tbuckley/cabot-search huggingface dataset:
Effective untestability and bounded rationality help in seeing religion as adaptive misbelief
Authors: Konrad Talmont-Kaminski
Journal: Behavioral and Brain Sciences (2009)

Abstract McKay &amp; Dennett (M&amp;D) look for adaptive misbeliefs that result from the normal, though fallible, functioning of human cognition. Their account can be substantially improved by the addition of two elements: (1) significance of a belief's testability for its functionality, and (2) an account of reason appropriate to understanding systemic misbelief. Together, these points show why religion probably is an adaptive misbelief.
Comparison of Psychiatric Symptoms in Carcinoma of the Pancreas with Those in Some Other Intra-abdominal Neoplasms
Authors: IVAN FRAS, EDWARD M. LITIN, JOHN S. PEARSON
Journal: American Journal of Psychiatry (1967)

Study of 46 consecutive patients who had carcinoma of the pancreas revealed that 76 percent had psychiatric symptoms which appeared to be closely related to the presence of the neoplasm. Symptoms of depression, anxiety, and premonition of serious illness were characteristic. Since the psychiatric symptoms appeared before any other symptoms in nearly half of the patients, these symptoms should be regarded as an aid in the diagnosis of carcinoma of the pancreas.
Radiation therapy for the management of patients with HTLV-1–associated adult T-cell leukemia/lymphoma
Authors: Charles B. Simone, John C. Morris, Donn M. Stewart, Nicole E. Urquhart, John E. Janik, Robert J. Kreitman, Elena Lita, Kevin Conlon, Gilian Wharfe, Thomas A. Waldmann, Aradhana Kaushal
Journal: Blood (2012)
Small variable segments constitute a major type of diversity of bacterial genomes at the species level
Authors: Fabrice Touzain, Erick Denamur, Claudine Médigue, Valérie Barbe, Meriem El Karoui, Marie-Agnès Petit
Journal: Genome biology (2010)

Abstract Background Analysis of large scale diversity in bacterial genomes has mainly focused on elements such as pathogenicity islands, or more generally, genomic islands. These comprise numerous genes and confer important phenotypes, which are present or absent depending on strains. We report that despite this widely accepted notion, most diversity at the species level is composed of much smaller DNA segments, 20 to 500 bp in size, which we call microdiversity. Results We performed a systematic analysis of the variable segments detected by multiple whole genome alignments at the DNA level on three species for which the greatest number of genomes have been sequenced: Escherichia coli , Staphylococcus aureus , and Streptococcus pyogenes . Among the numerous sites of variability, 62 to 73% were loci of microdiversity, many of which were located within genes. They contribute to phenotypic variations, as 3 to 6% of all genes harbor microdiversity, and 1 to 9% of total genes are located downstream from a microdiversity locus. Microdiversity loci are particularly abundant in genes encoding membrane proteins. In-depth analysis of the E. coli alignments shows that most of the diversity does not correspond to known mobile or repeated elements, and it is likely that they were generated by illegitimate recombination. An intriguing class of microdiversity includes small blocks of highly diverged sequences, whose origin is discussed. Conclusions This analysis uncovers the importance of this small-sized genome diversity, which we expect to be present in a wide range of bacteria, and possibly also in many eukaryotic genomes.
Egr-1 Mediates Hypoxia-Inducible Transcription of the <i>NDRG1</i> Gene through an Overlapping Egr-1/Sp1 Binding Site in the Promoter
Authors: Ping Zhang, Kam-Meng Tchou-Wong, Max Costa
Journal: Cancer Research (2007)

N-myc down-regulated gene 1 (NDRG1/Cap43) is inducible by a variety of environmental stressors, including hypoxia. The present study identified a cis-acting element mediating the transactivation of the NDRG1 gene in murine RAW264.7 macrophage cells treated with hypoxia or deferoxamine, an iron chelator mimicking hypoxia. Through a series of deletions of the promoter of NDRG1 luciferase constructs, a minimal cis-acting element conferring inducibility by hypoxia and deferoxamine was localized to an early growth response 1 (Egr-1) and Sp1 overlapping binding site. Electrophoretic mobility shift assay, antibody supershift assay, and mutations of the Egr-1 binding site confirmed the specific binding of Egr-1 protein to this Egr-1/Sp1 motif. In addition, hypoxia increased the level of Egr-1 protein that correlated with induction of NDRG1 expression at both RNA and protein levels. Transient transfection of the Egr-1 gene into HeLa cells also resulted in up-regulation of the NDRG1 mRNA. The role of Egr-1 was further verified by mutations in the Egr-1 binding site, which reduced promoter inducibility by hypoxia and deferoxamine. Furthermore, the induction of NDRG1 expression by hypoxia and deferoxamine was diminished by RNA interference knockdown of Egr-1 gene expression and in Egr-1-/- mouse embryonic fibroblasts (MEF) compared with Egr-1+/- MEFs. These results showed for the first time that Egr-1 regulates NDRG1 transcription through an overlapping Egr-1/Sp1 binding site that acts as a major site of positive regulation of the NDRG1 promoter by hypoxia signaling.
Pcif1 modulates Pdx1 protein stability and pancreatic β cell function and survival in mice
Authors: Kathryn C. Claiborn, Mira M. Sachdeva, Corey E. Cannon, David N. Groff, Jeffrey D. Singer, Doris A. Stoffers
Journal: Journal of Clinical Investigation (2010)

The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. Heterozygous mutations in PDX1 are associated with the development of diabetes in humans. Understanding how Pdx1 expression levels are controlled is therefore of intense interest in the study and treatment of diabetes. Pdx1 C terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 heterozygosity normalized Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of key Pdx1 transcriptional targets. Remarkably, Pcif1 heterozygosity improved glucose homeostasis and β cell function and normalized β cell mass in Pdx1(+/-) mice by modulating β cell survival. These findings indicate that in adult mouse β cells, Pcif1 limits Pdx1 protein accumulation and thus the expression of insulin and other gene targets important in the maintenance of β cell mass and function. They also provide evidence that targeting the turnover of a pancreatic transcription factor in vivo can improve glucose homeostasis.
Potential Strategies to Prevent Ventilator-associated Events
Authors: Michael Klompas
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The Centers for Disease Control and Prevention (CDC) released ventilator-associated event (VAE) definitions in 2013. The new definitions were designed to track episodes of sustained respiratory deterioration in mechanically ventilated patients after a period of stability or improvement. More than 2,000 U.S. hospitals have reported their VAE rates to the CDC, but there has been little guidance to date on how to prevent VAEs. Existing ventilator-associated pneumonia prevention bundles are unlikely to be optimal insofar as pneumonia accounts for only a minority of VAEs. This review proposes a framework and potential intervention set to prevent VAEs on the basis of studies of VAE epidemiology, risk factors, and prevention. Work to date suggests that the majority of VAEs are caused by four conditions: pneumonia, fluid overload, atelectasis, and acute respiratory distress syndrome. Interventions that minimize ventilator exposure and target one or more of these conditions may therefore prevent VAEs. Potential strategies include avoiding intubation, minimizing sedation, paired daily spontaneous awakening and breathing trials, early exercise and mobility, low tidal volume ventilation, conservative fluid management, and conservative blood transfusion thresholds. Interventional studies have thus far affirmed that minimized sedation, paired daily spontaneous awakening and breathing trials, and conservative fluid management can reduce VAE rates and improve patient-centered outcomes. Further studies are needed to evaluate the impact of the other proposed interventions, to identify additional modifiable risk factors for VAEs, and to measure whether combining strategies into VAE prevention bundles confers additional benefits over implementing one or more of these interventions in isolation.
Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults
Authors: Eugenia E. Calle, Carmen Rodriguez, Kimberly Walker-Thurmond, Michael J. Thun
Journal: New England Journal of Medicine (2003)

The influence of excess body weight on the risk of death from cancer has not been fully characterized.In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population.The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women.Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4
Authors: Liang Li, Jing Tang, Baohua Zhang, Wen Yang, Miyang LiuGao, Ruoyu Wang, Yexiong Tan, Jianling Fan, Yanxin Chang, Jing Fu, Feng Jiang, Caiyang Chen, Yingcheng Yang, Jin Gu, Dingming Wu, Linna Guo, Dan Cao, Hengyu Li, Guangwen Cao, Mengchao Wu, Michael Q Zhang, Lei Chen, Hongyang Wang
Journal: Gut (2014)

