tbuckley/cabot-search huggingface dataset:
Association of Serum Retinoic Acid With Risk of Mortality in Patients With Coronary Artery Disease
Authors: Yan Liu, Hongen Chen, Di Mu, Di Li, Yuan Zhong, Nan Jiang, Yuan Zhang, Min Xia
Journal: Circulation Research (2016)

Retinoic acid (RA) and its mediated nuclear receptor signaling have broad protective effects on vascular systems. Whether circulating levels of RA are associated with mortality in patients with coronary artery disease is still unknown.To evaluate the association of circulating RA with the risk of mortality.We measured serum RA concentrations in 1499 patients with angiographically confirmed coronary artery disease (mean age, 61 years; male, 67%) recruited from October 2008 and December 2011 in the Guangdong Coronary Artery Disease Cohort. During a median (interquartile range) period of 4.4 (3.6 to 6.1) years of follow-up, there were 295 all-cause mortality, among which 208 had cardiovascular mortality. Serum RA level was significantly lower in participants with mortality (median 21 [11-47] nmol/L) than in those without mortality (median 39 [19-86] nmol/L). In multivariate analyses, the hazard ratios for total mortality among those in the lowest (referent) to highest quartiles of serum RA measured at study entry were 1.0, 0.83, 0.74, and 0.56, respectively (P-trend<0.001). For cardiovascular mortality, the comparable hazard ratios were 1.0, 0.76, 0.69, and 0.60 (P-trend<0.001). Furthermore, high RA levels (defined as >median) were associated with lower risk of total mortality (adjusted hazard ratios, 0.68; 95% confidence interval, 0.50-0.85; P=0.001) and cardiovascular mortality (adjusted hazard ratios, 0.62; 95% confidence interval, 0.45-0.78; P<0.001) compared with low RA (defined as ≤median).Serum RA level was associated with lower risk of mortality in a population-based coronary artery disease cohort.
Mechanism of Experimental Tumorigenesis. II. Effect of Mole Ratio Distribution of Span 60 and Span 20 Derivatives on Hyperplasia in Mouse Epidermis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: K SETALA, L MERENMIES, L STJERNVALL, Y AHO
Journal: JNCI Journal of the National Cancer Institute (1959)
Next-generation sequencing diagnostics of bacteremia in septic patients
Authors: Silke Grumaz, Philip Stevens, Christian Grumaz, Sebastian O. Decker, Markus A. Weigand, Stefan Hofer, Thorsten Brenner, Arndt von Haeseler, Kai Sohn
Journal: Genome Medicine (2016)

Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria. Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing. We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram-negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible. The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections.
Increased epidermal thickness and abnormal epidermal differentiation in keloid scars
Authors: G.C. Limandjaja, L.J. Broek, T. Waaijman, H.A. Veen, V. Everts, S. Monstrey, R.J. Scheper, F.B. Niessen, S. Gibbs
Journal: British Journal of Dermatology (2016)

The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse‐transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring.
Association of Marijuana Use With Blunted Nucleus Accumbens Response to Reward Anticipation
Authors: Meghan E. Martz, Elisa M. Trucco, Lora M. Cope, Jillian E. Hardee, Jennifer M. Jester, Robert A. Zucker, Mary M. Heitzeg
Journal: JAMA Psychiatry (2016)

Marijuana use may alter ventral striatal response to reward, which might heighten susceptibility to substance use disorder. Longitudinal research is needed to determine the effects of marijuana use on neural function involved in reward response.To determine whether marijuana use among young adults prospectively affects nucleus accumbens (NAcc) activation during reward anticipation.One hundred eight young adults were recruited from the Michigan Longitudinal Study, an ongoing study of youth at high risk for substance use disorder and a contrast sample of control families. Participants underwent 3 consecutive functional magnetic resonance imaging scans at approximate ages of 20 (time 1), 22 (time 2), and 24 (time 3) years. Self-report data on marijuana and other drug use occasions were collected annually since age 11 years.Cross-lagged models were used to test the association of marijuana use with neural response in the NAcc to reward anticipation during a monetary incentive delay task controlling for sex, age, other substance use, and family history of substance use disorder.Of 108 participants, 39 (36.1%) were female and mean (SD) age at baseline was 20.1 (1.4) years. Greater marijuana use was associated with later blunted activation in the NAcc during reward anticipation (time 1 to time 2: β = -0.26, P = .04; time 2 to time 3: β = -0.25, P = .01). When the cross-lagged model was tested with the inclusion of previous and concurrent cigarette use, the effect of marijuana use from time 2 to time 3 remained significant (β = -0.29; P = .005) and the effect of cigarette use was nonsignificant.The findings of this study indicate that marijuana use is associated with decreased neural response in the NAcc during the anticipation of nondrug rewards. Over time, marijuana use may alter anticipatory reward processing in the NAcc, which may increase the risk for continued drug use and later addiction.
Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long-Lived Tumor-Specific Memory Mediated by CD8+ T Cells
Authors: Kanako Shimizu, Satoru Yamasaki, Jun Shinga, Yusuke Sato, Takashi Watanabe, Osamu Ohara, Kiyotaka Kuzushima, Hideo Yagita, Yoshiko Komuro, Miki Asakura, Shin-ichiro Fujii
Journal: Cancer Research (2016)

Abstract Strategies to reprogram the tumor microenvironment are being explored to improve cancer immunotherapy. In one approach, we have targeted dendritic cells (DC) to improve their function with adjuvant vector cells (aAVC) that are engineered from NKT ligand-loaded CD1d+ allogeneic cells transfected with tumor antigen mRNAs. Here, we report the finding that this approach also programs local immune responses by establishing tertiary lymphoid structures (TLS), which include expanded antigen-specific CD8+ T-cell clones, mobilized DCs, and normalized tumor vasculature. aAVC therapy also expanded specific Vβ-expressing antitumor T-cell clones, leading to the formation of long-term memory T cells. When combined with PD-1 blockade, aAVC infusion triggered regression of poorly immunogenic tumor cells that did not respond to PD-1 blockade alone, as well as expansion of antigen-specific CD8+ T-cell clones in the tumor. The findings of this study help to inform a next-generation platform for the generation of efficacious cancer vaccines. Cancer Res; 76(13); 3756–66. ©2016 AACR.
High burden of prevalent tuberculosis among previously treated people in Southern Africa suggests potential for targeted control interventions
Authors: Florian M. Marx, Sian Floyd, Helen Ayles, Peter Godfrey-Faussett, Nulda Beyers, Ted Cohen
Journal: European Respiratory Journal (2016)

Several studies from Southern Africa report a high risk of tuberculosis (TB) among individuals who have previously been treated for the disease compared to those never before treated [1–5]. In high-burden settings, recurrent TB may affect large numbers of individuals even after successful treatment, with exogenous reinfection as an important underlying mechanism [2–4]. For example, in Cape Town, South Africa, a city with a high incidence of TB, previously treated individuals constitute one-third of the burden of notified TB [6]. High TB prevalence in previously treated people suggests potential for targeted interventions in high-burden settings <http://ow.ly/ihG83015s4l> We would like to thank the ZAMSTAR study team, in particular, Ab Schaap (London School of Hygiene and Tropical Medicine, London, UK), Rory Dunbar (Stellenbosch University, Tygerberg, South Africa) and those involved in the prevalence surveys. We are grateful to those who agreed to participate in the surveys. We thank the City of Cape Town Health Dept, and the Provincial and National Tuberculosis Programs of South Africa and Zambia for their support.
Does all teaching rest on evolved traits?
Authors: Laura Chouinard-Thuly, Simon M. Reader
Journal: Behavioral and Brain Sciences (2015)

Abstract Classification schemes are useful when they elucidate common underlying mechanisms, bring together diverse examples, or illustrate gaps in knowledge for empirical investigation. Kline's scheme merges different approaches, but is orthogonal to existing schemes and overemphasizes evolved specializations, potentially at the detriment of clarifying teaching processes. Focus on underlying mechanisms, what is learned, and consequences for information transfer may provide additional utility.
Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments
Authors: Ji Yang, Wen-Rong Li, Feng-Hua Lv, San-Gang He, Shi-Lin Tian, Wei-Feng Peng, Ya-Wei Sun, Yong-Xin Zhao, Xiao-Long Tu, Min Zhang, Xing-Long Xie, Yu-Tao Wang, Jin-Quan Li, Yong-Gang Liu, Zhi-Qiang Shen, Feng Wang, Guang-Jian Liu, Hong-Feng Lu, Juha Kantanen, Jian-Lin Han, Meng-Hua Li, Ming-Jun Liu
Journal: Molecular Biology and Evolution (2016)

Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8–9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.
Investigation of a frequently mutated transcriptional repressor in prostate cancer, in particular its role in modulating androgen signaling and its effects on TMPRSS2-ERG dependent tumor maintenance.
Authors: Rohit Bose, Wassim Abida, Phillip Iaquinta, Wouter Karthaus, Joshua Armenia, John Wongvipat, Michael Doran, Haley Hieronymus, Watson Philip, Yupu Liang, Nikolaus Schultz, Charles L. Sawyers
Journal: Journal of Clinical Oncology (2016)

274 Background: Recent genomic profiling of primary and metastatic prostate cancers revealed up to 27% of tumors contain putative loss-of-function point mutations or copy number deletions within the gene ERF, an ETS transcriptional repressor with a remarkably similar DNA-binding domain to the TMPRSS2-ERG gene product. Methods: Bioinformatic analysis of 450 patient tumors was obtained from the TCGA and SU2C datasets. Transcriptomic and cistromic analysis was achieved by RNA-seq and ChIP-seq on VCaP cells, as well as patient-derived organoid cultures of both normal and neoplastic prostates. Gene expression was inhibited by CRISPR or shRNA technology. Results: ERF copy number deletions are associated with Gleason 8+ primary disease (p = 0.0369), and ERF mRNA level inversely correlates with androgen-driven transcription (p &lt; 0.0001) in the absence of androgen receptor amplification. Transient inhibition of ERG expression in TMPRSS2-ERG+ cancer models leads to a contraction of the androgen transcriptome. On the other hand, inhibition of ERF leads to an expansion of the androgen transcriptome, and moreover, supersedes the opposing effects of ERG. ERF and the TMPRSS2-ERG gene product have overlapping ETS cistromes that are associated with androgen-receptor binding sites; inhibition of one leads to occupancy at the vacated sites by the other. CRISPR-mediated inhibition of ERG in TMPRSS2-ERG+ models leads to a complete halt of growth, but concomitant loss of ERF partially restores cellular proliferation. Conclusions: ERF is a tumor suppressor with genomic loss-of-function mutations in up to 27% of prostate cancers, thereby expanding the concept of an ETS positive subtype. ERF occupies ETS sites of androgen-regulated genes and is an endogenous dampener of their transcription. Moreover, even in tumors lacking ERF mutations, upregulated ERG now occupies many of these same ETS sites, unmasking their transcriptional control by androgen. Thus, a key oncogenic activity of TMPRSS2-ERG is to antagonize endogenous ERF.
Effect of Pyridoxine Availability on the Activity of Serine Dehydratase of Normal Liver, Host Liver, and Three Morris Hepatomas 2
Authors: George P. Tryfiates
Journal: JNCI Journal of the National Cancer Institute (1975)

The effect(s) of dietary pyridoxine availability on serine dehydratase (SD) specific activity levels of normal liver. Morris hepatomas "5123A, 7316B, 7800, and of respective host livers was studied. Buffalo female weanling rats were fed ad libitum a pyridoxine-free diet or the same diet supplemented with the vitamin. They were inoculated intramuscularly in the hind leg muscles with hepatoma cells after 3 weeks on the respective diets, and those bearing hepatomas "5123A, 7316B, 7800 were killed at 28, 30, and 48 days, respectively, after inoculation. SD activity was highly affected by pyridoxine. Absence of the vitamin from the diet resulted in greatly reduced activity levels in normal liver and the three hepatomas. Tumors grown in animals fed the pyridoxine-supplemented diet had 39j ("5123A), 3.5 ("7316B), and 2.1 ("7800) times more SD specific activity tan respective tumors grown in animals fed the deficient diet. A 1.7-fold increase was observed in normal liver. In contrast to these findings, the specific activity of the enzyme was reduced by 6.3, 1.5, and 3.0 times, respectively, in the host livers of animals fed the vitamin-supplemented diet and bearing hepatomas "5123A, 7316B, and 7800. Serine dehydratase activity depends greatly on dietary vitamin B6 and hence I propose that activity levels in vivo are regulated by its presence or absence.
Brain Peptides
Authors: Dorothy T. Krieger, Joseph B. Martin
Journal: New England Journal of Medicine (1981)

Peptide Functions in the Central Nervous SystemBrain Peptides as Neuronal MarkersMost degenerative neurologic disorders are characterized by premature cell death in discrete neuronal populations. In some cases, the cellular components affected can be characterized partly by their functional roles in neuronal systems. Further delineation of the cellular basis of such neurologic disorders may contribute important new information about their pathogeneses. Immunocytochemical characterization of the cell types that are commonly affected in degenerative diseases, together with measurement of regional peptide concentrations, may provide clues to the neuronal specificity (or lack of it) involved in a given disorder. It is . . .
Development Of a 47 Gene Sequencing Panel For Common Mutations Present In Multiple Myeloma : Preliminary Results In 77 p53 Deleted Patients
Authors: Christian Langer, Esteban Braggio, Scott Van Wier, Jan Egan, Laura Bruins, Jessica Schmidt, Lars Bullinger, Miriam Kull, Stefan Knop, Hermann Einsele, A. Keith Stewart, Chb
Journal: Blood (2013)
Inverse relationship between CSF TRH concentrations and the TSH response to TRH in abstinent alcohol-dependent patients
Authors: B Adinoff, C B Nemeroff, G Bissette, P R Martin, M Linnoila
Journal: American Journal of Psychiatry (1991)

The authors performed the thyrotropin-releasing hormone (TRH) stimulation test and measured CSF concentrations of TRH in 13 abstinent alcohol-dependent subjects. They found an inverse correlation between the thyrotropin (TSH) response to TRH and endogenous CSF TRH concentrations. This finding supports the hypothesis that as the concentration of CSF TRH increases, anterior pituitary TRH receptor density decreases, resulting in a blunted TSH response to TRH stimulation.
Early thymectomy leads to premature immunologic ageing: An 18-year follow-up
Authors: Judith Gudmundsdottir, Sólveig Óskarsdóttir, Gabriel Skogberg, Susanne Lindgren, Vanja Lundberg, Martin Berglund, Anna-Carin Lundell, Håkan Berggren, Anders Fasth, Esbjörn Telemo, Olov Ekwall
Journal: Journal of Allergy and Clinical Immunology (2016)
Deciphering The Molecular Impact Of Myc Overexpression On B Cell Receptor Signaling and Its Implications For Burkitt Lymphoma Treatment
Authors: Thomas Oellerich, Jasmin Corso, Simone Lemeer, Ekkehard Schütz, Julia Beck, Stephan Lorenzen, Tim Beissbarth, Silvia Münch, Pascal Degenhardt, Michael Engelke, Christoph Lenz, Bernhard Küster, Henning Urlaub, Hubert Serve
Journal: Blood (2013)
Engraftment Of Human Polycythemia Vera CD34+ Cells In hSIRPα-Transgenic-Human-TPO-Expressing RAG2-/-, IL2Rγ-/- Immunodeficient Mice
Authors: Rouven Müller, Alexandre Theocharides, Renate Looser, Radek C. Skoda, Richard A. Flavell, Markus G. Manz
Journal: Blood (2013)
Matrix Glycoprotein Osteopontin Is a Stem Cell Niche Constituent That Constrains the Hematopoietic Stem Cell Pool Size.
Authors: Sebastian Stier, Yon Ko, Randolf Forkert, Christoph Lutz, Thomas Neuhaus, Elisabeth Gruenewald, David Dombkowski, Susan R. Rittling, David T. Scadden
Journal: Blood (2004)
Reply
Authors: Sasan Roayaie
Journal: Hepatology (2013)

I agree with Dr. Cho that radiofrequency ablation (RFA) and surgical resection each offer certain advantages and are also each associated with certain shortcomings. In fact, the main objective of our article was not to directly compare the outcomes of resection and RFA for patients with hepatocellular carcinoma (HCC) ≤2 cm.1 This is better done by large cohort studies such as the one recently published by Hasegawa et al.2 Rather, the main aim was to report the outcomes achieved with resection at two large-volume Western centers, thereby providing some context by which to judge the relative role of resection for treatment of very early HCC. A secondary objective was to demonstrate the heterogeneity that exists even among such early tumors and determine which characteristics were associated with survival and recurrence. The mean size of the tumors in the study by Livraghi et al. is never reported. While our study included patients with arterial enhancement >2 cm, none of the tumors were larger than 2 cm on pathological examination, which is the gold standard for assessing tumor size. Like the true size of the tumors treated, the incidence of vascular invasion in the Livraghi et al. study will also never be known due to lack of pathological data. We found that the incidence of vascular invasion was only marginally lower in patients with tumors ≤15 mm (22%) compared to those with tumors 16-20 mm (29%) (P = NS, unpublished data). Nevertheless, Dr. Cho may be correct in that the Livraghi et al. study treated significantly smaller tumors with a lower incidence of vascular invasion using RFA in order to achieve results similar to what we obtained by resecting larger tumors with a higher incidence of vascular invasion. Due to the lack of pathological data, we will never know. In conclusion, I agree with Dr. Cho that direct comparisons should not be made between our study and the study by Livraghi et al. These types of discussions highlight one of the fundamental advantages of resection over RFA, pathological data from the resected tumor and the surrounding liver, both of which have been shown to have a significant impact on prognosis. Because there is such a wide range of heterogeneity, even among such early tumors, clinicians cannot truly know what it is that they have treated without tissue. Sasan Roayaie, M.D. Department of Surgery, Mount Sinai Medical Center, New York, NY
Research in Smoking and Health at the National Cancer Institute&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Gio B. Gori
Journal: JNCI Journal of the National Cancer Institute (1972)

Research in Smoking and Health at the National Cancer Institute Get access Gio B. Gori Gio B. Gori National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 6, June 1972, Pages 1759–1762, https://doi.org/10.1093/jnci/48.6.1759 Published: 01 June 1972