tbuckley/cabot-search huggingface dataset:
Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood
Authors: Juha Koskinen, Markus Juonala, Terence Dwyer, Alison Venn, Russell Thomson, Lydia Bazzano, Gerald S. Berenson, Matthew A. Sabin, Trudy L. Burns, Jorma S.A. Viikari, Jessica G. Woo, Elaine M. Urbina, Ronald Prineas, Nina Hutri-Kähönen, Alan Sinaiko, David Jacobs, Julia Steinberger, Stephen Daniels, Olli T. Raitakari, Costan G. Magnussen
Journal: Circulation (2017)

Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model. In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P<0.05). The addition of lipids into the nonlaboratory risk model slightly but significantly improved discrimination in predicting high cIMT compared with nonlaboratory-based risk factors only (C statistics for laboratory-based model 0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95% confidence interval, 0.667-0.731]; P=0.02). Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood.
Rescue of high-specificity Cas9 variants using sgRNAs with matched 5’ nucleotides
Authors: Sojung Kim, Taegeun Bae, Jaewoong Hwang, Jin-Soo Kim
Journal: Genome biology (2017)

We report that engineered Cas9 variants with improved specificity-eCas9-1.1 and Cas9-HF1-are often poorly active in human cells, when complexed with single guide RNAs (sgRNAs) with a mismatch at the 5' terminus, relative to target DNA sequences. Because the nucleotide at the 5' end of sgRNAs, expressed under the control of the commonly-used U6 promoter, is fixed to a guanine, these attenuated Cas9 variants are not useful at many target sites. By using sgRNAs with matched 5' nucleotides, produced by linking them to a self-cleaving ribozyme, the editing activity of Cas9 variants can be rescued without sacrificing high specificity.
ROR-1 Is a Highly Discriminative Marker in Flow Cytometric Minimal Residual Disease (MRD) Detection in Chronic Lymphocytic Leukemia (CLL)
Authors: Michaela Patz, Barbara Pentok, Kathrin Cremer, Stefanie Linnartz, Esther Lilienweiss, Fanni Kleinert, Michael Hallek, Karl-Anton Kreuzer
Journal: Blood (2016)
Safety of nivolumab in patients with advanced or metastatic non-small cell lung cancer who have received at least one prior systemic regimens: Expanded access program in Korea (ONO-4538-X04)
Authors: S -W Kim, B.C. Cho, J.H. Kang, M -J Ahn, K.H. Lee, D -W Kim, Y -C Kim, J.S. Lee, J -S Lee, S.Y. Lee, K.U. Park, S -J Yong, H.J. An, E.K. Cho, T.W. Jang, B -S Kim, J -H Kim, S.S. Lee, I.I. Na, S.S. Yoo
Journal: Annals of Oncology (2017)
Access to early palliative care in a cancer center in Mexico.
Authors: Mirza Alcalde Castro, Enrique Soto Perez De Celis, Alfredo Covarrubias-Gómez, Africa Navarro-Lara, Sofía Sánchez-Román, Viridiana Pérez-Montessoro, Andrea De La O Murillo, Eucario León-Rodriguez, Yanin Chávarri-Guerra
Journal: Journal of Clinical Oncology (2017)

139 Background: Early palliative care (PC) improves the outcomes of patients with advanced cancer, and ASCO has issued guidelines to encourage the integration of PC into standard oncology care. However, even in developed nations, many patients fail to obtain a timely PC evaluation. We reviewed current practices in the assessment of PC needs and use of PC services in a cancer center in a developing country. Methods: All patients with newly diagnosed advanced solid tumors seen at the National Institute of Medical Science &amp; Nutrition in Mexico City from 10/2015 to 03/2016 were included. Demographic and clinical characteristics, data regarding assessment of PC needs, and referrals to PC services were retrospectively obtained from chart reviews for the first year after diagnosis. Frequencies and summary statistics were utilized. Results: 77 patients were included (median age 62 years; range 19-88; 55% male). 53% had gastrointestinal, 21% genitourinary, and 16% other tumors. The most commonly assessed symptom by oncologists (in at least one visit) was pain in 77% of patients, followed by anorexia (75%), fatigue (70%), nausea (57%), dyspnea (28%), and depression/anxiety (13%). 30% of patients were referred to PC in the first year after diagnosis. Median time from diagnosis to PC referral was 138 days (range 25-467). The most common causes for PC referral were pain (38%), delirium (23%), dyspnea (20%) and fatigue (20%). Only 1% of patients completed advance directives. 42% died during follow-up, of which 38% had previous PC visits. Median time from first PC visit to death was 15.5 days (range 1-70). Median time from last chemotherapy to death was 72.5 days (range 2-1201). Conclusions: Less than a third of the patients were referred to PC early in the course of their disease, and many PC needs were not routinely evaluated. Novel strategies are needed to improve access to early PC in developing countries.
Tolerability and efficacy of concurrent chemoradiotherapy comparing carboplatin/paclitaxel vs platinum/5-FU regimen for locally advanced esophageal and esophagogastric junction cancers
Authors: A. Tamtai, C. Jiarpinitnun, P. Hiranyatheb, N. Unwanatham, E. Sirachainun, C. Supsamutchai, P. Pattaranutaporn, N. Ngamphaiboon
Journal: Annals of Oncology (2017)
High-Energy Collimator Is Preferable to Medium-Energy Collimator for Evaluating 223Ra Uptake in Bone Metastasis at 2 Weeks Postinjection
Authors: Akira Ichimura, Tadaki Nakahara, Yoshiki Owaki, Kiyotaka Nakajima, Masahiro Jinzaki
Journal: Clinical Nuclear Medicine (2017)

Abstract An 80-year-old man with castration-resistant prostate cancer received 223 Ra injection to treat bone metastases. Two weeks after the injection, the patient underwent static 223 Ra scan of the chest with medium-energy and high-energy collimators for 30 minutes each. Images obtained with the 2 collimators showed that uptake in metastatic lesions was visually clearer and semiquantitatively higher with the high-energy collimator. The use of HE collimator for 223 Ra imaging in the early phase has been reported, and the present case suggests that in the late phase HE collimator would also be preferable to medium-energy collimator in terms of lesion-based evaluation.
Positivity versus negativity is a matter of timing
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2017)

Abstract “Negative” emotions are never purely negative. They attract attention at the very least and often stay attractive enough to make rehearsing them an addictive activity. As the authors point out, they also counteract a relentless tendency for positive emotions to become boring. Analysis in terms of reward suggests why this tendency occurs and how symbiosis with negative emotions may arise, in art and in life.
O impacto das ondas de calor do verão de 2003 sobre a mortalidade em quatro cidades italianas
Authors: P Michelozzi, F de Donato, L Bisanti, A Russo, E Cadum, M DeMaria, M D'Ovidio, G Costa, C. A. Perucci
Journal: Eurosurveillance (2005)

Este relatorio avalia o impacto da onda de calor de 2003 sobre a taxa de mortalidade especifica por causa e o papel das caracteristicas demograficas e das condicoes socioeconomicas capazes de terem aumentado o risco de mortalidade em quatro cidades italianas : Bolonha, Milao, Roma e Turim. 
Foi realizado um calculo diario da mortalidade para a populacao permanente por idade, sexo e causa da morte. A diferenca entre o numero observado e o numero medio ajustado de obitos serviu para calcular o excesso diario de mortalidade. O impacto do calor sobre a saude foi medido em termos de temperatura maxima aparente. 
O excesso de temperatura mais importante foi observado no nordeste da Italia, sendo superior de 23% em Turim e Milao. As pessoas idosas (75-84 anos) e as muito idosas (de mais de 85 anos) foram os grupos de idade mais afetados, e a estratificacao por sexo mostrou um aumento da mortalidade superior nas mulheres. Em Roma, o excesso de mortalidade mais alto, superior de 17,8%, afetou os mais pobres, e em Turim as pessoas com niveis de educacao mais baixos (mais 43%). 
A analise da taxa de mortalidade por causa confirma os resultados de estudos previos sobre o aumento da mortalidade associado ao calor em doencas respiratorias e cardiovasculares, e tambem mostra um excesso de mortalidade significativo em casos de doencas do sistema nervoso central e de perturbacoes metabolicas/endocrinas.
Os resultados de 2003 sublinham a necessidade de dirigirse nos futuros programas de prevencao a estes grupos susceptiveis identificados. A implementacao de sistemas de alerta junto a programas de prevencao eficazes e a monitorizacao da mortalidade durante as ondas de calor podem representar um instrumento util para a disminuicao do numero de obitos associados ao calor.
Induction of senescence-like growth arrest in melanocytes and malignant melanoma cells by human polynucleotide phosphorylase (hPNPaseold-35).
Authors: Devanand Sarkar, Magdalena Leszczyniecka, Dong-Chul Kang, Kristoffer Valerie, Tej K. Pandita, Paul B. Fisher
Journal: Cancer Research (2004)

