tbuckley/cabot-search huggingface dataset:
Assessment of illness severity in community acquired pneumonia: a useful new prediction tool?
Authors: M Woodhead
Journal: Thorax (2003)

The clinical heterogeneity of CAP means that no severity scoring system will ever be able consistently to separate all patients into correct management subgroups, but the recently developed CURB-65 prediction tool appears to be an advance.

Illness severity might usefully guide a number of management decisions in the care pathway of a patient with community acquired pneumonia (CAP). Whether to refer to hospital by the primary care physician, whether to admit by the hospital junior doctor, what investigations to perform, what antibiotic(s) to give, and whether to admit to the intensive care unit (ICU) are just some examples. This approach is captured to a varying extent in a number of the published management guidelines for CAP.1–5 While a clinical prediction tool to assess severity might therefore be helpful, there is no agreement on what constitutes the best approach to this. Additional caveats are that such a tool would need to be better than current practice, would need to accurately do what it sets out to do (that is, predict outcome), would need to be simple to use in a variety of settings, would need to have been shown to alter outcomes, and would need to actually be usable in clinical practice.

That current practice is inadequate is suggested by a number of studies. The mortality rate of 5–10% of adults admitted to hospital is well recognised—some of these deaths might be preventable. Routine clinical judgement was found to underestimate illness severity in one study6 and another found illness severity assessment to be the most common failing in the management of young adults dying from CAP.7 Severity assessment before ICU admission has been found to be suboptimal for a wide variety of conditions,8 and the variation in hospital9–13 and ICU14 admission rates for …
Abstract 4651: Sorafenib and its derivatives induce apoptosis and autophagy in canine mammary tumor cells
Authors: Yi-Yen Lee, Kuen-Feng Chen, Chung-Hsi Chou, Chen-Si Lin
Journal: Cancer Research (2012)

Abstract Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Radiation treatment, chemotherapy and surgical removal are conventionally applied for treating CMTs; however, the efficacy is limited and a study showed around 48% of dogs died or were euthanized within one year due to recurrence or metastasis of the tumor after surgical removal. Recently, Sorafenib (Nexavar®), a multiple kinase inhibitor, has shown survival benefits in human patients with human hepatocellualr carcinoma (HCC) and is the first clinically approved drug for treating HCC. Except HCC, Sorafenib also showed certain effect on the treatment of human renal cell carcinoma, thyroid cancer, and, also, breast cancer. In this study, derivatives of sorafenib (SC-1 &amp; CY-13) made by depleting the kinase inhibitory activities were investigated for their therapeutic efficacy in canine mammary tumors. Three CMT cell lines including CMT-1, CF41.mg and MPG were treated with sorafenib, SC-1 and CY-13. The results showed SC-1 owned stronger potency than other two compounds in suppressing tumor cell growth. Lower LD50 and earlier onset of cell death were found in SC-1-treated groups. The SC-1-mediated CMT cell death was through both apoptosis and autophagy since DNA fragmentation and autophagosome were observed in treated cells. These sorafenib derivatives were previously reported as novel inhibitors for STAT3. Here we also found that SC-1 down-regulated phospho-STAT3 (p-STAT3) at tyrosine 705 in all tested CMT cells. Expression of STAT3-driven genes, including cylcin D1 and survivin, was also repressed by SC-1. Although the in vivo anti-tumor efficacy of SC-1 will be soon evaluated, our preliminary results have provided a lead for drug development of canine mammary tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4651. doi:1538-7445.AM2012-4651
FOREIGN BODY IN SIGMOID
Authors: E. W. Simmons
Journal: JAMA (1924)

A. K., a man, aged 43, was brought to my office with a rectal hemorrhage. He had inserted an "electric" dilator into the rectum for the treatment of constipation, and had allowed it to slip by the sphincter. In trying to extract it, he had forced it up the rectum to the flexure of the sigmoid. When I saw him, the lower end of the appliance was 7 or 8 inches above the anus. The patient had tried to remove it with a pair of pliers, and had badly torn the rectal mucosa and had lost a large amount of blood. A rectal speculum was introduced under general anesthesia, and I attempted to remove the object by means of a sponge forceps, without success, as the point of the dilator was rammed into a curve of the sigmoid, and a fold of mucosa was caught around the electric terminals of
Prevention of Injuries to Children-Reply
Authors: J. Alex Haller
Journal: JAMA (1983)

