bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting fibroblast growth factor receptors to combat aggressive ependymoma
Authors: Lötsch Daniela , Kirchhofer Dominik , Englinger Bernhard , Jiang Li , Okonechnikov Konstantin , Senfter Daniel , Laemmerer Anna , Gabler Lisa , Pirker Christine , Donson Andrew M. , Bannauer Peter , Korbel Pia , Jaunecker Carola N. , Hübner Jens-Martin , Mayr Lisa , Madlener Sibylle , Schmook Maria T. , Ricken Gerda , Maaß Kendra , Grusch Michael , Holzmann Klaus , Grasl-Kraupp Bettina , Spiegl-Kreinecker Sabine , Hsu Jennifer , Dorfer Christian , Rössler Karl , Azizi Amedeo A. , Foreman Nicholas K. , Peyrl Andreas , Haberler Christine , Czech Thomas , Slavc Irene , Filbin Mariella G. , Pajtler Kristian W. , Kool Marcel , Berger Walter , Gojo Johannes 
Published: May 2021

AbstractEpendymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.
The coracoscapular joint of neornithine birds—extensive homoplasy in a widely neglected articular surface of the avian pectoral girdle and its possible functional correlates
Authors: Mayr Gerald 
Published: May 2021

AbstractA survey is given of the morphological variation of the coracoscapular joint of neornithine birds. In Mesozoic stem group representatives, the coracoid exhibits a deeply concave cotyla scapularis, which articulates with a globose tuberculum coracoideum of the scapula. This morphology is likely to be functionally related to the development of a powerful supracoracoideus muscle and the formation of a triosseal canal as a pulley for the tendon of this muscle. In neornithine birds, the coracoid articulates with the scapula either via a concave cotyla or a flat facies articularis, with the latter largely restricting movements of the coracoid to the paramedian plane. Ancestral state reconstruction suggests that a cotyla scapularis is plesiomorphic for Neornithes and that a flat facies articularis scapularis evolved at least 13 times independently within the clade. For several lineages, the transition to a flat facies articularis scapularis can be traced in the fossil record, and the replacement of a cup-shaped cotyla by a flat articular facet seems to have been due to various functional demands. Often, a flat facies articularis scapularis is associated with reduced shafts of the furcula. A weakly developed furcula enables transverse movements of the coracoid and therefore enables a restriction of the mobility of the coracoscapular joint to the paramedian plane. In taxa with a large crop, a flat facies articularis scapularis is likely to be associated with a reorganization of the pectoral musculature, whereas in procellariiform birds, the transition from a cotyla to a facies articularis appears to have been correlated with the capacity for sustained soaring without wing flapping.
Feasibility of sentinel node navigated surgery in high-risk T1b esophageal adenocarcinoma patients using a hybrid tracer of technetium-99 m and indocyanine green
Authors: Overwater Anouk , Weusten Bas L. A. M. , Ruurda Jelle P. , van Hillegersberg Richard , Bennink Roel J. , de Keizer Bart , Meijer Sybren L. , Brosens Lodewijk A. A. , Pouw Roos E. , Bergman Jacques J. G. H. M. , van Berge Henegouwen Mark I. , Gisbertz Suzanne S. 
Published: May 2021

Abstract
Background
Minimally invasive esophagectomy with two-field lymphadenectomy is standard of care for T1b esophageal adenocarcinoma (EAC) with a high risk of lymph node metastasis. Sentinel node navigation surgery (SNNS) is a well-known concept to tailor the extent of lymphadenectomy. The aim of this study was to evaluate the feasibility and safety of SNNS with a hybrid tracer (technetium-99 m/indocyanine green/nanocolloid) for patients with high-risk T1b EAC.

Methods
In this prospective, multicenter pilot study, 5 patients with high-risk T1b EAC were included. The tracer was injected endoscopically around the endoscopic resection scar the day before surgery, followed by preoperative imaging (lymphoscintigraphy/SPECT-CT). During surgery, first the SNs were localized and resected based on preoperative imaging and intraoperative gammaprobe- and fluorescence-based detection, followed by esophagectomy. Primary endpoints were the percentage of patients with detectable SNs, concordance between preoperative and intraoperative SN detection, and the additive value of indocyanine green.

Results
SNs could be identified and resected in all patients (median 3 SNs per patient, range 2–7). There was a high concordance between preoperative and intraoperative SN detection. In 2 patients additional peritumoral SNs were identified with fluorescence-based detection. None of the resected lymph nodes showed signs of (micro)metastases and no nodal metastases were detected in the surgical resection specimen.

