tbuckley/cabot-search huggingface dataset:
Incidence, Evolution, and Spatial Distribution of Functional Reentry During Ventricular Fibrillation in Pigs
Authors: Jack M. Rogers, Jian Huang, William M. Smith, Raymond E. Ideker
Journal: Circulation Research (1999)

Abstract —Functional reentry has been hypothesized to be an underlying mechanism of ventricular fibrillation (VF); however, its contribution to activation patterns during fully developed VF is unclear. We applied new quantitative pattern analysis techniques to mapping data acquired from a 21×24 unipolar electrode array (2-mm spacing) located on the ventricular epicardium of 7 open-chest, unsupported pigs. Data epochs 4 seconds long beginning 1, 10, 20, 30, and 40 seconds after electrical induction were analyzed. Reentrant circuits were automatically identified and quantified. We found that 2.3% of activation pathways could unambiguously be classified as reentrant. From scaling analysis, an additional 28% of the pathways may also have been reentrant. Reentry was short-lived with 1.5±1.5 (mean±SD) complete cycles per circuit. The fraction of reentrant pathways, number of cycles per circuit, cycle duration, and area and perimeter of the cores all increased significantly as VF progressed. Core drift speed decreased significantly. Neither the orientation of the cores nor the direction of drift was well predicted by the epicardial fiber orientation ( r 2 =0.108 and 0.138, respectively, by linear regression). Reentrant circuits were clustered in regions of the epicardium. We conclude the following: (1) Epicardial reentry is relatively uncommon and short-lived during VF, suggesting either that sustained reentry is transmural or that mechanisms governing sustained reentry are relatively unimportant to the dynamics of VF. (2) Reentrant circuits become more common, larger, and longer-lived as VF progresses, which may explain a recently observed increase in VF organization during the first minute of VF. (3) The conditions necessary to induce and sustain reentry are distributed nonuniformly.
<i>NGALR</i> Is Overexpressed and Regulated by Hypomethylation in Esophageal Squamous Cell Carcinoma
Authors: Lei Cui, Li-Yan Xu, Zhong-Ying Shen, Qian Tao, Shu-Ying Gao, Zhuo Lv, Ze-Peng Du, Wang-Kai Fang, En-Min Li
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Neutrophil gelatinase-associated lipocalin receptor (NGALR) mRNA level is reduced in isolated chronic myelogenous leukemia blasts but up-regulated in esophageal squamous cell carcinoma (ESCC). The mechanism of NGALR regulation is unknown. Here, we show the expression pattern of NGALR and examine the aberrant methylation of its gene in ESCC and esophageal carcinoma cell lines. Experimental Design: The expression pattern of NGALR was analyzed by immunohistochemistry in 59 ESCCs and compared with noncancerous tissues. The DNA methylation status was investigated by methylation-specific PCR and by bisulfite genomic sequencing in esophageal carcinoma cell lines and surgically resected samples. Methylated cell lines were treated with a methylation inhibitor to restore NGALR expression. Results: The expression of NGALR in ESCC was significantly higher in tumor cell membrane and cytoplasm than in normal esophageal epithelium (P &amp;lt; 0.01). Methylated alleles were detected in three NGALR-nonexpressing cell lines but were not detected in three NGALR-expressing cell lines. Treatment of methylated cell lines with 5-aza-2′-deoxycytidine, a methylation inhibitor, restored NGALR expression. In surgically resected samples, 31 of 77 (40.3%) primary esophageal carcinomas and 46 of 77 (59.7%) paired normal tissues contained methylated NGALR alleles (P &amp;lt; 0.05). Conclusions: Our results suggest that NGALR hypomethylation contributes to its expression in esophageal carcinomas and that this overexpression may play a role in the pathogenesis of esophageal carcinomas.
Somatic Delusion or Self-Mutilation in a Schizophrenic Woman: A Psychiatric Emergency Room Case Report
Authors: DAVID P. KRAFT, HAROUTUN M. BABIGIAN
Journal: American Journal of Psychiatry (1972)

The authors describe a schizophrenic woman who came to a psychiatric emergency room because of pain from needles in her arms. Her history suggested that she was experiencing somatic delusions as part of her chronic schizophrenic process. Radiological studies showed actual needles in one arm due to past episodes of self-mutilation. The case illustrates the hazards involved in basing diagnostic and therapeutic assumptions on inadequate data.
Risk of subsequentin situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinomain situ
Authors: G. Curigliano, D. Disalvatore, A. Esposito, G. Pruneri, M. Lazzeroni, A. Guerrieri-Gonzaga, A. Luini, R. Orecchia, A. Goldhirsch, N. Rotmensz, B. Bonanni, G. Viale
Journal: Annals of Oncology (2015)
Higher Red Blood Cell Distribution Width Is Associated With the Metabolic Syndrome
Authors: Miguel Angel Sánchez-Chaparro, Eva Calvo-Bonacho, Arturo González-Quintela, Martha Cabrera, Juan Carlos Sáinz, Carlos Fernández-Labandera, Luis Quevedo Aguado, Ana Fernández Meseguer, Pedro Valdivielso, Javier Román-García
Journal: Diabetes Care (2010)

A high level of erythrocyte distribution width (RDW) is a novel prognostic marker that may reflect an underlying inflammatory state (1–3). Metabolic syndrome (MetS) is a chronic inflammatory disorder (4). We investigated the potential association between high levels of RDW and MetS.

This cross-sectional study is part of the Ibermutuamur CArdiovascular RIsk Assessment (ICARIA) plan. A detailed description has been published elsewhere (5). A total of 217,567 workers (73.1% male, mean age 35.8 years) who underwent a routine medical checkup were included in the study. The Adult Treatment Panel III (ATPIII, 2001) definition for MetS was used.

The mean RDW in the whole sample was 13.4% (SD 0.82%; range 10.1–33.4%; 75th percentile 14.0%). The …
MMPs in the gut: inflammation hits the matrix
Authors: D SCHUPPAN
Journal: Gut (2000)

See articles on pages 57 and 63 

Two papers in this issue of Gut focus on RNA and protein levels of matrix metalloproteinases (MMPs) in diagnostic biopsies of patients with inflammatory bowel disease (see pages 57 and 63).1 2 Both reports are congruent in that in ulcerated lesions, MMP-3 mRNA, which encodes a key enzyme in matrix degradation, is highly increased (up to 15- and 100-fold, depending on the methodology used), paralleled by a more moderate increase in MMP-3 protein levels, whereas there is little change in levels of the physiological inhibitor of most MMPs, tissue inhibitor of metalloproteinases 1 (TIMP-1). Thus the elevated ratio of MMP-3 over TIMP-1 would favour matrix degradation. Similar data were obtained for MMP-1/TIMP-1 (degradation of fibrillar collagens), MMP-2/TIMP-2 (degradation of basement membrane collagen and denatured collagens), and for membrane-type MMP-1 (MMP-14) which can activate MMP-2.2 

Whereas matrix dissolution is plausible for ulcerative colitis (UC), it comes as a surprise that comparable levels of expression for MMPs and MMP/TIMP-1 ratios were found in ulcers of Crohn's disease (CD) which rather leads to intestinal fibrosis. As expression of several collagens which are the major components of scar tissue was also not different between lesions of CD and UC,3 the factors that determine fibrogenesis (that …
Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells
Authors: Ning Kong, Qin Lan, Maogen Chen, Tina Zheng, Wenru Su, Julie Wang, Ziyan Yang, Ryan Park, Grant Dagliyan, Peter S Conti, David Brand, Zhongmin Liu, Hejian Zou, William Stohl, Song Guo Zheng
Journal: Annals of the Rheumatic Diseases (2012)

