tbuckley/cabot-search huggingface dataset:
Systematic identification of regulatory variants associated with cancer risk
Authors: Song Liu, Yuwen Liu, Qin Zhang, Jiayu Wu, Junbo Liang, Shan Yu, Gong-Hong Wei, Kevin P. White, Xiaoyue Wang
Journal: Genome biology (2017)

Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities.From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach.By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.
Evaluación epidemiológica y virológica de la actividad gripal en Europa durante el invierno de 2004-2005
Authors: A Meijer, W J Paget, T J Meerhoff, C S Brown, L. E. Meuwissen, J Van Der Velden
Journal: Eurosurveillance (2006)

La temporada gripal 2004-2005 comenzo a finales de diciembre de 2004, manifestandose primero en el sur y oeste de Europa (Espana, Reino-Unido e Irlanda). La actividad gripal se desplazo despues poco a poco hacia el este atravesando Europa en enero y comienzo de Febrero de 2005, y al final principalmente de sur al norte entre finales de febrero y finales de marzo. En diez paises de 23, la actividad gripal fue mas intensa que en la temporada 2003-2004, y presento una intensidad igual o inferior en los otros 13. Las tasas mas altas de consultas se observaron generalmente en ninos de 0 a 14 anos. No hubo aumentos notables en los picos de consultas para sindromes gripales o infecciones respiratorias agudas, comparados con datos historicos. Fue predominante la cepa viral A (83% de las detecciones totales), con un sub-tipo H3 (85% de los virus A sub-tipos H), seguida por la cepa B (17% de las detecciones) o A(H1) (15% de los virus A sub-tipos H). La mayor parte de los virus A(H3) eran similares a las cepas de referencia A/Wellington/1/2004 (H3N2) y en consecuencia a las cepas A/California/7/2004 (H3N2), que son variantes muy cercanas de la cepa A/Fujian/411/2002 (H3N2) de la vacuna prototipo. Los virus A y B co-circularon durante toda la temporada gripal en 11 de los 24 paises. 
Siete de ellos estan situados en el noroeste del Europa, y en ellos, la proporcion de virus B fue mas elevada (31 a 60%) que en el resto de Europa (6 a 26%). En 13 de 24 paises, los virus B circularon relativamente tarde en la temporada. Aproximadamente el 43% de todos los virus B con antigeno caracterizado eran del tipo B/Hong Kong/330/2001 (linea de los B/Victoria/2/87), una cepa distinta de la cepa vacunal anti-gripal B, o sea un virus de tipo B/Yamagata/16/88. Basandose en los virus detectados por el mundo hasta Febrero de 2005, la Organizacion Mundial de la Salud cambio la composicion de la vacuna anti-gripal 2005-2006, anadiendo a la vacuna de la temporada 2004-2005 un nuevo componente : una cepa similar al virus A/California/7/2004 (H3N2).
Highlights for the 6th International Ion Channel Conference: ion channel structure, function, disease and therapeutics
Authors: Limei Wang, Kewei Wang
Journal: Acta Pharmaceutica Sinica B (2017)

To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6th International Ion Channel Conference (IICC-2017) was held between June 23-27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on (1) Ion channel structure and function; (2) Ion channel physiology and human diseases; (3) Ion channels as targets for drug discovery; (4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC (No mechanoreceptor potential C), a member of the transient receptor potential (TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1 (TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.
Abstract 15798: Real Time MRI Based Atrial Cryoablation
Authors: Ravi Ranjan, Eugene Kholmovski, Nicolas Coulombe, Joshua Silvernagel, Nassir Marrouche
Journal: Circulation (2014)

Introduction: Balloon cryoablation is being increasingly used for pulmonary vein isolation. Acute determination of lesion permanency cannot be ascertained directly, but is inferred by PV occlusion and acute PV isolation. We aimed to determine if direct confirmation of vessel occlusion and lesion formation could be visualized in real time in a MRI system using a novel MRI compatible cryo balloon catheter. Methods: We used a canine model (n=3) and a MRI compatible cryo balloon catheter built for animal use (Medtronic CryoCath, Montreal, Canada). The procedure was performed in a 3T (Verio, Siemens) MR scanner. The MRI compatible 28 mm cryo balloon was advanced into the right atrium (RA) via the femoral vein under MRI guidance. Gadolinium based contrast (Multihance) was injected to confirm vessel occlusion. The superior vena cava (SVC) - RA junction was frozen for 3 mins. Post ablation, late gadolinium enhancement MRI (LGE-MRI) was obtained acutely to confirm the ablation. The heart was excised to confirm the tissue changes. Results: Panel A shows the inflated balloon at the SVC ostium. Panel B shows contrast injected in the SVC confirming its occlusion. Panel C is an MR image taken during the freeze cycle. Panel D is an LGE-MRI showing enhancement along the SVC wall confirming ablation. Panel E is an axial view of the SVC confirming circumferential ablation with no apparent gaps. The ablation completeness was confirmed in pathology. Conclusion: A real time MR-based balloon cryo ablation system was implemented. It allows real time confirmation of vessel occlusion, visualization of a freeze zone and visual confirmation of tissue changes from ablation in the pre-clinical setting.
Epidemia di Salmonella bongori 48:z35:- enterite in Sicilia
Authors: A Nastasi, C Mammina, L Salsa
Journal: Eurosurveillance (1999)

Salmonella bongori 48:z35:- e stata isolata per la prima volta, nel 1966, in Chad da una lucertola ed e stata classificata come ceppo biochimicamente atipico del sottogenere I di Kauffmann (1). In seguito, sono stati identificati altri ceppi, con formule antigeniche diverse ma con proprieta biochimiche simili, che sono stati assegnati al 'gruppo bongoro' del genere salmonella (2). Piu recentemente, e stato appurato, sulla base di caratteristiche genetiche e biochimiche, che S. bongori costituisce una specie diversa di salmonella (3).
Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study
Authors: A.M.W. Efsen, A. Schultze, R.F. Miller, A. Panteleev, A. Skrahin, D.N. Podlekareva, J.M. Miro, E. Girardi, H. Furrer, M.H. Losso, J. Toibaro, J.A. Caylà, A. Mocroft, J.D. Lundgren, F.A. Post, O. Kirk, I. Karpov, A. Vassilenko, A. Skrahina, D. Klimuk, A. Skrahin, O. Kondratenko, A. Zalutskaya, V. Bondarenko, V. Mitsura, E. Kozorez, O. Tumash, O. Suetnov, D. Paduto, V. Iljina, T. Kummik, N. Bolokadze, K. Mshvidobadze, N. Lanchava, L. Goginashvili, L. Mikiashvili, N. Bablishvili, B. Rozentale, I. Zeltina, I. Janushkevich, I. Caplinskiene, S. Caplinskas, Z. Kancauskiene, R. Podlasin, A. Wiercinska-Drapalo, M. Thompson, J. Kozlowska, A. Grezesczuk, M. Bura, B. Knysz, M. Inglot, A. Garlicki, J. Loster, S. Tetradov, D. Duiculescu, A. Rakhmanova, O. Panteleeva, A. Yakovlev, A. Kozlov, A. Tyukalova, Y. Vlasova, A. Panteleev, T. Trofimov, G. Kyselyova, A.B. Andersen, K. Thorsteinsson, M.C. Payen, K. Kabeya, C. Necsoi, F. Dabis, M. Bruyand, P. Morlat, A. Dupont, Y. Gerard, F. Bonnal, J. Ceccaldi, S. De Witte, E. Monlun, P. Lataste, I. Chossat, R. Miller, N. Vora, G. Cooke, S. Mullaney, E. Wilkins, V. George, P. Collini, D. Dockrell, F. Post, L. Campbell, R. Brum, E. Mabonga, P. Saigal, S. Kegg, J. Ainsworth, A. Waters, J. Dhar, L. Mashonganyika, E. Girardi, A. Rianda, V. Galati, C. Pinnetti, C. Tommasi, G. Lapadula, A. Di Biagio, A. Parisini, S. Carbonara, G. Angarano, M. Purgatorio, A. Matteelli, A. Apostoli, J. Toibaro, L. Moreno Macias, E. Warley, S. Tavella, O. Garcia Messina, O. Gear, H. Laplume, C. Marson, J. Contarelia, M. Michaan, P. Scapellato, D.D. Alessandro, B. Bartoletti, D. Palmero, C. Elias, C. Cortes, B. Crabtree, J.L. Mosqueda Gomez, A. Villanueva, L.A. Gonzalez Hernandez
Journal: Journal of Infection (2017)
TCT-779 Impact of Conscious Sedation Versus General Anesthesia on TAVR Outcomes: A Propensity-Matched Study
Authors: Brett Hiendlmayr, Joseph Hinchey, Lauren Curtis, Jeff Mather, Richard Seip, Marcin Dada, Robert Veenstra, Robert Hagberg, Immad Sadiq, Talhat Azemi, Mohiuddin Cheema, David Underhill, Francis Kiernan, William Duvall, Raymond McKay, Alexa Clement
Journal: Journal of the American College of Cardiology (2017)
Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?
Authors: Laura Hondebrink, Anne Zwartsen, Remco H.S. Westerink
Journal: Pharmacology & Therapeutics (2017)

The use of new psychoactive substances (NPS) is increasing and currently > 600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP). Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT2receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABAAreceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure. Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks.
Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies
Authors: Samad Ahadian, Robert Civitarese, Dawn Bannerman, Mohammad Hossein Mohammadi, Rick Lu, Erika Wang, Locke Davenport‐Huyer, Ben Lai, Boyang Zhang, Yimu Zhao, Serena Mandla, Anastasia Korolj, Milica Radisic
Journal: Advanced Healthcare Materials (2017)

Abstract Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ‐on‐a‐chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.
Challenges in the Study of Genetic Variants of Comorbid Alcohol Use Disorder and Major Depression
Authors: Alexis C. Edwards
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
The negative regulation of p53 by hedgehog signaling
Authors: Yoshinori Abe, Eri Oda-Sato, Kei Tobiume, Keiko Kawauchi, Koji Okamoto, Yoichi Taya, Nobuyuki Tanaka
Journal: Cancer Research (2006)

4836   The hedgehog (Hh) signal regulates the development of many organs in mammals and the activation of this signal is widely observed in human cancers. Hh signal activation in human cancers is caused by genetic mutations in its signaling molecules that result in the constitutive activation of the Hh signal pathway, such as loss-of-function mutations in the negative regulators of this pathway, e.g.  Patched  and  Suppressor of Fused , and gain-of-function mutations in  Smoothened  (Smo). These genetic alterations are mainly observed in basal-cell carcinomas and medulloblastomas. Recently, it has been shown that aberrant Hh signal activation is widely observed in human cancers, for example, cancers of the esophagus, stomach, pancreas and lungs, suggesting its role in oncogenesis. However, the precise role of the Hh signal in cancer development is still unclear. To analyze the role of Hh signal in oncogenesis, we test the effect of Hh signal molecules against the activity of tumor suppressor p53. The expression vector for activating mutation of Smo was cotransfected with the p53-expression vector, and we found that mutant Smo efficiently inhibits p53-mediated transcriptional activation and the p53 protein level. Moreover, we found that mutant Smo decreases the endogenous expression level of p53. This inhibition was also observed in the presence of the Hh ligand or with the overexpression of transcription factors Gli1 or Gli2, the downstream effectors of Smo, indicating that this inhibition is specific for the Hh signal pathway. We next analyzed the stability of p53 in response to Hh signal, since amount of p53 in cells is mainly regulated by the ubiquitin-proteasome system. We found that ectopical expression of mutant Smo accelerates the ubiquitination of the p53 protein. This result suggests that the Hh signal accelerates the degradation of the p53 protein by the ubiquitin-proteasome system. Indeed mutant Smo induced the cytoplasmic translocation of p53 from the nucleus and accelerated binding of p53 with Mdm2. Finally, to understand the role of the Hh signal in oncogenesis, we analyzed whether mutant Smo inhibits the DNA-damage-induced accumulation of the p53 protein or not. We found that p53 protein induction in response to adriamycin is suppressed by mutant Smo. Moreover, mutant Smo partially inhibited the p53-dependent apoptosis of oncogene-expressing mouse embryonic fibloblasts. On the other hand, Hh signal activation induced cell proliferation and expression levels of Cyclin D. Therefore, the Hh signal may be a powerful accelerator of oncogenesis, that is, it activates cell growth and inhibits the p53-mediated anti-cancer barrier.
Abstract P050: Perceived Discrimination and Incident Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Kara M Whitaker, Susan A Everson-Rose, James S Pankow, Carlos J Rodriguez, Tene T Lewis, Kiarri N Kershaw, Ana V Diez Roux, Pamela L Lutsey
Journal: Circulation (2016)

Introduction: Perceived discrimination is associated with risk factors for type 2 diabetes, including measures of adiposity. However, the relationship between perceived discrimination and incident diabetes is unknown. Objectives: To determine whether perceived discrimination is related to incident diabetes, and whether this association varies by race/ethnicity, age or sex. Methods: Included in this analysis were 5,310 MESA participants aged 45-84 years, without a history of diabetes at baseline. Perceived discrimination was measured using the Lifetime Discrimination scale, which assessed experiences of unfair treatment in 6 life domains (e.g. fired or denied a promotion, unfair treatment by police, not hired for a job, having life made difficult by neighbors). Participants were also asked to attribute their experiences of discrimination to various factors (e.g. race/ethnicity, age, sex, religion). Incident diabetes was identified at four follow-up examinations as fasting glucose ≥126 mg/dL or use of diabetes medications. Multivariable-adjusted Cox proportional hazard regression was used to model lifetime discrimination as a continuous and categorical variable (0, 1, ≥2 domains). Results: A total of 654 incident diabetes cases accrued over a median follow-up of 9.4 years (range 0.9-11.4). Lifetime discrimination reported in ≥ 2 domains (versus none) was associated with a 34% increased risk of incident diabetes, after adjustment for potential confounders or mediators (Table). Similar patterns were observed when we evaluated discrimination attributed to race/ethnicity only, or to a combination of other sources. There were no differences in the strength of association by race/ethnicity, age or sex. Conclusions: Lifetime discrimination was associated with increased risk of incident diabetes, regardless of attribution. These associations were independent of obesity, behavioral and psychosocial factors. Future research is needed to explore the mechanisms of the discrimination-diabetes relationship.
Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value
Authors: Giulia Mazzaschi, Denise Madeddu, Angela Falco, Giovanni Bocchialini, Matteo Goldoni, Francesco Sogni, Giovanna Armani, Costanza Annamaria Lagrasta, Bruno Lorusso, Chiara Mangiaracina, Rocchina Vilella, Caterina Frati, Roberta Alfieri, Luca Ampollini, Michele Veneziani, Enrico Maria Silini, Andrea Ardizzoni, Konrad Urbanek, Franco Aversa, Federico Quaini, Marcello Tiseo
Journal: Clinical Cancer Research (2017)

Purpose: The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed.Experimental Design: Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25, and Granzyme B TILs were immunohistochemically assessed.Results: PD-L1 levels inversely correlated with N involvement, although they did not show a statistically significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC versus ADC, in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8pos lymphocytes lacking PD-1 inhibitory receptor had a longer overall survival (OS: HR = 2.268; 95% CI, 1.056-4.871, P = 0.03). PD-1-to-CD8 ratio resulted in a prognostic factor both on univariate (HR = 1.952; 95% CI, 1.34-3.12, P = 0.001) and multivariate (HR = 1.943; 95% CI, 1.38-2.86, P = 0.009) analysis. Moreover, low PD-1 incidence among CD8pos cells was a distinctive feature of nivolumab-treated patients, showing clinical benefit with a prolonged progression-free survival (PFS: HR = 4.51; 95% CI, 1.45-13.94, P = 0.004).Conclusions: In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1-negative effector T lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC. Clin Cancer Res; 24(2); 407-19. ©2017 AACR.