bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Fuel Property Data Platform: Overview and Potential Applications
Authors: Blakey Simon , Rauch Bastian , Oldani Anna , Lee Tonghun
Published: March 2022

This report outlines the establishment of distributed databases for management and integration of current and future aviation fuels. Aviation fuel property and performance data has been gathered for many years in public and company specific fuel surveys. These surveys are suitable for use as overall quality control information and for monitoring changes and trends in the fuels in used for flight. In recent years, significant data has been generated for alternative fuels as part of the due diligence of their approval for use through ASTM D4054, including those outside of the specification. Recently, this data, along with fundamental chemistry data has led to the creation of the Fast Track route for fuels approval when the fuel is constrained to a necessarily narrowly defined composition. The data behind these developments are often stored in a disparate, unindexed way, resulting in their underutilisation for a range of research, engineering design, specification, and in service quality control applications. To make the best use of this data, we present a scalable, Json based format for the storing of fuels data. This concept has been proposed by the Horizon 2020 Jet Fuel SCREENing and Optimization (JETSCREEN) project in conjunction with the Center of Excellence for Alternative Jet Fuels and Environment (ASCENT) programme. We have worked collaboratively to develop a joint database which currently contains data from around 30,000 conventional and 400 alternative fuels/fuel blends from a range of European and United States of America (U.S.) lead research programmes and data sources. This database can be used for a variety of purposes, both in conjunction with, or in isolation of commercially sensitive data with a greater degree of restriction. We present a number of test cases for how we see this model for data storage could be used for the benefit of all. We invite further suggestions as to how this approach could be used and welcome opportunities to work with the wider fuels community to develop this idea further.
A Hierarchical Strategy for Multi-Objective Optimization of Distribution Network Considering DGs and V2G-Enabled EVs Integration
Authors: Huang Zhao , Ma Pengbo , Wang Mengmeng , Fang Baling , Zhang Ming
Published: March 2022

As an important part of smart grid construction, the distribution network (DN) optimization problem has always attracted great attention, especially under the background that large-scale penetration of distributed generators (DGs) and electric vehicles (EVs) into building cluster poses both opportunities and challenges to the energy management. This research presents a hierarchical optimization strategy, for improving the safe and economical operation of DN considering the DGs and EVs integration. In Stage 1, the MPPT control model of DGs is designed to obtain the best energy conversion efficiency. In Stage 2, load models of EVs and battery energy storage system (BESS) under coordinate charging/discharging stimulated by a time-of-use incentive mechanism are established respectively, to achieve a load curve with a minimized peak-to-valley difference (PVD). In Stage 3, aiming for the best compromise between the active power loss and node voltage excursion, daily optimal scheduling of the static Var compensator (SVC) capacitors is dynamically worked out according to the varying power demand, as the solution for the defined multi-objective optimization problem. For enhancing the convergence speed, an advanced genetic algorithm with elite preservation strategy is employed. The proposed hierarchical strategy is demonstrated on an IEEE 33-node DN test case, and the simulation results show that first, the MPPT control ensures the maximum power outputs of DGs; next, power supply pressure could be relieved by the load shifting effects of the coordinated vehicle-to-grid (V2G) service and BESS configuration, reflected in the decreased load peak from 4,370.1 to 3,424.99 kW, and the optimized PVD from 1763.8 to 703.8 kW; meanwhile, via applicable power planning of the SVC components, optimized power loss and voltage quality can both be achieved, proving the feasibility of the optimization strategy, which promotes the economic and reliable operation of the DN system.
Adaptive Fusion of Multi-Source Tropospheric Delay Estimates for InSAR Deformation Measurements
Authors: Zhang Li , Dong Jie , Zhang Lu , Wang Yian , Tang Wei , Liao Mingsheng
Published: March 2022

Atmospheric propagation delay correction is the key to improving the accuracy of deformation measurement of satellite interferometric synthetic aperture radar (InSAR). The empirical phase-elevation models and external data-based models present uneven performances of atmospheric delay correction for InSAR deformation monitoring. In this study, based on our previous fusion of delays predicted by multiple weather models (FDWM), we propose a new approach of adaptive fusion of multi-source tropospheric delay (AFMTD) estimates derived from multiple models over wide areas, i.e., ERA5, GACOS, WRF, MERRA2, NARR, MODIS, Linear model, and Powerlaw model. The spatially varying scaling algorithm is employed to refine the tropospheric delays predicted by the weather models. Meanwhile, we adopt a multiple-window strategy to cope with the spatially lateral variation of tropospheric delays. The AFMTD not only improves the spatial heterogeneity of tropospheric delay, but also adaptively combines multiple models to achieve a more reliable delay estimation. This AFMTD method is incorporated into the StaMPS-SBAS procedure. We compared the AFMTD with other single models using ENVISAT ASAR and Sentinel-1 datasets over Los Angeles of Southern California. The result of ASAR first demonstrates the effectiveness and reliability of the AFMTD method by referring to the assumed ground truth of simultaneous MERIS observations. The results of Sentinel-1 data show that over 95% of unwrapped interferograms have the minimum root-mean-square values after AFMTD correction for both descending and ascending tracks. The validation against GPS observation presents that the RMSEs of InSAR displacement time series after AFMTD correction decreases at more than 90% of 125 GPS stations. The average reductions of RMSE are 35.79% and 36.28% for descending and ascending data, respectively, and the maximum improvement is more than 70%. Overall, the proposed AFMTD method outperforms any single model for InSAR tropospheric delay correction and provides an open framework to fuse multi-source tropospheric delay estimates.
Modeling Skull Network Integrity at the Dawn of Amniote Diversification With Considerations on Functional Morphology and Fossil Jaw Muscle Reconstructions
Authors: Werneburg Ingmar , Abel Pascal
Published: March 2022

