bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived Causes of Students’ Poor Performance in Mathematics: A Case Study at Ba and Tavua Secondary Schools
Authors: Chand Samlesh , Chaudhary Kaylash , Prasad Avinesh , Chand Vishal
Published: April 2021

Poor achievement in mathematics is an issue of great concern for many countries across the globe. Fiji is one of the countries in the South Pacific experiencing the same trends, pressures, and concerns. This study aims to seek the views of stakeholders (students, teachers, heads of departments, and school heads) with regards to the causes of poor achievement in mathematics at the senior grades of secondary schools in the districts of Ba and Tavua, Fiji. A descriptive design using both quantitative and qualitative approaches were utilized whereby data were collected from 201 upper secondary school respondents comprising 171 students, 16 mathematics teachers, 7 department heads, and 7 school heads from seven randomly selected schools in the districts of Ba and Tavua. The study found that the students had a negative attitude toward mathematics. It was also found that an ineffective mathematics curriculum in secondary schools was the reason behind poor performance in the subject. Moreover, many of the primary school teachers lacked potential and competence to teach mathematics at primary school levels, and this largely contributed toward the lack of interest amongst students, hence translating into poor achievement at both upper and lower secondary levels. On the other hand, however, it was gathered that secondary school teachers were rather positive, good quality, performing, and fully qualified as far as the teaching of mathematics and delivery of the subject matter was concerned. Review and amendments to the year 12 and 13 mathematics curriculum, use of technologies to teach mathematics, improving the quality of primary school mathematics teachers, reducing the emphasis on exams, introducing internal assessments, projects, and field work in the mathematics curriculum were a few of the significant recommendations made from this study.
Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons
Authors: Barbosa Marta , Gomes Cátia , Sequeira Catarina , Gonçalves-Ribeiro Joana , Pina Carolina Campos , Carvalho Luís A. , Moreira Rui , Vaz Sandra H. , Vaz Ana Rita , Brites Dora
Published: April 2021

Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Thus, ALS astrocyte secretome may disrupt cell homeostasis and impact on ALS pathogenesis. Previously, we identified a specific aberrant signature in the cortical brain of symptomatic SOD1-G93A (mSOD1) mice, as well as in astrocytes isolated from the same region of 7-day-old mSOD1 mice, with upregulated S100B/HMGB1/Cx43/vimentin and downregulated GFAP. The presence of downregulated miR-146a on both cases suggests that it can be a promising target for modulation in ALS. Here, we upregulated miR-146a with pre-miR-146a, and tested glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS) for their immunoregulatory properties. VS was more effective in restoring astrocytic miR-146a, GFAP, S100B, HMGB1, Cx43, and vimentin levels than GUDCA, which only recovered Cx43 and vimentin mRNA. The miR-146a inhibitor generated typical ALS aberrancies in wild type astrocytes that were abolished by VS. Similarly, pre-miR-146a transfection into the mSOD1 astrocytes abrogated aberrant markers and intracellular Ca2+ overload. Such treatment counteracted miR-146a depletion in sEVs and led to secretome-mediated miR-146a enhancement in NSC-34-motor neurons (MNs) and N9-microglia. Secretome from mSOD1 astrocytes increased early/late apoptosis and FGFR3 mRNA in MNs and microglia, but not when derived from pre-miR-146a or VS-treated cells. These last strategies prevented the impairment of axonal transport and synaptic dynamics by the pathological secretome, while also averted microglia activation through either secretome, or their isolated sEVs. Proteomic analysis of the target cells indicated that pre-miR-146a regulates mitochondria and inflammation via paracrine signaling. We demonstrate that replenishment of miR-146a in mSOD1 cortical astrocytes with pre-miR-146a or by VS abrogates their phenotypic aberrancies and paracrine deleterious consequences to MNs and microglia. These results propose miR-146a as a new causal and emerging therapeutic target for astrocyte pathogenic processes in ALS.
Investigation of Triple Symmetric Non-halogen Benzene Derivative Solvent for Spray-Coated Polymer Solar Cells
Authors: Tang Yang , Tang Hua , Bai Youjun , Hu Rong , Yan Xinwu , Li Lu , Cheng Jiang
Published: April 2021

