bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the Continental Crust in the Northern Tibetan Plateau: Constraints From Geochronology and Hf Isotopes of Detrital Zircons
Authors: Liu Zeyu , Zhang Guibin , Xiong Lu , Chang Feng , Liu Shuaiqi
Published: April 2022

To investigate the evolution of the continental crust in the northern Tibetan Plateau, detrital zircon U–Pb geochronology and Hf isotopes analysis were performed on two fluvial sand samples from North Qaidam (the Yuka and Shaliu rivers). A total of 443 detrital zircon U–Pb ages and 244 Hf isotopic results were obtained and reveal that the South Qilian, North Qaidam, and East Kunlun terranes show affinity to the western Yangtze Block. Age distributions of detrital zircons from the Yuka River cluster mainly in two age intervals of 1,000–700 and 480–400 Ma. The corresponding εHf(t) values are mostly negative, with depleted two-stage Hf model ages (TDM2) of 2.1–1.6 Ga. In contrast, age data for the Shaliu River fall in the ranges of 1,000–700, 460–380, and 260–200 Ma, with TDM2 ages of 2.0–1.6 and 1.6–1.2 Ga. In addition, zircons with Neoproterozoic ages from both river samples possess common Paleoproterozoic TDM2 ages (2.0–1.6 Ga, with a peak of 1.8–1.7 Ga), indicating that the South Qilian, North Qaidam and East Kunlun terranes were probably part of the same Neoproterozoic continent. The East Kunlun and North Qaidam terranes are inferred to include Mesoproterozoic continental crust (1.6–1.0 Ga), suggesting differences in crustal evolution between the East Kunlun–North Qaidam and Qilian terranes. Phanerozoic magmatism in these three terranes was sourced mainly from the recycling of ancient continental crust with minor contributions from the juvenile crust.
Internal Jugular Vein Thrombosis After Microwave Ablation of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Case Report
Authors: Liu Ying , Wang Xi-Ju , Wang Jin-Ling , Liu Li-Hong , Zhao Shuo-Ran , Yu Shou-Jun , Yang Bei-Bei , Xu Qing-Ling , Li Jin-Ke , Wang Shu-Rong
Published: April 2022

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang’s team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.
Altered Gut Microbiota in Children With Hyperuricemia
Authors: Yuan Xin , Chen Ruimin , Zhang Ying , Lin Xiangquan , Yang Xiaohong
Published: April 2022

Background

In adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored.

Objective

This present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences.

Methods

A total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing.

Results

Principal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman’s correlation analysis revealed that serum UA level positively correlated with genera Actinomyces, Morganella, and Streptococcus, and negatively associated with the producers of short-chain fatty acids (SCFAs), such as Alistipes, Faecalibacterium, and Oscillospira, and the sulfidogenic bacteria Bilophila. The members of the genera Alistipes and Bilophila in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide de novo biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased.

Conclusion

The composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.
Role of Innate lymphoid Cells in Obesity and Insulin Resistance
Authors: Chen Hong , Sun Lijun , Feng Lu , Yin Yue , Zhang Weizhen
Published: April 2022

Obesity, a growing chronic metabolic disease, greatly increases the risk of metabolic syndrome which includes type 2 diabetes, fatty liver and cardiovascular diseases. Obesity-associated metabolic diseases significantly contribute to mortality and reduce life expectancy. Recently, innate lymphoid cells (ILCs) have emerged as crucial regulators of metabolic homeostasis and tissue inflammation. This review focuses on the roles of ILCs in different metabolic tissues, including adipose tissue, liver, pancreas, and intestine. We briefly outline the relationship between obesity, inflammation, and insulin resistance. We then discuss how ILCs in distinct metabolic organs may function to maintain metabolic homeostasis and contribute to obesity and its associated metabolic diseases. The potential of ILCs as the therapeutic target for obesity and insulin resistance is also addressed.
Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma
Authors: Luo Yi , Yang Yi-Chen , Shen Cen-Kai , Ma Ben , Xu Wei-Bo , Wang Qi-Feng , Zhang Yan , Liao Tian , Wei Wen-Jun , Wang Yu
Published: April 2022

Background

Patients with advanced thyroid carcinoma (TC), such as anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and locally advanced papillary thyroid carcinoma (PTC), have poor prognoses and require novel treatments. Immune checkpoint (ICP) inhibitors have demonstrated encouraging and good results; nevertheless, their effect in advanced TCs remains largely unclear. Thus, we demonstrated ICP profiles and investigated their potential clinical significance.

Methods

A total of 234 TC patients were involved, with 22 ATCs, 44 PDTCs, and 168 PTCs, including 58 advanced PTCs. Immunohistochemistry was performed to evaluate nine ICPs [programmed cell death ligand 1 (PDL1), Programmed cell death 1 (PD1), cytotoxic T lymphocyte-associated protein 4 (CTLA4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), lymphocyte activation gene 3 (LAG3), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B7 homolog 3 (B7-H3), and T-cell immunoglobulin and mucin domain- 3 protein (TIM3)] expression via tissue microarrays (TMAs), and clinical correlations were analyzed simultaneously.

Results

ATC had the highest positive rate of ICPs among the three pathological types, as well as relatively high ICP co-expression. ATC with high expression of PDL1 positivity had a poor prognosis. Shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression in PDTC. The greater the co-expression of these four ICPs, the poorer the prognosis in PDTC patients. VISTA and B7H3 were the two most commonly expressed ICPs in advanced PTC, both of which were linked to a poor prognosis.

Conclusions

PDL1 is linked to the overall survival (OS) of ATC. A subset of PDTC is likely immunogenic with poor prognosis and co-expression of VISTA, B7H3, TIM3, and TIGIT. Furthermore, VISTA and B7H3 are prognostic biomarkers in advanced PTC. Single or combined blockade targeting these ICPs might be effective for advanced TCs in the future.
Effects of Time-Restricted Feeding on Energy Balance: A Cross-Over Trial in Healthy Subjects
Authors: Bao Riqiang , Sun Yingkai , Jiang Yiran , Ye Lei , Hong Jie , Wang Weiqing
Published: April 2022

Time-restricted feeding (TRF) has been recently reported as an effective dietary intervention for losing body weight, implying a negative energy balance, without restricting nutrient intake. However, the detailed energy balance alteration caused by TRF remains unclear. This study was a randomized controlled clinical trial using a within-subject cross-over design. Twelve healthy, normal-weighted volunteers (age: 24 ± 2.3 years; BMI: 21.9 ± 1.71 kg/m2; 7 females) were studied under a rigorous control for calorie intakes, physical activities as well as sleep-wake cycle to evaluate the energy balance systematically. Each participant consumed an isocaloric diet within either a 5.5-hour TRF or 11-hour control schedule. All energy intake and excretion were traced and collected and accessed by bomb calorimetry. Energy expenditure and substrates oxidation were monitored in a metabolic chamber. TRF compared with control schedule is associated with a 22.7% increase in fecal energy loss (Δ = 32.25 ± 9.33 Kcal, p = 0.005) and a trend in increasing 14.5% urine energy loss (Δ = 6.67 ± 3.14 Kcal, p = 0.058) without change energy expenditure. In total, a negative energy balance (Δ = -45.95 ± 19.00 Kcal, p = 0.034), which was equal to -2.6% of total energy intake, has been observed during TRF interventions. In the meantime, glycemic profiles, heart rate, respiration rate as well as metabolic flexibility were also improved during TRF intervention. Taken together, our findings unravel the mystery of how TRF regulates energy balance, supporting the use of TRF as an alternative dietary strategy for weight loss.
Robust State Estimation Method for Power System Based on Maximum Exponential Square and Data Fusion
Authors: Yu Tong , Da Kai , Wang Zhiwen , Ling Ying , Li Xin , Bin Dongmei , Yang Chunyan
Published: April 2022

In order to solve the problem of the time offset between the supervisory control and data acquisition system and phasor measurement unit and the unknown distribution of non-Gauss noise, this paper proposes a robust state estimation method for power systems based on the Maximum Exponential Square and data fusion. Firstly, the robust Mahalanobis distance is used to detect system outliers and assign appropriate weights to the selected PMU buffer measurement. Then, the MES-based estimator uses these weights to filter out non-Gauss PMU measurement noise to generate a set of state estimation results. At the same time, the MES estimator is used to process the received SCADA measurement with unknown measurement noise, thereby generating another set of state estimation results. Finally, the two sets of estimation results from two independent MES estimators are fused by using data fusion theory to obtain the final optimal state estimation results. Based on IEEE-14 and 30-buses standard system, the simulation results prove the effectiveness and robustness of the method proposed in this paper.
Global Exponential Stability of a Class of Memristor-Based RNN and Its Application to Design Stable Voltage Circuits
Authors: Yao Zhao , Li Yingshun
Published: April 2022

In this article, we study the global exponential stability of the equilibrium point for a class of memristor-based recurrent neural networks (MRNNs). The MRNNs are based on a realistic memristor model and can be implemented by a very large scale of integration circuits. By introducing a proper Lyapunov functional, it is proved that the equilibrium point of the MRNN is globally exponentially stable under two less conservative assumptions. Furthermore, an algorithm is proposed for the design of MRNN-based circuits with stable voltages. Finally, an illustration example is performed to show the validation of the proposed theoretical results; an MRNN-based circuit with stable voltages is designed according to the proposed algorithm.
Growth and Pb Uptake of Brassica campestris Enhanced by Two Ecological Earthworm Species in Relation to Soil Physicochemical Properties
Authors: Tibihenda Cevin , Zhang Menghao , Zhong Hesen , Xiao Ling , Wu Ling , Dai Jun , Liu Kexue , Zhang Chi
Published: April 2022

