tbuckley/cabot-search huggingface dataset:
Pediatric Sleep Apnea
Authors: Carolyn E. Ievers-Landis, Susan Redline
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Over the last 30 years, the prevalence of overweight across all pediatric age groups and ethnicities has increased substantially, with the current prevalence of overweight among adolescents estimated to be approximately 30%. Current evidence suggests that overweight is modestly associated with obstructive sleep apnea syndrome (OSAS) among young children, but strongly associated with OSAS in older children and adolescents. The rising incidence of pediatric overweight likely will impact the prevalence, presentation, and treatment of childhood OSAS. The subgroup of children who may be especially susceptible include ethnic minorities and those from households with caregivers from low socioeconomic groups. OSAS, by exposing children to recurrent intermittent hypoxemia or oxidative stress, may amplify the adverse effects of adiposity on systemic inflammation and metabolic perturbations associated with vascular disease and diabetes. When these conditions manifest early in life, they have the potential to alter physiology at critical developmental stages, or, if persistent, provide cumulative exposures that may powerfully alter long-term health profiles. An increased prevalence of overweight also may impact the response to adenotonsillectomy as a primary treatment for childhood OSAS. The high and anticipated increased prevalence of pediatric OSAS mandates assessment of optimal approaches for preventing and treating both OSAS and overweight across the pediatric age range. In this Pulmonary Perspective, the interrelationships between pediatric OSAS and overweight are reviewed, and the implications of the overweight epidemic on childhood OSAS are discussed.
A critical review of epidemiologic studies of radiofrequency exposure and human cancers.
Authors: J M Elwood
Journal: Environmental Health Perspectives (1999)

This paper reviews studies that have assessed associations between likely exposure to radiofrequency (RF) transmissions and various types of human cancer. These studies include three cluster investigations and five studies relating to general populations; all of these studies consider place of residence at the time of cancer diagnosis in regard to proximity to radio or television transmitters. There are also five relevant occupational cohort studies and several case-control studies of particular types of cancer. These studies assessed a large number of possible associations. Several positive associations suggesting an increased risk of some types of cancer in those who may have had greater exposure to RF emissions have been reported. However, the results are inconsistent: there is no type of cancer that has been consistently associated with RF exposures. The epidemiologic evidence falls short of the strength and consistency of evidence that is required to come to a reasonable conclusion that RF emissions are a likely cause of one or more types of human cancer. The evidence is weak in regard to its inconsistency, the design of the studies, the lack of detail on actual exposures, and the limitations of the studies in their ability to deal with other likely relevant factors. In some studies there may be biases in the data used
Albumin Replacement in Patients with Severe Sepsis or Septic Shock
Authors: Pietro Caironi, Gianni Tognoni, Serge Masson, Roberto Fumagalli, Antonio Pesenti, Marilena Romero, Caterina Fanizza, Luisa Caspani, Stefano Faenza, Giacomo Grasselli, Gaetano Iapichino, Massimo Antonelli, Vieri Parrini, Gilberto Fiore, Roberto Latini, Luciano Gattinoni
Journal: New England Journal of Medicine (2014)

Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established.In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital.During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups.In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).
Changes in Gene Expression Induced by Phosphorothioate Oligodeoxynucleotides (Including G3139) in PC3 Prostate Carcinoma Cells Are Recapitulated at Least in Part by Treatment with Interferon-β and -γ
Authors: Luba Benimetskaya, Timo Wittenberger, C. A. Stein, Hans-Peter Hofmann, Claudia Weller, Johnathan C. Lai, Paul Miller, Volker Gekeler
Journal: Clinical Cancer Research (2004)

