tbuckley/cabot-search huggingface dataset:
Searching for unpublished data for Cochrane reviews: cross sectional study
Authors: J. B. Schroll, L. Bero, P. C. Gotzsche
Journal: BMJ (2013)

<b>Objective</b> To describe the experiences of authors of Cochrane reviews in searching for, getting access to, and using unpublished data. <b>Design</b> Cross sectional study. <b>Setting</b> Cochrane reviews. <b>Participants</b> 2184 corresponding authors of Cochrane reviews as of May 2012. <b>Main outcome measure</b> Frequencies of responses to open ended and closed questions in an online survey. <b>Results</b> Of 5915 authors contacted by email, 2184 replied (36.9% response rate). Of those, 1656 (75.8%) had searched for unpublished data. In 913 cases (55.1% of 1656), new data were obtained and we received details about these data for 794 data sources. The most common data source was "trialists/investigators," accounting for 73.9% (n=587) of the 794 data sources. Most of the data were used in the review (82.0%, 651/794) and in 53.4% (424/794) of cases data were provided in less than a month. Summary data were most common, provided by 50.8% (403/794) of the data sources, whereas 20.5% (163/794) provided individual patient data. In only 6.3% (50/794) of cases were data reported to have been obtained from the manufacturers, and this group waited longer and had to make more contacts to get the data. The data from manufacturers were less likely to be for individual patients and less likely to be used in the review. Data from regulatory agencies accounted for 3.0% (24/794) of the obtained data. <b>Conclusions</b> Most authors of Cochrane reviews who searched for unpublished data received useful information, primarily from trialists. Our response rate was low and the authors who did not respond were probably less likely to have searched for unpublished data. Manufacturers and regulatory agencies were uncommon sources of unpublished data.
Demonstration of Large Bladder Diverticulum on Bone Scan
Authors: Cheng-Pei Chang, Chin-Hsien Tsai, Jyh-Hwa Chen, Ming-Huei Sheu, Hung-Jen Hsieh, Wei-Da Chang, Shu-Quinn Liao, Ren-Shyan Liu
Journal: Clinical Nuclear Medicine (2005)

A 74-year-old man underwent low anterior resection for rectal cancer. Technetium-99m methylene diphosphonate (MDP) bone scanning was performed as part of the patient's postoperative follow-up study. Scans revealed an area of increased tracer uptake in the left hemipelvis. Coronal single-photon emission computed tomography and caudal images clearly separated the lesion from the skeletal structures. Transverse magnetic resonance images showed a large diverticulum originating from the left lateral wall of the bladder. The pelvic findings on the bone scan were the result of tracer retained within this diverticulum.
Histone deacetylase inhibitors (HDACIs). Structure—activity relationships: history and new QSAR perspectives
Authors: Eleni Pontiki, Dimitra Hadjipavlou‐Litina
Journal: Medicinal Research Reviews (2010)

Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. HDAC inhibitors (HDACIs) block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumor cells. In this article, a survey of published quantitative structure-activity relationships (QSARs) studies are presented and discussed in the hope of identifying the structural determinants for anticancer activity. Secondly a two-dimensional QSAR study was carried out on biological results derived from various types of HDACIs and from different assays using the C-QSAR program of Biobyte. The QSAR analysis presented here is an attempt to organize the knowledge on the HDACIs with the purpose of designing new chemical entities with enhanced inhibitory potencies and to study the mechanism of action of the compounds. This study revealed that lipophilicity is one of the most important determinants of activity. Additionally, steric factors such as the overall molar refractivity (CMR), molar volume (MgVol), the substituent's molar refractivity (MR) (linear or parabola), or the sterimol parameters B(1) and L are important. Electronic parameters indicated as σ(p), are found to be present only in one case.
RISK OF CARDIOVASCULAR EVENTS IN CORONARY ARTERY DISEASE PATIENTS ON CLOPIDOGREL WITH AND WITHOUT CYP2C19*2 POLYMORPHISM: AN UPDATED COMPREHENSIVE META-ANALYSIS
Authors: Mukesh Singh, Tejaskumar Shah, Sasikanth Adigopula, Evyan Jawad, Sandeep Khosla, Rohit Arora
Journal: Journal of the American College of Cardiology (2011)
Antagonistic Regulation by the Transcription Factors C/EBPα and MITF Specifies Basophil and Mast Cell Fates
Authors: Xiaopeng Qi, Jessie Hong, Lee Chaves, Yonghua Zhuang, Yuhong Chen, Demin Wang, Jacob Chabon, Brian Graham, Keitaro Ohmori, Yapeng Li, Hua Huang
Journal: Immunity (2013)
The Importance of Being Cis: Evolution of Orthologous Fish and Mammalian Enhancer Activity
Authors: Deborah I. Ritter, Qiang Li, Dennis Kostka, Katherine S. Pollard, Su Guo, Jeffrey H. Chuang
Journal: Molecular Biology and Evolution (2010)

Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers, but a critical issue is how well orthologous CNE sequences retain the same activity in their respective species, a characteristic important for generalization of model organism studies. To quantify how well CNE enhancer activity has been preserved, we compared the anatomy-specific activities of 41 zebra fish CNEs in zebra fish embryos with the activities of orthologous human CNEs in mouse embryos. We found that 13/41 (∼30%) of the orthologous CNE pairs exhibit conserved positive activity in zebra fish and mouse. Conserved positive activity is only weakly associated with either sequence conservation or the absence of bases undergoing accelerated evolution. A stronger effect is that disparate activity is associated with transcription factor binding site divergence. To distinguish the contributions of cis- versus trans-regulatory changes, we analyzed 13 CNEs in a three-way experimental comparison: human CNE tested in zebra fish, human CNE tested in mouse, and orthologous zebra fish CNE tested in zebra fish. Both cis- and trans-changes affect a significant fraction of CNEs, although human and zebra fish sequences exhibit disparate activity in zebra fish (indicating cis regulatory changes) twice as often as human sequences show disparate activity when tested in mouse and zebra fish (indicating trans regulatory changes). In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of ∼30% of human CNEs can be determined from experiments in zebra fish alone, and to identify these CNEs, both the zebra fish and the human sequences should be tested.
Multiple Organ Failure: Pathophysiology and Basic Concepts of Therapy
Authors: John H. Wulsin
Journal: JAMA (1991)

Multiple organ failure plagues the care of patients admitted to intensive care settings and accounts for most of the deaths during prolonged stays, hence the vital importance of this subject for physicians. Recognition and understanding of the patterns that this syndrome can evince have evolved relatively recently, over the past 15 or so years, coincidentally with the explosive growth of intensive care units in secondary and tertiary medical centers. This volume, edited by E. A. Deitch, MD, professor of surgery at Louisiana State University, compiles basic information on the various aspects of this puzzling and imperfectly known group of conditions, seemingly interrelated under the title of multiple organ failure. Some 30 authors, mostly surgeons, discuss the syndrome according to systems, including gastrointestinal tract, cardiovascular system, respiratory tract, liver, and kidneys. There are also chapters on nutrition, infection, and metabolic changes as they apply. In an excellent summary and overview, Dr
IgE‐binding activity to enzyme‐digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion
Authors: K. Yamada, A. Urisu, H. Koyama, R. Tokuda, E. Wada, Y. Kondo, H. Ando, Y. Morita, S. Torii
Journal: Allergy (2000)

