tbuckley/cabot-search huggingface dataset:
Brain Activity Associated with Placebo Suppression of the Urge-to-Cough in Humans
Authors: Jennifer Leech, Stuart B. Mazzone, Michael J. Farrell
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Antitussive therapies are accompanied by a substantial placebo effect, indicating that inhibitory circuits in the brain have a significant capacity to regulate cough neural processing. However, essentially nothing is known about the identity of these inhibitory circuits or how they reduce coughing. Understanding these processes may help develop more effective antitussive therapies in the future.Objectives: To identify regional changes in human brain activity related to the urge-to-cough after placebo antitussive administration.Methods: Seventeen healthy participants undertook functional magnetic resonance imaging while completing a series of inhalations of capsaicin to induce the urge-to-cough. The resultant brain responses associated with capsaicin inhalation without any treatment were compared with those induced by capsaicin after placebo antitussive administration.Measurements and Main Results: There was a significant decrease in participants’ ratings of urge-to-cough after the placebo antitussive administration. Brain activity associated with capsaicin inhalation was less in the somatosensory, primary motor, insula, and cingulate cortices during placebo antitussive trials compared with no treatment control subjects. By contrast, placebo trials were associated with increased activation in the prefrontal and left parietal cortices.Conclusions: Placebo-related decreases in urge-to-cough are accompanied by commensurate decreases in several brain regions activated during capsaicin inhalation, suggesting that beliefs about treatment can modify the central processing of inputs arising from the airways. The prefrontal cortex and posterior parietal cortex are likely to play an active role in the modification of airway sensory processing after administration of a placebo.
Re-Expression of Transcription Factor<i>ATF5</i>in Hepatocellular Carcinoma Induces G2-M Arrest
Authors: Jennifer W-M. Gho, Wai-Ki Ip, Kathy Y-Y. Chan, Priscilla T-Y. Law, Paul B-S. Lai, Nathalie Wong
Journal: Cancer Research (2008)

Abstract Transcription factors represent an important class of genes that play key roles in controlling cellular proliferation, cell cycle modulation, and attractive targets for cancer therapy. Here, we report on the novel finding of common ATF5 down-regulations in hepatocellular carcinoma (HCC), a highly malignant tumor with a dismal clinical course. Array-based mapping in HCC highlighted a high and consistent incidence of transcription factor ATF5 repressions on regional chr.19q13. By quantitative reverse transcription-PCR, profound down-regulations of ATF5 were further suggested in 78% of HCC tumors (60 of 77 cases) compared to their adjacent nontumoral liver (P = 0.0004). Restoration of ATF5 expression in 3 nonexpressing HCC cell lines demonstrated a consistent growth inhibitory effect (P &amp;lt; 0.029) but minimal induction on cellular apoptosis. Subsequent flow cytometric investigations revealed a G2-M cell cycle arrest in HCC cells that were ectopically transfected with ATF5 (P &amp;lt; 0.002). The differential expressed genes from the functional effects of ATF5 were examined by array profiling. Over a hundred genes were identified, among which ID1 contains the ATF/CREB target binding sequences within its promoter region. An inverse relationship between ATF5 expressions with ID1 transcriptions was verified in HCC (P = 0.019), and a direct interaction of ATF5 on the promoter of ID1 was further demonstrated from electromobility shift assay. Examination of causal events underlying the silencing of ATF5 in HCC suggested copy number losses, promoter hypermethylation, histone deacetylation, and DNA mutations to be the likely inactivating mechanisms. In conclusion, our finding supports a tumor suppressive role for ATF5 in HCC, and highlighted ID1 as a potential downstream target. [Cancer Res 2008;68(16):6743–51]
Preventive Effect of Erythropoietin on Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy
Authors: Longhu Li, Genzou Takemura, Yiwen Li, Shusaku Miyata, Masayasu Esaki, Hideshi Okada, Hiromitsu Kanamori, Ngin Cin Khai, Rumi Maruyama, Atsushi Ogino, Shinya Minatoguchi, Takako Fujiwara, Hisayoshi Fujiwara
Journal: Circulation (2006)

Doxorubicin is a highly effective antineoplastic drug, but its clinical use is limited by its adverse side effects on the heart. We investigated possible protective effects of erythropoietin against doxorubicin-induced cardiomyopathy.Cardiomyopathy was induced in mice by a single intraperitoneal injection of doxorubicin (15 mg/kg). In some cases, human recombinant erythropoietin (5000 U/kg) was started simultaneously. Two weeks later, left ventricular dilatation and dysfunction were apparent in mice given doxorubicin but were significantly attenuated by erythropoietin treatment. Erythropoietin also protected hearts against doxorubicin-induced cardiomyocyte atrophy and degeneration, myocardial fibrosis, inflammatory cell infiltration, and downregulation of expression of GATA-4 and 3 sarcomeric proteins, myosin heavy chain, troponin I, and desmin. Cyclooxygenase-2 expression was upregulated in doxorubicin-treated hearts, and that, too, was attenuated by erythropoietin. No doxorubicin-induced apoptotic effects were seen, nor were any changes seen in the expression of tumor necrosis factor-alpha or transforming growth factor-beta1. Antiatrophic and GATA-4 restoring effects of erythropoietin were demonstrated in the in vitro experiments with cultured cardiomyocytes exposed to doxorubicin, which indicated the direct cardioprotective effects of erythropoietin beyond erythropoiesis. Cardiac erythropoietin receptor expression was downregulated in doxorubicin-induced cardiomyopathy but was restored by erythropoietin. Among the downstream mediators of erythropoietin receptor signaling, activation of extracellular signal-regulated kinase was reduced by doxorubicin but restored by erythropoietin. By contrast, erythropoietin was ineffective when administered after cardiac dysfunction was established in the chronic stage.The present study indicates a protective effect of erythropoietin against doxorubicin-induced cardiomyopathy.
Breast cancer molecular profiling with single sample predictors: a retrospective analysis
Authors: Britta Weigelt, Alan Mackay, Roger A'hern, Rachael Natrajan, David SP Tan, Mitch Dowsett, Alan Ashworth, Jorge S Reis-Filho
Journal: The Lancet Oncology (2010)

Microarray expression profiling classifies breast cancer into five molecular subtypes: luminal A, luminal B, basal-like, HER2, and normal breast-like. Three microarray-based single sample predictors (SSPs) have been used to define molecular classification of individual samples. We aimed to establish agreement between these SSPs for identification of breast cancer molecular subtypes.Previously described microarray-based SSPs were applied to one in-house (n=53) and three publicly available (n=779) breast cancer datasets. Agreement was analysed between SSPs for the whole classification system and for the five molecular subtypes individually in each cohort.Fair-to-substantial agreement between every pair of SSPs in each cohort was recorded (kappa=0.238-0.740). Of the five molecular subtypes, only basal-like cancers consistently showed almost-perfect agreement (kappa>0.812). The proportion of cases classified as basal-like in each cohort was consistent irrespective of the SSP used; however, the proportion of each remaining molecular subtype varied substantially. Assignment of individual cases to luminal A, luminal B, HER2, and normal breast-like subtypes was dependent on the SSP used. The significance of associations with outcome of each molecular subtype, other than basal-like and luminal A, varied depending on SSP used. However, different SSPs produced broadly similar survival curves.Although every SSP identifies molecular subtypes with similar survival, they do not reliably assign the same patients to the same molecular subtypes. For molecular subtype classification to be incorporated into routine clinical practice and treatment decision making, stringent standardisation of methodologies and definitions for identification of breast cancer molecular subtypes is needed.Breakthrough Breast Cancer, Cancer Research UK.
Distinct Roles of Lymphotoxin α and the Type I Tumor Necrosis Factor (TNF) Receptor in the Establishment of Follicular Dendritic Cells from Non–Bone Marrow–derived Cells
Authors: Mitsuru Matsumoto, Yang-Xin Fu, Hector Molina, Guangming Huang, Jinho Kim, Dori A. Thomas, Moon H. Nahm, David D. Chaplin
Journal: The Journal of Experimental Medicine (1997)

In mice deficient in either lymphotoxin α (LT-α) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen. We investigated the role of LT-α and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LT-α–deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-α–expressing cells required to establish organized FDC are derived from BM. The role of LT-α in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)–deficient BM cells into LT-α–deficient mice. Organized FDC were identified with both the FDC-M1 and anti-CR1 monoclonal antibodies in these BM-chimeric mice, indicating that these cells were derived from the LT-α–deficient recipient. Thus, expression of LT-α in the BM-derived cells, but not in the non–BM-derived cells, is required for the maturation of FDC from non-BM precursor cells. In contrast, when TNFR-I–deficient mice were reconstituted with wild-type BM, they showed no detectable FDC clusters or GC formation. This indicates that TNFR-I expression on non–BM-derived cellular components is necessary for the establishment of these lymphoid structures. TNFR-I–deficient BM was able to restore FDC organization and GC formation in LT-α–deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM-derived cells. The data in this study demonstrate that FDC organization and GC formation are controlled by both LT-α–expressing BM-derived cells and by TNFR-I-expressing non–BM-derived cells.
Protective role of gluteofemoral obesity in erosive oesophagitis and Barrett's oesophagus
Authors: Joel H Rubenstein, Hal Morgenstern, William D Chey, Joseph Murray, James M Scheiman, Philip Schoenfeld, Henry D Appelman, Laurence McMahon, Val Metko, Joan Kellenberg, Tal Kalish, Jason Baker, John M Inadomi
Journal: Gut (2013)

Objective Abdominal obesity has been associated with erosive oesophagitis (EO) and Barrett's oesophagus (BO). As gluteofemoral obesity protects against diabetes mellitus and cardiovascular disease, we hypothesised that gluteofemoral obesity would be inversely associated with EO and BO. Design We conducted a cross-sectional study on 822 male colorectal cancer screenees who were recruited to also undergo upper endoscopy. An additional 80 patients with BO clinically detected by upper endoscopy referred for clinical indications were recruited shortly after their diagnoses of BO. Logistic regression was used to estimate the effects of abdominal obesity (waist circumference), gluteofemoral obesity (hip circumference) and waist-to-hip ratio (WHR) on EO and BO (vs neither condition). Results There were 225 cases of either BO or EO and 675 controls. After adjustment for potential confounders, a positive association was observed between waist circumference and BO and/or EO, which became stronger with further adjustment for hip circumference. In contrast, hip circumference was inversely associated with BO and/or EO. Compared with the lowest quartile of WHR, the adjusted ORs were 1.32 (95% CI 0.747 to 2.33) for the 2nd quartile, 1.54 (95% CI 0.898 to 2.63) for the 3rd quartile, and 2.68 (95% CI 1.57 to 4.55) for the highest quartile. Similar results were obtained for BO and EO treated as separate outcomes. Conclusions In a population of older, mostly overweight men, the distribution of obesity is associated with the presence of EO and BO. Abdominal obesity appears to increase the risk of these outcomes, whereas gluteofemoral obesity may be protective.
Abortus Fever Treated with Sulphonamides and Blood Transfusion
Authors: C. Romer
Journal: BMJ (1949)

JDoUL 1035 purgatives and lacto-vegetarian diet were the basis of treat- ment in the past, when a mucous plug in the ampulla of Vater and catarrhal inflammation of the bile ducts were thought to be the cause of jaundice.Duodenal intubation and lavage with magnesium sulphate solution were tried for the same reason.After animal experiments deficiency of proteins and vitamins was blamed, patients were put on high protein diet and massive doses of methionine, cystine, and vitamin B complex.Miraculous cures were claimed for protein hydrolysates and plasma transfusion.Equally miraculous cures have resulted from transfusion of glucose- saline.Rapid improvement has also been reported due to direct irrigation of the biliary tract with saline during laparotomy.When good results are claimed for such widely different treatments none of these can be specific.The assessment of the value of any form of treatment is exceed- ingly difficult owing to the natural tendency of the disease towards spontaneous cure.It is only when large numbers of patients have been treated that inefficacy of certain methods can be proved.The liver has a marvellous capacity for recovery and regeneration.In the acute stage, when the liver cells are inflamed, rest to the organ is indicated more than any- thing else.Glucose, liberal fluids, and mild laxatives are beneficial.The diet should be light, low in fat, but other- wise balanced.The patient can leave the bed soon after the urine becomes bile-free.In venereal disease treatment centres extreme care is essential for the prevention of post-arsenical hepatitis.Besides care in sterilizing syringes and needles, each patient receiving injections should be carefully examined before injection.Malaise, nausea, urobilinogen in urine, a trace of bile, or dark urine are all contraindications to arsenical treatment.If arsenic is given after the urine has turned dark, acute necrosis is likely to result.In relapse cases arsenic should be given up for good.Once cirrhosis is established there is nothing at our disposal to prevent its progress.All that can be done is to prevent the surviving hepatic cells from degeneration.Restricted activities, well-balanced but low-fat diet, and glucose are helpful.All hepatotoxins should be scrupu- lously avoided.Ascites should be tapped if there is con- siderable fluid.Anaemia should be treated with iron and liver extracts.If bleeding occurs vitamin K should be injected.All measures to improve general health should be
Adaptive Immunity to Fungi
Authors: Marcel Wüthrich, George S. Deepe, Bruce Klein
Journal: Annual Review of Immunology (2012)

Only a handful of the more than 100,000 fungal species on our planet cause disease in humans, yet the number of life-threatening fungal infections in patients has recently skyrocketed as a result of advances in medical care that often suppress immunity intensely. This emerging crisis has created pressing needs to clarify immune defense mechanisms against fungi, with the ultimate goal of therapeutic applications. Herein, we describe recent insights in understanding the mammalian immune defenses deployed against pathogenic fungi. The review focuses on adaptive immune responses to the major medically important fungi and emphasizes how dendritic cells and subsets in various anatomic compartments respond to fungi, recognize their molecular patterns, and signal responses that nurture and shape the differentiation of T cell subsets and B cells. Also emphasized is how the latter deploy effector and regulatory mechanisms that eliminate these nasty invaders while also constraining collateral damage to vital tissue.
Genome-Wide Linkage Scan Identifies a Novel Genetic Locus on Chromosome 5p13 for Neonatal Atrial Fibrillation Associated With Sudden Death and Variable Cardiomyopathy
Authors: Carlos Oberti, Lejin Wang, Lin Li, Jiamei Dong, Shaoqi Rao, Wei Du, Qing Wang
Journal: Circulation (2004)

Background— Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF have a significantly increased risk for ischemic stroke. Approximately 15% of all strokes are caused by AF. The molecular basis and underlying mechanisms and pathophysiology of AF remain largely unknown. Methods and Results— We have identified a large AF family with an autosomal recessive inheritance pattern. The AF in the family manifests with early onset at the fetal stage and is associated with neonatal sudden death and, in some cases, ventricular tachyarrhythmias and waxing and waning cardiomyopathy. Genome-wide linkage analysis was performed for 36 family members and generated a 2-point logarithm of the odds (LOD) score of 3.05 for marker D5S455 . The maximum multipoint LOD score of 4.10 was obtained for 4 markers: D5S426 , D5S493 , D5S455 , and D5S1998 . Heterozygous carriers have significant prolongation of P-wave duration on ECGs compared with noncarriers (107 versus 85 ms on average; P =0.000012), but no differences between these 2 groups were detected for the PR interval, QRS complex, ST-segment duration, T-wave duration, QTc, and R-R interval ( P &gt;0.05). Conclusions— Our findings demonstrate that AF can be inherited as an autosomal recessive trait and define a novel genetic locus for AF on chromosome 5p13 ( arAF1 ). A genetic link between AF and prolonged P-wave duration was identified. This study provides a framework for the ultimate cloning of the arAF1 gene, which will increase the understanding of the fundamental molecular mechanisms of atrial fibrillation.
Dual Kinase Inhibition of EGFR and HER2 Overcomes Resistance to Cetuximab in a Novel <i>In Vivo</i> Model of Acquired Cetuximab Resistance
Authors: Kelly M. Quesnelle, Jennifer R. Grandis
Journal: Clinical Cancer Research (2011)

Acquired resistance to cetuximab, a chimeric epidermal growth factor receptor (EGFR)-targeting monoclonal antibody, is a widespread problem in the treatment of solid tumors. The paucity of preclinical models has limited investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. The purpose of this study was to generate cetuximab-resistant tumors in vivo to characterize mechanisms of acquired resistance.We generated cetuximab-resistant clones from a cetuximab-sensitive bladder cancer cell line in vivo by exposing cetuximab-sensitive xenografts to increasing concentrations of cetuximab, followed by validation of the resistant phenotype in vivo and in vitro using invasion assays. A candidate-based approach was used to examine the role of HER2 on mediating cetuximab resistance both in vitro and in vivo.We generated a novel model of cetuximab resistance, and, for the first time in the context of EGFR-inhibitor resistance, we identified increased phosphorylation of a C-terminal fragment of HER2 (611-CTF) in cetuximab-resistant cells. Afatinib (BIBW-2992), an irreversible kinase inhibitor targeting EGFR and HER2, successfully inhibited growth of the cetuximab-resistant cells in vitro. When afatinib was combined with cetuximab in vivo, we observed an additive growth inhibitory effect in cetuximab-resistant xenografts.These data suggest that the use of dual EGFR-HER2 kinase inhibitors can enhance responses to cetuximab, perhaps in part due to downregulation of 611-CTF. This study conducted in a novel in vivo model provides a mechanistic rationale for ongoing phase I clinical trials using this combination treatment modality.
Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide
Authors: T. C. Hoffmann, P. P. Glasziou, I. Boutron, R. Milne, R. Perera, D. Moher, D. G. Altman, V. Barbour, H. Macdonald, M. Johnston, S. E. Lamb, M. Dixon-Woods, P. McCulloch, J. C. Wyatt, A.-W. Chan, S. Michie
Journal: BMJ (2014)

Without a complete published description of interventions, clinicians and patients cannot reliably implement interventions that are shown to be useful, and other researchers cannot replicate or build on research findings. The quality of description of interventions in publications, however, is remarkably poor. To improve the completeness of reporting, and ultimately the replicability, of interventions, an international group of experts and stakeholders developed the Template for Intervention Description and Replication (TIDieR) checklist and guide. The process involved a literature review for relevant checklists and research, a Delphi survey of an international panel of experts to guide item selection, and a face to face panel meeting. The resultant 12 item TIDieR checklist (brief name, why, what (materials), what (procedure), who provided, how, where, when and how much, tailoring, modifications, how well (planned), how well (actual)) is an extension of the CONSORT 2010 statement (item 5) and the SPIRIT 2013 statement (item 11). While the emphasis of the checklist is on trials, the guidance is intended to apply across all evaluative study designs. This paper presents the TIDieR checklist and guide, with an explanation and elaboration for each item, and examples of good reporting. The TIDieR checklist and guide should improve the reporting of interventions and make it easier for authors to structure accounts of their interventions, reviewers and editors to assess the descriptions, and readers to use the information.
Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study
Authors: Fan Fan Hou, Di Xie, Xun Zhang, Ping Yan Chen, Wei Ru Zhang, Min Liang, Zhi Jian Guo, Jian Ping Jiang
Journal: Journal of the American Society of Nephrology (2007)

<h3>Background/aims</h3> The authors estimated the association between corneal biomechanical properties and axial length in myopic children and verified the relationship between axial length and intraocular pressure (IOP). <h3>Methods</h3> This cross-sectional study included 126 eyes of 63 children, aged 12.02±3.19 years. Corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT) and IOP were recorded with the Reichert Ocular Response Analyzer. Axial length (AL) and anterior chamber depth (ACD) were measured by the IOLMaster, whereas corneal curvature was measured by an autorefractor. <h3>Results</h3> In multivariable mixed model analysis, CH correlated significantly with AL (p&lt;0.0001), ACD (p=0.044) and CCT (p&lt;0.0001), but not with curvature; CRF correlated significantly with AL (p=0.004) and CCT (p&lt;0.0001) but not ACD or curvature. The difference in CH between the two eyes of each patient correlated significantly with the difference in the AL between the two eyes (p=0.002). IOP did not correlate with age, gender or AL. <h3>Conclusion</h3> Lower CH and CRF were associated with longer AL but not corneal curvature. The association between lower CH and deeper ACD demonstrated the importance of CH as a determinant of ocular biometry in both the anterior and posterior segments. Differences in corneal biomechanical properties may indicate more generalised structural differences between eyes.
FEMALE GENDER IN STEMI: INFLUENCE ON MORTALITY AND REPERFUSION: RESULTS FROM THE BELGIAN STEMI REGISTRY
Authors: Sofie Agnes Gevaert, Antoine De Meester, Patrick Evrard, Marc Renard, Christophe Beauloye, Patrick Coussement, Herbert De Raedt, Marc Claeys
Journal: Journal of the American College of Cardiology (2010)