Conclusions
SNNS using technetium-99 m/indocyanine green/nanocolloid seems feasible and safe in patients with high-risk T1b EAC. Indocyanine green fluorescence seems to be of additive value for detection of peritumoral SNs. Whether this approach can optimize selection for esophagectomy needs to be studied in future research.
Mathematical modeling of the magnetoelectric effect of the nano bi-layer L-T mode bar structure in high frequency regime
Authors: Saengow Treetep , Choowitsakunlert Salinee , Silapunt Rardchawadee 
Published: May 2021

AbstractThis paper describes the magnetoelectric (ME) coupling behavior of the nano bi-layer L-T (longitudinal-transverse) mode bar structure through the ME coefficient mathematical model that is developed in high frequency regime. Terfenol-D and Lead Zirconate Titanate (PZT) are used as ferromagnetic (FM) and ferroelectric (FE) layers, respectively. The ME coefficients are determined at different layer thickness ratios and products of the operating frequency (f) and structure length (l). It is found that the ME coefficient and optimal thickness ratio increases and decreases exponentially respectively, with fl. The minimum and maximum peak ME coefficients at fl values of 0.1 and 1,200 respectively, are around 1,756 and 5,617 mV/Oe$$\cdot $$
·
cm with the optimal thickness ratio of 0.43 and 0.19, respectively. The ME coupling behavior depends largely on the magnetostrictive effect in the FM layer that is altered by the applied magnetic field and fl. The demonstration as the read sensor for the hard disk drive (HDD) with 2 Tbit/in2 areal density and 190 Oe/bit applied magnetic field shows the output voltage across the FE layer of around 0.43 mV, which is more than sufficient for the raw signal readback.
Pullout tests on the connection to an existing foundation of a steel warehouse rebuilt after the 2012 Emilia (Italy) earthquakes
Authors: Minghini Fabio , Lippi Francesco , Tullini Nerio , Salvatore Walter 
Published: May 2021

AbstractThe tests described in this paper were aimed at evaluating the tensile capacity of the anchorages connecting an automated pallet warehouse with an existing RC foundation. The warehouse is a new steel structure erected in the place of a previous warehouse collapsed due to the Emilia earthquake, but whose foundation remained undamaged. The investigated fastening consists of 10 post-installed, bonded threaded rods with diameter (d) and embedment depth (hef) of 20 and 500 mm, respectively. Neither anchor arrangement nor embedment depth (hef > 20d) was covered by current standards for fastening design. To reproduce thein-situactual conditions of the fastening, an unconfined test configuration was used. The maximum loads achieved were more than 3 times greater than the seismic demand for the fastening. The tests highlighted the crucial role played by the reinforcing steel which was present in the foundation. Concrete-related failure mechanisms, such as the combined pullout and concrete cone failure mechanism typical of bonded anchors, were not activated. The observed crack patterns rather suggest the onset of a flexural failure mechanism of the concrete slab. This feature is confirmed by analytical calculations showing that, at the maximum loads achieved in the tests, the top reinforcement was likely to be yielded. In six preliminary unconfined tension tests on single anchors, steel rod failure was achieved, associated with limited cracking of the concrete surface in proximity of the anchor.
The impact of economic complexity on embodied carbon emission in trade: new empirical evidence from cross-country panel data
Authors: Qayyum Muhammad , Yu Yuyuan , Li Shijie 
Published: May 2021

AbstractEstablishing a fair platform for allocating carbon emission responsibility worldwide determines the sustainability and efficiency of the world’s climate policy and framework. In the context of global environmental load displacement and CO2 transfer, this paper endeavors to examine the relationship between economic complexity and embodied carbon emissions based on cross-country panel data. Our study utilizes the generalized method of moments (GMM) approach to estimate our dynamic models covering 34 OECD countries and 24 non-OECD countries from 1995 to 2015. The empirical results show a heterogeneous impact of economic complexity on embodied carbon emissions in exports (EEE) and imports (EEI). Besides, the scale effect, composition effect, and technology effect are also significant drivers of embodied carbon emissions. The improvement of economic complexity can decrease the marginal effects of export scale and export structure on foreign EEE (but not domestic EEE) significantly, while the marginal positive impacts of technology on EEE can be further enhanced by economic complexity growth. Moreover, there is no strong evidence to prove the significant indirect impacts of economic complexity on foreign carbon emission embodied in imports, while economic complexity has significantly positive indirect impacts on domestic carbon emission embodied in imports only through import scale. In the subsample regressions, we found asymmetric impacts of economic complexity between high-income countries and low- and middle-income countries.
Evaluation of somatic embryo production during embryogenic tissue proliferation stage using morphology, maternal genotype, proliferation rate and tissue age of Pinus thunbergii Parl
Authors: Sun Tingyu , Wang Yanli , Zhu Lihua , Liu Xiaowei , Wang Qingtong , Ye Jianren 
Published: May 2021

AbstractTo determine the optimal embryogenic capacity (somatic embryo production) of the selected elite nematode-resistant genotypes of Pinus thunbergii, variables such as embryogenic tissue (ET) morphology, maternal genotype, proliferation rate and tissue age were analyzed. ET morphology and histological evaluation of the proliferation stage showed a decrease in filamentous clump and protuberant surfaces and a decline in the acetocarmine-staining area, which indicates a decrease in somatic embryo production (SEP). Variations in cell physiology during the proliferation stage showed that SEP was positively correlated with soluble sugars and proteins, but negatively correlated with starch, peroxidase, and superoxidase. In addition, SEP was significantly (p < 0.001) affected by maternal genotype, tissue age and proliferation rate. Moreover, SEP was positively correlated with proliferation rate (r = 0.98, p < 0.001), but negatively correlated with tissue age (r =  − 0.95, p < 0.001). In general, the results suggest that SEP could be assessed in ET proliferation stages by the apparent cell morphology, histology, proliferation rate and tissue age, which provides novel insights for evaluating the ET maturation capacity (number of somatic embryos) during the proliferation stage of P. thunbergii somatic embryogenesis.
Effects of grazing disturbance of spatial distribution pattern and interspecies relationship of two desert shrubs
Authors: Zhang Lei , Gao Yong , Li Jinrong , Zhang Chao , Li Minyu , Hu Zhao , Cui Xiangxin 
Published: May 2021

AbstractGrazing significantly affects the distribution, growth, and productivity of shrubs. In this study, we evaluated the effects of grazing disturbance on the spatial distribution patterns and interspecific relationships of two desert shrubs, Ammopiptanthus mongolicus and Sarcozygium xanthoxylon. Three types of grazing conditions were considered, including enclosed area (EA), seasonal rotational grazing area (SRGA), and grazing area (GA) (100 m × 100 m), in the West Ordos Nature Reserve of Inner Mongolia, China. The results showed that A. mongolicus and S. xanthoxylon populations were uniformly distributed at a small scale, and the distribution in EA and SRGA became gradually random. In GA, A. mongolicus population showed aggregated distribution but S. xanthoxylon population showed random distribution at a small scale. Moreover, both A. mongolicus and S. xanthoxylon populations at the 5–7 m scale showed random distribution. At the small and intermediate scales, the two species showed positive interspecific relationships of GA. However, no interspecific relationship was noted between the two species in EA and SRGA. A significant positive relationship (P < 0.01) was noted between the two species at 2–9 m and a negative relationship (P < 0.01) at 13–17 m scales in GA. Positive relationship (P < 0.01) was noted between the two species at 6–13 m scales and a significant negative relationship (P < 0.01) at 14–24 m scales in SRGA. The two species of desert shrubs showed positive interspecific relationships at the small scale, and they showed negative relationships as the interspecific competition intensified in the presence of grazing disturbance. When the grazing intensity exceeds a certain threshold, the interspecific relationships become weak. Therefore, moderate grazing would facilitate interspecific competition and species succession, whereas excessive grazing would disrupt natural competition causing desertification ultimately.
Infarct-related chronic total coronary occlusion and the risk of ventricular tachyarrhythmic events in out-of-hospital cardiac arrest survivors
Authors: van der Graaf M. , Jewbali L. S. D. , Lemkes J. S. , Spoormans E. M. , van der Ent M. , Meuwissen M. , Blans M. J. , van der Harst P. , Henriques J. P. , Beishuizen A. , Camaro C. , Bleeker G. B. , van Royen N. , Yap S. C. 
Published: May 2021

Abstract
Introduction
Chronic total coronary occlusion (CTO) has been identified as a risk factor for ventricular arrhythmias, especially a CTO in an infarct-related artery (IRA). This study aimed to evaluate the effect of an IRA-CTO on the occurrence of ventricular tachyarrhythmic events (VTEs) in out-of-hospital cardiac arrest survivors without ST-segment elevation.

Methods
We conducted a post hoc analysis of the COACT trial, a multicentre randomised controlled trial. Patients were included when they survived index hospitalisation after cardiac arrest and demonstrated coronary artery disease on coronary angiography. The primary endpoint was the occurrence of a VTE, defined as appropriate implantable cardioverter-defibrillator (ICD) therapy, sustained ventricular tachyarrhythmia or sudden cardiac death.

Results
A total of 163 patients from ten centres were included. Unrevascularised IRA-CTO in a main vessel was present in 43 patients (26%). Overall, 61% of the study population received an ICD for secondary prevention. During a follow-up of 1 year, 12 patients (7.4%) experienced at least one VTE. The cumulative incidence rate of VTEs was higher in patients with an IRA-CTO compared to patients without an IRA-CTO (17.4% vs 5.6%, log-rank p = 0.03). However, multivariable analysis only identified left ventricular ejection fraction < 35% as an independent factor associated with VTEs (adjusted hazard ratio 8.7, 95% confidence interval 2.2–35.4). A subanalysis focusing on CTO, with or without an infarct in the CTO territory, did not change the results.

