tbuckley/cabot-search huggingface dataset:
Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark
Authors: Sidsel Arnspang Pedersen, David Gaist, Sigrun Alba Johannesdottir Schmidt, Lisbet Rosenkrantz Hölmich, Søren Friis, Anton Pottegård
Journal: Journal of the American Academy of Dermatology (2017)

Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer.To examine the association between hydrochlorothiazide use and the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).From the Danish Cancer Registry, we identified patients (cases) with nonmelanoma skin cancer (NMSC) during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (in 1995-2012) was assessed from the Danish Prescription Registry. Using conditional logistic regression, we calculated odds ratios (ORs) for BCC and SCC associated with hydrochlorothiazide use.High use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI], 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg of HCTZ) had ORs of 1.54 (95% CI, 1.38-1.71) and 7.38 (95% CI, 6.32-8.60) for BCC and SCC, respectively. Use of other diuretics and antihypertensives was not associated with NMSC.No data on sun exposure were available.Hydrochlorothiazide use is associated with a substantially increased risk of NMSC, especially SCC.
Analysis of OXA-204 carbapenemase-producing Enterobacteriaceae reveals possible endoscopy-associated transmission, France, 2012 to 2014
Authors: Anaïs Potron, Sandrine Bernabeu, Gaëlle Cuzon, Valérie Pontiès, Hervé Blanchard, Elise Seringe, Thierry Naas, Patrice Nordmann, Laurent Dortet
Journal: Eurosurveillance (2017)

OXA-48-like beta-lactamase producing bacteria are now endemic in several European and Mediterranean countries. Among this carbapenemase family, the OXA-48 and OXA-181 variants predominate, whereas other variants such as OXA-204 are rarely reported. Here, we report the molecular epidemiology of a collection of OXA-204-positive enterobacterial isolates (n = 29) recovered in France between October 2012 and May 2014. This study describes the first outbreak of OXA-204-producing Enterobacteriaceae in Europe, involving 12 isolates of an ST90 Escherichia coli clone and nine isolates of an ST147 Klebsiella pneumoniae clone. All isolates co-produced the cephalosporinase CMY-4, and 60% of them co-produced the extended-spectrum beta-lactamase CTX-M-15. The bla OXA-204 gene was located on a 150-kb IncA/C plasmid, isolated from various enterobacterial species in the same patient, indicating a high conjugative ability of this genetic vehicle.
T-cell therapy in combination with vemurafenib in BRAF mutated metastatic melanoma patients
Authors: T.H. Borch, R. Andersen, M.A.H. Rana, P. Kongsted, M. Pedersen, M. Nielsen, J.W. Kjeldsen, A. Kverneland, Ö Met, M. Donia, I.M. Svane
Journal: Annals of Oncology (2017)
Impact of London's road traffic air and noise pollution on birth weight: retrospective population based cohort study
Authors: Rachel B Smith, Daniela Fecht, John Gulliver, Sean D Beevers, David Dajnak, Marta Blangiardo, Rebecca E Ghosh, Anna L Hansell, Frank J Kelly, H Ross Anderson, Mireille B Toledano
Journal: BMJ (2017)

<h3>Abstract</h3> <h3>Objective</h3> To investigate the relation between exposure to both air and noise pollution from road traffic and birth weight outcomes. <h3>Design</h3> Retrospective population based cohort study. <h3>Setting</h3> Greater London and surrounding counties up to the M25 motorway (2317 km<sup>2</sup>), UK, from 2006 to 2010. <h3>Participants</h3> 540 365 singleton term live births. <h3>Main outcome measures</h3> Term low birth weight (LBW), small for gestational age (SGA) at term, and term birth weight. <h3>Results</h3> Average air pollutant exposures across pregnancy were 41 μg/m<sup>3</sup> nitrogen dioxide (NO<sub>2</sub>), 73 μg/m<sup>3</sup> nitrogen oxides (NO<sub>x</sub>), 14 μg/m<sup>3</sup> particulate matter with aerodynamic diameter &lt;2.5 μm (PM<sub>2.5</sub>), 23 μg/m<sup>3</sup> particulate matter with aerodynamic diameter &lt;10 μm (PM<sub>10</sub>), and 32 μg/m<sup>3</sup> ozone (O<sub>3</sub>). Average daytime (L<sub>Aeq,16hr</sub>) and night-time (L<sub>night</sub>) road traffic A-weighted noise levels were 58 dB and 53 dB respectively. Interquartile range increases in NO<sub>2</sub>, NO<sub>x</sub>, PM<sub>2.5</sub>, PM<sub>10</sub>, and source specific PM<sub>2.5</sub> from traffic exhaust (PM<sub>2.5 traffic exhaust</sub>) and traffic non-exhaust (brake or tyre wear and resuspension) (PM<sub>2.5 traffic non-exhaust</sub>) were associated with 2% to 6% increased odds of term LBW, and 1% to 3% increased odds of term SGA. Air pollutant associations were robust to adjustment for road traffic noise. Trends of decreasing birth weight across increasing road traffic noise categories were observed, but were strongly attenuated when adjusted for primary traffic related air pollutants. Only PM<sub>2.5 traffic exhaust</sub> and PM<sub>2.5</sub> were consistently associated with increased risk of term LBW after adjustment for each of the other air pollutants. It was estimated that 3% of term LBW cases in London are directly attributable to residential exposure to PM<sub>2.5</sub>&gt;13.8 μg/m<sup>3</sup>during pregnancy. <h3>Conclusions</h3> The findings suggest that air pollution from road traffic in London is adversely affecting fetal growth. The results suggest little evidence for an independent exposure-response effect of traffic related noise on birth weight outcomes.
Mechanistic divergence of immune checkpoint inhibition by an ex vivo platform derived from patient tumors where tumor and immune microenvironment is preserved
Authors: M. Biswas, N. Brijwani, B. Balakrishnan, O. Muthusamy, S. Thiyagarajan, D.G. Mehrotra, B. Majumder, P. Radhakrishnan, P.K. Majumder
Journal: Annals of Oncology (2017)
Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer
Authors: Pallabita Chowdhury, Prashanth K.B. Nagesh, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu
Journal: Acta Pharmaceutica Sinica B (2017)

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81 nm as detected by transmission electron microscopy (TEM). FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation (MTS) and clonogenic (colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein (Bcl-xL), upregulation of apoptosis-associated proteins (Bid, Bax, cleaved caspase 7, and cleaved PARP) and β-tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.
Bone marrow drives central nervous system regeneration after radiation injury
Authors: Jorg Dietrich, Ninib Baryawno, Naema Nayyar, Yannis K. Valtis, Betty Yang, Ina Ly, Antoine Besnard, Nicolas Severe, Karin U. Gustafsson, Ovidiu C. Andronesi, Tracy T. Batchelor, Amar Sahay, David T. Scadden
Journal: Journal of Clinical Investigation (2017)

Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow and brain in the setting of radiation injury. Specifically, we demonstrate that bone marrow-derived monocytes and macrophages are essential for structural and functional repair mechanisms, including regeneration of cerebral white matter and improvement in neurocognitive function. Using a granulocyte-colony stimulating factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell transplantation, MRI, and neurocognitive functional assessments, we demonstrate that bone marrow-derived G-CSF-responsive cells home to the injured brain and are critical for altering neural progenitor cells and brain repair. Additionally, compared with untreated animals, animals that received G-CSF following radiation injury exhibited enhanced functional brain repair. Together, these results demonstrate that, in addition to its known role in defense and debris removal, the hematopoietic system provides critical regenerative drive to the brain that can be modulated by clinically available agents.
Synovial Sarcoma: Current Concepts and Future Perspectives
Authors: Silvia Stacchiotti, Brian Andrew Van Tine
Journal: Journal of Clinical Oncology (2017)

Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities. In this review, we focus on the pharmacologic management of SS, both in the curative setting, where the standard approach is wide surgical excision combined with radiotherapy and/or (neo)adjuvant chemotherapy as appropriate, and in the palliative setting. In advanced disease, chemotherapy with anthracyclines and/or ifosfamide, trabectedin, or pazopanib has been demonstrated to be more active compared with other soft tissue sarcomas. In addition, a better understanding of the molecular and immunologic characteristics of SS has allowed for the identification of new potential targets and the development of novel biology-driven therapies that are all at different stages of testing. There include targeted agents, immunotherapy, and metabolic therapies. Because the impact of these strategies for improving SS outcome is still limited, current and future research is strongly needed to better understand the tumor biology, to identify predictive biomarkers, and to improve the outcomes for patients with SS.
Redes de vigilancia internacionales y normas de colaboración
Authors: I. S.T. Fisher, O N Gill
Journal: Eurosurveillance (2001)

A la vista de la creacion y el desarrollo de varias redes internacionales para la vigilancia de enfermedades transmisibles, surgen muchas preguntas relacionadas con la transmision de datos e informacion personal. La indole confidencial de los datos compartidos y su divulgacion internacional dentro y fuera de la red son, en consecuencia, una fuente de conflictos en potencia. Para solucionar estos problemas, Enter-net ha desarrollado unas 'Normas de Colaboracion' cuyo contenido es valido para todos los participantes de la red y para aquellas personas o entidades que puedan participar en un futuro. Estas normas proponen soluciones a asuntos relacionados con el acceso a las bases de datos creadas dentro del marco de la red, la calidad y la confidencialidad de los datos en circulacion, la responsabilidad individual en la identificacion de un producto incriminado cuando se produce un brote e incluso con la transmision de informacion fuera de la red. El objetivo principal de estas normas, que seran revisadas periodicamente, es mejorar la deteccion precoz y el manejo de los brotes transmitidos por alimentos, y adoptar las medidas adecuadas para la salud publica. Ademas, teniendo en cuenta el tipo de problemas contemplados por estas normas, algunas tambien resultaran utiles para otras redes de vigilancia.
Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma
Authors: Sandra Salvi, Jean Louis Ravetti, Giuseppe Arena, Clementina Musso, Serena Varesano, Maria Pia Pistillo, Pier Aldo Canessa, Paola Ferro, Franco Fedeli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2017)
Abstract 17385: CPR Education in High-need Schools to Increase Student Knowledge and Comfort Performing CPR
Authors: Debra Heard, Comilla Sasson
Journal: Circulation (2015)

Introduction: Low-income neighborhoods are important targets for CPR trainings as they typically have high incidence of out-of-hospital cardiac arrest and low prevalence of bystander CPR. Training middle school students in these neighborhoods is a novel intervention to increase CPR awareness. Objective: Conduct a school-based CPR intervention using classroom teachers as facilitators at 1131 middle schools across the United States with a high proportion of students from lower-income families. Methods: Population: 1131 public middle and high schools in 34 states (including the District of Columbia) were selected for the 2014-2015 school year to participate based on close proximity to sponsor’s U.S. store locations and 50% or more student eligibility for free or reduced-price lunch. Intervention: Participants completed a pre-test survey to assess baseline knowledge of CPR and comfort performing CPR. A classroom Hands-Only CPR training lasting one class period was conducted with the CPR in Schools Training Kit™, which includes an educational DVD, 10 manikins and resources for any classroom teacher to conduct trainings. Participants then completed post-training knowledge and comfort survey. McNemar’s tests on paired data and chi square and t-tests on aggregated unpaired data were conducted to assess for differences in CPR knowledge and comfort performing CPR pre- and post-training. Results: Training data were returned by 563 (49.8%) participating schools training a total of 150,409 students in Hands-Only CPR. Using a sample of returned data, the mean number of questions answered correctly on CPR knowledge increased from 2.5 to 4.2 (out of 5). The majority of participants (75.8%) felt comfortable performing Hands-Only CPR after the intervention. Conclusion: A total of 150,409 students from 563 schools were trained in Hands-Only CPR (average 267 students/CPR in Schools Training Kit). At $625 per CPR in Schools Training Kit (with 10 manikins and materials), training cost $4.70 for each student trained. Participants demonstrated increased knowledge of and comfort performing CPR. The CPR in Schools Training Kit is a low cost and promising method for increasing bystander CPR awareness in the student population in low-income neighborhoods.
Disease activity in ankylosing spondylitis: the global therapeutic target
Authors: Daniel Wendling, Clément Prati, Joachim Sieper
Journal: Annals of the Rheumatic Diseases (2017)

Spondyloarthritis (SpA) is a multifaceted disease with frequent predominant axial involvement.1 Typical sacroiliac radiographic changes allow to classify the patients as ankylosing spondylitis (AS). Imaging is able to classify patients as AS or non-radiographic axial spondyloarthritis  (axSpA) and illustrate and recognise the several steps from inflammation to structural damage, particularly in sacroiliac joints and spine. For decades, these radiographic findings have been the cornerstone for the classification and diagnosis of the disease.1 Contrary to other chronic rheumatic diseases such as rheumatoid arthritis, radiographic progression over time is only of limited interest as an outcome measure of the disease in the follow-up of patients with AS in current practice. In fact, radiographic progression is slow and does not even occur in all patients, has a low sensitivity to change over time and is associated with unidirectional evolution without regression. The tool used in current research to quantify the structural damage of the spine in AS is the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), which gives higher scores for ossification and bridging of the vertebrae (which may represent a repair mechanism) than for erosive (‘inflammatory’) changes. Advanced structural changes are associated with functional and spinal mobility impairment.2 

During the last decade, the use of anti-TNF agents has represented a major breakthrough in the treatment of patients with AS …
Health and Development at Age 19–24 Months of 19 Children Who Were Born with Microcephaly and Laboratory Evidence of Congenital Zika Virus Infection During the 2015 Zika Virus Outbreak — Brazil, 2017
Authors: Ashley Satterfield-Nash, Kim Kotzky, Jacob Allen, Jeanne Bertolli, Cynthia A. Moore, Isabela Ornelas Pereira, André Pessoa, Flavio Melo, Ana Carolina Faria e Silva Santelli, Coleen A. Boyle, Georgina Peacock
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In November 2015, the Brazilian Ministry of Health (MOH) declared the Zika virus outbreak a public health emergency after an increase in microcephaly cases was reported in the northeast region of the country (1). During 2015-2016, 15 states in Brazil with laboratory-confirmed Zika virus transmission reported an increase in birth prevalence of microcephaly (2.8 cases per 10,000 live births), significantly exceeding prevalence in four states without confirmed transmission (0.6 per 10,000) (2). Although children with microcephaly and laboratory evidence of Zika virus infection have been described in early infancy (3), their subsequent health and development have not been well characterized, constraining planning for the care and support of these children and their families. The Brazilian MOH, the State Health Secretariat of Paraíba, and CDC collaborated on a follow-up investigation of the health and development of children in northeastern Brazil who were reported to national surveillance with microcephaly at birth. Nineteen children with microcephaly at birth and laboratory evidence of Zika virus infection were assessed through clinical evaluations, caregiver interviews, and review of medical records. At follow-up (ages 19-24 months), most of these children had severe motor impairment, seizure disorders, hearing and vision abnormalities, and sleep difficulties. Children with microcephaly and laboratory evidence of Zika virus infection have severe functional limitations and will require specialized care from clinicians and caregivers as they age.
Abstract 16388: Fibrinogen Genetic Variants Promote Atherosclerosis by Altering the Inflammatory Process and Coagulation in Patients With Essential Hypertension and Diabetes Mellitus
Authors: Nikolaos Papageorgiou, Alexandros Briasoulis, George Hatzis, Antigoni Miliou, Maria Kozanitou, Emmanuel Androulakis, Marietta Charakida, Gerasimos Siasos, Kostas Toutouzas, Zoi Pallantza, Dimitris Tousoulis
Journal: Circulation (2015)

Introduction: Hypertension (HTN) and diabetes mellitus (DM) are associated with atherosclerosis and affect coagulation and inflammation. Hypothesis: We aimed to investigate the role of fibrinogen genetic variants (rs180070 and rs2070011) on coagulation and inflammation in patients with combined DM and HTN. Methods: 744 subjects (HTN and DM) were enrolled in our study. Fibrinogen polymorphisms were determined by PCR-RFLP technique. Fibrinogen, interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) CD40L, D-dimers and factors V, X activity were measured with appropriate laboratory methods. Results: In HTN patients, hsCRP levels were higher in the group of patients with higher fibrinogen levels compared to patients with lower and intermediate fibrinogen levels [0.28(0.12-0.42) vs 0.17(0.04-0.38) vs 0.18 (0.09-0.39), p=0.032)]. In addition, we found a significant effect of the rs180070 polymophism on IL-6 levels among HTN and DM. In HTN, IL-6 levels were higher in AA homozygotes of the rs180070 compared to all other genotypes (AG or GG) (4.96±0.69 vs 3.7±0.2, p=0.046). Similarly, DM patients homozygotes for the A allele (rs180070) had higher IL-6 levels (6.72±0.99 vs 4.01±0.35, p=0.016). In multivariable analysis, the only independent predictor of IL-6 levels in DM was the AA genotype [β(SE): 0.216 (1.76), P = 0.047]. In hypertensives, AA (rs180070) homozygosity was the only adjusted independent predictor of IL-6 levels [β(SE): 0.151 (0.642), P = 0.032]. Subgroup analysis of HTN and DM patients did not reveal any differences of CD40L levels in the presence of AA genotype (rs180070) (p=0.919 for DM and p=0.144 for HTN). We did not observe any significant change in IL-6 or CD40L levels with the presence of the AA genotype of the rs2070011 among the studied subgroups. Finally, we found that the AA homozygosity (rs180070) was associated with increases D-dimer levels in both DM and HTN (DM: 741.6±109,4 vs 487.3±35.6, p=0.028, HTN 623.3±79.6 vs 388.6±23.5, p=0.048). Conclusions: The AA homozygosity (rs180070) was associated with higher IL-6 levels and CD40L. We demonstrated for the first time, that the AA homozygosity (rs180070) is associated with increased D-dimer levels. These were also associated with higher fibrinogen levels.
A Stack-Based Ensemble Framework for Detecting Cancer MicroRNA Biomarkers
Authors: Sriparna Saha, Sayantan Mitra, Ravi Kant Yadav
Journal: Genomics Proteomics & Bioinformatics (2017)

MicroRNA (miRNA) plays vital roles in biological processes like RNA splicing and regulation of gene expression. Studies have revealed that there might be possible links between oncogenesis and expression profiles of some miRNAs, due to their differential expression between normal and tumor tissues. However, the automatic classification of miRNAs into different categories by considering the similarity of their expression values has rarely been addressed. This article proposes a solution framework for solving some real-life classification problems related to cancer, miRNA, and mRNA expression datasets. In the first stage, a multiobjective optimization based framework, non-dominated sorting genetic algorithm II, is proposed to automatically determine the appropriate classifier type, along with its suitable parameter and feature combinations, pertinent for classifying a given dataset. In the second page, a stack-based ensemble technique is employed to get a single combinatorial solution from the set of solutions obtained in the first stage. The performance of the proposed two-stage approach is evaluated on several cancer and RNA expression profile datasets. Compared to several state-of-the-art approaches for classifying different datasets, our method shows supremacy in the accuracy of classification.