Background : We occasionally see egg‐allergic children who develop contact urticaria to hen's egg despite the absence of the overt symptoms on ingestion. The mechanisms remain to be elucidated. Methods : Twenty‐one subjects with positive reactions to 20‐min patch tests for egg‐white antigens were divided into subgroups with positive ( n =10) and negative ( n =11) results to oral challenge tests by the same antigens. We measured IgE antibody for egg white and its components, and IgE‐binding activities to digestive enzyme‐treated ovomucoid by RAST inhibition. Results : There were no significant differences in IgE antibody titers to egg white (positive vs negative: 30.3% vs 15.3%, P =0.130), ovomucoid (21.5% vs 10.2%, P =0.078), ovotransferrin (9.9% vs 3.7%, P =0.105), and lysozyme (3.4% vs 2.9%, P =0.944), except ovalbumin (16.8% vs 5.6%, P =0.024), between the positive and negative subjects in the provocation tests. In contrast, the concentration (1.93 μg/ml) of pepsin‐treated ovomucoid needed for 50% RAST inhibition in the challenge‐positive subjects was significantly ( P =0.0003) lower than that(114.9 μg/ml) of negative subjects. Similar but less significant differences were obtained when ovomucoid fragments treated with chymotrypsin (0.91 μg/ml vs 6.86 μg/ml, P =0.014) and trypsin (0.75 μg/ml vs 4.67 μg/ml, P =0.041) were used as inhibitors. Conclusions : We suggest that IgE antibodies from subjects showing contact urticaria despite the absence of reactions to the ingestion of egg white recognize the epitope(s) unstable to digestive enzymes.
Transplantation of insulin-secreting multicellular spheroids for the treatment of type 1 diabetes in mice
Authors: Kosuke Kusamori, Makiya Nishikawa, Narumi Mizuno, Tomoko Nishikawa, Akira Masuzawa, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Journal: Journal of Controlled Release (2013)
Adenovirus Infection in Intussusception in Children in Taiwan
Authors: Eugene J. Clarke
Journal: JAMA (1969)

Fifty-seven cases of intussusception were evaluated in Taipei, Taiwan, in a two-year period. Fifteen (26%) of the patients showed adenovirus infection as evidenced by recovery from throat swab, rectal swab, or mesenteric node removed at surgery. Adenovirus infection was demonstrated in only 3 (3%) of 85 neighborhood or wellbaby-clinic controls each matched for age, sex, and time of occurrence. Enterovirus infection was found to be equally frequent in each of the three groups. These study cases were shown to be similar to a ten-year case record review of hospitalized patients in Taipei (1955 to 1964), in regard to predominance of infant patients, high male-female ratio, and predominant seasonal occurrence in the first half of the year. The observations in this study that intussusception of infancy is often associated with adenovirus infection would tend to support the hypothesis that the early enteric spread of adenovirus in Taipei contributes to intussusception.
Spread of contraction in rabbit ear artery preparations in response to stimulation by norepinephrine.
Authors: M Vonderlage
Journal: Circulation Research (1981)

To investigate the spread of contraction in the rabbit ear artery, changes in segment diameter were measured after local stimulation. No spread of contraction was produced by direct current or local application of norepinephrine (NE). Repetitive electrical stimulation caused contraction which spread far from the point of excitation. Since 2 x 10(-7) g/ml tetrodotoxin (TTX) or 10(-5) M phentolamine prevented this spread of contraction, we concluded that it depends on normal function of periarterial nerves and of the alpha-adrenergic receptors at the site of the smooth muscle cells. To check this conclusion and exclude the possibility of myogenic propagation, which normally is due to the conduction of action potentials, the relation between membrane potential of smooth muscle cells and the rapid phase of the contractile response after rapid addition of NE was investigated. In both polarized and depolarized tissues NE induces a biphasic contractile response with no difference in latency. Membrane potential does not change during mechanical latency after the rapid addition of 5 x 10(-9) - 5 x 10(-6) g/ml NE. There are only slight differences in contraction amplitude and maximum rate of tension development when strips from polarized and depolarized tissues incubated in Ca2+-free solution are stimulated by NE. These findings support the conclusion that spread of contraction is not due to myogenic propagation.
A Further Report on the Chorda Tympani Syndrome
Authors: A. G. Young, G. E. Stein
Journal: BMJ (1960)

MlUICAL JOURNAL palliative, but any therapy capable of affording sympto- matic relief to over two-thirds of otherwise untreatable patients should not remain neglected.Summary 25 patients with advanced lung cancer were treated with HN2.The results are described, and some correlation with the tumour cytology is made.A regime for minimizing the side-effects of HN2 is described in detail.The literature is briefly reviewed.It is a pleasure to thank Drs.
Environmentally relevant metal and transition metal ions enhance Fc epsilon RI-mediated mast cell activation.
Authors: Aurelia Walczak-Drzewiecka, Janina Wyczólkowska, Jaroslaw Dastych
Journal: Environmental Health Perspectives (2003)

Upon contact with allergen, sensitized mast cells release highly active proinflammatory mediators. Allergen-mediated mast cell activation is an important mechanism in the pathogenesis of atopic asthma. Asthmatic patients are especially susceptible to air pollution. Epidemiologic studies found a positive correlation between severity of symptoms among asthmatic patients and the level of particulate matter (PM) in the air. Among the constituents of PM are metals and transition metals, which could mediate some of its adverse effects on human health. We sought to determine the effect of metal and transition metal ions on allergen-mediated mast cell activation. We observed that several metal and transition metal ions activated mast cells and enhanced allergen-mediated mast cell activation. Thus, Al(3+), Cd(2+), and Sr(2+) induced release of granule-associated N-acetyl-ss-d-hexosaminidase, and Al(3+) and Ni(2+) enhanced antigen-mediated release. Metal and transition metal ions also induced significant secretion of interleukin (IL)-4 and increased antigen-mediated IL-4 secretion in mast cells. These effects of metal and transition metal ions on mast cells were observed at concentrations that do not result in direct cytotoxicity and might be relevant for environmental exposure. Thus, metals and transition metals could increase the level of allergen-mediated mast cell activation, which might be one of the mechanisms mediating exacerbation of allergen-driven asthma symptoms by air pollution.
STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION
Authors: Fred Allison, Mary Ruth Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1955)

A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions. 1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium. 2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells. 3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood. 4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury. 5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis. 6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass. 7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure. 8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations occur as the result of proximal arteriolar dilatation and distal occlusion of vessels. 9. Once they have reached the extravascular tissues the leucocytes move about more or less at random, apparently uninfluenced by any compelling chemotactic force. Their resultant migration, however, is toward the site of injury around which they eventually tend to congregate. 10. The histiocytes normally present in the connective tissue appear to play no role in the type of acute inflammatory reaction produced in these experiments.
Indian government denies health impact of brown cloud
Authors: S. Kumar
Journal: BMJ (2002)

Scientists in India are claiming that the Asian brown cloud is not something specific to Asia and does not have a knock-on effect on pollution related mortality.

The cloud, almost the size of United States, has been described by experts from the United Nations' environment programme as a blanket of brown haze 3 km deep. They say that it hangs over a vast territory encompassing the northern Indian Ocean, India, Pakistan, and much of South Asia, South East Asia, and China for as long as four winter months a year.

The cloud is caused mostly by …
CHARACTERIZATION OF IMMUNOGLOBULIN STRUCTURES FROM THE SURFACE OF CHRONIC LYMPHOCYTIC LEUKEMIA CELLS
Authors: Trond Eskeland, Eva Klein, Masaharu Inoue, Bo Johansson
Journal: The Journal of Experimental Medicine (1971)

Chronic lymphocytic leukemia cells with relatively large amounts of mu and kappa immunoglobulin structures on the surface, and apparently very small amounts intracellularly, were subjected to homogenization or washing after freezing and thawing. After a light centrifugation, which sedimented the nuclei and unbroken cells, most of the immunoglobulin structures were found in the supernatant. Ultracentrifugation, which was performed to remove the membranes from the supernatant, sedimented only half the amount of the immunoglobulin structures. By sucrose density gradient ultracentrifugation and Sephadex G-200 filtration, the unsedimented immunoglobulin structures were shown to consist of 7S IgM and free kappa chains. About 80,000 7S IgM molecules were calculated to be present on each cell. The amount of kappa chains not associated with IgM was estimated to be equal to the amount of kappa chains in IgM. Inhibition of passive hemagglutination was used to detect and quantitate the immunoglobulin structures.
Infective Endocarditis in Drug Addicts
Authors: DAVID Y. GRAHAM, GEORGE J. REUL, RUSSELL MARTIN, JEREMY MORTON, JOHN H. KENNEDY
Journal: Circulation (1973)

Isolated tricuspid valvular endocarditis is no longer rare, and its increasing incidence has paralleled the rise in heroin addiction. In the period between December, 1969 and December, 1971, 16 episodes of bacterial endocarditis occurred in 13 individual drug abusers at the Ben Taub General Hospital, Houston. The tricuspid valve (TV) was involved in all cases. Two patients required surgery during the acute infection; one underwent total excision of the TV without replacement, and one received aortic and TV prostheses because of progressive heart failure. Antibiotic therapy was individualized and guided by tube dilution sensitivities and serum bactericidal levels. In view of the excellent response to antibiotic therapy, surgery for infected prosthetic or natural valves is presently reserved for those patients with progressive cardiac failure or infections unresponsive to medical therapy.
Antiubiquitin antibody in localised and systemic scleroderma.
Authors: M Fujimoto, S Sato, H Ihn, K Kikuchi, T Tamaki, K Tamaki, K Takehara
Journal: Annals of the Rheumatic Diseases (1996)

To determine the presence of antiubiquitin antibody (AUbA) in localised scleroderma and systemic sclerosis, as it is frequently found in the sera of patients with systemic lupus erythematosus (SLE) and has also been shown to have a close relationship with antihistone antibodies that have an important role in scleroderma.Serum samples from patients with localised scleroderma (n = 48) and systemic sclerosis (n = 52) were examined by enzyme linked immunosorbent assay. Twenty samples from patients with SLE, 20 from patients with dermatomyositis, and 30 samples from healthy individuals were used as controls.AUbA was demonstrated in 44% of patients with localised scleroderma and in 42% of those with systemic sclerosis. The presence of AUbA correlated with the presence of antihistone antibodies in both localised scleroderma and systemic sclerosis.AUbA is frequently present in patients with localised scleroderma and systemic sclerosis. Induction of AUbA is closely associated with that of antihistone antibodies, suggesting that ubiquitinated histone may be the target in autoimmune responses of these disorders.
Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials
Authors: A.K. Brimhall, L.N. King, J.C. Licciardone, H. Jacobe, A. Menter
Journal: British Journal of Dermatology (2008)

The relatively recent introduction of biological agents to treat psoriasis presents clinicians with the need to objectively compare and contrast these agents to allow more effective treatment of their patients.To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasis.(i)Four parallel systematic reviews conducted through July 2006, including peer-reviewed data and U.S. Food and Drug Administration (FDA) reports. (ii)Randomized, controlled, double-blind, monotherapy trials of alefacept (n = 3), efalizumab (n = 5), etanercept (n = 4) and infliximab (n = 4); 16 studies comprising 7931 patients met inclusion criteria. (iii)Efficacy was measured by Psoriasis Area and Severity Index (PASI) 75 achievement after 10-14 weeks of treatment, using intention-to-treat analysis. Safety was evaluated by the incidence of one or more adverse event(s) (AEs) and serious adverse event(s) (SAEs) during 10-30 weeks of treatment.Pooled relative risk (RR) and number needed to treat (NNT) of PASI 75 achievement compared with placebo was computed using Mantel-Haenszel methods and the random effects model. All biological agents for psoriasis were efficacious (P < 0.001); however, there was a graded response for achievement of PASI 75: infliximab (RR = 17.40, NNT = 2), etanercept (RR = 11.73, NNT = 3), efalizumab (RR = 7.34, NNT = 4) and alefacept (RR = 3.70, NNT = 8). The risk of one or more AEs was evaluated by RR and number needed to harm (NNH). This was increased in the alefacept (RR = 1.09, P = 0.03, NNH = 15), efalizumab (RR = 1.15, P < 0.001, NNH = 9) and infliximab (RR = 1.18, P < 0.001, NNH = 9) groups compared with placebo. SAEs were increased in a sensitivity analysis of four efalizumab trials (n = 2443, RR = 1.92, P = 0.03, NNH = 60).The decreasing rank order for pooled efficacy was infliximab, etanercept, efalizumab and alefacept when compared with placebo. Pooling safety data revealed a previously unreported increased risk of AEs for alefacept, efalizumab and infliximab.