2413   Terminal differentiation and senescence are two physiological processes that show overlapping properties including irreversible growth arrest and changes in gene expression profiles. To identify genes that lie at the core of these two phenomena we employed an overlapping pathway screening strategy that involved probing a library from melanoma cells, that are induced to differentiate with interferon-β and the protein kinase C activator mezerein, with cDNAs from senescent progeroid cells. This led to the identification of human polynucleotide phosphorylase (hPNPaseold-35), an early interferon-responsive gene having 3’-5’ exoribonuclease properties, that is upregulated during differentiation and senescence. Overexpression of hPNPaseold-35 in melanoma cells via a replication-incompetent adenovirus (Ad.hPNPaseold-35) inhibited growth and colony formation indicating the involvement of hPNPaseold-35 in differentiation and senescence-associated growth arrest. We presently investigated the molecular mechanism of growth inhibition by hPNPaseold-35. Infection of melanoma cells with Ad.hPNPaseold-35 resulted in cell cycle arrest in G1 phase, followed by apoptotic death, with concomitant reduction in S phase indicating inhibition of DNA synthesis. Ad.hPNPaseold-35 infection in melanocytes and melanoma cells resulted in a significant increase in senescence-associated β-galatosidase positive cells, a classical marker of senescence. At the molecular level, Ad.hPNPaseold-35 infection modulated the expression of genes that control G1 check-point, such as cyclin-dependent kinase inhibitors, Rb, E2F1 and c-myc. In melanoma cells, infection with Ad.hPNPaseold-35 reduced c-myc, both mRNA and protein, and hPNPaseOLD-35 protein could degrade c-myc mRNA in vitro indicating that c-myc might be a direct target of hPNPaseold-35. This observation was supported by the finding that overexpression of c-myc could rescue melanoma cells from hPNPaseold-35-mediated growth arrest. Additionally, Ad.hPNPaseold-35 infection significantly inhibited telomerase activity, which is also a feature of senescence. These findings indicate that hPNPaseold-35 might be a novel component of the molecular machinery governing senescence and inhibition of hPNPaseold-35 expression might serve as a potential approach for prolonging longevity.
Can checkpoint inhibitor therapy improve response to chemotherapy?
Authors: Michael Constantin Kirchberger, Bastian Schilling, Sebastian Haferkamp, Anja Bosserhoff, Gerold Schuler, Lucie Heinzerling
Journal: Journal of Clinical Oncology (2017)

e21024 Background: Even though immune checkpoint inhibitors (ICPI) are very effective with the wider use of single or combination treatment an increasing number of patients show resistance to treatment. If patients with metastatic melanoma progress and targeted therapy has also failed or is not feasible due to the lack of targetable mutations chemotherapy remains a treatment option. There is strong evidence that high mutational load leading to formation of so-called neoantigens is a major determinant of ICPI benefit. Additionally, chemotherapy has been described to modulate the microenvironment and the immune system. Here, we assess the efficacy of chemotherapy after checkpoint inhibitor failure in a series of advanced melanoma patients. Methods: We evaluated overall survival and response to chemotherapy of patients with progressive disease under previous treatment with the immune checkpoint inhibitors anti-CTLA4 and anti-PD1. Three skin cancer centers included a total of 17 patients. All BRAF-mutated patients had also progressed under previous BRAF/MEK-inhibitor therapy. Of all patients, 71% showed an elevated LDH, 41% had brain metastases and 35% an ECOG of 2 at initiation of chemotherapy. Results: Tumor control, defined as complete response, partial response, mixed response or stable disease was achieved in 53% (n = 9) of the patients who had previously been clearly progressive. The mean overall survival was 13.1 months with 65% (n = 11) of the patients still being alive. The choice of chemotherapy did not seem to influence the overall survival or tumor control rate. Conclusions: Immune checkpoint inhibitors could increase response to chemotherapy. The combination of chemotherapy and immunotherapy might be beneficial and increase tumor control.
Negative emotions in art reception: Refining theoretical assumptions and adding variables to the Distancing-Embracing model
Authors: Winfried Menninghaus, Valentin Wagner, Julian Hanich, Eugen Wassiliwizky, Thomas Jacobsen, Stefan Koelsch
Journal: Behavioral and Brain Sciences (2017)