The performance of spray-coated polymer solar cells could be largely improved via morphologies and phase optimization by solvent engineering. However, there is still a lack of fundamental knowledge and know-how in controlling blend morphology by using various solvents. Here, the effect of adding low polar benzene and non-halogen benzene derivatives with triple symmetric molecular has been systematically investigated and discussed. It is found that the triple symmetric non-halogen benzene could promote the formation of preferential face-on molecule orientation for PBDB-T-2Cl:IT4F films by grazing incidence wide-angle X-ray scattering. The X-ray photoelectron spectroscopy shows that PBDB-T-2Cl could be transported to the surface of the blend film during drying process. A 3D opt-digital microscope shows that triple symmetric non-halogen benzene could also improve the morphologies of active layers by reducing the coffee ring or other micro-defects. Due to the appropriate vapor pressures, devices with mixing 20% benzene or the triple symmetric non-halogen in spray solution could significantly improve the device performance. Device prepared using 20% 1,3,5-trimethylbenzene (TMB) and 80% chlorobenzene (CB) mixture solvent has the best morphology and phase structure, and the power conversion efficiency (PCE) of the device was increased nearly 60 to 10.21% compared with the device using CB as the only solvent.
Seeded Growth of Au@CuxO Core–Shell Mesoporous Nanospheres and Their Photocatalytic Properties
Authors: Zhang Gongguo , Ma Yanyun , Liu Feng , Tong Zhibo , Sha Jingquan , Zhao Wenjun , Liu Maochang , Zheng Yiqun
Published: April 2021

We report a facile synthesis of Au@CuxO core–shell mesoporous nanospheres with tunable size in the aqueous phase via seeded growth. The success of the current work relies on the use of a halide-free copper (Cu) precursor and n-oleyl-1,3-propanediamine as a capping agent to facilitate the formation of a copperish oxide shell with a mesoporous structure and the presence of mixed oxidation states of Cu. By varying the amount of spherical Au seeds while keeping other parameters unchanged, their diameters could be readily tuned without noticeable change in morphology. As compared with commercial Cu2O, the as-prepared Au@CuxO core–shell mesoporous nanospheres exhibit the higher adsorption ability, enhanced activity, and excellent stability toward photocatalytic degradation of methyl orange (MO) under visible light irradiation, indicating their potential applications in water treatment.
Hemodynamic Parameters Predict In-stent Thrombosis After Multibranched Endovascular Repair of Complex Abdominal Aortic Aneurysms: A Retrospective Study of Branched Stent-Graft Thrombosis
Authors: Liu Ming-Yuan , Jiao Yang , Liu Junjun , Zhang Simeng , Li Wei
Published: April 2021

Background: Branch vessel occlusion is reported in endovascular repair of aortic pathology. This study aimed to evaluate the hemodynamic indicators associated with in-stent thrombosis (IST) of a branched stent-graft (BSG) after endovascular aortic repair (EVAR) of a complex abdominal aortic aneurysm.

Methods: A retrospective evaluation was performed based on the computed tomography (CT) scans and clinical data of three patients who underwent multi-branched endovascular repair. Patient-specific 3-dimensional models were reconstructed, and hemodynamic analysis was performed for IST. Hemodynamics-related parameters including time-averaged wall shear stress (TAWSS), oscillatory shear stress index (OSI), and relative residence time (RRT) were compared among the individual patients.

Results: The flow velocity, TAWSS, OSI, and RRT were radically changed in the area of the IST. In BSGs, IST tended to occur in the regions of hemodynamic alteration near the bends in the device, where a decreased flow velocity (<0.6 m/s) and TAWSS (<0.8 Pa) and an elevated OSI (>0.2) and RRT (>5 s) were consistently observed.

Conclusions: Hemodynamic perturbations in BSGs cause a predisposition to IST, which can be predicted by a series of changes in the flow parameters. Early hemodynamic analysis might be useful for identifying and remediating IST after multibranched endovascular repair.
Effect of Day 3 and Day 5/6 Embryo Quality on the Reproductive Outcomes in the Single Vitrified Embryo Transfer Cycles
Authors: Wang Ningling , Zhao Xinxi , Ma Meng , Zhu Qianqian , Wang Yao
Published: April 2021

Objective

To explore the live birth rate and neonatal outcome after single vitrified blastocyst transfer versus single vitrified cleavage-stage embryo transfer at different grades of embryo quality.

Methods

A retrospective cohort study including 6077 single vitrified-thawed embryo transfer cycles was performed in the time-period from January 2013 to December 2018.

Results

After controlling for potential confounding variables, there are 161% increased odds of a live birth after transfer of single good quality embryo at day 5, 152% increased odds of a live birth after transfer of single poor quality embryo at day 5, 60% increased odds of a live birth after transfer of single good quality embryo at day 6 compared with transfer of single good quality embryo at day 3. Results from the generalized estimated equation regression showed significant relationship of unadjusted birth weight with development stage of embryo and embryo quality (good quality embryo on day 5 vs. Good quality embryo on day 3:β=108.55, SE=34.89, P=0.002; good quality embryo on day 6 vs. Good quality embryo on day 3:β=68.80, SE=33.75, P=0.041). However, no significant differences were seen in birth weight between transfer single poor quality embryo on day 5, 6 and transfer single good quality embryo on day 3.

