bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Margins, Getting By, Persevering, or Flying High? The Intersection of Wellbeing, Attainment, and Transitions in a Scottish Longitudinal Study
Authors: Dunlop Aline-Wendy
Published: January 2021

This paper draws on a Scottish longitudinal study. It focuses on the variability of a sample of focal children's wellbeing and attainment trajectories on the journey through education from the age of 3 to school leaving at 16–18 years old in one Scottish Council area, in order to respond to the questionWhat aspects of the intersection of wellbeing, attainment, and school transitions help to explain school leaving outcomes?The relationships between wellbeing and attainment either side of primary and secondary school start are explored and the ways these may link to transition experiences and educational outcomes at school leaving are raised. A new interpretation of Bronfenbrenner's “mature” bioecological system model which considers person, processes and educational contexts over time frames the methodology, methods and findings of a data rich exploratory-interpretive longitudinal study and discusses their relationship to current dilemmas surrounding educational outcomes in Scotland at the present time. The role of wellbeing and attainment measures as proxies for school success is considered and found to be too narrow a concept in the form experienced by the focal group of study participants. While wellbeing needs to be much more clearly defined and fostered, concepts of attainment predicated only on maths and literacy (and on some measures, science) are found to be insufficient in that they may discriminate against too many. Attention to the opportunities offered and risks inherent in periods of educational transition allow identification of, and reflection upon the qualities of a good educational transition from both early childhood education to school start, and subsequently in the move to secondary education. It is found that a “good transition” though it exists, is not available to all children: consequently more equitable approaches are advocated, and alternatives for practical and policy action are proposed. Study of educational transitions dates back fifty years: is it not time for systems themselves to change?
Macroinvertebrate Recovery to Varying Hydropeaking Frequency: A Small Hydropower Plant Experiment
Authors: Aksamit Claire Kathryn , Carolli Mauro , Vanzo Davide , Weber Christine , Schmid Martin
Published: January 2021

As the demand for hydroelectricity progresses worldwide, small hydropower operators are increasingly examining the feasibility of using existing infrastructure (e.g., settling basins) in run-of-the-river schemes for intermittent power production. Such flexible production causes short-term discharge fluctuations (hydropeaking) in downstream reaches with potential adverse effects for the sensitive fauna and flora in alpine streams. In an experimental field study on a previously unregulated section of the upper Rhone River (Switzerland), we measured density and composition of macroinvertebrate drift in two habitats (riffle, pool) following a 15-minute hydropeaking wave. The experimental hydropeaking was replicated five times over 14 days with decreasing recovery times between peaks (8, 3, 2 days, and 24 h), and drift measurements were compared with kick samples for the benthic community. Results from the kick sampling showed that benthic macroinvertebrate abundance and composition did not significantly change between the experimental peaks. There were habitat specific reactions in macroinvertebrate drift to hydropeaking, with the pool experiencing more pronounced drift abundances than the riffle. Overall, drift abundance was not significantly correlated with recovery time, but results indicate taxa-specific differences. This research advocates for the importance of completing more in-situ field experiments in order to better understand the ecological impact of flexible power production in small hydropower plants.
Anthropogenic Disturbance Impacts Mycorrhizal Communities and Abiotic Soil Properties: Implications for an Endemic Forest Disease
Authors: Sapsford Sarah J. , Paap Trudy , Hardy Giles E. St. J. , Burgess Treena I.
Published: January 2021

In forest ecosystems, habitat fragmentation negatively impacts stand structure and biodiversity; the resulting fragmented patches of forest have distinct, disturbed edge habitats that experience different environmental conditions than the interiors of the fragments. In southwest Western Australia, there is a large-scale decline of the keystone tree species Corymbia calophylla following fragmentation and land use change. These changes have altered stand structure and increased their susceptibility to an endemic fungal pathogen, Quambalaria coyrecup, which causes chronic canker disease especially along disturbed forest habitats. However, the impacts of fragmentation on belowground processes in this system are not well-understood. We examined the effects of fragmentation on abiotic soil properties and ectomycorrhizal (ECM) and arbuscular mycorrhizal (AM) fungal communities, and whether these belowground changes were drivers of disease incidence. We collected soil from 17 sites across the distribution range of C. calophylla. Soils were collected across a gradient from disturbed, diseased areas to undisturbed, disease-free areas. We analysed soil nutrients and grew C. calophylla plants as a bioassay host. Plants were harvested and roots collected after 6 months of growth. DNA was extracted from the roots, amplified using fungal specific primers and sequenced using Illumina MiSeq. Concentrations of key soil nutrients such as nitrogen, phosphorus and potassium were much higher along the disturbed, diseased edges in comparison to undisturbed areas. Disturbance altered the community composition of ECM and AM fungi; however, only ECM fungal communities had lower rarefied richness and diversity along the disturbed, diseased areas compared to undisturbed areas. Accounting for effects of disturbance, ECM fungal diversity and leaf litter depth were highly correlated with increased disease incidence in C. calophylla. In the face of global change, increased virulence of an endemic pathogen has emerged in this Mediterranean-type forest.
An Evaluation of the Fasciola hepatica miRnome Predicts a Targeted Regulation of Mammalian Innate Immune Responses
Authors: Ricafrente Alison , Nguyen Hieu , Tran Nham , Donnelly Sheila
Published: January 2021

