tbuckley/cabot-search huggingface dataset:
Expression Analysis of Barrett's Esophagus–Associated High-Grade Dysplasia in Laser Capture Microdissected Archival Tissue
Authors: Edmond Sabo, Patricia A. Meitner, Rosemarie Tavares, Christopher L. Corless, Gregory Y. Lauwers, Steven F. Moss, Murray B. Resnick
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Identifying genes differentially expressed in nondysplastic BE (NDBE) from those expressed in high-grade dysplasia (HGD) should be of value in improving our understanding of this transition and may yield new diagnostic and/or prognostic markers. The aim of this study was to determine the differential transcriptome of HGD compared with NDBE through gene microarray analysis of epithelial cells microdissected from archival tissue specimens. Experimental Design: Laser capture microdissection was used to isolate epithelial cells from adjacent inflammatory and stromal cells. Epithelial mRNA was extracted from areas of NDBE and HGD in matched biopsies from 11 patients. mRNA was reverse transcribed and applied on Affymetrix cDNA microarray chips customized for formalin-exposed tissue. For a subset of these genes, differential gene expression was confirmed by real-time PCR and immunohistochemistry. Results: There were 131 genes overexpressed by at least 2.5-fold in HGD versus NDBE and 16 genes that were underexpressed by at least 2.5-fold. Among the overexpressed genes are several previously shown to be increased in the neoplastic progression of BE, as well as novel genes such as lipocalin-2, S100A9, matrix metallopeptidase 12, secernin 1, and topoisomerase IIα. Genes decreased in dysplastic epithelium include MUC5AC, trefoil factor 1 (TFF1), meprin A, and CD13. Real-time PCR validated the changes in expression in 24 of 28 selected genes. Immunohistochemistry confirmed increased protein expression for topoisomerase IIα, S100A9, and lipocalin-2 and decreased expression of TFF1 across the spectrum of BE-associated dysplasia from NDBE through adenocarcinoma. Conclusions: This is the first study to identify epithelial genes differentially expressed in HGD versus NDBE in matched patient samples. The genes identified include several previously implicated in the pathogenesis of BE-associated dysplasia and new candidates for further investigation.
Do mouthguards prevent concussion?
Authors: Paul McCrory
Journal: British Journal of Sports Medicine (2001)

One of the most commonly held myths in sports medicine is the premise that wearing a mouthguard will prevent concussion. The origins of this contention are obscure, but an evidence based review of the scientific support for this concept has not been previously published.

Mouthguards or “gum shields” were originally developed in 1890 by Woolf Krause, a London dentist, as a means of protecting boxers from lip lacerations. Such injuries were a common and often disabling accompaniment of boxing contests in that era.1–3 These gum shields were originally made from gutta percha and were held in place by clenching the teeth. Philip Krause, his son, who was both a dentist and amateur boxer, subsequently refined the design of the gum shield and made them from vella rubber.1 In the United States, the first mouthguard was probably manufactured by Thomas Carlos, a Chicago dentist, in 1916.1, 4

By the 1930s, mouthguards were part of the standard boxers' equipment and have remained so since that time. Jack Dempsey and Gene Tunney, before the second world war, were probably the last of the heavyweight champions to fight without a mouthpiece.

There are several distinct types of mouthguard. The simplest are the stock mouthguards, which may be purchased from sporting goods stores. The second type are the mouth formed or boil and bite guards, which are heated and immediately worn by the athlete allowing some adaptation to the dentition to occur. The more complex mouthguards are custom made …
The effect of short-term pre-exposure to ambient bioaerosols, anthropogenic pollutants and noise on cardiopulmonary health baseline parameters
Authors: Thomas Cole-Hunter, Nadine Kubesch, David Martinez, Marta Cirach, Jordina Belmonte, Audrey de Nazelle, Mark Nieuwenhuijsen
Journal: European Respiratory Journal (2013)