Background Although natural regulatory T cells (nTregs) can suppress osteoclastogenesis, the role of TGF-β-induced CD4+Foxp3+ Tregs (iTregs) in osteoclastogenesis remains unknown. Objective To determine the effects of iTregs on osteoclastogenesis in vitro and on bone erosion in vivo in collagen-induced arthritis (CIA). Methods Osteoclastogenesis was induced in bone marrow CD11b+ cells with receptor activator of nuclear factor κ B (NF-κB) ligand (RANKL) and macrophage colony stimulating factor. Graded doses of Tregs were added to inhibit osteoclastogenesis. Transwell and antibody blockade experiments were performed to assess the roles for cell contact and soluble cytokines. NF-κB activation was determined by western blot. iTregs or nTregs were adoptively transferred to mice with CIA to assess in vivo effects on disease incidence and bone erosion, the latter determined by CT scanning. Results Both nTregs and iTregs greatly suppressed osteoclastogenesis in vitro, but only iTregs sustained this effect when interleukin-6 was present. iTregs, but not nTregs, significantly suppressed development of CIA. Bone erosions in iTregs-treated mice were diminished compared with untreated mice or nTregs-treated mice. Treatment with iTregs, but not with nTregs, dramatically decreased NF-κB p65/p50 levels in osteoclasts in vitro and p65/50 and RANKL expression by synovial tissues in vivo. Conclusion iTregs may be therapeutically beneficial in rheumatoid arthritis and related diseases associated with bone erosions.
Low BMI in emphysema patients: A contraindication for lung transplantation?
Authors: David Ruttens, Stijn Verleden, Robin Vos, Elly Vandermeulen, Annemie Vaneylen, Dirk Vanraemdonck, Bart Vanaudenaerde, Geert Verleden
Journal: European Respiratory Journal (2012)

Lung transplantation (LTx) is an accepted therapeutic option for patient with end-stage emphysema. These emphysema patients can be subdivided in blue bloaters and pink puffers,although most patients have characteristics of both groups. BMI is an important tool in distinguishing these subgroups. A low BMI is associated with a poor nutritional status which may predict a poor outcome after LTx. We aimed to investigate the outcome of emphysema patients with a low pre-transplant BMI (<20) in terms of acute rejection (AR), lymphocytic bronchiolitis (LB), infections, BOS and survival. All 193 patients transplanted for emphysema between 1991-2011 and surviving more than 60 days post transplant, were included (53 SLTx(single) and 140 SSLTx(double)). AR, LB and BOS are diagnosed according to the ISHLT criteria. Multivariate analyzes were done using SAS software.

Patients with a lower BMI ( 20 for the total population (p=0.01) (figure).

Prevalence of BOS was significantly lower within the lower BMI group, independent from other covariates (table). There is a statistical association between the prevalence of BOS, infection and LB (table).

We conclude from this single centre observation that emphysema patients with a BMI below 20 have a better outcome in terms of BOS and mortality and this should therefore no longer be regarded as contra- indication for LTx.

![Figure][1]  [1]: pending:yes
Enhancer variants: evaluating functions in common disease
Authors: Olivia Corradin, Peter C Scacheri
Journal: Genome Medicine (2014)

Abstract Gene enhancer elements are noncoding segments of DNA that play a central role in regulating transcriptional programs that control development, cell identity, and evolutionary processes. Recent studies have shown that noncoding single nucleotide polymorphisms (SNPs) that have been associated with risk for numerous common diseases through genome-wide association studies frequently lie in cell-type-specific enhancer elements. These enhancer variants probably influence transcriptional output, thereby offering a mechanistic basis to explain their association with risk for many common diseases. This review focuses on the identification and interpretation of disease-susceptibility variants that influence enhancer function. We discuss strategies for prioritizing the study of functional enhancer SNPs over those likely to be benign, review experimental and computational approaches to identifying the gene targets of enhancer variants, and highlight efforts to quantify the impact of enhancer variants on target transcript levels and cellular phenotypes. These studies are beginning to provide insights into the mechanistic basis of many common diseases, as well as into how we might translate this knowledge for improved disease diagnosis, prevention and treatments. Finally, we highlight five major challenges often associated with interpreting enhancer variants, and discuss recent technical advances that may help to surmount these challenges.
Domestic use of cleaning sprays and asthma activity in females
Authors: Nicole Le Moual, Raphaelle Varraso, Valérie Siroux, Orianne Dumas, Rachel Nadif, Isabelle Pin, Jan-Paul Zock, Francine Kauffmann
Journal: European Respiratory Journal (2012)

