis, Magne Nylenna
Journal: JAMA (1991)

The classical ideal of the good patient-doctor relationship implicity accepts the doctor's access to the patient's physical, social, and mental "nudity," as long as this intrusion serves the patient's best interests. Without such an implicit confidence, most clinical work would be impossible. Yet breaches of confidence do occur, sometimes deliberately, sometimes by accident or simply by lack of consideration. Examples may include release of sensitive patient information to the press, gossip in the local medical community, and public disclosures through administrative or legal statements. A relatively new ethical transgression is intrusion into a patient's bodily or social integrity by clinical descriptions and photographs printed in textbooks or medical journals. The phenomenon itself is not new. A quick glance into many old and new textbooks will demonstrate patients portrayed in the nude without any masking or any statement on the patients' informed consent. What is new, however, is that public and
Galectin‐3 and left ventricular reverse remodelling after surgical mitral valve repair
Authors: Kirsten A. Kortekaas, Georgette E. Hoogslag, Rudolf A. de Boer, Martin M. Dokter, Michel I.M. Versteegh, Jerry Braun, Nina Ajmone Marsan, Hariette F. Verwey, Victoria Delgado, Martin J. Schalij, Robert J.M. Klautz
Journal: European Journal of Heart Failure (2013)
Anthropometric, body composition and somatotype differences of Iranian elite female basketball and handball players
Authors: Mandana Gholami, Lila Sabbaghian Rad
Journal: British Journal of Sports Medicine (2010)

The aims of the present study were: (1) to determine the anthropometric profile, body composition and somatotype of female basketball (B) and handball (H) players, (2) to compare the mean scores among sports and (3) to detect possible differences in relation to competition level. A total of 28 female athletes, all members of the Iranian national teams, participated in the present study. Anthropometric measures required for the calculation of body composition indexes and somatotype components were obtained according to the established literature. Although B and H group had homogeneity in somatotype characteristics (p&lt;0.05). There was a significant difference somatotype characteristics among B and H group (p&lt;0.001). Somatotype characterised as meso-endomorph in B group (3.6, 3.5, 2.4) and H athletes' somatotype was meso-endomorph (3.6, 4.7, 1.7). There is no significant difference of body mass index, waist to hip ratio (WHR), fat weight, fat percent, fat free weight, WHR and stature, weight and triceps skinfold thickness among B and H group. Anthropometric and body composition variables of elite female basketball and handball players were same. But they had different somatotype characteristics. Selection criteria, hours of training and sport-specific physiological demands during the game could explain the observed differences.
Role of interleukin-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis.
Authors: D I Heath, A Cruickshank, M Gudgeon, A Jehanli, A Shenkin, C W Imrie
Journal: Gut (1993)

A number of laboratory and clinical studies have shown that interleukin-6 is the principal mediator of the acute phase protein response. In this study the relationship between serum concentrations of interleukin-6 and C-reactive protein in acute pancreatitis are examined and the ability of interleukin-6 to discriminate between severe and mild attacks is assessed. We have studied 24 patients (10 severe and 14 mild). Serum samples were collected on admission, six hourly for 48 hours and then 12 hourly for a further three days. When the areas under the curves of individual patients were compared there was a strong correlation between the total production of interleukin-6 and C-reactive protein (r = 0.73) (Spearman rank correlation) and peak interleukin-6 and C-reactive protein concentrations (r = 0.75), suggesting a close relationship between interleukin-6 and C-reactive protein production. Both on admission and peak interleukin-6 concentrations were significantly higher in patients with severe than mild disease. There was no significant difference in on admission C-reactive protein concentrations, although significant differences were seen when peak concentrations were considered. Utilising a peak interleukin-6 concentration of > 130 u/ml, we were able to distinguish between severe and mild attacks of acute pancreatitis with a sensitivity of 100% and specificity of 71%. These figures were comparable with those for peak C-reactive protein, a C-reactive protein of > 150 mg/l detecting severe attacks of acute pancreatitis with a sensitivity of 90% and specificity of 79%. In view of the fact that interleukin-6 concentrations peaked earlier than those of C-reactive protein, interleukin-6 is capable of providing comparable, but earlier severity prediction than C-reactive protein.
Electronic preprints: what should the BMJ do?
Authors: T. Delamothe
Journal: BMJ (1998)

What should journals do about the circulation of “preprints”—drafts of scientific papers that have not yet been formally published? Within the research community they serve several purposes. Some researchers routinely send such drafts to colleagues for their comments. Others use them as an early warning system, to keep colleagues abreast of research that may take months to get into print. Until recently distributing preprints entailed making multiple photocopies of a manuscript and posting them. The advent of faxes quickened the pace but did little to reduce the workload, which effectively limited their circulation. All this has changed with the internet. Draft manuscripts can now be posted on institutional or individual websites. Hundreds of colleagues, instead of a handful, may now see a preprint before its formal publication. Thousands more internet users may be led to a preprint by search engines, which scour the web's pages for key words.