Conclusion
In out-of-hospital cardiac arrest survivors with coronary artery disease without ST-segment elevation, an IRA-CTO was not an independent factor associated with VTEs in the 1st year after the index event.
The Florence Emotional Eating Drive (FEED): a validation study of a self-report questionnaire for emotional eating
Authors: Cassioli Emanuele , Calderani Enrico , Fioravanti Giulia , Lazzeretti Lisa , Rotella Carlo Maria , Rossi Eleonora , Ricca Valdo , Mannucci Edoardo , Rotella Francesco 
Published: May 2021

Abstract
Purpose
Emotional eating is a trans-diagnostic dimension in eating disorders and is present in many other conditions that could affect eating attitudes. At present, there is no instrument that measures emotional eating evaluating both the intensity and the frequency of emotion-induced desire to eat. The aim of the study was the validation of the Florence Emotional Eating Drive (FEED).

Methods
A sample of healthy volunteers was initially enrolled to explore internal consistency and test–retest reliability. The Emotional Eating Scale (EES), Eating Disorders Evaluation-Questionnaire (EDE-Q), Binge Eating Scale (BES) and Symptom Checklist-90 (SCL-90-R), together with the final version of FEED, were administered to a clinical sample composed by patients with eating disorders, obesity, and type 2 diabetes, to explore the underlying structure of the questionnaire and verify its validity.

Results
FEED showed excellent internal consistency (Cronbach’s alpha = 0.96) and test–retest reliability (r = 0.93). FEED scores were higher in patients with BN and BED than in AN patients, negatively correlated with age and positively with BES and EES. Multiple regression analysis showed that FEED, but not EES, was independently associated with SCL-90-R and EDE-Q scores.

Conclusion
FEED internal consistency and test–retest reliability were excellent. The addition of specific questions on the frequency of behaviours led to a better component structure and robustness compared to EES. A tool that reliably and specifically assesses eating behaviours driven by emotional states may be extremely useful in clinical settings.

Level of evidence
Level V, cross-sectional study.
Clinical Quality Considerations when Using Next-Generation Sequencing (NGS) in Clinical Drug Development
Authors: Ménard Timothé , Barros Alaina , Ganter Christopher 
Published: May 2021

AbstractNext-generation sequencing (NGS) and decreased costs of genomic testing are changing the paradigm in precision medicine and continue to fuel innovation. Integration of NGS into clinical drug development has the potential to accelerate clinical trial conduct and ultimately will shape the landscape of clinical care by making it easier to identify patients who would benefit from particular therapy(ies) and to monitor treatment outcomes with less invasive tests. This has led to an increased use of NGS service providers by pharmaceutical sponsors: to screen patients for clinical trials eligibility and for patient stratification, expanded Companion Diagnostic (CDx) development for treatment recommendations and Comprehensive Genomic profiling (CGP). These changes are reshaping the face of clinical quality considerations for precision medicine. Although some clinical quality considerations do exist in Health Authorities (HA) guidances and regulations (e.g., International Conference of Harmonization Good Clinical Practices—GCP), there is currently no holistic GxP-like detailed framework for pharmaceutical sponsors using NGS service providers in clinical trials, or for the development of CDx and CGP. In this research, we identified existing and applicable regulations, guidelines and recommendations that could be translated into clinical quality considerations related to technology, data quality, patients and oversight. We propose these considerations as a basis for pharmaceutical sponsors using NGS service providers in clinical drug development to develop a set of guidelines for NGS clinical quality.
REDUCING RISK: MAYA LITHIC PRODUCTION AND ECONOMIC DIVERSIFICATION AT CALLAR CREEK QUARRY, BELIZE
Authors: Horowitz Rachel A. 
Published: May 2021

AbstractThe role of craft producers in past economies provides information that helps contextualize the role of economies in broader sociopolitical systems. Through this examination of lowland Maya lithic producers in the Late to Terminal Classic period (a.d.600–890), this article explores the centrality of economic activities in integrating craft producers into larger regional political communities and simultaneously buffering them against regional political conflicts. Through a study of lithic extraction and production at Callar Creek Quarry, Belize, this article examines the relevance of crafting activities in the minimization of economic uncertainty. These data indicate that lithic reduction served to diversify economic activities for lithic producers, and thus minimized economic risk. The use of economic activity to minimize risk provides evidence for the continuity of small-scale householders. This illustrates the independence of economic activities from political frameworks, and suggests that economic diversification serves as a critical stabilizing force for rural Classic-period Maya residents.