Conclusion

A significant increase in live birth rate and birth weight after transfer of single good quality embryo on day 5 and day 6 compared with transfer of single good quality embryo on day 3 in the vitrified embryo transfer cycles.
Investigating the Effect of Cloud Cover on Radiative Cooling Potential With Artificial Neural Network Modeling
Authors: Mokhtari Reza , Fakouriyan Samaneh , Ghasempour Roghayeh
Published: April 2021

Radiative cooling is a novel and promising technology in which, heat is radiated through the infrared wavelength (8–13 μm) to the cold outer space, while the incident solar radiation (0.3–4 μm) is reflected. This leads to a temperature reduction in the material that can be utilized as a free and renewable resource of cooling for different applications. For the sake of increasing the efficiency and the cooling potential of these systems, scientists have precisely studied the affecting parameters and developed analytical equations. The sky cloud coverage is one of the major affecting parameters that is challenging to model due to its inherent complexity and diversity. Therefore, in this article, we investigated the effect of cloud cover on the radiative cooling potential by utilizing machine learning techniques. In this regard, a non-linear autoregressive with exogenous feedback (NARX) neural network has been developed to predict the temperature of the system in different climate conditions by taking cloud coverage into account. Results of this investigation indicate that there is an intensely indirect relationship between cloud coverage and the performance of the system. Accordingly, a cloudy sky can lead to 15°C inaccuracy in the modeling of the system and may even lead to a temperature increase relative to the ambient, which inhibits the applicability of the system. It was eventually concluded that the cloud cover, as one of the major parameters that determine the performance of the system, must be taken into account in radiative cooling system designs.
Research on Optimal Operation of Electricity Heat Hydrogen System Based on Evaluation of New Energy Consumption Potential
Authors: Liu Xinrui , Zhao Xinying , Zhong Weiyang
Published: April 2021

Under the background of the “double high” power system, the electricity heat hydrogen system (EHHS) plays a significant role in the process of energy decarbonization. In order to meet the different optimization objectives of the system under different new energy consumption states, a new energy consumption potential assessment and optimized operation method based on intuitionistic fuzzy rough set theory is proposed. By using the intuitionistic fuzzy rough set theory, the continuous attribute data is divided into different levels and the results of its membership and non-membership are gotten at different levels. The membership results of real-time consumption data are matched with the rule sets, and then the system consumption state judgment result is obtained. In this article, the system consumption situation is divided into five states, and compared with the traditional division method, so the system state can be described more comprehensively. At the same time, the fuzzy set is used to deal with the ambiguity of the boundary between each state. The intuition theory is used to solve the problem of the uncertainty of the consumption state, and then the accurate judgment can be realized. In response to different consumption states, an optimal scheduling model is established in which a hydrogen heat energy system (HHES) is involved to meet different requirements, and a hybrid particle swarm optimization algorithm is used to solve the model. Adopting the IEEE-30 bus system as the network structure of EHHS in the simulation, the analysis shows that the dynamic state division method based on intuitionistic fuzzy rough set theory can better be used to judge the system state according to real-time variable factors. The system optimization based on the consumption state division has the advantages of improving the operating economy and increasing the consumption of new energy.
LCZ Generator: A Web Application to Create Local Climate Zone Maps
Authors: Demuzere Matthias , Kittner Jonas , Bechtel Benjamin
Published: April 2021

Since their introduction in 2012, Local Climate Zones (LCZs) emerged as a new standard for characterizing urban landscapes, providing a holistic classification approach that takes into account micro-scale land-cover and associated physical properties. In 2015, as part of the community-based World Urban Database and Access Portal Tools (WUDAPT) project, a protocol was developed that enables the mapping of cities into LCZs, using freely available data and software packages, yet performed on local computing facilities. The LCZ Generator described here further simplifies this process, providing an online platform that maps a city of interest into LCZs, solely expecting a valid training area file and some metadata as input. The web application (available athttps://lcz-generator.rub.de) integrates the state-of-the-art of LCZ mapping, and simultaneously provides an automated accuracy assessment, training data derivatives, and a novel approach to identify suspicious training areas. As this contribution explains all front- and back-end procedures, databases, and underlying datasets in detail, it serves as the primary “User Guide” for this web application. We anticipate this development will significantly ease the workflow of researchers and practitioners interested in using the LCZ framework for a variety of urban-induced human and environmental impacts. In addition, this development will ease the accessibility and dissemination of maps and their metadata.
The Volatilome: A Vital Piece of the Complete Soil Metabolome
Authors: Honeker Linnea K. , Graves Kelsey R. , Tfaily Malak M. , Krechmer Jordan E. , Meredith Laura K.
Published: April 2021

Soils harbor complex biological processes intertwined with metabolic inputs from microbes and plants. Measuring the soil metabolome can reveal active metabolic pathways, providing insight into the presence of specific organisms and ecological interactions. A subset of the metabolome is volatile; however, current soil studies rarely consider volatile organic compounds (VOCs), contributing to biases in sample processing and metabolomic analytical techniques. Therefore, we hypothesize that overall, the volatility of detected compounds measured using current metabolomic analytical techniques will be lower than undetected compounds, a reflection of missed VOCs. To illustrate this, we examined a peatland metabolomic dataset collected using three common metabolomic analytical techniques: nuclear magnetic resonance (NMR), gas chromatography-mass spectroscopy (GC-MS), and fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). We mapped the compounds to three metabolic pathways (monoterpenoid biosynthesis, diterpenoid biosynthesis, and polycyclic aromatic hydrocarbon degradation), chosen for their activity in peatland ecosystems and involvement of VOCs. We estimated the volatility of the compounds by calculating relative volatility indices (RVIs), and as hypothesized, the average RVI of undetected compounds within each of our focal pathways was higher than detected compounds (p< 0.001). Moreover, higher RVI compounds were absent even in sub-pathways where lower RVI compounds were observed. Our findings suggest that typical soil metabolomic analytical techniques may overlook VOCs and leave missing links in metabolic pathways. To more completely represent the volatile fraction of the soil metabolome, we suggest that environmental scientists take into consideration these biases when designing and interpreting their data and/or add direct online measurement methods that capture the integral role of VOCs in soil systems.
Emergent Rarity Properties in Carabid Communities From Chinese Steppes With Different Climatic Conditions
Authors: Tsafack Noelline , Borges Paulo A. V. , Xie Yingzhong , Wang Xinpu , Fattorini Simone
Published: April 2021

Species abundance distributions (SADs) are increasingly used to investigate how species community structure changes in response to environmental variations. SAD models depict the relative abundance of species recorded in a community and express fundamental aspects of the community structure, namely patterns of commonness and rarity. However, the influence of differences in environmental conditions on SAD characteristics is still poorly understood. In this study we used SAD models of carabid beetles (Coleoptera: Carabidae) in three grassland ecosystems (desert, typical, and meadow steppes) in China. These ecosystems are characterized by different aridity conditions, thus offering an opportunity to investigate how SADs are influenced by differences in environmental conditions (mainly aridity and vegetation cover, and hence productivity). We used various SAD models, including the meta-community zero sum multinomial (mZSM), the lognormal (PLN) and Fisher’s logseries (LS), and uni- and multimodal gambin models. Analyses were done at the level of steppe type (coarse scale) and for different sectors within the same steppe (fine scale). We found that the mZSM model provided, in general, the best fit at both analysis scales. Model parameters were influenced by the scale of analysis. Moreover, the LS was the best fit in desert steppe SAD. If abundances are rarefied to the smallest sample, results are similar to those without rarefaction, but differences in models estimates become more evident. Gambin unimodal provided the best fit with the lowest α-value observed in desert steppe and higher values in typical and meadow steppes, with results which were strongly affected by the scale of analysis and the use of rarefaction. Our results indicate that all investigated communities are adequately modeled by two similar distributions, the mZSM and the LS, at both scales of analyses. This indicates (1) that all communities are characterized by a relatively small number of species, most of which are rare, and (2) that the meta-communities at the large scale maintain the basic SAD shape of the local communities. The gambin multimodal models produced exaggerated α-values, which indicates that they overfit simple communities. Overall, Fisher’s α, mZSM θ, and gambin α-values were substantially lower in the desert steppe and higher in the typical and meadow steppes, which implies a decreasing influence of environmental harshness (aridity) from the desert steppe to the typical and meadow steppes.
The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda
Authors: Kalungi Allan , Womersley Jacqueline S. , Kinyanda Eugene , Joloba Moses L. , Ssembajjwe Wilber , Nsubuga Rebecca N. , Seedat Soraya , Hemmings Sian M. J.
Published: April 2021

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.

Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.

Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs.

Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs.

Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.
Gene Targeting in Disease Networks
Authors: Weighill Deborah , Ben Guebila Marouen , Glass Kimberly , Platig John , Yeh Jen Jen , Quackenbush John
Published: April 2021

Profiling of whole transcriptomes has become a cornerstone of molecular biology and an invaluable tool for the characterization of clinical phenotypes and the identification of disease subtypes. Analyses of these data are becoming ever more sophisticated as we move beyond simple comparisons to consider networks of higher-order interactions and associations. Gene regulatory networks (GRNs) model the regulatory relationships of transcription factors and genes and have allowed the identification of differentially regulated processes in disease systems. In this perspective, we discuss gene targeting scores, which measure changes in inferred regulatory network interactions, and their use in identifying disease-relevant processes. In addition, we present an example analysis for pancreatic ductal adenocarcinoma (PDAC), demonstrating the power of gene targeting scores to identify differential processes between complex phenotypes, processes that would have been missed by only performing differential expression analysis. This example demonstrates that gene targeting scores are an invaluable addition to gene expression analysis in the characterization of diseases and other complex phenotypes.
Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age
Authors: Kulkarni-Munje Archana , Malshe Nandini , Palkar Sonali , Amlekar Aniket , Lalwani Sanjay , Mishra Akhilesh Chandra , Arankalle Vidya
Published: April 2021

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.
Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?
Authors: Ohl Kim , Tenbrock Klaus
Published: April 2021

Oxidative stress is a major component of cellular damage in T cells from patients with systemic lupus erythematosus (SLE) resulting amongst others in the generation of pathogenic Th17 cells. The NRF2/Keap1 pathway is the most important antioxidant system protecting cells from damage due to oxidative stress. Activation of NRF2 therefore seems to represent a putative therapeutic target in SLE, which is nevertheless challenged by several findings suggesting tissue and cell specific differences in the effect of NRF2 expression. This review focusses on the current understanding of oxidative stress in SLE T cells and its pathophysiologic and therapeutic implications.
The NLRP3-Inflammasome-Caspase-1 Pathway Is Upregulated in Idiopathic Pulmonary Fibrosis and Acute Exacerbations and Is Inducible by Apoptotic A549 Cells
Authors: Jäger Benedikt , Seeliger Benjamin , Terwolbeck Oliver , Warnecke Gregor , Welte Tobias , Müller Meike , Bode Christian , Prasse Antje
Published: April 2021

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease harboring significant morbidity and mortality despite recent advances in therapy. Regardless of disease severity acute exacerbations (IPF-AEs) may occur leading to considerable loss of function and are the leading cause of death in IPF. Histologic features of IPF-AE are very similar to acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the role of the NLRP3 inflammasome in IPF and IPF-AE. Bronchoalveolar lavage (BAL) cells were sampled from patients with IPF (n = 32), IPF-AE (n = 10), ARDS (n = 7) and healthy volunteers (HV, n = 37) and the NLRP3-inflammasome was stimulated in-vitro. We found the NLRP3 inflammasome to be hyper-inducible in IPF compared to HV with increased IL-1ß and pro-IL-1ß levels on ELISA upon stimulation as well as increased caspase-1 activity measured by caspase-1p20 immunoblotting. In IPF-AE, IL-1ß was massively elevated to an extent similar to ARDS. To evaluate potential mechanisms, we co-cultured BAL cells with radiated A549 cells (a model to simulate apoptotic alveolar epithelial cells), which led to increased NLRP3 mRNA expression and increased caspase-1 dependent IL-1ß production. In the presence of a reactive oxygen species (ROS) inhibitor (diphenyleneiodonium) and a cathepsin B inhibitor (E64D), NLRP3 expression was suppressed indicating that induction of NLRP3 activation following efferocytosis of apoptotic A549 cells is mediated via ROS and cathepsin-B. In summary, we present evidence of involvement of the NLRP3 inflammasome-caspase pathway in the pathogenesis of IPF-AE, similarly to ARDS, which may be mediated by efferocytosis of apoptotic alveolar epithelial cells in IPF.
Immunopathology of Acute Kidney Injury in Severe Malaria
Authors: Katsoulis Orestis , Georgiadou Athina , Cunnington Aubrey J.
Published: April 2021

Acute kidney injury (AKI) is a common feature of severe malaria, and an independent risk factor for death. Previous research has suggested that an overactivation of the host inflammatory response is at least partly involved in mediating the kidney damage observed inP. falciparumpatients with AKI, however the exact pathophysiology of AKI in severe malaria remains unknown. The purpose of this mini-review is to describe how different aspects of malaria pathology, including parasite sequestration, microvascular obstruction and extensive intravascular hemolysis, may interact with each other and contribute to the development of AKI in severe malaria, by amplifying the damaging effects of the host inflammatory response. Here, we highlight the importance of considering how the systemic effects and multi-organ involvement of malaria are intertwined with the localized effects on the kidney.
From the Immune Profile to the Immunoscore: Signatures for Improving Postsurgical Prognostic Prediction of Pancreatic Neuroendocrine Tumors
Authors: Wei Miaoyan , Xu Jin , Hua Jie , Meng Qingcai , Liang Chen , Liu Jiang , Zhang Bo , Wang Wei , Yu Xianjun , Shi Si
Published: April 2021

Objective

Immune infiltration plays an important role in tumor development and progression and shows promising prognostic value in numerous tumors. In this study, we aimed to identify the role of immune infiltration in pancreatic neuroendocrine tumors (Pan-NETs) and to establish an Immunoscore system to improve the prediction of postsurgical recurrence-free survival.

Methods

To derive transcriptional signatures and deconvolute specific immune populations, two GEO datasets containing 158 Pan-NET patients were reanalyzed to summarize the immune infiltration landscape and identify immune-related signatures. Using real-time reverse transcription-polymerase chain reaction, immunofluorescence and immunochemistry methods, candidate signatures were further detected. The least absolute shrinkage and selection operator (LASSO) logistic regression model used statistically significant survival predicators in the training cohort (n=125) to build an Immunoscore system. The prognostic and predictive accuracy was validated in an external independent cohort of 77 patients.

Results

The immune infiltration profile in Pan-NETs showed significant heterogeneity, among which accumulated immune cells, T lymphocytes and macrophages were predominant. Fourteen statistically significant immune-related signatures were further identified in the screening cohort. The Immunoscore system for Pan-NETs (ISpnet) consisting of six immune features (CCL19, IL-16, CD163, IRF4, CD8PT and CD8IT) was constructed to classify patients as high and low risk in the training cohort (cutoff value = 2.14). Low-risk patients demonstrated longer 5-year recurrence-free survival (HR, 0.061; 95% CI, 0.026 to 0.14; p < 0.0001), with fewer recurrences and better prognoses. To predict the individual risk of recurrence, a nomogram incorporating both immune signatures and clinicopathological characteristics was developed.

Conclusion

Our model, ISpnet, captures immune feature-associated prognostic indicators in Pan-NETs and represents the first immune feature-based score for the postsurgical prognostic prediction. The nomogram based on the ISpnet and independent clinical risk factors might facilitate decision-making regarding early recurrence risk monitoring, identify high-risk patients in need of adjuvant therapy, and provide auxiliary guidance for patients with Pan-NETs that may benefit from immunotherapy in clinical trials.
Endometrial Cancer Suppresses CD8+ T Cell-Mediated Cytotoxicity in Postmenopausal Women
Authors: Patel Mickey V. , Shen Zheng , Rodriguez-Garcia Marta , Usherwood Edward J. , Tafe Laura J. , Wira Charles R.
Published: April 2021

Endometrial cancer is the most common gynecological cancer. To investigate how it suppresses host immune function, we isolated CD8+ T cells from endometrial endometroid carcinomas and adjacent non-cancerous endometrium and determined if the tumor environment regulates cytotoxic capacity. Endometrial carcinomas had increased numbers of CD8+ T cells compared to adjacent non-cancerous endometrium. Tumor CD8+ T cells expressed significantly less granzyme A (GZA), B (GZB), and PD-1 than those in adjacent non-cancerous tissues and also had significantly lower cytotoxic killing of allogeneic target cells. CD103-CD8+ T cells, but not CD103+CD8+ T cells, from both adjacent and tumor tissue were primarily responsible for killing of allogeneic target cells. Secretions recovered from endometrial carcinoma tissues suppressed CD8+ cytotoxic killing and lowered perforin, GZB and PD-1 expression relative to non-tumor CD8+ T cells. Furthermore, tumor secretions contained significantly higher levels of immunosuppressive cytokines including TGFβ than non-tumor tissues. Thus, the tumor microenvironment suppresses cytotoxic killing by CD8+ T cellsviathe secretion of immunosuppressive cytokines leading to decreased expression of intracellular cytolytic molecules. These studies demonstrate the complexity of CD8+ T cell regulation within the endometrial tumor microenvironment and provide a foundation of information essential for the development of therapeutic strategies for gynecological cancers.
Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis
Authors: Zhou Ran , Jiang Fei , Cai Haobing , Zeng Qiuming , Yang Huan
Published: April 2021

The association between multiple sclerosis and anti-N-Methyl-D-Aspartate receptor encephalitis is limited to merely a few case reports, and the exploration of the pathogenic mechanisms underlying the overlap of these two disease entities is very limited. Therefore, case reports and literature review on N-Methyl-D-aspartate receptor antibody in patients with multiple sclerosis are unusual and noteworthy. A young female had the first episode of paresthesia and motor symptoms with positive anti-N-Methyl-D-Aspartate receptor antibody and recovered after immunotherapy, and at the first relapse, the patient developed disorders of consciousness with positive anti-N-Methyl-D-Aspartate receptor antibody, findings of magnetic resonance imaging showed features of autoimmune encephalitis, which was also controlled by immunotherapy. At the second relapse, anti-N-Methyl-D-Aspartate receptor antibody turned negative while oligoclonal bands presented positive, and findings of magnetic resonance imaging showed features of multiple sclerosis. Afterwards, we followed the patient after receiving disease modifying treatment to monitor the efficacy and safety of teriflunomide. Based on literature review, demyelinating diseases patients with anti-neuronal antibody have complex, diverse and atypical symptoms; therefore, high attention and increased alertness are necessary for neurologists. Conclusively, anti-neuronal antibody may present in many neuroinflammatory conditions, and diagnostic criteria should be used with caution if the clinical presentation is atypical, and neurologists should not rely excessively on laboratory tests to diagnose neurological diseases. Timely and comprehensive examination and consideration as well as early standardized treatment are the key factors to reduce patient recurrence and obtain a good prognosis.
CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment
Authors: Chen Yanzhu , Meng Zhishang , Zhang Lin , Liu Feng
Published: April 2021