Some journals, such as the New England Journal of Medicine, have come down unequivocally against electronic preprints: “Posting a manuscript, including its figures …
Abstract 2485: The Hippo downstream effector YAP promotes survival, radiation resistance and chromosome instability in medulloblastoma
Authors: Africa Fernandez-L, Anna M. Kenney
Journal: Cancer Research (2011)

Abstract Medulloblastoma, the most common solid pediatric tumor, originates in the cerebellum during postnatal development. It is postulated that cerebellar granule neuron precursors (CGNPs) are cells-of-origin for certain classes of medulloblastomas. CGNPs require the mitogen/morphogen Shh to proliferate. We identified YAP as a new Shh target that promotes CGNP proliferation. YAP is a transcriptional co-activator negatively regulated by the Hippo pathway, a signaling cascade involved in organ size regulation and cell contact inhibition. We found YAP to be highly expressed in human and mouse Shh-driven medulloblastomas. Moreover, YAP was strikingly amplified in a subset of human medulloblastomas. YAP was localized to the peri-vascular niche where cancer stem cells have recently been described to reside in brain tumors. When we irradiated medulloblastoma-bearing mice, most of the cells in the tumor underwent apoptosis 6 hours after radiation. However, cells expressing YAP were resistant to radiation-induced apoptosis. These radiation-resistant cells have been described to have the ability to re-populate the tumor. In concordance with this, mouse medulloblastoma cells over-expressing YAP and injected in P0-P4 pups grow faster than those overexpressing GFP and give rise to more aggressive tumors. In vitro, YAP-overexpressing CGNPs and medulloblastoma cells produce higher levels of IGF2, which activates Akt and promotes their survival. 24 hours after radiation, YAP-overexpressing cells contain more damaged DNA; however, they skip the G2/M checkpoint and don't arrest despite the damage in their DNA. Our results indicate that YAP promotes both chromosome instability and survival of medulloblastoma cells, thus is a new attractive potential target for medulloblastoma therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2485. doi:10.1158/1538-7445.AM2011-2485
QUESTION OF THE MONTH
Authors: JOSEPH M. MAUCERI
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 July 1969QUESTION OF THE MONTHJOSEPH M. MAUCERI, M.D.JOSEPH M. MAUCERI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-71-1-216 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:The Question of the Month (700) on cardiovascular diseases in the April ANNALSincluded the statement that direct arterial measurements of diastolic blood pressure were best correlated with changes in auscultatory sound rather than the final sound heard. This was considered incorrect vis à vis the answer given. It is a well-known clinical observation that in patients with high output states and low diastolic pressures the diastolic reading between the third and fourth auscultatory phases—that is, that point where Korotkoff sounds change from a soft thud to a softer blowing quality, "muffling"—more accurately reflects intra-arterial diastolic levels....Reference1. GOLDSTEINKILLIP ST: Comparison of direct and indirect arterial pressures in aortic regurgitation. New Eng. J. Med. 267: 1122, 1962. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Albany Medical Center Albany, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1969Volume 71, Issue 1Page: 216-216KeywordsBlood pressureCardiovascular diseases Issue Published: 1 July 1969 PDF downloadLoading ...
Enhanced expression of vascular endothelial growth factor-A in ground glass hepatocytes and its implication in hepatitis B virus hepatocarcinogenesis
Authors: Jui‐Chu Yang, Chiao‐Fang Teng, Han‐Chieh Wu, Hung‐Wen Tsai, Huai‐Chia Chuang, Ting‐Fen Tsai, Yung‐Hsiang Hsu, Wenya Huang, Li‐Wha Wu, Ih‐Jen Su
Journal: Hepatology (2009)

Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants in endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, and growth advantage. The presence of pre-S mutants in serum has been shown to predict the development of hepatocellular carcinoma (HCC) in HBV carriers. GGHs hence represent a potentially preneoplastic lesion. Whether a specific growth factor is overexpressed and activated in GGHs remains to be clarified. In this study, growth factor(s) up-regulated by pre-S mutants was identified using a growth factor array in HuH-7 cells. Immunohistochemistry, reverse-transcriptase polymerase chain reaction, and Western blot analysis were performed to study the participation of these genes and their signal pathways in HuH-7 cells and liver tissues. We demonstrate that vascular endothelial growth factor-A (VEGF-A) was up-regulated by pre-S mutants in HuH-7 cells and further confirmed in GGHs by immunostaining. The VEGF-A up-regulation by pre-S mutants could be suppressed by vomitoxin, an ER stress inhibitor. Furthermore, pre-S mutants-expressed HuH-7 cells exhibited activation of Akt/mTOR (mammalian target of rapamycin) signaling and increased growth advantage, which could be inhibited by VEGF-A neutralization. Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV-related nontumorous livers. Conclusion: The enhanced expression of VEGF-A in GGHs provides potential mechanism to explain the progression from preneoplastic GGHs to HCC in chronic HBV infection. (HEPATOLOGY 2009;49:1962–1971.)
Association between plasma concentrations of plasminogen activator inhibitor-1 and survival in patients with colorectal cancer
Authors: H. J. Nielsen, H. Pappot, I. J. Christensen, N. Brunner, O. Thorlacius-Ussing, F. Moesgaard, K. Dano, J. Grondahl-Hansen
Journal: BMJ (1998)

Editorial by Verspaget 

Invasion by cancer cells requires proteases such as the serine protease plasmin to degrade the cellular matrix. Plasmin is formed from its zymogen, plasminogen, a reaction catalysed by urokinase type plasminogen activator—which is implicated in invasion1—and partly regulated by plasminogen activator inhibitors. The active form of the inhibitor complexes with free and receptor bound active urokinase plasminogen activator and is bound by vitronectin in plasma and extracellular matrix.2

A high concentration of plasminogen activator inhibitor-1 in biopsy specimens from tumours is associated with a poor prognosis,3 and some patients with ovarian cancer have raised plasma concentrations of plasminogen activator inhibitor-1.4 We studied the prognostic importance of plasma concentrations of plasminogen activator inhibitor-1 in patients with colorectal …
Third World's Complex Disease Problems Compounded by Economic, Cultural Factors
Authors: Chris Anne Raymond
Journal: JAMA (1988)

WILL VACCINES eradicate parasitic diseases? Not in the near future, concluded a recent symposium on biomedical problems confronting the Third World. Those problems can seem insurmountable. At least 27 million children die each year of one of the top four killers—acute respiratory and circulatory diseases, low birth weight, or diarrhea—according to Julia A. Walsh, MD, Office of International Health, Harvard University School of Public Health, Boston. That understates the impact of other disabling but not immediately fatal diseases, such as onchocerciasis, tuberculosis, and leprosy, she noted at the New York Academy of Sciences meeting, "Under the Volcano: Biomedical Science and the Third World." The statistics are staggering, but there are success stories. Overall, experts estimate that close to 1 1/2 million children each year owe their lives to the Expanded Immunization Program instituted in 1974 by the World Health Organization (WHO) of the United Nations. But there are more diseases
THE DIAGNOSIS OF ULCER OF THE STOMACH AND DUODENUM BY THE ROENTGEN RAY
Authors: HARRY ADLER
Journal: JAMA (1910)

The recognition of ulcer of the stomach and duodenum is always so important and the diagnosis at times so difficult that any method must be welcomed which promises aid in those atypical cases where the absence of the cardinal symptoms permits only of a suspicion or, at most, of a presumption. The finding of blood in the stool, either visible or occult, has proved of great importance and constitutes a decided step in the forward direction; but when we remember that not infrequently in chronic ulcer even occult blood is absent for weeks at a time, this important means of diagnosis is often unavailable. Also, Murdock's orthoform test, being based on subjective symptoms, is usually untrustworthy. It is not my purpose to enter into the general subject of diagnosis of ulcer, but simply to call attention to the valuable aid the<i>x</i>-ray examination has furnished in a number of
IMMUNITY FACTORS IN PNEUMOCOCCUS INFECTION IN THE DOG
Authors: Carroll G. Bull
Journal: The Journal of Experimental Medicine (1916)

Intravenous inoculations of from 1 to 3 cc. per kilo of body weight of a bouillon culture of virulent pneumococci produce septicemia and meningitis in dogs. The injected pneumococci leave the circulation rapidly, but begin to reinvade the blood from 24 to 48 hours later. The septicemia reaches its climax between the 4th and 5th days and then abruptly declines, the blood becoming sterile within from 1 to 3 days after the height of the septicemia is reached. The initial disappearance of the pneumococci from the circulation has been found to be due to agglutination of the diplococci in the blood stream and accumulation of the clumps in the lungs, liver, spleen, etc. If the dogs are reinoculated during the ascension of the septicemia, the injected diplococci leave the circulation as rapidly as in normal dogs. Cultures isolated in this stage of the infection, both before and from 3 to 4 hours after the reinoculation, are resistant to the agglutinins and opsonins of immune sera that agglutinate and opsonize the cultures with which the dogs were originally infected. Thus it follows that the pneumococci are able to reinvade the circulation because they have acquired a fastness to the existing antibodies and not because the antibodies have been bound or exhausted. By reinoculating dogs at the time of the crisis in the septicemia it has been shown that the agglutination of the pneumococci is more rapid and complete and that the diplococci leave the circulation much more rapidly than in normal dogs. Hence acquired antibodies are operative within the animals at this time although they cannot be demonstrated in vitro until from 24 to 48 hours later. Pneumococci isolated as the infection is subsiding are more susceptible to the action of immune sera than the original cultures injected. It is probable that all the dogs would have survived the infection if a meningitis had not developed. In the acutely fatal cases of meningitis few pneumococci are phagocyted, while in the milder and convalescent cases much phagocytosis occurs. It is suggested that the incubation period of infectious diseases is due to the fact that the infecting agents must become adapted to the adverse conditions encountered in the newly infected host before they can multiply sufficiently to produce the symptoms of disease. It is further suggested that epidemics may arise because the infectious agent is passed from person to person in the ascending stage of the disease and thus enters new hosts in a state of maximum resistance to the natural antibodies of such individuals. When early contacts are avoided, epidemics tend to subside because the infectious agent is weakened by the action of acquired antibodies during the period of convalescence.
The Common Cold
Authors: Arnold S. Monto
Journal: JAMA (1994)

The common cold has long been recognized as the acute condition most frequently affecting individuals of all ages.<sup>1</sup>In several community-based studies, the illness frequency ranged between four and six episodes per year in children aged 5 to 9 years and from three to five episodes in young adults, with higher rates in those living in crowded conditions or mothers exposed to young children.<sup>2,3</sup>Median duration varied from 7 to 13 days, in part dependent on age.<sup>4,5</sup>Given the frequency and duration of these illnesses it is not surprising that considerable public attention has been directed to their treatment. The expression "finding a cure for the common cold" has been heard frequently in the media. Identifying etiology was the first approach taken by the scientific community. Rhinoviruses were the agents most frequently isolated from persons with common colds, and their predominance became more apparent as techniques for
Creation of a Double Chimera after the Transplantation of Umbilical-Cord Blood from Two Partially Matched Unrelated Donors
Authors: J.N. Barker, D.J. Weisdorf, J.E. Wagner
Journal: New England Journal of Medicine (2001)

To the Editor: Despite promising outcomes in the transplantation into pediatric recipients of umbilical-cord blood from unrelated donors, the low cell dose adversely affects both the rate of hematopoietic recovery and the probability of survival.1–3 The cell dose is a major limitation of the procedure, particularly in adults. An alternative to the ex vivo expansion of cells, which has yet to be shown to be efficacious, is the transplantation of 2 closely HLA-matched units of umbilical-cord blood. We transplanted 2 units of umbilical-cord blood from male infant donors into a 53-year-old, 84-kg woman with accelerated-phase chronic myelogenous leukemia and . . .
Incurable Physician: An Autobiography.
Authors: John H. Raach
Journal: JAMA (1963)

This autobiography is fascinating reading. Dr. Alvarez has used the medium of autobiography with restraint, admirably recounting the events in a busy and full life. The story is told in a style that is lucid, concise, and chatty. Anyone having the privilege of knowing Dr. Alvarez could open the book to any page and, after a paragraph of reading, identify the author. Unlike so many autobiographies, it is not overloaded with the first person pronoun, nor is it limited to recounting events in the author's life. Almost a third of the book is devoted to meditations and reflections, and a philosophy of life for a professional man. His chapter, "Faith of a Physician," impresses this reviewer as being a splendid 20th century corollary to Sir Thomas Browne's<i>Religio Medici</i>. Many of the aphorisms scattered throughout reveal a strong Oslerian influence. Delightful, inspiring, and provocative reading—the book is a must for
Increased, tissue plasminogen activator antigen is predictive of cardiovascular events in the Veterans Affairs HDL Intervention Trial (VA-HIT)
Authors: Geoffrey H. Tofler, Sander J. Robins, Dorothea Collins, Izabela Lipinska, Prakash C. Deedwania, Hanna C. Rubins
Journal: Journal of the American College of Cardiology (2002)
Nutrition, Physical Fitness and Health
Authors: William R. Barclay
Journal: JAMA (1979)

This volume contains 22 chapters written by 39 authors, only two of whom are American; the others are largely from Europe. The book describes in great detail the metabolic requirements of athletes and those who perform heavy labor. It outlines the utilization of food for energy purposes by various body organs and describes the principal metabolic pathways by which food is ultimately reduced to energy plus metabolic byproducts. The diagrams, graphs, and tables are plentiful, are well done, and greatly aid the reader in following the text. The references are extensive, and I would judge them to be carefully selected and reasonably complete. This is one volume in an international series of sport sciences, and Richard C. Nelson and Chauncey A. Morehouse at Pennsylvania State University (who edit the series) have done a fine job of editing this text, for it reads as if written by someone whose native tongue