bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels
Authors: Niculescu Dan Alexandru , Deacu Laura Georgiana , Caragheorgheopol Andra , Popescu Nicoleta , Ghemigian Adina , Procopiuc Camelia , Rosca Roxana , Poiana Catalina
Published: April 2021

Background

Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum.

Methods

We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay.

Results

There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (β-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (β-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL.

Conclusions

We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.
Fabrication of Functional Materials for Dye-sensitized Solar Cells
Authors: Tontapha Sarawut , Uppachai Pikaned , Amornkitbamrung Vittaya
Published: April 2021

Dye-sensitized solar cells (DSSCs) have been developed as a promising photovoltaic cell type in recent decades because of their low cost, environmental friendliness, ease of fabrication, and suitability for a wide range of indoor and outdoor applications, especially under diverse shaded and low-light condition. They are typically composed of three main components: a transparent conducting oxide (TCO) substrate-based working electrode with wide-bandgap semiconductors and dye sensitizer molecules, an electrolytic mediator based on redox couple species, and a TCO-based counter electrode consisting of catalyst materials. The development of intrinsic and functional organic, inorganic, metal oxide, composite, and carbon-based materials has been intensively studied to enhance the efficiency of DSSCs. A simple and low-cost fabrication process that uses natural products is also considered essential for further large-scale production. In this article, we review the fabrication of various functional materials and their effects on DSSC performance.
Coastal Risk Cultures: Local and Regional Formation of Knowledge and Action
Authors: Martinez Grit
Published: April 2021

This paper deals with how culture is expressed through the interplay of socially, politically, and economically driven processes and practices in place-based biophysical contexts as well as the role played by narrative expressions in the formation of coastal risk management, knowledge and action. It draws upon ethnographic, comparative, and historical approaches to understand how culture frames what we know and how we respond differently to risks. The research is based on the theoretical position that interpretation of risks and responses of social groups are shaped by frames of cultural knowledge and values, and investigates the influence resident’s values have in shaping the resilience of their community in two coastal regions in Germany and Italy. Information was derived from desk research, semi-structured, narrative interviews, and observation. Specifically, the author was interested in how residents’ views and narratives affected their risk behavior, shaped their needs and which role path dependencies and societal contexts played in the formation of risk knowledge, risk management and action. The author found that values, knowledge and identity highly matter in building community resilience. Moreover, the cases illustrate how past and present societal trajectories shape local and regional responses to climate change and why this concerns political decision makers at all levels, who are aiming to mainstream mitigation and adaptation strategies confronting climate change effects and in turn shaping resilience at local and regional levels.
“Omics” Technologies for the Study of Soil Carbon Stabilization: A Review
Authors: Overy David P. , Bell Madison A. , Habtewold Jemaneh , Helgason Bobbi L. , Gregorich Edward G.
Published: April 2021

Evidence-based decisions governing sustainable agricultural land management practices require a mechanistic understanding of soil organic matter (SOM) transformations and stabilization of carbon in soil. Large amounts of carbon from organic fertilizers, root exudates, and crop residues are input into agricultural soils. Microbes then catalyze soil biogeochemical processes including carbon extracellular transformation, mineralization, and assimilation of resources that are later returned to the soil as metabolites and necromass. A systems biology approach for a holistic study of the transformation of carbon inputs into stable SOM requires the use of soil “omics” platforms (metagenomics, metatranscriptomics, metaproteomics, and metabolomics). Linking the data derived from these various platforms will enhance our knowledge of structure and function of the microbial communities involved in soil carbon cycling and stabilization. In this review, we discuss the application, potential, and suitability of different “omics” approaches (independently and in combination) for elucidating processes involved in the transformation of stable carbon in soil. We highlight biases associated with these approaches including limitations of the methods, experimental design, and soil sampling, as well as those associated with data analysis and interpretation.
Qualitative and Quantitative Loss of Habitat at Different Spatial Scales Affects Functional Moth Diversity
Authors: Uhl Britta , Wölfling Mirko , Fiedler Konrad
Published: April 2021

Land use change has led to large-scale insect decline, threatening ecosystem resilience through reduced functional diversity. Even in nature reserves, losses in insect diversity have been detected. Hereby, changes in local habitat quality and landscape-scale habitat quantity can play a role driving functional diversity toward erosion. Our aim was to analyze how local and landscape-scale factors simultaneously affect functional insect diversity. Therefore, we sampled moths in two Italian coastal forest reserves at 60 sites. Our focus was on functional richness, redundancy and niche occupation, being important for ecosystem resilience, following the insurance framework. Ecological information about 387 species and 14 traits was used to analyze functional diversity. Twenty-five functional groups were recognized and used to estimate niche occupation and redundancy. Fourteen local and 12 landscape-scale factors were measured and condensed by using Principal Components Analysis. The resulting PC-axes served as predictors in linear mixed effects models. Functional richness, redundancy and niche occupation of moths were lower at sites with low habitat quality and quantity, indicating reduced ecosystem resilience. Especially landscape diversity and habitat structure, viz. a humidity-nutrient gradient, but also plant diversity, were promoting functional richness. Landscape fragmentation, indicating increased impermeability for insects, reduced local functional richness, redundancy and niche occupation. Local habitat quality and landscape-wide habitat quantity are both important for maintaining functional insect diversity inside reserves. Therefore, small and isolated nature reserves might fail in preserving biodiversity and ecosystem functions through adverse effects acting from the surrounding landscape structure and configuration.
Entomopathogenic Fungi for Tick Control in Cattle Livestock From Mexico
Authors: Alonso-Díaz Miguel Angel , Fernández-Salas Agustín
Published: April 2021

