bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Cancer Prevention through Precision Medicine and Immune-oncology
Authors: Kensler Thomas W. , Spira Avrum , Garber Judy E. , Szabo Eva , Lee J. Jack , Dong Zigang , Dannenberg Andrew J. , Hait William N. , Blackburn Elizabeth , Davidson Nancy E. , Foti Margaret , Lippman Scott M. 
Published: January 2016

Abstract
We have entered a transformative period in cancer prevention (including early detection). Remarkable progress in precision medicine and immune-oncology, driven by extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study the biology of premalignancy. The pace of research and discovery in precision medicine and immunoprevention has been astonishing and includes the following clinical firsts reported in 2015: driver mutations detected in circulating cell-free DNA in patients with premalignant lesions (lung); clonal hematopoiesis shown to be a premalignant state; molecular selection in chemoprevention randomized controlled trial (RCT; oral); striking efficacy in RCT of combination chemoprevention targeting signaling pathway alterations mechanistically linked to germline mutation (duodenum); molecular markers for early detection validated for lung cancer and showing promise for pancreatic, liver, and ovarian cancer. Identification of HPV as the essential cause of a major global cancer burden, including HPV16 as the single driver of an epidemic of oropharyngeal cancer in men, provides unique opportunities for the dissemination and implementation of public health interventions. Important to immunoprevention beyond viral vaccines, genetic drivers of premalignant progression were associated with increasing immunosuppressive TME; and Kras vaccine efficacy in pancreas genetically engineered mouse (GEM) model required an inhibitory adjuvant (Treg depletion). In addition to developing new (e.g., epigenetic) TME regulators, recent mechanistic studies of repurposed drugs (aspirin, metformin, and tamoxifen) have identified potent immune activity. Just as precision medicine and immune-oncology are revolutionizing cancer therapy, these approaches are transforming cancer prevention. Here, we set out a brief agenda for the immediate future of cancer prevention research (including a “Pre-Cancer Genome Atlas” or “PCGA”), which will involve the inter-related fields of precision medicine and immunoprevention – pivotal elements of a broader domain of personalized public health. Cancer Prev Res; 9(1); 2–10. ©2016 AACR.
Hypercoagulabilty, venous thromboembolism, and death in patients with cancer
Authors: Posch Florian , Riedl Julia , Reitter Eva-Maria , Kaider Alexandra , Zielinski Christoph , Pabinger Ingrid , Ay Cihan 
Published: January 2016

SummaryVenous thromboembolism (VTE) is a frequent complication of malignancy. The aim of this study was to investigate whether multi-state modelling may be a useful quantitative approach to dissect the complex epidemiological relationship between hypercoagulability, VTE, and death in cancer patients. We implemented a three-state/three-transition unidirectional illness-death model of cancer-associated VTE in data of 1,685 cancer patients included in a prospective cohort study, the Vienna Cancer and Thrombosis Study (CATS). During the two-year follow-up period, 145 (8.6%) patients developed VTE, 79 (54.5%) died after developing VTE, and 647 (38.4%) died without developing VTE, respectively. VTE events during follow-up were associated with a three-fold increase in the risk of death (Transition Hazard ratio (HR)=2.98, 95% confidence interval [CI]: 2.36-3.77, p< 0.001). This observation was independent of cancer stage. VTE events that occurred later during follow-up exerted a stronger impact on the risk of death than VTE events that occurred at earlier time points (HR for VTE occurrence one year after baseline vs at baseline=2.30, 95% CI: 1.28-4.15, p=0.005). Elevated baseline D-dimer levels emerged as a VTE-independent risk factor for mortality (HR=1.07, 95% CI: 1.05-1.08, p< 0.001), and also predicted mortality risk in patients who developed VTE. A higher Khorana Score predicted both the risk for VTE and death, but did not predict mortality after cancer-associated VTE. In conclusion, multi-state modeling represents a very potent approach to time-to-VTE cohort data in the cancer population, and should be used for both observational and interventional studies on cancer-associated VTE.
Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction
Authors: Chen Qiumei , Varga Monika , Wang Xiaoyin , Haddad Daniel J. , An Songtao , Medzikovic Lejla , Derakhshandeh Ronak , Kostyushev Dmitry S. , Zhang Yan , Clifford Brian T. , Luu Emmy , Danforth Olivia M. , Rafikov Ruslan , Gong Wenhui , Black Stephen M. , Suchkov Sergey V. , Fineman Jeffrey R. , Heiss Christian , Aschbacher Kirstin , Yeghiazarians Yerem , Springer Matthew L. 
Published: January 2016

Background

Circulating angiogenic cells (
CAC
s) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease (
CAD
) impairs the therapeutic potential of
CAC
s for myocardial infarction (
MI
) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (
NO
) synthase (
eNOS
) overcomes these defects.

Methods and Results

We recruited 40 volunteers varying by sex, age (< or ≥45 years), and
CAD
and subjected their
CAC
s to well‐established functional tests. Age and
CAD
were associated with reduced
CAC
intrinsic migration (but not specific response to vascular endothelial growth factor, adherence of
CAC
s to endothelial tubes,
eNOS mRNA
and protein levels, and
NO
production. To determine how
CAC
function influences therapeutic potential, we injected the 2 most functional and the 2 least functional
CAC
isolates into mouse hearts post
MI
. The high‐function isolates substantially improved cardiac function, whereas the low‐function isolates led to cardiac function only slightly better than vehicle control. Transduction of the worst isolate with
eNOS cDNA
adenovirus increased
NO
production, migration, and cardiac function of post‐
MI
mice implanted with the
CAC
s. Transduction of the best isolate with
eNOS
small interfering
RNA
adenovirus reduced all of these capabilities.

Conclusions

Age and
CAD
impair multiple functions of
CAC
s and limit therapeutic potential for the treatment of
MI
.
eNOS
gene therapy in
CAC
s from older donors or those with
CAD
has the potential to improve autologous cell therapy outcomes.
In vitro and in vivo evaluation of cord blood hematopoietic stem and progenitor cells amplified with glycosaminoglycan mimetic
Authors: Faivre Lionel , Parietti Véronique , Siñeriz Fernando , Chantepie Sandrine , Gilbert-Sirieix Marie , Albanese Patricia , Larghero Jérôme , Vanneaux Valérie 
Published: January 2016

Abstract
Background
Expansion protocols aim at both increasing the number of umbilical cord blood (UCB) hematopoietic stem cells and progenitor cells (HSPCs) and reducing the period of neutropenia in UCB HSPC graft. Because glycosaminoglycans (GAGs) are known to be important components of the hematopoietic niche and to modulate growth factor effects, we explored the use of GAG mimetic OTR4131 to potentiate HSPC’s in vitro expansion and in vivo engraftment.

Methods
UCB CD34+ cells were expanded with serum-free medium, SCF, TPO, FLT3-lig and G-CSF during 12 days in the absence or the presence of increasing OTR4131 concentrations (0-100 μg/mL). Proliferation ratio, cell viability and phenotype, functional assays, migration capacity and NOD-scid/γc-/- mice engraftment were assessed after expansion.

Results
At Day 12, ratios of cell expansion were not significantly increased by OTR4131 treatment. Better total nucleated cell viability was observed with the use of 1 μg/mL GAG mimetic compared to control (89.6 % ± 3.7 % and 79.9 % ± 3.3 %, respectively). Phenotype analysis showed a decrease of monocyte lineage in the presence of OTR4131 and HSPC migration capacity was diminished when GAG mimetic was used at 10 μg/mL (10.9 % ± 4.1 % vs. 52.9 % ± 17.9 % for control). HSPC clonogenic capacities were similar whatever the culture conditions. Finally, in vivo experiments revealed that mice successfully engrafted in all conditions, even if some differences were observed during the first month. Three months after graft, bone marrow chimerism and blood subpopulations were similar in both groups.

