tbuckley/cabot-search huggingface dataset:
The Undiagnosed Diseases Network of the National Institutes of Health
Authors: William A. Gahl, Anastasia L. Wise, Euan A. Ashley
Journal: JAMA (2015)

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Postoperative atrial fibrillation and mortality after coronary artery bypass surgery
Authors: Rollo P. Villareal, Ramesh Hariharan, Brant C. Liu, Biswajit Kar, Vei-Vei Lee, MacArthur Elayda, J.Alberto Lopez, Abdi Rasekh, James M. Wilson, Ali Massumi
Journal: Journal of the American College of Cardiology (2004)
Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts
Authors: N. Lazic, G. Roberts, A. Custovic, D. Belgrave, C. M. Bishop, J. Winn, J. A. Curtin, S. Hasan Arshad, A. Simpson
Journal: Allergy (2013)

Abstract Background Although atopic sensitization is one of the strongest risk factors for asthma, its relationship with asthma is poorly understood. We hypothesize that ‘atopy’ encompasses multiple sub‐phenotypes that relate to asthma in different ways. Methods In two population‐based birth cohorts (Manchester and Isle of Wight – IoW), we used a machine learning approach to independently cluster children into different classes of atopic sensitization in an unsupervised manner, based on skin prick and sIgE tests taken throughout childhood and adolescence. We examined the qualitative cluster properties and their relationship to asthma and lung function. Results A five‐class solution best described the data in both cohorts, with striking similarity between the classes across the two populations. Compared with nonsensitized class, children in the class with sensitivity to a wide variety of allergens (~1/3 of children atopic by conventional definition) were much more likely to have asthma ( aOR [95% CI0; 20.1 [10.9–40.2] in Manchester and 11.9 [7.3–19.4] in IoW). The relationship between asthma and conventional atopy was much weaker (5.5 [3.4–8.8] in Manchester and 5.8 [4.1–8.3] in IoW). In both cohorts, children in this class had significantly poorer lung function (FEV 1 /FVC lower by 4.4% in Manchester and 2.6% in IoW; P &lt; 0.001), most reactive airways, highest eNO and most hospital admissions for asthma ( P &lt; 0.001). Conclusions By adopting a machine learning approach to longitudinal data on allergic sensitization from two independent unselected birth cohorts, we identified latent classes with strikingly similar patterns of atopic response and association with clinical outcomes, suggesting the existence of multiple atopy phenotypes.
Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing
Authors: Qi Zhao, Ewen F Kirkness, Otavia L Caballero, Pedro A Galante, Raphael B Parmigiani, Lee Edsall, Samantha Kuan, Zhen Ye, Samuel Levy, Ana Tereza R Vasconcelos, Bing Ren, Sandro J de Souza, Anamaria A Camargo, Andrew JG Simpson, Robert L Strausberg
Journal: Genome biology (2010)

Abstract Background To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL. Results By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1 , MSH3 and SETX , which participate in DNA repair pathways. Conclusions Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities.
Impaired Renal Blood Flow Autoregulation in Two-Kidney, One-Clip Hypertensive Rats Is Caused by Enhanced Activity of Nitric Oxide
Authors: ERIKA TURKSTRA, BRANKO BRAAM, HEIN A. KOOMANS
Journal: Journal of the American Society of Nephrology (2000)

Increases in renal perfusion pressure will induce shear stress-mediated nitric oxide (NO) release, which could oppose autoregulation of renal blood flow (RBF). Although cardiac, cerebral, and mesenteric autoregulation is enhanced during nitric oxide (NO) synthesis inhibition, this has not been reported for renal autoregulation of blood flow. In the present study, the lower limit and efficiency of RBF autoregulation (as assessed by the degree of compensation) were studied before and during NO inhibition in normotensive Sprague Dawley rats (control; n = 9) and in the non-clipped kidney of two-kidney, one-clip Goldblatt hypertensive animals (2K1C; n = 9; 3 wk; 0.25-mm silver clip). In both groups, renal autoregulation curves were obtained before and during infusion of N(G) -nitro-L-arginine (L-NNA) (bolus 1.5 mg/kg intravenously, infusion 10 microg/kg per min intravenously), using a transit-time flow probe around the left renal artery. In control rats, mean arterial pressure (MAP) increased, RBF decreased, and renal vascular resistance (RVR) increased in response to L-NNA infusion. The lower limit of autoregulation in control animals did not significantly change during L-NNA infusion (78 +/- 3 to 70 +/- 2 mmHg). The degree of compensation in these rats slightly increased during L-NNA infusion, however, this was only significant below 90 mmHg. The 2K1C rats had elevated MAP under baseline conditions. L-NNA infusion resulted in a decrease in RBF and an increase in MAP and RVR. During L-NNA infusion, RVR in 2K1C rats greatly exceeded RVR in control rats. A significant decrease was observed in the lower limit of autoregulation from 85 +/- 3 to 72 +/- 5 mmHg (P < 0.05). In the contralateral kidney of 2K1C rats, the degree of compensation was lower than in control rats under baseline conditions. L-NNA infusion resulted in significantly higher degrees of compensation compared to baseline. In conclusion, the contralateral kidney displayed a high NO dependency, as RBF greatly decreased and RVR dramatically increased in response to L-NNA infusion. The contralateral kidney of 2K1C rats exhibited impaired RBF autoregulation, which was improved by NO inhibition, as judged from a decrease in the lower limit of autoregulation and an increase in the degree of compensation. This study indicates that perfusion pressure-dependent NO release can oppose autoregulation in the kidney. However, the enhanced influence of NO on pressure-dependent RBF may facilitate the preservation of renal function in the nonclipped kidney of 2K1C rats.
Abstract 2411: Hurp deficiency causes mitotic infidelity and impairs liver regeneration in mice
Authors: Ting-Fen Tsai, Chiao-Ming Huang, Chao-Chin Li, Cheng-Heng Kao
Journal: Cancer Research (2011)

Abstract Aberrant expression of hepatoma up-regulated protein, HURP, was found in hepatocellular carcinoma (HCC). Recent studies revealed that HURP is an essential factor during mitosis. However, the function of HURP in an in vivo context has not been well studied. In this study, we have concentrated our efforts on the pathological effects of Hurp deficiency during liver regeneration. We generated Hurp knockout (KO) mice to investigate the function of Hurp involved in hepatocyte cell cycle progression; we used the in vivo model of two-third partial-hepatectomy (PH) to induce synchronous cell cycle entry in liver. Our results revealed striking phenotypes of mitotic errors and chromosome instability in the Hurp KO livers. These phenotypes include impaired cell cycle progression as revealed by delayed entry of S-phase and M-phase of hepatocytes post-PH; mitotic infidelity as revealed by lagging chromosomes, multi-polar segregation and unequal segregation; aberrant nuclei of micro-nucleus, multi-nucleus and atypical nuclear morphology were frequently observed in the Hurp KO livers. Mechanistically, these abnormalities caused by Hurp deficiency did not turn on the spindle checkpoint machinery, such as BubR1 and Mad2, but up-regulated p21 expression to delay the cell cycle progression in liver. As an evidence of chronic liver damage, we observed continuously elevated serum ALT levels in Hurp KO mice post-PH. Together, these phenotypes in liver indicated that Hurp deficiency interferes spindle checkpoint (directly or indirectly), leading to mitotic infidelities, and possibly causes DNA breakage during chromatin segregation; this DNA breakage can further induce p21 to delay cell cycle during liver regeneration which is accompanying by chronic liver damages. All of these abnormalities may further lead to enhanced carcinogenesis in liver, which is currently under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2411. doi:10.1158/1538-7445.AM2011-2411
Antitumor Activity with CYP17 Blockade Indicates That Castration-Resistant Prostate Cancer Frequently Remains Hormone Driven
Authors: Gerhardt Attard, Alison H.M. Reid, David Olmos, Johann S. de Bono
Journal: Cancer Research (2009)

Abiraterone acetate is a potent, selective, and orally bioavailable small molecule inhibitor of CYP17, an enzyme that catalyzes two key serial reactions (17 alpha hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis. Clinical trials have confirmed that specific inhibition of CYP17 is safe and results in clinically important antitumor activity in up to 70% of castrate patients with advanced prostate cancer resistant to currently available endocrine therapies. These clinical data indicate that castration-resistant prostate cancer frequently remains hormone dependent and has confirmed that this disease should no longer be described as "hormone resistant or refractory". Biomarker studies, including the analysis of ETS gene fusion status, on patients treated with abiraterone acetate may allow enrichment of patients with a sensitive phenotype in future studies of therapeutics targeting CYP17.
DAR, a New RhD Variant Involving Exons 4, 5, and 7, Often in Linkage With ceAR, a New Rhce Variant Frequently Found in African Blacks
Authors: M.B. Hemker, P.C. Ligthart, L. Berger, D.J. van Rhenen, C.E. van der Schoot, P.A. Maaskant-van Wijk
Journal: Blood (1999)
Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements
Authors: Tsuyoshi Inoue, Takahide Kohro, Toshiya Tanaka, Yasuharu Kanki, Guoliang Li, Huay-Mei Poh, Imari Mimura, Mika Kobayashi, Akashi Taguchi, Takashi Maejima, Jun-ichi Suehiro, Akira Sugiyama, Kiyomi Kaneki, Hirofumi Aruga, Shoulian Dong, Junko F Stevens, Shogo Yamamoto, Shuichi Tsutsumi, Toshiro Fujita, Xiaoan Ruan, Hiroyuki Aburatani, Masaomi Nangaku, Yijun Ruan, Tatsuhiko Kodama, Youichiro Wada
Journal: Genome biology (2014)

Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated.We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPARβ/δ agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements.To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes.
Performance of two ELISAs for antifilaggrin autoantibodies, using either affinity purified or deiminated recombinant human filaggrin, in the diagnosis of rheumatoid arthritis
Authors: L Nogueira, M Sebbag, C Vincent, M Arnaud, B Fournié, A Cantagrel, M Jolivet, G Serre
Journal: Annals of the Rheumatic Diseases (2001)

To develop a standardisable enzyme linked immunosorbent assay (ELISA), using human filaggrin, for detection of antifilaggrin autoantibodies in rheumatoid arthritis (RA). To compare the diagnostic performance of the ELISA with those of reference tests: "antikeratin antibodies" ("AKA"), and antibodies to human epidermis filaggrin detected by immunoblotting (AhFA-IB).Two ELISAs were developed using either affinity purified neutral-acidic human epidermis filaggrin (AhFA-ELISA-pur) or a recombinant human filaggrin deiminated in vitro (AhFA-ELISA-rec) as immunosorbent. Antifilaggrin autoantibodies were assayed in 714 serum samples from patients with well characterised rheumatic diseases, including 241 RA and 473 other rheumatic diseases, using the two ELISAs. "AKA" and AhFA-IB tests were carried out in the same series of patients. The diagnostic performance of the four tests was compared and their relationships analysed.The titres of "AKA", AhFA-IB, and the AhFA-ELISAs correlated strongly with each other. The diagnostic sensitivity of the AhFA-ELISA-rec, which was better than that of AhFA-ELISA-pur, was 0.52 for a specificity of 0.95. This performance was similar to those of "AKA" or AhFA-IB. However, combining AhFA-ELISA-rec with AhFA-IB led to a diagnostic sensitivity of 0.55 for a specificity of 0.99.A simple and easily standardisable ELISA for detection of antifilaggrin autoantibodies was developed and validated on a large series of patients using a citrullinated recombinant human filaggrin. The diagnostic performance of the test was similar to that of the "AKA" and AhFA-IB. Nevertheless, combining the AhFA-ELISA-rec with one of the other tests clearly enhanced the performance.
Understanding Bayesian procedures
Authors: Robert A. M. Gregson
Journal: Behavioral and Brain Sciences (1998)

Chow's account of Bayesian inference logic and procedures is replete with fundamental misconceptions, derived from secondary sources and not adequately informed by modern work. The status of subjective probabilities in Bayesian analyses is misrepresented and the cogent reasons for the rejection by many statisticians of the curious inferential hybrid used in psychological research are not presented.
Developmental Characteristics of Apnea in Infants Who Succumb to Sudden Infant Death Syndrome
Authors: INEKO KATO, JOSE GROSWASSER, PATRICIA FRANCO, SONIA SCAILLET, IGOR KELMANSON, HAJIME TOGARI, ANDRE KAHN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.
Prevalence Estimates of Problem and Pathological Gambling in Hong Kong
Authors: Irene L.K. Wong, Ernest M.T. So
Journal: American Journal of Psychiatry (2003)

This government-commissioned survey gauged the prevalence of problem and pathological gambling in the general population of Hong Kong and advised the government on preventative and treatment services.A modified Chinese version of the DSM-IV Gambling-Behavior Index was administered to 2,004 Hong Kong residents by means of telephone interviews. The respondents were recruited through random sampling.Results showed that 4.0% and 1.8% of the respondents could be classified as problem and pathological gamblers, respectively. Significant differences between the survey sample and the respondents classified as problem and pathological gamblers were found in sex and education. The predictors of problem and pathological gambling were sex, education level, family income, and three specific forms of gambling: betting on horse racing, soccer games, and casino games.Survey results promoted preventative and treatment services.
Evolution of allostery in the cyclic nucleotide binding module
Authors: Natarajan Kannan, Jian Wu, Ganesh S Anand, Shibu Yooseph, Andrew F Neuwald, J Craig Venter, Susan S Taylor
Journal: Genome biology (2007)

Abstract Background The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we analyze the evolutionary information embedded in genomic sequences to explore the diversity of signaling through the CNB domain and also how the CNB domain elicits a cellular response upon binding to cAMP. Results Identification and classification of CNB domains in Global Ocean Sampling and other protein sequences reveals that they typically are fused to a wide variety of functional domains. CNB domains have undergone major sequence variation during evolution. In particular, the sequence motif that anchors the cAMP phosphate (termed the PBC motif) is strikingly different in some families. This variation may contribute to ligand specificity inasmuch as members of the prokaryotic cooA family, for example, harbor a CNB domain that contains a non-canonical PBC motif and that binds a heme ligand in the cAMP binding pocket. Statistical comparison of the functional constraints imposed on the canonical and non-canonical PBC containing sequences reveals that a key arginine, which coordinates with the cAMP phosphate, has co-evolved with a glycine in a distal β2-β3 loop that allosterically couples cAMP binding to distal regulatory sites. Conclusion Our analysis suggests that CNB domains have evolved as a scaffold to sense a wide variety of second messenger signals. Based on sequence, structural and biochemical data, we propose a mechanism for allosteric regulation by CNB domains.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients With Heart Failure and Chronic Atrial Fibrillation
Authors: Michele Brignole, Carlo Menozzi, Lorella Gianfranchi, Giacomo Musso, Roberto Mureddu, Nicola Bottoni, Gino Lolli
Journal: Circulation (1998)

Background —Uncontrolled studies have suggested that atrioventricular junction ablation and pacemaker implantation have beneficial effects on quality of life in patients with chronic atrial fibrillation (AF). Methods and Results —We performed a multicenter, controlled, randomized, 12-month evaluation of the clinical effects of atrioventricular junction ablation and VVIR pacemaker (Abl+Pm) versus pharmacological (drug) treatment in 66 patients with chronic (lasting &gt;6 months) AF who had clinically manifest heart failure and heart rate &gt;90 bpm on 3 standard ECGs recorded at rest during stable clinical conditions on different days. Before completion of the study, withdrawals occurred in 8 patients of the drug group and in 4 patients of the Abl+Pm group. At the end of the 12 months, the 28 Abl+Pm patients who completed the study showed lower scores in palpitations (−78%; P =0.000) and effort dyspnea (−22%; P =0.05) than the 26 of the drug group. Lower scores, although not significant, were also observed for exercise intolerance (−20%), easy fatigue (−17%), chest discomfort (−50%), Living with Heart Failure Questionnaire (−14%), New York Heart Association functional classification (−4%), and Activity scale (−12%). The intrapatient comparison between enrollment and month 12 showed that in the Abl+Pm group, all variables except easy fatigue improved significantly from 14% to 82%. However, because an improvement was also observed in the drug group, the difference between the 2 groups was significant only for palpitations ( P =0.000), effort dyspnea ( P =0.01), exercise intolerance ( P =0.005), easy fatigue ( P =0.02), and chest discomfort ( P =0.02). Cardiac performance, evaluated by means of standard echocardiogram and exercise test, did not differ significantly between the 2 groups and remained stable over time. Conclusions —In patients with heart failure and chronic AF, Abl+Pm treatment is effective and superior to drug therapy in controlling symptoms, although its efficacy appears to be less than that observed in uncontrolled studies because some improvement can also be expected in medically treated patients. Cardiac performance is not modified by the treatment.