G3139 is an antisense bcl-2 phosphorothioate oligodeoxyribonucleotide that is currently being evaluated in Phase III clinical trials in several human cancers. The aim of the present work was to further identify the apparent non-bcl-2-dependent mechanism of this action of this compound in PC3 prostate cancer cells.We performed Affymetrix U95A oligonucleotide microarray studies on mRNA isolated from cells treated with G3139 and related oligonucleotides.Hierarchical clustering revealed the presence of a set of genes of which the expression was elevated on both 1 and 3 days after oligonucleotide treatment. Significantly, the persistence of expression of the up-regulation of these genes, many of which are members of the IFN cascade, was greater for G3139 than for any other oligomer evaluated. Furthermore, many of the genes with the greatest up-regulation of expression are also those of which the expression is up-regulated after treatment of cells with IFNs. Treatment of PC3 cells with either IFN-beta or -gamma recapitulated some of the aspects of the molecular and phenotypic changes observed after treatment with a G3139/Lipofectin complex. These include down-regulation of bcl-2 protein expression itself, down-regulation of protein kinase C alpha protein expression (but not that of other protein kinase C isoforms), alteration in p21/Waf1/Cip1 protein expression, up-regulation of MHC-I cell surface expression, and profound suppression of cell growth in the absence of a notable increase in cellular apoptosis. However, G3139 (when complexed with Lipofectin) did not induce the up-regulation of expression of either type I or type II IFNs, nor could IFNs be found in conditioned media from treated cells.Oligonucleotide microarray experiments demonstrated that G3139 could induce elements of the IFN cascade in PC3 cells in vitro. In addition, the cellular phenotype obtained after treatment with exogenous IFN could, at least in part, recapitulate that obtained after G3139 treatment. Nevertheless, the oligonucleotide microarray experiments we performed also demonstrated that there are extremely large qualitative and quantitative differences between the two treatments.
Incidence of abiraterone acetate withdrawal response measured by PSA declines.
Authors: Rajasree Pia Chowdry, Brian E. Lewis, Elisa M. Ledet, Jonathan L. Silberstein, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

280 Background: The anti-androgen withdrawal effect is a well-described phenomenon occurring in patients with castrate resistant prostate cancer (CRPC) after discontinuing anti-androgen therapy. There is limited data on withdrawal responses after newer hormonal therapies such as Abiraterone Acetate (AA). Discontinuation of AA may lead to PSA declines but the frequency remains unclear. The goal of our study was to assess the incidence and duration of PSA decreases after stopping AA. Methods: We reviewed 51 patients with CRPC who had discontinued AA therapy at a single institution (6/2009-6/2014). PSA values were assessed before, during, and after stopping AA therapy. Response was defined as &gt;50% PSA decline post-AA stoppage, with no additional therapy added. Results: From 51 patients treated with AA, only 22 (43%) were eligible for withdrawal response evaluation. A total of 29 patients (57%) were changed to alternate therapies too soon for withdrawal response evaluation. Of the 22 evaluable patients, AA withdrawal was seen in 2 patients (9%). The first patient had a 72% reduction in PSA upon discontinuation of AA, with PSA dropping from 330 (ng/mL) to 93 over 16 days. Previously administered dexamethasone was continued. He had been on AA therapy for 12 months. Time to next treatment was only 1 month so PFS was not ascertainable. The second patient had a 60% reduction in PSA after simultaneously discontinuing both AA and prednisone. His PSA declined from 25.1 to 9.9 over 2 months. He had received only 2 prior months of AA and prednisone and had a clear PSA rise during this therapy. PFS after AA and prednisone discontinuation was 3 months. Time to next treatment was 6 months. Neither patient who responded to AA withdrawal had a prior bicalutamide withdrawal response. Conclusions: PSA response to AA withdrawal is a known, but poorly understood phenomenon that occurs in a subset of patients. Larger studies with longer follow-up are needed to define the incidence of this observation. The potential role of glucocorticoids in this process needs additional elucidation.
InSite: a computational method for identifying protein-protein interaction binding sites on a proteome-wide scale
Authors: Haidong Wang, Eran Segal, Asa Ben-Hur, Qian-Ru Li, Marc Vidal, Daphne Koller
Journal: Genome biology (2007)

We propose InSite, a computational method that integrates high-throughput protein and sequence data to infer the specific binding regions of interacting protein pairs. We compared our predictions with binding sites in Protein Data Bank and found significantly more binding events occur at sites we predicted. Several regions containing disease-causing mutations or cancer polymorphisms in human are predicted to be binding for protein pairs related to the disease, which suggests novel mechanistic hypotheses for several diseases.
PWE-185 The diagnostic yield of duodenal biopsy in coeliac disease relative to clinical indications and serology findings: an analysis of 2109 patients: Abstract PWE-185 Table 1
Authors: N Sagar, K Muthirulandi, N Sharma
Journal: Gut (2012)

<h3>Introduction</h3> Serology testing with IgA tissue transglutaminase (TTG) is relatively cheap and non-invasive which NICE guidelines for coeliac disease (CD) advocate as a first choice test for patients with unexpected weight loss or anaemia.<sup>1</sup> Referral for duodenal biopsy is indicated if serology is positive or if negative but there is still a clinical suspicion of CD. The sensitivity, specificity and negative predictive value for IgA TTG have been found to be 90.9%, 90.9% and 99.6% respectively thus demonstrating IgA TTG to be a sensitive marker for CD.<sup>2</sup> Our aim was to evaluate the diagnostic yield of duodenal biopsies relative to clinical indications and serology findings. <h3>Methods</h3> This is a retrospective review of 2109 adult patients from the Heart of England Trust, between January 2009 and December 2010. Coeliac serology (IgA TTG), immunoglobulin levels and D2 biopsy results were recorded for patients referred for upper gastrointestinal endoscopy for anaemia (n=1550) or weight loss (n=559). <h3>Results</h3> In the anaemia group, 7/27 (25.9%) with positive serology had a negative biopsy, 19/27 (70.4%) with positive serology had a positive biopsy and 1/27 (3.7%) with positive serology had no biopsy taken. 6/27 (22.2%) with positive biopsy had negative serology. In the weight loss group, 4/12 (33.3%) with positive serology had a negative biopsy, 5/12 (41.7%) with positive serology had a positive biopsy and 3/12 (25.0%) with positive serology had no biopsy taken. 7/14 (50.0%) with positive biopsy had negative serology. <h3>Conclusion</h3> Our review demonstrates that anaemia or weight loss are good indicators to attempt to diagnose CD by duodenal biopsy. If we corrected for the diagnosis of upper GI cancer, in our cohort, an additional 14 cases of CD would have been diagnosed if all patients had a duodenal biopsy. Furthermore, a significant proportion of patients in our study with a biopsy positive for CD had negative serology, strengthening the argument that all such patients should have a duodenal biopsy. Rates of serology testing were poor. However, we suggest regardless of serology patients referred with anaemia or weight loss should have a duodenal biopsy to look for evidence of coeliac disease. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>NICE Guidelines</b>. <i>Coeliac Disease: Recognition and Assessment of Coeliac Disease</i>. 2009. 2. <b>Hopper AD</b>, Hadjivassiliou M, Hurlstone DP, <i>et al.</i> What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. <i>Clin Gastroenterol Hepatol</i> 2008;<b>6</b>:314–20.
Neuropsychological Outcome in Chemotherapy-Only–Treated Children With Acute Lymphoblastic Leukemia
Authors: Nathalie C.A.J. Jansen, Annette Kingma, Arnout Schuitema, Anke Bouma, Anjo J.P. Veerman, Willem A. Kamps
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and systemic chemotherapy were included in a nationwide, prospective-longitudinal, sibling-controlled study. Patients and siblings completed three extensive neuropsychological assessments: at diagnosis, 3 to 6 months after completion of (2-year) treatment and 4.5 years after diagnosis. Assessments included measures of learning, memory, attention, speed, executive functioning, visual-constructive functioning, and fine-motor functioning. Multilevel analyses were applied to evaluate patients' performances over time and to compare patients to 29 siblings (median age of siblings at first assessment, 8.2 years; range, 4.5 to 12.6 years) and to normative data. Results No major differences were found in neuropsychological performance between patients and siblings, with both groups performing mainly in the normal range. The patient group as a whole, however, scored significantly lower than the siblings on complex fine-motor functioning at the last evaluation. Large practice effects were found for both patients and siblings in four of 11 tasks. Patients who uttered physical complaints (ie, pain and/or tiredness) at the first pretreatment assessment scored significantly lower than siblings on attention and speed at the last two evaluations. Conclusion Despite intensive and potentially neurotoxic treatment, no evident negative, neuropsychological late effects were found 4.5 years after diagnosis, except for effects on complex fine-motor functioning. Both the large practice effects observed and the poorer performances on sustained attention for patients with physical complaints should be reckoned with in prospective, longitudinal neuropsychological research in children.
Abstract 13369: Chronic Kidney Disease Predicts New Lesion Revascularization after Acute Myocardial Infarction
Authors: Hiroki Ikenaga, Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Fumiharu Miura, Yasuharu Nakama, Kazuoki Dai, Takayuki Ohtani, Yoshimasa Morimoto, Kentaro Ejiri, Nozomu Oda, Masayuki Nakamura, Takashi Miki
Journal: Circulation (2010)
The U.S. Plays Catch Up
Authors: M. Fillon
Journal: JNCI Journal of the National Cancer Institute (2011)

According to the Centers for Disease Control and Prevention, tobacco kills more than 5 million people per year worldwide — more than HIV, tuberculosis, and malaria combined. The CDC estimates that more than 1 billion people will die this century from tobacco-related illness unless urgent action is taken. The World Health Organization is well aware of these statistics. To date, 172 countries have adopted the WHO’s Framework Convention on Tobacco Control (FCTC), the world’s first public health treaty. The framework, which uses a global approach to combating the tobacco epidemic, requires tobacco products to carry warning labels covering at least 30% – 50% of the package’s principal display areas — preferably with graphic pictures or illustrations — portraying the harmful effects of tobacco use. Although the U.S. has not officially signed on to WHO FCTC, the new U.S. warning labels match the labeling initiatives efforts adopted by countries that have. To assess how the health warnings will affect individual interest in quitting smoking, CDC researchers reviewed data from the 2008 – 2010 Global Adult Tobacco Survey culled from 14 FCTC countries. Their findings appeared in the May 26, 2011, issue of the CDC’s Morbidity and Mortality Weekly Report. Their study found that most men and women smokers surveyed said they noticed the warnings on the cigarette packages and more than 25% in all countries (excluding Poland) were thinking about quitting because of the warnings. In Bangladesh, Brazil, India, Thailand, Ukraine, and Vietnam, 50% said they were considering quitting. For further evidence that the labels can work, the U.S. only needs to look north. Although the U.S. was first with warning labels in 1966, approximately 10 years ago, Canada became the first country to carry graphic warning labels. Between 1999 and 2009, the number of Canadian smokers aged 15 – 19 years has dropped from 28% to 13%, and adult smoking has decreased from 25% to 17.5%. According to Hammond, “While not all of that is due to the labels, about 30% – 40% of Canadian smokers have said the warning helped them to make a quit attempt, and of those who did quit, about 30% say the warnings helped them to ‘stay quit. ’ ”
A conserved region within interferon regulatory factor 5 controls breast cancer cell migration through a cytoplasmic and transcription-independent mechanism
Authors: Erica Pimenta, Betsy J Barnes
Journal: Molecular Cancer (2015)

Migration of breast cancer cells out of a duct or lobule is a prerequisite for invasion and metastasis. However, the factors controlling breast cancer cell migration are not fully elucidated. We previously found that expression of the transcription factor interferon regulatory factor 5 (IRF5) is significantly decreased as a breast lesion progresses from a non-malignant stage to ductal carcinoma in situ and is eventually lost in ~80% of invasive ductal carcinomas examined. Human in vitro and murine in vivo models of invasive breast cancer confirmed an important role for IRF5 in regulating cell motility, invasion and/or metastasis; yet, the mechanism(s) by which this occurs is not known. Since IRF5 is primarily expressed in the cytoplasm of human mammary epithelial cells, we hypothesized that IRF5 may function in a transcription-independent manner to control intrinsic cell migration.A series of IRF5 deletion mutants were tested in cell motility, invasion and migration assays. A novel, conserved 10 amino acid domain was identified that regulates mammary epithelial cell migration. This region (∆115-125) is downstream of IRF5's DNA binding domain and therefore when absent, retains IRF5 transcription activity but loses cell migration control. An IRF5 construct with a mutated nuclear localization signal further confirmed that IRF5 controls migration in a cytoplasmic and transcription-independent manner. Candidate cytoskeletal molecules were identified in MDA-MB-231 cells to interact with IRF5 by immunoprecipitation and mass spectrometry analysis. α6-tubulin was independently confirmed to interact with endogenous IRF5 in MCF-10A cells. Alterations in F-actin bundling after staining EV- and IRF5-231 cells with phalloidin suggests that IRF5 may control cell migration/motility through its interaction with cytoskeletal molecules that contribute to the formation of F-actin networks. Last and most notably, we found that IRF5's control of cell migration is not restricted to mammary epithelial cells but functions in other epithelial cell types suggesting a more global role for this newly identified cell migratory function of IRF5.These findings are significant as they identify a new regulator of epithelial cell migration and provide specific insight into the mechanism(s) by which loss of IRF5 expression in mammary epithelial cells contributes to breast cancer metastasis.
MANAGEMENT OF PARAVALVULAR AORTIC REGURGITATION AFTER TAVR: PROSPECTIVE EVALUATION OF THE AORTIC REGURGITATION INDEX
Authors: Jan–Malte Sinning, Mariuca Vasa–Nicotera, Christoph Hammerstingl, Alexander Ghanem, Alexander Sedaghat, Eberhard Grube, Georg Nickenig, Nikos Werner
Journal: Journal of the American College of Cardiology (2013)
Medically unexplained neurological symptoms
Authors: M. D O' Brien
Journal: BMJ (1998)

See p 582 

A psychological component exists in all illness, contributing a variable amount to the clinical presentation. At the benign end of this range are patients who describe their symptoms in more florid terms than seem to be justified. At the malignant end is malingering and the Munchausen syndrome. Between these extremes are a range of patients who present with non-organic signs or symptoms, with or without underlying neurological disease, usually called hysterical elaboration or hysterical conversion disorder.

Again a range of clinical presentation exists. If patients present with apparent non-organic signs or symptoms and are later found to have an underlying disease which might account for some or most of their original problems this is perceived as a hysterical elaboration of the underlying deficit. For example, a patient who seems to have a hysterical paraplegia might be found to have white matter changes on magnetic resonance imaging and oligoclonal bands in the cerebrospinal fluid. Patients already known to have a neurological condition might develop non-organic signs or symptoms, sometimes related to the original condition, but often …
p27: A Barometer of Signaling Deregulation and Potential Predictor of Response to Targeted Therapies
Authors: Seth A. Wander, Dekuang Zhao, Joyce M. Slingerland
Journal: Clinical Cancer Research (2010)

Phosphorylation of the cyclin-dependent kinase inhibitor p27 by upstream mitogenic signaling pathways regulates its stability, localization, and biological function. In human cancers, loss of the antiproliferative action of p27 can arise through reduced protein levels and/or cytoplasmic mislocalization, leading to increased cell proliferation and/or cell migration, respectively. Reduced p27 expression levels and p27 mislocalization have potential prognostic and therapeutic implications in various types of human cancers. This review highlights mechanisms of functional deregulation of p27 by oncogenic signaling that provide an important molecular rationale for pathway targeting in cancer treatment.