Female breast cancer (BCa) is the most commonly occurring cancer worldwide. The tumor microenvironment (TME) plays an essential role in tumor invasion, angiogenesis, unlimited proliferation, and even immune escape, but we know little about the TME of BCa. In this study, we aimed to find a TME-related biomarker for BCa, especially for invasive breast carcinoma (BRCA), that could predict prognosis and immunotherapy efficacy. Based on RNA-seq transcriptome data and the clinical characteristics of 1222 samples (113 normal and 1109 tumor samples) from The Cancer Genome Atlas (TCGA) database, we used the ESTIMATE algorithm to calculate the ImmuneScore and StromalScore and then identified differentially expressed genes (DEGs) between the high and low ImmuneScore groups and the high and low StromalScore groups. Thereafter, a protein–protein interaction (PPI) network analysis and univariate Cox regression analyses of overall survival were used to identify potential key genes. Five candidate genes were identified, comprising CD2, CCL19, CD52, CD3E, and ITK. Thereafter, we focused on CD2, analyzing CD2 expression and its association with survival. CD2 expression was associated with tumor size (T stage) to some extent, but not with overall TNM stage, lymph node status (N stage), or distant metastasis (M stage). High CD2 expression was associated with longer survival. METABRIC data were used to validate the survival result (n = 276). Gene set enrichment analysis (GSEA) showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly associated with high CD2 expression were mainly immune-related pathways. Furthermore, CD2 expression was correlated with 16 types of tumor-infiltrating immune cells (TICs). Hence, CD2 might be a novel biomarker in terms of molecular typing, and it may serve as a complementary approach to TNM staging to improve clinical outcome prediction for BCa patients.
A Double-Antibody Sandwich ELISA for Sensitive and Specific Detection of Swine Fibrinogen-Like Protein 1
Authors: Zhang Xin , Zhu Haipeng , Zheng Xu , Jiao Yunjie , Ning Lulu , Zhou En-Min , Mu Yang
Published: April 2021

Fibrinogen-like protein 1 (FGL1), a member of the fibrinogen family, is a specific hepatocyte mitogen. Recently, it has been reported that FGL1 is the main inhibitory ligand of lymphocyte activating gene 3 (LAG3). Furthermore, the FGL1-LAG3 pathway has a synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway and is regarded as a promising immunotherapeutic target. However, swine FGL1 (sFGL1) has not been characterized and its detection method is lacking. In the study, the sFGL1 gene was amplified from the liver tissue of swine and then inserted into a prokaryotic expression vector, pQE-30. The recombinant plasmid pQE30-sFGL1 was transformed into JM109 competent cells. The recombinant sFGL1 was induced expression by isopropyl-β-d-thiogalactoside (IPTG) and the purified sFGL1 was used as an antigen to produce mouse monoclonal antibody (mAb) and rabbit polyclonal antibody (pAb). After identification, a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) for sensitive and specific detection of sFGL1 was developed. Swine FGL1 in samples was captured by anti‐sFGL1 mAb followed by detection with anti‐sFGL1 rabbit pAb and HRP-conjugated goat anti-rabbit IgG. The limit of detection of the developed sFLG1-DAS-ELISA is 35 pg/ml with recombinant sFLG1. Besides, it does not show cross‐reactivity with the control protein. Then serum samples of PRRSV-negative and -positive pigs were tested with the established DAS-ELISA and calculated according to the equation of y=0.0735x+0.0737. The results showed that PRRSV infection enhanced the serum FGL1 levels significantly. Our research provides a platform for the research on the functional roles of swine FGL1.
Spatial and Temporal Effects of Whale Watching on a Tourism-Naive Resident Population of Bottlenose Dolphins (Tursiops truncatus) in the Humboldt Penguin National Reserve, Chile
Authors: Toro Frederick , Alarcón Jaime , Toro-Barros Bárbara , Mallea Gabriela , Capella Juan , Umaran-Young Clara , Abarca Paulette , Lakestani Nelly , Peña Claudia , Alvarado-Rybak Mario , Cruz Franco , Vilina Yerko , Gibbons Jorge
Published: April 2021