One of the major questions in evolutionary vertebrate morphology is the origin and meaning of temporal skull openings in land vertebrates. Partly or fully surrounded by bones, one, two, or even three openings may evolve behind the orbit, within the ancestrally fully roofed anapsid (scutal) skull. At least ten different morphotypes can be distinguished in tetrapods with many modifications and transitions in more crownward representatives. A number of potential factors driving the emergence and differentiation of temporal openings have been proposed in the literature, but only today are proper analytical tools available to conduct traceable tests for the functional morphology underlying temporal skull constructions. In the present study, we examined the anatomical network in the skull of one representative of early amniotes, †Captorhinus aguti, which ancestrally exhibits an anapsid skull. The resulting skull modularity revealed a complex partitioning of the temporal region indicating, in its intersections, the candidate positions for potential infratemporal openings. The framework of †C. agutiwas then taken as a template to model a series of potential temporal skull morphotypes in order to understand how skull openings might influence the modular composition of the amniote skull in general. We show that the original pattern of skull modularity (†C. aguti) experiences comprehensive changes by introducing one or two temporal openings in different combinations and in different places. The resulting modules in each skull model are interpreted in regard to the feeding behavior of amniotes that exhibit(ed) the respective skull morphotypes. An important finding is the alternative incorporation of the jugal and palate to different modules enforcing the importance of an integrated view on skull evolution: the temporal region cannot be understood without considering palatal anatomy. Finally, we discuss how to better reconstruct relative jaw muscle compositions in fossils by considering the modularity of the skull network. These considerations might be relevant for future biomechanical studies on skull evolution.
Behavioral Responses of Drosophila suzukii (Diptera: Drosophilidae) to Blends of Synthetic Fruit Volatiles Combined With Isoamyl Acetate and β-Cyclocitral
Authors: Bolton L. Grant , Piñero Jaime C. , Barrett Bruce A.
Published: March 2022

Baits and lures for trapping and monitoring the invasive vinegar fly Drosophila suzukii Matsumura (Diptera: Drosophilidae) are currently derived from fermentation volatiles. Volatile organic compounds from alternative sources could improve monitoring efforts and optimize capture of gravid females. Through electroantennography and behavioral assays, we evaluated male and female D. suzukii responses to blends of selected synthetic fruit volatiles in combination with the fruit compound isoamyl acetate and the strawberry leaf terpenoid β-cyclocitral. Blends that were attractive to both male and female D. suzukii were then evaluated for attractiveness to a non-target drosophilid, Drosophila melanogaster. A simple 3-component blend of isoamyl acetate, β-cyclocitral and methyl butyrate was attractive to D. suzukii, particularly females, relative to fresh blueberry volatiles. The 3-component blend was not attractive to D. melanogaster. Additional research is needed to determine the effectiveness of this blend to attract D. suzukii under field conditions.
Functional Wetland Loss Drives Emerging Risks to Waterbird Migration Networks
Authors: Donnelly J. Patrick , Moore Johnnie N. , Casazza Michael L. , Coons Shea P.
Published: March 2022

Migratory waterbirds (i.e., shorebirds, wading birds, and waterfowl) rely on a diffuse continental network of wetland habitats to support annual life cycle needs. Emerging threats of climate and land-use change raise new concerns over the sustainability of these habitat networks as water scarcity triggers cascading ecological effects impacting wetland habitat availability. Here we use important waterbird regions in Oregon and California, United States, as a model system to examine patterns of landscape change impacting wetland habitat networks in western North America. Wetland hydrology and flooded agricultural habitats were monitored monthly from 1988 to 2020 using satellite imagery to quantify the timing and duration of inundation—a key delimiter of habitat niche values associated with waterbird use. Trends were binned by management practice and wetland hydroperiods (semi-permanent, seasonal, and temporary) to identify differences in their climate and land-use change sensitivity. Wetland results were assessed using 33 waterbird species to detect non-linear effects of network change across a diversity of life cycle and habitat needs. Pervasive loss of semi-permanent wetlands was an indicator of systemic functional decline. Shortened hydroperiods caused by excessive drying transitioned semi-permanent wetlands to seasonal and temporary hydrologies—a process that in part counterbalanced concurrent seasonal and temporary wetland losses. Expansion of seasonal and temporary wetlands associated with closed-basin lakes offset wetland declines on other public and private lands, including wildlife refuges. Diving ducks, black terns, and grebes exhibited the most significant risk of habitat decline due to semi-permanent wetland loss that overlapped important migration, breeding, molting, and wintering periods. Shorebirds and dabbling ducks were beneficiaries of stable agricultural practices and top-down processes of functional wetland declines that operated collectively to maintain habitat needs. Outcomes from this work provide a novel perspective of wetland ecosystem change affecting waterbirds and their migration networks. Understanding the complexity of these relationships will become increasingly important as water scarcity continues to restructure the timing and availability of wetland resources.
Core Competencies for Training Conservation Paleobiology Students in a Wicked World
Authors: Kelley Patricia H. , Dietl Gregory P.
Published: March 2022

