bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chapter 7.5 Active subglacial volcanism in West Antarctica
Authors: Quartini Enrica , Blankenship Donald D. , Young Duncan A. 
Published: March 2021

Abstract
A combination of aerogeophysics, seismic observations and direct observation from ice cores, and subglacial sampling, has revealed at least 21 sites under the West Antarctic Ice Sheet consistent with active volcanism (where active is defined as volcanism that has interacted with the current manifestation of the West Antarctic Ice Sheet). Coverage of these datasets is heterogeneous, potentially biasing the apparent distribution of these features. Also, the products of volcanic activity under thinner ice characterized by relatively fast flow are more prone to erosion and removal by the ice sheet, and therefore potentially under-represented. Unsurprisingly, the sites of active subglacial volcanism that we have identified often overlap with areas of relatively thick ice and slow ice surface flow, both of which are critical conditions for the preservation of volcanic records. Overall, we find the majority of active subglacial volcanic sites in West Antarctica concentrate strongly along the crustal-thickness gradients bounding the central West Antarctic Rift System, complemented by intra-rift sites associated with the Amundsen Sea–Siple Coast lithospheric transition.
Stopping Power Modulation by Pump Waves of Charged Particles Moving above Two-Dimensional Electron Gases
Authors: Yang Yahong , Zhang Ya , Yi Lin , Jiang Wei 
Published: March 2021

The perturbation electron density and stopping power caused by the movement of charged particles above two-dimensional quantum electron gases (2DQEG) have been studied in numerous works using the quantum hydrodynamic (QHD) theory. In this paper, the QHD is modified by introducing the two-dimensional electron exchange-correlation potential at high density Vxc2DH and the pump wave modulations. Based on the modified QHD, the perturbation electron density and stopping power are calculated for pump waves with various parameters. The results show that the stopping power values are more accurate after considering Vxc2DH. Under the modulation of pump waves with the wavelength from 0.1nm to 0.1cm, the perturbation electron density of 2DQEG and the stopping power of charged particles show periodic changes. Under the modulation of pump waves with λ = 1.76 × 10−4 cm and Φ0=2×1010e/λf, the average stopping power with respect to the time phase θ becomes negative, which means that the charged particles will gain energy and can be accelerated. This is a new phenomenon in the fields of 2DQEG and of great significance in surface physics and surface modification in nanoelectronic devices with beam matter interactions.
Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas
Authors: Wu Jing , Yuan Ying , Long Priel Debra A. , Fink Danielle , Peer Cody J. , Sissung Tristan M. , Su Yu-Ting , Pang Ying , Yu Guangyang , Butler Madison K. , Mendoza Tito R. , Vera Elizabeth , Ahmad Salman , Bryla Christine , Lindsley Matthew , Grajkowska Ewa , Mentges Kelly , Boris Lisa , Antony Ramya , Garren Nancy , Siegel Christine , Lollo Nicole , Cordova Christine , Aboud Orwa , Theeler Brett J. , Burton Eric M. , Penas-Prado Marta , Leeper Heather , Gonzales Javier , Armstrong Terri S. , Calvo Katherine R. , Figg William D. , Kuhns Douglas B. , Gallin John I. , Gilbert Mark R. 
Published: March 2021

AbstractPurpose:To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma.Patients and Methods:This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden.Results:Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12–24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2_5347T&gt;C (rs2470890) polymorphism was associated with higher AUCinf value.Conclusions:Zotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib.
Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo
Authors: Iuliano Luca , Drioli Sara , Pignochino Ymera , Cafiero Claudia Maria , Minisini Martina , D'Este Francesca , Picco Raffaella , Dalla Emiliano , Giordano Giorgia , Grignani Giovanni , Di Giorgio Eros , Benedetti Fabio , Felluga Fulvia , Brancolini Claudio 
Published: March 2021

Abstract
Leiomyosarcomas are rare and aggressive tumors characterized by a complex karyotype. Surgical resection with or without radiotherapy and chemotherapy is the standard curative treatment. Unfortunately, a high percentage of leiomyosarcomas recurs and metastasizes. In these cases, doxorubicin and ifosfamide represent the standard treatment but with low response rates. Here, we evaluated the induction of proteotoxic stress as a possible strategy to kill leiomyosarcoma cells in a therapeutic perspective. We show that aggressive leiomyosarcomas coexist with high levels of proteotoxic stress. As a consequence, we hypothesized that leiomyosarcoma cells are vulnerable to further increases of proteotoxic stress. The small compound 2c is a strong inducer of proteotoxic stress. In leiomyosarcoma cells, it triggers cell death coupled to a profound reorganization of the mitochondrial network. By using stimulated emission depletion microscopy, we have unveiled the existence of DIABLO/SMAC clusters that are modulated by 2c. Finally, we have engineered a new version of 2c linked to polyethylene glycol though a short peptide, named 2cPP. This new prodrug is specifically activated by proteases present in the tumor microenvironment. 2cPP shows a strong antitumor activity in vivo against leiomyosarcomas and no toxicity against normal cells.
In Vivo Efficacy of Tesevatinib in EGFR-Amplified Patient-Derived Xenograft Glioblastoma Models May Be Limited by Tissue Binding and Compensatory Signaling
Authors: Kizilbash Sani H. , Gupta Shiv K. , Parrish Karen E. , Laramy Janice K. , Kim Minjee , Gampa Gautham , Carlson Brett L. , Bakken Katrina K. , Mladek Ann C. , Schroeder Mark A. , Decker Paul A. , Elmquist William F. , Sarkaria Jann N. 
Published: March 2021

Abstract
Tesevatinib is a potent oral brain penetrant EGFR inhibitor currently being evaluated for glioblastoma therapy. Tesevatinib distribution was assessed in wild-type (WT) and Mdr1a/b(-/-)Bcrp(-/-) triple knockout (TKO) FVB mice after dosing orally or via osmotic minipump; drug–tissue binding was assessed by rapid equilibrium dialysis. Two hours after tesevatinib dosing, brain concentrations in WT and TKO mice were 0.72 and 10.03 μg/g, respectively. Brain-to-plasma ratios (Kp) were 0.53 and 5.73, respectively. With intraperitoneal infusion, brain concentrations were 1.46 and 30.6 μg/g (Kp 1.16 and 25.10), respectively. The brain-to-plasma unbound drug concentration ratios were substantially lower (WT mice, 0.03–0.08; TKO mice, 0.40–1.75). Unbound drug concentrations in brains of WT mice were 0.78 to 1.59 ng/g. In vitro cytotoxicity and EGFR pathway signaling were evaluated using EGFR-amplified patient-derived glioblastoma xenograft models (GBM12, GBM6). In vivo pharmacodynamics and efficacy were assessed using athymic nude mice bearing either intracranial or flank tumors treated by oral gavage. Tesevatinib potently reduced cell viability [IC50 GBM12 = 11 nmol/L (5.5 ng/mL), GBM6 = 102 nmol/L] and suppressed EGFR signaling in vitro. However, tesevatinib efficacy compared with vehicle in intracranial (GBM12, median survival: 23 vs. 18 days, P = 0.003) and flank models (GBM12, median time to outcome: 41 vs. 33 days, P = 0.007; GBM6, 44 vs. 33 days, P = 0.007) was modest and associated with partial inhibition of EGFR signaling. Overall, tesevatinib efficacy in EGFR-amplified PDX GBM models is robust in vitro but relatively modest in vivo, despite a high brain-to-plasma ratio. This discrepancy may be explained by drug-tissue binding and compensatory signaling.
RNA-Binding Protein Polymorphisms as Novel Biomarkers to Predict Outcomes of Metastatic Colorectal Cancer: A Meta-analysis from TRIBE, FIRE-3, and MAVERICC
Authors: Arai Hiroyuki , Cao Shu , Battaglin Francesca , Wang Jingyuan , Kawanishi Natsuko , Tokunaga Ryuma , Loupakis Fotios , Stintzing Sebastian , Soni Shivani , Zhang Wu , Mancao Christoph , Salhia Bodour , Mumenthaler Shannon M. , Cremolini Chiara , Heinemann Volker , Falcone Alfredo , Millstein Joshua , Lenz Heinz-Josef 
Published: March 2021

Abstract
RNA-binding proteins (RBPs) regulate many posttranscriptional cellular activities. Accumulating evidence suggests associations between RBPs with colonic tumorigenesis and chemosensitivity. We investigated the prognostic and predictive values of SNPs of genes encoding RBPs in metastatic colorectal cancer (mCRC), using clinical and genomic data from three randomized clinical trials of standard first-line chemotherapy for mCRC (TRIBE, FIRE-3, and MAVERICC). Genomic DNA extracted from blood samples was genotyped using an OncoArray. We tested 30 candidate SNPs of 10 major RBP-related genes with additive models. Prognostic values were estimated by meta-analysis approach. Treatment-by-SNP interactions were tested to estimate predictive values for targeted drugs and cytotoxic backbone chemotherapies. This study included 884 patients. The meta-analysis revealed prognostic values of LIN28B rs314277 [HR, 1.26; 95% confidence interval (CI), 1.06–1.49, P = 0.005, FDR-adjusted P = 0.072 for overall survival (OS)] and LIN28B rs314276 (HR, 1.25; 95% CI, 1.08–1.44, P = 0.002, FDR-adjusted P = 0.062 for OS). Although some SNPs showed potentially predictive values, these associations were not confirmed after FDR adjustment. In conclusion, the results of this study are warranting additional studies to provide the evidence that RBP-related SNPs may be associated with the prognosis of patients with mCRC treated with standard first-line chemotherapies. In addition, further studies are warranted to study the predictive value.
Macrophage Activation Status Rather than Repolarization Is Associated with Enhanced Checkpoint Activity in Combination with PI3Kγ Inhibition
Authors: Carnevalli Larissa S. , Taylor Molly A. , King Matthew , Coenen-Stass Anna M.L. , Hughes Adina M. , Bell Sigourney , Proia Theresa A. , Wang Yanjun , Ramos-Montoya Antonio , Wali Neha , Carroll Danielle , Singh Maneesh , Moschetta Michele , Gutierrez Pablo Morentin , Gardelli Cristina , Critchlow Susan E. , Klinowska Teresa , Fawell Stephen E. , Barry Simon T. 
Published: March 2021

Abstract
Suppressive myeloid cells mediate resistance to immune checkpoint blockade. PI3Kγ inhibition can target suppressive macrophages, and enhance efficacy of immune checkpoint inhibitors. However, how PI3Kγ inhibitors function in different tumor microenvironments (TME) to activate specific immune cells is underexplored. The effect of the novel PI3Kγ inhibitor AZD3458 was assessed in preclinical models. AZD3458 enhanced antitumor activity of immune checkpoint inhibitors in 4T1, CT26, and MC38 syngeneic models, increasing CD8+ T-cell activation status. Immune and TME biomarker analysis of MC38 tumors revealed that AZD3458 monotherapy or combination treatment did not repolarize the phenotype of tumor-associated macrophage cells but induced gene signatures associated with LPS and type II INF activation. The activation biomarkers were present across tumor macrophages that appear phenotypically heterogenous. AZD3458 alone or in combination with PD-1–blocking antibodies promoted an increase in antigen-presenting (MHCII+) and cytotoxic (iNOS+)-activated macrophages, as well as dendritic cell activation. AZD3458 reduced IL-10 secretion and signaling in primary human macrophages and murine tumor-associated macrophages, but did not strongly regulate IL-12 as observed in other studies. Therefore, rather than polarizing tumor macrophages, PI3Kγ inhibition with AZD3458 promotes a cytotoxic switch of macrophages into antigen-presenting activated macrophages, resulting in CD8 T-cell–mediated antitumor activity with immune checkpoint inhibitors associated with tumor and peripheral immune activation.
Anti-Epidemic Emergency Regimes under Polish Law in Comparative, Historical and Jurisprudential Perspective
Authors: Bosek Leszek 
Published: March 2021

Abstract
The SARS-CoV-2 crisis of 2020 triggered a number of unprecedented reactions of European states, in particular in the form of either constitutional emergency measures or statutory anti-epidemic emergency measures. Poland chose to deal with the crisis by delegating powers to the executive by ordinary legislative means and declared a nationwide state of epidemic emergency on 13 March 2020 and a week later a state of epidemic on the basis of the Act of 5 December 2008 on preventing and combating infections and infectious diseases. For a century, Poland has been dealing with epidemics by delegating powers to the executive by ordinary legislative means. Anti-epidemic emergency measures were developed under the relevant acts of 1919, 1935, 1963, 2001, 2008 and now form an autonomous normative model authorised directly by Article 68 (4) of the Constitution of the Republic of Poland of 2 April 1997. The Constitution of 2 April 1997 authorises also extraordinary measures in situations of particular danger, “if ordinary constitutional measures are inadequate”. This article analyses anti-epidemic emergency regimes under Polish law in a comparative, historical and jurisprudential perspective.
Medieval Translation in the Light of the Polysystem and Rewriting Theories
Authors: Doborjginidze Nino , Mataradze Nino , Tatishvili Elene 
Published: March 2021

Abstract
This paper examines through the lens of translation studies (TS) the pattern of sociocultural and linguistic evolution to which medieval vernaculars of the Christian East adhered. It aims to contribute to discussions in medieval studies and TS with regard to vernacular translations. The medieval Georgian tradition of translation is examined from the perspective of descriptivist translation theories, namely, in the light of Even-Zohar’s polysystem and Lefevere’s rewriting theories. The Georgian literary polysystem is viewed as part of a larger mega-polysystem of the Christian East, with Greek being at its centre. This explains parallels in the emancipation of vernacular languages. From the viewpoint of the rewriting theory, emphasis is given to the roles of professional circles, patronage and dominant poetics. The evolution of the Georgian translation tradition from free rendering to a higher concern for precision reflects the impact of different sociocultural factors, evidencing the validity of the mentioned descriptivist models.
The Old Testament in the First Discourse on Martyrs
Authors: Francisco Hector Ricardo 
Published: March 2021

Abstract
The aim of this paper is to analyze the use of Biblical Testimonia in the First Discourse of the Holy Martyrs of the Land of Orient (BHO 706). It will be argued that the main purpose of the author was not only to promote the cult of their relics but also to demonstrate that the persecution was part of God’s plan for the Church. As long as Christ, the Apostles and the Prophets were Models for those suffering persecution, the Biblical text was the testimony of the truth of Christian Martyrdom. Moreover, by stressing the continuity between the Heroes of both Testaments and the Martyrs, the author was engaged in a controversy against Marcionism.
Social Media Representations of the Pilgrimage to Mecca
Authors: Al-Ajarma Kholoud , Buitelaar Marjo 
Published: March 2021

Abstract
In this article, we compare representations of the pilgrimage to Mecca posted on Facebook and Youtube by ‘ordinary’ pilgrims from Morocco and (semi)professional bloggers of Moroccan parentage in the Netherlands. We discuss how such posts challenge representations that circulate in the mainstream media in both countries about Islam in general and the hajj in particular. For Morocco we demonstrate that this kind of digital mediation of pilgrimage contests the ways in which the state-organized hajj is framed in Morocco’s national media. For the Netherlands, we argue that bloggers deconstruct dominant images of the Muslim ‘other’ in their self-presentations as specifically Dutch Muslim pilgrims by connecting the meanings they attribute to the pilgrimage to Mecca to universal issues.
An EnKF-based method to produce rainfall maps from simulated satellite-to-ground MW-link signal attenuation
Authors: Ortolani Alberto , Caparrini Francesca , Melani Samantha , Baldini Luca , Giannetti Filippo 
Published: March 2021

AbstractMeasuring rainfall is complex, due to the high temporal and spatial variability of precipitation, especially in a changing climate, but it is of great importance for all the scientific and operational disciplines dealing with rainfall effects on the environment, human activities, and economy.Microwave (MW) telecommunication links carry information on rainfall rates along their path, through signal attenuation caused by raindrops, and can become measurements of opportunity, offering inexpensive chances to augment information without deploying additional infrastructures, at the cost of some smart processing. Processing satellite telecom signals bring some specific complexities related to the effects of rainfall boundaries, melting layer, and non-weather attenuations, but with the potential to provide worldwide precipitation data with high temporal and spatial samplings. These measurements have to be processed according to the probabilistic nature of the information they carry. An EnKF-based (Ensemble Kalman Filter) method has been developed to dynamically retrieve rainfall fields in gridded domains, which manages such probabilistic information and exploits the high sampling rate of measurements. The paper presents the EnKF method with some representative tests from synthetic 3D experiments. Ancillary data are assumed as from worldwide-available operational meteorological satellites and models, for advection, initial and boundary conditions, rain height. The method reproduces rainfall structures and quantities in a correct way, and also manages possible link outages. It results computationally viable also for operational implementation and applicable to different link observation geometries and characteristics.
Short-term outcomes of Chinese transient ischaemic attack patients in an Emergency department in Hong Kong: Result of management with an agreed protocol with neurologists
Authors: Chiu Simon Lai Hong , Wong William Cheung Lun , Yu Ellen Lok Man 
Published: March 2021

Introduction: Emergency department management of transient ischaemic attack varies from admission for all to outpatient referral. We studied the short-term outcomes of transient ischaemic attack managed with an agreed protocol. Predictors of stroke can be different for Asians and non-Asians. ABCD2 as initial triage of transient ischaemic attack is debatable. The predictive ability of ABCD2 score was studied as well. Methods: This was a prospective observational study with consecutive subject recruitment in Emergency department. All transient ischaemic attacks were admitted, hard and e-records of Emergency department, transient ischaemic attack clinic, Medical and Neurosurgical department and general follow-ups in Hospital Authority hospitals were studied up to 1 year. Stroke-day was measured from symptom-onset to time-of-stroke. Results: In 18-month period, 124 patients were recruited. The median onset-to-door time was 3.5 h. All computed tomography brain positive findings, except one subdural haematoma, were ischaemic in origin. Six strokes, all disabling, recurred within 90 days, three on day 1–3, two died in 6 months. The stroke risks at 2, 7, 90 days and 1 year were 1.61%, 3.23%, 4.84% and 4.84%, respectively. No significant trend was observed in stroke risk across ABCD2 scores ( p = 0.783) with area under the curve of 0.537 (95% confidence interval = 0.380–0.694; p = 0.762). The short-term stroke risk was associated with atrial fibrillation ( p = 0.002). The median Emergency Medicine ward length of stay was 1.33 days. Conclusion: In our Emergency department–based management, the short-term stroke risk of transient ischaemic attack is low, and the predictivity of ABCD2 score in risk stratification cannot be validated. Stroke recurrences were associated with atrial fibrillation. A low ABCD2 could be falsely reassuring. As half of the strokes recurred very early, we recommend admission in the hyperacute phase.
The crowding-out effect of elderly support expenditure on household consumption from the perspective of population aging: evidence from China
Authors: Huo Congjia , Xiao Guoan , Chen Lingming 
Published: March 2021

AbstractThe pace of aging in China is accelerating, from the introduction of family planning to the liberalization of the two-child policy, with a growing proportion of families in the 4–2-1 structure. With filial piety in mind, most adult children will live with their elderly parents and share income and expenditure. Concurrently, due to the inadequacy of the social security system, a heavy supplementary burden of supporting the elderly has been placed on adult children. Based on data from the 2011, 2013, 2015, and 2017 Chinese Social Survey (CSS) of the Chinese Academy of Social Sciences (CASS), this study analyzes the objective factors affecting household elderly support expenditure using the ordinary least squares (OLS) estimation method. It also examines the crowding-out effect of elderly support expenditure on the consumption of different types of households through a panel generalized method of moments (GMM) approach. Finally, the crowding-out effect of elderly support expenditure is discussed in a sub-sample according to the number of households needing to support the elderly aged 60 and above. The empirical results illustrate that there is a crowding-out effect of elderly support expenditure on household consumption, and the magnitude of the crowding-out effect varies for diverse consumption. Our study reveals that the crowding-out effect of elderly support expenditure on core consumption is the largest in a sample with different numbers of elderly persons in families. The empirical results for the sub-sample show that the larger the elderly population, the stronger the crowding-out effect of elderly support expenditure on core consumption and the less pronounced the effect on marginal consumption.