bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1 Inhibitor–Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course
Authors: Nishino Mizuki , Ramaiya Nikhil H. , Awad Mark M. , Sholl Lynette M. , Maattala Jennifer A. , Taibi Myriam , Hatabu Hiroto , Ott Patrick A. , Armand Philippe F. , Hodi F. Stephen 
Published: August 2016

Abstract
Purpose: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor–related pneumonitis in advanced cancer patients.
Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.
Results: Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.
Conclusions: PD-1 inhibitor–related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051–60. ©2016 AACR.
See related commentary by Castanon, p. 5956
In Vitro and In Vivo Efficacy of a Novel CD33-Targeted Thorium-227 Conjugate for the Treatment of Acute Myeloid Leukemia
Authors: Hagemann Urs B. , Wickstroem Katrine , Wang Ellen , Shea Adam O. , Sponheim Kristine , Karlsson Jenny , Bjerke Roger M. , Ryan Olav B. , Cuthbertson Alan S. 
Published: August 2016

Abstract
The clinical efficacy of the first approved alpha pharmaceutical, Xofigo (radium-223 dichloride, 223RaCl2), has stimulated significant interest in the development of new alpha-particle emitting drugs in oncology. Unlike radium-223 (223Ra), the parent radionuclide thorium-227 (227Th) is able to form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. We describe the preparation and use of a CD33-targeted thorium-227 conjugate (CD33-TTC), which binds to the sialic acid receptor CD33 for the treatment of acute myeloid leukemia (AML). A chelator was conjugated to the CD33-targeting antibody lintuzumab via amide bonds, enabling radiolabeling with the alpha-emitter 227Th. The CD33-TTC induced in vitro cytotoxicity on CD33-positive cells, independent of multiple drug resistance (MDR) phenotype. After exposure to CD33-TTC, cells accumulated DNA double-strand breaks and were arrested in the G2 phase of the cell cycle. In vivo, the CD33-TTC demonstrated antitumor activity in a subcutaneous xenograft mouse model using HL-60 cells at a single dose regimen. Dose-dependent significant survival benefit was further demonstrated in a disseminated mouse tumor model after single dose injection or administered as a fractionated dose. The data presented support the further development of the CD33-TTC as a novel alpha pharmaceutical for the treatment of AML. Mol Cancer Ther; 15(10); 2422–31. ©2016 AACR.
Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia
Authors: Kühn Michael W.M. , Song Evelyn , Feng Zhaohui , Sinha Amit , Chen Chun-Wei , Deshpande Aniruddha J. , Cusan Monica , Farnoud Noushin , Mupo Annalisa , Grove Carolyn , Koche Richard , Bradner James E. , de Stanchina Elisa , Vassiliou George S. , Hoshii Takayuki , Armstrong Scott A. 
Published: August 2016

Abstract
Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known about how mutant NPM1 (NPM1mut) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1mut AML. Using a CRISPR/Cas9 genome editing domain screen, we show NPM1mut AML to be exceptionally dependent on the menin binding site in MLL1. Pharmacologic small-molecule inhibition of the menin–MLL1 protein interaction had profound antileukemic activity in human and murine models of NPM1mut AML. Combined pharmacologic inhibition of menin–MLL1 and DOT1L resulted in dramatic suppression of HOX and FLT3 expression, induction of differentiation, and superior activity against NPM1mut leukemia.
Significance: MLL1 and DOT1L are chromatin regulators that control HOX, MEIS1, and FLT3 expression and are therapeutic targets in NPM1mut AML. Combinatorial small-molecule inhibition has synergistic on-target activity and constitutes a novel therapeutic concept for this common AML subtype. Cancer Discov; 6(10); 1166–81. ©2016 AACR.
See related commentary by Hourigan and Aplan, p. 1087.
This article is highlighted in the In This Issue feature, p. 1069
Inflammation and thrombosis – testing the hypothesis with anti- inflammatory drug trials
Authors: D’Ugo Emilia , Libby Peter , De Caterina Raffaele 
Published: August 2016

SummaryThe hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammation-related plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.
Downfront Winds over Buoyant Coastal Plumes
Authors: Spall Michael A. , Thomas Leif N. 
Published: August 2016

AbstractDownfront, or downwelling favorable, winds are commonly found over buoyant coastal plumes. It is known that these winds can result in mixing of the plume with the ambient water and that the winds influence the transport, spatial extent, and stability of the plumes. In the present study, the interaction of the Ekman velocity in the surface layer and baroclinic instability supported by the strong horizontal density gradient of the plume is explored with the objective of understanding the potential vorticity and buoyancy budgets. The approach makes use of an idealized numerical model and scaling theory. It is shown that when winds are present the weak stratification resulting from vertical mixing and the strong baroclinicity of the front results in near-zero average potential vorticity q. For weak to moderate winds, the reduction of q by diapycnal mixing is balanced by the generation of q through the geostrophic stress term in the regions of strong horizontal density gradients and stable stratification. However, for very strong winds the wind stress overwhelms the geostrophic stress and leads to a reduction in q, which is balanced by the vertical mixing term. In the absence of winds, the geostrophic stress dominates mixing and the flow rapidly restratifies. Nonlinearity, extremes of relative vorticity and vertical velocity, and mixing are all enhanced by the presence of a coast. Scaling estimates developed for the eddy buoyancy flux, the surface potential vorticity flux, and the diapycnal mixing rate compare well with results diagnosed from a series of numerical model calculations.
Curved Density Fronts: Cyclogeostrophic Adjustment and Frontogenesis
Authors: Shakespeare Callum J. 
Published: August 2016

AbstractCurvature can play a significant role in the dynamics of density fronts at small scales and in low-latitude regions of the ocean. Fronts can be displaced from balance by rapid forcing and undergo an adjustment toward a more stable state or be strained and sharpened by surrounding flow in a process known as frontogenesis. This study investigates the role of curvature in adjustment and frontogenesis using the idealized configuration of an axisymmetric eddy and associated circular front. As a result of the curvature, the balanced state of this system is not geostrophic balance, where pressure and Coriolis forces exactly balance, but cyclogeostrophic balance, where pressure and Coriolis forces combine to supply a net inwards centripetal force on fluid parcels. The parameter range for which cyclogeostrophically balanced states exist for a given unbalanced initial condition is determined. This parameter range is smaller for anticyclonic fronts (i.e., fronts curved around a warm core), which have larger angular velocities than comparable straight fronts, implying they are more likely to break down during adjustment. The reverse is true for cyclonic fronts. A model for the sharpening of a curved front in a background strain flow, analogous to the Hoskins and Bretherton (1972) model for a straight front, is developed. Relative to a straight front subject to the same strain rate, vertical velocities are weaker for an anticyclonic front and stronger for a cyclonic front. Anticyclonic fronts collapse to a near discontinuity during frontogenesis far more rapidly than cyclonic fronts for the same strain rate.
Risk of Malignancy in Dermatomyositis and Polymyositis
Authors: Qiang Judy K. , Kim Whan B. , Baibergenova Akerke , Alhusayen Raed 
Published: August 2016

Background: There is variation in the risk of malignancy in dermatomyositis (DM) and polymyositis (PM) in the existing literature. Objective: To conduct a meta-analysis to estimate the risk of malignancy in DM and PM as compared with the general population. Methods: Medline and Embase Database abstracts were searched through August 2014 using the search terms myositis, neoplasms, and paraneoplastic syndromes. Population-based, observational studies in English were included. Meta-analyses were conducted using random-effects models. Results: A total of 5 studies with 4538 DM or PM patients were included in the analysis. The overall relative risk was 4.66 for DM and 1.75 for PM. By gender, the standardized incidence ratio (SIR) of malignancy among DM patients was 5.29 for males and 4.56 for females; the SIR of malignancy among PM patients was 1.62 for males and 2.02 for females. By time since diagnosis, the SIR of malignancy among DM patients was 17.29 in the first year, 2.7 between 1 and 5 years, and 1.37 after 5 years. By age group, the SIR among DM patients was 2.79 for patients between 15 and 44 years and 3.13 beyond 45 years. Conclusions: Both DM and PM are associated with increased risk of malignancy, but the risk is higher in DM. The risk of malignancy is present in both genders and all age groups and is highest in the first year after diagnosis but persists beyond the fifth year in DM. Adults should be evaluated for malignancy at diagnosis, followed by long-term surveillance.
A systematic review of technology-based interventions for co-occurring substance use and trauma symptoms
Authors: Gilmore Amanda K , Wilson Sarah M , Skopp Nancy A , Osenbach Janyce E , Reger Greg 
Published: August 2016

Introduction Technology-based mental health interventions are becoming increasingly common, and several have begun to target multiple outcomes in a single intervention. Recent developments in the treatment of co-occurring posttraumatic stress disorder and substance use disorder has led to the development and testing of technology-based interventions for these disorders. The current systematic review examined technology-based interventions designed to improve mental health outcomes among patients with co-occurring trauma symptoms and substance use. Methods Of 601 articles reviewed, 14 included a technology-based intervention for patients with these co-occurring problems. Results Seven of these studies provided preliminary evidence that technology-based interventions are likely to be efficacious in reducing either trauma symptoms or substance use. The seven remaining studies demonstrated that technology-based interventions for co-occurring trauma symptoms and substance use are feasible. Discussion This review suggests that technology-based interventions for co-occurring trauma symptoms and substance use are feasible, but more work is needed to assess efficacy using scientifically rigorous studies.
Oral and oropharynx cancer in South America
Authors: Curado Maria Paula , Johnson Newell W , Kerr Alexander Ross , Silva Diego Rodrigues Mendonça e , Lanfranchi Hector , Pereira Débora Lima , Fonseca Felipe Paiva , Lopes Márcio Ajudarte , Kowalski Luiz Paulo , Vargas Pablo Agustin 
Published: August 2016

Objectives: To describe the incidence and mortality of oral and oropharynx cancers in South America using available public databases and to discuss the main pitfalls for acquiring reliable data. Methods: The incidence data for oral cavity and oropharynx cancers for South America were obtained from Cancer Incidence in Five Continents/International Agency for Research on Cancer for the period 1998–2007. Mortality rates in South America were obtained from the World Health Organization/IARC database for the period 1999–2012. The number of cases for Brazil was obtained from the National Cancer Institute/missing stage for the period 2000–2010, whereas the São Paulo cancer registry was used to collect data from the most populated state in Brazil for the period 2000–2008. Results: The incidence of oral and oropharynx cancers in South America varied, with the highest rates observed in Brazil among males. The mortality data in selected South American countries ranged from 0.72 to 6.04/100,000 and the proportion of ill-defined deaths in South America varied from 5.0% to 22.0%. Mortality trends for males decreased about 2.5% in most of the countries, excluding Brazil, whereas among females, a significant decrease occurred only in Colombia, with an increase in Brazil and Peru. Conclusion: Although there is a lack of reliable databases in South America, the available data demonstrate a decrease in mortality trends in most countries and the highest incidence in Brazil. The development and improvement of national cancer public databases in South America are highly desirable and necessary to better understand the characteristics and distribution of these neoplasms.
Chimeric antigen receptor T cells targeting Fc μ receptor selectively eliminate CLL cells while sparing healthy B cells
Authors: Faitschuk Elena , Hombach Andreas A. , Frenzel Lukas P. , Wendtner Clemens-Martin , Abken Hinrich 
Published: August 2016

Key Points
FcμR is a more selective target for the CAR T-cell therapy of CLL compared with currently used targets, including CD19.
RES-Scanner: a software package for genome-wide identification of RNA-editing sites
Authors: Wang Zongji , Lian Jinmin , Li Qiye , Zhang Pei , Zhou Yang , Zhan Xiaoyu , Zhang Guojie 
Published: August 2016

Abstract

Background
High-throughput sequencing (HTS) provides a powerful solution for the genome-wide identification of RNA-editing sites. However, it remains a great challenge to distinguish RNA-editing sites from genetic variants and technical artifacts caused by sequencing or read-mapping errors.

Results
Here we present RES-Scanner, a flexible and efficient software package that detects and annotates RNA-editing sites using matching RNA-seq and DNA-seq data from the same individuals or samples. RES-Scanner allows the use of both raw HTS reads and pre-aligned reads in BAM format as inputs. When inputs are HTS reads, RES-Scanner can invoke the BWA mapper to align reads to the reference genome automatically. To rigorously identify potential false positives resulting from genetic variants, we have equipped RES-Scanner with sophisticated statistical models to infer the reliability of homozygous genotypes called from DNA-seq data. These models are applicable to samples from either single individuals or a pool of multiple individuals if the ploidy information is known. In addition, RES-Scanner implements statistical tests to distinguish genuine RNA-editing sites from sequencing errors, and provides a series of sophisticated filtering options to remove false positives resulting from mapping errors. Finally, RES-Scanner can improve the completeness and accuracy of editing site identification when the data of multiple samples are available.