Exposure to ambient air pollution is known to affect some health outcomes (such as asthma exacerbation and CVA); however, findings on short-term effects are inconsistent and have important implications for baseline measurements in experimental studies of acute health effects. The current study aimed to investigate the 3-day pre-exposure lag effect of ambient bioaerosols, anthropogenic pollutants and noise on cardiopulmonary baseline measurements in an experimental acute health effect study. Participants (N = 31; 58% female) had their residing addresses geo-coded for spatiotemporal modeling of NOX and PM2.5, and temporal modeling of bioaerosols and noise. Health baseline parameters (FEV1, PEF, eNO, blood pressure and pulse) were collected from each participant on four different occasions and analysed via multivariate-adjusted linear mixed modeling. FEV1 was associated with 2-day-lag NOX and PM2.5 (p
The biphasic spirogram: a clue to unilateral narrowing of a mainstem bronchus.
Authors: A D Gascoigne, P A Corris, J H Dark, G J Gibson
Journal: Thorax (1990)

Two patients with narrowing of a mainstem bronchus each showed two unusual functional features that are likely to be characteristic of this condition. The maximum inspiratory flow-volume curve showed an end inspiratory "tail" and the forced expiratory spirogram had a biphasic shape with normal initial curvature but a "straight line" appearance in later expiration. In one patient relief of the bronchial stenosis by the insertion of a stent restored normal contours to the spirogram and flow-volume curves.
Clinical Significance of Micrometastatic Cells Detected by E48 (Ly-6D) Reverse Transcription-Polymerase Chain Reaction in Bone Marrow of Head and Neck Cancer Patients
Authors: David R. Colnot, Eline J. C. Nieuwenhuis, Dirk J. Kuik, C. René Leemans, Janny Dijkstra, Gordon B. Snow, Guus A. M. S. van Dongen, Ruud H. Brakenhoff
Journal: Clinical Cancer Research (2004)

Despite improvements in locoregional treatment of head and neck squamous cell carcinoma (HNSCC), local and distant failure rates remain high. The strongest prognostic indicator of HNSCC is the presence of lymph node metastases in the neck, but the value of this indicator has limitations when using for the individual patient. The presence of micrometastatic cells in bone marrow has been shown to be a putative prognostic indicator in HNSCC and other epithelial malignancies, which might allow more accurate staging and selection of patients for whom adjuvant or experimental therapy is recommended. The gene encoding the E48 antigen is selectively expressed by HNSCC, and the detection of E48 transcripts in bone marrow by reverse transcription-polymerase chain reaction (RT-PCR) presumably represents the presence of micrometastatic cells. The purpose of this study was to determine the association between the presence of micrometastatic cells in bone marrow of HNSCC patients and clinical outcome.A total of 162 patients treated surgically for primary HNSCC underwent a single bone marrow aspiration from the upper iliac crest for detection of micrometastatic cells using E48 RT-PCR. In total, 139 patients were evaluable. The primary statistical endpoints were disease-free survival and distant metastasis-free survival. In addition, bone marrow samples of 30 noncancer controls were evaluated.E48 RT-PCR indicated the presence of micrometastatic cells in the bone marrow in 56 of 139 (40%) of the HNSCC patients and 0 of 30 of the noncancer controls (P < 0.0001). The presence of micrometastatic cells had no significant influence on disease-free survival or distant metastasis-free survival for the whole group of HNSCC patients (P = 0.1460 and P = 0.2912, respectively). For patients with >or=2 lymph node metastases, however, the presence of micrometastatic cells was associated with a poor distant metastasis-free survival (P = 0.0210).The presence of micrometastatic cells in bone marrow of HNSCC patients with >or=2 lymph node metastases is correlated with a poor distant metastasis-free survival. In this subgroup of HNSCC patients, E48 RT-PCR seems to be a valuable tool to identify patients who are at increased risk for development of distant metastases and therefore might benefit from experimental adjuvant systemic therapy.
Napkin (diaper) dermatitis and gastrointestinal carriage of Candida albicans
Authors: A. REBORA, J. J. LEYDEN
Journal: British Journal of Dermatology (1981)

The correlation of recovery of Candida albicans from the skin, rectum and faeces of four clinically distinct groups of infants with napkin (diaper) dermatitis has been studied. We found that: (I) C. albicans is largely and constantly present both on the skin and in faeces of subjects with clinically overt Candidiasis of the napkin area; (2) C. albicans is lacking from both the skin and faeces of subjects with chafing or atopic dermatitis; (3) C. albicans can be found in faeces of subjects with unclassifiable napkin dermatitis in a direct relationship with its clinical severity; (4) failure to recover C. albicans from the skin can be due to the inhibitory effect of the inflammatory host reaction and therefore can be misleading.
Body composition and exercise performance in patients with chronic obstructive pulmonary disease (COPD)
Authors: G B Drummond
Journal: Thorax (1992)

Body composition and exercise per- formance in patients with chronic ob- structive pulmonary disease (COPD)The original article ofDr A M W J Schols and others in the October issue of Thorax' shows that exercise performance, as indicated by the distance walked in 12 minutes, is related to the fat free mass of the patient.Fat free mass was taken to be an indicator of muscle mass, but the investigators found that arm muscle size was not well related to other measures of muscle mass.Several possible reasons for the relation- ship, two of which were related to respiratory muscle performance, were considered.There are, however, two other obvious possibilities.Firstly, muscle loss may well be from the lower limbs.If this were so, then exercise capacity could be reduced because of the smaller capacity for this type of exercise, irrespective of respiratory muscle function.Secondly, the patients who performed badly might take little regular exercise, or indeed may be limited by their symptoms in their exercise.Such patients would display lower limb muscle wasting.Consequently, performance may be related to muscle mass (particularly in the legs) by loss of activity.In the clinical evaluation of patients who are housebound with severe lung or cardiac dis- ease wasting of the quadriceps femoris and calf muscles is often a striking feature.Dr Schols and his colleagues suggest that a compromised nutritional state may con- tribute to impaired performance, and that muscle mass determines exercise performance.Unwary readers may be led to conclude that patients do badly because of malnutrition, or even that improved nutrition might be beneficial.This is not necessarily so.Correlation does not indicate cause and effect: even if there is such a relationship, which is cause and which is effect may not be self evident.
Cytosolic prostaglandin E2 synthase/p23 but not apoptosis-linked gene 2 is downregulated in human atherosclerotic plaques
Authors: W Martinet
Journal: Cardiovascular Research (2003)

In the November issue of Cardiovascular Research, we reported a strong downregulation of apoptosis-linked gene 2 (ALG-2) protein in advanced human atherosclerotic plaques as compared with non-atherosclerotic mammary arteries [1]. Because ALG-2 is a positive mediator of apoptosis, we proposed a novel survival mechanism against cell death in human plaques. Downregulation of ALG-2 protein was identified via the Western array screening facility of BD Biosciences. This technique included polyacrylamide gel electrophoresis and Western blotting followed by screening of the blots with unique cocktails of monoclonal antibodies. In …
ACTIVATED PROTEIN C RESISTANCE DUE TO A COMMON FACTOR V GENE MUTATION IS A MAJOR RISK FACTOR FOR VENOUS THROMBOSIS
Authors: B. Zöller, MD, A. Hillarp, PhD, E. Berntorp, MD, B. Dahlbäck, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution of arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q 506 ) is more slowly degraded by activated protein C than normal FVa (FVa:R 506 ) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found in fewer than 10–15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20–60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1–15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.
Early-Onset, Coexisting Autoimmunity and Decreased HLA-Mediated Susceptibility Are the Characteristics of Diabetes in Down Syndrome
Authors: Rachel J. Aitken, Kay L. Mehers, Alistair J. Williams, Jamie Brown, Polly J. Bingley, Reinhard W. Holl, Tilman R. Rohrer, Edith Schober, Majedah M. Abdul-Rasoul, Julian P.H. Shield, Kathleen M. Gillespie
Journal: Diabetes Care (2012)

Down syndrome (DS) is associated with an increased risk of diabetes, particularly in young children. HLA-mediated risk is however decreased in children with DS and diabetes (DSD). We hypothesized that early-onset diabetes in children with DS is etiologically different from autoimmune diabetes.Clinical and immunogenetic markers of autoimmune diabetes were studied in 136 individuals with DSD and compared with 194 age- and sex-matched individuals with type 1 diabetes, 222 with DS, and 671 healthy controls. HLA class II was analyzed by sequence-specific primed PCR. Islet autoantibodies were measured by radioimmunoassay.Age at onset of diabetes was biphasic, with 22% of DS children diagnosed before 2 years of age, compared with only 4% in this age-group with type 1 diabetes in the general population (P < 0.0001). The frequency of the highest-risk type 1 diabetes-associated HLA genotype, DR3-DQ2/DR4-DQ8, was decreased in both early- and later-onset DSD compared with age-matched children with type 1 diabetes (P < 0.0001), although HLA DR3-DQ2 genotypes were increased (P = 0.004). Antibodies to GAD were observed in all five samples tested from children diagnosed at ≤2 years of age, and persistent islet autoantibodies were detected in 72% of DSD cases. Thyroid and celiac disease were diagnosed in 74 and 14%, respectively, of the DSD cohort.Early-onset diabetes in children with DS is unlikely to be etiologically different from autoimmune diabetes occurring in older DS children. Overall, these studies demonstrate more extreme autoimmunity in DSD typified by early-onset diabetes with multiple autoimmunity, persistent islet autoantibodies, and decreased HLA-mediated susceptibility.
Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study
Authors: Hisayoshi Daito, Motoi Suzuki, Jun Shiihara, Paul E Kilgore, Hitoshi Ohtomo, Konosuke Morimoto, Masayuki Ishida, Taro Kamigaki, Hitoshi Oshitani, Masahiro Hashizume, Wataru Endo, Koichi Hagiwara, Koya Ariyoshi, Shoji Okinaga
Journal: Thorax (2013)

<h3>Background</h3> On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals. <h3>Methods</h3> A multicentre survey was conducted at three hospitals in Kesennuma City (population 74 000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia. <h3>Results</h3> A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period and 225 cases during the post-disaster period. The majority (90%) of the post-disaster pneumonia patients were aged ≥65 years, and only eight cases (3.6%) were associated with near-drowning in the tsunami waters. The clinical pattern and causative pathogens were almost identical among the pre-disaster and post-disaster pneumonia patients. A marked increase in the incidence of pneumonia was observed during the 3-month period following the disaster; the weekly incidence rates of pneumonia hospitalisations and pneumonia-associated deaths increased by 5.7 times (95% CI 3.9 to 8.4) and 8.9 times (95% CI 4.4 to 17.8), respectively. The increases were largest among residents in nursing homes followed by those in evacuation shelters. <h3>Conclusions</h3> A substantial increase in the pneumonia burden was observed among adults after the Tohoku earthquake and tsunami. Although the exact cause remains unresolved, multiple factors including population aging and stressful living conditions likely contributed to this pneumonia outbreak.
Emerging hepatotoxicity biomarkers and their potential to improve understanding and management of drug-induced liver injury
Authors: Jiri Aubrecht, Shelli J Schomaker, David E Amacher
Journal: Genome Medicine (2013)

Biomarkers of drug-induced liver injury (DILI) are essential for the diagnosis of severe cases of DILI in clinical trials and clinical practice, but the currently used biomarker paradigm detects damage after it has occurred and has limited prognostic value. The development of new biomarker strategies that improve the diagnosis of DILI by providing increased specificity and/or by identifying individual patients who are at risk for DILI is therefore crucial. See related Research, http://genomemedicine.com/content/5/9/86.
S29 Prognostic Value Of Platelet Count In Patients Admitted With An Acute Exacerbation Of Copd (aecopd)
Authors: C. Echevarria, J. Steer, G. Gibson, S. Bourke
Journal: Thorax (2014)

<h3>Introduction</h3> In an observational cohort of patients admitted with AECOPD, thrombocytosis was associated with inpatient and 1-year mortality.<sup>1</sup> We aimed to validate, and explore mechanisms for, this association within our original DECAF cohort (n = 920).<sup>2</sup> <h3>Methods</h3> Admission platelet counts were categorised as low (&lt;150), normal (150–400), or high (&gt;400) x10<sup>9</sup> cells/mm<sup>3</sup> and odds ratios assessed for inpatient and, among those surviving to discharge, 1-year mortality (normal platelet count=reference). For inpatient mortality, platelet category and DECAF indices were included in multivariate logistic regression. The areas under the ROC curves for DECAF and DECAF+Platelets were compared by the method of DeLong. Associations with thrombocytosis were analysed using Mann-Whitney or Fisher’s exact test. Causes of death at 1-year due to respiratory, cardiac or malignant disease were recorded. <h3>Results</h3> Thrombocytosis was associated with inpatient (OR 1.83, 95% CI 1.12–3.00, p = 0.016) and 1-year mortality (OR 1.62 95% CI 1.09–2.30, p = 0.017). Thrombocytopenia was associated with inpatient (OR 3.5, 95% CI 1.51–8.12, p = 0.004), but not 1-year mortality (OR 1.81, 95% CI 0.76–4.312.08, p = 0.181). On multivariate analysis, thrombocytosis (OR 1.85, 95% CI 1.03–3.33 p = 0.039) and thrombocytopenia (OR 3.00 95% CI 1.09–8.24 p = 0.033) independently predicted inpatient mortality, but did not improve predictive power of DECAF (AUROC: DECAF=0.86, DECAF+Platelets=0.86; p = 0.93). Thrombocytosis was associated with a higher white cell count (p&lt;0.001) and eMRCD score (i.e. more breathless when stable; p = 0.001), lower: albumin (p = 0.004), BMI (p = 0.002), FEV1 (p = 0.010), haemoglobin (p&lt;0.001), and a lower proportion of women (p = 0.004), and patients with eosinopenia (&lt;0.05 x 10<sup>9</sup>/l) (p = 0.008), cardiac death (p = 0.044), current smoking (p = 0.046), AF (p = 0.029) and diabetes (p = 0.006). Thrombocytosis was not related to cardiovascular disease, prior exacerbation and readmission rates or LTOT use, admission PaO<sub>2</sub>, pH or NIV, or length of stay. <h3>Discussion</h3> Thrombocytosis was an independent predictor of both inpatient mortality and, amongst survivors to discharge, 1-year mortality. Thrombocytosis was not associated with cardiovascular disease and the higher 1-year mortality was not due excess cardiovascular or cancer deaths, suggesting that other mechanisms are responsible. Whilst thrombocytosis was not associated with LTOT use or PaO<sub>2</sub>, it was associated with other indices of disease severity, including breathlessness and lower FEV1, BMI and albumin level. <h3>References</h3> Harrison <i>Thorax</i> 2014 Steer <i>Thorax</i> 2012
4E-Binding Protein 1: A Key Molecular “Funnel Factor” in Human Cancer with Clinical Implications
Authors: Gemma Armengol, Federico Rojo, Josep Castellví, Carmela Iglesias, Miriam Cuatrecasas, Berta Pons, José Baselga, Santiago Ramón y Cajal
Journal: Cancer Research (2007)

Abstract In an attempt to identify molecules that clearly reflect the oncogenic role of cell signaling pathways in human tumors, we propose a concept we term “funnel factor”, a factor where several oncogenic signals converge and drive the proliferative signal downstream. In studies done in various tumor types, the expression of key cell signaling factors, including Her1 and Her2 growth factor receptors, as well as the RAS-RAF-mitogen-activated protein kinase and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways was correlated with the associated clinicopathologic characteristics of these tumors. The downstream factors p70, S6, 4E-binding protein 1 (4E-BP1), and eukaryotic translation initiation factor 4E, which play a critical role in the control of protein synthesis, survival, and cell growth, were also analyzed. We found that phosphorylated 4E-BP1 (p-4E-BP1) expression in breast, ovary, and prostate tumors is associated with malignant progression and an adverse prognosis regardless of the upstream oncogenic alterations. Thus, p-4E-BP1 seems to act as a funnel factor for an essential oncogenic capability of tumor cells, self-sufficiency in growth signals, and could be a highly relevant molecular marker of malignant potential. Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets. [Cancer Res 2007;67(16):7551–5]