bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking of Tumor Cell–Derived Extracellular Vesicles In Vivo Reveals a Specific Distribution Pattern with Consecutive Biological Effects on Target Sites of Metastasis
Authors: Gerwing Mirjam , Kocman Vanessa , Stölting Miriam , Helfen Anne , Masthoff Max , Roth Johannes , Barczyk-Kahlert Katarzyna , Greune Lilo , Schmidt M. Alexander , Heindel Walter , Faber Cornelius , König Simone , Wildgruber Moritz , Eisenblätter Michel 
Published: July 2020

Abstract
Purpose
Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis.

Procedures
Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum.

Results
In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV.

Conclusions
In conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo.
Automatic quality measurement of aortic contrast-enhanced CT angiographies for patient-specific dose optimization
Authors: Pallenberg René , Fleitmann Marja , Soika Kira , Stroth Andreas Martin , Gerlach Jan , Fürschke Alexander , Barkhausen Jörg , Bischof Arpad , Handels Heinz 
Published: July 2020

Abstract
Purpose
Iodine-containing contrast agent (CA) used in contrast-enhanced CT angiography (CTA) can pose a health risk for patients. A system that adjusts the frequently used standard CA dose for individual patients based on their clinical parameters can be useful. As basis the quality of the image contrast in CTA volumes has to be determined, especially to recognize excessive contrast induced by CA overdosing. However, a manual assessment with a ROI-based image contrast classification is a time-consuming step in everyday clinical practice.

Methods
We propose a method to automate the contrast measurement of aortic CTA volumes. The proposed algorithm is based on the mean HU values in selected ROIs that were automatically positioned in the CTA volume. First, an automatic localization algorithm determines the CTA image slices for certain ROIs followed by the localization of these ROIs. A rule-based classification using the mean HU values in the ROIs categorizes images with insufficient, optimal and excessive contrast.

Results
In 95.89% (70 out of 73 CTAs obtained with the ulrich medical CT motion contrast media injector) the algorithm chose the same image contrast class as the radiological expert. The critical case of missing an overdose did not occur with a positive predicative value of 100%.

Conclusion
The resulting system works well within our range of considered scan protocols detecting enhanced areas in CTA volumes. Our work automized an assessment for classifying CA-induced image contrast which reduces the time needed for medical practitioners to perform such an assessment manually.
MicroRNA Expression Signature in Mild Cognitive Impairment Due to Alzheimer’s Disease
Authors: De Felice Bruna , Montanino Concetta , Oliva Mariano , Bonavita Simona , Di Onofrio Valeria , Coppola Cinzia 
Published: July 2020

AbstractMild cognitive impairment (MCI) defines an intermediate state between normal ageing and dementia, including Alzheimer’s disease (AD). Identification of MCI subjects who will progress to AD (MCI-AD) is today of crucial importance, especially in light of the possible development of new pathogenic therapies. Several evidences suggest that miRNAs could play relevant roles in the biogenesis of AD, and the links between selected miRNAs and specific pathogenic aspects have been partly explored. In this study, we analysed the composition of microRNA transcriptome in blood, serum and cerebrospinal fluid samples from MCI-AD subjects, from an enriched small RNA library. Real-time qPCR from MCI-AD and AD patients and normal controls was performed to profile miRNA expression. In particular, four microRNAs, hsa-mir-5588-5p, hsa-mir-3658, hsa-mir-567 and hsa-mir-3908, among all selected microRNAs, are dysregulated. Hsa-mir-567 was found to be differentially expressed in cerebrospinal fluid samples, blood and serum from MCI-AD patients, showing the highest fold change and statistical significance. Target prediction analysis have been performed to evaluate mRNAs whose expression was controlled by miRNAs found to be dysregulated here, showing that hsa-mir-567 target genes are functionally active in neuronal cells. We propose that miRNA profiles found in samples from MCI-AD patients might be relevant for a better understanding of AD-related cognitive decline and could lead to set up suitable and potential biomarkers for MCI-AD progression to AD.
Quantifying the Benefits of Estuarine Habitat Restoration in the Gulf of Mexico: an Introduction to the Theme Section
Authors: Carle Melissa Vernon , Benson Kristopher G. , Reinhardt James F. 
Published: July 2020

AbstractThis collection of papers provides insights into methods and data currently available to quantify the benefits associated with estuarine habitat restoration projects in the northern Gulf of Mexico, USA, with potential applicability to other coastal systems. Extensive habitat restoration is expected to occur in the northern Gulf of Mexico region over the next several decades through funding associated with the 2010 Deepwater Horizon oil spill. Papers in this section examine the development of vegetation, soil properties, invertebrate fauna, and nekton communities in restored coastal marshes and provide a conceptual framework for applying these findings to quantify the benefits associated with compensatory marsh restoration. Extensive meta-analysis of existing data for Gulf of Mexico coastal habitats further confirms that structured habitats such as marsh, submerged aquatic vegetation, and oyster reefs support greater nekton densities than nonvegetated bottom habitat, with oyster reefs supporting different species assemblages than marsh and submerged aquatic vegetation. Other papers demonstrate that while vegetation cover can establish rapidly within the first 5 years of restoration, belowground parameters such as root biomass and soil organic matter remain 44% to 92% lower at restored marshes than reference marshes 15 years after restoration. On average, amphipod and nekton densities are also not fully restored until at least 20 and 13 years following restoration, respectively. Additional papers present methods to estimate the benefits associated with marsh restoration projects, nekton productivity associated with coastal and estuarine habitats, and the benefits associated with the removal of derelict crab traps in Gulf of Mexico estuaries.
The edge of the Empire: diet characterization of medieval Rome through stable isotope analysis
Authors: Varano Sara , De Angelis Flavio , Battistini Andrea , Brancazi Luca , Pantano Walter , Ricci Paola , Romboni Marco , Catalano Paola , Gazzaniga Valentina , Lubritto Carmine , Santangeli Valenzani Riccardo , Martínez-Labarga Cristina , Rickards Olga 
Published: July 2020

AbstractThis paper aims to define the dietary profile of the population of early medieval Rome (fifth–eleventh centuries CE) by carbon and nitrogen stable isotope analysis. This period was characterized by deep changes in the city’s economic, demographic, and social patterns, probably affecting its inhabitants’ nutritional habits. Carbon and nitrogen stable isotope analysis of bone collagen was used to detect the nutritional profile of 110 humans from six communities inhabiting the city center of Rome and one from the ancient city of Gabii. Thirteen faunal remains were also analyzed to define the ecological baseline of the medieval communities. The isotopic results are consistent with a diet mainly based on the exploitation of C3plant resources and terrestrial fauna, while the consumption of aquatic resources was detected only among the San Pancrazio population. Animal protein intake proved to be similar both among and within the communities, supporting a qualitatively homogenous dietary landscape in medieval Rome. The comparison with isotopic data from the Imperial Age allowed us to detect a diachronic nutritional transition in ancient Rome, in which the collapse of the Empire, and in particular the crisis of economic power and the trade system, represented a tipping point for its population’s nutritional habits.
Quantitative evaluation of watershed attributes for water resources management in the Rift Valley Lakes Basin, Ethiopia: a case from Tikur Wuha river watershed
Authors: Girma Rediet , Abraham Tesfalem , Muluneh Alemayehu 
Published: July 2020

AbstractCharacterization of watershed hydrological process is vital for sustainable water resource management. The principal goal of this study was to investigate the inference of drainage attributes on basic hydrological processes using spatial-based morphometric analysis on Tikur Wuha river watershed. The result obtained indicated that the area was characterized with fifth-order stream. Drainage area with higher stream order has lower infiltration capacity, and the shorter stream lengths were associated with the steepness of the area which affects water flow. Based on Nu value, sub-watersheds were categorized in the active erosion stage (SW7) and matured topography development (SW6). The interpretation from watershed geometry identified circular areas most susceptible to rapid hydrological response (SW11). Hydrological process and underlying materials are mainly correlated with the drainage texture parameter, and the lower the values indicated less rocky terrain and very high infiltration capacity which contributes toward less erosion (SW11). Relief parameters such as Rr value indicate the rate of stream flow and are well used in sediment yield estimation. The findings of this investigation will provide core information for water resource planning and further studies like identification of groundwater potential zones; flood risk assessment; erosion-prone area prioritization; and to select suitable sites for the construction of water harvesting structures.
Response surface modelling of the biosorption of Zn(II) and Pb(II) onto Micropogonias undulatus scales: Box–Behnken experimental approach
Authors: Ighalo Joshua O. , Eletta Omodele A. A. 
Published: July 2020

AbstractIn this study, the scales of Micropogonias undulatus fish were investigated as precursors for the development of low-cost biosorbent for the removal of Pb(II) and Zn(II) from aqueous media.
The biosorbent was characterised using Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and X-ray diffractometry (XRD). Adsorption parameters (temperature, biosorbent dosage and contact time) were optimised using response surface methodology Box–Behnken experimental design. The optimal factors for Zn(II) removal by croaker fish scale were 145.5 min, 7.01 g/L biosorbent dosage, 30 °C and pH 5.4. The optimal factors for the removal of Pb(II) were 179.3 min, 6.61 g/L biosorbent dosage, 20 °C and pH 3.4. The numerical optimisation revealed that the optimal removal efficiency for Zn(II) and Pb(II) sorption is 96.45% and 98.76%, respectively. The biosorption of both heavy metals was best fit to Freundlich isotherm and pseudo-second-order kinetic models. Thermodynamics studies revealed that the biosorption process was exothermic and spontaneous.
Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation
Authors: Wang Chengcheng , Zhang Taiping , Liao Quan , Dai Menghua , Guo Junchao , Yang Xinyu , Tan Wen , Lin Dongxin , Wu Chen , Zhao Yupei 
Published: July 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03–2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14–0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.
Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults
Authors: Reginster Jean-Yves , Beaudart Charlotte , Al-Daghri Nasser , Avouac Bernard , Bauer Jürgen , Bere Nathalie , Bruyère Olivier , Cerreta Francesca , Cesari Matteo , Rosa Mario Miguel , Cooper Cyrus , Cruz Jentoft Alfonso J. , Dennison Elaine , Geerinck Anton , Gielen Evelien , Landi Francesco , Laslop Andrea , Maggi Stefania , Prieto Yerro María Concepción , Rizzoli René , Sundseth Hildrun , Sieber Cornel , Trombetti Andrea , Vellas Bruno , Veronese Nicola , Visser Marjolein , Vlaskovska Mila , Fielding Roger A. 
Published: July 2020

Abstract
Background
In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia.

Aims
The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations.

Methods
This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations.

Results
The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure.

Conclusion
The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.
HOSS: an implementation of the combined finite-discrete element method
Authors: Knight Earl E. , Rougier Esteban , Lei Zhou , Euser Bryan , Chau Viet , Boyce Samuel H. , Gao Ke , Okubo Kurama , Froment Marouchka 
Published: July 2020

AbstractNearly thirty years since its inception, the combined finite-discrete element method (FDEM) has made remarkable strides in becoming a mainstream analysis tool within the field of Computational Mechanics. FDEM was developed to effectively “bridge the gap” between two disparate Computational Mechanics approaches known as the finite and discrete element methods. At Los Alamos National Laboratory (LANL) researchers developed the Hybrid Optimization Software Suite (HOSS) as a hybrid multi-physics platform, based on FDEM, for the simulation of solid material behavior complemented with the latest technological enhancements for full fluid–solid interaction. In HOSS, several newly developed FDEM algorithms have been implemented that yield more accurate material deformation formulations, inter-particle interaction solvers, and fracture and fragmentation solutions. In addition, an explicit computational fluid dynamics solver and a novel fluid–solid interaction algorithms have been fully integrated (as opposed to coupled) into the HOSS’ solid mechanical solver, allowing for the study of an even wider range of problems. Advancements such as this are leading HOSS to become a tool of choice for multi-physics problems. HOSS has been successfully applied by a myriad of researchers for analysis in rock mechanics, oil and gas industries, engineering application (structural, mechanical and biomedical engineering), mining, blast loading, high velocity impact, as well as seismic and acoustic analysis. This paper intends to summarize the latest development and application efforts for HOSS.
Lightweight in Automotive Components by Forming Technology
Authors: Rosenthal Stephan , Maaß Fabian , Kamaliev Mike , Hahn Marlon , Gies Soeren , Tekkaya A. Erman 
Published: July 2020

AbstractLightweight design is one of the current key drivers to reduce the energy consumption of vehicles. Design methodologies for lightweight components, strategies utilizing materials with favorable specific properties and hybrid materials are used to increase the performance of parts for automotive applications. In this paper, various forming processes to produce light parts are described. Material lightweight design is discussed, covering the manufacturing processes to produce hybrid components like fiber–metal, polymer–metal and metal–metal composites, which can be used in subsequent deep drawing or combined forming processes. Approaches to increasing the specific strength and stiffness with thermomechanical forming processes as well as the in situ control of the microstructure of such components are presented. Structure lightweight design discusses possibilities to plastically form high-strength or high-performance materials like magnesium or titanium in sheet, profile and tube forming operations. To join those materials and/or dissimilar materials, new joining by forming technologies are shown. To economically produce lightweight parts with gears or functional elements, incremental sheet-bulk metal forming is presented. As an important part property, the damage evolution during the forming operations will be discussed to enable even lighter parts through a more reliable design. New methods for predicting and tailoring the mechanical properties like strength and residual stresses will be shown. The possibilities of system lightweight design with forming technologies are presented. A combination of additive manufacturing and forming to produce highly complex parts with integrated functions will be shown. The integration of functions by a hot extrusion process for the manufacturing of shape memory alloys is presented. An in-depth understanding of the newly developed processes, methodologies and effects allows for a more accurate dimensioning of components. This facilitates a reduction in the total mass and an increasing performance of vehicle components.
Photoautotrophic picoplankton – a review on their occurrence, role and diversity in Lake Balaton
Authors: Somogyi Boglárka , Felföldi Tamás , Tóth László G. , Bernát Gábor , Vörös Lajos 
Published: July 2020

AbstractOccurrence of the smallest phototrophic microorganisms (photoautotrophic picoplankton, APP) in Lake Balaton was discovered in the early 1980s. This triggered a series of systematic studies on APP and resulted in the setting of a unique long-term picoplankton dataset. In this review, we intend to summarize the obtained results and to give a new insight on APP ecology and diversity in Lake Balaton. According to the results, APP dynamics depends on trophic state, temperature, nutrient, and light availability, as well as grazing pressure. APP abundance in Lake Balaton decreased to a low level (1–2 × 105 cells mL−1) as a consequence of decreasing nutrient supply (oligotrophication) during the past more than two decades, and followed a characteristic seasonal dynamics with higher abundance values from spring to autumn than in winter. Concomitantly, however, the APP contribution to both phytoplankton biomass and primary production increased (up to 70% and 40–50%, respectively) during oligotrophication. Regarding annual pattern, picocyanobacteria are dominant from spring to autumn, while in winter, picoeukaryotes are the most abundant, most likely due to the different light and temperature optima of these groups. Within picocyanobacteria, single cells and microcolonies were both observed with mid-summer dominance of the latter which correlated well with the density of cladocerans. Community-level chromatic adaptation (i.e., dominance of phycoerythrin- or phycocyanin-rich forms) of planktonic picocyanobacteria was also found as a function of underwater light quality. Sequence analysis studies of APP in Lake Balaton revealed that both picocyanobacteria and picoeukaryotes represent a diverse and dynamic community consisting several freshwater genotypes (picocyanobacteria:Synechococcus, Cyanobium; picoeukaryotes:Choricystis, Stichococcus,Mychonastes, Nannochloris, andNannochloropsis).
Ten Guidelines for Better Tables
Authors: Schwabish Jonathan A. 
Published: July 2020

AbstractTables are a unique form of visualizing data because, unlike many charts, they are not usually intended to give a quick, visual representation of data. Instead, tables are useful when you want to show the exact values of your data or estimates. They are not the best solution if you want to show a lot of data or if you want to show the data in a compact space, but a well-designed table can help your reader find specific numbers and discover patterns and outliers. In this article, I present 10 guidelines for creating better, more effective tables; I then model these lessons by redesigning six tables from articles previously published in the Journal of Benefit-Cost Analysis.