bluuebunny/crossref_metadata_2025_split huggingface dataset:
New solitary waves for the Klein–Gordon–Zakharov equations
Authors: Nestor Savaissou , Houwe Alphonse , Rezazadeh Hadi , Bekir Ahmet , Betchewe Gambo , Doka Serge Y. 
Published: April 2020

This paper studies new solitary waves for the Klein–Gordon–Zakharov equations. The obtained results are diverse and some specific ones emerge as dark, bright and bell-shape. The two integration schemes lead to obtaining waves which propagate without deformation as illustrated in graphical representations. Our obtained results are more specific compared to those obtained by Refs. 8 and 31 [C. H. Zhao and Z. M. Sheng, Acta Phys. Sin. 53 (2004) 29; S. Yakada, B. Depelair, G. Betchewe and S. Y. Doka, Optik 197 (2019) 163108].
Petrogenesis of Siluro-Devonian rhyolites of the Tobique Group in the northwestern Appalachians (northern New Brunswick, Canada): tectonic implications for the accretion history of peri-Gondwanan terranes along the Laurentian margin
Authors: Dostal Jaroslav , Wilson Reginald A. , Jutras Pierre 
Published: April 2020

Abstract

Uppermost Silurian–Lower Devonian felsic rocks in the bimodal volcanic suite of the Tobique Group in the northwestern mainland Appalachians (northern New Brunswick, Canada) form part of an overstep sequence deposited across the accreted vestiges of Iapetus Ocean on composite Laurentia. Whereas the mafic rocks of the bimodal volcanic suite are continental tholeiites, the felsic rocks are peraluminous and possess geochemical characteristics of A2-type granites emplaced in post-collisional extensional settings. The major and trace element compositions of the felsic rocks indicate that they were generated by dehydration melting of late Precambrian granitoid rocks triggered by heat derived from the rising mafic magma. Unlike the basalts, which have positive
ε
Nd
(
t
) values, the felsic rocks have values close to chondrites (−1.6 to +1.1), which is consistent with derivation from a crustal source. The rapid transition from compressional to extensional magmatism in latest Silurian–Early Devonian times in this part of Ganderia is probably due to Late Silurian Ganderia–Laurentia collision followed by slab breakoff. Based on Sm–Nd isotopic characteristics in their respective igneous rocks, both Ganderia and Avalonia are underlain by similar Neoproterozoic lower–middle crust and subcontinental lithospheric mantle.
Microtubule Engagement with Taxane Is Altered in Taxane-Resistant Gastric Cancer
Authors: Galletti Giuseppe , Zhang Chao , Gjyrezi Ada , Cleveland Kyle , Zhang Jiaren , Powell Sarah , Thakkar Prashant V. , Betel Doron , Shah Manish A. , Giannakakou Paraskevi 
Published: April 2020

Abstract

Purpose:
Although taxane-based therapy is standard treatment for advanced gastric cancer, a majority of patients exhibit intrinsic resistance to taxanes. Here, we aim to identify the molecular basis of taxane resistance in gastric cancer.

Experimental Design:
We performed a post hoc analysis of the TAX-325 clinical trial and molecular interrogation of gastric cancer cell lines to assess the benefit of docetaxel in diffuse (DIF-GC) versus intestinal (INT-GC) gastric cancer. We assessed drug-induced microtubule stabilization in gastric cancer cells and in biopsies of patients with gastric cancer treated with taxanes. We performed transcriptome analysis in taxane-treated gastric cancer cells and patients to identify molecular drivers of taxane resistance.

Results:
Patients with DIF-GC did not derive a clinical benefit from taxane treatment suggesting intrinsic taxane resistance. DIF-GC cell lines displayed intrinsic resistance specific to taxanes because of impaired drug-induced microtubule stabilization, in the absence of tubulin mutations or decreased drug accumulation. Using taxane-treated gastric cancer patient biopsies, we demonstrated that absence of drug–target engagement was correlated with clinical taxane resistance. Taxane-sensitive cell lines displayed faster microtubule dynamics at baseline, implicating proteins that regulate cytoskeletal dynamics in intrinsic taxane resistance. Differential gene expression analysis of untreated and docetaxel-treated gastric cancer lines and patient samples identified kinesins to be associated with taxane sensitivity in vitro and in patient samples.

Conclusions:
Our data reveal that taxane resistance is more prevalent in patients with DIF-GC, support assessment of drug–target engagement as an early read-out of taxane clinical efficacy, and encourage the investigation of kinesins and other microtubule-associated proteins as potentially targetable mediators of taxane resistance in gastric cancer.
Safety, Efficacy, and Biomarker Analysis of Toripalimab in Previously Treated Advanced Melanoma: Results of the POLARIS-01 Multicenter Phase II Trial
Authors: Tang Bixia , Chi Zhihong , Chen Yingbo , Liu Xiufeng , Wu Di , Chen Jing , Song Xin , Wang Weifeng , Dong Lihou , Song Haifeng , Wu Hai , Feng Hui , Yao Sheng , Qin Shuikui , Zhang Xiaoshi , Guo Jun 
Published: April 2020

Abstract

Purpose:
In contrast to the predominant chronic UV exposure–induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China.

Patients and Methods:
This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate.

Results:
128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months [95% confidence interval (CI) 2.7–5.3] and median overall survival was 22.2 months (95% CI, 15.3–NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%, P = 0.0065), PFS (7.7 months vs. 2.7 months, P = 0.013), and OS (not reached vs. 14.4 months, P = 0.0005) than PD-L1–negative patients.

Conclusions:
This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy.
See related commentary by Shoushtari et al., p. 4171
AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells
Authors: Hampsch Riley A. , Wells Jason D. , Traphagen Nicole A. , McCleery Charlotte F. , Fields Jennifer L. , Shee Kevin , Dillon Lloye M. , Pooler Darcy B. , Lewis Lionel D. , Demidenko Eugene , Huang Yina H. , Marotti Jonathan D. , Goen Abigail E. , Kinlaw William B. , Miller Todd W. 
Published: April 2020

Abstract

Purpose:
Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies.

Experimental Design:
Mimicking the aromatase inhibitor–induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER+ breast cancer induced by estrogen withdrawal in mice. We analyzed tumor xenografts and cultured cancer cells for molecular and cellular responses to estrogen withdrawal and drug treatments. Publicly available clinical breast tumor gene expression datasets were analyzed for responses to neoadjuvant endocrine therapy.

Results:
Dormant breast cancer cells exhibited upregulated 5′ adenosine monophosphate-activated protein kinase (AMPK) levels and activity, and upregulated fatty acid oxidation. While the antidiabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation. Pharmacologic or genetic inhibition of AMPK or fatty acid oxidation promoted clearance of dormant residual disease, while dietary fat increased tumor cell survival.

Conclusions:
AMPK has context-dependent effects in cancer, cautioning against the widespread use of an AMPK activator across disease settings. The development of therapeutics targeting fat metabolism is warranted in ER+ breast cancer.
Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes Mellitus
Authors: Hoyer Friedrich Felix , Zhang Xinyi , Coppin Emilie , Vasamsetti Sathish Babu , Modugu Ganesh , Schloss Maximilian J. , Rohde David , McAlpine Cameron S. , Iwamoto Yoshiko , Libby Peter , Naxerova Kamila , Swirski Filip K. , Dutta Partha , Nahrendorf Matthias 
Published: April 2020

Background:
Diabetes mellitus is a prevalent public health problem that affects about one-third of the US population and leads to serious vascular complications with increased risk for coronary artery disease. How bone marrow hematopoiesis contributes to diabetes mellitus complications is incompletely understood. We investigated the role of bone marrow endothelial cells in diabetic regulation of inflammatory myeloid cell production.

Methods:
In 3 types of mouse diabetes mellitus, including streptozotocin, high-fat diet, and genetic induction using leptin-receptor-deficient db/db mice, we assayed leukocytes, hematopoietic stem and progenitor cells (HSPC). In addition, we investigated bone marrow endothelial cells with flow cytometry and expression profiling.

Results:

In diabetes mellitus, we observed enhanced proliferation of HSPC leading to augmented circulating myeloid cell numbers. Analysis of bone marrow niche cells revealed that endothelial cells in diabetic mice expressed less
Cxcl12
, a retention factor promoting HSPC quiescence. Transcriptome-wide analysis of bone marrow endothelial cells demonstrated enrichment of genes involved in epithelial growth factor receptor (Egfr) signaling in mice with diet-induced diabetes mellitus. To explore whether endothelial Egfr plays a functional role in myelopoiesis, we generated mice with endothelial-specific deletion of Egfr (
Cdh5

Cre

Egfr

fl/fl

). We found enhanced HSPC proliferation and increased myeloid cell production in
Cdh5

Cre

Egfr

fl/fl

mice compared with wild-type mice with diabetes mellitus. Disrupted Egfr signaling in endothelial cells decreased their expression of the HSPC retention factor angiopoietin-1. We tested the functional relevance of these findings for wound healing and atherosclerosis, both implicated in complications of diabetes mellitus. Inflammatory myeloid cells accumulated more in skin wounds of diabetic
Cdh5

Cre

Egfr

fl/fl

mice, significantly delaying wound closure. Atherosclerosis was accelerated in
Cdh5

Cre

Egfr

fl/fl

mice, leading to larger and more inflamed atherosclerotic lesions in the aorta.

Conclusions:
In diabetes mellitus, bone marrow endothelial cells participate in the dysregulation of bone marrow hematopoiesis. Diabetes mellitus reduces endothelial production of Cxcl12, a quiescence-promoting niche factor that reduces stem cell proliferation. We describe a previously unknown counterregulatory pathway, in which protective endothelial Egfr signaling curbs HSPC proliferation and myeloid cell production.
Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease
Authors: Wada Hiromichi , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , Shimizu Masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Iguchi Moritake , Masunaga Nobutoyo , Ishii Mitsuru , Yamakage Hajime , Kusakabe Toru , Yasoda Akihiro , Shimatsu Akira , Kotani Kazuhiko , Satoh‐Asahara Noriko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji ,   ANOX Study Investigators
Published: April 2020

Background
VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients.

Methods and Results
We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old.

Conclusions
In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.
Speaking in the Brain: The Interaction between Words and Syntax in Sentence Production
Authors: Takashima Atsuko , Konopka Agnieszka , Meyer Antje , Hagoort Peter , Weber Kirsten 
Published: April 2020

Abstract
This neuroimaging study investigated the neural infrastructure of sentence-level language production. We compared brain activation patterns, as measured with BOLD-fMRI, during production of sentences that differed in verb argument structures (intransitives, transitives, ditransitives) and the lexical status of the verb (known verbs or pseudoverbs). The experiment consisted of 30 mini-blocks of six sentences each. Each mini-block started with an example for the type of sentence to be produced in that block. On each trial in the mini-blocks, participants were first given the (pseudo-)verb followed by three geometric shapes to serve as verb arguments in the sentences. Production of sentences with known verbs yielded greater activation compared to sentences with pseudoverbs in the core language network of the left inferior frontal gyrus, the left posterior middle temporal gyrus, and a more posterior middle temporal region extending into the angular gyrus, analogous to effects observed in language comprehension. Increasing the number of verb arguments led to greater activation in an overlapping left posterior middle temporal gyrus/angular gyrus area, particularly for known verbs, as well as in the bilateral precuneus. Thus, producing sentences with more complex structures using existing verbs leads to increased activation in the language network, suggesting some reliance on memory retrieval of stored lexical–syntactic information during sentence production. This study thus provides evidence from sentence-level language production in line with functional models of the language network that have so far been mainly based on single-word production, comprehension, and language processing in aphasia.
Preparatory Template Activation during Search for Alternating Targets
Authors: Grubert Anna , Eimer Martin 
Published: April 2020

AbstractVisual search is guided by representations of target-defining features (attentional templates). We tracked the time course of template activation processes during the preparation for search in a task where the identity of color-defined search targets switched across successive trials (ABAB). Task-irrelevant color probes that matched either the upcoming relevant target color or the previous now-irrelevant target color were presented every 200 msec during the interval between search displays. N2pc components (markers of attentional capture) were measured for both types of probes at each time point. A reliable probe N2pc indicates that the corresponding color template is active at the time when the probe appears. N2pcs of equal size emerged from 1000 msec before search display onset for both relevant-color and irrelevant-color probes, demonstrating that both color templates were activated concurrently. Evidence for color-selective attentional control was found only immediately before the arrival of the search display, where N2pcs were larger for relevant-color probes. These results reveal important limitations in the executive control of search preparation in tasks where two targets alternate across trials. Although the identity of the upcoming target is fully predictable, both task-relevant and task-irrelevant target templates are coactivated. Knowledge about target identity selectively biases these template activation processes in a temporally discrete fashion, guided by temporal expectations about when the target template will become relevant.
Politics, Experience, and the Languages of Holiness
Authors: Flood Gavin 
Published: April 2020

Abstract
During the last half century, the category of holiness fell into disrepair although there are recent signs of its revitalization with the Pope’s apostolic exhortation on holiness, Gaudete et Exultate and attention being paid to the category in political philosophy (the work of Agamben and Esposito) and sociology (the work of Hans Joas). In this context, this article argues for the philosophical justification of linking holiness with prepredicative experience as it shows itself through hermeneutical phenomenology, grounded in bio-sociology, but which cannot be isolated from the particular languages of its articulation. Holiness comes into view through the languages of holiness, which in the broadest sense, include human act, and comportment toward world. This involves a discussion about holiness itself being located either in prepolitical experience or being inseparable from political and legal discourse. Of relevance here is also a philosophical discussion of holiness in relation to metaphysical realism.
The Fraternité Notre Dame: From Emergence in Fréchou to Sojourn in Chicago
Authors: Zeller Benjamin E. 
Published: April 2020

Abstract
The Fraternité Notre Dame is a traditionalist Catholic Marian movement founded in 1977 by Bishop Jean Marie Kozik, né Roger Kozik. Kozik received monthly visions, primarily of the Virgin Mary, and established the Fraternité as a Marian devotional movement in Fréchou, southern France. This article analyzes and contextualizes the history of the Fraternité Notre Dame and its founder Bishop Jean Marie, showing how Jean Marie and his movement responded as religious entrepreneurs, innovating in response to the growing tension between the Fraternites and their religious-cultural context, which culminated in their choice to leave France and reestablish themselves in Chicago. The article analyzes the content of the visions, which both reflected this disconnect as well as spurred it onwards. The visions are contextualized within postconciliar Catholicism and the conservative backlash to the reforms of the Second Vatican Council, and reflect both a specific French Catholic context and a global apocalyptic vision of a threatened Catholic Church. Finally, the article considers the group’s institutionalization in Chicago as the culmination of the friction between the Fraternité Notre Dame and its cultural and religious origin in Catholic France.
Religion and Empire in Transnational Perspective: a Response to Pamela Klassen’s Story of Radio Mind and Jennifer Graber’s Gods of Indian Country
Authors: Johnson Sylvester A. 
Published: April 2020

Abstract
This article examines the parallels and contrasts between Pamela Klassen’s and Jennifer Graber’s recent studies of settler colonialism and Indigenous nations of North America. I identify major themes in their analysis and assess the import of their work for the greater understanding of religion, settler-states, and Indigeneity. I note especially the challenge they raise for scholars concerned with missionary friendship with Indians, as both authors complicate facile assumptions about this history.
Deprivation of Liberty in Care. An ECHR and CRPD Approach and its Consequences for Belgium
Authors: Opgenhaffen Tim 
Published: April 2020

Abstract
This contribution examines deprivation of liberty in Belgian healthcare within the frameworks of the ECHR and CRPD. We develop and apply an ECHR-based framework to demonstrate that it is not the admissions to care facilities based on Belgium’s involuntary commitment law that give rise to the unjustified deprivation of liberty, but those based on representation regimes. This can be remedied by broadening Belgium’s involuntary commitment law. However, doing so would go against a CRPD-based framework, which is incompatible with the ECHR; the former opposes disability-based laws. Building on the right to legal capacity and to liberty, the scope of the CRPD’s approach is uncovered. It is suggested that to reconcile the two frameworks, Belgium’s involuntary commitment law should be abolished, and representation regimes should be changed to avoid (rather than to justify) deprivation of liberty. Although its desirability is open for discussion, this could solve a problem that occurs worldwide.
Tornadoes in Northern Eurasia: From the Middle Age to the Information Era
Authors: Chernokulsky Alexander , Kurgansky Michael , Mokhov Igor , Shikhov Andrei , Azhigov Igor , Selezneva Evgeniya , Zakharchenko Denis , Antonescu Bogdan , Kühne Thilo 
Published: April 2020

AbstractThe last comprehensive statistics of tornadoes in northern Eurasia (NE) were published more than 30 years ago. This paper introduces a new database of tornadoes in NE that spans from the tenth century to 2016. The database, compiled using various sources, contains 2879 tornado cases over land and water and includes tornado characteristics. Tornadoes are common for most regions of NE, with a density reaching four cases per 104 km2 in 1900–2016 in some regions. Tornadoes over land have distinct annual and diurnal cycles: they form mostly in May–August, with a maximum in June, and during daytime, with a maximum at 1700–1800 local time. Waterspouts form in all months with a maximum in late summer and mostly at 0900–1300 local time. Most tornadoes are weak and short lived. The Fujita-scale intensity is ≤F1 for 80% and ≥F3 for 3% out of all rated tornadoes. Half last less than 10 min. The average annual number of all tornadoes over land is around 150, including 10 and 2 tornadoes with ≥F2 and ≥F3 intensity, respectively. Annually, 1–2 tornadoes lead to casualties and result in 2.9 fatalities and 36.3 injuries. Despite the incompleteness of the dataset, our results show that tornadoes in NE, although being rare, are not as extremely rare as has been thought before. The results illustrate the substantial underestimation of tornado threat by the general public, researchers, and meteorologists, and unambiguously indicate the need for systematic assessments and forecasting of tornadoes by national weather services.