tbuckley/cabot-search huggingface dataset:
School-age Outcomes of Very Preterm Infants After Antenatal Treatment With Magnesium Sulfate vs Placebo
Authors: Lex W. Doyle, Peter J. Anderson, Ross Haslam, Katherine J. Lee, Caroline Crowther
Journal: JAMA (2014)

<h3>Importance</h3> Antenatal magnesium sulfate given to pregnant women at imminent risk of very preterm delivery reduces the risk of cerebral palsy in early childhood, although its effects into school age have not been reported from randomized trials. <h3>Objective</h3> To determine the association between exposure to antenatal magnesium sulfate and neurological, cognitive, academic, and behavioral outcomes at school age. <h3>Design, Setting, and Participants</h3> The ACTOMgSO4 was a randomized clinical trial conducted in 16 centers in Australia and New Zealand, comparing magnesium sulfate with placebo given to pregnant women (n = 535 magnesium; n = 527 placebo) for whom imminent birth was planned or expected before 30 weeks’ gestation. Children who survived from the 14 centers who participated in the school-age follow-up (n = 443 magnesium; n = 424 placebo) were invited for an assessment at 6 to 11 years of age between 2005 and 2011. <h3>Main Outcomes and Measures</h3> Mortality, cerebral palsy, motor function, IQ, basic academic skills, attention and executive function, behavior, growth, and functional outcomes. Main analyses were imputed for missing data. <h3>Results</h3> Of the 1255 fetuses known to be alive at randomization, the mortality rate to school age was 14% (88/629) in the magnesium sulfate group and 18% (110/626) in the placebo group (risk ratio [RR], 0.80; 95% CI, 0.62-1.03,<i>P</i> = .08). Of 867 survivors available for follow-up, outcomes at school age (corrected age 6-11 years) were determined for 669 (77%). Comparing the magnesium sulfate and placebo groups revealed no statistically significant difference in proportions with cerebral palsy (23/295 [8%] and 21/314 [7%], respectively; odds ratio [OR], 1.26; 95% CI, 0.84-1.91;<i>P</i> = .27) or abnormal motor function (80/297 [27%] and 80/300 [27%], respectively; OR, 1.16; 95% CI, 0.88-1.52;<i>P</i> = .28). There was also little difference between groups on any of the cognitive, behavioral, growth, or functional outcomes. <h3>Conclusions and Relevance</h3> Magnesium sulfate given to pregnant women at imminent risk of birth before 30 weeks’ gestation was not associated with neurological, cognitive, behavioral, growth, or functional outcomes in their children at school age, although a mortality advantage cannot be excluded. The lack of long-term benefit requires confirmation in additional studies. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12606000252516
Choosing Sides in Polarized Endothelial Adaptation to Shear Stress
Authors: Brian P. Helmke
Journal: Circulation Research (2008)

An Integrin Whose Function Is Not Adhesion Strengthening?3][14] In these models, ␣5␤1 or ␣V␤3 integrins interact with "synergy" and "cell-binding" domains in type III repeats 9 and 10,
Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides.
Authors: D. Mimouni, M. David, M. Feinmesser, C.I. Coire, E. Hodak
Journal: British Journal of Dermatology (2001)

We describe four patients with mycosis fungoides (MF) in whom depigmentation, and also leucotrichia in one, occurred following the resolution of the eruption during phototherapy (psoralen plus ultraviolet A treatment in three patients, climatotherapy in one). In all cases, the depigmentation was localized to the area of the pre‐existing MF lesions. There was no clinically obvious phototoxicity. Biopsy study including S100 staining in all cases, and electron microscopy in one case, demonstrated the total absence of melanocytes, with no evidence of MF. It is suggested that the phototherapy may have activated a cell‐mediated immunity leading to destruction of the melanocytes. We recommend that vitiligo‐like leucoderma be added to the list of untoward effects of phototherapy in MF.
Precipitous fall of the forced expiratory volume
Authors: P. Howard, T. W. Astin
Journal: Thorax (1969)

