tbuckley/cabot-search huggingface dataset:
Etude cas-témoins des facteurs de risque de la Fièvre Q dans le sud-ouest de l’Angleterre et l’Irlande du Nord
Authors: H J Orr, H Christensen, B Smyth, D Ab Dance, D Carrington, I Paul, J M Stuart
Journal: Eurosurveillance (2006)

La fievre Q (Coxiella burnetti), dont il est estime qu’elle represente 1% (700 cas) des pneumonies acquises dans la communaute au Royaume-Uni chaque annee, peut entrainer des complications severes comme les endocardites. Bien que des epidemies aient ete frequemment rapportees dans le monde, les causes sont rarement identifiees et les etudes sur les facteurs de risques des cas sporadiques sont peu nombreuses. 
Nous avons mene une etude cas-temoin appariee. Des cas aigus de fievre Q ont ete identifies chez des personnes de plus de 15 ans dans le sud-ouest de l’Angleterre et en Irlande du Nord entre janvier 2002 et decembre 2004. Les controles ont ete apparies sur l’âge, le sexe, et selon le cabinet generaliste qu’ils consultaient. Des questionnaires portant sur les contacts avec les animaux, les activites de loisirs et de travail, ont ete envoyes par la poste aux cas et aux temoins. 
Les questionnaires ont ete remplis par 39/50 cas (78%) et 90/180 (50%) des temoins. Selon l’analyse univariee, l’exposition professionnelle a des animaux ou a des produits animaux etait le seul facteur de risque associe aux cas avec un risque de 5% (P=0,05, odds ratio (OR) 3,4). Une longue maladie aurait un effet protecteur significatif (P=0.03, OR 0.3). Lors de l’analyse multivariee, l’association entre l’exposition professionnelle et la maladie demeurait forte (OR 3.6, 95% confidence interval (CI) 0.9 to 14.8) et le fait de fumer est apparu comme un facteur de risque possible. 
Cette etude cas-temoins est la premiere a identifier l’exposition professionnelle aux animaux ou aux produits animaux comme etant la voie d’infection la plus probable chez les cas sporadiques, contrairement aux cas epidemiques.
Interim baseline characteristics from RIFTOS MKI, a global non-interventional study assessing the use of multikinase inhibitors (MKIs) in the treatment of patients with asymptomatic radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC): A European subgroup analysis
Authors: J.W.A. Smit, M.S. Brose, F. Pitoia, C-C. Lin, I. Sugitani, M. Alevizaki, Y. Godbert, J. Aller, R.P. Peeters, K. Pazaitou-Panayiotou, L. Leenhardt, M.M. Fellous, Y. De Sanctis, M. Schlumberger
Journal: Annals of Oncology (2017)
Genome-Wide Analysis of Starvation-Selected Drosophila melanogaster—A Genetic Model of Obesity
Authors: Christopher M Hardy, Molly K Burke, Logan J Everett, Mira V Han, Kathryn M Lantz, Allen G Gibbs
Journal: Molecular Biology and Evolution (2017)

Experimental evolution affords the opportunity to investigate adaptation to stressful environments. Studies combining experimental evolution with whole-genome resequencing have provided insight into the dynamics of adaptation and a new tool to uncover genes associated with polygenic traits. Here, we selected for starvation resistance in populations of Drosophila melanogaster for over 80 generations. In response, the starvation-selected lines developed an obese condition, storing nearly twice the level of total lipids than their unselected controls. Although these fats provide a ∼3-fold increase in starvation resistance, the imbalance in lipid homeostasis incurs evolutionary cost. Some of these tradeoffs resemble obesity-associated pathologies in mammals including metabolic depression, low activity levels, dilated cardiomyopathy, and disrupted sleeping patterns. To determine the genetic basis of these traits, we resequenced genomic DNA from the selected lines and their controls. We found 1,046,373 polymorphic sites, many of which diverged between selection treatments. In addition, we found a wide range of genetic heterogeneity between the replicates of the selected lines, suggesting multiple mechanisms of adaptation. Genome-wide heterozygosity was low in the selected populations, with many large blocks of SNPs nearing fixation. We found candidate loci under selection by using an algorithm to control for the effects of genetic drift. These loci were mapped to a set of 382 genes, which associated with many processes including nutrient response, catabolic metabolism, and lipid droplet function. The results of our study speak to the evolutionary origins of obesity and provide new targets to understand the polygenic nature of obesity in a unique model system.
A first-in-human study of a novel monoclonal antibody INCSHR01210 directed against programmed cell death protein 1 (PD-1) in patients with advanced or metastatic cancer
Authors: J. Lickliter, H. Gan, B. Gao, P. Grimison, J. Zou, H. Kallender, K. Sun, X. Chen, A. Behren, P. Fernandez-Penas, A. Nagrial, M. Voskoboynik, K. Woods, M. Millward, T. Meniawy
Journal: Annals of Oncology (2017)
Doctor-patient perceptions and discourse on side effects related to metastatic breast cancer (MBC) treatment: The Make Your Dialogue Count survey.
Authors: Adam Brufsky, Marc L. Citron, Stephen E. Jones, Dian M. Corneliussen-James, Deana Percassi
Journal: Journal of Clinical Oncology (2015)

e20575 Background: About 5% of newly diagnosed BC cases in the US are metastatic, and up to 30% of women diagnosed with early-stage BC later develop MBC. The Make Your Dialogue Count survey probed potential gaps in doctor-patient discourse. Methods: The survey was conducted (June-August 2014) online, by paper, and by telephone among US women (age ≥ 21 y) with MBC and licensed US medical oncologists who treat ≥ 5 women with MBC per month. Survey respondents were not necessarily associated with one another. Patient data were unweighted. Oncologist data were weighted by geographic region and years in practice by sex to match proportions in the population. Statistically significant differences between groups were determined by standard t-test of column proportions and means at the 95% confidence level. Results: The survey was completed by 359 women (median age 53 y) and 252 oncologists (median 15 y in practice). At initial MBC diagnosis, oncologists practicing longer ( ≥ 15 vs < 15 y) were more likely to feel it is important/very important to discuss side-effect management (95%* vs 84%); yet only 58% of patients stated that this topic was actually discussed. At the time of treatment change, oncologists practicing longer were more likely to perceive in their patients anxiety about managing treatment side effects (80%* vs 60%) and adjusting to a new regimen (78%* vs 61%), and determination to treat their MBC without interfering with daily life (56%* vs 36%); only 44%, 33%, and 41% of patients reported having these feelings, respectively. Oncologists practicing longer were more likely to strongly agree that they wish they could do more to help patients manage side effects (53%* vs 34%). Oncologists practicing longer were less likely to let their emotions keep them from providing some information to patients (17%* vs 29%). Notwithstanding, oncologists practicing longer (31%) and shorter (24%) sometimes did not discuss with patients that MBC is incurable. *Significance at 5% risk level. Conclusions: Our findings suggest that oncologist-patient dialogue must improve to ensure that doctors understand and address patient needs and that frank discussions of difficult and/or emotional topics occur.
Immunogenomic profiling of non-small cell lung cancer: The ICON project.
Authors: Boris Sepesi, Lara Lacerda, Jianjun Zhang, Chantale Bernatchez, Tatiana Karpinets, Ara A. Vaporciyan, Ignacio Ivan Wistuba, Emily Roarty, John Heymach, Don Lynn Gibbons
Journal: Journal of Clinical Oncology (2017)

e20034 Background: Previous attempts to define tumor immune environment in non-small cell lung cancer (NSCLC) did not present comprehensive analyses. We established immunogenomic profiling project of NSCLC (ICON) to integrate immune, proteomic, genomic, transcriptomic, demographic, clinical, pathologic, and outcome data from surgically resected lung cancers. Methods: Tumor, normal lung tissue, and blood are collected at the time of surgery and blood after surgery up to 1 year. Samples are processed for tumor infiltrating lymphocyte (TILs) isolation and expansion; generation of patient derived xenografts (PDX), immunohistochemical (IHC) evaluation of immune cells and markers, genomic and proteomic analyses. Results: 73 (75%) out of 98 enrolled patients, median age 66 years, contributed samples to ICON; 33 (46%) males, 62 (85%) former smokers, 11 (15%) never smokers. 50 (68%) had adenocarcinoma, 17 (23%) squamous cell carcinoma, 3 (4%) small cell, and 3 (4%) pleomorphic carcinoma. 30 (41%) had stage I, 28 (38%) stage II, and 14 (19%) stage III disease, and one stage 4; 9 (12%) patients received neoadjuvant chemotherapy. Median tumor size was 4.0 cm and 67 (92%) underwent R0 resection. TIL expansion was successful in 47/67 (70%) cases. Phenotypic and functional analysis of freshly isolated and cultured TIL is ongoing. Preliminary results show suppression of intratumoral CD8+ cells as demonstrated by low perforin (p = 0.0002) and high CD8+ PD1 (p = 0.0007) levels as compared to normal tissue; however tumor CD8+CD28 co-stimulatory molecule expression was high p = 0.0003. PDX success rate has been 27%. IHC analyses show higher CD8+PD1, CD3, CD8+BTLA expression in SCC than in adenocarcinoma (p = 0.05). Exome sequencing and RNA sequencing from 19 patients show median mutation burden 466/tumor. Subclonal analysis, neoantigen prediction and expression status of predicted neoantigens are ongoing. Conclusions: ICON is an ambitious multi-team project designed to integrate wide range of tumor related data. Preliminary analysis demonstrates the project to be feasible with high rate of data acquisition. Tumors profiled from ICON will serve as a reference for the upcoming neoadjuvant single and dual checkpoint immunotherapy trial.
Association Between Type 2 Diabetes and All-Cause Hospitalization and Mortality in the UK General Heart Failure Population
Authors: Claire A. Lawson, Peter W. Jones, Lucy Teece, Sandra B. Dunbar, Petar M. Seferovic, Kamlesh Khunti, Mamas Mamas, Umesh T. Kadam
Journal: JACC Heart Failure (2017)
Efficacy and safety of Sym004 in refractory metastatic colorectal cancer with acquired resistance to anti-EGFR therapy: Results of a randomized phase II study (RP2S)
Authors: J. Tabernero, F. Ciardiello, C. Montagut, C. Ding, S. Kopetz, T. Tuxen Poulsen, A. Bardelli, L. Wyrwicz, A. Cubillo, C. Santos, G. Fumi, V. Zagonel, J. Bennouna, S. Siena, A. Falcone, M. Benavent, G. Argiles, M. Kragh, I.D. Horak, M. Dvorkin
Journal: Annals of Oncology (2017)
Overexpression of PRL-1 and PRL-2 in pancreatic cancer cell lines and tumor samples
Authors: Bret Stephens, Haiyong Han, Galen Hostetter, Michael Demeure, Daniel Von Hoff
Journal: Cancer Research (2007)

270   The PRL phosphatases (which consist of PRL-1, PRL-2 and PRL-3 in humans) have been implicated in cancer cell growth and metastasis, and are currently being validated as biomarkers and therapeutic targets in a variety of tumor types. Using cDNA microarray, we previously identified and reported PRL-1 as being highly upregulated in pancreatic cancer cell lines (Cancer Res 2002. 62:10;2890-6). In addition, mRNA levels of PRL-1, PRL-2, and PRL-3 in a large panel of cell lines have been described recently (Proc AACR 2006;47:[5028]), showing that PRL-2 might also be highly expressed in pancreatic cancer cell lines. Examination of PRL expression at the protein level, however, has remained less explored. We sought to further evaluate the expression of the PRL phosphatases at the protein level in pancreatic cancer cell lines and extend our findings to in situ analysis of pancreatic tumors by using tissue microarray (TMA) technology. As determined by Western blot, we found that PRL-1 and PRL-2, but not PRL-3 were highly expressed in pancreatic cancer cell lines, with expression comparable to that of other cancer cell lines previously described as having high PRL-1 or PRL-2 levels. Focusing on PRL-1 and PRL-2, TMA slides containing 53 tumor samples and 38 normal samples (20 of which were matched adjacent to tumor) were stained using PRL-1 or PRL-2 antibodies. Staining over background of PRL-1 or PRL-2 in adenocarcinoma was moderate to strong for ~40% of the tumors. In contrast over 90% of the normal pancreas counterparts stained negative or weak for both PRL proteins. Our results suggest that PRL-1 and PRL-2 are expressed in a subset of pancreatic tumors and further experiments are being undertaken to determine the role that PRL phosphatases play in the biology of these tumors.  This work was supported by a grant from the National Foundation for Cancer Research (NFCR).
Association of Delays in Surgery for Melanoma With Insurance Type
Authors: Adewole S. Adamson, Lei Zhou, Christopher D. Baggett, Nancy E. Thomas, Anne-Marie Meyer
Journal: JAMA Dermatology (2017)

Timely receipt of treatment for cancer is an important aspect of health care quality. It is unknown how delays of surgery for melanoma vary by insurance type.To analyze factors associated with delays between diagnosis and surgery for melanoma in patients with Medicare, Medicaid, or private insurance.Retrospective cohort study of patients who received a diagnosis of melanoma between 2004 and 2011 in North Carolina using data from the North Carolina Cancer Registry linked to administrative claims from Medicare, Medicaid, and private insurance. Inclusion criteria were incident patients with a diagnosis of melanoma stage 0 to III and with continuous insurance enrollment from at least 1 month prior to the month of diagnosis to 12 months after diagnosis of melanoma.Surgical delay, defined as definitive surgical excision occurring more than 6 weeks after melanoma diagnosis. Generalized linear models with log link, Poisson distributions, and robust standard errors were used to estimate adjusted risk ratios (RRs) to model risk of delay in definitive surgery.A total of 7629 patients were included (4210 [55%] female; mean [SD] age, 64 [15] years), 48% (n = 3631) Medicare, 48% (n = 3667) privately insured, and 4% (n = 331) Medicaid patients. Privately insured patients were least likely to experience a delay in definitive surgery, followed by Medicare and Medicaid patients (519 [14%], 609 [17%], and 79 [24%], respectively; P < .001). After demographic adjustment, the risk of surgical delay was significantly increased in patients with Medicaid compared with private insurance (RR, 1.36; 95% CI, 1.09-1.70). Delays were more likely in nonwhite patients (RR, 1.38; 95% CI, 1.02-1.87). Surgical delays were less likely if the physician performing the surgery (RR, 0.82; 95% CI, 0.72-0.93) or the diagnosing clinician (RR, 0.81; 95% CI, 0.71-0.93) was a dermatologist as compared with a nondermatologist.Surgical treatment delays were common but were less prevalent in patients diagnosed or surgically treated by a dermatologist. Medicaid patients experienced the most surgical delays. A reduction in delays in melanoma surgery could be achieved through better access to specialty care and cross-disciplinary coordination.
Recomendações europeias para a gestão dos profissionais de saúde expostos aos virus da Hepatite B (VHB) e C (VHC)
Authors: V Puro, G De Carli, S Cicalini, F Soldani, U Balslev, J Begovac, L Boaventura, M Campins Marti, M J Hernández Navarrete, R Kammerlander, C Larsen, F Lot, S Lunding, U Marcus, L Payne, A A Pereira, T Thomas, G Ippolito
Journal: Eurosurveillance (2005)

A prevencao da exposicao profissional aos VHB e VHC e a estrategia mais eficace para a reducao do risco de infeccoes transmitidas pelo sangue en pessoal sanitario. Os professionais de saude tambem deveriam estar sensibilisados da importância em termos medico-legais e clinicos de declarar qualquer exposicao, e poder aceder a peritos para receber os conselhos, os cuidados e o controle adequados. 
Esta especialmente recomendada a vacina conta o virus da Hepatite B (VHB) e uma prova da imunidade anti-VHB antes da contratacao. O pessoal sanitario com niveis de anticorpos anti-VHB pos-vacinais gou=10 mUI/mL, 1-2 meses depois de ser administrada a vacina, serao considerados como respondedores, estando protegidos contra a infeccao pelo VHB. Por essa razao, nao se aconselha para este pessoal as segundas doses nem o despitagem periodico da concentracao de anticorpos. Teriam que ser adoptadas estrategias alternativas para vencer a nao-resposta. 
Os profissionais de saude positivos anti-HBc teriam que fazer analises para os niveles de IgM anti-HBc e de ADN-VHB : se esses foram negativos, a resposta anti-HBs a vacina pode differenciar uma infeccao antigua (anti-HBs gou= 50 mUI/ml 30 dias apos a primeira dose de vacina: resposta anamnesica) ou falsos resultados positivos (anti-HBs gou= 10 mUI/ml 30 dias depois da terceira dose: resposta primaria) : os pacientes verdadeiramente positivos resistem a uma re-infeccao. 
A gestao da exposicao profissional ao VHB depende da susceptibilidade do pessoal exposto e do estatuto serologico da fonte. Se for indicado, deve-se iniciar o mais cedo possivel a profilaxia pos-exposicao com a vacina anti-VHB, as immunoglobinas da hepatite B ou ambos (dentro dos sete primeiros dias). 
Em ausencia de profilaxia contra o virus da hepatite C (VHC), a gestao do seguimento das exposicoes ao VHC depende de se foi decidido aplicar um tratamento antiviral durante a fase aguda. Testes de anticorpos VHC teriam que ser realisados nos profissionais de saude, immediatamente apos a exposicao e 6 meses mais tarde ; e de novo aos 12 meses para as fontes de co-infeccao VIH-VHC. No caso de ser recomendado um tratamento, tera que ser controlada a actividade de ALT (alanina aminotransferase) ao inicio e cada mes durante os cuatro meses seguindo a exposicao e o ARN-VHC qualitativo se um aumento for detectado.
Number of British doctors working in Australia and New Zealand is rising
Authors: Abi Rimmer
Journal: BMJ (2017)

Registry data are showing a rise in the number of UK trained doctors who are registered to work in Australia and New Zealand. A total of 699 more doctors from the UK were registered to practise in Australia in 2016 than in 2014, a 17% rise (from 4182 to 4881), show data from the Australian Health Practitioner Regulation Agency (Table 1).

View this table:

Table 1 
No of UK trained doctors registered to work in Australia, New Zealand, and US



Over the same period the number of UK doctors who were registered to practise in New Zealand also rose by 17% (from 424 to 497), but the …
A phase I dose-escalation study of the novel peptide ALM201 in patients (pts) with advanced solid tumours
Authors: A. El-Helali, R. Plummer, G. Jayson, V. Coyle, Y. Drew, N. Mescallado, N. Harris, A. Clamp, J. McCann, R. Kennedy, A. Cranston, R. Wilson
Journal: Annals of Oncology (2017)
Endothelial transplantation rejuvenates aged hematopoietic stem cell function
Authors: Michael G. Poulos, Pradeep Ramalingam, Michael C. Gutkin, Pierre Llanos, Katherine Gilleran, Sina Y. Rabbany, Jason M. Butler
Journal: Journal of Clinical Investigation (2017)

Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, HSC-supportive BM ECs enhanced hematopoietic recovery following myelosuppressive injury and restored endogenous HSC function in aged mice. Coinfusion of young ECs augmented aged HSC engraftment and enhanced overall survival in lethally irradiated mice by mitigating damage to the BM vascular microenvironment. These data lay the groundwork for the exploration of EC therapies that can serve as adjuvant modalities to enhance HSC engraftment and accelerate hematopoietic recovery in the elderly population following myelosuppressive regimens.
Gadolinium Deposition in the Pediatric Brain
Authors: Donna R. Roberts, Cynthia A. Welsh, W. Clay Davis
Journal: JAMA Pediatrics (2017)

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Nanotherapeutics for Gene Modulation that Prevents Apoptosis in the Brain and Fatal Neuroinflammation
Authors: Sang-Soo Kim, Antonina Rait, Emilio R. Garrido-Sanabria, Kathleen F. Pirollo, Joe B. Harford, Esther H. Chang
Journal: Molecular Therapy (2017)

The failure of therapeutic agents to cross the blood-brain barrier (BBB) has been a major impediment in the treatment of neurological disorders and brain tumors. We have addressed this issue using an immunoliposome nanocomplex (designated scL) that delivers therapeutic nucleic acids across the BBB into the deep brain via transcytosis mediated by transferrin receptors. We validated brain delivery of payloads after systemic administration by monitoring uptake of fluorescently labeled payloads and by confirming up- or down-modulation of specific target gene expression in the brain, mainly in neuronal cells. As proof of concept for the therapeutic potential of our delivery system, we employed scL delivering an siRNA targeting tumor necrosis factor alpha to suppress neuroinflammation and neuronal apoptosis and to protect mice in lethal endotoxemia triggered by bacterial lipopolysaccharide. Brain delivery of therapeutic payloads via scL has major implications for the development of treatments for neurological disorders and brain tumors. The failure of therapeutic agents to cross the blood-brain barrier (BBB) has been a major impediment in the treatment of neurological disorders and brain tumors. We have addressed this issue using an immunoliposome nanocomplex (designated scL) that delivers therapeutic nucleic acids across the BBB into the deep brain via transcytosis mediated by transferrin receptors. We validated brain delivery of payloads after systemic administration by monitoring uptake of fluorescently labeled payloads and by confirming up- or down-modulation of specific target gene expression in the brain, mainly in neuronal cells. As proof of concept for the therapeutic potential of our delivery system, we employed scL delivering an siRNA targeting tumor necrosis factor alpha to suppress neuroinflammation and neuronal apoptosis and to protect mice in lethal endotoxemia triggered by bacterial lipopolysaccharide. Brain delivery of therapeutic payloads via scL has major implications for the development of treatments for neurological disorders and brain tumors.