Ticks are one of the main economic threats to the cattle industry worldwide affecting productivity, health and welfare. The need for alternative methods to control tick populations is prompted by the high prevalence of multiresistant tick strains to the main chemical acaricides and their ecological consequences. Biological control using entomopathogenic fungi (EPF) is one of the most promising alternative options. The objective of this paper is to review the use of EPF as an alternative control method against cattle ticks in Mexico. Metarhizium anisopliae sensu lato (s.l.) and Beauveria bassiana s.l. are the most studied EPF for the biological control of ticks in the laboratory and in the field, mainly against Rhipicephalus microplus; however, evaluations against other important cattle ticks such as Amblyomma mixtum and R. annulatus, are needed. A transdisciplinary approach is required to incorporate different types of tools, such as genomics, transcriptomics and proteomics in order to better understand the pathogenicity/virulence mechanism in EPF against ticks. Laboratory tests have demonstrated the EPF efficacy to control susceptible and resistant/multiresistant tick populations; whereas, field tests have shown satisfactory control efficiency of M. anisopliae s.l. against different stages of R. microplus when applied both on pasture and on cattle. Epidemiological aspects of ticks and environmental factors are considered as components that influence the acaricidal behavior of the EPF. Finally, considering all these aspects, some recommendations are proposed for the use of EPF in integrated control schemes for livestock ticks.
Exploitation of Aggregate Mobility Sensing Data for the Synthesis of Disaggregate Multimodal Tours in Megacities
Authors: Ballis Haris , Dimitriou Loukas
Published: April 2021

The unprecedented volume of urban sensing data has allowed the tracking of individuals at remarkably high resolution. As an example, Telecommunication Service Providers (TSPs) cannot provide their service unless they continuously collect information regarding the location of their customers. In conjunction with appropriate post-processing methodologies, these traces can be augmented with additional dimensions such as the activity of the user or the transport mode used for the completion of journeys. However, justified privacy concerns have led to the enforcement of legal regulations aiming to hinder, if not entirely forbid, the use of such private information even for purely scientific purposes. One of the most widely applied methods for the communication of mobility information without raising anonymity concerns is the aggregation of trips in origin–destination (OD) matrices. Previous work has showcased the possibility to exploit multi-period and purpose-segmented ODs for the synthesis of realistic disaggregate tours. The current study extends this framework by incorporating the multimodality dimension into the framework. In particular, the study evaluates the potential of synthesizing multimodal, diurnal tours for the case where the available ODs are also segmented by the transport mode. In addition, the study proves the scalability of the method by evaluating its performance on a set of time period-, trip purpose-, and transport mode-segmented, large-scale ODs describing the mobility patterns for millions of citizens of the megacity of Tokyo, Japan. The resulting modeled tours utilized over 96% of the inputted trips and recreated the observed mobility traces with an accuracy exceeding 80%. The high accuracy of the framework establishes the potential to utilize privacy-safe, aggregate urban mobility data for the synthesis of highly informative and contextual disaggregate mobility information. Implications are significant since the creation of such granular mobility information from widely available data sources like aggregate ODs can prove particularly useful for deep explanatory analysis or for advanced transport modeling purposes (e.g., agent-based, microsimulation modeling).
Identification of Hub Genes and Their Correlation With Immune Infiltration Cells in Hepatocellular Carcinoma Based on GEO and TCGA Databases
Authors: Huang Rui , Liu Jinying , Li Hui , Zheng Lierui , Jin Haojun , Zhang Yaqing , Ma Wei , Su Junhong , Wang Min , Yang Kun
Published: April 2021

Hepatocellular carcinoma (HCC) is a primary liver cancer with extremely high mortality in worldwide. HCC is hard to diagnose and has a poor prognosis due to the less understanding of the molecular pathological mechanisms and the regulation mechanism on immune cell infiltration during hepatocarcinogenesis. Herein, by performing multiple bioinformatics analysis methods, including the RobustRankAggreg (RRA) rank analysis, weighted gene co-expression network analysis (WGCNA), and a devolution algorithm (CIBERSORT), we first identified 14 hub genes (NDC80, DLGAP5, BUB1B, KIF20A, KIF2C, KIF11, NCAPG, NUSAP1, PBK, ASPM, FOXM1, TPX2, UBE2C, and PRC1) in HCC, whose expression levels were significantly up-regulated and negatively correlated with overall survival time. Moreover, we found that the expression of these hub genes was significantly positively correlated with immune infiltration cells, including regulatory T cells (Treg), T follicular helper (TFH) cells, macrophages M0, but negatively correlated with immune infiltration cells including monocytes. Among these hub genes, KIF2C and UBE2C showed the most significant correlation and were associated with immune cell infiltration in HCC, which was speculated as the potential prognostic biomarker for guiding immunotherapy.
Gene Replacement Therapies for Genodermatoses: A Status Quo
Authors: Koller Ulrich , Bauer Johann W.
Published: April 2021

Epidermolysis bullosa (EB) is a genodermatosis, characterized by the formation of extended blisters and lesions on the skin and mucous membranes upon minimal mechanical trauma. The disease is caused by mutations in genes encoding proteins that are essential for skin stability. Functional impairment, reduction, or absence of one of these proteins results in skin fragility due to reduced connectivity between dermis and epidermis. Currently, gene therapy represents the only treatment option with the potential to cure this severe blistering skin disease. Two promising forms of gene therapy are potentially feasible for EB: gene replacement and genome editing. While genome editing for genodermatoses remains at the preclinical stage, gene replacement approaches are clinically advanced and have been applied already to a small number of patients with junctional and dystrophic forms of EB. Here, the viral transduction of the “wild-type” transgene into skin stem cells, followed by autologous grafting of corrected epidermal sheets, led to the regeneration of stable skin. Recent developments regarding designer nuclease-based gene editing strategies enable the establishment of alternative options to restore the gene function in genodermatoses. This is particularly true in cases wherein genetic constellation hinders gene therapy-based gene replacement.
Transcriptome and Co-expression Network Analyses Reveal Differential Gene Expression and Pathways in Response to Severe Drought Stress in Peanut (Arachis hypogaea L.)
Authors: Zhao Nannan , Cui Shunli , Li Xiukun , Liu Bokuan , Deng Hongtao , Liu Yingru , Hou Mingyu , Yang Xinlei , Mu Guojun , Liu Lifeng
Published: April 2021

Drought is one of the major abiotic stress factors limiting peanut production. It causes the loss of pod yield during the pod formation stage. Here, one previously identified drought-tolerant cultivar, “L422” of peanut, was stressed by drought (35 ± 5%) at pod formation stage for 5, 7, and 9 days. To analyze the drought effects on peanut, we conducted physiological and transcriptome analysis in leaves under well-watered (CK1, CK2, and CK3) and drought-stress conditions (T1, T2, and T3). By transcriptome analysis, 3,586, 6,730, and 8,054 differentially expressed genes (DEGs) were identified in “L422” at 5 days (CK1 vs T1), 7 days (CK2 vs T2), and 9 days (CK3 vs T3) of drought stress, respectively, and 2,846 genes were common DEGs among the three-time points. Furthermore, the result of weighted gene co-expression network analysis (WGCNA) revealed one significant module that was closely correlated between drought stress and physiological data. A total of 1,313 significantly up-/down-regulated genes, including 61 transcription factors, were identified in the module at three-time points throughout the drought stress stage. Additionally, six vital metabolic pathways, namely, “MAPK signaling pathway-plant,” “flavonoid biosynthesis,” “starch and sucrose metabolism,” “phenylpropanoid biosynthesis,” “glutathione metabolism,” and “plant hormone signal transduction” were enriched in “L422” under severe drought stress. Nine genes responding to drought tolerance were selected for quantitative real-time PCR (qRT-PCR) verification and the results agreed with transcriptional profile data, which reveals the reliability and accuracy of transcriptome data. Taken together, these findings could lead to a better understanding of drought tolerance and facilitate the breeding of drought-resistant peanut cultivars.
Defective Interfering Genomes and the Full-Length Viral Genome Trigger RIG-I After Infection With Vesicular Stomatitis Virus in a Replication Dependent Manner
Authors: Linder Andreas , Bothe Viktoria , Linder Nicolas , Schwarzlmueller Paul , Dahlström Frank , Bartenhagen Christoph , Dugas Martin , Pandey Dharmendra , Thorn-Seshold Julia , Boehmer Daniel F. R. , Koenig Lars M. , Kobold Sebastian , Schnurr Max , Raedler Johannes , Spielmann Giulia , Karimzadeh Hadi , Schmidt Andreas , Endres Stefan , Rothenfusser Simon
Published: April 2021

Replication competent vesicular stomatitis virus (VSV) is the basis of a vaccine against Ebola and VSV strains are developed as oncolytic viruses. Both functions depend on the ability of VSV to induce adequate amounts of interferon-α/β. It is therefore important to understand how VSV triggers interferon responses. VSV activates innate immunity via retinoic acid-inducible gene I (RIG-I), a sensor for viral RNA. Our results show that VSV needs to replicate for a robust interferon response. Analysis of RIG-I-associated RNA identified a copy-back defective-interfering (DI) genome and full-length viral genomes as main trigger of RIG-I. VSV stocks depleted of DI genomes lost most of their interferon-stimulating activity. The remaining full-length genome and leader-N-read-through sequences, however, still triggered RIG-I. Awareness for DI genomes as trigger of innate immune responses will help to standardize DI genome content and to purposefully deplete or use DI genomes as natural adjuvants in VSV-based therapeutics.
Uveitis: Molecular Pathogenesis and Emerging Therapies
Authors: Egwuagu Charles E. , Alhakeem Sahar A. , Mbanefo Evaristus C.
Published: April 2021

The profound impact that vision loss has on human activities and quality of life necessitates understanding the etiology of potentially blinding diseases and their clinical management. The unique anatomic features of the eye and its sequestration from peripheral immune system also provides a framework for studying other diseases in immune privileged sites and validating basic immunological principles. Thus, early studies of intraocular inflammatory diseases (uveitis) were at the forefront of research on organ transplantation. These studies laid the groundwork for foundational discoveries on how immune system distinguishes self from non-self and established current concepts of acquired immune tolerance and autoimmunity. Our charge in this review is to examine how advances in molecular cell biology and immunology over the past 3 decades have contributed to the understanding of mechanisms that underlie immunopathogenesis of uveitis. Particular emphasis is on how advances in biotechnology have been leveraged in developing biologics and cell-based immunotherapies for uveitis and other neuroinflammatory diseases.
Bridging Therapy for Acute Stroke as the Initial Manifestation of Takayasu Arteritis: A Case Report and Review of Literature
Authors: Dai Yongqiang , Zhong Yi , Jian Banghao , Liu Ping , Song Kangyu , Li Yu , Wu Aimin , Zhang Bingjun
Published: April 2021

Takayasu arteritis (TA) is a chronic inflammatory disease involving the aorta and its principal branches. Acute ischaemic stroke (AIS) as the initial manifestation of TA is uncommon. There is little evidence on the efficacy of bridging therapy for AIS induced by TA. A 23-year-old Chinese woman with a suspected stroke presented to our hospital with sudden onset of right-sided weakness, right facial palsy, and aphasia that occurred 1 hour ago. After physical and ancillary examinations, recombinant tissue plasminogen activator was administered to the patient, which led to partial recovery. Her neurological function deteriorated with a large salvageable ischaemic penumbra on computed tomography perfusion. Cerebrovascular angiography showed multiple stenoses in the brachiocephalic trunk, the beginning of the right common carotid artery (CCA), and the bilateral subclavian arteries, as well as occlusion of the left CCA and its branches. Mechanical thrombectomy of the left middle cerebral artery was performed immediately. Percutaneous transluminal balloon angioplasty of the left CCA followed by stent implantation of the proximal left CCA was then performed. A diagnosis of TA was made based on the findings. The patient’s neurological deficit fully recovered with immunosuppressants at the 3 month-follow-up. We report a rare case of a patient with TA initially presenting with AIS treated with bridging therapy with full recovery of neurological function. Bridging therapy should be taken into consideration for AIS in patients with TA. Further study is needed in this regard.
Unsupervised Analysis of Flow Cytometry Data in a Clinical Setting Captures Cell Diversity and Allows Population Discovery
Authors: Baumgaertner Petra , Sankar Martial , Herrera Fernanda , Benedetti Fabrizio , Barras David , Thierry Anne-Christine , Dangaj Denarda , Kandalaft Lana E. , Coukos George , Xenarios Ioannis , Guex Nicolas , Harari Alexandre
Published: April 2021

Data obtained with cytometry are increasingly complex and their interrogation impacts the type and quality of knowledge gained. Conventional supervised analyses are limited to pre-defined cell populations and do not exploit the full potential of data. Here, in the context of a clinical trial of cancer patients treated with radiotherapy, we performed longitudinal flow cytometry analyses to identify multiple distinct cell populations in circulating whole blood. We cross-compared the results from state-of-the-art recommended supervised analyses with results from MegaClust, a high-performance data-driven clustering algorithm allowing fast and robust identification of cell-type populations. Ten distinct cell populations were accurately identified by supervised analyses, including main T, B, dendritic cell (DC), natural killer (NK) and monocytes subsets. While all ten subsets were also identified with MegaClust, additional cell populations were revealed (e.g. CD4+HLA-DR+ and NKT-like subsets), and DC profiling was enriched by the assignment of additional subset-specific markers. Comparison between transcriptomic profiles of purified DC populations and publicly available datasets confirmed the accuracy of the unsupervised clustering algorithm and demonstrated its potential to identify rare and scarcely described cell subsets. Our observations show that data-driven analyses of cytometry data significantly enrich the amount and quality of knowledge gained, representing an important step in refining the characterization of immune responses.
The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation
Authors: Peters Karin , Peters Marcus
Published: April 2021

More than fifty c-type lectin receptors (CLR) are known and have been identified so far. Moreover, we know the group of galectins and sialic acid-binding immunoglobulin-type lectins that also belong to the carbohydrate-binding receptors of the immune system. Thus, the lectin receptors form the largest receptor family among the pathogen recognition receptors. Similar to the toll-like receptors (TLRs), the CLR do not only recognize foreign but also endogenous molecules. In contrast to TLRs, which have a predominantly activating effect on the immune system, lectin receptors also mediate inhibitory signals. They play an important role in innate and adaptive immunity for the induction, regulation and shaping of the immune response. The hygiene hypothesis links enhanced infection to protection from allergic disease. Yet, the microbial substances that are responsible for mediating this allergy-protective activity still have to be identified. Microbes contain both ligands binding to TLRs and carbohydrates that are recognized by CLR and other lectin receptors. In the current literature, the CLR are often recognized as the ‘bad guys’ in allergic inflammation, because some glycoepitopes of allergens have been shown to bind to CLR, facilitating their uptake and presentation. On the other hand, there are many reports revealing that sugar moieties are involved in immune regulation. In this review, we will summarize what is known about the role of carbohydrate interaction with c-type lectins and other sugar-recognizing receptors in anti-inflammation, with a special focus on the regulation of the allergic immune response.
High-Resolution Analysis Identifies High Frequency of KIR-A Haplotypes and Inhibitory Interactions of KIR With HLA Class I in Zhejiang Han
Authors: Tao Sudan , He Yanmin , Kichula Katherine M. , Wang Jielin , He Ji , Norman Paul J. , Zhu Faming
Published: April 2021

Killer cell immunoglobulin-like receptors (KIR) interact with human leukocyte antigen (HLA) class I molecules, modulating critical NK cell functions in the maintenance of human health. Characterizing the distribution and characteristics of KIR and HLA allotype diversity across defined human populations is thus essential for understanding the multiple associations with disease, and for directing therapies. In this study of 176 Zhejiang Han individuals from Southeastern China, we describe diversity of the highly polymorphicKIRandHLA class Igenes at high resolution.KIR-Ahaplotypes, which carry four inhibitory receptors specific for HLA-A, B or C, are known to associate with protection from infection and some cancers. We show the Chinese Southern Han from Zhejiang are characterized by a high frequency ofKIR-Ahaplotypes and a high frequency of C1 KIR ligands. Accordingly, interactions of inhibitory KIR2DL3 with C1+HLA are more frequent in Zhejiang Han than populations outside East Asia. Zhejiang Han exhibit greater diversity of inhibitory than activating KIR, with three-domain inhibitory KIR exhibiting the greatest degree of polymorphism. As distinguished by gene copy number and allele content, 54 centromeric and 37 telomeric haplotypes were observed. We observed 6% of the population to haveKIRhaplotypes containing large-scale duplications or deletions that include complete genes. A unique truncated haplotype containing onlyKIR2DL4in the telomeric region was also identified. An additional feature is the high frequency ofHLA-B*46:01, which may have arisen due to selection pressure from infectious disease. This study will provide further insight into the role ofKIRandHLApolymorphism in disease susceptibility of Zhejiang Chinese.
Mucosal Immunoregulatory Properties of Tsukamurella inchonensis to Reverse Experimental Food Allergy
Authors: Smaldini Paola L. , Trejo Fernando M. , Rizzo Gastón P. , Comerci Diego J. , Kampinga Jaap , Docena Guillermo H.
Published: April 2021

The intestinal mucosa is lined by epithelial cells, which are key cells to sustain gut homeostasis. Food allergy is an immune-mediated adverse reaction to food, likely due to defective regulatory circuits. Tsukamurella inchonensis is a non-pathogenic bacterium with immunomodulatory properties. We hypothesize that the anti-inflammatory effect of dead T. inchonensis on activated epithelial cells modulates milk allergy through the restoration of tolerance in a mouse model. Epithelial cells (Caco-2 and enterocytes from mouse gut) and macrophages were stimulated with T. inchonensis and induction of luciferase under the NF-κB promoter, ROS and cytokines production were studied. Balb/c mice were mucosally sensitized with cow´s milk proteins plus cholera toxin and orally challenged with the allergen to evidence hypersensitivity symptoms. After that, mice were orally administered with heat-killed T. inchonensis as treatment and then challenged with the allergen. The therapeutic efficacy was in vivo (clinical score and cutaneous test) and in vitro (serum specific antibodies and cytokines-ELISA, and cell analysis-flow cytometry) evaluated. Heat-killed T. inchonensis modulated the induction of pro-inflammatory chemokines, with an increase in anti-inflammatory cytokines by intestinal epithelial cells and by macrophages with decreased OX40L expression. In vivo, oral administration of T. inchonensis increased the frequency of lamina propria CD4+CD25+FoxP3+ T cells, and clinical signs were lower in T. inchonensis-treated mice compared with milk-sensitized animals. In vivo depletion of Tregs (anti-CD25) abrogated T. inchonensis immunomodulation. In conclusion, these bacteria suppressed the intestinal inflammatory immune response to reverse food allergy.
Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade
Authors: Bozward Amber G. , Warricker Frazer , Oo Ye H. , Khakoo Salim I.
Published: April 2021

Despite major advances in immunotherapy, hepatocellular carcinoma (HCC) remains a challenging target. Natural Killer (NK) cells are crucial components of the anti-HCC immune response, which can be manipulated for immunotherapeutic benefit as primary targets, modulators of the tumour microenvironment and in synchronising with tumour antigen specific effector CD8 cells for tumour clearance. Regulatory T cells shape the anti-tumour response from effector T cellsviamultiple suppressive mechanisms. Future research is needed to address the development of novel NK cell-targeted immunotherapy and on restraining Treg frequency and function in HCC. We have now entered a new era of anti-cancer treatment using checkpoint inhibitor (CPI)-based strategies. Combining GMP-NK cell immunotherapy to enhance the frequency of NK cells with CPI targeting both NK and CD8 T cells to release co-inhibitory receptors and enhance the cells anti-tumour immunity of HCC would be an attractive therapeutic option in the treatment of HCC. These therapeutic approaches should now be complemented by the application of genomic, proteomic and metabolomic approaches to understanding the microenvironment of HCC which, together with deep immune profiling of peripheral blood and HCC tissue before and during treatment, will provide the much-needed personalised medicine approach required to improve clinical outcomes for patients with HCC.
Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation
Authors: van der List Amy C. J. , Litjens Nicolle H. R. , Klepper Mariska , Betjes Michiel G. H.
Published: April 2021

Development of T-cell hyporesponsiveness to donor antigen may explain the substantial decreased risk for acute rejection in the years following kidney transplantation. The underlying mechanisms of donor-specific hyporesponsiveness (DSH) are largely unknown but may allow for lowering of immunosuppressive medication. Due to the onset of DSH being more rapid and pronounced in older recipients (+55 years), we hypothesized that immunosenescence/exhaustion of T lymphocytes would be a contributing factor. This study tested whether donor-reactive recipient T cells become hyporesponsive due to exhaustion from continuous stimulation by donor antigen. Circulating donor-reactive T cells of both young and elderly stable kidney transplant recipients (N=17) before and 3-5 years after transplantation were analyzed at the single cell level for expression of exhaustion markers by multi-parameter flow cytometry followed by unsupervised and unbiased clustering. Clusters containing cells of a particular expression profile with significant differential abundance after transplantation were identified and further analyzed. Unexpectedly, our results do not demonstrate an increase in exhausted donor antigen-reactive T cells post transplantation. Instead, we demonstrate a significant decrease in donor antigen-reactive CD4+ T cells expressing T cell immunoglobulin and ITIM domain (TIGIT) long after transplantation. Further analysis at earlier timepoints indicated that this decrease is already present at six months post transplantation. Characterization of these CD4+ T donor-reactive cells expressing TIGIT revealed them to have a predominantly central and effector memory T cell phenotype and a highly poly-functional cytokine expression profile. This study has therefore identified TIGIT as a marker for a previously undescribed polyfunctional donor-reactive CD4+ T cell population whose decline following kidney transplantation may explain development of DSH.
Alcohol Consumption Accumulation of Monocyte Derived Macrophages in Female Mice Liver Is Interferon Alpha Receptor Dependent
Authors: Alharshawi Khaled , Fey Holger , Vogle Alyx , Klenk Tori , Kim Miran , Aloman Costica
Published: April 2021

Monocytes develop in the bone marrow from the hematopoietic stem cells and represent heterogeneous phagocyte cells in the circulation. In homeostatic and inflammatory conditions, after recruitment into tissues, monocytes differentiate into macrophages and dendritic cells. Alcohol use causes about 3.3 million worldwide deaths per year, which is about 5.9% of all deaths. In the United States and Europe, alcohol use disorders represent the fifth leading cause of death. Females are more susceptible to alcoholic liver injury in both humans and mice. Strikingly, we still do not know how much of this difference in tissue injury is due to the differential effect of alcohol and its toxic metabolites on a) parenchymal or resident cells and/or b) immune response to alcohol. Therefore, we used a model of chronic alcohol exposure in mice to investigate the dynamics of monocytes, an innate immune cell type showed to be critical in alcoholic liver injury, by using immunophenotypic characterization. Our data reveal a sex-dimorphism of alcohol response of hepatic monocytes in female mice that is interferon receptor alpha dependent. This dimorphism could shed light on potential cellular mechanism(s) to explain the susceptibility of females to alcoholic immunopathogenesis and suggests an additional targetable pathway for alcoholic liver injury in females.
Von Willebrand Factor, Factor VIII, and Other Acute Phase Reactants as Biomarkers of Inflammation and Endothelial Dysfunction in Chronic Graft-Versus-Host Disease
Authors: Lelas Antonela , Greinix Hildegard Theresia , Wolff Daniel , Eissner Günther , Pavletic Steven Zivko , Pulanic Drazen
Published: April 2021

Chronic graft-versus-host disease (cGvHD) is an immune mediated late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Discovery of adequate biomarkers could identify high-risk patients and provide an effective pre-emptive intervention or early modification of therapeutic strategy, thus reducing prevalence and severity of the disease among long-term survivors of alloHSCT. Inflammation, endothelial injury, and endothelial dysfunction are involved in cGvHD development. Altered levels of acute phase reactants have shown a strong correlation with the activity of several immune mediated disorders and are routinely used in clinical practice. Since elevated von Willebrand factor (VWF) and factor VIII (FVIII) levels have been described as acute phase reactants that may indicate endothelial dysfunction and inflammation in different settings, including chronic autoimmune diseases, they could serve as potential candidate biomarkers of cGvHD. In this review we focused on reported data regarding VWF and FVIII as well as other markers of inflammation and endothelial dysfunction, evaluating their potential role in cGvHD.
Study on Shear Behavior of Multi-Bolt Connectors for Prefabricated Steel–Concrete Composite Beams
Authors: Wang Wei , Zhang Xie-dong , Zhou Xi-long , Wu Lin , Zhu Hao-jie
Published: April 2021

Multi-bolt shear connectors (MBSCs), arranging bolts as a group in several rows, can be applied in prefabricated steel–concrete composite beams or bridges (SCCBs) to reduce the construction time and meet the requirements of sustainable development. The mechanical behavior of bolt shear connectors has been broadly investigated in recent years, but they were mainly focused on the normal arrangement. The shear performance of MBSCs is not consistent with that of the same number of single bolts. In this study, a three-dimensional (3D) finite element model (FEM) was developed to investigate the multiple bolts effect and its mechanical performance. Material non-linearities and the interactions among all components were included in the FEM. The accuracy and reliability of the proposed FEM were initially verified against the available push-out test results. The validated FEM further studied the load–slip relationship, shear capacity, and shear stiffness of the MBSCs. A parametric study was carried out to determine the effect of the bolt spacing, bolt row numbers, the concrete strength, and the bolt diameter on the shear performance of MBSCs. Based on the extensive parametric analyses, design recommendations considering the multiple bolts effect for predicting the shear resistance per bolt in multi-bolt connectors were proposed and verified.
Monitoring and Analysis of Pore and Earth Pressure at the Pile Surface Using Piezoresistive Silicon Pressure Transducers
Authors: Wang Yonghong , Huang Yongfeng , Zhang Mingyi , Ma Jiaxiao
Published: April 2021

The piezoresistive silicon pressure transducers based on the piezoresistive effect have demonstrated their potential in the accurate monitoring of pressure. However, their usage in the pore and earth pressure monitoring at the pile surface under hydraulic jacking has not yet been explored. In this study, two self-made model piles (one is a closed-ended pile and the other is an open-ended pile) were instrumented with piezoresistive silicon earth transducers and pore pressure transducers and then driven into the soil using a hydraulic jack. A comprehensive investigation was first carried out for the structure of the model piles, the installation procedure of the transducers, and the composition of the test system. The pore and earth pressure measurements of the transducers were used for the evaluation of the distribution of the pore pressure, excess pore pressure, radial earth pressure, and radial effective earth pressure. The model test results indicate that the piezoresistive silicon pressure transducers are suitable for monitoring the pore and earth pressure at the pile surface during jacking. In addition, the pore pressure, excess pore pressure, radial earth pressure, and effective radial earth pressure along the test piles were affected by the penetration depth and the pile end form.
A Review of Recycling Status of Decommissioned Lithium Batteries
Authors: Chen Yaodong , Dou Aichun , Zhang Ye
Published: April 2021

This review analyzes the current global use of lithium batteries and the recycling of decommissioned lithium batteries, focusing on the recycling process, and introduces the status of domestic and foreign recycling industry of decommissioned lithium batteries. It also points out the existing problems and the prospects for the future development of the decommissioned lithium batteries recycling in China.
TiO2 Nanowire Arrays in situ Grown on Ti Foil Exhibiting Superior Uranyl-Adsorption Properties
Authors: Chen Chun , Zhong Yi , Liu Xuxu , Li Xijian , Chu Jian , Yu Libing , Yang Zhenliang , Li Bingqing , Tang Wei , Xiong Zhonghua , Gao Rui
Published: April 2021

TiO2 nanowire arrays in situ grown on Ti foil (TiO2/Ti) were prepared to remove uranium (VI) from aqueous solution. As the Ti foil serves as a carrier for TiO2, the TiO2/Ti adsorbent can be effortlessly retrieved from aqueous solutions by tweezers after adsorption. The presence of TiO2 nanowire arrays on Ti foil was verified by X-ray diffraction and scanning electron microscopy. Parameters in the adsorption process were fully evaluated, including solution pH, contact time, temperature, and uranium (VI) concentration. The adsorption was most efficient in the pH range of 5.0 to 9.0. The maximum uranium (VI) adsorption capacity of TiO2/Ti, based on the Langmuir model, was 354.5 mg g–1 at pH 5.0 and T = 323 K. Thermodynamic parameters showed that the adsorption of uranium (VI) on TiO2/Ti is endothermic and spontaneous. The adsorption capacity of TiO2/Ti remained essentially unchanged after three adsorption–desorption cycles in uranium (VI) solutions. Our results support the application of this adsorbent to removal of uranium (VI) from diversified aqueous samples.
Short-Term Outcomes of Refractory Diabetic Macular Edema Switch From Ranibizumab to Dexamethasone Implant and the Influential Factors: A Retrospective Real World Experience
Authors: Hsia Ning-Yi , Lin Chun-Ju , Chen Huan-Sheng , Chang Cheng-Hsien , Bair Henry , Lai Chun-Ting , Lin Jane-Ming , Chen Wen-Lu , Tien Peng-Tai , Wu Wen-Chuan , Tsai Yi-Yu
Published: April 2021

Introduction: To evaluate the effectiveness and safety of intravitreal dexamethasone (DEX) implants in refractory diabetic macular edema (DME) treated by intravitreal ranibizumab.

Materials and Methods: We retrospectively analyzed DME patients who received DEX implant treatment after being refractory to at least 3 monthly intravitreal ranibizumab injections. The main outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP).

Results: Twenty-nine eyes of 26 patients who had previously received an average of 8.1 ± 4.4 ranibizumab injections were included. Patients received between one and three DEX implants during 12.4 ± 7.4 months of follow-up. The mean final CRT significantly decreased from 384.4 ± 114.4 μm at baseline to 323.9 ± 77.7 μm (p = 0.0249). The mean final BCVA was 51.4 ± 21.3 letters, which was not significant compared to baseline (44.9 ± 30.2 letters, p = 0.1149). Mean IOP did not increase significantly. All patients tolerated the treatment well without serious adverse events. Higher baseline CRT and worse BCVA correlated with better therapeutic responses.

Conclusion: Switching to DEX implant is feasible and safe for treating patients of DME refractory to intravitreal ranibizumab in real world. Further larger-scale or multicenter studies would be conducted to explore different DEX treatment strategies for DME, such as first-line or early switch therapy, for better BCVA improvement.
Colonization With Extensively Drug-Resistant Acinetobacter baumannii and Prognosis in Critically Ill Patients: An Observational Cohort Study
Authors: Zheng Yue , Xu Nana , Pang Jiaojiao , Han Hui , Yang Hongna , Qin Weidong , Zhang Hui , Li Wei , Wang Hao , Chen Yuguo
Published: April 2021

Background:Acinetobacter baumannii is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients.

Methods: We prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively.

Results: Out of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174–2.608).

Conclusions: XDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.
COVID-19 and Sarcoidosis, Readiness for Vaccination: Challenges and Opportunities
Authors: Manansala Michael , Chopra Amit , Baughman Robert P. , Novak Richard , Lower Elyse E. , Culver Daniel A. , Korsten Peter , Drake Wonder P. , Judson Marc A. , Sweiss Nadera
Published: April 2021

Sarcoidosis is an immune mediated chronic inflammatory disorder that is best characterized by non-caseating granulomas found in one or more affected organs. The COVID-19 pandemic poses a challenge for clinicians caring for sarcoidosis patients who may be at increased risk of infection compared to the general population. With the recent availability of COVID-19 vaccines, it is expected that clinicians raise questions regarding efficacy and safety in sarcoidosis. However, studies examining safety and efficacy of vaccines in sarcoidosis are lacking. In this review, we examine the current literature regarding vaccination in immunocompromised populations and apply them to sarcoidosis patients. The available literature suggests that vaccines are safe and effective in patients with autoimmune disorders and in those taking immunosuppressive medications. We strongly recommend the administration of COVID-19 vaccines in patients with sarcoidosis. We also present a clinical decision algorithm to provide guidance on vaccination of sarcoidosis patients against COVID-19.