Understanding mechanisms by which parasitic worms (helminths) control their hosts’ immune responses is critical to the development of effective new disease interventions. Fasciola hepatica, a global scourge of humans and their livestock, suppresses host innate immune responses within hours of infection, ensuring that host protective responses are quickly incapacitated. This allows the parasite to freely migrate from the intestine, through the liver to ultimately reside in the bile duct, where the parasite establishes a chronic infection that is largely tolerated by the host. The recent identification of micro(mi)RNA, small RNAs that regulate gene expression, within the extracellular vesicles secreted by helminths suggest that these non-coding RNAs may have a role in the parasite-host interplay. To date, 77 miRNAs have been identified in F. hepatica comprising primarily of ancient conserved species of miRNAs. We hypothesized that many of these miRNAs are utilized by the parasite to regulate host immune signaling pathways. To test this theory, we first compiled all of the known published F. hepatica miRNAs and critically curated their sequences and annotations. Then with a focus on the miRNAs expressed by the juvenile worms, we predicted gene targets within human innate immune cells. This approach revealed the existence of targets within every immune cell, providing evidence for the universal management of host immunology by this parasite. Notably, there was a high degree of redundancy in the potential for the parasite to regulate the activation of dendritic cells, eosinophils and neutrophils, with multiple miRNAs predicted to act on singular gene targets within these cells. This original exploration of the Fasciola miRnome offers the first molecular insight into mechanisms by which F. hepatica can regulate the host protective immune response.
Cytokines Orchestrating the Natural Killer-Myeloid Cell Crosstalk in the Tumor Microenvironment: Implications for Natural Killer Cell-Based Cancer Immunotherapy
Authors: Gaggero Silvia , Witt Kristina , Carlsten Mattias , Mitra Suman
Published: January 2021

Natural killer (NK) cells are endowed with germline-encoded receptors that enable them to detect and kill malignant cells without prior priming. Over the years, overwhelming evidence has identified an essential role for NK cells in tumor immune surveillance. More recently, clinical trials have also highlighted their potential in therapeutic settings. Yet, data show that NK cells can be dysregulated within the tumor microenvironment (TME), rendering them ineffective in eradicating the cancer cells. This has been attributed to immune suppressive factors, including the tumor cellsper se, stromal cells, regulatory T cells, and soluble factors such as reactive oxygen species and cytokines. However, the TME also hosts myeloid cells such as dendritic cells, macrophages, neutrophils, and myeloid-derived suppressor cells that influence NK cell function. Although the NK-myeloid cell crosstalk can promote anti-tumor responses, myeloid cells in the TME often dysregulate NK cellsviadirect cell-to-cell interactions down-regulating key NK cell receptors, depletion of nutrients and growth factors required for NK cell growth, and secretion of metabolites, chemokines and cytokines that ultimately alter NK cell trafficking, survival, and cytotoxicity. Here, we review the complex functions of myeloid-derived cytokines in both supporting and suppressing NK cells in the TME and how NK cell-derived cytokines can influence myeloid subsets. We discuss challenges related to these interactions in unleashing the full potential of endogenous and adoptively infused NK cells. Finally, we present strategies aiming at improving NK cell-based cancer immunotherapiesviapathways that are involved in the NK-myeloid cell crosstalk in the TME.
SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection
Authors: Scheper Henk , Wubbolts Julia M. , Verhagen Joanne A. M. , de Visser Adriëtte W. , van der Wal Robert J. P. , Visser Leo G. , de Boer Mark G. J. , Nibbering Peter H.
Published: January 2021

Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.
Denser Retinal Microvascular Network Is Inversely Associated With Behavioral Outcomes and Sustained Attention in Children
Authors: Provost Eline B. , Nawrot Tim S. , Int Panis Luc , Standaert Arnout , Saenen Nelly D. , De Boever Patrick
Published: January 2021

Changes in geometry of the retinal microvascular network, including vessel width, vessel density, and tortuosity, have been associated with neurological disorders in adults. We investigated metrics of the retinal microvasculature in association with behavior and cognition in 8- to 12-year-old children. Digital fundus images of 190 children (48.2% girls, mean age 9.9 years) were used to calculate retinal vessel diameters, fractal dimension, lacunarity, and tortuosity. Parents filled out a Strengths and Difficulties Questionnaire (SDQ) for behavioral screening. Cognitive performance testing included a computerized version of the Stroop test (selective attention), the Continuous Performance (sustained attention), the Digit-Symbol (visual scanning and information-processing speed) and the Pattern Comparison (visuospatial analytic ability) tests from the Neurobehavioral Evaluation System (NES3) battery. Retinal vessel geometry was significantly associated with the SDQ problem score, which increased with 1.1 points (95% CI: 0.3 to 1.9 points) per interquartile (IQR) increment in retinal fractal dimension, and decreased 1.4 points (95% CI: −2.4 to −0.4 points) or decreased 1.0 points (95% CI: −2.1 to 0.1 points) per IQR increment in retinal vascular lacunarity or tortuosity, respectively. Sensitivity analyses showed that results were driven by the hyperactivity/inattention and conduct problem scales of the SDQ. Correspondingly, mean reaction time on the Continuous Performance test increased by 11 ms (95% CI: 4.4 to 17.6 ms) with an IQR increase in fractal dimension. The results indicate that a denser retinal microvascular network, exemplified by a higher fractal dimension and lower lacunarity, are inversely associated with behavioral outcomes and sustained attention in children.
Case Report: Myopathy in Critically Ill COVID-19 Patients: A Consequence of Hyperinflammation?
Authors: Versace Viviana , Sebastianelli Luca , Ferrazzoli Davide , Saltuari Leopold , Kofler Markus , Löscher Wolfgang , Uncini Antonino
Published: January 2021