In Reply.—  I strongly agree with Dr King's thoughtful emphasis on the primary need for better programs of injury prevention, but I hope he does not mean as opposed to these... remedies but rather along with these... remedies! Physicians should lead the way toward control of drunk driving, handguns, flammable fabrics, and caustic and toxic substances, but an informed, concerned  must demand the enforcement. Along the way, better systems of tertiary care for trauma victims will decrease morbidity and mortality from this disease of modern society until  will enable us to have a higher rate of prevention. I wholeheartedly join Dr King in his suggested programs for decreasing the number of childhood injuries.
It's Over, Debbie
Authors: John G. Manesis
Journal: JAMA (1988)

<h3>To the Editor.</h3> —I was both saddened and angry when I read "It's Over, Debbie"<sup>1</sup>in a recent issue of<i>JAMA</i>. The author revealed, quite unintentionally, I think, a great deal about himself aside from the fact that he committed murder. This physician is obviously very angry and cynical; at an early stage in his medical career he resents telephone calls and intrusions on his privacy when he is on call. Without discussing the case with the attending physician and after a very cursory review of the medical record, he took it on himself to give the patient a lethal injection after telling her that he was going to "let her rest and to say good-bye." This injection was made in the presence of an older woman at the bedside who "seemed relieved" when the patient died. I am outraged by the action of the physician in this case
Hypnotism and Double Personality.
Authors: R. Osgood Mason
Journal: JAMA (1895)

New York, Dec. 16, 1895. <h3>To the Editor:</h3> —I am in doubt whether such a tirade as your correspondent on "Hypnotism" in the last number of theJournalhas indulged in deserves notice; for I very much doubt whether of the 5,000 or 6,000 intelligent physicians who read theJournalmany will be found who sympathize with the spirit which it manifests. Passing by its scurrility, let me say to the readers of theJournalthat in these days it is scarcely necessary to discuss the "views" of men who on account of their dense ignorance of the subject have no right to have an opinion, but it<i>is</i>necessary to become acquainted with<i>facts</i>and to discuss them in a scientific spirit. Judging by the number of letters of inquiry I have received since the appearance of the articles on hypnotism in theJournalof Nov. 30, I am
How to Read a Paper: T Greenhalgh. London: BMJ Publishing Group, 2001, pound16.95, illustrated, pp 222. ISBN 0 7279 1578 9
Authors: G Misiewicz
Journal: Gut (2002)

I suppose people still read scientific papers, or so editors of scientific journals and their publishers would like to believe, and this is the assumption implicit in the title of this excellent book. On the other hand, the abundance of reviews, summaries, and refresher courses sometimes makes me wonder who actually reads them. Apart from researchers active in their particular corner of the field and referees engaged in peer review, most people, I fancy, only read the abstract.

When a while ago I was appointed to the editorship of Gut , I had my introductory meeting with Stephen Lock, the then editor of the BMJ and editor in chief of all of the BMA journals. George, …
Head and Neck Injuries in High School Football
Authors: Richard H. Alley
Journal: JAMA (1964)

Of 19,413 high school football players that were studied, the incidences of head and neck injury were found to be 1.0% and 0.6% respectively. Comparison with results of a 1948 study revealed a decrease in head injury incidence of 57% since that time. This reduction corresponds with the more widespread use of the hardshell plastic helmet and the double-bar faceguard. Factors producing injury in 182 head and neck injuries studied included improper fitting of headgear, the practice of "spearing," violations of basic fundamentals of football play, and inadequate physical conditioning. The vast majority of neck injuries were sustained in flexion, and the faceguard was found not culpable in the production of those injuries. Efforts to cause helmets to impinge on the posterior neck during hyperextension were unsuccessful when helmets were properly fitted.
Efficacy of Oral Psychosedative Drugs for Preanesthetic Medication
Authors: William J Murray
Journal: JAMA (1968)