Despite the promise conservation paleobiology holds for using geohistorical data and insights to solve conservation problems, training in the field typically does not equip students to be competent environmental problem solvers. The intention of this perspective piece is to start a conversation about how we might train conservation paleobiology students better, focusing on the competencies needed to promote deep engagement with “wicked” conservation problems that are difficult to solve. Ongoing conversations regarding design of academic programs in sustainability, a field allied with conservation science, can inform our discussion. The sustainability literature has defined an interrelated set of “core competencies” that go beyond general academic competencies to enable real-world sustainability problem solving: systems thinking, temporal thinking, normative thinking, strategic thinking, and interpersonal competence. Conservation paleobiology is usually taught within geology programs, where students are exposed to systems thinking and temporal thinking. However, the remaining competencies typically are absent or insufficiently developed. To infuse these competencies into conservation paleobiology curricula, we recommend: (1) enhancing connections with sustainability programs and encouraging a more cross-disciplinary approach to training; (2) developing a “menu” of concepts and methodologies for each competence from which to choose; and (3) recognizing that different skills are appropriate at different levels of education and experience. The proposed competency-based framework serves as a shared reference that can be used to develop pedagogies to better prepare conservation paleobiology students to navigate the wicked conservation challenges of our time.
Dysregulation of the HOTAIR-miR-152-CAMKIIα Axis in Craniosynostosis Results in Impaired Osteoclast Differentiation
Authors: Dong Chenbin , Liu Xiangqi , Li Jun , Lan Dongyi , Zheng Shan
Published: March 2022

Craniosynostosis is one of the most common craniofacial deformities demanding surgical treatment in infancy. LncRNA HOTAIR has verified its important role in osteogenesis and osteoarthritis. However, whether HOTAIR plays an essential role in the development of craniosynostosis is still unclear. In this study, we aimed to investigate the molecular role of HOTAIR in the osteoclast function and development of craniosynostosis.For osteoclast differentiation, RAW264.7 cells were induced by 50 ng/ml of RANKL and 10 ng/mL M-CSF, followed by TRAP staining. Cell proliferation and apoptosis were assayed by the CCK-8 kit and Annexin V-FITC apoptosis detection kit, respectively. The expression of HOTAIR was determined in PBMCs by qRT-PCR. Protein levels of all those involved genes were measured by Western blot assay. A luciferase reporter assay was used to determine the miRNA target validation. The HOTAIR expression in PBMCs from children with craniosynostosis was significantly downregulated. The results of cell proliferation and apoptosis assays indicated that silencing of HOTAIR could inhibit osteoclast differentiation and increase cell apoptosis. Moreover, the luciferase reporter assay revealed that the regulatory axis and HOTAIR-miR-152-CAMKIIα were the regulatory mechanisms of HOTAIR in the osteoclast function and development of craniosynostosis.In this study, our data showed that HOTAIR could promote osteoclast differentiation by binding miR-152. Furthermore, the HOTAIR/HOTAIR-miR-152-CAMKIIα axis was found to regulate osteoclast differentiation. These results indicate that the HOTAIR plays a crucial role in the development of osteoclasts.
ASF1B is a Promising Prognostic Biomarker and Correlates With Immunotherapy Efficacy in Hepatocellular Carcinoma
Authors: Zhang Shirong , Xu Longwen , Feng Jinteng , Tan Deli , Zhu Yue , Hou Jia , Li Wenyuan , Lv Kejia , Wang Wenjuan , Jiang Lili , Jiao Min , Guo Hui
Published: March 2022

Background: Anti-silencing function 1B (ASF1B), a histone H3-H4 chaperone, is crucial for S-phase progression and cell proliferation. Recent studies have shown that ASF1B may be used as a new proliferation marker for cancer prognosis. However, the prognostic value and effect of ASF1B on tumor cells and the immune microenvironment in hepatocellular carcinoma (HCC) remain unclear.

Methods: We analyzed the expression of ASF1B and its prognostic value using The Cancer Genome Atlas (TCGA) database (as a training set) and other databases, and we validated the findings by immunohistochemistry in our clinical database, containing 141 HCC patients (as a validation set). Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to probe the tumor-associated biological processes of ASF1B in HCC. The interrelationships between ASF1B expression and tumor immunological characteristics were analyzed by multiple databases. The Imvigor210 cohort was retrieved to assess the ability of ASF1B to predict immunotherapy efficacy.

Results: ASF1B was highly expressed in tumor tissue compared to paracancerous tissue. High ASF1B expression was associated with worse overall survival (OS) and progression-free survival (PFS) in the training set (p = 0.005, p < 0.001) and validation set (p < 0.001, p < 0.001). Multivariate analysis revealed that ASF1B was an independent prognostic factor associated with OS and PFS. GSEA and GSVA suggested that ASF1B was involved in tumor-associated biological processes, including the cell cycle, DNA replication, base excision repair, mismatch repair, RNA degradation, ubiquitin-mediated proteolysis, and nucleotide excision repair. Further analysis revealed that the levels of ASF1B were positively correlated with the immune cells infiltration of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells. However, ASF1B was positively correlated with Treg cell infiltration and inhibitory immune checkpoints in exhausted T cells. Patients who received anti-PD-L1 immunotherapy with high ASF1B expression had a higher objective response.

Conclusion: The ASF1B level is an independent prognostic factor and may serve as a potential immunotherapeutic target.
Prevalence, Abundance, and Virulence of Adherent-Invasive Escherichia coli in Ulcerative Colitis, Colorectal Cancer, and Coeliac Disease
Authors: López-Siles Mireia , Camprubí-Font Carla , Gómez del Pulgar Eva M. , Sabat Mir Miriam , Busquets David , Sanz Yolanda , Martinez-Medina Margarita
Published: March 2022

Background & Aims

Adherent-invasive E. coli (AIEC) has largely been implicated in the pathogenesis of Crohn’s disease (CD). E. coli strains with similar genetic backgrounds and virulence genes profiles have been associated with other intestinal disorders, such as ulcerative colitis (UC), colorectal cancer (CRC), and coeliac disease (CeD), but the role of AIEC in these diseases remains unexplored. We aimed to assess the distribution, abundance, and pathogenic features of AIEC in UC, CRC, and CeD.

Methods

The AIEC phenotype was investigated in 4,233 E. coli isolated from the ileum and colon of 14 UC and 15 CRC patients and in 38 fecal E. coli strains obtained from 17 CeD and 10 healthy (H) children. AIEC prevalence and abundance were compared with previous data from CD patients and H controls. Clonality, virulence gene carriage, and phylogenetic origin were determined for the AIEC identified.

Results

In UC, AIEC prevalence was intermediate between CD and H subjects (UC: 35.7%, CD: 55.0%, H: 21.4%), and similar to CD patients with colonic disease (C-CD: 40.0%). In CRC, the prevalence was lower (6.7%) than these groups. In patients with AIEC, the estimated abundance was similar across all intestinal conditions. All AIEC strains isolated from UC and CRC belonged to the B1 phylogroup, except for a strain of the A phylogroup, and the majority (75% of clonally distinct AIEC) harbored the Afa/Dr operon and the cdt gene. None of the E. coli isolated from the CeD cohort were AIEC. Nonetheless, E. coli strains isolated from active CeD patients showed higher invasion indices than those isolated from H and inactive CeD pediatric patients.

Conclusion

We support the hypothesis that AIEC-like strains can be involved not only in CD but also in UC. Further works are needed to study the virulence particularities of these groups of strains and to determine if there is a causative link between AIEC and UC. In contrast, we rule out the possible association of AIEC with CRC. In addition, to further study the E. coli strains in CeD for their possible pathogenic role would be of interest.
ICS/LABA Combined With Subcutaneous Immunotherapy Modulates the Th17/Treg Imbalance in Asthmatic Children
Authors: Dai Huan , Zheng Rongying , Wang Like , Wan Jinyi , Tong Yu , Zhao Wei , Zhang Weixi
Published: March 2022

Rationale

The imbalance of T helper (Th17) cell and regulatory T (Treg) cell are involved in allergic asthma pathogenesis. We hypothesized that ICS/LABA could modulate the Th17/Treg imbalance and that subcutaneous immunotherapy (SCIT) could coordinate with ICS/LABA to rebalance the dysfunction of Th17/Treg.

Methods

Thirty house dust mites (HDM) allergic asthmatic children and fifteen healthy control subjects were enrolled in this study. Fifteen asthmatic children were treated by ICS/LABA powder inhalation, while the other fifteen asthmatic children were treated by ICS/LABA powder inhalation combined with HDM-SCIT. Asthmatic subjects were followed up for 6 months, but 2 asthmatics treated with ICS/LABA were lost to follow-up. Flow cytometry was used to determine the proportions of Th17 and Treg in CD4+ T cells from peripheral blood mononuclear cells (PBMCs). Serum levels of IL-17A and IL-10 were assessed by ELISA.

Result

ICS/LABA treatment significantly reduced the percentage of Th17 cells (1.252 ± 0.134% vs. 2.567 ± 0.386%), serum IL-17A (49.42 ± 2.643 pg/ml vs. 66.75 ± 3.442 pg/ml) and Th17/Treg ratio (0.194 ± 0.025 vs. 0.439 ± 0.072) compared to baseline (P<0.01). The ICS/LABA+HDM-SCIT treatment group showed similar reduction in the percentage of Th17 cells (1.11 ± 0.114% vs. 2.654 ± 0.276%), serum IL-17A (49.23 ± 2.131 pg/ml vs. 66.41 ± 2.616 pg/ml) and the Th17/Treg ratio (0.133 ± 0.015 vs. 0.4193 ± 0.050) (P<0.01). ICS/LABA+HDM-SCIT treatment group demonstrated elevated Treg percentages (8.483 ± 0.408% vs. 6.549 ± 0.299%) and serum IL-10 levels (127.4 ± 4.423 pg/ml vs. 93.15 ± 4.046 pg/ml), resulting in a lower Th17/Treg ratio than the ICS/LABA group.

Conclusion

ICS/LABA treatment regulates Th17/Treg imbalance mainly by mitigating Th17-induced inflammation in asthma patients. The addition of SCIT further enhanced such effect by upregulating Treg cells.
Cutting-Edge Technologies for Inflamed Joints on Chip: How Close Are We?
Authors: Kahraman Emine , Ribeiro Ricardo , Lamghari Meriem , Neto Estrela
Published: March 2022

Osteoarthritis (OA) is a painful and disabling musculoskeletal disorder, with a large impact on the global population, resulting in several limitations on daily activities. In OA, inflammation is frequent and mainly controlled through inflammatory cytokines released by immune cells. These outbalanced inflammatory cytokines cause cartilage extracellular matrix (ECM) degradation and possible growth of neuronal fibers into subchondral bone triggering pain. Even though pain is the major symptom of musculoskeletal diseases, there are still no effective treatments to counteract it and the mechanisms behind these pathologies are not fully understood. Thus, there is an urgent need to establish reliable models for assessing the molecular mechanisms and consequently new therapeutic targets. Models have been established to support this research field by providing reliable tools to replicate the joint tissuein vitro. Studies firstly started with simple 2D culture setups, followed by 3D culture focusing mainly on cell-cell interactions to mimic healthy and inflamed cartilage. Cellular approaches were improved by scaffold-based strategies to enhance cell-matrix interactions as well as contribute to developing mechanically more stablein vitromodels. The progression of the cartilage tissue engineering would then profit from the integration of 3D bioprinting technologies as these provide 3D constructs with versatile structural arrangements of the 3D constructs. The upgrade of the available tools with dynamic conditions was then achieved using bioreactors and fluid systems. Finally, the organ-on-a-chip encloses all the state of the art on cartilage tissue engineering by incorporation of different microenvironments, cells and stimuli and pave the way to potentially simulate crucial biological, chemical, and mechanical features of arthritic joint. In this review, we describe the several available tools ranging from simple cartilage pellets to complex organ-on-a-chip platforms, including 3D tissue-engineered constructs and bioprinting tools. Moreover, we provide a fruitful discussion on the possible upgrades to enhance thein vitrosystems making them more robust regarding the physiological and pathological modeling of the joint tissue/OA.
The Neuroimmune Interplay in Joint Pain: The Role of Macrophages
Authors: Vasconcelos Daniela P. , Jabangwe Clive , Lamghari Meriem , Alves Cecília J.
Published: March 2022

Chronic pain associated with joint disorders, such as rheumatoid arthritis (RA), osteoarthritis (OA) and implant aseptic loosening (AL), is a highly debilitating symptom that impacts mobility and quality of life in affected patients. The neuroimmune crosstalk has been demonstrated to play a critical role in the onset and establishment of chronic pain conditions. Immune cells release cytokines and immune mediators that can activate and sensitize nociceptors evoking pain, through interaction with receptors in the sensory nerve terminals. On the other hand, sensory and sympathetic nerve fibers release neurotransmitters that bind to their specific receptor expressed on surface of immune cells, initiating an immunomodulatory role. Macrophages have been shown to be key players in the neuroimmune crosstalk. Moreover, macrophages constitute the dominant immune cell population in RA, OA and AL. Importantly, the targeting of macrophages can result in anti-nociceptive effects in chronic pain conditions. Therefore, the aim of this review is to discuss the nature and impact of the interaction between the inflammatory response and nerve fibers in these joint disorders regarding the genesis and maintenance of pain. The role of macrophages is highlighted. The alteration in the joint innervation pattern and the inflammatory response are also described. Additionally, the immunomodulatory role of sensory and sympathetic neurotransmitters is revised.
Targeting the Interaction Between Spike Protein and Nucleocapsid Protein for Suppression and Detection of Human Coronavirus OC43
Authors: Kim Jinsoo , Kim Minyoung , Kim Dongbum , Park Sangkyu , Kang Mijeong , Baek Kyeongbin , Choi Jun-Kyu , Maharjan Sony , Akauliya Madhav , Lee Younghee , Kwon Hyung-Joo
Published: March 2022