Introduction: COVID-19-associated muscular complications may comprise myalgia, weakness, wasting, and rhabdomyolysis. Skeletal muscle damage in COVID-19 may be due to direct infection by the virus SARS-CoV-2 through interaction with the ACE2 receptor, systemic hyper-inflammatory state with cytokine release and homeostatic perturbation, an autoimmune process, or myotoxic drugs. Disclosing the cause of weakness in an individual patient is therefore difficult.

Case Description: We report two patients, who survived typical COVID-19 pneumonia requiring intensive care treatment and who developed early on myalgia and severe proximal weakness in all four limbs. Laboratory exams revealed elevated serum creatine kinase and markedly increased C-reactive protein and interleukin 6, concurring with a systemic inflammatory response. On admission in neurorehabilitation (4 and 7 weeks after COVID-19 onset, respectively), the patients presented with proximal flaccid tetraparesis and limb-girdle muscle atrophy. Motor nerve conduction studies showed decreased amplitude and prolonged duration of compound muscle action potentials (CMAPs) with normal distal motor latencies and normal conduction velocities in median and ulnar nerves. Needle electromyography in proximal muscles revealed spontaneous activity in one and myopathic changes in both patients.

Discussion: Clinical, laboratory, and electrodiagnostic findings in these patients were unequivocally consistent with myopathy. Interestingly, increased distal CMAP duration has been described in patients with critical illness myopathy (CIM) and reflects slow muscle fiber conduction velocity due to membrane hypo-excitability, possibly induced by inflammatory cytokines. By analogy with CIM, the pathogenesis of COVID-19-related myopathy might also depend on hyperinflammation and metabolic pathways that may affect muscles in a pathophysiological continuum from hypo-excitability to necrosis.
Feature-Based Attentional Weighting and Re-weighting in the Absence of Visual Awareness
Authors: Güldener Lasse , Jüllig Antonia , Soto David , Pollmann Stefan
Published: January 2021

Visual attention evolved as an adaptive mechanism allowing us to cope with a rapidly changing environment. It enables the facilitated processing of relevant information, often automatically and governed by implicit motives. However, despite recent advances in understanding the relationship between consciousness and visual attention, the functional scope of unconscious attentional control is still under debate. Here, we present a novel masking paradigm in which volunteers were to distinguish between varying orientations of a briefly presented, masked grating stimulus. Combining signal detection theory and subjective measures of awareness, we show that performance on unaware trials was consistent with visual selection being weighted towards repeated orientations of Gabor patches and reallocated in response to a novel unconsciously processed orientation. This was particularly present in trials in which the prior feature was strongly weighted and only if the novel feature was invisible. Thus, our results provide evidence that invisible orientation stimuli can trigger the reallocation of history-guided visual selection weights.
The Effects of Priming Intermittent Theta Burst Stimulation on Movement-Related and Mirror Visual Feedback-Induced Sensorimotor Desynchronization
Authors: Zhang Jack Jiaqi , Fong Kenneth N. K.
Published: January 2021

The potential benefits of priming intermittent theta burst stimulation (iTBS) with continuous theta burst stimulation (cTBS) have not been examined in regard to sensorimotor oscillatory activities recorded in electroencephalography (EEG). The objective of this study was to investigate the modulatory effect of priming iTBS (cTBS followed by iTBS) delivered to the motor cortex on movement-related and mirror visual feedback (MVF)-induced sensorimotor event-related desynchronization (ERD), compared with iTBS alone, on healthy adults. Twenty participants were randomly allocated into Group 1: priming iTBS—cTBS followed by iTBS, and Group 2: non-priming iTBS—sham cTBS followed by iTBS. The stimulation was delivered to the right primary motor cortex daily for 4 consecutive days. EEG was measured before and after 4 sessions of stimulation. Movement-related ERD was evaluated during left-index finger tapping and MVF-induced sensorimotor ERD was evaluated by comparing the difference between right-index finger tapping with and without MVF. After stimulation, both protocols increased movement-related ERD and MVF-induced sensorimotor ERD in high mu and low beta bands, indicated by significant time effects. A significant interaction effect favoring Group 1 in enhancing movement-related ERD was observed in the high mu band [F(1,18) = 4.47, p = 0.049], compared with Group 2. Our experiment suggests that among healthy adults priming iTBS with cTBS delivered to the motor cortex yields similar effects with iTBS alone on enhancing ERD induced by MVF-based observation, while movement-related ERD was more enhanced in the priming iTBS condition, specifically in the high mu band.
Rhabdomyosarcoma Cells Produce Their Own Extracellular Matrix With Minimal Involvement of Cancer-Associated Fibroblasts: A Preliminary Study
Authors: D’Agostino Stefania , Tombolan Lucia , Saggioro Mattia , Frasson Chiara , Rampazzo Elena , Pellegrini Stefania , Favaretto Francesca , Biz Carlo , Ruggieri Pietro , Gamba Piergiorgio , Bonvini Paolo , Aveic Sanja , Giovannoni Roberto , Pozzobon Michela
Published: January 2021

Background

The interplay between neoplastic cells and surrounding extracellular matrix (ECM) is one of the determinant elements for cancer growth. The remodeling of the ECM by cancer-associated fibroblasts (CAFs) shapes tumor microenvironment by depositing and digesting ECM proteins, hence promoting tumor growth and invasion. While for epithelial tumors CAFs are well characterized, little is known about the stroma composition of mesenchymal cancers, such as in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma during childhood and adolescence. The aim of this work is to identify the importance of CAFs in specifying RMS microenvironment and the role of these stromal cells in RMS growth.

Methods

We assessed in two dimensional (2D) and three dimensional (3D) systems the attraction between RMS cells and fibroblasts using epithelial colon cancer cell line as control. CAFs were studied in a xenogeneic mouse model of both tumor types and characterized in terms of fibroblast activation protein (FAP), mouse PDGFR expression, metalloproteases activation, and ECM gene and protein expression profiling.

Results

In 2D model, the rate of interaction between stromal and malignant cells was significantly lower in RMS with respect to colon cancer. Particularly, in 3D system, RMS spheroids tended to dismantle the compact aggregate when grown on the layer of stromal cells. In vivo, despite the well-formed tumor mass, murine CAFs were found in low percentage in RMS xenogeneic samples.

Conclusions

Our findings support the evidence that, differently from epithelial cancers, RMS cells are directly involved in their own ECM remodeling, and less dependent on CAFs support for cancer cell growth.
Image-Guided Radiofrequency Hyperthermia (RFH)-Enhanced Direct Chemotherapy of Hepatic Tumors: The Underlying Biomolecular Mechanisms
Authors: Qian Kun , Chen Minjiang , Zhang Feng , Chick Jeffrey Forris Beecham , Ji Hongxiu , Zheng Chuansheng , Yang Xiaoming
Published: January 2021

Purpose

To evaluate the treatment effect of radiofrequency-induced hyperthermia (RFH) combined with intra-tumoral chemotherapy for rabbit VX2 liver tumors and explore the underlying mechanism that drives local hyperthermia-enhanced chemotherapy.

Materials and Methods

VX2 cell lines and rabbits with liver VX2 tumors were randomly allocated to four treatment groups including: (1) combination therapy of Doxorubicin (DOX) plus hyperthermia/RFH (n=6); (2) DOX only; (3) hyperthermia/RFH only (n=6); and (4) phosphate-buffered saline-treated control (n=6). Cell viability and doxorubicin uptake by VX2 tumor cells were assayed using flow cytometry and fluorescence microscopy 24 h after treatments. Western blot was used to evaluate the expression level of heat shock protein 70 (HSP70) in tumor cells and tissues. For the harvested VX2 tumors, fluorescence microscopy was used to evaluate the distribution and penetration of doxorubicin in tumor tissues and HSP70 expression was analyzed by Western blot and immunohistochemistry.

Results

RFH enhanced the chemotherapeutic effect of doxorubicin in VX2 cells and rabbit liver VX2 tumors resulting in higher apoptosis and lower cell viability. Flowcytometry of VX2 cells showed more apoptotic cells in combination therapy of hyperthermia and DOX, compared with other three groups in-vitro experiments (45.80 ± 1.27% vs 20.66 ± 0.71%, vs 15.16 ± 0.81% and 0.62 ± 0.06%, respectively, p<0.01). The quantitative analysis by Western blot and immunohistochemistry showed increased expression of HSP70 in both VX2 tumor cells (1.28 ± 0.13 vs 0.64 ± 0.13 vs 0.83 ± 0.10 vs 0.15 ± 0.03, respectively, p<0.05) and tumors (1.47 ± 0.13 vs 0.51 ± 0.13 vs 0.74 ± 0.11 vs 0.16 ± 0.04, respectively, p <0.01). Fluorescence microscopy showed increased uptake of DOX in tumor cells in the combination therapy group.

Conclusions

RFH/hyperthermia enhanced the chemotherapeutic effect of DOX in VX2 tumors by promoting the uptake of DOX and the expression HSP70 in tumors.
Case Report: Fatal Multiorgan Failure and Heterochronous Pneumonitis Following Pembrolizumab Treatment in a Patient With Large-Cell Neuroendocrine Carcinoma of Lung
Authors: Xie Xiaohong , Wang Fei , Qin Yinyin , Lin Xinqing , Xie Zhanhong , Liu Ming , Ouyang Ming , Luo Bihui , Gu Yingying , Li Shiyue , Gu Dejian , Chen Rongrong , Zhou Chengzhi
Published: January 2021

Immune checkpoint inhibitors have radically changed the landscape of antitumor therapies in several malignancies. Despite the long-term efficacy, severe immune-related adverse events (irAEs) were not uncommon. However, fatal simultaneous multiorgan failure was rare. Here, we described a patient who developed multiorgan failure, including fulminant myocarditis, myasthenia gravis crisis, hepatic dysfunction, and delayed pneumonitis after pembrolizumab therapy for lung large-cell neuroendocrine carcinoma. After failure of high-dose steroid treatment, implantation of cardiac pacemaker combined with high-dose steroids successfully controlled myocarditis caused by immune checkpoint inhibitors (ICIs). Delayed pneumonitis occurred unexpectedly, and it was treated successfully with steroids. With wild adoption of ICIs in clinical practice, investigations for predictive markers of irAEs are warranted, and more successful treatment strategies are worth sharing.
Asiatic Acid, a Natural Compound that Exerts Beneficial Effects on the Cystometric and Biochemical Parameters in the Retinyl Acetate-Induced Model of Detrusor Overactivity
Authors: Wróbel Andrzej , Serefko Anna , Szopa Aleksandra , Poleszak Ewa
Published: January 2021

Scientists have been constantly looking for new synthetic and natural compounds that could have beneficial effects in bladder overactivity. Our attention was drawn by asiatic acid that influences a number of molecules and signaling pathways relevant for the proper functioning of the urinary tracts in humans. In the present project we wanted to check whether asiatic acid would have positive effects in the confirmed animal model of detrusor overactivity (DO) and whether it would affect the bladder blood flow, urothelium thickness, inflammatory and oxidative stress markers, neurotrophic and growth factors, and other parameters important for the activity of the urinary bladder. The outcomes of our study showed that a 14-day administration of asiatic acid (30 mg/kg/day) by oral gavage normalizes the cystometric parameters corresponding to DO and reduces the accompanying oxidative stress (measured by the levels of malondialdehyde–61,344 ± 24,908 pg/ml vs. 33,668 ± 5,071 pg/ml, 3-nitrotyrosine–64,615 ± 25,433 pg/ml vs. 6,563 ± 1,736 pg/ml, and NOS2–2,506 ± 411.7 vs. 3,824 ± 470.1 pg/ml). Moreover, it decreases the urinary secretion of neurotrophins (BDNF–304.4 ± 33.21 pg/ml vs. 119.3 ± 11.49 pg/ml and NGF–205.5 ± 18.50 vs. 109.7 ± 15.94 pg/ml) and prevents the changes in a range of biomarkers indicating the dysfunction of the urinary bladder, CGRP (421.1 ± 56.64 vs. 108.1 ± 11.73 pg/ml), E-Cadherin (773.5 ± 177.5 pg/ml vs. 1,560 ± 154.5 pg/ml), OCT3 (3,943 ± 814.6 vs. 1,018 ± 97.07 pg/ml), SNAP-23 (6,763 ± 808.9 pg/ml vs. 3,455 ± 554.5 pg/ml), SNAP-25 (2,038 ± 162.7 pg/ml vs. 833.3 ± 65.48), substance P (171.7 ± 16.86 pg/ml vs. 65.07 ± 8.250 pg/ml), SV2A (1,927 ± 175.3 pg/ml vs. 1,154 ± 254.9 pg/ml), tight junction protein 1 (360.1 ± 95.05 pg/ml vs. 563.4 ± 65.43 pg/ml), VAChT (16,470 ± 2,419 pg/ml vs. 7,072 ± 1,339 pg/ml), VEGFA (318.3 ± 37.89 pg/ml vs. 201.5 ± 22.91 pg/ml). The mentioned parameters are associated with smooth muscle contractions, urothelial barrier, transportation and release of transmitters, or bladder compensation. Thus, the presented findings allow to suggest a possible future role of asiatic acid in the prevention of conditions accompanied by DO, such as overactive bladder.
Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury
Authors: Shi Zhuo , Zhu Jing-xiao , Guo Yu-ming , Niu Ming , Zhang Le , Tu Can , Huang Ying , Li Peng-yan , Zhao Xu , Zhang Zi-teng , Bai Zhao-fang , Zhang Guang-qin , Lu Yang , Xiao Xiao-he , Wang Jia-bo
Published: January 2021

Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called “fat burning” effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands’ cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the “drug-host” interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.
USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway
Authors: Liu Gang , Liu Qingbai , Yan Bin , Zhu Ziqiang , Xu Yaozeng
Published: January 2021

Osteoarthritis (OA), the most common form of arthritis, is a very common joint disease that often affects middle-aged to elderly people. However, current treatment options for OA are predominantly palliative. Thus, understanding its pathological process and exploring its potential therapeutic approaches are of great importance. Rat chondrocytes were isolated and exposed to hydrogen peroxide (H2O2) to mimic OA. The effects of H2O2 on ubiquitin-specific protease 7 (USP7) expression, reactive oxygen species (ROS) levels, proliferation, inflammatory cytokine release, and pyroptosis were measured. USP7 was knocked down (KD) or overexpressed to investigate the role of USP7 in OA. Co-immunoprecipitation (Co-IP) was used to study the interaction between USP7 and NAD(P)H oxidases (NOX)4 as well as NOX4 ubiquitination. NOX4 inhibitor was applied to study the involvement of NOX4 in USP7-mediated OA development. USP7 inhibitor was given to OA animals to further investigate the role of USP7 in OA in vivo. Moreover, H2O2 treatment significantly increased USP7 expression, enhanced ROS levels, and inhibited proliferation in rat chondrocytes. The overexpression of USP7 enhanced pyroptosis, ROS production, interleukin (IL)-1β and IL-18 levels, and the expression level of NLRP3, GSDMD-N, active caspase-1, pro-caspase-1, matrix metalloproteinases (MMP) 1, and MMP13, which was abolished by ROS inhibition. The USP7 KD protected rat chondrocytes against H2O2-induced injury. Co-IP results showed that USP7 interacted with NOX4, and USP7 KD enhanced NOX4 ubiquitinylation. The inhibition of NOX4 blocked the pro-OA effect of USP7. Moreover, the USP7 inhibitor given to OA animals suppressed OA in vivo. USP7 inhibited NOX4 ubiquitination for degradation which leads to elevated ROS production. ROS subsequently activates NLPR3 inflammasome, leading to enhanced production of IL-1β and IL-18, GSDMD-N-dependent pyroptosis, and extracellular matrix remodeling. Thus, UPS7 contributes to the progression of OA via NOX4/ROS/NLPR3 axis.
Investigation on the Efficiency of Chinese Herbal Injections for Treating Non-small Cell Lung Cancer With Vinorelbine and Cisplatin Based on Multidimensional Bayesian Network Meta-Analysis
Authors: Ni Mengwei , Wang Haojia , Wang Miaomiao , Zhou Wei , Zhang Jingyuan , Wu Jiarui , Zhang Dan , Jing Zhiwei , Liu Xinkui , Wu Zhishan , Guo Siyu , Jia Shanshan , Zhang Xiaomeng , Sheng Xiaoguang
Published: January 2021

Background: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) combined with vinorelbine and cisplatin (NP) are beneficial. This multidimensional network meta-analysis was performed to explore the preferable options among different CHIs for treating NSCLC.

Methods: A literature search was performed in several databases to identify randomized controlled trials (RCTs) of CHIs in the treatment of NSCLC from inception to January 31, 2019. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 13.0 and WinBUGS 14.0 software. Each outcome was presented as an odds ratio and the surface under the cumulative ranking curve value (SCURA). The “scatterplot3d” package in R 3.6.1 software was used to perform multidimensional cluster analysis.

Results: Ultimately, 97 eligible RCTs involving 7,440 patients and 14 CHIs were included in this network meta-analysis. Combined with NP chemotherapy, Kanglaite injection plus NP exhibited a better impact on the clinical effectiveness rate (SCURA probability: 78.34%), and Javanica oil emulsion injection plus NP was better in the performance status (95.44%). Huachansu injection plus NP was dominant in reducing thrombocytopenia (92.67%) and gastrointestinal reactions (92.52%). As to multidimensional cluster analysis, Shenmai injection plus NP was superior considering improving the clinical effectiveness rate, performance status and relieving leukopenia.

Conclusions: The combination of CHIs and NP has a better impact on patients with NSCLC than NP alone. Among them, Shenmai injection plus NP, Kanglaite injection plus NP and Javanica oil emulsion injection plus NP were notable. Nevertheless, more multicenter and better designed RCTs are needed to validate our findings.
A Novel Robust Strategy for Discontinuous Galerkin Methods in Computational Fluid Mechanics: Why? When? What? Where?
Authors: Gassner Gregor J. , Winters Andrew R.
Published: January 2021