Abstract While covering all commentaries, our response specifically focuses on the following issues: How can the hypothesis of emotional distancing (qua art framing) be compatible with stipulating high levels of felt negative emotions in art reception? Which concept of altogether pleasurable mixed emotions does our model involve? Can mechanisms of predictive coding, social sharing, and immersion enhance the power of our model?
La exhaustividad de la notificación del paludismo en los Países-Bajos entre 1995 y 2003 mediante el método de captura-recaptura
Authors: S Klein, A Bosman
Journal: Eurosurveillance (2005)

En 1999 en los Paises Bajos, debido a la nueva ley sobre las enfermedades transmisibles, la obligacion de notificar el paludismo se transfirio de los medicos a los laboratorios. Para estimar el impacto de ese cambio, se llevo a cabo una evaluacion de la exhaustividad de la notificacion del paludismo en los Paises-Bajos entre 1995 y 2003. Esta fue calculada en relacion a los datos de los laboratorios centinela y de las hospitalizaciones. El numero total de casos se estimo mediante el metodo de captura-recaptura (CRM) para evaluar la exhaustividad en relacion a ese valor. 
La exhaustividad de la notificacion para los datos centinela fue del 18,2% (IC 95% de 15,7-20,7) en 1995-1998 y del 56,4 % (IC 95% de 47,0-65,8) para 2000-2003. Esta fue del 35,1% para el periodo 1995-2003 comparada con los datos de declaracion hospitalaria. El numero estimado de casos de paludismo entre 1995 y 1998 fue de 3.123 (IC 95% de 2796-3449) y de 5.043 (IC 95% de 4343-5742) entre 2000 y 2003. En relacion a estas cifras, la exhaustividad de la declaracion aumento del 35,5 % (IC 95% de 32,1-39,7) en 1995-1998 al 36,1 % (IC 95% de 31,7-41,9) para el periodo 2000-2003.
Con el sistema de notificacion basado en los laboratorios, el numero absoluto de declaraciones de paludismo aumento de manera significativa, aunque la exhaustividad permaneciera estable en relacion a los datos de hospitalizacion. El aumento de los casos estimados de paludismo puede ser artificial, pues los requisitos necesarios para el metodo de captura-recaptura no se respetaron durante todo el periodo del estudio.
Intraductal radiofrequency ablation of an intraductal papillary mucinous neoplasia of the main pancreatic duct
Authors: Diane Lorenzo, Maximilien Barret, Benoit Bordacahar, Sarah Leblanc, Stanislas Chaussade, Pierre Cattan, Frédéric Prat
Journal: Endoscopy (2017)

An 82-year-old man was referred for exploration and treatment of a stenosis of the main pancreatic duct that was found incidentally during a computed tomography (CT) scan. He reported no symptoms.
Surveillance de la syphilis en France, 2000-2003
Authors: E Couturier, A Michel, M Janier, N Dupin, C Semaille
Journal: Eurosurveillance (2004)

Cet article decrit les tendances de la syphilis en France et les caracteristiques des patients (2000-2003) de meme que les tendances des ventes d’Extencilline® 2,4 MUI (2001-2003). Depuis 2001, un systeme de surveillance des cas de syphilis a ete mis en place dans des sites volontaires prenant en charge les infections sexuellement transmissibles et appartenant principalement au systeme public. Les donnees cliniques sont associees a des donnees comportementales recueillies a l’aide d’un auto-questionnaire.
De 2000 a 2003, 1 089 cas de syphilis ont ete declares, respectivement de 37 cas en 2000 a 428 en 2003. Les cas de syphilis concernaient majoritairement des hommes (96%), d’âge moyen 36,5 ans et 70% d’entre eux etaient nes en France. La proportion de cas de syphilis co-infecte par le VIH a diminue au cours du temps, de 60% en 2000 a 33% en 2003. 
La region la plus touchee par l’epidemie de syphilis etait la region Ile-de-France, principalement Paris. Dans cette region, la majorite des cas de syphilis a ete diagnostiquee chez les homosexuels (87%) comparee a 75% parmi ceux des autres regions. Parmi les patients ayant complete l’auto-questionnaire comportemental, 83% ont declare avoir des partenaires occasionnels dans les 3 mois avant le diagnostic de syphilis. 
Les tendances des ventes d’Extencilline® 2,4 MU dans les pharmacies privees sont proches de celles observees dans le systeme de surveillance, une augmentation entre 2001 et 2003.
En conclusion, la transmission de la syphilis continue en France en 2003. Il est necessaire d’insister sur le role de la fellation non protegee dans la transmission de la syphilis.
Abstract 16409: Gender Disparities Among Patients Receiving Bystander Cardiopulmonary Resuscitation in the United States
Authors: Audrey L Blewer, Shaun K McGovern, Rob Schmicker, Laurie J Morrison, Susanne May, Tom P Aufderheide, Mohamud Daya, Ahamed H Idris, Clifton W Callaway, Peter J Kudenchuk, Gary M Vilke, Benjamin S Abella
Journal: Circulation (2017)

Introduction:  Bystander cardiopulmonary resuscitation (B-CPR) increases survival from out of hospital cardiac arrest (OHCA), but B-CPR rates remain low in the US. It is unknown whether disparities of B-CPR delivery exist based on the gender of OHCA victims.   Objectives:  We sought to assess whether there is variation in B-CPR rates by gender in the home and the public environment. We hypothesized that females would be less likely than males to receive B-CPR in the public, and assessed the impact on survival.   Methods:  We conducted a retrospective cohort study, using adult, non-traumatic OHCA events from US sites of the Resuscitation Outcomes Consortium (ROC). We modeled the likelihood of receiving B-CPR by gender and stratified by arrest location. Patient and neighborhood-level variables were assessed in a univariate analysis with admission into a multivariate model (p   Results:  From 2011-2015, the ROC registry contained 27,481 SCA events. Excluding pediatric, EMS witnessed, and healthcare facility arrests, 19,331 were analyzed. Mean age was 64±17; 63% were male. B-CPR was administered in 37% events and varied by location. Overall, 35% females and 36% males received B-CPR in the home (p=ns), and 39% females and 45% males received B-CPR in public (p   Conclusion:  Males had an increased likelihood of receiving B-CPR compared to females in public locations. B-CPR improved survival, and survival was greater among males compared to females. These findings identify an important gap in B-CPR delivery that can inform future messaging to lay responders, health care providers and dispatchers.
Exosome Theranostics: Biology and Translational Medicine
Authors: Chuanjiang He, Shu Zheng, Yan Luo, Ben Wang
Journal: Theranostics (2017)

Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids.Exosomes are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells.Exosome secretion is a constitutive phenomenon that is involved in both physiological and pathological processes and determines both the exosomal surface molecules and the contents.Hence, we can exploit exosomes as biomarkers, vaccines and drug carriers and modify them rationally for therapeutic interventions.However, it is still a challenge to identify, isolate and quantify exosomes accurately, efficiently and selectively.Further studies on exosomes will explore their potential in translational medicine and provide new avenues for the creation of effective clinical diagnostics and therapeutic strategies; the use of exosomes in these applications can be called exosome theranostics.This review describes the fundamental processes of exosome formation and uptake.In addition, the physiological and pathological roles of exosomes in biology are also illustrated with a focus on how exosomes can be exploited or engineered as powerful tools in translational medicine.