Human coronavirus OC43 (HCoV-OC43) is the coronavirus most associated with “common colds”, infections of the upper respiratory tract. Previously, we reported that direct interactions of nucleocapsid (N) protein and C-terminal domain of Spike protein (Spike CD) are essential for replication of SARS-CoV-2 and MERS-CoV. Thus, we developed a novel ELISA-based strategy targeting these specific interactions to detect SARS-CoV-2 and MERS-CoV. Here, we investigated whether the same principles apply to HCoV-OC43. We discovered that the S protein of HCoV-OC43 interacts with N protein and that cell penetrating Spike CD peptide inhibits virus protein expression and replication of HCoV-OC43. The interaction between HCoV-OC43 S and N proteins were recapitulated with a recombinant HCoV-OC43 Spike CD fusion protein and a recombinant HCoV-OC43 N fusion protein in vitro. By producing an anti-HCoV-OC43 N protein-specific monoclonal antibody, we established a virus detection system based on the interaction between recombinant Spike CD and N protein of HCoV-OC43. We suggest that the interaction between Spike CD and N protein is conserved in coronaviruses and therefore could be a target for therapeutics against both novel coronavirus and its variants.
PD-L1 Antibody Pharmacokinetics and Tumor Targeting in Mouse Models for Infectious Diseases
Authors: Sandker Gerwin G. W. , Adema Gosse , Molkenboer-Kuenen Janneke , Wierstra Peter , Bussink Johan , Heskamp Sandra , Aarntzen Erik H. J. G.
Published: March 2022

Background

Programmed death-ligand 1 (PD-L1) regulates immune homeostasis by promoting T-cell exhaustion. It is involved in chronic infections and tumor progression. Nuclear imaging using radiolabeled anti-PD-L1 antibodies can monitor PD-L1 tissue expression and antibody distribution. However, physiological PD-L1 can cause rapid antibody clearance from blood at imaging doses. Therefore, we hypothesized that inflammatory responses, which can induce PD-L1 expression, affect anti-PD-L1 antibody distribution. Here, we investigated the effects of three different infectious stimuli on the pharmacokinetics and tumor targeting of radiolabeled anti-PD-L1 antibodies in tumor-bearing mice.

Materials/Methods

Anti-mouse-PD-L1 and isotype control antibodies were labelled with indium-111 ([111In]In-DTPA-anti-mPD-L1 and [111In]In-DTPA-IgG2a, respectively). We evaluated the effect of inflammatory responses on the pharmacokinetics of [111In]In-DTPA-anti-mPD-L1 in RenCa tumor-bearing BALB/c mice in three conditions: lipopolysaccharide (LPS), local Staphylococcus aureus, and heat-killed Candida albicans. After intravenous injection of 30 or 100 µg of [111In]In-DTPA-anti-mPD-L1 or [111In]In-DTPA-IgG2a, blood samples were collected 1, 4, and 24 h p.i. followed by microSPECT/CT and ex vivo biodistribution analyses. PD-L1 expression, neutrophil, and macrophage infiltration in relevant tissues were evaluated immunohistochemically.

Results

In 30 µg of [111In]In-DTPA-anti-mPD-L1 injected tumor-bearing mice the LPS-challenge significantly increased lymphoid organ uptake compared with vehicle controls (spleen: 49.9 ± 4.4%ID/g versus 21.2 ± 6.9%ID/g, p < 0.001), resulting in lower blood levels (3.6 ± 1.6%ID/g versus 11.5 ± 7.2%ID/g; p < 0.01) and reduced tumor targeting (8.1 ± 4.5%ID/g versus 25.2 ± 5.2%ID/g, p < 0.001). Local S. aureus infections showed high PD-L1+ neutrophil influx resulting in significantly increased [111In]In-DTPA-anti-mPD-L1 uptake in affected muscles (8.6 ± 2.6%ID/g versus 1.7 ± 0.8%ID/g, p < 0.001). Heat-killed Candida albicans (Hk-C. albicans) challenge did not affect pharmacokinetics. Increasing [111In]In-DTPA-anti-mPD-L1 dose to 100 µg normalized blood clearance and tumor uptake in LPS-challenged mice, although lymphoid organ uptake remained higher. Infectious stimuli did not affect [111In]In-DTPA-IgG2a pharmacokinetics.

Conclusions

This study shows that anti-PD-L1 antibody pharmacokinetics and tumor targeting can be significantly altered by severe inflammatory responses, which can be compensated for by increasing the tracer dose. This has implications for developing clinical PD-L1 imaging protocols in onco-immunology. We further demonstrate that radiolabeled anti-PD-L1 antibodies can be used to evaluate PD-L1 expression changes in a range of infectious diseases. This supports the exploration of using these techniques to assess hosts’ responses to infectious stimuli.
Mind the “Vaccine Fatigue”
Authors: Su Zhaohui , Cheshmehzangi Ali , McDonnell Dean , da Veiga Claudimar Pereira , Xiang Yu-Tao
Published: March 2022

Background

Omicron scares and speculations are gaining momentum. Amid the nonstop debates and discussions about COVID-19 vaccines, the “vaccine fatigue” phenomenon may become more prevalent. However, to date, no research has systematically examined factors that shape people’s vaccine fatigue. To bridge the research gap, this study aims to investigate the antecedents that cause or catalyze people’s vaccine fatigue.

Methods

A narrative literature review was conducted in PubMed, Scopus, and PsycINFO to identify factors that shape people’s vaccine fatigue. The search was completed on December 6, 2021, with a focus on scholarly literature published in English.

Results

A total of 37 articles were reviewed and analyzed. Vaccine fatigue was most frequently discussed in the context of infectious diseases in general at the pre-vaccination stage. Vaccine fatigue has been identified in the general public, the parents, and the doctors. Overall, a wide range of antecedents to vaccine fatigue has been identified, ranging from the frequency of immunization demands, vaccine side effects, misconceptions about the severity of the diseases and the need for vaccination, to lack of trust in the government and the media.