In this paper we will review a recent emerging paradigm shift in the construction and analysis of high order Discontinuous Galerkin methods applied to approximate solutions of hyperbolic or mixed hyperbolic-parabolic partial differential equations (PDEs) in computational physics. There is a long history using DG methods to approximate the solution of partial differential equations in computational physics with successful applications in linear wave propagation, like those governed by Maxwell’s equations, incompressible and compressible fluid and plasma dynamics governed by the Navier-Stokes and the Magnetohydrodynamics equations, or as a solver for ordinary differential equations (ODEs), e.g., in structural mechanics. The DG method amalgamates ideas from several existing methods such as the Finite Element Galerkin method (FEM) and the Finite Volume method (FVM) and is specifically applied to problems with advection dominated properties, such as fast moving fluids or wave propagation. In the numerics community, DG methods are infamous for being computationally complex and, due to their high order nature, as having issues with robustness, i.e., these methods are sometimes prone to crashing easily. In this article we will focus on efficient nodal versions of the DG scheme and present recent ideas to restore its robustness, its connections to and influence by other sectors of the numerical community, such as the finite difference community, and further discuss this young, but rapidly developing research topic by highlighting the main contributions and a closing discussion about possible next lines of research.
South East European International Institute for Sustainable Technologies (SEEIIST)
Authors: Amaldi Ugo , Benedetto Elena , Damjanovic Sanja , Dosanjh Manjit , Durante Marco , Georgieva Petya , Haberer Thomas , Plesko Mark , Ristova Mimoza , Rossi Sandro , Sammut Nicholas , Sapinski Mariusz , Schopper Herwig , Specht Hans , Voss Rudiger , Vretenar Maurizio , Wenninger Horst
Published: January 2021

The South East European International Institute for Sustainable Technologies (SEEIIST) was proposed in 2016 at the World Academy of Art and Science, with the objective of building a facility for charged particle cancer therapy for the South Eastern European countries. SEEIIST will offer the world-class research needed to reduce or even revert the brain drain that is causing a shortage of talent and economic losses in South East Europe. There is no particle therapy in South-East Europe in spite of a growing number of cancers being diagnosed. The facility beam time will be shared 50:50 between treating patients and performing research with a wide spectrum of different light ions beyond the presently used protons and carbon ions, which will make the facility unique in the world. SEEIIST Project is presently in a Conceptual to a Design Phase, implemented with the support of the EU and the involvement of CERN and GSI. The next phase of the project realization will include a final technical design for the facility, a structure and a business plan for the organization and the definition of conditions for the site selection.
A Review on Metasurface: From Principle to Smart Metadevices
Authors: Hu Jie , Bandyopadhyay Sankhyabrata , Liu Yu-hui , Shao Li-yang
Published: January 2021

Metamaterials are composed of periodic subwavelength metallic/dielectric structures that resonantly couple to the electric and magnetic fields of the incident electromagnetic waves, exhibiting unprecedented properties which are most typical within the context of the electromagnetic domain. However, the practical application of metamaterials is found challenging due to the high losses, strong dispersion associated with the resonant responses, and the difficulty in the fabrication of nanoscale 3D structures. The optical metasurface is termed as 2D metamaterials that inherent all of the properties of metamaterials and also provide a solution to the limitation of the conventional metamaterials. Over the past few years, metasurfaces; have been employed for the design and fabrication of optical elements and systems with abilities that surpass the performance of conventional diffractive optical elements. Metasurfaces can be fabricated using standard lithography and nanoimprinting methods, which is easier campared to the fabrication of the counterpart 3 days metamaterials. In this review article, the progress of the research on metasurfaces is illustrated. Concepts of anomalous reflection and refraction, applications of metasurfaces with the Pancharatanm-Berry Phase, and Huygens metasurface are discussed. The development of soft metasurface opens up a new dimension of application zone in conformal or wearable photonics. The progress of soft metasurface has also been discussed in this review. Meta-devices that are being developed with the principle of the shaping of wavefronts are elucidated in this review. Furthermore, it has been established that properties of novel optical metasurface can be modulated by the change in mechanical, electrical, or optical stimuli which leads to the development of dynamic metasurface. Research thrusts over the area of tunable metasurface has been reviewed in this article. Over the recent year, it has been found that optical fibers and metasurface are coagulated for the development of optical devices with the advantages of both domains. The metasurface with lab-on fiber-based devices is being discussed in this review paper. Finally, research trends, challenges, and future scope of the work are summarized in the conclusion part of the article.‬‬‬‬‬‬‬
Acute Exercise-Induced Set Shifting Benefits in Healthy Adults and Its Moderators: A Systematic Review and Meta-Analysis
Authors: Oberste Max , Sharma Sophia , Bloch Wilhelm , Zimmer Philipp
Published: January 2021

Background: Positive effects of acute exercise on cognitive performances in general inspired research that investigated the effects of acute exercise on specific cognitive subdomains. Many existing studies examined beneficial effects of acute exercise on subsequent set shifting performance in healthy adults. Set shifting, a subdomain of executive function, is the ability to switch between different cognitive sets. The results of existing studies are inconsistent. Therefore, a meta-analysis was conducted that pooled available effect sizes. Additionally, moderator analyses were carried out to identify covariates that determine the magnitude of exercise-induced set shifting benefits.

Methods: Medline, PsycINFO, and SPORTDiscus were searched for eligible studies. Hedges' g corrected standardized mean difference values were used for analyses. Random-effects weights were applied to pool effects. Potential moderation of the effect of acute exercise on subsequent set shifting performance by exercise intensity, type of exercise, participants' age, and type of control group were examined.

Results: Twenty-two studies (N = 1,900) were included into analysis. All aggregated effect sizes ranged from small to moderate. Overall, a small significant beneficial effect was revealed (g = −0.32, 95 % CI −0.45 to −0.18). Heterogeneity of included effect sizes was moderate and significant (T2 = 0.0715, I2 = 46.4%, (p < 0.0016). Moderator analyses revealed a larger average effect in older adults than for studies examining younger adults (−0.42 vs. −0.29). Light exercise (−0.51) led to larger effects than moderate (−0.24) or vigorous exercise (−0.29). Studies testing acute exercise against active control groups showed a noticeably smaller average effect (−0.13) than studies that used passive (−0.38) or cognitive engaging control groups (−0.34). Interestingly, application of resistance or aerobic exercise led to no different average effect sizes (−0.30 vs. −0.32). However, none of the tested covariates reached statistical significance.

Conclusion: Acute exercise improves subsequent set shifting performance. However, effect sizes are small, making the relevance for everyday life questionable. The results indicate that older adults benefit more from acute exercise than younger adults do. Light intensity exercise seems most effective while the type of exercise does not seem to influence the magnitude of effects. Research designs with active control groups show the smallest average effect, raising concerns about placebo effects.

PROSPERO registration number: CRD42019138799
Benefits of Baculovirus Use in IPM Strategies for Open Field and Protected Vegetables
Authors: Landwehr Anna
Published: January 2021

Widespread use of synthetic chemical insecticides causes growing concern regarding the risks to human health and negative impacts on the environment. At the same time, many insects have become resistant toward synthetic chemical insecticides. Baculoviruses bring many benefits and allow reduced use of synthetic insecticides when included in integrated pest management (IPM). They are specific to their target pest and thus do not have any negative effects on plants, mammals, and non-target insects including natural enemies and pollinators. In addition, their unique mode of action makes them suitable for resistance management. We provide examples of how baculoviruses can be applied in IPM strategies for open field and protected vegetable crops. In field trials, baculovirus products were applied in rotations and tankmixes with chlorantraniliprole, Bacillus thuringiensis products, and spinosad and provided promising control of target pests. The conducted trials in open field and protected vegetables show that baculoviruses can offer an effective solution to control pests in open field and protected vegetable production. Including baculoviruses gave results as good as other application strategies tested while conferring important benefits in reducing residues and improving the resistance management strategy.
Non-Overlapping LZ77 Factorization and LZ78 Substring Compression Queries with Suffix Trees
Authors: Köppl Dominik
Published: January 2021

We present algorithms computing the non-overlapping Lempel–Ziv-77 factorization and the longest previous non-overlapping factor table within small space in linear or near-linear time with the help of modern suffix tree representations fitting into limited space. With similar techniques, we show how to answer substring compression queries for the Lempel–Ziv-78 factorization with a possible logarithmic multiplicative slowdown depending on the used suffix tree representation.
Wind-Tunnel Measurement of Differential Pressure on the Surface of a Dynamically Inflatable Wing Cell
Authors: Benedetti Diego Muniz , Veras Carlos Alberto Gurgel
Published: January 2021

An instrumentation system for in-situ measurement of the inner-outer pressure differential at the upper and lower surfaces of dynamically inflatable wings is designed and tested, revealing important insights into the aerodynamic characteristics of inflatable airfoils. Wind tunnel tests demonstrated full capability of low-pressure differential readings in the range of 1.0–120 Pa, covering speeds from 3 to 10 m/s at angles of attack from −20 to +25°. Readings were stable, presenting coefficients of variation from 2% to 7% over the operational flight envelope. The experimental data confirmed the occurrence of a bottom leading-edge recirculation bubble, linked to the low Reynolds regime and the presence of an air intake. It supported the proposition of a novel approach to aerodynamic characterization based on local pressure differentials, which takes in account the confined airflow structure and provides lift forces estimations compatible with practical observation. The results were also compatible with data previously obtained following different strategies and were shown to be effective for parameterizing the inflation and stall phenomena. Overall, the instrumentation may be applied straightforwardly as a flight-test equipment, and it can be further converted into collapse alert and prevention systems.
Cortisol Levels of Shelter Dogs in Animal Assisted Interventions in a Prison: An Exploratory Study
Authors: d’Angelo Danila , d’Ingeo Serenella , Ciani Francesca , Visone Michele , Sacchettino Luigi , Avallone Luigi , Quaranta Angelo
Published: January 2021

Previous studies regarding the Animal Assisted Interventions (AAI) have mainly focused on the beneficial effects of human–animal interactions on human health; whereas the impact of such activities on the welfare of the animals involved has received limited attention. So far, few studies have addressed this issue by evaluating the physiological and behavioral reactions of therapy dogs during the interventions. The aim of this study was to evaluate the potential effect of AAI on the cortisol levels of shelter dogs. Five dogs participated in weekly AAI working activities with adult inmates held at a prison of the South of Italy for two months. Saliva samples were collected every two weeks in three conditions: at the kennel (baseline), after transportation and at the end of the working sessions. The results revealed a significant decrease in the cortisol baseline at the end of the AAI program, suggesting that the activities carried out with humans and in a different environment could improve the welfare of dogs housed in kennels. Moreover, we found that transportation significantly increased subjects’ cortisol levels, suggesting that it is a critical phase that deserves particular care.