bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual search in virtual 3D space: the relation of multiple targets and distractors
Authors: Plewan Thorsten , Rinkenauer Gerhard
Published: January 2021

Visual search and attentional alignment in 3D space are potentially modulated by information in unattended depth planes. The number of relevant and irrelevant items as well as their spatial relations may be regarded as factors which contribute to such effects. On a behavioral level, it might be different whether multiple distractors are presented in front of or behind target items. However, several studies revealed that attention cannot be restricted to a single depth plane. To further investigate this issue, two experiments were conducted. In the first experiment, participants searched for (multiple) targets in one depth plane, while non-target items (distractors) were simultaneously presented in this or another depth plane. In the second experiment, an additional spatial cue was presented with different validities to highlight the target position. Search durations were generally shorter when the search array contained two additional targets and were markedly longer when three distractors were displayed. The latter effect was most pronounced when a single target and three distractors coincided in the same depth plane and this effect persisted even when the target position was validly cued. The study reveals that the depth relation of target and distractor stimuli was more important than the absolute distance between these objects. Furthermore, the present findings suggest that within an attended depth plane, irrelevant information elicits strong interference. In sum, this study provides further evidence that allocation of attention is a flexible process which may be modulated by a variety of perceptual and cognitive factors.
Mesenchymal stem cell therapy in hypertrophic and keloid scars
Authors: Bojanic Christine , To Kendrick , Hatoum Adam , Shea Jessie , Seah K. T. Matthew , Khan Wasim , Malata Charles M.
Published: January 2021

Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.
Consequences of vertical basic wood density variation on the estimation of aboveground biomass with terrestrial laser scanning
Authors: Demol Miro , Calders Kim , Krishna Moorthy Sruthi M. , Van den Bulcke Jan , Verbeeck Hans , Gielen Bert
Published: January 2021

Key message

Stump-to-tip trends in basic wood density complicate the conversion of tree volume into aboveground biomass. We use 3D tree models from terrestrial laser scanning to obtain tree-level volume-weighted wood density.

Terrestrial laser scanning (TLS) is used to generate realistic 3D tree models that enable a non-destructive way of quantifying tree volume. An accurate value for basic wood density is required to convert tree volume into aboveground biomass (AGB) for forest carbon assessments. However, basic density is characterised by high inter-, intra-species and within-tree variability and a likely source of error in TLS-derived biomass estimates. Here, 31 adult trees of 4 important European timber species (Fagus sylvatica, Larix decidua, Pinus sylvestris, Fraxinus excelsior) were scanned using TLS and then felled for several basic wood density measurements. We derived a reference volume-weighted basic density (ρw) by combining volume from 3D tree models with destructively assessed vertical density profiles. We compared this to basic density retrieved from a single basal disc over bark (ρbd), two perpendicular pith-to-bark increment cores at breast height (ρic), and sourcing the best available local basic wood density from publications. Stump-to-tip trends in basic wood density caused site-average woody AGB estimation biases ranging from −3.3 to + 7.8% when using ρbd and from −4.1 to + 11.8% when using ρic. Basic wood density from publications was in general a bad predictor for ρw as the bias ranged from −3.2 to + 17.2%, with little consistency across different density repositories. Overall, our density-attributed biases were similar to several recently reported biases in TLS-derived tree volume, leading to potentially large compound errors in biomass assessments with TLS if patterns of vertical basic wood density variation are not properly accounted for.
Improvement of similarity–diversity trade-off in recommender systems based on a facility location model
Authors: Panteli Antiopi , Boutsinas Basilis
Published: January 2021

There is a growing interest in the offering of novel alternative choices to users of recommender systems. These recommendations should match the target query while at the same time they should be diverse with each other in order to provide useful alternatives to the user, i.e., novel recommendations. In this paper, the problem of extracting novel recommendations, under the similarity–diversity trade-off, is modeled as a facility location problem. The results from tests in the benchmark Travel Case Base were satisfactory when compared to well-known recommender techniques, in terms of both similarity and diversity. It is shown that the proposed method is flexible enough, since a parameter of the adopted facility location model constitutes a regulator for the trade-off between similarity and diversity. Also, our work can broaden the perspectives of the interaction and combination of different scientific fields in order to achieve the best possible results.
Association between maternal triglycerides and disturbed glucose metabolism in pregnancy
Authors: Eppel Daniel , Feichtinger Michael , Lindner Tina , Kotzaeridi Grammata , Rosicky Ingo , Yerlikaya-Schatten Guelen , Eppel Wolfgang , Husslein Peter , Tura Andrea , Göbl Christian S.
Published: January 2021

Aims

Dyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy.

Methods

Sixty-seven pregnant women received a detailed metabolic characterization at 12+0–22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0–27+6 weeks of gestation.

Results

Elevated triglycerides in early gestation were associated with insulin resistance and β-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03–1.34, p=0.022 for an increase of 10 mg/dl).

Conclusions

Hypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and β-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.
Pull-out and Critical Embedment Length of Grouted Rebar Rock Bolts-Mechanisms When Approaching and Reaching the Ultimate Load
Authors: Høien Are Håvard , Li Charlie C. , Zhang Ning
Published: January 2021

Rock bolts are one of the main measures used to reinforce unstable blocks in a rock mass. The embedment length of fully grouted bolts in the stable and competent rock stratum behind the unstable rock blocks is an important parameter in determining overall bolt length. It is required that the bolt section in the stable stratum must be longer than the critical embedment length to ensure the bolt will not slip when loaded. Several series of pull tests were carried out on fully grouted rebar bolts to evaluate the pull-out mechanics of the bolts. Bolt specimens with different embedment lengths and water/cement ratios were installed in either a concrete block of one cubic meter or in steel cylinders. Load displacement was recorded during testing. For some of the bolts loaded beyond the yield load, permanent plastic steel deformation was also recorded. Based on the test results, three types of failure mechanisms were identified, corresponding to three loading conditions: (1) pull-out below the yield strength of the bolt steel; (2) pull-out between the yield and ultimate loads, that is, during strain hardening of the steel; and (3) steel failure at the ultimate load. For failure mechanisms 2 and 3, it was found that the critical embedment length of the bolt included three components: an elastic deformation length, a plastic deformation length and a completely debonded length due to the formation of a failure cone at the borehole collar.
Complications of external cerebrospinal fluid drainage in aneurysmal subarachnoid haemorrhage
Authors: Arts Sebastian , van Lindert Erik J. , Aquarius Rene , Bartels Ronald H. M. A. , Boogaarts Hieronymus D.
Published: January 2021

Background

The need for external cerebrospinal fluid (CSF) drains in aneurysmal subarachnoid haemorrhage (aSAH) patients is common and might lead to additional complications.

Objective

A relation between the presence of an external CSF drain and complication risk is investigated.

Methods

A prospective complication registry was analysed retrospectively. We included all adult aSAH patients admitted to our academic hospital between January 2016 and January 2018, treated with an external CSF drain. Demographic data, type of external drain used, the severity of the aSAH and complications, up to 30 days after drain placement, were registered. Complications were divided into (1) complications with a direct relation to the external CSF drain and (2) complications that could not be directly related to the use of an external CSF drain referred to as medical complications

Results

One hundred and forty drains were implanted in 100 aSAH patients. In total, 112 complications occurred in 59 patients. Thirty-six complications were drain related and 76 were medical complications. The most common complication was infection (n = 34). Drain dislodgement occurred 16 times, followed by meningitis (n = 11) and occlusion (n = 9). A Poisson model showed that the mean number of complications raised by 2.9% for each additional day of drainage (95% CI: 0.6–5.3% p = 0.01).

Conclusion

Complications are common in patients with aneurysmal subarachnoid haemorrhage of which 32% are drain-related. A correlation is present between drainage period and the number of complications. Therefore, reducing drainage period could be a target for further improvement of care.
Simple fistula-in-ano: is it all simple? A systematic review
Authors: Litta F. , Parello A. , Ferri L. , Torrecilla N. O. , Marra A. A. , Orefice R. , De Simone V. , Campennì P. , Goglia M. , Ratto C.
Published: January 2021

Background

Simple anal fistula is one of the most common causes of proctological surgery and fistulotomy is considered the gold standard. This procedure, however, may cause complications. The aim of this systematic review was to assess the surgical treatment of simple anal fistula with traditional and sphincter-sparing techniques.

Methods

A literature research was performed using PubMed, Cochrane, and Google Scholar to identify studies on the surgical treatment of simple anal fistulas. Observational studies and randomized clinical trials were included. We assessed the risk of bias of included studies using the Jadad scale for randomized controlled trials, and the MINORS Scale for the remaining studies.

Results

The search returned 456 records, and 66 studies were found to be eligible. The quality of the studies was generally low. A total of 4883 patients with a simple anal fistula underwent a sphincter-cutting procedure, mainly fistulotomy, with a weighted average healing rate of 93.7%, while any postoperative continence impairment was reported in 12.7% of patients. Sphincter-sparing techniques were adopted to treat 602 patients affected by simple anal fistula, reaching a weighted average success rate of 77.7%, with no study reporting a significant postoperative incontinence rate. The postoperative onset of fecal incontinence and the recurrence of the disease reduced patients’ quality of life and satisfaction.

Conclusions

Surgical treatment of simple anal fistulas with sphincter-cutting procedures provides excellent cure rates, even if postoperative fecal incontinence is not a negligible risk. A sphincter-sparing procedure could be useful in selected patients.
Taxonomic study of a new green alga, Annulotesta cochlephila gen. et sp. nov. (Kornmanniaceae, Ulvales, Ulvophyceae), growing on the shells of door snails
Authors: Namba Noriaki , Nakayama Takeshi
Published: January 2021

Some algae are known to grow on shellfish shells. Most of these have been reported in aquatic environments. The species specificity for substrate shells varies, and some algae grow only on the shells of a certain species of shellfish, such asPseudocladophora conchopheria(Cladophorales, Ulvophyceae) onLunella coreensis(Trochida, Gastropoda). There are very few reports of algae that grow on land snails. In this study, we discovered green algae growing on the shells of six species of door snails (Clausiliidae) from nine localities in Japan. These green algae formed a green mat composed of thalli embedded in the extracellular matrix. The thallus was composed of aggregated oval cells and peripheral branched filaments. The cells possessed a single parietal chloroplast with a pyrenoid surrounded by two starch sheaths and transversed by a thylakoid. Oil droplets in the cell and ring-like structures on the cell wall surface were frequently observed. The 18S rDNA sequences of all shell-attached algae on different clausiliid species from different localities were almost identical and formed a new clade in the family Kornmanniaceae (Ulvales, Ulvophyceae). No other algae forming visible colonies on the clausiliid shell were found. These findings indicate the presence of specificity between the alga and clausiliid shells. Based on the results of morphological observation and molecular phylogenetic analysis, we propose a new genus and new species of shell-attached green alga,Annulotesta cochlephila.
Estimation of Parental Effects Using Polygenic Scores
Authors: Balbona Jared V. , Kim Yongkang , Keller Matthew C.
Published: January 2021

Offspring resemble their parents for both genetic and environmental reasons. Understanding the relative magnitude of these alternatives has long been a core interest in behavioral genetics research, but traditional designs, which compare phenotypic covariances to make inferences about unmeasured genetic and environmental factors, have struggled to disentangle them. Recently, Kong et al. (2018) showed that by correlating offspring phenotypic values with the measured polygenic score of parents’ nontransmitted alleles, one can estimate the effect of “genetic nurture”—a type of passive gene–environment covariation that arises when heritable parental traits directly influence offspring traits. Here, we instantiate this basic idea in a set of causal models that provide novel insights into the estimation of parental influences on offspring. Most importantly, we show how jointly modeling the parental polygenic scores and the offspring phenotypes can provide an unbiased estimate of the variation attributable to the environmental influence of parents on offspring, even when the polygenic score accounts for a small fraction of trait heritability. This model can be further extended to (a) account for the influence of different types of assortative mating, (b) estimate the total variation due to additive genetic effects and their covariance with the familial environment (i.e., the full genetic nurture effect), and (c) model situations where a parental trait influences a different offspring trait. By utilizing structural equation modeling techniques developed for extended twin family designs, our approach provides a general framework for modeling polygenic scores in family studies and allows for various model extensions that can be used to answer old questions about familial influences in new ways.
Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways
Authors: Li Ying , Yan Jing , Wang Minjia , Lv Jing , Yan Fei , Chen Jin
Published: January 2021

Evidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.
The Roles of Familiarity and Context in Processing Chinese Xiehouyu: An ERP Study
Authors: Wang Xiaolu , Wang Yizhen , Tian Wanning , Zheng Wei , Chen Xiaoli
Published: January 2021

This study conducts an ERP experiment to explore the online processing mechanism of Chinese xiehouyu, a subcategory of Chinese idiomatic expressions with a metaphorical two-part allegorical saying, regarded as a non-literal language construct. Using a 2 × 2 design, (high familiarity (HF)/low familiarity (LF)) × (literally-biasing context (LC)/metaphorically-biasing context (MC)), the researchers have obtained the following findings: (1) familiarity plays an important role in Chinese xiehouyu processing, i.e. the metaphorical meaning of a HF Chinese xiehouyu can be directly activated while that of a LF one has to be derived from its literal meaning first; (2) contextual information also weighs in the process, i.e. the metaphorical meaning of a Chinese xiehouyu can be promoted in MC condition but suppressed in LC condition; (3) the interactive effect of familiarity and contextual information can be explained by the career of metaphor hypothesis; and (4) the Standard Pragmatic Model (SPM) of non-literal languages can explain the processing of LF xiehouyu, and the Direct Access Model (DAM) may to some extent account for the mechanism of HF one but fails to explain the case of LF one, while the Graded Salience Hypothesis (GSH) can provide an acceptable explanation for the processing mechanism of Chinese xiehouyus of varied familiarity.
Fracture formation due to differential compaction under glacial load: a poro-elastoplastic simulation of the Hugin Fracture
Authors: Landschulze Karin , Landschulze Marcus
Published: January 2021

The Hugin Fracture, discovered in 2011, is an approximately 3.5 km long seafloor fracture in the North Sea. This fracture was unexpected and, due to the geology in the North Sea no obvious explanation could be found. In our study, we adopt the hypothesis that the Hugin fracture was formed by differential compaction controlled by glacial load. We construct a simplified 2D geomechanical model partly covered by top load (ice sheet) and test this hypothesis. We employ transient poro-elastoplastic simulation with a finite element method. For the simulations, we had to make assumptions regarding the material properties, because the fracture is located in-between well locations. We used descriptions from drilling site survey reports and literature values and performed seismic matching form well paths to the Hugin Fracture. Nearby well data were only partly useful due to incomplete logging in the first 400 m below seafloor. To overcome this problem, we introduced a mixing k-value which allows us to easily change the material properties from pure clay to sand. Changing the mixing k-value for each simulation provided information about the limits and robustness of the simulation results. Simulation results show isotropic stress and strain distribution in the horizontally layered, isotropic part of the model that is totally covered by the ice. In the central, channelized part of the model a composite stress and strain pattern develops with sub-vertical focus areas tangential to channel edges. Low stress, strain and deformation values under total load increase drastically soon after the load starts to decrease, resulting in the development of fractures along the focussed zones. Surface deformation such as formation of compaction ridges above stiff clay-filled channels and depression associated with plastic deformation is observed. A fracture and associated surface deformation develop above the shallowest sand-filled channel, very much resembling the observed geometry at the Hugin Fracture. The simulation supports the formation hypothesis for the Hugin Fracture as a compaction fracture and suggests that thin ice sheets may induce differential compaction to a depth of several hundred meters.
Biochemical markers for clinical monitoring of tissue perfusion
Authors: Janotka Marek , Ostadal Petr
Published: January 2021

The assessment and monitoring of the tissue perfusion is extremely important in critical conditions involving circulatory shock. There is a wide range of established methods for the assessment of cardiac output as a surrogate of oxygen delivery to the peripheral tissues. However, the evaluation of whether particular oxygen delivery is sufficient to ensure cellular metabolic demands is more challenging. In recent years, specific biochemical parameters have been described to indicate the status between tissue oxygen demands and supply. In this review, the authors summarize the application of some of these biochemical markers, including mixed venous oxygen saturation (SvO2), lactate, central venous–arterial carbon dioxide difference (PCO2 gap), and PCO2 gap/central arterial-to-venous oxygen difference (Ca–vO2) for hemodynamic assessment of tissue perfusion. The thorough monitoring of the adequacy of tissue perfusion and oxygen supply in critical conditions is essential for the selection of the most appropriate therapeutic strategy and it is associated with improved clinical outcomes.
Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device
Authors: Amemiya Takeo , Hata Nobuhiro , Mizoguchi Masahiro , Yokokawa Ryuji , Kawamura Yoichiro , Hatae Ryusuke , Sangatsuda Yuhei , Kuga Daisuke , Fujioka Yutaka , Takigawa Kosuke , Akagi Yojiro , Yoshimoto Koji , Iihara Koji , Miura Takashi
Published: January 2021

High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.
Role of MDA5 in regulating CXCL10 expression induced by TLR3 signaling in human rheumatoid fibroblast-like synoviocytes
Authors: Saruga Tatsuro , Imaizumi Tadaatsu , Kawaguchi Shogo , Seya Kazuhiko , Matsumiya Tomoh , Sasaki Eiji , Sasaki Norihiro , Uesato Ryoko , Ishibashi Yasuyuki
Published: January 2021

C-X-C motif chemokine 10 (CXCL10) is an inflammatory chemokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Melanoma differentiation-associated gene 5 (MDA5) is an RNA helicase that plays a role in innate immune and inflammatory reactions. The details of the regulatory mechanisms of CXCL10 production and the precise role of MDA5 in RA synovitis have not been fully elucidated. The aim of this study was to examine the role of MDA5 in regulating CXCL10 expression in cultured human rheumatoid fibroblast-like synoviocytes (RFLS). RFLS was stimulated with Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA mimetic. Expression of interferon beta (IFN-β), MDA5, and CXCL10 was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay. A neutralizing antibody of IFN-β and siRNA-mediated MDA5 knockdown were used to determine the role of these molecules in regulating CXCL10 expression downstream of TLR3 signaling in RFLS. Poly I:C induced IFN-β, MDA5, and CXCL10 expression in a concentration- and time-dependent manner. IFN-β neutralizing antibody suppressed the expression of MDA5 and CXCL10, and knockdown of MDA5 decreased a part of CXCL10 expression (p < 0.001). The TLR3/IFN-β/CXCL10 axis may play a crucial role in the inflammatory responses in RA synovium, and MDA5 may be partially involved in this axis.
Anthracycline-induced cytotoxicity in the GL261 glioma model system
Authors: Tavener Amber M. , Phelps Megan C. , Daniels Richard L.
Published: January 2021

Glioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.
A new sustained system performance metric for scientific performance evaluation
Authors: Tsuji Miwako , Kramer William T. C. , Weill Jean-Christophe , Nominé Jean-Philippe , Sato Mitsuhisa
Published: January 2021

Because of the increasing complexities of systems and applications, the performance of many traditional HPC benchmarks, such as HPL or HPCG, no longer correlates strongly with the actual performance of real applications. To address the discrepancy between simple benchmarks and real applications, and to better understand the application performance of systems, some metrics use a set of either real applications or mini applications. In particular, the Sustained System Performance (SSP) metric Kramer et al. (The NERSC sustained system performance (SSP) metric. Tech Rep LBNL-58868, 2005), which indicates the expected throughput of different applications executing with different datasets, is widely used. Whereas such a metric should lead to direct insights on the actual performance of real applications, sometimes more effort is necessary to port and evaluate complex applications. In this study, to obtain the approximate performance of SSP representing real applications, without running real applications, we propose a metric called the Simplified Sustained System Performance (SSSP) metric, which is computed based on several benchmark scores and their respective weighting factors, and we construct a method evaluating the SSSP metric of a system. The weighting factors are obtained by minimizing the gap between the SSP and SSSP scores based on a small set of reference systems. We evaluated the applicability of the SSSP method using eight systems and demonstrated that our proposed SSSP metrics produce appropriate performance projections of the SSP metrics of these systems, even when we adopted a simple method for computing the weighting factors. Additionally, the robustness of our SSSP metric was confirmed via computation of the weighting factors based on a smaller set of reference systems and computation of the SSSP metrics of other systems.
The risk of venous thromboembolism and physical activity level, especially high level: a systematic review
Authors: Danin-Mankowitz H. , Ugarph-Morawski A. , Braunschweig F. , Wändell P.
Published: January 2021

Venous thromboembolism (VTE) is the third most common cause of cardiovascular disease. Connection between high level of physical activity (PA) and the onset of VTE is unknown. We searched the literature on the possible association between PA level, especially high levels, and the risk of VTE. A systematic review was carried out to identify relevant articles on the relation between PA level and VTE. The initial search was conducted together with the Karolinska Institutet University Library in February 2018, with follow-up searches after that. In total, 4383 records were found and then screened for exclusion of duplicates and articles outside the area of interest. In total, 16 articles with data on 3 or more levels of PA were included. Of these, 12 were cohort and 4 were case-control studies. Totally 13 studies aimed at investigating VTE cases primarily, while three studies had other primary outcomes. Of the 16 studies, five found a U-shaped association between PA level and VTE risk, although non-significant in three of them. Two articles described an association between a more intense physical activity and a higher risk of VTE, which was significant in one. Nine studies found associations between increasing PA levels and a decreasing VTE risk. Available literature provides diverging results as to the association between high levels of PA and the risk of venous thromboembolism, but with several studies showing an association. Further research is warranted to clarify the relationship between high level PA and VTE.
Ozone potential to fight against SAR-COV-2 pandemic: facts and research needs
Authors: Blanco Angeles , Ojembarrena Francisco de Borja , Clavo Bernardino , Negro Carlos
Published: January 2021

The greatest challenge the world is facing today is to win the battle against COVID-19 pandemic as soon as possible. Until a vaccine is available, personal protection, social distancing, and disinfection are the main tools against SARS-CoV-2. Although it is quite infectious, the SARS-CoV-2 virus itself is an enveloped virus that is relatively fragile because its protective fatty layer is sensitive to heat, ultraviolet radiation, and certain chemicals. However, heat and liquid treatments can damage some materials, and ultraviolet light is not efficient in shaded areas, so other disinfection alternatives are required to allow safe re-utilization of materials and spaces. As of this writing, evidences are still accumulating for the use of ozone gas as a disinfectant for sanitary materials and ambient disinfection in indoor areas. This paper reviews the most relevant results of virus disinfection by the application of gaseous ozone. The review covers disinfection treatments of both air and surfaces carried out in different volumes, which varies from small boxes and controlled chambers to larger rooms, as a base to develop future ozone protocols against COVID-19. Published papers have been critically analyzed to evaluate trends in the required ozone dosages, as a function of relative humidity (RH), contact time, and viral strains. The data have been classified depending on the disinfection objective and the volume and type of the experimental set-up. Based on these data, conservative dosages and times to inactivate the SARS-CoV-2 are estimated. In small chambers, 10–20 mg ozone/m3over 10 to 50 min can be sufficient to significantly reduce the virus load of personal protection equipment. In large rooms, 30 to 50 mg ozone/m3would be required for treatments of 20–30 min. Maximum antiviral activity of ozone is achieved at high humidity, while the same ozone concentrations under low RH could result inefficient. At these ozone levels, safety protocols must be strictly followed. These data can be used for reducing significantly the viral load although for assuring a safe disinfection, the effective dosages under different conditions need to be confirmed with experimental data.
Degradation pathway of triazole fungicides and synchronous removal of transformation products via photo-electrocatalytic oxidation tandem MoS2 adsorption
Authors: Wang Junwen , Chen Xiaoxin , Sun Xiaoli , Liu Miao , Wu Xingqiang , Gong Yichao , Du Jianfang
Published: January 2021

A simple and effective tandem process of photo-electrocatalytic oxidation (PECO)-MoS2 adsorption was developed for the synchronous removal of triazole fungicides (TFs) and toxicological transformation products (TPs). In order to accurately identify trace TPs and evaluate degradation pathway during water treatment, a sensitive analytical method was developed on the basis of the stir bar sorptive extraction (SBSE) pretreatment tandem LC-MS/MS technique. Firstly, the typical TFs (PRO, TET, and DIN, C0 = 1.0 mg/L) in actual water samples were treated under the optimal process (bias voltage 1.8 V, pH 4, irradiation intensity 50 mW/cm2, 0.05 g MoS2/100 mL, 350 rpm, adsorption of 5 min). The result indicated that the residues of PRO, TET, and DIN in secondary effluent were 0.0973, 0.0617, and 0.0012 mg/L, respectively, with the removal rates of 90.3%, 93.8%, and 99.9%, respectively, undergoing 30-min photo-electrocatalysis and 5-min adsorption. The alkaline medium was favorable for the adsorption of MoS2 to TFs. The assessment results of potential cancer risk indicated that the residues of TFs in secondary effluent were safe for drinking water consumption. Besides, the major TPs were identified via the SBSE-HRLC-MS/MS technique, and one possible transformation pathway of TFs was proposed. TFs mainly underwent dehydrochlorination, cyclization, hydroxylation, etc. to produce a series of nitrogenous heterocyclic compounds that possess higher polarity than parents, hinting that TPs might pose potential aquatic toxicity. However, TPs can be removed synchronously by this tandem technique. The current study can provide a theoretical basis for the harmless treatment of TFs in the water environment.
Students’ multimodal knowledge practices in a makerspace learning environment
Authors: Kajamaa Anu , Kumpulainen Kristiina
Published: January 2021

In this study, we aim to widen the understanding of how students’ collaborative knowledge practices are mediated multimodally in a school’s makerspace learning environment. Taking a sociocultural stance, we analyzed students’ knowledge practices while carrying out STEAM learning challenges in small groups in the FUSE Studio, an elementary school’s makerspace. Our findings show how discourse, digital and other “hands on” materials, embodied actions, such as gestures and postures, and the physical space with its arrangements mediated the students’ knowledge practices. Our analysis of these mediational means led us to identifying four types of multimodal knowledge practice, namely orienting, interpreting, concretizing, and expanding knowledge, which guided and facilitated the students’ creation of shared epistemic objects, artifacts, and their collective learning. However, due to the multimodal nature of knowledge practices, carrying out learning challenges in a makerspace can be challenging for students. To enhance the educational potential of makerspaces in supporting students’ knowledge creation and learning, further attention needs to be directed to the development of new pedagogical solutions, to better facilitate multimodal knowledge practices and their collective management.
Grasping at digitalisation: turning imagination into fact in the sugarcane farming community
Authors: Fielke Simon J. , Taylor Bruce M. , Jakku Emma , Mooij Martijn , Stitzlein Cara , Fleming Aysha , Thorburn Peter J. , Webster Anthony J. , Davis Aaron , Vilas Maria P.
Published: January 2021

Nutrient runoff from catchments that drain into the Great Barrier Reef (GBR) is a significant source of stress for this World Heritage Area. An alliance of collaborative on-ground water quality monitoring (Project 25) and technologically driven digital application development (Digiscape GBR) projects were formulated to provide data that highlighted the contribution of a network of Australian sugar cane farmers, amongst other sources, to nutrient runoff. This environmental data and subsequent information were extended to the farming community through scientist-led feedback sessions and the development of specialised digital technology (1622™WQ) that help build an understanding of the nutrient movements, in this case nitrogen, such that farmers might think about and eventually act to alter their fertilizer application practices. This paper reflects on a socio-environmental sustainability challenge that emerged during this case study, by utilising the nascent concept of digi-grasping. We highlight the importance of the entire agricultural knowledge and advice network being part of an innovation journey to increase the utility of digital agricultural technologies developed to increase overall sustainability. We develop the digi-MAST analytical framework, which explores modes of being and doing in the digital world, ranging from ‘the everyday mystery of the digital world (M)’, through digital ‘awareness (A)’, digitally ‘sparked’ being/s (S), and finally the ability of individuals and/or groups to ‘transform (T)’ utilising digital technologies and human imaginations. Our digi-MAST framework allows us to compare agricultural actors, in this case, to understand present modes of digi-grasping to help determine the resources and actions likely to be required to achieve impact from the development of various forms of digital technological research outputs.
Transdisciplinary sustainability research in real-world labs: success factors and methods for change
Authors: Bergmann Matthias , Schäpke Niko , Marg Oskar , Stelzer Franziska , Lang Daniel J. , Bossert Michael , Gantert Marius , Häußler Elke , Marquardt Editha , Piontek Felix M. , Potthast Thomas , Rhodius Regina , Rudolph Matthias , Ruddat Michael , Seebacher Andreas , Sußmann Nico
Published: January 2021

The transdisciplinary research mode has gained prominence in the research on and for sustainability transformations. Yet, solution-oriented research addressing complex sustainability problems has become complex itself, with new transdisciplinary research formats being developed and tested for this purpose. Application of new formats offers learning potentials from experience. To this end, we accompanied fourteen research projects conceptualized as real-world labs (RwLs) from 2015 to 2018. RwLs were part of a funding program on ‘Science for Sustainability’ in the German federal state of Baden-Württemberg. Here, we combine conceptual and empirical work to a structured collection of experiences and provide a comprehensive account of RwLs. First, we outline characteristics of RwLs as transformation oriented, transdisciplinary research approach, using experiments, enabling learning and having a long-term orientation. Second, we outline eleven success factors and concrete design notes we gained through a survey of the 14 RwLs: (1) find the right balance between scientific and societal aims, (2) address the practitioners needs and restrictions, (3) make use of the experimentation concept, (4) actively communicate, (5) develop a ‘collaboration culture’, (6) be attached to concrete sites, (7) create lasting impact and transferability, (8) plan for sufficient time and financial means, (9) adaptability, (10) research-based learning, and (11) recognize dependency on external actors. Characteristics and success factors are combined to illustrate practical challenges in RwLs. Third, we show which methods could be used to cope with challenges in RwLs. We conclude discussing the state of debate on RwLs and outline future avenues of research.
Proteins moonlighting in tumor metabolism and epigenetics
Authors: Lv Lei , Lei Qunying
Published: January 2021

Cancer development is a complicated process controlled by the interplay of multiple signaling pathways and restrained by oxygen and nutrient accessibility in the tumor microenvironment. High plasticity in using diverse nutrients to adapt to metabolic stress is one of the hallmarks of cancer cells. To respond to nutrient stress and to meet the requirements for rapid cell proliferation, cancer cells reprogram metabolic pathways to take up more glucose and coordinate the production of energy and intermediates for biosynthesis. Such actions involve gene expression and activity regulation by the moonlighting function of oncoproteins and metabolic enzymes. The signal — moonlighting protein — metabolism axis facilitates the adaptation of tumor cells under varying environment conditions and can be therapeutically targeted for cancer treatment.
An enhanced damage plasticity model for predicting the cyclic behavior of plain concrete under multiaxial loading conditions
Authors: Azadi Kakavand Mohammad Reza , Taciroglu Ertugrul
Published: January 2021

Some of the current concrete damage plasticity models in the literature employ a single damage variable for both the tension and compression regimes, while a few more advanced models employ two damage variables. Models with a single variable have an inherent difficulty in accounting for the damage accrued due to tensile and compressive actions in appropriately different manners, and their mutual dependencies. In the current models that adopt two damage variables, the independence of these damage variables during cyclic loading results in the failure to capture the effects of tensile damage on the compressive behavior of concrete and vice-versa. This study presents a cyclic model established by extending an existing monotonic constitutive model. The model describes the cyclic behavior of concrete under multiaxial loading conditions and considers the influence of tensile/compressive damage on the compressive/tensile response. The proposed model, dubbed the enhanced concrete damage plasticity model (ECDPM), is an extension of an existing model that combines the theories of classical plasticity and continuum damage mechanics. Unlike most prior studies on models in the same category, the performance of the proposed ECDPM is evaluated using experimental data on concrete specimens at the material level obtained under cyclic multiaxial loading conditions including uniaxial tension and confined compression. The performance of the model is observed to be satisfactory. Furthermore, the superiority of ECDPM over three previously proposed constitutive models is demonstrated through comparisons with the results of a uniaxial tension-compression test and a virtual test.