Two patients are described who showed a precipitous loss of forced expiratory volume from normal to low levels within a few years. They did not have bronchial asthma and we suggest that this pattern of deterioration may occur occasionally in patients before they attend hospital with the symptoms of chronic bronchitis.
A Molecular Signature Predictive of Indolent Prostate Cancer
Authors: Shazia Irshad, Mukesh Bansal, Mireia Castillo-Martin, Tian Zheng, Alvaro Aytes, Sven Wenske, Clémentine Le Magnen, Paolo Guarnieri, Pavel Sumazin, Mitchell C. Benson, Michael M. Shen, Andrea Califano, Cory Abate-Shen
Journal: Science Translational Medicine (2013)

A three-gene panel derived from mechanistic models of cell senescence predicts outcome of low Gleason score prostate tumors.
The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility
Authors: T. Karasu, T. H. Marczylo, M. Maccarrone, J. C. Konje
Journal: Human Reproduction Update (2011)

BACKGROUNDMarijuana, the most used recreational drug, has been shown to have adverse effects on human reproduction. Endogenous cannabinoids (also called endocannabinoids) bind to the same receptors as those of Δ9-tetrahydrocannabinol (THC), the psychoactive component of Cannabis sativa. The most extensively studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol. The endocannabinoids, their congeners and the cannabinoid receptors, together with the metabolic enzymes and putative transporters form the endocannabinoid system (ECS). In this review, we summarize current knowledge about the relationships of ECS, sex steroid hormones and cytokines in female fertility, and underline the importance of this endocannabinoid–hormone–cytokine network.
Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial
Authors: Peter Barrett-Lee, Angela Casbard, Jacinta Abraham, Kerenza Hood, Robert Coleman, Peter Simmonds, Hayley Timmins, Duncan Wheatley, Robert Grieve, Gareth Griffiths, Nick Murray
Journal: The Lancet Oncology (2013)
Early negative sputum culture among patients treated for multidrug resistant tuberculosis (MDR-TB) in a government hospital in Rio de Janeiro
Authors: Janice Subilhaga, Regina Almeida, Leila Marques, Silvana Romano
Journal: European Respiratory Journal (2014)

Background:MDR-TB is a major problem of public health in Rio de Janeiro, notably in slums and informal settlements. Sputum smear and cultures results are included in the follow-up of MDR-TB cases might suggest treatment outcomes.  Objectives:HFSE is a governmental hospital in Rio de Janeiro responsible for the outpatient care of MDR-TB patients from neighbouring areas. In this study we describe early negative sputum cultures rates among MDR-TB patients in a high-TB prevalent and challenging setting.  Methods:This is a retrospective study which included all patients aged >12 years with positive baselines cultures and confirmed MDR-TB who started treatment between November 2011 and November 2013. The patients were treated with a standardized regimen of streptomycin (or amikacin) and pyrazinamide for 6 months, levofloxacin, terizidone and ethambutol for 18 months.  Results:52 patients initiated the treatment. Of these, four were excluded from this study because they abandoned the treatment in the first month. Of the 48 patients, 35(78,9%)had negative sputum culture within 4 months, 10(20,8%) had negative sputum culture after 5 months and 3(6,25%) were not able to provide sputum smear. Of the 35 patients who had negative sputum culture within 4 months, 10(20,8%) ended the treatment. Up to this moment, of the 48 patients included in this study, 13(27%) patients were discharged.  Conclusion:Although MDR-TB treatment is a challenge in high population density area we have been able to accomplish good results. Directly observed therapy strategy, treatment support and improvement in the detection of MDR-TB cases contributed to satisfactory outcomes.
MOTION PICTURE STUDIES ON DEGRANULATION OF HORSE EOSINOPHILS DURING PHAGOCYTOSIS
Authors: Gordon T. Archer, James G. Hirsch
Journal: The Journal of Experimental Medicine (1963)

Horse eosinophil function has been studied in vitro by means of phase contrast cinemicrophotography. Locomotion of horse eosinophils was inhibited by serum factors reacting with glass surfaces. Under appropriate conditions which eliminated this inhibitory effect, eosinophils moved about and ingested some particles as rapidly as did neutrophils. Eosinophils were attracted to and readily engulfed such diverse materials as yeast cell walls, foreign erythrocytes, and antigen-antibody precipitates. Specific antibody was required for phagocytosis of red cells, and greatly accelerated the uptake of yeast cell walls. Horse eosinophil granules situated adjacent to material being engulfed disrupted with discharge of granule contents into or alongside the phagocytic vacuole. Granule disruption resulted in a clear zone and deposition of amorphous, phase-dense material. A heat-labile serum factor was required for degranulation of eosinophils ingesting foreign red cells, but not for degranulation during engulfment of yeast cell walls or antigen-antibody precipitates. Horse eosinophils were incapable under these conditions of engulfing an entire human red cell. The eosinophil commonly put out a large pseudopod to surround about half the red cell, and then appeared to constrict this pseudopod distally to cut the erythrocyte in half. It is concluded that eosinophils are phagocytic cells, resembling neutrophils in many of their properties. Any specific functions of eosinophils, distinguishing them from other phagocytes, remain to be discovered.
Autoantigen-Specific B Cell Activation in FAS-Deficient Rheumatoid Factor Immunoglobulin Transgenic Mice
Authors: Haowei Wang, Mark J. Shlomchik
Journal: The Journal of Experimental Medicine (1999)

In systemic autoimmune disease, self-tolerance fails, leading to autoantibody production. A central issue in immunology is to understand the origins of activated self-reactive B cells. We have used immunoglobulin (Ig) transgenic mice to investigate the regulation of autoreactive B cells with specificity for self-IgG2a (the rheumatoid factor [RF] specificity) to understand how normal mice regulate RF autoantibodies and how this fails in autoimmune mice. We previously showed that normal mice do not tolerize the AM14 RF clone, nor do they appear to activate it. Here we show that in Fas-deficient autoimmune mice, the picture is quite different. RF B cells are activated to divide and secrete, but only when the autoantigen is present. Thus, B cells that are ignored rather than anergized in normal mice can be stimulated to produce autoantibody in Fas-deficient mice. This demonstrates a novel developmental step at which intact Fas–Fas ligand signaling is required to regulate B cells in order to prevent autoimmunity. These data also establish the relevance of ignorant self-specific B cells to autoantibody production in disease and prove that in the case of the RF specificity, the nominal autoantigen IgG2a is the driving autoantigen in vivo.
IL-23 and Th17 Cells Enhance Th2-Cell–mediated Eosinophilic Airway Inflammation in Mice
Authors: Hidefumi Wakashin, Koichi Hirose, Yuko Maezawa, Shin-ichiro Kagami, Akira Suto, Norihiko Watanabe, Yasushi Saito, Masahiko Hatano, Takeshi Tokuhisa, Yoichiro Iwakura, Paolo Puccetti, Itsuo Iwamoto, Hiroshi Nakajima
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The IL-23-IL-17A-producing CD4(+) T-cell (Th17 cell) axis plays an important role in the development of chronic inflammatory diseases, including autoimmune diseases. However, the role of the IL-23-Th17 cell axis in the regulation of allergic airway inflammation is still largely unknown.To determine the role of IL-23 and Th17 cells in allergic airway inflammation.We examined the effect of anti-IL-23 antibody on antigen-induced airway inflammation. We also investigated the effect of enforced expression of IL-23 on allergic airway inflammation by generating lung-specific IL-23 transgenic mice. Moreover, we examined the effect of adoptive transfer of antigen-specific Th17 cells on allergic airway inflammation.IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation, and the neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. The enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil and neutrophil recruitment into the airways; Th2 cytokine, IL-17A, and tumor necrosis factor (TNF)-alpha production in the airways; goblet cell hyperplasia; and airway hyperresponsiveness. Moreover, IL-23-mediated enhancement of antigen-induced Th2 cytokine production and eosinophil recruitment in the airways was still observed in the mice lacking IL-17A. Furthermore, although adoptive transfer of antigen-specific Th17 cells alone induced neutrophil but not eosinophil recruitment into the airways upon antigen inhalation, cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced Th2-cell-mediated eosinophil recruitment into the airways and airway hyperresponsiveness.IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.
Suicide Rates in Clinical Trials of SSRIs, Other Antidepressants, and Placebo: Analysis of FDA Reports
Authors: Arif Khan, Shirin Khan, Russell Kolts, Walter A. Brown
Journal: American Journal of Psychiatry (2003)

Previous reports suggesting that selective serotonin reuptake inhibitor (SSRI) use is associated with increased suicidal risk have not assessed completed suicides. The authors analyzed reports from randomized controlled trials to compare suicide rates among depressed patients assigned to an SSRI, other antidepressants, or placebo.Food and Drug Administration (FDA) summary reports of the controlled clinical trials for nine modern FDA-approved antidepressants provided data for comparing rates of suicide.Of 48,277 depressed patients participating in the trials, 77 committed suicide. Based on patient exposure years, similar suicide rates were seen among those randomly assigned to an SSRI (0.59%, 95% confidence interval [CI]=0.31%-0.87%), a standard comparison antidepressant (0.76%, 95% CI=0.49%-1.03%), or placebo (0.45%, 95% CI=0.01%-0.89%).These findings fail to support either an overall difference in suicide risk between antidepressant- and placebo-treated depressed subjects in controlled trials or a difference between SSRIs and either other types of antidepressants or placebo.
Familial GI Stromal Tumor With Loss of Heterozygosity and Amplification of Mutant <i>KIT</i>
Authors: Patrick M. Forde, Rory L. Cochran, Sosipatros A. Boikos, Daniel J. Zabransky, Julia A. Beaver, Christian F. Meyer, Katherine A. Thornton, Elizabeth A. Montgomery, Anne O. Lidor, Ross C. Donehower, Ben Ho Park
Journal: Journal of Clinical Oncology (2014)
Massive Habitat-Specific Genomic Response in D. melanogaster Populations during Experimental Evolution in Hot and Cold Environments
Authors: Ray Tobler, Susanne U. Franssen, Robert Kofler, Pablo Orozco-terWengel, Viola Nolte, Joachim Hermisson, Christian Schlötterer
Journal: Molecular Biology and Evolution (2013)

Experimental evolution in combination with whole-genome sequencing (evolve and resequence [E&R]) is a promising approach to define the genotype–phenotype map and to understand adaptation in evolving populations. Many previous studies have identified a large number of putative selected sites (i.e., candidate loci), but it remains unclear to what extent these loci are genuine targets of selection or experimental noise. To address this question, we exposed the same founder population to two different selection regimes—a hot environment and a cold environment—and quantified the genomic response in each. We detected large numbers of putative selected loci in both environments, albeit with little overlap between the two sets of candidates, indicating that most resulted from habitat-specific selection. By quantifying changes across multiple independent biological replicates, we demonstrate that most of the candidate SNPs were false positives that were linked to selected sites over distances much larger than the typical linkage disequilibrium range of Drosophila melanogaster. We show that many of these mid- to long-range associations were attributable to large segregating inversions and confirm by computer simulations that such patterns could be readily replicated when strong selection acts on rare haplotypes. In light of our findings, we outline recommendations to improve the performance of future Drosophila E&R studies which include using species with negligible inversion loads, such as D. mauritiana and D. simulans, instead of D. melanogaster.
Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib after Cardiac Surgery
Authors: Nancy A. Nussmeier, Andrew A. Whelton, Mark T. Brown, Richard M. Langford, Andreas Hoeft, Joel L. Parlow, Steven W. Boyce, Kenneth M. Verburg
Journal: New England Journal of Medicine (2005)

Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG.In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications.As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03).The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.
Effect of guanethidine on the natural history of post-traumatic algodystrophy.
Authors: J Field, R M Atkins
Journal: Annals of the Rheumatic Diseases (1993)

To determine the effect of intravenous regional guanethidine on post-traumatic algodystrophy.Ten of 20 consecutive patients with algodystrophy after Colles' fracture were treated with serial intravenous regional guanethidine blockades and the other 10 were treated with physiotherapy alone. Patients were assessed before and after each block and then monthly over a six month period.The treated patients had subjective and objective improvements in the assessed features of algodystrophy; treatment resulted in a significant reduction in finger tenderness at five and six months.Guanethidine blockade induces short term benefits in the symptoms of algodystrophy but improves finger tenderness only in the long term.
Analysis of 94 Candidate Genes and 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia
Authors: Tiffany A. Greenwood, Laura C. Lazzeroni, Sarah S. Murray, Kristin S. Cadenhead, Monica E. Calkins, Dorcas J. Dobie, Michael F. Green, Raquel E. Gur, Ruben C. Gur, Gary Hardiman, John R. Kelsoe, Sherry Leonard, Gregory A. Light, Keith H. Nuechterlein, Ann Olincy, Allen D. Radant, Nicholas J. Schork, Larry J. Seidman, Larry J. Siever, Jeremy M. Silverman, William S. Stone, Neal R. Swerdlow, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Robert Freedman, David L. Braff
Journal: American Journal of Psychiatry (2011)

The authors used a custom array of 1,536 single-nucleotide polymorphisms (SNPs) to interrogate 94 functionally relevant candidate genes for schizophrenia and identify associations with 12 heritable neurophysiological and neurocognitive endophenotypes in data collected by the Consortium on the Genetics of Schizophrenia.
Mechanical Ventilation–induced Diaphragm Disuse in Humans Triggers Autophagy
Authors: Sabah N. A. Hussain, Mahroo Mofarrahi, Ioanna Sigala, Ho Cheol Kim, Theodoros Vassilakopoulos, Francois Maltais, Ion Bellenis, Rakesh Chaturvedi, Stewart B. Gottfried, Peter Metrakos, Gawiyou Danialou, Stefan Matecki, Samir Jaber, Basil J. Petrof, Peter Goldberg
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Controlled mechanical ventilation (CMV) results in atrophy of the human diaphragm. The autophagy-lysosome pathway (ALP) contributes to skeletal muscle proteolysis, but its contribution to diaphragmatic protein degradation in mechanically ventilated patients is unknown.To evaluate the autophagy pathway responses to CMV in the diaphragm and limb muscles of humans and to identify the roles of FOXO transcription factors in these responses.Muscle biopsies were obtained from nine control subjects and nine brain-dead organ donors. Subjects were mechanically ventilated for 2 to 4 hours and 15 to 276 hours, respectively. Activation of the ubiquitin-proteasome system was detected by measuring mRNA expressions of Atrogin-1, MURF1, and protein expressions of UBC2, UBC4, and the α subunits of the 20S proteasome (MCP231). Activation of the ALP was detected by electron microscopy and by measuring the expressions of several autophagy-related genes. Total carbonyl content and HNE-protein adduct formation were measured to assess oxidative stress. Total AKT, phosphorylated and total FOXO1, and FOXO3A protein levels were also measured.Prolonged CMV triggered activation of the ALP as measured by the appearance of autophagosomes in the diaphragm and increased expressions of autophagy-related genes, as compared with controls. Induction of autophagy was associated with increased protein oxidation and enhanced expression of the FOXO1 gene, but not the FOXO3A gene. CMV also triggered the inhibition of both AKT expression and FOXO1 phosphorylation.We propose that prolonged CMV causes diaphragm disuse, which, in turn, leads to activation of the ALP through oxidative stress and the induction of the FOXO1 transcription factor.