<h3>Objective</h3> Liver tumour-initiating cells (T-ICs) are critical for hepatocarcinogenesis. However, the underlying mechanism regulating the function of liver T-ICs remains unclear. <h3>Methods</h3> Tissue microarrays containing 242 hepatocellular carcinoma (HCC) samples were used for prognostic analysis. Magnetically activated cell sorting was used to isolate epithelial cell adhesion molecule (EPCAM)-positive cells. The gene expressions affected by miR-429 were determined by arrays. Co-immunoprecipitation was used to study interactions among retinoblastoma protein (RB1), Rb binding protein 4 (RBBP4) and E2F transcription factor 1 (E2F1). The DNA methylation status in CpG islands was detected by quantitative methylation analysis. miRNAs in microvesicles were isolated by a syringe filter system. <h3>Results</h3> The significant prognosis factor miR-429 was upregulated in HCC tissues and also in primary liver T-ICs isolated from clinical samples. The enrichment of miR-429 in EPCAM<sup>+</sup> T-ICs contributed to hepatocyte self-renewal, malignant proliferation, chemoresistance and tumorigenicity<i>.</i> A novel functional axis involving miR-429, RBBP4, E2F1 and POU class 5 homeobox 1 (POU5F1 or OCT4) governing the regulation of liver EPCAM<sup>+</sup> T-ICs was established in vitro and in vivo. The molecular mechanism regulating miR-429 expression, involving four abnormal hypomethylated sites upstream of the miR-200b/miR-200a/miR-429 cluster, was first defined in both EPCAM<sup>+</sup> liver T-ICs and very early-stage HCC tissues. miR-429 secreted by high-expressing cells has the potential to become a proactive signalling molecule to mediate intercellular communication. <h3>Conclusions</h3> Epigenetic modification of miR-429 can manipulate liver T-ICs by targeting the RBBP4/E2F1/OCT4 axis. This miRNA might be targeted to inactivate T-ICs, thus providing a novel strategy for HCC prevention and treatment.
Notification of tuberculosis: can the pathologist help?
Authors: B. L. Bradley, K. M. Kerr, A. G. Leitch, D. Lamb
Journal: BMJ (1988)

thyrotoxicosis, two thirds of the affected sibling pairs shared both parental haplotypes.It was postulated that both parental haplotypes were important for the development of thyrotoxicosis.In other words the human leucocyte antigen gene contributing to the development of thyrotoxicosis may be inherited in a recessive fashion.'Separate alleles (Bw22 and B 17) have been suggested as markers for thyrotoxic periodic paralysis.It remains unclear whether the mode of inheritance of thyrotoxic periodic paralysis is similar to that of thyrotoxicosis per se.This family provided us with a unique opportunity to glimpse the genetic mechanisms occurring in thyrotoxic periodic paralysis.The occurrence of identical haplotypes in the sibling pair who had thyrotoxic periodic paralysis suggests that the mode of inheritance of thyrotoxic periodic paralysis and thyrotoxicosis may indeed be similar.I Mittal KK, Mickey MR, Singal DP, Terasaki PI.Serotyping for homotrans- plantation 18: refinement of microdroplet lymphocyte cytotoxicity test.
Utilization of Multiple CD4+ T Regulatory Cell Markers Reveals Heterogeneity in a Pediatric Population at Risk for Development of Atopic Disease
Authors: A SINGH, K BURMEISTER, M EVANS, R GANGNON, C TISLER, L SALAZAR, R LEMANSKEJR, J GERN, C SEROOGY
Journal: Journal of Allergy and Clinical Immunology (2008)
Personalized genomic analyses for cancer mutation discovery and interpretation
Authors: Siân Jones, Valsamo Anagnostou, Karli Lytle, Sonya Parpart-Li, Monica Nesselbush, David R. Riley, Manish Shukla, Bryan Chesnick, Maura Kadan, Eniko Papp, Kevin G. Galens, Derek Murphy, Theresa Zhang, Lisa Kann, Mark Sausen, Samuel V. Angiuoli, Luis A. Diaz, Victor E. Velculescu
Journal: Science Translational Medicine (2015)

Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients.
SYNTHESIS OF INOSITOL IN MICE
Authors: D. W. Woolley
Journal: The Journal of Experimental Medicine (1942)

It has been shown that mice are able to synthesize inositol. This synthesis was not observed when pantothenic acid was absent from the diet. Cultures from the intestinal tract of animals which exhibited spontaneous cure of alopecia yielded microorganisms which synthesized much more inositol than did organisms isolated in the same fashion from the tracts of mice that had become hairless. Some observations on the distribution of free and combined inositol have been made and it has been shown that several biological materials contain combined inositol. It has been found that deficiency of inositol can develop even when inositol is present in the diet if pantothenic acid is omitted.
Mitochondrial Electron Transport Complex I Is a Potential Source of Oxygen Free Radicals in the Failing Myocardium
Authors: Tomomi Ide, Hiroyuki Tsutsui, Shintaro Kinugawa, Hideo Utsumi, Dongchon Kang, Nobutaka Hattori, Koji Uchida, Ken-ichi Arimura, Kensuke Egashira, Akira Takeshita
Journal: Circulation Research (1999)

Abstract —Oxidative stress in the myocardium may play an important role in the pathogenesis of congestive heart failure (HF). However, the cellular sources and mechanisms for the enhanced generation of reactive oxygen species (ROS) in the failing myocardium remain unknown. The amount of thiobarbituric acid reactive substances increased in the canine HF hearts subjected to rapid ventricular pacing for 4 weeks, and immunohistochemical staining of 4-hydroxy-2-nonenal ROS-induced lipid peroxides was detected in cardiac myocytes but not in interstitial cells of HF animals. The generation of superoxide anion was directly assessed in the submitochondrial fractions by use of electron spin resonance spectroscopy with spin trapping agent, 5,5′-dimethyl-1-pyrroline- N -oxide, in the presence of NADH and succinate as a substrate for NADH–ubiquinone oxidoreductase (complex I) and succinate–ubiquinone oxidoreductase (complex II), respectively. Superoxide production was increased 2.8-fold ( P &lt;0.01) in HF, which was due to the functional block of electron transport at complex I. The enzymatic activity of complex I decreased in HF (274±13 versus 136±9 nmol · min −1 · mg −1 protein, P &lt;0.01), which may thus have caused the functional uncoupling of the respiratory chain and the deleterious ROS production in HF mitochondria. The present study provided direct evidence for the involvement of ROS in the mitochondrial origin of HF myocytes, which might be responsible for both contractile dysfunction and structural damage to the myocardium.
Immunoprevention of Basal Cell Carcinomas with Recombinant Hedgehog-interacting Protein
Authors: Annika Vogt, Pao-Tien Chuang, Jennifer Hebert, Jimmy Hwang, Ying Lu, Levy Kopelovich, Mohammad Athar, David R. Bickers, Ervin H. Epstein
Journal: The Journal of Experimental Medicine (2004)

Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptch1+/− mice treated with ionizing radiation. Hip1 mRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/− mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P &amp;lt; 0.001) and 32% (P &amp;lt; 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs.
Incremental value of parametric quantitative assessment of myocardial perfusion by triggered Low-Power myocardial contrast echocardiography
Authors: Eric H.C Yu, Danny M Skyba, Howard Leong-Poi, Cairrine Sloggett, Michal Jamorski, Rohit Garg, R.Mark Iwanochko, Samuel C Siu
Journal: Journal of the American College of Cardiology (2004)
Simultaneous increase of Cryptosporidium infections in the Netherlands, the United Kingdom and Germany in late summer season, 2012
Authors: N Fournet, M P Deege, A T Urbanus, G Nichols, B M Rosner, R M Chalmers, R Gorton, K G Pollock, J  W van der Giessen, P C Wever, J  W Dorigo-Zetsma, B Mulder, T G Mank, I Overdevest, J G Kusters, W van Pelt, L M Kortbeek
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
Role of Magnesium Ion in the Initiation of Ventricular Fibrillation Produced by Acute Coronary Occlusion
Authors: NORMAN L. GARDEN, JOHN E. STEINHAUS
Journal: Circulation Research (1957)

The incidence of ventricular fibrillation following acute coronary occlusion in dogs was reduced by perfusing the ischemic area of the myocardium with Locke-Ringer's solution and solutions of magnesium ion in physiological saline. In contrast, normal serum concentrations of magnesium in 5 per cent dextrose appeared to induce ventricular fibrillation in these circumstances. The results suggest that changes in the concentration of magnesium and sodium ion in extracellular fluid may initiate ventricular fibrillation in the ischemic heart.
Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial
Authors: Julien Taieb, Josep Tabernero, Enrico Mini, Fabien Subtil, Gunnar Folprecht, Jean-Luc Van Laethem, Josef Thaler, John Bridgewater, Lone Nørgård Petersen, Hélène Blons, Laurence Collette, Eric Van Cutsem, Philippe Rougier, Ramon Salazar, Laurent Bedenne, Jean-François Emile, Pierre Laurent-Puig, Come Lepage
Journal: The Lancet Oncology (2014)
Variant of<i>TYR</i>and Autoimmunity Susceptibility Loci in Generalized Vitiligo
Authors: Ying Jin, Stanca A. Birlea, Pamela R. Fain, Katherine Gowan, Sheri L. Riccardi, Paulene J. Holland, Christina M. Mailloux, Alexandra J.D. Sufit, Saunie M. Hutton, Anita Amadi-Myers, Dorothy C. Bennett, Margaret R. Wallace, Wayne T. McCormack, E. Helen Kemp, David J. Gawkrodger, Anthony P. Weetman, Mauro Picardo, Giovanni Leone, Alain Taïeb, Thomas Jouary, Khaled Ezzedine, Nanny van Geel, Jo Lambert, Andreas Overbeck, Richard A. Spritz
Journal: New England Journal of Medicine (2010)

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases.