bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Selection of Syngeneic Preclinical Tumor Models for Immunotherapeutic Drug Discovery
Authors: Mosely Suzanne I.S. , Prime John E. , Sainson Richard C.A. , Koopmann Jens-Oliver , Wang Dennis Y.Q. , Greenawalt Danielle M. , Ahdesmaki Miika J. , Leyland Rebecca , Mullins Stefanie , Pacelli Luciano , Marcus Danielle , Anderton Judith , Watkins Amanda , Coates Ulrichsen Jane , Brohawn Philip , Higgs Brandon W. , McCourt Matthew , Jones Hazel , Harper James A. , Morrow Michelle , Valge-Archer Viia , Stewart Ross , Dovedi Simon J. , Wilkinson Robert W. 
Published: December 2016

Abstract
Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We used array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles. We identified strong differential gene expression in immune-related pathways and changes in immune cell–specific genes that suggested differences in tumor immune infiltrates between models. Further investigation using flow cytometry showed differences in both the composition and magnitude of the tumor immune infiltrates, identifying models that harbor “inflamed” and “non-inflamed” tumor immune infiltrate phenotypes. We also found that immunosuppressive cell types predominated in syngeneic mouse tumor models that did not respond to immune-checkpoint blockade, whereas cytotoxic effector immune cells were enriched in responsive models. A cytotoxic cell–rich tumor immune infiltrate has been correlated with increased efficacy of immunotherapies in the clinic, and these differences could underlie the varying response profiles to immunotherapy between the syngeneic models. This characterization highlighted the importance of extensive profiling and will enable investigators to select appropriate models to interrogate the activity of immunotherapies as well as combinations with targeted therapies in vivo. Cancer Immunol Res; 5(1); 29–41. ©2016 AACR.
Human Dendritic Cells Mitigate NK-Cell Dysfunction Mediated by Nonselective JAK1/2 Blockade
Authors: Curran Shane A. , Shyer Justin A. , St. Angelo Erin T. , Talbot Lillian R. , Sharma Sneh , Chung David J. , Heller Glenn , Hsu Katharine C. , Betts Brian C. , Young James W. 
Published: December 2016

AbstractJanus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. Selective JAK2 inhibition may also have a role in preventing and treating graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined. Using common γc cytokines and distinct human dendritic cell (DC) subtypes, we compared the effects of a JAK2-specific (TG101348) with a less selective JAK1/2 (ruxolitinib) inhibitor on NK-cell activation and function. Ruxolitinib treatment completely blocked IL2, IL15, and DC-mediated STAT5 phosphorylation, along with the capacity of NK cells to secrete IFNγ or lyse NK cell–sensitive targets. Only NK-cell proliferation stimulated by moDCs resisted ruxolitinib treatment. In contrast, TG101348 treatment of stimulated NK cells resulted in far less functional compromise. TG101348 completely inhibited only soluble IL15-mediated STAT5 phosphorylation, which Langerhans-type DCs (LCs), presenting membrane-bound IL15 in trans, could salvage. These results demonstrate that ruxolitinib's nonselective inhibition of JAK1/2 results in profound NK-cell dysfunction by blocking downstream pSTAT5, hence providing a persuasive rationale for the development of selective JAK2 inhibitors for immunotherapeutic applications. Cancer Immunol Res; 5(1); 52–60. ©2016 AACR.
Mulheres pela perspectiva masculina na literatura japonesa: As protagonistas-narradoras de Dazai
Authors: Kawana Karen Kazue 
Published: December 2016

Na literatura japonesa, homens escrevem como mulheres ao menos desde o século X, portanto, o fato de Dazai Osamu (1909-1948) escrever contos com narradoras na segunda metade do século XX não é algo novo, entretanto, neste artigo, procuramos mostrar que elas possuem características peculiares que as distinguem das figuras femininas presentes nas obras de contemporâneos como Kawabata Yasunari e Tanizaki Jun’ichirô.
Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging
Authors: Farhad Hoshang , Staziaki Pedro V. , Addison Daniel , Coelho-Filho Otavio R. , Shah Ravi V. , Mitchell Richard N. , Szilveszter Balint , Abbasi Siddique A. , Kwong Raymond Y. , Scherrer-Crosbie Marielle , Hoffmann Udo , Jerosch-Herold Michael , Neilan Tomas G. 
Published: December 2016

Background—
Anthracyclines are cardiotoxic; however, there are limited data characterizing the serial changes in cardiac structure and function after anthracyclines. The aim of this study was to use cardiac magnetic resonance to characterize anthracycline-induced cardiotoxicity in mice.

Methods and Results—

This was a longitudinal cardiac magnetic resonance and histological study of 45 wild-type male mice randomized to doxorubicin (n=30, 5 mg/kg of doxorubicin/week for 5 weeks) or placebo (n=15). A cardiac magnetic resonance was performed at baseline and at 5, 10, and 20 weeks after randomization. Measures of primary interest included left ventricular ejection fraction, myocardial edema (multiecho short-axis spin-echo acquisition), and myocardial fibrosis (Look-Locker gradient echo). In doxorubicin-treated mice versus placebo, there was an increase in myocardial edema at 5 weeks (T2 values of 32±4 versus 21±3 ms;
P
<0.05), followed by a reduction in left ventricular ejection fraction (54±6 versus 63±5%;
P
<0.05) and an increase in myocardial fibrosis (extracellular volume of 0.34±0.03 versus 0.27±0.03;
P
<0.05) at 10 weeks. There was a strong association between the early (5 weeks) increase in edema and the subacute (10 weeks) increase in fibrosis (
r
=0.90;
P
<0.001). Both the increase in edema and fibrosis predicted the late doxorubicin-induced mortality in mice (
P
<0.001).

Conclusions—
Our data suggest that, in mice, anthracycline-induced cardiotoxicity is associated with an early increase in cardiac edema and a subsequent increase in myocardial fibrosis. The early increase in edema and subacute increase in fibrosis are strongly linked and are both predictive of late mortality.
Lifestyle Interventions to Prevent Cardiovascular Events After Stroke and Transient Ischemic Attack
Authors: Deijle Inger A. , Van Schaik Sander M. , Van Wegen Erwin E.H. , Weinstein Henry C. , Kwakkel Gert , Van den Berg-Vos Renske M. 
Published: December 2016

Background and Purpose—
Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events. The purpose of this systematic review and meta-analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of (1) preventing recurrent cardiovascular events, (2) reducing mortality, and (3) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke.

Methods—
For this systematic review and meta-analysis, we systematically searched PubMed, Embase, PsycInfo, and the Cochrane Library from the start of the database to May 7, 2015. Subgroup analyses were conducted to explore the influence of therapy-related factors.

Results—

Twenty-two randomized controlled trials were identified with a total of 2574 patients. Pooling showed a significant reduction in systolic blood pressure by the lifestyle interventions applied, compared with usual care (mean difference, −3.6 mm Hg; 95% confidence interval, −5.6 to −1.6,
I
2
=33%). No significant effect was found on cardiovascular events, mortality, diastolic blood pressure, or cholesterol. In the subgroup analyses, the trials with cardiovascular fitness interventions, trials with an intervention that lasted longer than 4 months, and interventions that used >3 behavior change techniques were more effective in reducing systolic blood pressure.

Conclusions—
We found that lifestyle interventions are effective in lowering systolic blood pressure. About other end points, this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality, diastolic blood pressure, or total cholesterol.
Increased Stroke Burdens Among the Low-Income Young and Middle Aged in Rural China
Authors: Ning Xianjia , Sun Jian , Jiang Rongcai , Lu Hongyan , Bai Lingling , Shi Min , Tu Jun , Wu Yanan , Wang Jinghua , Zhang Jianning 
Published: December 2016

Background and Purpose—
Although stroke in the young and middle aged accounts for 31% of all strokes in China, the disease burden is unknown. We aimed to determine the secular trends in stroke incidence and the transition of subtypes in rural China over a 24-year period.

Methods—
In 1992, 14 920 residents were recruited to participate in the Tianjin Brain Study. Stroke events and all deaths were registered annually. We assessed the trends in incidence of first-ever stroke, including intracerebral hemorrhage and ischemic stroke, among adults aged 35 to 64 years during 1992 to 1999, 2000 to 2007, and 2008 to 2015. The annual proportion of change in stroke incidence was evaluated from 1992 to 2015.

Results—

The age-standardized incidence of first-ever stroke per 100 000 person-years increased significantly, from 122 in 1992 to 1999, to 215.8 in 2000 to 2007, to 471.8 in 2008 to 2015. The incidence of first-ever stroke increased annually by 11.9% overall (12.4% in men, 9.0% in women, 8.7% for intracerebral hemorrhage, and 10.7% for ischemic stroke;
P
<0.001). The greatest increases were observed in adults aged 55 to 64 years, with an annual increase of 11.6% for ischemic stroke (10.8% in men and 6.9% in women). However, the proportion of intracerebral hemorrhage has not changed over the past 24 years.

Conclusions—
In contrast with that in developed countries, the burden of stroke in China originates primarily from young and middle-aged adults. Thus, control of risk factors in this population is required to reduce the future burden of stroke in China.
The Meaning of the Supreme Court’s Decision on the Rejection of an Establishment Application for the Migrants’ Trade Union
Authors: Lee Seokwoo , Cho Youngkwan 
Published: December 2016

A group of 91 migrant workers, including undocumented workers, working in Seoul, Incheon and Gyeonggi Province organized the Migrants’ Trade Union (“mtu”) which is in the form of regional trade union on April 24, 2005. On May 3 of the same year, it submitted an establishment application for labor union accompanied by its bylaws to the Minister of Labor (now the Minister of Employment and Labor).
This mtu case, which has been pending before the Supreme Court for eight years was decided to “dismiss the defendant’s appeal.” This case will probably be named as the longest pending case of the Supreme Court.
Recent Advances in Satellite Data Rescue
Authors: Poli Paul , Dee Dick P. , Saunders Roger , John Viju O. , Rayer Peter , Schulz Jörg , Holmlund Kenneth , Coppens Dorothee , Klaes Dieter , Johnson James E. , Esfandiari Asghar E. , Gerasimov Irina V. , Zamkoff Emily B. , Al-Jazrawi Atheer F. , Santek David , Albani Mirko , Brunel Pascal , Fennig Karsten , Schröder Marc , Kobayashi Shinya , Oertel Dieter , Döhler Wolfgang , Spänkuch Dietrich , Bojinski Stephan 
Published: December 2016

Abstract
To better understand the impacts of climate change, environmental monitoring capabilities must be enhanced by deploying additional and more accurate satellite- and ground-based (including in situ) sensors. In addition, reanalysis of observations collected decades ago but long forgotten can unlock precious information about the recent past. Historical, in situ observations mainly cover densely inhabited areas and frequently traveled routes. In contrast, large selections of early meteorological satellite data, waiting to be exploited today, provide information about remote areas unavailable from any other source. When initially collected, these satellite data posed great challenges to transmission and archiving facilities. As a result, data access was limited to the main teams of scientific investigators associated with the instruments. As archive media have aged, so have the mission scientists and other pioneers of satellite meteorology, who sometimes retired in possession of unique and unpublished information.
This paper presents examples of recently recovered satellite data records, including satellite imagery, early infrared hyperspectral soundings, and early microwave humidity soundings. Their value for climate applications today can be realized using methods and techniques that were not yet available when the data were first collected, including efficient and accurate observation simulators and data assimilation into reanalyses. Modern technical infrastructure allows serving entire mission datasets online, enabling easy access and exploration by a broad range of users, including new and old generations of climate scientists.
An Investigation of the Influences of Mesoscale Ocean Eddies on Tropical Cyclone Intensities
Authors: Ma Zhanhong , Fei Jianfang , Liu Lei , Huang Xiaogang , Li Yan 
Published: December 2016

Abstract
The impact of mesoscale ocean eddies on tropical cyclone intensities is investigated based on a combination of observations and atmosphere–ocean coupling simulations. A statistical analysis reveals that the tropical cyclone–eddy interactions occur at very high frequencies; over 90% of the recorded tropical cyclones over the western North Pacific have encountered ocean eddies from 2002 to 2011. The chances of confronting a cold core eddy (CCE) are slightly larger than confronting a warm core eddy (WCE). The observational sea surface temperature data have statistically evidenced that CCEs tend to promote the sea surface temperature decrease caused by tropical cyclones while WCEs tend to restrain such ocean responses. The roles of CCEs are statistically more significant than those of WCEs in modulating the sea surface temperature response. It is therefore proposed that CCEs should be paid no less attention than WCEs during the TC–ocean interaction process. The CCE-induced changes in sea surface temperature decreases are observed to be more remarkable for more intense and slower-moving tropical cyclones and for thinner depth of mixed layers. A set of numerical experiments reveal that the effects of ocean eddies are positively related to their strengths and storm intensities, and the eddy feedback is less pronounced when the eddy is located at one side of storm tracks than right below the tropical cyclone center. The eddy-induced moisture disequilibrium sooner vanishes after the departure of tropical cyclones. The intensity recoveries last for 1–2 days because of the dependence of surface enthalpy fluxes on surface winds.
Prior Familiarization With Takeover Requests Affects Drivers’ Takeover Performance and Automation Trust
Authors: Hergeth Sebastian , Lorenz Lutz , Krems Josef F. 
Published: December 2016

Objective: The objective for this study was to investigate the effects of prior familiarization with takeover requests (TORs) during conditional automated driving on drivers’ initial takeover performance and automation trust. Background: System-initiated TORs are one of the biggest concerns for conditional automated driving and have been studied extensively in the past. Most, but not all, of these studies have included training sessions to familiarize participants with TORs. This makes them hard to compare and might obscure first-failure-like effects on takeover performance and automation trust formation. Method: A driving simulator study compared drivers’ takeover performance in two takeover situations across four prior familiarization groups (no familiarization, description, experience, description and experience) and automation trust before and after experiencing the system. Results: As hypothesized, prior familiarization with TORs had a more positive effect on takeover performance in the first than in a subsequent takeover situation. In all groups, automation trust increased after participants experienced the system. Participants who were given no prior familiarization with TORs reported highest automation trust both before and after experiencing the system. Conclusion: The current results extend earlier findings suggesting that prior familiarization with TORs during conditional automated driving will be most relevant for takeover performance in the first takeover situation and that it lowers drivers’ automation trust. Application: Potential applications of this research include different approaches to familiarize users with automated driving systems, better integration of earlier findings, and sophistication of experimental designs.
BCR-ABL–specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors
Authors: Comoli Patrizia , Basso Sabrina , Riva Giovanni , Barozzi Patrizia , Guido Ilaria , Gurrado Antonella , Quartuccio Giuseppe , Rubert Laura , Lagreca Ivana , Vallerini Daniela , Forghieri Fabio , Morselli Monica , Bresciani Paola , Cuoghi Angela , Paolini Ambra , Colaci Elisabetta , Marasca Roberto , Cuneo Antonio , Iughetti Lorenzo , Trenti Tommaso , Narni Franco , Foà Robin , Zecca Marco , Luppi Mario , Potenza Leonardo 
Published: December 2016

Key Points
BCR-ABL–specific CTLs may be obtained by stimulation with peptides derived from BCR-ABL junctional region and alternative splicing. T-cell therapy with BCR-ABL–specific CTLs from healthy donors or patients mediates molecular or hematologic CR in patients with Ph+ ALL.
Finding an appropriate equation to measure similarity between binary vectors: case studies on Indonesian and Japanese herbal medicines
Authors: Wijaya Sony Hartono , Afendi Farit Mochamad , Batubara Irmanida , Darusman Latifah K. , Altaf-Ul-Amin Md , Kanaya Shigehiko 
Published: December 2016

Abstract
Background
The binary similarity and dissimilarity measures have critical roles in the processing of data consisting of binary vectors in various fields including bioinformatics and chemometrics. These metrics express the similarity and dissimilarity values between two binary vectors in terms of the positive matches, absence mismatches or negative matches. To our knowledge, there is no published work presenting a systematic way of finding an appropriate equation to measure binary similarity that performs well for certain data type or application. A proper method to select a suitable binary similarity or dissimilarity measure is needed to obtain better classification results.

Results
In this study, we proposed a novel approach to select binary similarity and dissimilarity measures. We collected 79 binary similarity and dissimilarity equations by extensive literature search and implemented those equations as an R package called bmeasures. We applied these metrics to quantify the similarity and dissimilarity between herbal medicine formulas belonging to the Indonesian Jamu and Japanese Kampo separately. We assessed the capability of binary equations to classify herbal medicine pairs into match and mismatch efficacies based on their similarity or dissimilarity coefficients using the Receiver Operating Characteristic (ROC) curve analysis. According to the area under the ROC curve results, we found Indonesian Jamu and Japanese Kampo datasets obtained different ranking of binary similarity and dissimilarity measures. Out of all the equations, the Forbes-2 similarity and the Variant of Correlation similarity measures are recommended for studying the relationship between Jamu formulas and Kampo formulas, respectively.

Conclusions
The selection of binary similarity and dissimilarity measures for multivariate analysis is data dependent. The proposed method can be used to find the most suitable binary similarity and dissimilarity equation wisely for a particular data. Our finding suggests that all four types of matching quantities in the Operational Taxonomic Unit (OTU) table are important to calculate the similarity and dissimilarity coefficients between herbal medicine formulas. Also, the binary similarity and dissimilarity measures that include the negative match quantity d achieve better capability to separate herbal medicine pairs compared to equations that exclude d.
Economic evaluation of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital-Cameroon: a cost analysis
Authors: Maka Daniel Ethe , Chiabi Andreas , Obadeyi Bolaji , Mah Evelyn , Nguefack Séraphin , Nana Pamela , Mbacham Wilfred , Mbonda Elie 
Published: December 2016

Abstract
Background
Severe malaria is a leading cause of morbidity and mortality in under-fives in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. Artesunate has been shown to be cost-effective in African children, but whether these findings are transferable to Cameroonian children remains to be explored.

Objectives
To conduct a cost-analysis of four different regimens used in the treatment from the perspective of the healthcare payer.

Methods
An economic evaluation alongside a randomized comparative study was conducted in children aged 3 months to 15 years, admitted at the Ebolowa Regional Hospital with severe malaria due to Plasmodium falciparum. Patients were randomized to receive one of the four treatment alternatives. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H0, H12, H24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 h later by an 8-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 h, and Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. The main outcome measure for effectiveness of treatment was the parasite reduction rate. Based on a healthcare perspective, an evaluation of direct medical costs was done, including costs of anti-malarials, nursing care materials, adjuvant treatment, laboratory investigations, hospitalisation and professional fees. Guided by a cost minimalization approach, the relative costs of these treatment alternatives was compared and reported.

Results
Overall cost was higher for ARTES group at $65.14 (95% CI $57.68–72.60) than for quinine groups ($52.49–$62.40), but the difference was not statistically significant. Cost of the anti-malarial drug was significantly higher for artesunate-treated patients than for quinine-treated patients, whereas cost of hospitalization was significantly lower for artesunate-treated patients than for quinine-treated patients. Incremental analysis of ARTES against QLD as a baseline resulted in an ICER of $46.8/PRR24 and suggests ARTES as the most cost effective of all four treatment options.

Conclusion
Artesunate is a cost effective malaria treatment option relative to quinine alternatives with the lowest incremental cost per unit of effectiveness.
Trial registration clinicaltrials.gov identifier: NCT02563704. Registered 19 September 2015, retrospectively registered