We aimed to study the associations between the household use of cleaning sprays and asthma symptoms and control of asthma, in females from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Data were available for 683 females (mean age 44 yrs, 55% never smokers, 439 without asthma and 244 with current asthma). Both domestic exposures and asthma phenotypes (asthma symptom score, current asthma, poorly-controlled asthma (56%)) were evaluated as previously described in the European Community Respiratory Health Survey. Associations between the use of sprays and asthma phenotypes were evaluated using logistic and nominal regressions, adjusted for age, smoking, body mass index and occupational exposures. Significant associations were observed between the weekly use of at least two types of sprays and a high asthma symptom score (OR (95% CI) 2.50 (1.54–4.03)) compared with a null score. Consistent results were observed for current asthma (1.67 (1.08–2.56)) and poorly-controlled asthma (2.05 (1.25–3.35)) compared with females without asthma. The association for current asthma was higher in females not reporting avoidance of polluted places (2.12 (1.27–3.54)) than in those reporting such avoidance (0.99 (0.53–1.85)). The common use of household cleaning sprays is positively associated with a high asthma symptom score, current asthma and poorly-controlled asthma in females.
OC-099 Increased at risk screening and recognition of atypical presentation does not fully explain the 6.5-fold increase in paediatric coeliac disease (CD) incidence in the last 20 years in SE Scotland
Authors: V Merrick, L White, E Bannerman, R K Russell, D Basude, P Henderson, D C Wilson, P M Gillett
Journal: Gut (2012)

<h3>Introduction</h3> Current diagnostic practice for paediatric CD in the UK includes increased screening of family members and at- risk groups for example, diabetes mellitus. <h3>Aims</h3> To identify all incident cases of CD in SE Scotland over the 20-year period of 1990–2009 to assess trends in incidence, symptomatology, age at diagnosis and the impact of active screening of at-risk groups. Utility of routine laboratory tests at diagnosis was also evaluated (2005–2009 diagnoses only). <h3>Methods</h3> A retrospective review of case notes, pathology databases, endoscopy and patient records was performed for all children diagnosed with CD &lt;16 years from 1990 to 2009 on duodenal biopsy in SE Scotland (at-risk population group of 233 000 aged &lt;16 years). Data were age-sex standardised and analysed in 5-year epochs, with Poisson regression models used to calculate changes in incidence over time. <h3>Results</h3> 266 biopsy positive children were diagnosed from 1990 to 2009 with an increase in incidence from 1.8 (95% CI 1.1 to 2.7) to 11.7 (95% CI 9.8 to 13.9) per 100 000 children aged &lt;16 years during the 1990–1994 and 2005–2009 epochs respectively (p=0.001). The median age (IQR) at diagnosis also increased significantly from 29 (16–53) months to 90 (53–132) between these epochs (p&lt;0.0001), and non-classical presentation (children with a mono-symptomatic presentation and those with extra-intestinal symptoms for example, fatigue, pallor, irritability) increased significantly from 5% to 21% respectively (p=0.008). Additionally, 7% of children were diagnosed through targeted screening in 1990–1994 compared to 23% in 2005–2009 (p=0.002). When cases identified via active screening or with non-classical symptoms were removed, a significant rise from 1.51 (95% CI 0.91 to 2.38) in 1990–1994 to 6.59 (95% CI 5.17 to 8.28) in 2005–2009 (p=0.006) remained. Routine blood investigations demonstrated that over 25% were anaemic and over 50% were iron deficient at presentation in 2005–2009. <h3>Conclusion</h3> The incidence of paediatric CD has increased 6.5-fold over the last 20 years in SE Scotland. Children are older at diagnosis, presenting with fewer classical and more varied symptoms, and with iron deficiency anaemia the commonest laboratory abnormality. We show that both increased screening of at-risk groups and a lower threshold for serological screening (as a result of greater clinician awareness of the condition9s heterogeneic nature) do not fully explain the overall rise in incidence. <h3>Competing interests</h3> None declared.
Gene Transfer May Be Preventive But Not Curative for a Lysosomal Transport Disorder
Authors: Claire Hippert, Grégor Dubois, Carole Morin, Olivier Disson, Sandy Ibanes, Chantal Jacquet, Reto Schwendener, Corinne Antignac, Eric J Kremer, Vasiliki Kalatzis
Journal: Molecular Therapy (2008)

Cystinosis belongs to a growing class of lysosomal storage disorders (LSDs) caused by defective transmembrane proteins. The causative CTNS gene encodes the lysosomal cystine transporter, cystinosin. Currently the aminothiol cysteamine is the only drug available for reducing cystine storage but this treatment has non-negligible side effects and administration constraints. In this study, for the first time, we report viral vector-mediated CTNS gene transfer and evaluate the feasibility of this strategy as a complementary treatment. Initially, we transduced human CTNS(-/-) fibroblast cell lines and primary murine Ctns(-/-) hepatocyte cultures in vitro and demonstrated that gene transfer can reduce cystine storage. Because of age-related increase in cystine levels, we transduced hepatocytes from young (</=3 months of age) and older (>/=5 months of age) mice. Our in vitro data suggested that the efficiency of correction was age-dependent. We tested these observations in vivo: short-term (1 week) and long-term (4 weeks) CTNS-transduction significantly reduced hepatic cystine levels in young, but not older, Ctns(-/-) mice. Our data provide the proof-of-concept that gene transfer is feasible for correcting defective lysosomal transport, but suggest that, in the case of cystinosis, it could be preventive but not curative in some tissues.
Sleep and breathing in neuromuscular disease
Authors: S.C. Bourke, G.J. Gibson
Journal: European Respiratory Journal (2002)

Respiratory muscle weakness in neuromuscular disease causes significant morbidity and mortality. The published data on respiratory muscle activity and breathing during sleep in normal subjects, the impact of respiratory muscle weakness on sleep and breathing and the relations to daytime respiratory function in neuromuscular disease are reviewed here. In normal subjects during sleep upper airway resistance increases, chemosensitivity is reduced and the wakefulness drive to breathe is lost, resulting in a fall in ventilation. During rapid eye movement (REM) sleep, ribcage and accessory breathing muscles are suppressed, particularly during bursts of eye movements, and breathing is more irregular, rapid and shallow, with a further fall in ventilation. In subjects with respiratory muscle weakness sleep is fragmented, with shorter total sleep time, frequent arousals, an increase in stage 1 sleep and a reduction in, or complete suppression of, REM sleep. Sleep­disordered breathing and nocturnal desaturation are common and most severe during REM sleep. Correlations between daytime respiratory function and nocturnal desaturation are moderate or weak, but daytime respiratory function has greater prognostic value than nocturnal measurements. Noninvasive ventilation improves sleep quality and breathing in subjects with respiratory muscle weakness. However, the optimal criteria for initiation of ventilation and its role in rapidly progressive neuromuscular diseases are unclear.
The Ethics of Early Stopping Rules
Authors: Joseph Pater, Paul Goss, Jame Ingle, Wendy Shelley, Lois Shepherd
Journal: Journal of Clinical Oncology (2005)

As authors of the manuscript 2 and as chair of the Data Safety Monitoring Committee for one of the trials (the Intergroup MA17 trial of letrozole) he criticizes, we are concerned that this article has the potential to impair significantly the conduct of future trials in breast cancer adjuvant endocrine therapy and consequently be harmful to patients.Our major issues with the article are: (1) Dr Cannistra repeats some of the misunderstandings about MA17 that we have previously addressed. 3 Most important in this context is the implication that disease-free survival (DFS) was not the sole primary end point around which the study was designed and that the difference in DFS targeted was at a specific point in time, rather than, as was actually the case, a hazard ratio measured over time.(2) A one-size-fits-all approach to choosing end points in cancer clinical trials is wrong.The proper choice of end point is context (disease, stage, and therapy) -specific.DFS is an appropriate outcome in trials of endocrine therapy in early breast cancer.(3) The title and tone of the article implies that stopping MA17 "early" meant the goals of the trial had not been achieved because of the intervention of a Data Safety Monitoring Board (DSMB).On the contrary, the study question was answered sooner than we expected because the treatment effect was larger than anticipated.(4) The value of Dr Cannistra's comments and recommendations regarding DSMB's are undermined by an apparent lack of familiarity with how these bodies function under the auspices of a National Cancer Institute cooperative group program.Because of their importance, we will expand briefly on points 2 and 4 in the following paragraphs:2. Disease-free survival is commonly chosen as the end point of US Food and Drug Administration-and NCIapproved trials of adjuvant endocrine therapy in breast cancer.We feel strongly that this is appropriate, not only because the accumulated experience to date suggests that DFS is a surrogate for overall survival in this setting, 4 but also because preventing breast cancer recurrence has value in itself.Women who suffer an in-breast recurrence often require the mastectomy their initial management was intended to avoid; women who develop new breast cancer repeat the trauma of their initial diagnosis and treatment; and women with distant recurrence inevitably die of their disease.