bluuebunny/crossref_metadata_2025 huggingface dataset:
Projections of Future Marine Heatwaves for the Oceans Around New Zealand Using New Zealand's Earth System Model
Authors: Behrens Erik , Rickard Graham , Rosier Suzanne , Williams Jonny , Morgenstern Olaf , Stone Dáithí
Published: February 2022

This paper investigates marine heatwave (MHW) characteristics in New Zealand's Earth System Model (NZESM) simulations for present-day conditions and how they are projected to change in the future in relation to anthropogenic greenhouse gas emissions. Three emission scenarios following the state of the art shared-socioeconomic pathways (SSPs, SSP1 2.6, SSP2 4.5, and SSP3 7.0) are each evaluated with a set of three ensemble members. These analyses are focused on the ocean around New Zealand, where NZESM captures boundary currents and mesoscale eddies, due to its high-resolution nested ocean grid. For present-day conditions, the model overestimates MHW intensity and underestimates the number of annual MHW days for subtropical waters, while some smaller positive biases are present in subantarctic waters compared to observations. Despite this, NZESM agrees with the observational pattern that more intense MHWs and more annual MHW days are found in subtropical waters compared to subantarctic waters. NZESM projects that MHW intensity will increase more strongly in subtropical waters compared to subantarctic waters, while the largest changes in annual MHW days are projected south of Australia and the Tasman Sea in the Subtropical Front (STF) frontal region, which suggests a southward shift of the STF under increased greenhouse gas emissions. Results using a high-emission scenario (SSP3 7.0) show an increase between 80 and 100% of median MHW intensities by the end of the century relative to the present-day for all analyzed coastal regions, and MHW conditions could become permanent year-round by the end of the century.
Under-Ice Light Field in the Western Arctic Ocean During Late Summer
Authors: Veyssière Gaëlle , Castellani Giulia , Wilkinson Jeremy , Karcher Michael , Hayward Alexander , Stroeve Julienne C. , Nicolaus Marcel , Kim Joo-Hong , Yang Eun-Jin , Valcic Lovro , Kauker Frank , Khan Alia L. , Rogers Indea , Jung Jinyoung
Published: February 2022

The Arctic is no longer a region dominated by thick multi-year ice (MYI), but by thinner, more dynamic, first-year-ice (FYI). This shift towards a seasonal ice cover has consequences for the under-ice light field, as sea-ice and its snow cover are a major factor influencing radiative transfer and thus, biological activity within- and under the ice. This work describes in situ measurements of light transmission through different types of sea-ice (MYI and FYI) performed during two expeditions to the Chukchi sea in August 2018 and 2019, as well as a simple characterisation of the biological state of the ice microbial system. Our analysis shows that, in late summer, two different states of FYI exist in this region: 1) FYI in an enhanced state of decay, and 2) robust FYI, more likely to survive the melt season. The two FYI types have different average ice thicknesses: 0.74 ± 0.07 m (N = 9) and 0.93 ± 0.11 m (N = 9), different average values of transmittance: 0.15 ± 0.04 compared to 0.09 ± 0.02, and different ice extinction coefficients: 1.49 ± 0.28 and 1.12 ± 0.19 m−1. The measurements performed over MYI present different characteristics with a higher average ice thickness of 1.56 ± 0.12 m, lower transmittance (0.05 ± 0.01) with ice extinction coefficients of 1.24 ± 0.26 m−1 (N = 12). All ice types show consistently low salinity, chlorophyll a concentrations and nutrients, which may be linked to the timing of the measurements and the flushing of melt-water through the ice. With continued Arctic warming, the summer ice will continue to retreat, and the decayed variant of FYI, with a higher scattering of light, but a reduced thickness, leading to an overall higher light transmittance, may become a more relevant ice type. Our results suggest that in this scenario, more light would reach the ice interior and the upper-ocean.
What Happens Between Depositional Events, Stays Between Depositional Events: The Significance of Organic Mat Surfaces in the Capture of Ediacara Communities and the Sedimentary Rocks That Preserve Them
Authors: Droser Mary L. , Evans Scott D. , Tarhan Lidya G. , Surprenant Rachel L. , Hughes Ian V. , Hughes Emmy B. , Gehling James G.
Published: February 2022

In the absence of complex, bioturbating organisms, the seafloor during the Precambrian was covered in widespread organic matgrounds. The greatest diversity and complexity of organic mat textures occur in the Ediacaran fossil record as exemplified by the Ediacara Member of the Rawnsley Quartzite, which crops out in and around the Flinders Ranges, South Australia. This succession unambiguously demonstrates that heterogenous mats coexisted with and were central to the ecology and biology of the Ediacara Biota. Excavation of 33 fossiliferous beds with varying types and extents of organosedimentary surface textures provide the opportunity to utilize this record to develop criteria to evaluate the maturity or extent of growth of Ediacaran matgrounds and, using these characteristics, to examine the relationship between mat type, mat maturity and Ediacara Biota community structure. Based on the assumption that mat maturity represents an indicator of the duration of time between burial events, we can test predictions about the relationship between mat maturity and community development. We find that mat maturity, rather than the mat type itself, more strongly influenced the distribution of taxa and the development of Ediacara macroorganism communities. Using a ranked Mat Maturity Index, we find that although density of macroscopic body fossils and genus diversity correlate with mat maturity, evenness does not. We additionally find that the sessile taxaObamusandCoronacollinaare restricted to surfaces with mature mats whereas all other Ediacaran macrobiota show no connection to mat occurrence and maturity. However, we do observe that largeDickinsoniaare more likely to occur on surfaces recording mature matgrounds. The exceptional record of mat surfaces preserved in the Flinders Ranges area demonstrates that, in addition to the apparent ecological role played by mat surfaces in Ediacaran communities, they were also likely a significant component of the Ediacara Member biomass and were integral to community function.
Digital Tools and the Flipped Classroom Approach in Primary Education
Authors: Loizou Maria
Published: February 2022