The effectiveness of five oral preanesthetic medications has been evaluated in a blind, randomized study of 712 elective surgical patients predicted to become apprehensive preoperatively. A barbiturate (pentobarbital sodium, 200 mg), a nonbarbiturate hypnotic sedative (ethchlorvynol, 1,000 mg and 400 mg), and three minor tranquilizers (diazepam, 20 mg and 10 mg; hydroxyzine hydrochloride, 200 mg; and oxazepam, 60 mg) were the pharmacological classes investigated. Pentobarbital, ethchlorvynol, and diazepam were statistically differentiated from hydroxyzine, oxazepam, and a placebo. Antiapprehensive activity could only be demonstrated in patients who also became drowsy. Three methods of evaluation (nurse observerinterviewer, patient self-assessment, anesthetist's impression) were employed. It is proposed that when preanesthetic sedation is required, the use of oral drug forms can provide a safer route of administration and eliminate the risks of injection.
Abstract 2482: Development of novel small-molecule inhibitors of androgen receptor variants lacking the ligand-binding domain.
Authors: Xiaohong Tian, Weiguo Liu, Guoyan Geng, Jian Hui Wu
Journal: Cancer Research (2013)

Abstract Over 30,000 men die from prostate cancer in Canada and USA each year. Current therapeutic strategy for advanced prostate cancer is to suppress androgen receptor (AR) signaling by reducing level of androgens (via castration) and by antiandrogens to compete with endogenous androgens for binding in the AR ligand-binding domain (LBD). Despite of initial response, lethal ‘castration-resistant’ prostate cancer (CRPC) arises as a result of oncogenic reactivation of the AR. Current treatments for CRPC provide only a modest improvement in overall survival (a few months). It is now firmly established that reactivation of the AR signaling in CRPC is due to multiple mechanisms, including point mutations in the AR LBD and expression of AR variants lacking the LBD. Recently, a series of AR splice variants lacking the LBD, such as AR-v7, were identified from tissue specimen of CRPC patients. Significantly, AR-v7 is constitutively active even in the absence of androgens and it is thus no longer possible to be inhibited by conventional LBD-targeting antiandrogens (such as bicalutamide) or by androgen-depleting agents (such as Abirateron). This potentially provides a novel mechanism for the development of CRPC. Our recent work has identified a novel chemical compound that inhibits AR-v7 in reporter assays. We found this compound is also active against full-length ARs, including the wild type and multiple clinically-relevant mutant ARs, such as the T877A, H874Y and W741C mutants. Our study indicated this compound targets the N-terminal domain of the AR. We have obtained structure-activity relationship (SAR) of this compound. Citation Format: Xiaohong Tian, Weiguo Liu, Guoyan Geng, Jian Hui Wu. Development of novel small-molecule inhibitors of androgen receptor variants lacking the ligand-binding domain. [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 2482. doi:10.1158/1538-7445.AM2013-2482
Rare complete loss of function provides insight into a pleiotropic genome-wide association study locus
Authors: Vijay G. Sankaran, Mugdha Joshi, Akshat Agrawal, Klaus Schmitz-Abe, Meghan C. Towne, Nicholas Marinakis, Kyriacos Markianos, Gerard T. Berry, Pankaj B. Agrawal
Journal: Blood (2013)
Interleukin-28B polymorphisms and hepatitis C virus clearance
Authors: Kazuaki Chayama, C Nelson Hayes
Journal: Genome Medicine (2013)

In 2009, several independent studies revealed a strong association between genetic variation in the interleukin-28B (IL28B) locus and the outcome of treatment for chronic infection with hepatitis C virus (HCV). Hundreds of studies followed, and a recent meta-analysis reports more precise odds ratios than previously published for associations between commonly reported IL28B polymorphisms and spontaneous HCV clearance or treatment outcome. These results should facilitate the interpretation of IL28B genotyping as part of personalized treatment approaches.
Onchodermatitis—correlation between skin disease and parasitic load in an endemic focus in Ecuador
Authors: R.J. HAY, C.D. MACKENZIE, R. GUDERIAN, W.C. NOBLE, J.R. PROANO, J.F. WILLIAMS
Journal: British Journal of Dermatology (1989)

Onchocerciasis is a chronic parasitic infection in which infiltration of the skin by microfilariae has been associated with a number of different pathological changes. This survey compared the prevalence of different forms of skin disease in two villages, one of which was located within the endemic zone for onchocerciasis (Zapallo Grande), in a lowland rain forest area of western Ecuador. The commonest skin diseases in both villages were scabies, pyoderma and pityriasis versicolor. In addition changes closely correlated with the presence of microfilariae in skin snips were found in Zapallo Grande–such as atrophic gluteal changes, and acute and chronic papular dermatitis. The only other skin disease associated with onchocerciasis was widespread tinea corporis due to T. rubrum. The Amerindians in the endemic onchocerciasis area were more likely than Negroes to have generalized atrophic atrophic changes of the skin, whereas in the latter group significant numbers of individuals had no obvious skin lesions but large numbers of microfilariae were detected in skin snips. Acute papular dermatitis was common in both groups and in biopsied lesions microfilariae could usually be identified within the epidermis or close to the dermo-epidermal junction. One patient had developed severe reactive onchodermatitis (Sowda). Swabs taken from onchocercal skin lesions showed no evidence of skin surface carriage of Staphylococcus aureus. Changes classically associated with onchocerciasis such as pretibial hypopigmentation (leopard skin) and hanging groin were notably absent in this population.
Endothelium-dependent inhibition of ergonovine-induced contraction is impaired in porcine coronary arteries with regenerated endothelium.
Authors: H Shimokawa, N A Flavahan, J T Shepherd, P M Vanhoutte
Journal: Circulation (1989)

The inhibitory effects of the endothelium against ergonovine-induced contraction were examined in isolated porcine coronary arteries under normal conditions and after endothelial regeneration. Endothelium-dependent responses were examined in vitro in normal Yorkshire pigs (n = 16) and in pigs that had undergone balloon endothelium removal of the left anterior descending coronary artery (LAD) 4 weeks before the study (n = 10). The presence of a complete endothelial lining was confirmed histologically. In rings from normal arteries contracted with prostaglandin F2 alpha in the presence of indomethacin and ketanserin (a 5-HT2-serotonergic blocker), ergonovine caused endothelium-dependent relaxations. They were attenuated by rauwolscine (an alpha 2-adrenergic blocker), inhibited by methiothepin (a combined 5-HT1- and 5-HT2-serotonergic blocker) or by pertussis toxin (an inhibitor of several G proteins) and abolished by oxyhemoglobin (a selective inactivator of endothelium-derived relaxing factor). In quiescent rings from normal arteries, ergonovine caused contractions that were inhibited by the presence of the endothelium; this endothelium-dependent inhibition was abolished by oxyhemoglobin. The direct contractions were not affected by prazosin (an alpha 1-adrenergic blocker), rauwolscine, 6-hydroxydopamine (an agent causing chemical sympathetectomy), or diphenhydramine (an H1-histaminergic blocker) but were inhibited by ketanserin. In rings with regenerated endothelium contracted with prostaglandin F2 alpha, the endothelium-dependent relaxations to ergonovine were reduced significantly and were not inhibited by pertussis toxin. In quiescent rings with regenerated endothelium, the endothelium-dependent inhibition of ergonovine-induced contraction was less.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunogenicity Evaluation of Subcutaneous Administration of Peptide Hydrolysate from Lolium Perenne (gpASIT+™) in Combination with Bacterial HSP70 (DnaK) in Patients with Seasonal Allergic Rhinitis: A Double Blind Placebo Controlled Trial
Authors: Mohamed H. Shamji, Jan L. Ceuppens, Peter W. Hellings, Stephen Durham, Jean Duchateau, Rebecca Parkin, Thierry Legon, Sabine Pirotton
Journal: Journal of Allergy and Clinical Immunology (2015)
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: William J. Kuhns
Journal: The Journal of Experimental Medicine (1954)

The method of filter paper electrophoresis was used to study proteins and protein-bound polysaccharides in sera obtained from subjects before and after a single booster dose of diphtheria toxoid, and in sera from allergic subjects. The electrophoretic patterns of precipitating antitoxic sera resembled those found in normal non-immune sera. However, skin-sensitizing antitoxic sera were distinguished by a relatively large beta globulin component and a small or indistinct alpha2 globulin. Fusion of both components was present in some sera containing this variety of antitoxin. Considerable amounts of serum-bound polysaccharides in these sera migrated relatively slowly in contrast to the behavior of polysaccharides of precipitating antitoxic sera which migrated faster when tested under similar conditions. Alterations in proteins and carbohydrates were most readily observed in specimens containing high titers of antitoxin. There were no demonstrable differences between the electrophoretic behavior of sera obtained from subjects before or after immunization with toxoid. Electrophoretic patterns of serum from allergic subjects who developed marked eosinophilia showed attenuation of the alphas globulin associated with a relative preponderance of slow migrating protein-bound polysaccharides. These alterations were not present in sera obtained from the same persons before and after the development of eosinophilia. Changes in the proteins and polysaccharides could not be demonstrated with consistency in subjects with mild to moderate hay-fever symptoms. One person who developed severe acute hay-fever symptoms showed alterations in the beta and alpha2 globulins. Rheumatic fever subjects showed no unusual changes in the distribution of serum components. However, transition from the acute process to convalescence is graphically demonstrated by the marked decreases in gamma and alpha globulins and in protein-bound carbohydrates.
Cx30 in the sinus node of murine heart: just one connexin more, or more? Evidence for a construction principle?
Authors: S. Dhein
Journal: Cardiovascular Research (2009)

One of the differences between a mere accumulation of cells and a tissue or even an organ is that in organized forms (tissue, organ) cells typically communicate with each other. They coordinate their function, growth, and differentiation. In addition to cell adhesion molecules, increted hormones and local mediators, direct intercellular communication via gap junction channels plays a key role in this process. In cardiac tissue, these channels also provide the basis for the propagation of the action potential from cell to cell.

Gap junction channels are dodecameric proteins consisting of connexin subunits of one (homomeric channels) or more isoforms (heteromeric channels). The connexins belong to an evolutionarily old protein family comprising 21 members in the mouse and 20 in man.1 In the mammalian heart typically three connexins are expressed: Cx43, encoded by the gene Gja1, is the most abundant; Cx40, encoded by Gja5, is confined to atria and the specific conduction system; Cx45, encoded by Gjc1, is found in early stages of development and in the specific conduction system, including sinus nodal cells.

In recent years, murine Cx30.2, encoded by Gjd3, (the murine orthologue of human Cx31.9, encoded by Gjd3 Ref here?) and now Cx30, encoded by Gjb6, (see the report by Gros et al .2) have been found in the murine heart. Cx30 expression was limited to a narrow epicardial layer of the sinus node. Since Cx30-deficient … 

*Corresponding author. Tel: +49 341 865 1651, Fax: +49 341 865 1452, Email: dhes{at}medizin.uni-leipzig.de
Trends in Embryo-Transfer Practice and in Outcomes of the Use of Assisted Reproductive Technology in the United States
Authors: Tarun Jain, Stacey A. Missmer, Mark D. Hornstein
Journal: New England Journal of Medicine (2004)

During the past decade in the United States, increasing attention has been paid to lowering the incidence of multiple gestations resulting from the use of assisted reproductive technology. To determine whether such efforts have been successful, we assessed national trends in embryo-transfer practice patterns and in outcomes after the use of assisted reproductive technology.We analyzed data on outcomes of assisted reproductive technology procedures as reported to the Centers for Disease Control and Prevention from 1995 to 2001 by fertility clinics in the United States. We also analyzed data from the National Center for Health Statistics on the rates of twin births and triplet or higher-order multiple births.From 1995 to 2001 in the United States, the number of infertility clinics, the number of fresh-embryo cycles initiated, and the number of fresh-embryo transfers increased steadily. The average number of embryos transferred per cycle began decreasing in 1997, with the steepest decline (an 11.1 percent decrease) between 1998 and 1999. In contrast, the number of pregnancies and live births per cycle during the period from 1995 to 2001 steadily increased. Even though the percentage of pregnancies with twins did not change significantly between 1997 and 2001, the percentage of pregnancies with three or more fetuses significantly decreased every year, with the steepest decline (a 20.8 percent decrease) between 1998 and 1999, after the publication in 1998 of the American Society for Reproductive Medicine guidelines for embryo transfer.Since 1997 in the United States, there have been consistent decreases in both the number of embryos transferred per cycle and the percentage of pregnancies with three or more fetuses, as well as a consistent increase in the percentage of live births per cycle.