Conclusion

Vaccine fatigue is people’s inertia or inaction towards vaccine information or instruction due to perceived burden and burnout. Our study found that while some contributors to vaccine fatigue are rooted in limitations of vaccine sciences and therefore can hardly be avoided, effective and empathetic vaccine communications hold great promise in eliminating preventable vaccine fatigue across sectors in society.
It Takes a Village: The Multifaceted Immune Response to Mycobacterium tuberculosis Infection and Vaccine-Induced Immunity
Authors: Larsen Sasha E. , Williams Brittany D. , Rais Maham , Coler Rhea N. , Baldwin Susan L.
Published: March 2022

Despite co-evolving with humans for centuries and being intensely studied for decades, the immune correlates of protection againstMycobacterium tuberculosis(Mtb) have yet to be fully defined. This lapse in understanding is a major lag in the pipeline for evaluating and advancing efficacious vaccine candidates. While CD4+ T helper 1 (TH1) pro-inflammatory responses have a significant role in controlling Mtb infection, the historically narrow focus on this cell population may have eclipsed the characterization of other requisite arms of the immune system. Over the last decade, the tuberculosis (TB) research community has intentionally and intensely increased the breadth of investigation of other immune players. Here, we review mechanistic preclinical studies as well as clinical anecdotes that suggest the degree to which different cell types, such as NK cells, CD8+ T cells, γ δ T cells, and B cells, influence infection or disease prevention. Additionally, we categorically outline the observed role each major cell type plays in vaccine-induced immunity, includingMycobacterium bovisbacillus Calmette-Guérin (BCG). Novel vaccine candidates advancing through either the preclinical or clinical pipeline leverage different platforms (e.g., protein + adjuvant, vector-based, nucleic acid-based) to purposefully elicit complex immune responses, and we review those design rationales and results to date. The better we as a community understand the essential composition, magnitude, timing, and trafficking of immune responses against Mtb, the closer we are to reducing the severe disease burden and toll on human health inflicted by TB globally.
Immuno-Diagnosis of Active Tuberculosis by a Combination of Cytokines/Chemokines Induced by Two Stage-Specific Mycobacterial Antigens: A Pilot Study in a Low TB Incidence Country
Authors: Dirix Violette , Collart Philippe , Van Praet Anne , Hites Maya , Dauby Nicolas , Allard Sabine , Racapé Judith , Singh Mahavir , Locht Camille , Mascart Françoise , Corbière Véronique
Published: March 2022

Active tuberculosis (aTB) remains a major killer from infectious disease, partially due to delayed diagnosis and hence treatment. Classical microbiological methods are slow and lack sensitivity, molecular techniques are costly and often unavailable. Moreover, available immuno-diagnostic tests lack sensitivity and do not differentiate between aTB and latent TB infection (LTBI). Here, we evaluated the performance of the combined measurement of different chemokines/cytokines induced by two different stage-specific mycobacterial antigens, Early-secreted-antigenic target-6 (ESAT-6) and Heparin-binding-haemagglutinin (HBHA), after a shortin vitroincubation of either peripheral blood mononuclear cells (PBMC) or whole blood (WB). Blood samples were collected from a training cohort comprising 22 aTB patients, 22 LTBI subjects and 17 non-infected controls. The concentrations of 13 cytokines were measured in the supernatants. Random forest analysis identified the best markers to differentiateM. tuberculosis-infected from non-infected subjects, and the most appropriate markers to differentiate aTB from LTBI. Logistic regression defined predictive abilities of selected combinations of cytokines, first on the training and then on a validation cohort (17 aTB, 27 LTBI, 25 controls). Combining HBHA- and ESAT-6-induced IFN-γ concentrations produced by PBMC was optimal to differentiate infected from non-infected individuals in the training cohort (100% correct classification), but 2/16 (13%) patients with aTB were misclassified in the validation cohort. ESAT-6-induced-IP-10 combined with HBHA-induced-IFN-γ concentrations was selected to differentiate aTB from LTBI, and correctly classified 82%/77% of infected subjects as aTB or LTBI in the training/validation cohorts, respectively. Results obtained on WB also selected ESAT-6- and HBHA-induced IFN-γ concentrations to provided discrimination between infected and non-infected subjects (89%/90% correct classification in the training/validation cohorts). Further identification of aTB patients among infected subjects was best achieved by combining ESAT-6-induced IP-10 with HBHA-induced IL-2 and GM-CSF. Among infected subjects, 90%/93% of the aTB patients were correctly identified in the training/validation cohorts. We therefore propose a two steps strategy performed on 1 mL WB for a rapid identification of patients with aTB. After elimination of most non-infected subjects by combining ESAT-6 and HBHA-induced IFN-γ, the combination of IP-10, IL-2 and GM-CSF released by either ESAT-6 or HBHA correctly identifies most patients with aTB.
Stem Cell-Derived Extracellular Vesicles as Potential Therapeutic Approach for Acute Kidney Injury
Authors: Quaglia Marco , Merlotti Guido , Colombatto Andrea , Bruno Stefania , Stasi Alessandra , Franzin Rossana , Castellano Giuseppe , Grossini Elena , Fanelli Vito , Cantaluppi Vincenzo
Published: March 2022

Acute kidney injury is a frequent complication of hospitalized patients and significantly increases morbidity and mortality, worsening costs and length of hospital stay. Despite this impact on healthcare system, treatment still remains only supportive (dialysis). Stem cell-derived extracellular vesicles are a promising option as they recapitulate stem cells properties, overcoming safety issues related to risks or rejection or aberrant differentiation. A growing body of evidence based on pre-clinical studies suggests that extracellular vesicles may be effective to treat acute kidney injury and to limit fibrosis through direct interference with pathogenic mechanisms of vascular and tubular epithelial cell damage. We herein analyze the state-of-the-art knowledge of therapeutic approaches with stem cell-derived extracellular vesicles for different forms of acute kidney injury (toxic, ischemic or septic) dissecting their cytoprotective, regenerative and immunomodulatory properties. We also analyze the potential impact of extracellular vesicles on the mechanisms of transition from acute kidney injury to chronic kidney disease, with a focus on the pivotal role of the inhibition of complement cascade in this setting. Despite some technical limits, nowadays the development of therapies based on stem cell-derived extracellular vesicles holds promise as a new frontier to limit acute kidney injury onset and progression.
What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies
Authors: Shang Zhizhong , Li Dongliang , Chen Jinlei , Wang RuiRui , Wang Mingchuan , Zhang Baolin , Wang Xin , Wanyan Pingping
Published: March 2022

Objective

The optimal transplantation timing of neural stem cells in spinal cord injury is fully explored in animal studies to reduce the risk of transformation to clinical practice and to provide valuable reference for future animal studies and clinical research.

Method

Seven electronic databases, namely, PubMed, Web of Science, Embase, Wanfang, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched. The studies were retrieved from inception to November 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria.

Results and Discussion

Thirty-nine studies were incorporated into the final analyses. Based on the subgroup of animal models and transplantation dose, the results of network meta-analysis showed that the effect of transplantation in the subacute phase might be the best. However, the results of traditional meta-analysis were inconsistent. In the moderate-dose group of moderate spinal cord injury model and the low-dose group of severe spinal cord injury model, transplantation in the subacute phase did not significantly improve motor function. Given the lack of evidence for direct comparison between different transplantation phases, the indirectness of our network meta-analysis, and the low quality of evidence in current animal studies, our confidence in recommending cell transplantation in the subacute phase is limited. In the future, more high-quality, direct comparative studies are needed to explore this issue in depth.
CASE REPORT: Serial Cases of False-Positive Flow-Cytometry T Cell Crossmatch Associated With Anti–Blood Type Antibodies in Patients Undergoing ABO-Incompatible Kidney Transplantation
Authors: Hayashi Ayaka , Yamamoto Izumi , Kawabe Mayuko , Kobayashi Akimitsu , Ito Makoto , Hotta Kiyohiko , Shinohara Nobuo , Tasaki Tetsunori , Yokoo Takashi , Iwami Daiki
Published: March 2022

Background

A positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood.

Cases

In five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor’s T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes.

Discussion

False-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed.

Conclusion

False-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.
Adjuvants Differentially Modulate the Immunogenicity of Lassa Virus Glycoprotein Subunits in Mice
Authors: To Albert , Lai Chih-Yun , Wong Teri Ann S. , Namekar Madhuri , Lieberman Michael M. , Lehrer Axel T.
Published: March 2022

Lassa Fever (LF) is an acute viral hemorrhagic fever caused by Lassa virus (LASV) that is primarily transmitted through contact with wild rodents in West Africa. Although several advanced vaccine candidates are progressing through clinical trials, some effective vaccines are virally vectored and thus require a stringent cold-chain, making distribution to rural and resource-poor areas difficult. Recombinant subunit vaccines are advantageous in this aspect as they can be thermostabilized and deployed with minimal storage and transportation requirements. However, antigen dose and adjuvant formulation must be carefully selected to ensure both the appropriate humoral and cell-mediated immune responses are elicited. In this study, we examine the immunogenicity of a two-step immunoaffinity-purified recombinant LASV glycoprotein (GP) with five clinical- and preclinical-grade adjuvants. Swiss Webster mice immunized intramuscularly with 2 or 3 doses of each vaccine formulation showed complete seroconversion and maximal GP-specific antibody response after two immunizations. Formulations with GPI-0100, LiteVax, Montanide™ ISA 51, and Montanide™ ISA 720 induced both IgG1 and IgG2 antibodies suggesting a balanced Th1/Th2 response, whereas formulation of LASV GP with Alhydrogel elicited a IgG1-dominant response. Splenocytes secreting both Th1 and Th2 cytokines i.e., IFN-γ, TNF-α, IL-2, IL-4 and IL-5, were observed from mice receiving both antigen doses formulated with ISA 720, LiteVax and GPI-0100. However, robust, multifunctional T-cells were only detected in mice receiving a higher dose of LASV GP formulated with GPI-0100. Our results emphasize the importance of careful adjuvant selection and lay the immunological basis for a recombinant subunit protein LF vaccine formulation.