This article is an expansion of an existing research on the Flipped Classroom (FC) approach, adopted in five different primary schools in Cyprus and considering the experiences and perceptions of five teachers and 77 students (Loizou and Lee, 2020). It particularly expands in exploring the digital tools effectively used to teach primary school students through a FC. The FC approach is an innovative initiative which promotes blended learning methodology. It involves the use of digital technologies for developing and sharing flips/tutorials on the content traditionally taught through lecturing in class. Diverse technology tools have been used in FC research together with online learning platforms. The video tutorials, a basic form of a flip, are usually made by the educators with narration, text and enriched with various annotations and images. Many FC studies have added to the list of essential digital tools for FC implementation, especially the ones which showcase how flips can be developed. However, most of them have not indicated how can these be used for younger students, focusing mainly only in secondary or higher education. For example, how can the structure of a virtual learning environment can be simplified or how can administration of online documents in Drives be more suitable for young ages are scarcely explained. Hence, the significance of this study lies on the fact that research on the FC approach in primary education and the digital tools supporting it, has been so far kept to the minimum. Therefore, by collecting the experiences and perceptions of those involved in the process and assessing how the digital tools may or may not promote a positive learning experience could give an indication in how FC can be effectively implemented in primary education. A qualitative research methodology has been adopted by interviewing the five teachers and forming 11 different focus groups of students. Following the transcription, NVivo11 had been used for the thematic analysis. Research results have shown that the most effective digital tools can be categorized into software supporting: 1) Flips; 2) Activities in class; 3) Communication; 4) Entrance tickets; 5) Collaboration; and, 6) Assessment. These tools, recognized as simple and useful by students and teachers, have guided the creation of the ‟FC Technology tool” which incorporates examples for each category. Overall, a clear illustration of the kind of technology that could be used both at home and in-class for effective FC implementation in primary education is given in the study. Future studies should further evaluate how students can use these tools in forming their own flips and/or tutorials and be part of the pre and in-class session of FC learning classes.
Cold Exposure Induces Depot-Specific Alterations in Fatty Acid Composition and Transcriptional Profile in Adipose Tissues of Pigs
Authors: Zhou Yanbing , Xu Ziye , Wang Liyi , Ling Defeng , Nong Qiuyun , Xie Jintang , Zhu Xiaodong , Shan Tizhong
Published: February 2022

Cold exposure promotes fat oxidation and modulates the energy metabolism in adipose tissue through multiple mechanisms. However, it is still unclear about heat-generating capacity and lipid mobilization of different fat depots without functional mitochondrial uncoupling protein 1 (UCP1). In this study, we kept finishing pigs (lack a functional UCP1 gene) under cold (5-7°C) or room temperature (22-25°C) and determined the effects of overnight cold exposure on fatty acid composition and transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). And the plasma metabolomes of porcine was also studied by LC-MS-based untargeted metabolomics. We found that the saturated fatty acids (SFAs) content was decreased in SAT upon cold exposure. While in VAT, the relative content of lauric acid (C12:0), myristic acid (C14:0) and lignoceric acid (C24:0) were decreased without affecting total SFA content. RNA-seq results showed SAT possess active organic acid metabolism and energy mobilization upon cold exposure. Compared with SAT, cold-induced transcriptional changes were far less broad in VAT, and the differentially expressed genes (DEGs) were mainly enriched in fat cell differentiation and cell proliferation. Moreover, we found that the contents of organic acids like creatine, acamprosate, DL-3-phenyllactic acid and taurine were increased in plasma upon overnight cold treatment, suggesting that cold exposure induced lipid and fatty acid metabolism in white adipose tissue (WAT) might be regulated by functions of organic acids. These results provide new insights into the effects of short-term cold exposure on lipid metabolism in adipose tissues without functional UCP1.
Papillary Thyroid Carcinoma: Molecular Distinction by MicroRNA Profiling
Authors: Galuppini Francesca , Censi Simona , Merante Boschin Isabella , Fassan Matteo , Sbaraglia Marta , Valeri Nicola , Hahne Jens Claus , Bertazza Loris , Munari Giada , Galasso Marco , Cascione Luciano , Barollo Susi , Rugge Massimo , Vianello Federica , Dei Tos Angelo Paolo , Mian Caterina , Pennelli Gianmaria
Published: February 2022

Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription–PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted.
Optimal Design of Integrated Energy Supply System for Continuous Greenhouse Effect: A Study on Carbon Emission and Operational Cost
Authors: Tian Chongyi , Shao Zhuliang , Wang Ruiqi , Yan Yi , Wang Xuerui , Ren Ang
Published: February 2022

The cultivation of crops in greenhouses is well established in China. However, the greenhouse climate is complex, rendering it difficult to analyze the greenhouse load and control the energy supply system. It is important to ensure the optimal design of greenhouse operation to enable optimal crop growth and maintain low operation costs for improving the greenhouse crop production efficiency and economic benefits. To reduce the energy consumption , we propose a new integrated energy supply system. This system uses a combined cooling, heating and power system, and an air source heat pump. A two-stage integrated optimization model of the integrated energy supply system was built, with “minimum average daily economic cost” and “maximum CO2 emission reduction rate (ERR)” as the objectives in the first stage. The characteristics of the countryside were taken into consideration for optimizing the capacity of the combined cooling, heating and power supply, energy storage and air source heat pump. In the second stage, the objectives were “maximum annual operating saving rate (OSR)”, “maximum CO2 emission reduction rate”, and “maximum primary energy saving rate (PESR)”. The capacity of the equipment designed in the first stage is used as the constraint to optimize the operating output of the combined cooling, heating and power supply, air source heat pump. Finally, a greenhouse is used as a prototype to carry out simulation calculations for two typical days in summer and winter to verify the effectiveness of this method. The simulation results showed that after the first stage of optimization, the average daily operating cost was significantly lower and the CO2 emission rate was reduced by 49.53%. After the second stage, annual operating saving rate, CO2 emission reduction rate, and primary energy saving rate were 39.51, 48.88, and 27.57% for a typical summer day and 52.96, 50.18, and 50.13% for a typical winter day, respectively. Therefore, compared to the existing energy supply systems, the integrated energy supply system and the integrated optimization design of the system could effectively avoid energy wastage, significantly improve the degree of match between the system design and operation, reduce operating cost, and reduce CO2 emission.
Determination of Soil Cadmium Threshold for Potato
Authors: Li Wei , He Xue , Zhang Jie , Liu Ke
Published: February 2022

In this study, pot experiments were conducted to investigate the characteristics of Cd transfer to potato tubers from two types of soil. The results showed that the Log-normal and Burr III functions can be used to determine the sensitivity of different potato varieties to Cd as well as the soil Cd threshold. With regard to the prediction accuracy, the root mean squared error (RMSE) values for the total Cd biaoaccumulation factor (BAFtotal) calculated with both functions were smaller than those for exogenous Cd biaoaccumulation (BAFadd) in acidic and alkaline soils, indicating that BAFtotal is more appropriate for the calculation of the soil Cd threshold. The average Cd threshold values in acidic soil calculated with the Log-normal and Burr III functions were 0.411 and 0.461 mg kg−1, and the average values in alkaline soil were 0.716 and 0.888, respectively. The Log-normal function can also be applied to fit the sensitivity distributions of different species for the development of appropriate soil Cd threshold values for conservation purposes.
CircATRNL1 and circZNF608 Inhibit Ovarian Cancer by Sequestering miR-152-5p and Encoding Protein
Authors: Lyu Mengmeng , Li Xiujuan , Shen Yang , Lu Jin , Zhang Lihua , Zhong Shanliang , Wang Jinhua
Published: February 2022

Background: CircRNAs have been found to be involved in the pathogenesis of various diseases. We aimed to explore the roles of circRNAs in ovarian cancer.

Methods: The expression levels of circRNAs in ovarian cancer and normal ovarian tissues were analyzed using RNA sequencing. Fluorescent in situ hybridization (FISH), proliferation assays and transwell assays were used to assess the effects of circRNAs on ovarian cancer.

Results: CircATRNL1 and circZNF608 were downregulated in 20 ovarian cancer tissues compared to normal tissues. CircATRNL1 and circZNF608 are mainly located in the cytoplasm of ovarian cancer cells, and circATRNL1 is a highly conserved circRNA. The overexpression of circATRNL1 and circZNF608 inhibits the proliferation and invasion of ovarian cancer cells. We predicted miRNA–circRNA interactions for circZNF608 and circATRNL1 and obtained 63 interactions. However, a luciferase reporter assay showed that only miR-152-5p was sequestered by circZNF608. Bioinformatics analysis and experiments indicated that circATRNL1 contains an internal ribosome entry site and an open reading frame encoding a 131 aa protein.

Conclusion: In conclusion, circATRNL1 and circZNF608 are two downregulated circRNAs in ovarian cancer and work as tumor suppressors. CircZNF608 may exert antitumor activity in ovarian cancer by binding miR-152-5p, and circATRNL1 may encode a 131 aa protein.
A Systematic Evaluation of Supervised Machine Learning Algorithms for Cell Phenotype Classification Using Single-Cell RNA Sequencing Data
Authors: Cao Xiaowen , Xing Li , Majd Elham , He Hua , Gu Junhua , Zhang Xuekui
Published: February 2022

The new technology of single-cell RNA sequencing (scRNA-seq) can yield valuable insights into gene expression and give critical information about the cellular compositions of complex tissues. In recent years, vast numbers of scRNA-seq datasets have been generated and made publicly available, and this has enabled researchers to train supervised machine learning models for predicting or classifying various cell-level phenotypes. This has led to the development of many new methods for analyzing scRNA-seq data. Despite the popularity of such applications, there has as yet been no systematic investigation of the performance of these supervised algorithms using predictors from various sizes of scRNA-seq datasets. In this study, 13 popular supervised machine learning algorithms for cell phenotype classification were evaluated using published real and simulated datasets with diverse cell sizes. This benchmark comprises two parts. In the first, real datasets were used to assess the computing speed and cell phenotype classification performance of popular supervised algorithms. The classification performances were evaluated using the area under the receiver operating characteristic curve, F1-score, Precision, Recall, and false-positive rate. In the second part, we evaluated gene-selection performance using published simulated datasets with a known list of real genes. The results showed that ElasticNet with interactions performed the best for small and medium-sized datasets. The NaiveBayes classifier was found to be another appropriate method for medium-sized datasets. With large datasets, the performance of the XGBoost algorithm was found to be excellent. Ensemble algorithms were not found to be significantly superior to individual machine learning methods. Including interactions in the ElasticNet algorithm caused a significant performance improvement for small datasets. The linear discriminant analysis algorithm was found to be the best choice when speed is critical; it is the fastest method, it can scale to handle large sample sizes, and its performance is not much worse than the top performers.
Case Report: Rotavirus Vaccination and Severe Combined Immunodeficiency in Japan
Authors: Tanita Kay , Kawamura Yoshiki , Miura Hiroki , Mitsuiki Noriko , Tomoda Takahiro , Inoue Kento , Iguchi Akihiro , Yamada Masafumi , Yoshida Taro , Muramatsu Hideki , Tada Norimasa , Matsui Toshihiro , Kato Motohiro , Eguchi Katsuhide , Ishimura Masataka , Ohga Shouichi , Imai Kohsuke , Morio Tomohiro , Yoshikawa Tetsushi , Kanegane Hirokazu
Published: February 2022

Severe combined immunodeficiency (SCID) is an inborn error of immunity that occurs in approximately 1 in 50,000 births, mainly due to impaired lymphocyte differentiation. Without curative treatment, such as hematopoietic cell transplantation (HCT) or gene therapy, severe infection in the first year of life could make this condition fatal. The results of HCT are poor when patients have active infections, thus requiring early diagnosis before onset of infection. In five cases of SCID diagnosed in Japan, the oral rotavirus vaccine had been administered before diagnosis. In this study, we demonstrated that the rotavirus from their stools was a vaccine-derived strain. In some cases, severe gastroenteritis triggered the diagnosis of SCID. However, newborn screening for SCID is available before the first rotavirus vaccination using assays for the detection of T-cell receptor excision circles (TRECs). Therefore, to improve the prognosis of patients with SCID in Japan, we should establish a screening system of TRECs for newborns throughout Japan.
The Antibody Assay in Suspected Autoimmune Encephalitis From Positive Rate to Test Strategies
Authors: Deng Qun , Liu Ye , Mao Zhifeng , Chen Yun , Ping Yue , Zhu Guoqiang , Zhao Weiqing , Hu Xiao , Zhou Hao
Published: February 2022

Objective

The aim of this study was to analyze the positive rate and test strategies of suspected autoimmune encephalitis (SAE) based on an antibody assay.

Methods

Patients who were diagnosed with suspected autoimmune encephalitis in Guizhou Province between June 1, 2020, and June 30, 2021 and who had anti-neuronal autoantibodies detected by Guizhou KingMed Diagnostics Group Co., Ltd. were included in this study. The positive rate and the test strategies were analyzed based on the results of the anti-neuronal antibody assay.

Results

A total of 263 patients with SAE were included, 58.2% (153/263) of whom were males, with a median age of 33 years (1-84 years). 84% (221/263) of all patients completed both serum and CSF tests. A total of 46.0% (121/263) of SAE patients received the AE-6 examination package. The antibody-positive rate was 9.9% (26/263) in the current cohort, with an observed incidence of antibody positive of 0.2 in 100,000 (26/11,570,000, 95% CI: 0.15-0.30), and the estimated incidence was 0.9 in 100,000 (95% CI: 0.84-0.95) of the total population. A total of 9 different anti-neuronal antibodies were detected. Anti-NMDAR antibody was the most common antibody in 46.2% (12/26) of subjects, 70.0% (7/10) of whom were children, followed by anti-Caspr2 antibody in 30.8% (8/26); the remaining 7 antibodies were detected in 23.1% (6/26) of the population. There were no obvious differences among age, sex or season in the positive rate of anti-neuronal antibodies. The cost of antibody testing per capita was $439.30 (SD±$195.10). The total cost of AE-14 was the highest at $48.016.81 (41.56%) among all examination packages.

Conclusions

This study described the positive rate associated with AE-related anti-neuronal antibodies and test strategies in the current cohort, which provides a basis for clinicians in clinical practice.
Acute Symptomatic Seizures and Risk of Epilepsy in Autoimmune Encephalitis: A Retrospective Cohort Study
Authors: Zhong Rui , Zhang Xinyue , Chen Qingling , Li Mengmeng , Guo Xin , Lin Weihong
Published: February 2022

Purpose

To investigate the clinical characteristics of acute symptomatic seizures and the predictors of the development of epilepsy in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.

Methods

We retrospectively screened the medical records of 86 hospitalized patients with confirmed autoimmune encephalitis (AE). The clinical characteristics of acute symptomatic seizures were analyzed. The predictors of the development of epilepsy were investigated using logistic regression analysis.

Results

A total of 86 patients with AE were finally included. Eighty-six percent of patients (n = 74) experienced acute symptomatic seizures, and 28.4% of patients developed epilepsy during follow-up. Abnormal EEG findings were more frequent in AE patients with acute symptomatic seizures. A greater number of anti-seizure medications (ASMs), abnormal EEG findings, and delayed immunotherapy were found to be independently associated with the development of epilepsy.

Conclusion

Acute symptomatic seizures are a common manifestation in AE patients. During follow-up, 28.4% of AE patients developed epilepsy. The independent factors that predicted the development of epilepsy after the acute phase included a larger number of ASMs, EEG abnormalities, and delayed immunotherapy. In clinical practice, we should prioritize immunotherapy to control acute seizures as soon as possible. For AE patients with an increased risk of developing epilepsy, early withdrawal of ASM is not recommended.
Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut
Authors: Lemme-Dumit Jose M. , Song Yang , Lwin Hnin Wai , Hernandez-Chavez Claudia , Sundararajan Sripriya , Viscardi Rose M. , Ravel Jacques , Pasetti Marcela F. , Ma Bing
Published: February 2022

Intestinal barrier immaturity, or “leaky gut”, is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. Exacerbated intestinal immune responses, gut microbiota dysbiosis, and heightened barrier injury are considered primary triggers of aberrant intestinal maturation in early life. Inordinate host immunity contributes to this process, but the precise elements remain largely uncharacterized, leaving a significant knowledge gap in the biological underpinnings of gut maturation. In this study, we investigated the fecal cytokine profile and gut microbiota in a cohort of 40 early preterm infants <33-weeks-gestation to identify immune markers of intestinal barrier maturation. Three distinct microbiota types were demonstrated to be differentially associated with intestinal permeability (IP), maternal breast milk feeding, and immunological profiles. The Staphylococcus epidermidis- and Enterobacteriaceae-predominant microbiota types were associated with an elevated IP, reduced breast milk feeding, and less defined fecal cytokine profile. On the other hand, a lower IP was associated with increased levels of fecal IL-1α/β and a microbiota type that included a wide array of anaerobes with expanded fermentative capacity. Our study demonstrated the critical role of both immunological and microbiological factors in the early development of intestinal barrier that collectively shape the intestinal microenvironment influencing gut homeostasis and postnatal intestinal maturation in early preterm newborns.
Maternal Influences and Intervention Strategies on the Development of Food Allergy in Offspring
Authors: Jiao Lefei , Su Chien-Wen , Cao Tinglan , Zheng Shasha , Walker W. Allan , Shi Hai Ning
Published: February 2022

Food allergies and other immune-mediated diseases have become serious health concerns amongst infants and children in developed and developing countries. The absence of available cures limits disease management to allergen avoidance and symptomatic treatments. Research has suggested that the presence of maternal food allergies may expose the offspring to genetic predisposition, making them more susceptible to allergen sensitization. The following review has focused on epidemiologic studies regarding maternal influences of proneness to develop food allergy in offspring. The search strategy was “food allergy OR maternal effects OR offspring OR prevention”. A systematically search from PubMed/MEDLINE, Science Direct and Google Scholar was conducted. Specifically, it discussed the effects of maternal immunity, microbiota, breastfeeding, genotype and allergy exposure on the development of food allergy in offspring. In addition, several commonly utilized prenatal and postpartum strategies to reduce food allergy proneness were presented, including early diagnosis of high-risk infants and various dietary interventions.
Circulating Donor-Specific Anti-HLA Antibodies Associate With Immune Activation Independent of Kidney Transplant Histopathological Findings
Authors: Van Loon Elisabet , Lamarthée Baptiste , Barba Thomas , Claes Sandra , Coemans Maarten , de Loor Henriette , Emonds Marie-Paule , Koshy Priyanka , Kuypers Dirk , Proost Paul , Senev Aleksandar , Sprangers Ben , Tinel Claire , Thaunat Olivier , Van Craenenbroeck Amaryllis H. , Schols Dominique , Naesens Maarten
Published: February 2022

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation.
Case Report: Simultaneously Developed Amyopathic Dermatomyositis and Autoimmune Sclerosing Cholangitis – a Coincidence or a Shared Immunopathogenesis?
Authors: Ledenko Tomislav , Sorić Hosman Iva , Ćorić Marijana , Gagro Alenka
Published: February 2022

Inflammatory rheumatic diseases (IRD) and autoimmune liver diseases (AILD) share many similarities regarding epidemiology, genetics, immunology and therapeutic regimens, so it is not surprising that approximately 20% of patients with AILD are diagnosed with an IRD as well. Clinical features and biochemical hallmarks of IRD and AILD often intertwine and cross diagnostic criteria. Therefore, the real distinction of underlying disorders in a patient with these comorbidities may be challenging. The present report is the first report of simultaneously developed juvenile dermatomyositis (JDM) and autoimmune sclerosing cholangitis (ASC) with both entities fulfilling the latest guidelines for a definite diagnosis. Both of these diagnoses are difficult to definitely establish since ASC has a similar serologic profile as autoimmune hepatitis and liver histological analysis is frequently non-specific, whereas clinically amyopathic JDM diagnosis depends mostly on classical dermatological symptoms, while the rest of the diagnostic criteria, including the necessity for skin or muscle biopsy and the presence of myositis specific antibodies, are still not uniformed. In spite of these challenges, our patient clearly met European League Against Rheumatism/American College of Rheumatology classification criteria for CAJDM and The European Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria for ASC. Since elevated serum transaminases, the presence of serum antinuclear antibodies and hypergammaglobulinemia could be explained as a part of both JDM and ASC, the underlying pathophysiology remains debatable. Intriguingly, JDM and ASC share genetic predisposition including human leukocyte antigen allele DRB1*0301 and tumor necrosis factor α 308A allele. Furthermore, both humoral and cellular components of the adaptive immune system contribute to the pathogenesis of JDM and ASC. Moreover, recent findings indicate that the loss of the CD28 expression on T-cells plays a significant role in their pathogenesis along with the Th17 immune pathway. Despite these common features that suggest shared autoimmunity, AILD and autoimmune myositis are traditionally studied and managed independently. The lack of therapies that target the underlying cause results in a high rate of adverse events due to unspecific immunosuppressive therapy. Shared autoimmunity is an ideal area to develop new, targeted immunotherapy that would hopefully be beneficial for more than one disease.
Restoration of Default Blood Monocyte-Derived Macrophage Polarization With Adalimumab But Not Etanercept in Rheumatoid Arthritis
Authors: Paoletti Audrey , Ly Bineta , Bitoun Samuel , Nocturne Gaëtane , Rivière Elodie , Manson Jessica J. , Matucci Andrea , Pallardy Marc , De Vries Niek , Mariette Xavier
Published: February 2022

Introduction

We previously reported a specific defect of rheumatoid arthritis (RA) monocyte polarization to anti-inflammatory M2-like macrophages related to increased miR-155 expression in all RA patients except those receiving adalimumab (ADA). In this longitudinal study, we examined whether different tumor necrosis factor inhibitors were able to restore monocyte polarization to M2-like macrophages and their effect on the transcriptomic signature.

Methods

M2-like polarization induced by human serum AB was studied in 7 healthy donors and 20 RA patients included in the ABIRA cohort before and 3 months after starting ADA or etanercept (ETA). The differential gene expression of M2- and M1-related transcripts was studied in macrophage-derived monocytes after differentiation.

Results

At baseline, RA monocytes showed a defect of polarization to M2-like macrophages as compared with healthy donor monocytes, which was negatively correlated with disease activity. M2-like polarization from circulating monocytes was restored only with ADA and not ETA treatment. The transcriptomic signature demonstrated downregulation of M2-related transcripts and upregulation of M1-related transcripts in active RA. In patients receiving ADA, the transcriptomic signature of M2-related transcripts was restored.

Conclusion

This longitudinal study demonstrates that ADA but not ETA is able to restore the M2-like polarization of monocytes that is defective in RA.
NLRP3 Is Involved in Neutrophil Mobilization in Experimental Periodontitis
Authors: Cheat Banndith , Torrens Coralie , Foda Asmaa , Baroukh Brigitte , Sadoine Jeremy , Slimani Lotfi , Witko-Sarsat Véronique , Huck Olivier , Gosset Marjolaine , Bouchet Jérôme
Published: February 2022

The NLRP3 inflammasome is overexpressed in gingiva of periodontitis patients but its role remains unclear. In our study, we use a periodontitis mouse model of ligature, impregnated or not with Porphyromonas gingivalis, in WT or NLRP3 KO mice. After 28 days of induction, ligature alone provoked exacerbated periodontal destruction in KO mice, compared to WT mice, with an increase in activated osteoclasts. No difference was observed at 14 days, suggesting that NLRP3 is involved in regulatory pathways that limit periodontitis. In contrast, in the presence of P. gingivalis, this protective effect of NLRP3 was not observed. Overexpression of NLRP3 in connective tissue of WT mice increased the local production of mature IL−1β, together with a dramatic mobilization of neutrophils, bipartitely distributed between the site of periodontitis induction and the alveolar bone crest. P. gingivalis enhanced the targeting of NLRP3-positive neutrophils to the alveolar bone crest, suggesting a role for this subpopulation in bone loss. Conversely, in NLRP3 KO mice, mature IL-1β expression was lower and almost no neutrophils were mobilized. Our study sheds new light on the role of NLRP3 in periodontitis by highlighting the ambiguous role of neutrophils, and P. gingivalis which affects NLRP3 functions.
Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical Outcome via Effecting Tumor Immunity for ccRCC, Is Related to Cell Invasion, Metastasis, and Sunitinib Sensitivity
Authors: Jiang Aimin , Meng Jialin , Gong Wenliang , Zhang Zhonghua , Gan Xinxin , Wang Jie , Wu Zhenjie , Liu Bing , Qu Le , Wang Linhui
Published: February 2022

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma and is associated with poor prognosis and notorious for its immune dysfunction characteristic. SNRPA1 is a spliceosome component responsible for processing pre-mRNA into mRNA, while the biological effect of SNRPA1 in ccRCC remains elusive. The aim of this study was to decipher the effect of SNRPA1 on clinical effect and tumor immunity for ccRCC patients. Multi-databases were collected to evaluate the different expression, prognostic value, DNA methylation, tumor immune microenvironment, and drug sensitivity of SNRPA1 on ccRCC. IHC was utilized to validate the expression and prognostic value of SNRPA1 in ccRCC patients from the SMMU cohort. The knockout expression of SNRPA by sgRNA plasmid inhibited the cell proliferation, migration, and metastasis ability and significantly increased the sensitivity of sunitinib treatment. In addition, we explored the role of SNRPA1 in pan-cancer level. The results indicated that SNRPA1 was differentially expressed in most cancer types. SNRPA1 may significantly influence the prognosis of multiple cancer types, especially in ccRCC patients. Notably, SNRPA1 was significantly correlated with immune cell infiltration and immune checkpoint inhibitory genes. In addition, the aggressive and immune inhibitory effects shown in SNRPA1 overexpression and the effect of SNRPA1 on ccRCC cell line invasion, metastasis, and drug sensitivity in vitro were observed. Moreover, SNRPA1 was related to Myc, MTORC, G2M, E2F, and DNA repair pathways in various cancer types. In all, SNRPA1 may prove to be a new biomarker for prognostic prediction, effect tumor immunity, and drug susceptibility in ccRCC.
Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma
Authors: Bourayou Elsa , Golub Rachel
Published: February 2022

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide and its incidence continues to rise globally. Various causes can lead to its development such as chronic viral infections causing hepatitis, cirrhosis or nonalcoholic steatohepatitis (NASH). The contribution of immune cells to HCC development and progression has been extensively studied when it comes to adaptive lymphocytes or myeloid populations. However, the role of the innate lymphoid cells (ILCs) is still not well defined. ILCs are a family of lymphocytes comprising five subsets including circulating Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s and lymphocytes tissue-inducer cells (LTi). Mostly located at epithelial surfaces, tissue-resident ILCs and NK cells can rapidly react to environmental changes to mount appropriate immune responses. Here, we provide an overview of their roles and actions in HCC with an emphasis on the importance of diverse signaling pathways (Notch, TGF-β, Wnt/β-catenin…) in the tuning of their response to HCC.
Synthesis of Type-I and Type-II LacNAc-Repeating Oligosaccharides as the Backbones of Tumor-Associated Lewis Antigens
Authors: Phang Riping , Lin Chun-Hung
Published: February 2022

Type-I and Type-II LacNAc are Gal-GlcNAc disaccharides bearing a β1,3- or β1,4-linkage respectively. They exist as the backbones of Lewis antigens that are highly expressed in several cancers. Owing to the promise of developing carbohydrate-based anti-cancer vaccines, glycan synthesis at a large scale is indeed an important task. Synthesis of Type-I and Type-II tandem repeat oligomers has been hampered by the presence of GlcNAc residues. Particularly, N-protecting group plays a determining role in affecting glycosyl donor’s reactivity and acceptor’s nucleophilicity. This review discusses several representative studies that assembled desirable glycans in an efficient manner, such as chemoselective one-pot synthesis and chemoenzymatic methods. Additionally, we also highlight solutions that have been offered to tackle long-lasting problems, e.g., prevention of the oxazoline formation and change of donor/acceptor reactivity. In retrospect of scientific achievements, we present the current restrictions and remaining challenges in this less explored frontier.
Severe Bilateral Hyperkeratosis of the Nipples and Areolae: A Case Report and Literature Review
Authors: Wei Jiaying , Li Qingshu , Wu He , Yin Xuedong , Ren Guosheng
Published: February 2022

Background

Hyperkeratosis of the nipple and areola (HNA) is a rare skin disease with unknown etiology. Some patients are misdiagnosed or never diagnosed, especially during the early stage of this disease. In addition, the mechanism involved in the development of HNA is still unknown, and genomic alterations have not been reported anywhere.

Case Information

A 26-year-old female suffered gradual bilateral areola thickening and enlargement, with accompanying intense itching, and was diagnosed with HNA at the First Affiliated Hospital of Chongqing Medical University. No obvious abnormalities were found in laboratory test examinations such as hormone testing for estrogen, progesterone, or prolactin. Typical papillomatous skin with orthokeratotic hyperkeratosis and numerous infiltrating lymphocytes was detected through a histopathological examination. The results from RNA-sequencing showed that the molecular expression between HNA and a normal nipple and areola (NNA) was obviously different. No significant difference was found in the bilateral lesions. In addition, immune-related cell signaling pathways were overactivated in HNA compared to the control HNA.

Conclusion

The typical symptoms, clinical features, and histopathological alterations presented in this case lead to a profound understanding of HNA, which can avoid the misdiagnosis and missed diagnosis of this disease at an early stage. The dysfunction of the local immune system, which was demonstrated by pathological examination and genomic analysis, suggests that anti-autoimmune therapy, such as steroid medication, may be an effective treatment for HNA at an early stage.
Machine-Learning Approaches for Predicting the Need of Oxygen Therapy in Early-Stage COVID-19 in Japan: Multicenter Retrospective Observational Study
Authors: Yamanaka Syunsuke , Morikawa Koji , Azuma Hiroyuki , Yamanaka Maki , Shimada Yoshimitsu , Wada Toru , Matano Hideyuki , Yamada Naoki , Yamamura Osamu , Hayashi Hiroyuki
Published: February 2022

Background

Early prediction of oxygen therapy in patients with coronavirus disease 2019 (COVID-19) is vital for triage. Several machine-learning prognostic models for COVID-19 are currently available. However, external validation of these models has rarely been performed. Therefore, most reported predictive performance is optimistic and has a high risk of bias. This study aimed to develop and validate a model that predicts oxygen therapy needs in the early stages of COVID-19 using a sizable multicenter dataset.

Methods

This multicenter retrospective study included consecutive COVID-19 hospitalized patients confirmed by a reverse transcription chain reaction in 11 medical institutions in Fukui, Japan. We developed and validated seven machine-learning models (e.g., penalized logistic regression model) using routinely collected data (e.g., demographics, simple blood test). The primary outcome was the need for oxygen therapy (≥1 L/min or SpO2 ≤ 94%) during hospitalization. C-statistics, calibration slope, and association measures (e.g., sensitivity) evaluated the performance of the model using the test set (randomly selected 20% of data for internal validation). Among these seven models, the machine-learning model that showed the best performance was re-evaluated using an external dataset. We compared the model performances using the A-DROP criteria (modified version of CURB-65) as a conventional method.

Results

Of the 396 patients with COVID-19 for the model development, 102 patients (26%) required oxygen therapy during hospitalization. For internal validation, machine-learning models, except for the k-point nearest neighbor, had a higher discrimination ability than the A-DORP criteria (P < 0.01). The XGboost had the highest c-statistic in the internal validation (0.92 vs. 0.69 in A-DROP criteria; P < 0.001). For the external validation with 728 temporal independent datasets (106 patients [15%] required oxygen therapy), the XG boost model had a higher c-statistic (0.88 vs. 0.69 in A-DROP criteria; P < 0.001).

Conclusions

Machine-learning models demonstrated a more significant performance in predicting the need for oxygen therapy in the early stages of COVID-19.
Unraveling Nitrogen, Sulfur, and Carbon Metabolic Pathways and Microbial Community Transcriptional Responses to Substrate Deprivation and Toxicity Stresses in a Bioreactor Mimicking Anoxic Brackish Coastal Sediment Conditions
Authors: Dalcin Martins Paula , Echeveste Medrano Maider J. , Arshad Arslan , Kurth Julia M. , Ouboter Heleen T. , Op den Camp Huub J. M. , Jetten Mike S. M. , Welte Cornelia U.
Published: February 2022

Microbial communities are key drivers of carbon, sulfur, and nitrogen cycling in coastal ecosystems, where they are subjected to dynamic shifts in substrate availability and exposure to toxic compounds. However, how these shifts affect microbial interactions and function is poorly understood. Unraveling such microbial community responses is key to understand their environmental distribution and resilience under current and future disturbances. Here, we used metagenomics and metatranscriptomics to investigate microbial community structure and transcriptional responses to prolonged ammonium deprivation, and sulfide and nitric oxide toxicity stresses in a controlled bioreactor system mimicking coastal sediment conditions. Ca. Nitrobium versatile, identified in this study as a sulfide-oxidizing denitrifier, became a rare community member upon ammonium removal. The ANaerobic Methanotroph (ANME) Ca. Methanoperedens nitroreducens showed remarkable resilience to both experimental conditions, dominating transcriptional activity of dissimilatory nitrate reduction to ammonium (DNRA). During the ammonium removal experiment, increased DNRA was unable to sustain anaerobic ammonium oxidation (anammox) activity. After ammonium was reintroduced, a novel anaerobic bacterial methanotroph species that we have named Ca. Methylomirabilis tolerans outcompeted Ca. Methylomirabilis lanthanidiphila, while the anammox Ca. Kuenenia stuttgartiensis outcompeted Ca. Scalindua rubra. At the end of the sulfide and nitric oxide experiment, a gammaproteobacterium affiliated to the family Thiohalobacteraceae was enriched and dominated transcriptional activity of sulfide:quinone oxidoreductases. Our results indicate that some community members could be more resilient to the tested experimental conditions than others, and that some community functions such as methane and sulfur oxidation coupled to denitrification can remain stable despite large shifts in microbial community structure. Further studies on complex bioreactor enrichments are required to elucidate coastal ecosystem responses to future disturbances.