Standardized measures of behavior can be powerful tools for assessing the impact of whale watching activities on natural populations of cetaceans. To determine the possible impact of tourism on dolphins between a period without whale watching (1989–1992) (T1) and a period with whale watching (2010–2020) (T2), we examined the changes in the rate of surface behaviors, the group size of long-time resident bottlenose dolphins living in the waters of the Humboldt Current off Chile, and for T2 alone, we compared these differences between two localities, the Punta de Choros and Chañaral de Aceituno coves. We observed a significant decrease in the group size of the resident population and in the frequency of surface events associated with the absence and presence of tourism. For T2, we observed significant differences for the frequency of surface events between the Chañaral de Aceituno and Punta de Choros coves and differences in the frequency of surface events at different hours of the day. This was associated with the number of vessels at the time of the encounter. In addition, we observed for T2 that the most observed instantaneous response of the dolphins to the presence of tourist vessels was to avoid the boats, while approaching the boats was the least observed response. The number of vessels present in each dolphin encounter was the most important variable for our model as it explains these differences. These results show that tourism vessels have a significant impact on dolphin behavior and sociability, while the same population of dolphins have different spatial and temporal responses to different impacts of tourism. Further studies are needed to establish whether changes in the rate of surface behaviors are associated with higher levels of stress in dolphins and with effects on their health and reproductive success in the long term.
Molecular Evolutionary Analyses of Euplotes Species Living in Freshwater and Marine Habitats: A Mitogenomic Perspective
Authors: Huang Ning , Chen Shuai , He Ming , Song Qi , Hou Lina , Zhao Yan , Zhao Shuo , Miao Miao
Published: April 2021

Ciliates are the most complex unicellular eukaryotic organisms, which play important roles in various ecosystems. The Euplotes is a dominant genus in the ciliates Euplotida and consists of approximate one hundred species. They distribute widely in environments with various salinity levels including freshwater, brackish, seawater as well as hypersaline. In this study, we obtained four mitochondrial genomes of Euplotes species, using both high throughput sequencing and Sanger sequencing. Combined with two previously reported Euplotes mitochondrial genomes, we analyzed their gene structure, codon usage pattern as well as phylogenetic relationship. We found that gene rearrangement exists in Euplotes and codon usage bias is different among these species. Phylogenetic analyses based on both mitochondrial and nuclear genes further unveiled that Euplotes spp. living in similar salinity levels tend to be clustered together. Moreover, we found that the dN/dS ratios of two mitochondrial genes, cox1 and cox2, are significantly different between marine and freshwater species, indicating the salinity could act as a barrier for the Euplotes species distribution. We also recommended mitochondrial genes to discriminate the species with highly similarity of Euplotes which could not be easily distinguished by nuclear gene marker and morphological characteristics. This study provides novel resources to improve our understanding of Euplotes evolution and also its adaptation to habitats with different salinity levels.
Novel Magnesium Based Materials: Are They Reliable Drone Construction Materials? A Mini Review
Authors: Höche Daniel , Weber Wolfgang E. , Gazenbiller Eugen , Gavras Sarkis , Hort Norbert , Dieringa Hajo
Published: April 2021

Novel magnesium-based materials are ideal candidates for use in future aviation vehicles because they are extremely light and can therefore significantly increase the range of these vehicles. They show very good castability, are easy to machine and can be shaped into profiles or forgings to be used as components for next generation aerial vehicle construction. In the case of a large number of identical components, high-pressure die casting of magnesium alloys is clearly superior to high-pressure die casting of aluminum alloys. This is due to the lower solubility of iron in magnesium and thus tool/casting life is significantly longer. In addition, the die filling times for magnesium high-pressure die casting are approximately 30% shorter. This is due to the lower density: aluminum alloys are approximately 50% heavier than magnesium alloys, which is a significant disadvantage for aluminum alloys especially in the aerospace industry. There are cost-effective novel die casting alloys, besides AZ91 or AM50/60 such as DieMag633 or MRI230D, which show very good specific strength at room and elevated temperatures. In the case of magnesium-based wrought alloys, the choice is smaller, a typical representative of these materials is AZ31, but some new alloys based on Mg-Zn-Ca are currently being developed which show improved formability. However, magnesium alloys are susceptible to environmental influences, which can be eliminated by suitable coatings. Novel corrosion protection concepts for classical aerial vehicles currently under development might suitable but may need adaption to the construction constraints or to vehicle dependent exposure scenarios. Within this mini-review a paradigm change due to utilization of new magnesium materials as drone construction material is briefly introduced and future fields of applications within next-generation aerial vehicles, manned or unmanned, are discussed. Possible research topics will be addressed.