Conclusions
UCB HSPCs ex-vivo expansion in the presence of OTR4131 is a safe approach that did not modify cell function and engraftment capacities. In our experimental conditions, the use of a GAG mimetic did not, however, allow increasing cell expansion or optimizing their in vivo engraftment.
BRE facilitates skeletal muscle regeneration by promoting satellite cell motility and differentiation
Authors: Xiao Lihai , Lee Kenneth Ka Ho 
Published: January 2016

ABSTRACT
The function of the Bre gene in satellite cells was investigated during skeletal muscle regeneration. The tibialis anterior leg muscle was experimentally injured in Bre knockout mutant (BRE-KO) mice. It was established that the accompanying muscle regeneration was impaired as compared with their normal wild-type counterparts (BRE-WT). There were significantly fewer pax7+ satellite cells and smaller newly formed myofibers present in the injury sites of BRE-KO mice. Bre was required for satellite cell fusion and myofiber formation. The cell fusion index and average length of newly-formed BRE-KO myofibers were found to be significantly reduced as compared with BRE-WT myofibers. It is well established that satellite cells are highly invasive which confers on them the homing ability to reach the muscle injury sites. Hence, we tracked the migratory behavior of these cells using time-lapse microscopy. Image analysis revealed no difference in directionality of movement between BRE-KO and BRE-WT satellite cells but there was a significant decrease in the velocity of BRE-KO cell movement. Moreover, chemotactic migration assays indicated that BRE-KO satellite cells were significantly less responsive to chemoattractant SDF-1α than BRE-WT satellite cells. We also established that BRE normally protects CXCR4 from SDF-1α-induced degradation. In sum, BRE facilitates skeletal muscle regeneration by enhancing satellite cell motility, homing and fusion.
A historical section from Ottoman- Serbian musical interactions: Stevan Mokranjac’s Istanbul concerts<p>Osmanlı-Sırp müzik ilişkilerinden tarihsel bir kesit: Stevan Mokranjac’ın Dersaadet konserleri
Authors: Kutlay Evren 
Published: January 2016

<p>Stevan Mokranjac, who is among the founders of Serbian national music, came with the Belgrade Choral Society to Ottoman lands to give a concert in 1895, during the reign of Sultan Abdulhamid II. Mokranjac’s visit is important both in terms of presenting the developments in Western music area in Ottoman Empire as well as showing the diplomatic interactions of the two countries in relation to music. In this concerts it is observed that the Western music performance and composition practices that the Ottomans initiated during 19. century were adopted by the Serbian musicians. Moreover, the constructional similarities and interactions in institutionalization of Western music in both countries takes attention.</p><p>This article aims to reveal the Ottoman-Serbian musical interaction, about which no specific research was not traced, in line with the composer, musician, conductor Stevan Mokranjac, who is not very well known in Turkish music history, and Belgrad Choral Society’s Istanbul visit through the support of historical documents obtained by archival research.</p><p> </p><p><strong>Özet</strong></p><p>Sırp ulusal müziğinin kurucularından Stevan Mokranjac, Belgrad Koro Topluluğu’yla birlikte 1895 yılında, Sultan II. Abdülhamid’in hükümdarlığı döneminde konser vermek üzere Osmanlı topraklarına gelmiştir. Mokranjac’in bu ziyareti hem Osmanlı İmparatorluğu’nda Batı müziği alanındaki gelişmeleri gözler önüne sermek hem de iki ülke arasındaki diplomatik ilişkilerin müzik bağlamında etkileşimini göstermek bakımından önemlidir. Bu konserlerde Osmanlı’nın 19. yüzyılda temellerini attığı Batı müziği icra ve yaratı geleneklerinin Sırp müzisyenlerce adapte edildiği gözlemlenmiştir. Ayrıca iki ülkenin Batı müziği yapılanmasındaki kurumsal benzerlikler ve etkileşimler dikkat çekmektedir.</p><p>Bu makale, bugüne kadar hakkında hiç yayın tespit edilememiş Osmanlı-Sırp müzik ilişkilerini, yine Türk müzik tarihinde tanınmayan ve araştırılmamış besteci, müzisyen, şef Stevan Mokranjac’ın korosuyla İstanbul ziyareti düzleminde, konuyla ilgili tarihsel belgeleri arşiv çalışması ile ortaya koyarak gözler önüne sermeyi hedeflemektedir.</p>
Reducing Overutilization of Testing for Clostridium difficile Infection in a Pediatric Hospital System: A Quality Improvement Initiative
Authors: Klatte J. Michael , Selvarangan Rangaraj , Jackson Mary Anne , Myers Angela L. 
Published: January 2016

OBJECTIVES:
Study objectives included addressing overuse of Clostridium difficile laboratory testing by decreasing submission rates of nondiarrheal stool specimens and specimens from children ≤12 months of age and determining resultant patient and laboratory cost savings associated with decreased testing.

METHODS:
A multifaceted initiative was developed, and components included multiple provider education methods, computerized order entry modifications, and automatic declination from laboratory on testing stool specimens of nondiarrheal consistency and from children ≤12 months old. A run chart, demonstrating numbers of nondiarrheal plus infant stool specimens submitted over time, was developed to analyze the initiative’s impact on clinicians’ test-ordering practices. A p-chart was generated to evaluate the percentage of these submitted specimens tested biweekly over a 12-month period. Cost savings for patients and the laboratory were assessed at the study period’s conclusion.

RESULTS:
Run chart analysis revealed an initial shift after the interventions, suggesting a temporary decrease in testing submission; however, no sustained differences in numbers of specimens submitted biweekly were observed over time. On the p-chart, the mean percentage of specimens tested before the intervention was 100%. After the intervention, the average percentage of specimens tested dropped to 53.8%. Resultant laboratory cost savings totaled nearly $3600, and patient savings on testing charges were ∼$32 000.

CONCLUSIONS:
Automatic laboratory declination of nondiarrheal stools submitted for CDI testing resulted in a sustained decrease in the number of specimens tested, resulting in significant laboratory and patient cost savings. Despite multiple educational efforts, no sustained changes in physician ordering practices were observed.
Force decay and dimensional changes of thermoplastic and novel thermoset elastomeric ligatures
Authors: Masoud Ahmed I. , Bulic Milena , Viana Grace , Bedran-Russo Ana K. 
Published: January 2016

ABSTRACT

Objectives:
To compare over a period of 8 weeks (1) the force decay and (2) the dimensional changes between thermoplastic (TP) and thermoset (TS) elastomeric ligatures.

Materials and Methods:
TP and TS elastomeric ligatures were obtained from Rocky Mountain Orthodontics™. The TS ligatures were custom made specifically for this study. The sample included 72 clear TP and 72 clear TS elastomeric ligatures. The experiment was performed in a simulated oral environment (pH of 6.75) at 37°C. The remaining forces and the dimensional changes were measured at different time points over a period of 8 weeks.

Results:
Student’s t-tests revealed significant differences in percent force loss, percent change in outer diameter, percent change in inner diameter, and percent change in wall thickness between TP and TS elastomeric ligatures across all time points (P &lt; .001). The difference in percent change in width between TP and TS elastomeric ligatures was not significant at all time points (P &gt; .05). The mean difference in force loss between TP and TS across all time points was 22.91%. The TP and TS specimens exhibited 93.04% and 77.41% force loss, respectively, at the 28th day.

Conclusions:
This novel TS elastomeric ligature showed significantly less force decay and dimensional changes over time; therefore, it might be superior during initial leveling and aligning and during finishing stages. Using a transfer jig to prevent relaxation of the specimens before force measurement showed that force decay of commercially available elastomeric ligatures was greater than that described in previous publications.
Probability of detection of minute defects by ultrasonic automated testing equipment in view of Bayesian inference
Authors: Leybovich Alex 
Published: January 2016

AbstractThe method of Bayesian analysis of confidence in the testing evidence collected during ultrasonic automated testing of high quality aluminum ingots for minute defects of sub-millimeter size is discussed. These test results are assessed in the view of true or false evidence. The analysis demonstrates the significant influence of false evidence on the confidence in the test outcome where the evidence is skewed in the direction of false positive. At the same time the influence of the false negative evidence is shown to be more muted. To minimize the risk of false rejection of ingots with “ghost” indications not representing the physical defects, the off-line ingot retesting by an A-scan with defect waveform verification is implemented. Retesting of fabricated blanks made of the ingots previously passed the ingot testing is used to minimize the risk of passing products with defects earlier undetected.
Lorsque la prison (se) rend justice
Authors: Fernandez Fabrice 
Published: January 2016

À partir d’une enquête ethnographique menée sur une durée de 10 mois dans une maison d’arrêt de la région parisienne (en particulier l’observation de 81 jugements en commission de discipline), cette contribution vise à analyser et à questionner le contenu et le sens de la procédure disciplinaire en prison (du signalement d’incident à la réception des sanctions). Dans quel but sanctionne-t-on des détenus indisciplinés ? S’agit-il simplement de punir une conduite déviante et/ou de prévenir une récidive ? Au cœur de cette sanction, l’ordre n’est-il pas avant tout un ordre moral qui vise à transformer et rendre meilleurs les détenus ? Pour répondre à ce questionnement, je présente tout d’abord i) les enjeux politiques et moraux d’un traitement « humanisé » des indisciplinés, en retraçant les grandes réformes qui ont structuré la procédure disciplinaire. J’examine ensuite ii) les tensions entre les règles et les normes disciplinaires d’un côté et leur mise en pratique de l’autre en particulier à travers les décalages entre l’ordre moral des infractions et l’usage pragmatique des sanctions. J’analyse enfin iii) comment la commission de discipline est un espace de négociation au sein duquel les valeurs et les affects se conjuguent à des formes d’évaluation de la personnalité des détenus. À partir de l’ensemble de ces éléments, je montre comment malgré un souci d’humanisation, cette procédure disciplinaire produit de nouvelles formes de domination et de violence symbolique (infantilisation, responsabilisation, rectification morale).
Analisi spaziale in archeologia dei paesaggi: il progetto N.D.S.S. (Northern Daunian Subappennino Survey)
Authors: Stoico Felice , D'Altilia Luca 
Published: January 2016

<p>The Northern Daunian Subappennino Survey project, realised within the scientific research related to the PhD (Dottorato di ricerca) in "Archaeology and didactics of cultural heritage", proposes a methodological study of castles, aimed to rebuild the medieval landscape through the knowledge and interpretation of settlements. Starting from the results gained in the past researches and from many ideas offered by the analysis of medieval landscapes conducted by the University of Foggia, the project has been designed with a "global-type" analysis in mind, trying to redefine completely all the aspects involved in the archaeological documentation process and field-work, with the aid of archaeological computing, focusing on the use of free and open source software.</p>
From Colored Cosmopolitanism to Human Rights: A Historical Overview of the Transnational Black Freedom Struggle
Authors: Slate Nico 
Published: January 2016

Abstract
The last twenty years have witnessed an outpouring of scholarship on the transnational dimensions of the African American freedom struggle. Drawing on that scholarship, this essay offers a synthetic overview of the global civil rights movement from two specific and distinct lenses: human rights and colored solidarity. Beginning in the 1920s, notions of a dark or colored world connected African Americans to anti-imperial and antiracist movements abroad. In the 1950s and 1960s, solidarities based on notions of color were gradually replaced by a human rights framework and a new focus on the third world. The colored world lost its centrality as the leaders of postcolonial nations turned away from global antiracism toward state-centered visions of international relations. After 1968, however, colored cosmopolitanism experienced a resurgence within the United States as a result of shifting patterns of migration. On the global scale, by contrast, notions of human rights emerged triumphant in the discourse of international organizations and in the popular imagination of many countries. The achievement of those rights remains, however, woefully incomplete. While the promise of the colored world failed to survive decolonization, the promise of human rights endures more as a goal than a reality.
Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3
Authors: Alam Mohd S. , Rathore Sumit , Tyagi Rupesh K. , Sharma Yagya D. 
Published: January 2016

Tryptophan‐rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan‐rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor‐ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197–208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria.