bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy
Authors: Gibson Heather M. , McKnight Brooke N. , Malysa Agnes , Dyson Greg , Wiesend Wendy N. , McCarthy Claire E. , Reyes Joyce , Wei Wei-Zen , Viola-Villegas Nerissa T. 
Published: August 2018

Abstract
IFNγ is an attractive target for imaging active antitumor immunity due to its function in the T-cell signaling axis. Here, we test an IFNγ immuno-PET (immunoPET) probe for its capacity to identify adaptive immunotherapy response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFNγ immunoPET detected elevated cytokine levels in situ after vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy. In a model of induced T-cell anergy where CD8 T cells infiltrate the tumor, but upregulate PD-1, IFNγ tracer uptake was equivalent to isotype control, illustrating a lack of antitumor T-cell activity. The IFNγ immunoPET tracer detected IFNγ protein sequestered on the surface of tumor cells, likely in complex with the IFNγ receptor, which may explain imaging localization of this soluble factor in vivo. Collectively, we find that the activation status of cytotoxic T cells is annotated by IFNγ immunoPET, with reduced off-target binding to secondary lymphoid tissues compared with imaging total CD3+ tumor-infiltrating lymphocytes. Targeting of soluble cytokines such as IFNγ by PET imaging may provide valuable noninvasive insight into the function of immune cells in situ.
Significance: This study presents a novel approach to monitor therapeutic outcomes via IFNγ-targeted positron emission tomography. Cancer Res; 78(19); 5706–17. ©2018 AACR.
Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547
Authors: Kas Sjors M. , de Ruiter Julian R. , Schipper Koen , Schut Eva , Bombardelli Lorenzo , Wientjens Ellen , Drenth Anne Paulien , de Korte-Grimmerink Renske , Mahakena Sunny , Phillips Christopher , Smith Paul D. , Klarenbeek Sjoerd , van de Wetering Koen , Berns Anton , Wessels Lodewyk F.A. , Jonkers Jos 
Published: August 2018

Abstract
In human cancers, FGFR signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations, and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified Fgfr2 as a key driver of invasive lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the Sleeping Beauty transposon system. Here we explore whether these FGFR-driven ILCs are sensitive to the FGFR inhibitor AZD4547 and use transposon mutagenesis in these tumors to identify potential mechanisms of resistance to therapy. Combined with RNA sequencing-based analyses of AZD4547-resistant tumors, our in vivo approach identified several known and novel potential resistance mechanisms to FGFR inhibition, most of which converged on reactivation of the canonical MAPK–ERK signaling cascade. Observed resistance mechanisms included mutations in the tyrosine kinase domain of FGFR2, overexpression of MET, inactivation of RASA1, and activation of the drug-efflux transporter ABCG2. ABCG2 and RASA1 were identified only from de novo transposon insertions acquired during AZD4547 treatment, demonstrating that insertional mutagenesis in mice is an effective tool for identifying potential mechanisms of resistance to targeted cancer therapies.
Significance: These findings demonstrate that a combined approach of transcriptomics and insertional mutagenesis in vivo is an effective method for identifying potential targets to overcome resistance to therapy in the clinic. Cancer Res; 78(19); 5668–79. ©2018 AACR.
Colorectal Cancer Incidence Trends by Age, Stage, and Racial/Ethnic Group in California, 1990–2014
Authors: Ellis Libby , Abrahão Renata , McKinley Meg , Yang Juan , Somsouk Ma , Marchand Loic Le , Cheng Iona , Gomez Scarlett Lin , Shariff-Marco Salma 
Published: August 2018

Abstract
Background: The incidence of colorectal cancer in the United States declined substantially over the past 20 years, but evidence suggests that among younger adults (under 50 years at diagnosis), incidence is increasing. However, data on age- and stage-specific incidence trends across racial/ethnic groups are limited.
Methods: All incident cases of colorectal cancer diagnosed from 1990 through 2014 in adults aged 20 years and older were obtained from the California Cancer Registry. Incidence rates (per 100,000), incidence rate ratios, and triannual percent changes in incidence were estimated for each age group at diagnosis (20–49, 50–74, 75+ years), sex, stage, and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and 7 Asian American groups).
Results: Of 349,176 incident colorectal cancer cases diagnosed from 1990 through 2014, 9% were in adults younger than 50 years. Increases in incidence of early-onset colorectal cancer, especially in regional/distant stage disease, were observed in most racial/ethnic groups (statistically significant for non-Hispanic whites and Hispanics, ranging from 0.9% to 2.9% every 3 years). Incidence also increased in Vietnamese and other Southeast Asian groups of screening age (50–74 years). The incidence of colorectal cancer in non-Hispanic blacks aged 50+ declined over the 25-year period, but remained significantly higher than in non-Hispanic whites.
Conclusions: Further research is needed to understand the causes of the increasing incidence of early-onset colorectal cancer. The rising incidence of colorectal cancer among Southeast Asians of screening age and the persistently high incidence in non-Hispanic blacks also warrant attention.
Impact: Our findings may have implications for revisiting screening guidelines in the United States. Cancer Epidemiol Biomarkers Prev; 27(9); 1011–8. ©2018 AACR.
Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance
Authors: Quanz Maria , Bender Eckhard , Kopitz Charlotte , Grünewald Sylvia , Schlicker Andreas , Schwede Wolfgang , Eheim Ashley , Toschi Luisella , Neuhaus Roland , Richter Carmen , Toedling Joern , Merz Claudia , Lesche Ralf , Kamburov Atanas , Siebeneicher Holger , Bauser Marcus , Hägebarth Andrea 
Published: August 2018

Abstract
The lactate transporter SLC16A1/monocarboxylate transporter 1 (MCT1) plays a central role in tumor cell energy homeostasis. In a cell-based screen, we identified a novel class of MCT1 inhibitors, including BAY-8002, which potently suppress bidirectional lactate transport. We investigated the antiproliferative activity of BAY-8002 in a panel of 246 cancer cell lines and show that hematopoietic tumor cells, in particular diffuse large B-cell lymphoma cell lines, and subsets of solid tumor models are particularly sensitive to MCT1 inhibition. Associated markers of sensitivity were, among others, lack of MCT4 expression, low pleckstrin homology like domain family A member 2, and high pellino E3 ubiquitin protein ligase 1 expression. The antitumor effect of MCT1 inhibition was less pronounced on tumor xenografts, with tumor stasis being the maximal response. BAY-8002 significantly increased intratumor lactate levels and transiently modulated pyruvate levels. In order to address potential acquired resistance mechanisms to MCT1 inhibition, we generated MCT1 inhibitor–resistant cell lines and show that resistance can occur by upregulation of MCT4 even in the presence of sufficient oxygen, as well as by shifting energy generation toward oxidative phosphorylation. These findings provide insight into novel aspects of tumor response to MCT1 modulation and offer further rationale for patient selection in the clinical development of MCT1 inhibitors. Mol Cancer Ther; 17(11); 2285–96. ©2018 AACR.
“Religious” as a Category: A Comparative Case Study
Authors: Campany Robert Ford 
Published: August 2018

AbstractRightly noting that premodern non-Western cultures lacked a version of the modern Western category of “the religious,” some scholars have proposed simply abandoning it. Meanwhile, other scholars continue to wield it uncritically. In this article I propose a middle way, using premodern China as an example. Although China had no category exactly matching “the religious” in meaning and scope, it did, I argue, have an analogous category, one that functioned somewhat similarly in a partially analogous discourse that, like the Western category, formed part of an imperial project. More generally, I suggest that we do well to inquire into the extent to which the cultures we study possessed analogues to the categories and concepts in terms of which we characterize them, rather than assume either that they did or that they did not.
Halotolerant Copepoda in South American inland saline waters
Authors: De los Ríos Patricio , Bayly Ian A. E. 
Published: August 2018

Abstract
The zooplankton in South American saline waters is mainly dominated by copepods at salinities lower than 90 g/l, whereas at salinities above 90 g/l Artemia sp. is totally dominant. The aim of the present study is to analyse the salinity range of halophilic copepods on the basis of a literature review for South American saline inland waters. The calanoid Boeckella poopoensis Marsh, 1906, is widespread on the South American Altiplano and southern Argentinian plains, and in southern Patagonian shallow ponds. In the upper part of the salinity range, 20-90 g/l, B. poopoensis is the only copepod in the zooplankton of southern Patagonian and Altiplano shallow lakes. In the salinity range 5-20 g/l B. poopoensis may co-exist with B. palustris (Harding, 1955), two cyclopoids and an harpacticoid, and at salinities lower than 5 g/l it may co-exist with an even wider range of copepod species. Ecological and biogeographical aspects are also discussed.
The parasitic barnacle Sacculina lata Boschma, 1933 (Cirripedia, Rhizocephala, Sacculinidae) infecting the commercial swimming crab Charybdis miles (De Haan, 1835) (Decapoda, Portunidae) in the Beibu Gulf, South China Sea
Authors: Yang Chang-Ping , Sun Dian-Rong , Qiu Yong-Song , Liu Yan , Shan Binbin , Li Teng , Liu Shengnan 
Published: August 2018

AbstractA sacculinid rhizocephalan parasite,Sacculina lataBoschma, 1933, was discovered in the Beibu Gulf (= Gulf of Tonkin) west of Hainan Island, China, occurring in 7.4% of 363Charybdis miles(De Haan, 1835) collected by 30 trawls in July 2017. This is the first time thatS. latahas been recorded in Beibu Gulf and in the Chinese Exclusive Economic Zones (EEZs). Of the sampled crabs from 9 stations, 8 males and 19 females were found bearing externae ofS. lataon the abdomen, a prevalence of 4.1 and 11.2% in male and female crabs, respectively. The dominant size group of infected males was larger than that of females. There was no significant relationship between water depth and infection rate of the parasite. A positive correlation was found both between volume and weight of externae, and between surface area of externae and abdomen width of the host crabs. Carapace width and wet weight of infected crabs were significantly less than those of uninfected crabs. In male crabs, the first pleopods of infected individuals were shorter than normal, but their pleons were wider. The propodus of the chela of a parasitized crab was significantly larger than that of normal crabs, both in males and females. No rhizocephalan-infected female crab was found bearing eggs.
A Last-Minute Private Peace Initiative: Albert Ballin’s Mediation Efforts between Germany and Britain, 1908-1914
Authors: Lehrs Lior 
Published: August 2018

Summary
As relations between Germany and Britain were deteriorating during the years 1908-1914, Albert Ballin, a German businessman, became concerned and decided to promote Anglo–German talks on naval arms limitations in order to halt the naval arms race and improve relations between the two states. This article analyses Albert Ballin’s — and his British friend Ernest Cassel’s — private peace initiatives during the years 1908-1914 as a historical example of ‘unofficial diplomacy’ long before this term was discussed in International Relations literature. It examines the tools and conditions that created the basis for Ballin’s initiatives and explores his role in the diplomatic processes between Germany and Britain before the First World War. Ballin’s and Cassel’s unofficial, persistent peace efforts had some effect on the official diplomatic sphere and led to official negotiations, but they ultimately failed in their attempt to promote an agreement or to prevent the war.
Reporting to the Sage: Military Monuments in the Imperial Academy in Qing China
Authors: Tang Kwok-leong 
Published: August 2018

AbstractThis article presents a study of a unique kind of commemorative stele erected by Qing emperors in the Imperial Academy—the symbol of Confucian culture and civilian education—and also replicated in schools across China. Before the Qing dynasty (1644-1911), Chinese rulers did not install military monuments at the academy. In this article, I argue that the Qing emperors erected war monuments in the Imperial Academy to justify and commemorate their wars of conquest. As the emperors required the stelae to be replicated at some of the local schools across China, they became widely accessible to the public. However, the Qing emperors, particularly the Qianlong emperor, were concerned that the stelae could become symbols of abusive warfare, thereby undermining their claims to rule in accordance with Confucian ideals. For this reason, they carefully selected the campaigns to commemorate and ensured that inscriptions on the stelae explained that they had no choice but to embark on war in these instances.
Subutai: Sorting Fact from Fiction Surrounding the Mongol Empire’s Greatest General (With Translations of Subutai’s Two Biographies in the Yuan Shi)
Authors: Pow Stephen , Liao Jingjing 
Published: August 2018

AbstractSubutai [Sübe’etei], often referred to as the greatest of the Mongol Empire’s generals, has increasingly become a topic of popular interest. However, the literature about him continues to rely on secondary sources so that popular and scholarly work alike often contains and perpetuates ahistorical statements regarding his origins and his military career. Based on the assumption that many errors have been perpetuated because Chinese source material has not been sufficiently integrated into available Western literature, this paper aims to offer a two-part corrective to the problem. First, an introductory essay will analyze several aspects of Subutai’s life and career that are often misrepresented. Secondly, complete English translations of the two biographies of Subutai found in the 121st and 122nd chapters of theYuan Shiare provided.
The Rescue of British by Chinese at Yenangyaung and Slim’s Flawed Account of the Battle
Authors: Wang Z. George 
Published: August 2018

Abstract
Chinese and British troops fought shoulder to shoulder against the Japanese at Yenangyaung, Burma, in mid-April 1942. The official military histories of the two nations, however, record the Yenangyaung battle and appraise the Chinese contribution in striking disagreement. To find the truth through reconciling the significant discrepancies in existence for seven decades, materials of various countries have been comparatively studied. The article will present the following conclusions from this forensic inquiry: i) the narrative of the Yenangyaung battle by William Slim, the commanding officer of the British-Chinese joint forces in the battle, is fraught with misrepresentations; and ii) the official British military history errs in denying the Chinese rescue of the British troops.
The Unexpected Rapid Intensification of Tropical Cyclones in Moderate Vertical Wind Shear. Part I: Overview and Observations
Authors: Ryglicki David R. , Cossuth Joshua H. , Hodyss Daniel , Doyle James D. 
Published: August 2018

AbstractA satellite-based investigation is performed of a class of tropical cyclones (TCs) that unexpectedly undergo rapid intensification (RI) in moderate vertical wind shear between 5 and 10 m s−1 calculated as 200–850-hPa shear. This study makes use of both infrared (IR; 11 μm) and water vapor (WV; 6.5 μm) geostationary satellite data, the Statistical Hurricane Prediction Intensity System (SHIPS), and model reanalyses to highlight commonalities of the six TCs. The commonalities serve as predictive guides for forecasters and common features that can be used to constrain and verify idealized modeling studies. Each of the TCs exhibits a convective cloud structure that is identified as a tilt-modulated convective asymmetry (TCA). These TCAs share similar shapes, upshear-relative positions, and IR cloud-top temperatures (below −70°C). They pulse over the core of the TC with a periodicity of between 4 and 8 h. Using WV satellite imagery, two additional features identified are asymmetric warming/drying upshear of the TC relative to downshear, as well as radially thin arc-shaped clouds on the upshear side. The WV brightness temperatures of these arcs are between −40° and −60°C. All of the TCs are sheared by upper-level anticyclones, which limits the strongest environmental winds to near the tropopause.
Ensheathing cells utilize dynamic tiling of neuronal somas in development and injury as early as neuronal differentiation
Authors: Nichols Ev L. , Green Lauren A. , Smith Cody J. 
Published: August 2018

Abstract
Background
Glial cell ensheathment of specific components of neuronal circuits is essential for nervous system function. Although ensheathment of axonal segments of differentiated neurons has been investigated, ensheathment of neuronal cell somas, especially during early development when neurons are extending processes and progenitor populations are expanding, is still largely unknown.

Methods
To address this, we used time-lapse imaging in zebrafish during the initial formation of the dorsal root ganglia (DRG).

Results
Our results show that DRG neurons are ensheathed throughout their entire lifespan by a progenitor population. These ensheathing cells dynamically remodel during development to ensure axons can extend away from the neuronal cell soma into the CNS and out to the skin. As a population, ensheathing cells tile each DRG neuron to ensure neurons are tightly encased. In development and in experimental cell ablation paradigms, the oval shape of DRG neurons dynamically changes during partial unensheathment. During longer extended unensheathment neuronal soma shifting is observed. We further show the intimate relationship of these ensheathing cells with the neurons leads to immediate and choreographed responses to distal axonal damage to the neuron.

Conclusion
We propose that the ensheathing cells dynamically contribute to the shape and position of neurons in the DRG by their remodeling activity during development and are primed to dynamically respond to injury of the neuron.
Documenting Goals of Care Among Patients With Advanced Cancer: Results of a Quality Improvement Initiative
Authors: Karim Safiya , Harle Ingrid , O’Donnell Jennifer , Li Shirley , Booth Christopher M. 
Published: August 2018

Purpose: Guidelines recommend that oncologists discuss goals of care (GOC) with patients who have advanced cancer and that these patients be referred for early palliative care (PC). An audit of practice between 2010 and 2015 at the Cancer Centre of Southeastern Ontario suggested that these rates were suboptimal. We sought to improve the rate of documentation of GOC and referral to PC through the implementation of a quality improvement (QI) initiative. Methods: Patients receiving palliative systemic treatment of lung, pancreatic, colorectal, and breast cancer were identified via electronic pharmacy records and the electronic patient care system. Using the Define, Measure, Analyze, Improve, Control QI methodology, we drafted a guideline for GOC documentation and PC referral and designed a standardized documentation system. E-mail reminders were sent to physicians and a QI scorecard was displayed to document overall and individual physician rates of GOC documentation. Data were analyzed monthly and presented on statistical process control P charts. Results: Between May 2016 and November 2017, a total of 303 unique patients were identified (52%, 21%, 17%, and 10% with lung, breast, colorectal, and pancreatic cancer, respectively). GOC documentation increased significantly over the study period (baseline, 0%; passive phase, 3%; active phase, 31%); this increase was likely because of our intervention. PC referral rates also increased over the study period (baseline, 36%; passive phase, 35%; active phase 48%). We did not identify any patient, physician, or disease factors that were associated with GOC discussion or referral to PC. Conclusion: Our QI initiative was successful in improving rates of GOC documentation in patients with advanced cancer.
Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium
Authors: Carlo Maria I. , Giri Veda N. , Paller Channing J. , Abida Wassim , Alumkal Joshi J. , Beer Tomasz M. , Beltran Himisha , George Daniel J. , Heath Elisabeth I. , Higano Celestia S. , McKay Rana R. , Morgans Alicia K. , Patnaik Akash , Ryan Charles J. , Schaeffer Edward M. , Stadler Walter M. , Taplin Mary-Ellen , Kauff Noah D. , Vinson Jacob , Antonarakis Emmanuel S. , Cheng Heather H. 
Published: August 2018

Purpose Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials. Methods The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research. Results Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies. Conclusion As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease.