bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Thoughts on two cases of total anomalous pulmonary venous connection complicated with pulmonary artery hypertension
Authors: Yan Ling , Zhou Yaxin , Li Dayan , Li Lingli , Tang Hong
Published: January 2023

The two primary pathological alterations of total anomalous pulmonary venous connection (TAPVC), a rare cyanotic congenital heart disease (CHD), are right heart failure and pulmonary artery hypertension (PAH). The timing and prognosis of surgery depend on the level of pulmonary hypertension. Surgery will not be an option after Eisenmenger syndrome appears. In light of this, it is crucial to assess patients’ PAH. In order to aid in the following treatment of related types of diseases, this article studied and compared the echocardiographic features and disease development of one adult and one child TAPVC patients complicated with PAH.
Mineralization age and genesis of the makeng-style iron deposits in the Paleo-Pacific tectonic domain of South China: In situ LA-ICPMS garnet U-Pb chronological and geochemical constraints
Authors: Wang Sen , Cao Ke , Zhang Da , Yi Jin-Jun , Hu Bo-Jie , Yang Jing , Cai Meng-Ying , Zhang Yao-Yao , Yuan Yuan , Pan Tian-Wang
Published: January 2023

To reveal the genesis of Makeng-style iron polymetallic deposits from SE China in the paleo-Pacific tectonic domain, a new analytical method of LA-ICPMS garnet U-Pb dating and rare Earth element analysis was conducted for the Makeng, Luoyang, Dapai and Pantian deposits. The U-Pb dating results of nine garnet skarn samples from these deposits suggested that the Makeng-style iron polymetallic deposits mainly formed during 137–130 Ma, which is consistent with the zircon U-Pb and molybdenite Re-Os ages. This study provides more direct evidence of the mineralization age and the relationship between mineralization and granite, compared with previous studies on the zircon U-Pb dating for granites in the ore fields. Rare Earth element (REE) analysis results and REE patterns of four representative garnet samples from the Makeng, Luoyang, Dapai and Pantian deposits show that they are similar to typical skarn deposits, but obvious differences in the REE distribution types indicate that the ore-forming process may be distinct due to different mineralizing fluid for these Makeng-style deposits. Our new garnet U-Pb dating and rare Earth element analysis result not only provides new evidence for the mineralization age and genesis of the Makeng-style deposits but is also of great significance to promote the application of U-Pb dating methods to research skarn type deposits.
On the relationship between ENSO and overland accumulated cyclone energy of landfalling tropical cyclones over the western North Pacific
Authors: Fu Xinmiao , Song Jinjie , Duan Yihong
Published: January 2023

This study investigates the relationship between El Niño-Southern Oscillation (ENSO) and overland accumulated cyclone energy (ACE) of tropical cyclones (TCs) over the western North Pacific (WNP). We find that there is only a weak correlation between ENSO and overland ACE during 1979–2019, compared to the significant relationship between ENSO and basinwide ACE over the WNP as reported in previous publications. Overland ACE is generally smaller in El Niño and La Niña years than that in neutral years, which mainly results from lower landfall frequency and shorter duration after landfall. Relative to neutral years, overland ACE is lower over almost the entire China mainland in both El Niño and La Niña years, which can be related to the changes in the formation and movement of landfalling TCs. During El Niño and La Niña years, fewer landfalling TCs form over the western WNP, mainly resulting from reduced 850-hPa humidity, which leads to a less chance of TCs making landfall over China mainland. In addition, the eastward (westward) shift of the western Pacific subtropical high in El Niño (La Niña) years steers more TCs to make landfall over the southern (northern) China.
Three-dimensional elastic reverse-time migration using a high-order temporal and spatial staggered-grid finite-difference scheme
Authors: Fang Jinwei , Huang Lanying , Shi Ying , Chen Hanming , Wang Bo
Published: January 2023

Three-dimensional (3D) elastic reverse-time migration (ERTM) can image the subsurface 3D seismic structures, and it is an important tool for the Earth’s interior imaging. A common simulation kernel used in 3D ERTM is the current staggered-grid finite-difference (SGFD) method of the first-order elastic wave equation. However, the mere second-order accuracy in time of the current SGFD method can bring non-negligible time dispersion, which reduces the simulation accuracy and further leads to the distortion of the imaging results. This paper proposes a vector-based 3D ERTM using the high-order accuracy SGFD method in time to obtain high-accuracy images. This approach is a new high-resolution ERTM workflow that improves the imaging accuracy of conventional ERTM from numerical simulation. The proposed ERTM workflow is established on a quasi-stress–velocity wave equation and its vector wavefield decomposition form. Advanced SGFD schemes and their corresponding coefficients with fourth-order temporal accuracy solve the quasi-linear wave equation system. The normalized dot product imaging condition produces high-quality images using high-accuracy vector wavefields solved using the SGFD method. Through the numerical examples, we test the simulation efficiency and analyze how temporal accuracy in numerical simulations affects migration imaging quality. We include that the proposed method obtains highly accurate images.
Revealing karst water circulation based on the GIS and environmental isotopes methods—A case study in eastern Sichuan, southwestern China
Authors: Qin Zixuan , Zhang Qiang , Yu Siyao , Yang Yanna , Zhang Jiasen , Xu Mo , Liu Yang , Liu Maoyi , Nie Mi
Published: January 2023

Jura-type folds in eastern Sichuan Basin have created unique multi-type karst water circulation patterns. Understanding the karst water circulation features is helpful to the protection and management of water resources in this area. In this study, a typical Jura-type fold Mingyueshan in eastern Sichuan, Southwestern China is taken as an example. The geological conditions, natural geographical factors, and environmental isotopes data (δ2H, δ18O, δ3H) are analyzed, the GIS method was used to construct the groundwater flow system. The results reveal the karst water circulation patterns under the control of multiple drainage base levels. Finally, it comes to the conclusion that the north, middle and south sections of Mingyueshan present three water circulation patterns: unidirectional shallow circulation system, bidirectional shallow circulation system and unidirectional shallow-deep nested circulation system, respectively. These results are essentially qualitative, some numerical simulations of groundwater flow can be considered in future work, which will help to determine the groundwater flow system quantitatively. The research results can provide reference for the studies of karst aquifers in eastern Sichuan Jura-type folds area and other areas with similar characteristics.
Gender representation in government-endorsed Arabic language textbooks: Insights from Indonesia
Authors: Kuraedah St , Gunawan Fahmi , Alam Samsu , Ubaidillah M. Faruq , Alimin Alimin , Fitriyani Fitriyani
Published: January 2023

Much research on textbook analysis has looked at diverse perspectives nested by the textbook authors, including gender equality. Although a growing body of research on gender representation in textbooks has been undertaken, there is a paucity of research on Arabic textbooks. This study aims to examine gender representation in Arabic textbooks for Islamic school students approved by the Ministry of Religion of Indonesia to fill the research gap. This research employed a case study design focusing on three textbooks. The researchers utilized thematic analysis anchored in Rifkin’s theory. The findings show that (1) gender representation in Arabic textbooks, verbally and visually, is dominated by men, (2) gender representation is visualized from six themes showing male dominance except for the theme “traveling,” which is dominated by women, and (3) the pedagogical actions that need to be taken to overcome these problems are (a) Arabic language teachers need to develop materials when using government-endorsed Arabic textbooks and (b) the Ministry of Religious Affairs should promote gender equality through recommended textbooks.
Authenticity and interest in virtual reality: Findings from an experiment including educational virtual environments created with 3D modeling and photogrammetry
Authors: Fink Maximilian C. , Sosa Diana , Eisenlauer Volker , Ertl Bernhard
Published: January 2023

Virtual Reality (VR) and photogrammetry are emerging technologies that facilitate and shape the ongoing digital transformation of education. VR offers new opportunities for creating immersive and interactive educational experiences. Photogrammetry enables new ways to create lifelike educational virtual environments and is becoming an alternative to manual 3D modeling with graphics software. The manner in which VR affects the authenticity of educational experiences has been addressed in previous educational and psychological research. Empirical papers have so far focused on the authenticity of educational VR environments created by 3D modeling. However, little is known about the authenticity of educational VR environments developed with photogrammetry. Given that VR provides rich multi-sensory experiences and interests can be stimulated by engaging contexts, educational VR environments also possess great potential to support interest development. What is still unknown regarding this topic are the beneficial characteristics of VR environments and the individual variables required to trigger and explain interest development. Consequently, we conducted an experiment following up on the mentioned authenticity and interest research questions in the context of higher education. A two-group between-subjects design was used and N = 64 educational science and psychology university students gathered information about a railroad bridge wearing a head-mounted display (HMD). The control group encountered an educational virtual environment created with 3D modeling. The intervention group was presented with the same educational virtual environment but the main object of the railroad bridge was generated by photogrammetry. Situational interest was measured in the pretest and the posttest; authenticity-related variables (i.e., presence and representation fidelity) were assessed in the posttest. Concerning authenticity, there were no significant group differences. Photogrammetry might thus not affect authenticity in educational contexts in which participants focus on gathering information. Regarding interest development, there were two main findings. First, interest in VR for learning increased from pretest to posttest, supporting that interest can be induced in VR. Second, a large share of posttest interest was explained by presence and pretest interest, highlighting the importance of these variables.
Sub-macroscopic skin presentation of acromegaly and effect of pituitary tumor surgery: A study using dermatoscopy and ultra-high-frequency ultrasound
Authors: Guo Xiaopeng , Wang Yukun , Yao Yong , Bao Xinjie , Duan Lian , Zhu Huijuan , Xing Bing , Liu Jie
Published: January 2023

Objective

Excessive growth hormone and insulin-like growth factor 1 contribute to cutaneous changes in acromegaly. We investigated the sub-macroscopic skin manifestation of acromegaly patients and explored its reversibility upon hormone reduction after pituitary adenoma surgery.

Design

Prospectively cohort study.

Methods

We enrolled 26 patients with acromegaly and 26 patients with non-functioning pituitary adenomas undergoing pituitary adenomectomy at Peking Union Medical College Hospital from July 2021 to March 2022. Skin presentations were evaluated by dermatoscopy and ultra-high-frequency ultrasound before and after surgery.

Results

Skin thickening, follicular plugs, perifollicular pigmentations, perifollicular orange haloes, red structureless areas, increased hair shafts, honeycomb-like pigmentations, widened dermatoglyphics, dilated appendage openings, excessive seborrhea, hyperhidrosis, enlarged pores, and acne-like lesions were commonly occurring in acromegaly patients, and their incidences were higher than the controls (P<0.05). At 3-month follow-up after surgery, the thickness of skin reduced (4.0 ± 0.4 to 3.7 ± 0.4, P=0.007), the incidences of hyperhidrosis (92.3% to 69.2%, P=0.035) and acne-like lesions (53.8% to 26.9%, P=0.048) declined, and the severity of multiple cutaneous lesions improved. Patients with surgical endocrine remission (53.8%) had greater declines in the thickness of skin than those without remission. Patients with improvement of >1 skin lesions were younger (P=0.028) and had higher baseline GH levels (P=0.021) than those with improvement of ≤1 skin lesion.

Conclusions

Dermatoscopy and ultra-high-frequency ultrasound provided augmented visual examination of the cutaneous changes in acromegaly. Some of the skin lesions could improve or reverse after pituitary surgery. Baseline GH levels, age, and endocrine remission were correlated with skin improvement at 3-month follow-up.
Analysis of the Brayton cycle coupled with a small fluoride salt-cooled high-temperature reactor
Authors: Liu Xiuting , Huang Yanping , Liu Minyun , Min Luyue , Zhang Ting , Li Xinyu , Zhuo Wenbin
Published: January 2023

Considering the environmental conditions and transportation conditions of remote areas, an inherently safe integrated energy conversion system featuring miniaturization, modularization, and high environmental adaptability is needed. The small fluoride salt-cooled high-temperature reactor (FHR) coupled with the Brayton cycle is a promising design. In this paper, the efficiency, exergy efficiency, and exergy loss of four different configurations of the supercritical carbon dioxide (S-CO2) Brayton cycle coupled with a new small fluoride salt-cooled high-temperature reactor are compared. The S-CO2 recompressor Brayton cycle has the best overall performance. Meanwhile, the effects of the cooling conditions on the thermal efficiency and exergy efficiency of different cycle configurations are discussed. When the core outlet temperature is 700°C, the efficiency of the designed S-CO2 recompressor Brayton cycle is approximately 42–44% when the cycle minimum temperature is 20–40°C. In conclusion, the designed small FHR coupled with the Brayton cycle system offers interesting performances in power generation, mineral mining, industrial steam supply, molten salt energy storage, and high-temperature hydrogen production in remote areas.
A review on the methane emission detection during offshore natural gas hydrate production
Authors: Liu Shuangxing , Xue Ming , Cui Xiangyu , Peng Wenzheng
Published: January 2023

Due to the high energy density, large potential reserves and only release CO2 and water after combustion, natural gas hydrate (NGH) is considered as the most likely new clean energy source to replace traditional fossil energy (crude oil, natural gas, etc.). However, unlike the exploitation of traditional fossil energy, the essence of natural gas hydrate exploitation is to induce the production of methane by artificially decompose the natural gas hydrate and to simultaneously collect the generated methane. Because of the uncontrollable decomposition, the methane percolation and the gas collection efficiency, methane emission is inevitably occurred during natural gas hydrate exploitation, which could significantly affect the environmental friendliness of natural gas hydrate. In this review, the methane emission detection was divided into three interfaces: Seafloor and sediment, seawater, atmosphere. Meanwhile, according the summary and analysis of existing methane emission detection technologies and devices, it was concluded that the existing detection technologies can identify and quantify the methane emission and amount in the three interfaces, although the accuracy is different. For natural gas hydrate exploitation, quantifying the environmental impact of methane emission and predicting the diffusion path of methane, especially the methane diffusion in strata and seawater, should be the focus of subsequent research.
Responses of Phytoplanktonic Chlorophyll-a Composition to Inorganic Turbidity Caused by Mine Tailings
Authors: Nunes Patrícia , Roland Fabio , Amado André M. , Resende Nathália da Silva , Cardoso Simone Jaqueline
Published: January 2023

Inorganic turbidity can limit light penetration in water and reduce phytoplankton photosynthesis. Anthropogenic activities such as mining can produce or augment the amount of suspended inorganic particles in water. Recent mining disasters in Brazil have released tons of mine tailings into aquatic ecosystems, with known and unknown negative consequences for aquatic life, biodiversity, and ecosystem services beyond the human and material losses. Here, we investigated the effects of inorganic turbidity on phytoplankton chlorophyll content and composition caused by sediments from two areas in Lake Batata, one natural and the other impacted by bauxite tailings. We experimentally compared the effects of different levels of turbidity (12, 50, and 300 NTU) caused by the addition of sediments from the two lake areas on a chlorophyll-a gradient (5, 15, and 25 μg/L). Inorganic turbidity did not consistently reduce chlorophyll-a concentrations. In treatments with high chlorophyll-a, high turbidity was associated with lower chlorophyll-a concentrations at the end of the experiment. On the other hand, in low-chlorophyll treatments, high turbidity was associated with higher chlorophyll-a concentrations. In treatments with sediments from the natural area, overall chlorophyll-a levels were higher than in treatments with sediments from the impacted area. Phagotrophic algae dominated both in treatments with sediments from the impacted area (Chrysophyceae 34%, Chlorophyceae 26%, and Cyanobacteria 22% of total density) and in treatments with sediment from the natural area (Euglenophyceae 26%, Chrysophyceae 23%, and Chlorophyceae 20%). We conclude that high turbidity does not lead to a reduction in chlorophyll-a concentrations and sediment from the natural area allowed higher chlorophyll-a levels, indicating that impacted area sediment affected more phytoplankton.
An investigation of the influence of the morphological indexes of trees on the outdoor microclimate at high altitude in summer
Authors: Zhang Yingzi , Chen Lixing , Sun Chen , Fu Yunchao , Xie Yibing
Published: January 2023

Trees have significant effects of shading, humidifying, and cooling, and at the same time, they can create a more comfortable space for people. However, due to the complexity of their own biology, there are also some differences in the regulation mechanism of the space microclimate among different trees. Under the background of a high altitude and cold climate, based on field measurements and numerical simulation, this paper discussed the effects of the morphological indexes, including the height, crown width, leaf area index (LAI), and under branch height of trees and their interactions on the urban microclimate and thermal comfort in Lhasa city, which belongs to the Warm Summer Winter Dry Cold Climate (Dwb). The study revealed the following: 1) LAI is the key factor affecting the thermal environment and thermal comfort of the space under a tree, followed by height and crown width, and the improvement potential of under branch height is relatively weak. 2) The interaction between height and LAI and crown width affects the thermal comfort of the space under a tree. 3) In summer, the optimal combination of tree morphological indexes in Lhasa is LAI = 2, height = 12 m, crown width = 11 m, ground reflectance = 0.2.
The contrary conservation situations of two local critically endangered species, Vaccinium emarginatum (Ericaceae) and Elatostema platyphyllum (Urticaceae), growing on the eastern edge of the distribution
Authors: Shibabayashi Mayu , Shimizu Taiga , Tokuhiro Chinatsu , Suyama Yoshihisa , Sakaguchi Shota , Ito Takuro , Yu Chih-Chieh , Chung Kuo-Fang , Nagasawa Jun’ichi , Shiuchi Toshiaki , Kokubugata Goro , Abe Atsushi , Naiki Akiyo , Nagano Atsushi J. , Isagi Yuji
Published: January 2023

As biodiversity loss continues, there is an urgent need to develop efficient conservation measures to protect diversity with limited conservation resources. Conservation targets have generally been selected based on their population size, but more detailed assessments clarifying the phylogenetic genetic status, history, and phylogenetic uniqueness of rare species is crucial to set more appropriate and effective conservation measures. In Japan, the Act on Conservation of Endangered Species of Wild Fauna and Flora designated endangered plants with high conservation priority, but >40% of these species also grow overseas. We conducted comparative analyses based on ddRADseq and MIG-seq to evaluate the population conservation status and value of Vaccinium emarginatum and Elatostema platyphyllum which are growing across national borders at the eastern edge of their species distribution range. The analyses revealed contrasting conservation status between the two species; the Japanese population of V. emarginatum had lower genetic diversity at the individual level and phylogenetically differentiated from Taiwanese populations, while that of E. platyphyllum had higher diversity at the individual level and is a relatively recent migrant with little phylogenetical differentiation from Taiwanese populations. The two species, which share the common feature of being critically rare in Japan, showed contrasting genetic/phylogenetic characteristics. This study provided useful information for appropriate conservation measures based on species’ phylogenetic traits and genetic diversity.
New insights into the coevolutionary history of termites and their gut flagellates: Description of Retractinympha glossotermitis gen. nov. sp. nov. (Retractinymphidae fam. nov.)
Authors: Radek Renate , Platt Katja , Öztas Deniz , Šobotník Jan , Sillam-Dussès David , Hanus Robert , Brune Andreas
Published: January 2023

Lower termites harbor diverse consortia of symbiotic gut flagellates. Despite numerous evidence for co-cladogenesis, the evolutionary history of these associations remains unclear. Here, we present Retractinymphidae fam. nov., a monogeneric lineage of Trichonymphida from Serritermitidae. Although Retractinympha glossotermitis gen. nov. sp. nov. morphologically resembles members of the genus Pseudotrichonympha, phylogenetic analysis identified it as sister group of the Teranymphidae. We compared morphology and ultrastructure of R. glossotermitis to that of Pseudotrichonympha and other Teranymphidae, including the so-far undescribed Pseudotrichonympha solitaria sp. nov. from Termitogeton planus (Rhinotermitidae). Like all Teranymphidae, R. glossotermitis is a large, elongated flagellate with a bilaterally symmetric rostrum, an anterior, flagella-free operculum, and an internal rostral tube. However, it is readily distinguished by the length of its rostral flagella, which never exceeds that of the postrostral flagella, and its retractable anterior end. Inclusion of the hitherto unstudied Stylotermes halumicus (Stylotermitidae) in our survey of trichonymphid flagellates in Neoisoptera confirmed that the combined presence of Heliconympha and Retractinympha and absence of Pseudotrichonympha is unique to Serritermitidae. The close phylogenetic relatedness of Heliconympha in Serritermitidae to the spirotrichosomid flagellates in Stolotermitidae provides strong support for their acquisition by horizontal transmission.
N6-methyladenine regulator-mediated RNA methylation modification patterns in immune microenvironment regulation of osteoarthritis
Authors: Gu Yong , Wang Zhengming , Wang Rui , Yang Yunshang , Tong Peijian , Lv Shuaijie , Xiao Long , Wang Zhirong
Published: January 2023

Background: Osteoarthritis is a common chronic degenerative disease, and recently, an increasing number of studies have shown that immunity plays an important role in the progression of osteoarthritis, which is exacerbated by local inflammation. The role of N6-methyladenine (m6A) modification in immunity is being explored. However, the role of m6A modification in regulating the immune microenvironment of osteoarthritis remains unknown. In this study, we sought to discuss the association between the N6-methyladenine (m6A) modification and the immune microenvironment of osteoarthritis.

Methods: First, the data and gene expression profiles of 139 samples, including 33 healthy samples and 106 osteoarthritis samples, were obtained from the Genetics osteoARthritis and Progression (GARP) study. Then the differences in m6A regulators between healthy individuals and osteoarthritis patients were analyzed. The correlation between m6A regulators and immune characteristics was also investigated by single-sample gene set enrichment analysis (ssGSEA). Principal component analysis (PCA), Gene Set Variation Analysis (GSVA) enrichment analysis, weighted gene coexpression network analysis (WGCNA), and Associated R packages were used to identify the m6A phenotype and its biological functions.

Results: A total of 23 m6A regulators were involved in this study. We found a close correlation between most m6A regulators in all samples as well as in osteoarthritis samples. VIRMA and LRPPRC were the most highly correlated m6A regulators and showed a positive correlation, whereas VIRMA and RBM15B were the most negatively correlated. M6A regulators are associated with osteoarthritis immune characteristics. For example, MDSC cell abundance was strongly correlated with RBM15B and HNRNPC. Meanwhile, RBM15B and HNRNPC were important effectors of natural killer cell immune responses. IGFBP3 is an important regulator of cytolytic activity immune function. We performed an unsupervised consensus cluster analysis of the osteoarthritis samples based on the expression of 23 m6A regulators. Three different m6A subtypes of osteoarthritis were identified, including 27 samples in subtype C1, 21 samples in subtype C2, and 58 samples in subtype C3. Different m6A subtypes have unique biological pathways and play different roles in the immune microenvironment of osteoarthritis.

Conclusion: The m6A modification plays a crucial role in the diversity and complexity of the immune microenvironment in osteoarthritis.
Genome-wide analysis of dysregulated RNA-binding proteins and alternative splicing genes in keloid
Authors: Zhu Zhen , Ni Shuangying , Zhang Jiali , Yuan Ying , Bai Yun , Yin Xueli , Zhu Zhengwei
Published: January 2023

Introduction: The pathogenesis of keloids remains unclear.

Methods: In this study, we analyzed RNA-Seq data (GSE113619) of the local skin tissue of 8 keloid-prone individuals (KPI) and 6 healthy controls (HC) before and 42 days after trauma from the gene expression omnibus (GEO) database. The differential alternative splicing (AS) events associated with trauma healing between KPIs and HCs were identifified, and their functional differences were analyzed by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways. The co-expression relationship of differentially alternative splicing genes and differentially expressed RNA binding proteins (RBPs) was established subsequently.

Results: A total of 674 differential AS events between the KD42 and the KD0 and 378 differential AS events between the HD42 and the HD0 were discovered. Notably, most of the differential genes related to keloids are enriched in actin, microtubule cells, and cortical actin cytoskeletal tissue pathway. We observed a signifificant association between AS genes (EPB41, TPM1, NF2, PARD3) and trauma healing in KPIs and HCs. We also found that the differential expression of healthy controls-specifific trauma healing-related RBPs (TKT, FDPS, SAMHD1) may affect the response of HCs to trauma healing by regulating the AS of downstream trauma healing-related genes such as DCN and DST. In contrast, KPIs also has specifific differential expression of trauma healing related RBPs (S100A9, HspB1, LIMA1, FBL), which may affect the healing response of KPIs to trauma by regulating the AS of downstream trauma healing-related genes such as FN1 and TPM1.

Discussion: Our results were innovative in revealing early wound healing-related genes (EPB41, TPM1, NF2, PARD3) in KPI from the perspective of AS regulated by RBPs.
Identification of PDCD1 as a potential biomarker in acute rejection after kidney transplantation via comprehensive bioinformatic analysis
Authors: Wang Yucheng , Lin Xiaoli , Wang Cuili , Liu Xinyu , Wu Xiaoying , Qiu Yingying , Chen Ying , Zhou Qin , Zhao Haige , Chen Jianghua , Huang Hongfeng
Published: January 2023

Background

Acute rejection is a determinant of prognosis following kidney transplantation. It is essential to search for novel noninvasive biomarkers for early diagnosis and prompt treatment.

Methods

Gene microarray data was downloaded from the Gene Expression Omnibus (GEO) expression profile database and the intersected differentially expressed genes (DEGs) was calculated. We conducted the DEGs with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Distribution of immune cell infiltration was calculated by CIBERSORT. A hub gene marker was identified by intersecting the rejection-related genes from WGCNA and a selected KEGG pathway—T cell receptor signaling pathway (hsa04660), and building a protein-protein interaction network using the STRING database and Cytoscape software. We performed flow-cytometry analysis to validate the hub gene.

Results

A total of 1450 integrated DEGs were obtained from five datasets (GSE1563, GSE174020, GSE98320, GSE36059, GSE25902). The GO, KEGG and immune infiltration analysis results showed that AR was mainly associated with T cell activation and various T-cell related pathways. Other immune cells, such as B cells, Macrophage and Dendritic cells were also associated with the progress. After utilizing the WGCNA and PPI network, PDCD1 was identified as the hub gene. The flow-cytometry analysis demonstrated that both in CD4+ and CD8+ T cells, PD1+CD57-, an exhausted T cell phenotype, were downregulated in the acute rejection whole blood samples.

Conclusions

Our study illustrated that PDCD1 may be a candidate diagnostic biomarker for acute kidney transplant rejection via integrative bioinformatic analysis.
Risk factors and sequelae of epidermolysis bullosa acquisita: A propensity-matched global study in 1,344 patients
Authors: Kridin Khalaf , Vorobyev Artem , Papara Cristian , De Luca David A. , Bieber Katja , Ludwig Ralf J.
Published: January 2023

Identification of risk factors and sequelae of any given disease is of key importance. For common diseases, primary prevention and disease management are based on this knowledge. For orphan diseases, identification of risk factors and sequelae has been challenging. With the advent of large databases, e.g., TriNetX, this can now be addressed. We used TriNetX to identify risk factors and sequelae of epidermolysis bullosa acquisita (EBA), a severe and orphan autoimmune disease. To date, there is only enigmatic information on EBA comorbidity. We recruited 1,344 EBA patients in the Global Collaborative Network of TriNetX. Using the “explore outcomes” function we identified 55 diagnoses with a different prevalence between EBA and no-EBA patients. We next performed propensity-matched, retrospective cohort studies in which we determined the risk of EBA development following any of the identified 55 diseases. Here, 31/55 diseases were identified as risk factors for subsequent EBA. Importantly, the highest risk for EBA were other chronic inflammatory diseases (CID), especially lupus erythematosus and lichen planus. Lastly, we determined the risk to develop any of the identified diseases after EBA diagnosis. Here, 38/55 diseases were identified as sequelae. Notably, EBA patients showed an increased risk for metabolic and cardiovascular disease, and thrombosis. Furthermore, the risk for CIDs, especially lupus erythematosus and lichen planus, was elevated. These insights into risk factors and sequelae of EBA are not only of clinical relevance, e.g., optimizing cardiovascular disease risk, but in addition, point to shared pathogenetic pathways between EBA and other inflammatory diseases.
Extended genomic HLA typing identifies previously unrecognized mismatches in living kidney transplantation
Authors: Lehmann Claudia , Pehnke Sarah , Weimann Antje , Bachmann Anette , Dittrich Katalin , Petzold Friederike , Fürst Daniel , de Fallois Jonathan , Landgraf Ramona , Henschler Reinhard , Lindner Tom H. , Halbritter Jan , Doxiadis Ilias , Popp Bernt , Münch Johannes
Published: January 2023

Introduction

Antibody mediated rejection (ABMR) is the most common cause of long-term allograft loss in kidney transplantation (KT). Therefore, a low human leukocyte antigen (HLA) mismatch (MM) load is favorable for KT outcomes. Hitherto, serological or low-resolution molecular HLA typing have been adapted in parallel. Here, we aimed to identify previously missed HLA mismatches and corresponding antibodies by high resolution HLA genotyping in a living-donor KT cohort.

Methods

103 donor/recipient pairs transplanted at the University of Leipzig Medical Center between 1998 and 2018 were re-typed using next generation sequencing (NGS) of the HLA loci -A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1, and -DPB1. Based on these data, we compiled HLA MM counts for each pair and comparatively evaluated genomic HLA-typing with pre-transplant obtained serological/low-resolution HLA (=one-field) typing results. NGS HLA typing (=two-field) data was further used for reclassification of de novo HLA antibodies as “donor-specific”.

Results

By two-field HLA re-typing, we were able to identify additional MM in 64.1% (n=66) of cases for HLA loci -A, -B, -C, -DRB1 and -DQB1 that were not observed by one-field HLA typing. In patients with biopsy proven ABMR, two-field calculated MM count was significantly higher than by one-field HLA typing. For additional typed HLA loci -DRB345, -DQA1, -DPA1, and -DPB1 we observed 2, 26, 3, and 23 MM, respectively. In total, 37.3% (69/185) of de novo donor specific antibodies (DSA) formation was directed against these loci (DRB345 ➔ n=33, DQA1 ➔ n=33, DPA1 ➔ n=1, DPB1 ➔ n=10).

Conclusion

Our results indicate that two-field HLA typing is feasible and provides significantly more sensitive HLA MM recognition in living-donor KT. Furthermore, accurate HLA typing plays an important role in graft management as it can improve discrimination between donor and non-donor HLA directed cellular and humoral alloreactivity in the long range. The inclusion of additional HLA loci against which antibodies can be readily detected, HLA-DRB345, -DQA1, -DQB1, -DPA1, and -DPB1, will allow a more precise virtual crossmatch and better prediction of potential DSA. Furthermore, in living KT, two-field HLA typing could contribute to the selection of the immunologically most suitable donors.
Natural killer cells in sepsis: Friends or foes?
Authors: Wang Fangjie , Cui Yiqin , He Dongmei , Gong Lisha , Liang Huaping
Published: January 2023

Sepsis is one of the major causes of death in the hospital worldwide. The pathology of sepsis is tightly associated with dysregulation of innate immune responses. The contribution of macrophages, neutrophils, and dendritic cells to sepsis is well documented, whereas the role of natural killer (NK) cells, which are critical innate lymphoid lineage cells, remains unclear. In some studies, the activation of NK cells has been reported as a risk factor leading to severe organ damage or death. In sharp contrast, some other studies revealed that triggering NK cell activity contributes to alleviating sepsis. In all, although there are several reports on NK cells in sepsis, whether they exert detrimental or protective effects remains unclear. Here, we will review the available experimental and clinical studies about the opposing roles of NK cells in sepsis, and we will discuss the prospects for NK cell-based immunotherapeutic strategies for sepsis.
Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB
Authors: Cheng Peng , Jiang Fan , Wang Guiyuan , Wang Jie , Xue Yong , Wang Liang , Gong Wenping
Published: January 2023

Background

With the increasing incidence of tuberculosis (TB) and the shortcomings of existing TB vaccines to prevent TB in adults, new TB vaccines need to be developed to address the complex TB epidemic.

Method

The dominant epitopes were screened from antigens to construct a novel epitope vaccine termed HP13138PB. The immune properties, structure, and function of HP13138PB were predicted and analyzed with bioinformatics and immunoinformatics. Then, the immune responses induced by the HP13138PB were confirmed by enzyme-linked immunospot assay (ELISPOT) and Th1/Th2/Th17 multi-cytokine detection kit.

Result

The HP13138PB vaccine consisted of 13 helper T lymphocytes (HTL) epitopes, 13 cytotoxic T lymphocytes (CTL) epitopes, and 8 B-cell epitopes. It was found that the antigenicity, immunogenicity, and solubility index of the HP13138PB vaccine were 0.87, 2.79, and 0.55, respectively. The secondary structure prediction indicated that the HP13138PB vaccine had 31% of α-helix, 11% of β-strand, and 56% of coil. The tertiary structure analysis suggested that the Z-score and the Favored region of the HP13138PB vaccine were -4.47 88.22%, respectively. Furthermore, the binding energies of the HP13138PB to toll-like receptor 2 (TLR2) was -1224.7 kcal/mol. The immunoinformatics and real-world experiments showed that the HP13138PB vaccine could induce an innate and adaptive immune response characterized by significantly higher levels of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10.

Conclusion

The HP13138PB is a potential vaccine candidate to prevent TB, and this study preliminarily evaluated the ability of the HP13138PB to generate an immune response, providing a precursor target for developing TB vaccines.
Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations
Authors: Williams Kristian C. , Gault Abigail , Anderson Amy E. , Stewart Christopher J. , Lamb Christopher A. , Speight R. Ally , Rajan Neil , Plummer Ruth , Pratt Arthur G.
Published: January 2023

Checkpoint inhibitors (CPIs) are monoclonal antibodies which, by disrupting interactions of immune checkpoint molecules with their ligands, block regulatory immune signals otherwise exploited by cancers. Despite revolutionary clinical benefits, CPI use is associated with an array of immune-related adverse events (irAEs) that mirror spontaneous autoreactivity. Severe irAEs necessitate pausing or stopping of CPI therapy and use of corticosteroids and/or other immunomodulatory interventions. Despite increasingly widespread CPI use, irAE pathobiology remains poorly understood; its elucidation may point to targeted mitigation strategies and uncover predictive biomarkers for irAE onset in patients, whilst casting new light on mechanisms of spontaneous immune-mediated disease. This review focuses on common CPI-induced irAEs of the gut, skin and synovial joints, and how these compare to immune-mediated diseases such as ulcerative colitis, vitiligo and inflammatory arthritis. We review current understanding of the immunological changes reported following CPI therapy at the level of peripheral blood and tissue. Many studies highlight dysregulation of cytokines in irAE-affected tissue, particularly IFNγ and TNF. IrAE-affected tissues are also predominantly infiltrated by T-cells, with low B-cell infiltration. Whilst there is variability between studies, patients treated with anti-programmed cell death-1 (PD-1)/PDL-1 therapies seem to exhibit CD8+ T-cell dominance, with CD4+ T-cells dominating in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monotherapy. Interestingly, CD8+CXCR3+ T-cells have been reported to be elevated in gastrointestinal, dermatological and musculoskeletal -irAE affected tissues. These findings may highlight potential opportunities for therapeutic development or re-deployment of existing therapies to prevent and/or improve the outcome of irAEs.
Machine learning of flow cytometry data reveals the delayed innate immune responses correlate with the severity of COVID-19
Authors: Zhu Jing , Chen Tunan , Mao Xueying , Fang Yitian , Sun Heqi , Wei Dong-Qing , Ji Guangfu
Published: January 2023

Introduction

The COVID-19 pandemic has posed a major burden on healthcare and economic systems across the globe for over 3 years. Even though vaccines are available, the pathogenesis is still unclear. Multiple studies have indicated heterogeneity of immune responses to SARS-CoV-2, and potentially distinct patient immune types that might be related to disease features. However, those conclusions are mainly inferred by comparing the differences of pathological features between moderate and severe patients, some immunological features may be subjectively overlooked.

Methods

In this study, the relevance scores(RS), reflecting which features play a more critical role in the decision-making process, between immunological features and the COVID-19 severity are objectively calculated through neural network, where the input features include the immune cell counts and the activation marker concentrations of particular cell, and these quantified characteristic data are robustly generated by processing flow cytometry data sets containing the peripheral blood information of COVID-19 patients through PhenoGraph algorithm.

Results

Specifically, the RS between immune cell counts and COVID-19 severity with time indicated that the innate immune responses in severe patients are delayed at the early stage, and the continuous decrease of classical monocytes in peripherial blood is significantly associated with the severity of disease. The RS between activation marker concentrations and COVID-19 severity suggested that the down-regulation of IFN-γ in classical monocytes, Treg, CD8 T cells, and the not down-regulation of IL_17a in classical monocytes, Tregs are highly correlated with the occurrence of severe disease. Finally, a concise dynamic model of immune responses in COVID-19 patients was generalized.

Discussion

These results suggest that the delayed innate immune responses in the early stage, and the abnormal expression of IL-17a and IFN-γ in classical monocytes, Tregs, and CD8 T cells are primarily responsible for the severity of COVID-19.
Secreted glucose regulated protein78 ameliorates DSS-induced mouse colitis
Authors: Zhao Liang , Lv Yibing , Zhou Xiaoqi , Guo Zilong , Li Heli , Guo Yanyan , Liu Tao , Tu Lei , Zhu Liangru , Tao Juan , Shen Guanxin , He Yong , Lei Ping
Published: January 2023

The secreted form of 78-kDa glucose-regulated protein (sGRP78) has been widely reported for its property in aiding resolution of inflammatory. However, little is known on its potential in the treatment of colitis. To investigate the expression pattern and functional outcome of GRP78 in ulcerative colitis, its expression was measured in human and murine colitis samples. It was found that GRP78 was spontaneously secreted to a high level in gut, which is a physiological site of immune tolerance. During the active phase of DSS-induced colitis, the sGRP78 level was significantly reduced but rebounded quickly during resolving phase, making it a potential candidate for the treatment of colitis. In the following experiments, the administration of sGRP78 was proved to decrease susceptibility to experimental colitis, as indicated by an overall improvement of intestinal symptoms, restoration of TJ integrity, decreased infiltration of immune cells and impaired production of inflammatory cytokines. And specific cleavage of endogenous sGRP78 could aggravate DSS colitis. Adoptive transfer of sGRP78-conditioned BMDMs reduced inflammation in the gut. We linked sGRP78 treatment with altered macrophage biology and skewed macrophage polarization by inhibiting the TLR4-dependent MAP-kinases and NF-κB pathways. Based on these studies, as a naturally occurring immunomodulatory molecule, sGRP78 might be an attractive novel therapeutic agent for acute intestinal inflammation.
Impact of blue economy sectors using causality, correlation and panel data models
Authors: Martínez-Vázquez Rosa María , Milán-García Juan , Pires Manso Jose Ramos , De Pablo Valenciano Jaime
Published: January 2023

Introduction

Blue economics research is a research field that is achieving more and more interest among international scientists. This study adds more knowledge as it aims to investigate the causal relationships between blue economic factors – living and non-living resources, ocean energy, port activities, shipbuilding and repair, maritime transport, coastal tourism, human development indicator, per capita income, fish capture, internal renewable water resources per capita, marine protected areas, greenhouse gas emissions and population density, all factors related to maritime activities – and the blue economy (BE) itself.

Methods

In order to reach these objectives, some special analytical and econometric methods are used. Among them the multivariate Granger causality theory, the correlation analysis and panel data techniques are employed. This set of methods helps us to study the complex set of relationships among the various factors related to the BE and their influence on per capita income (PCI) and economic growth. The data used to conduct this research were collected from the Eurostat, the E.U. statistical database. Several European countries and the span period 2010-2018 are used too.

Results

The analysis showed evidence that per capita income is associated to other factors of the blue economy, that PCI (Granger) causes coastal tourism and population density, and that there are five other factors that positively influence PCI growth, namely, greenhouse gas emissions (GHG), maritime transport, nonliving resources and ports’ activities. This paper adds some new understandings to theory and calls the attention to society, in general, and the blue economics, in particular. For instance, if policymakers want to increase income per capita of these regions, they should take action on some variables such as human development indicator (HDI), greenhouse gas (GHG) emissions, living resources, maritime transport and ocean energy. The results reveal that blue economy is a good alternative to promote both economic growth and PCI.

Discussion

The concerns that make up the blue economy, such as ocean energy, port activities, ship building and repair, maritime transport, coastal tourism, HDI, maritime fish capture, marine protected areas, and GHG reductionare good factors to stimulate economic growth. Among these, the most influencing are maritime transport, living resources and the production of ocean energy. This study adds knowledge to theory, innovates in the methods and techniques used, in the results discovered, in its discussion, and in the mixture of blue economic factors, too. As far as we know, it is one of the first papers that fills this gap in the literature regarding the more and more important blue economy.