Conclusion
RES-Scanner, as a software package written in the Perl programming language, provides a comprehensive solution that addresses read mapping, homozygous genotype calling, de novo RNA-editing site identification and annotation for any species with matching RNA-seq and DNA-seq data. The package is freely available.
Therapeutic use of stem cells for cardiovascular disease
Authors: Faiella Whitney , Atoui Rony 
Published: August 2016

AbstractStem cell treatments are a desirable therapeutic option to regenerate myocardium and improve cardiac function after myocardial infarction. Several different types of cells have been explored, each with their own benefits and limitations. Induced pluripotent stem cells possess an embryonic‐like state and therefore have a high proliferative capacity, but they also pose a risk of teratoma formation. Mesenchymal stem cells have been investigated from both bone marrow and adipose tissue. Their immunomodulatory characteristics may permit the use of allogeneic cells as universal donor cells in the future. Lastly, studies have consistently shown that cardiac stem cells are better able to express markers of cardiogenesis compared to other cell types, as well improve cardiac function. The ideal source of stem cells depends on multiple factors such as the ease of extraction/isolation, effectiveness of engraftment, ability to differentiate into cardiac lineages and effect on cardiac function. Although multiple studies highlight the benefits and limitations of each cell type and reinforce the successful potential use of these cells to regenerate damaged myocardium, more studies are needed to directly compare cells from various sources. It is interesting to note that research using stem cell therapies is also expanding to treat other cardiovascular diseases including non‐ischemic cardiomyopathies.
A survey on MAC protocols for complex self-organizing cognitive radio networks
Authors: Shah Munam Ali , Zhang Sijing , Kamran Muhammad , Javaid Qaisar , Fatima Bahjat 
Published: August 2016

Abstract
Complex self-organizing cognitive radio (CR) networks serve as a framework for accessing the spectrum allocation dynamically where the vacant channels can be used by CR nodes opportunistically. CR devices must be capable of exploiting spectrum opportunities and exchanging control information over a control channel. Moreover, CR nodes should intelligently coordinate their access between different cognitive radios to avoid collisions on the available spectrum channels and to vacate the channel for the licensed user in timely manner. Since inception of CR technology, several MAC protocols have been designed and developed. This paper surveys the state of the art on tools, technologies and taxonomy of complex self-organizing CR networks. A detailed analysis on CR MAC protocols form part of this paper. We group existing approaches for development of CR MAC protocols and classify them into different categories and provide performance analysis and comparison of different protocols. With our categorization, an easy and concise view of underlying models for development of a CR MAC protocol is provided.
Thermo-oxidative and weathering degradation affecting coloration performance of lac dye
Authors: Nacowong Prapaipim , Saikrasun Sunan 
Published: August 2016

AbstractThermo-oxidative stability of lac dye was studied by simultaneous thermogravimetry (TG) and differential scanning calorimetry under nonisothermal and isothermal modes in air. The thermal stability change of lac dye was characterized by FTIR and UV–Vis spectroscopy. The TG profiles of lac dye showed at least three steps of mass loss. The first mass loss (about 8 %) found in the range of 40–150 °C mainly corresponded to the evaporation of moisture whereas the next two major steps were found with mass losses of 50 (150–440 °C) and 25 % (440–550 °C). The FTIR results indicate that the degradation of the major mass loss step (150–440 °C) mainly involved the thermo-oxidative reaction at carboxylic groups in conjugation with the C=C bonds of the anthraquinone ring. The absorbance profiles of lac dye solutions showed that the remarkable drop of absorbability was observed when the dye was heated to elevated temperatures (>150 °C). The results obtained from isothermal investigation also indicated the thermo-oxidative stability dependence of heating temperature. The apparent activation energy of lac dye calculated using isoconversional methods was higher under dynamic than under isothermal heating. Long period of weathering exposure mainly affected the O–H bonds of hydroxyl and carboxylic groups, and hence lowering the absorbability of lac dye. These results provided helpful information that can give support in the maintenance, preparation, dyeing and application stages of lac dye.