A comprehensive understanding of the influence of earthworms on the growth and Pb accumulation of leafy vegetables is significant for soil management and human health. This study was aimed to evaluate the different influences of two ecological earthworm species on the growth and Pb accumulation of Brassica campestris in a Pb-contaminated soil and their relationship with soil physico-chemical properties. In a 30-day microcosm experiment, the anecic and native earthworm species Amynthas aspergillum and the epigeic species Eisenia fetida were inoculated in soil artificially contaminated with Pb at different levels (i.e., 0, 100, 500, and 1,000 mg kg−1), and B. campestris was grown. With a survival rate of 81%–100%, A. aspergillum was more tolerant to Pb contamination than E. fetida with 46%–84%. At the same time, earthworm inoculation significantly increased soil Pb bioavailability (p < 0.05). At the 500 and 1,000 mg kg−1 Pb levels, the treatments with earthworm inoculation showed higher plant biomass, leaf area, and chlorophyll concentration than the treatments without earthworm. The principal component analysis (PCA) showed that earthworm inoculation exerted a stronger effect on soil properties than Pb contamination, but the latter had a stronger effect on plant growth and Pb accumulation. Compared with A. aspergillum, E. fetida had a greater effect on soil cation exchange capacity, available Pb, and plant growth and Pb accumulation. In contrast, A. aspergillum had a greater effect on soil C and N contents than E. fetida. The co-inertia analysis revealed that plant Pb accumulation was positively correlated with soil available Pb and CEC. The leaf chlorophyll concentration was closely related to soil Eh, pH, and Dissolved organic carbon. The findings of this study showed that in the Pb-contaminated soils, earthworm inoculation exerted a strong effect on soil physicochemical properties and the growth and Pb accumulation of the leafy vegetable B. campestris. Both the epigeic earthworm species E. fetida and the anecic species A. aspergillum were associated with higher Pb accumulation or concentration in B. campestris, which may bring a possible risk to food security.
Climate Change Adaptation: A Study of Digital Financial Inclusion and Consumption Among Rural Residents in China
Authors: He Chunyan , Qiu Weisong , Yu Junlin
Published: April 2022

Climate change impacts agricultural production negatively. Therefore, rural residents experience large income and consumption fluctuations when dealing with climate change risks. However, little is known about whether digital financial inclusion can help rural residents improve their ability to resist climate change. This study uses the Peking University Digital Financial Inclusion Index of China and China Household Finance Survey data, together with historical temperature data from major cities, to study the impact of digital financial inclusion on Chinese rural residents’ consumption in response to climate change. The results suggest that digital financial inclusion significantly promotes rural households’ total consumption and consumption upgrades. Heterogeneity analyses also show that digital financial inclusion predominantly affects low-income households, low-asset households, and households living in China’s central and western regions. The instrumental variable and control function methods were used for robustness, and our main conclusions are robust and reliable. Although climate change reduces rural residents’ consumption and increases their risks, digital finance inclusion significantly mitigates this negative effect. The government can increase the usage depth of digital financial inclusion in rural areas by promoting the construction of digital financial inclusion facilities. The government should strive to deepen the impact of digital financial inclusion on rural household income and consumption to further improve their ability to resist climate risks.
A Standardized Method for Experimental Human Approach Trials on Wild Wolves
Authors: Eriksen Ane , Versluijs Erik , Fuchs Boris , Zimmermann Barbara , Wabakken Petter , Ordiz Andrés , Sunde Peter , Wikenros Camilla , Sand Håkan , Gillich Benjamin , Michler Frank , Nordli Kristoffer , Carricondo-Sanchez David , Gorini Lucrezia , Rieger Siegfried
Published: April 2022

As wolves recolonize areas of Europe ranging from moderate to high anthropogenic impact, fear of wolves is a recurring source of conflict. Shared tools for evaluating wolf responses to humans, and comparing such responses across their range, can be valuable. Experiments in which humans approach wild wolves can increase our understanding of how wolves respond to humans, facilitating human-wolf coexistence. We have developed the first standardized protocol for evaluating wolf responses to approaching humans using high-resolution GPS data, and tested it on wild wolves. We present a field protocol for experimentally approaching GPS-collared wolves, a descriptive comparison of two statistical methods for detecting a measurable flight response, a tutorial for identifying wolf flight initiation and resettling positions, and an evaluation of the method when reducing GPS positioning frequency. The field protocol, a data collection form, and the tutorial with R code for extracting flight parameters are provided. This protocol will facilitate studies of wolf responses to approaching humans, applicable at a local, national, and international level. Data compiled in a standardized way from multiple study areas can be used to quantify the variation in wolf responses to humans within and between populations, and in relation to predictors such as social status, landscape factors, or human population density, and to establish a baseline distribution of wolf response patterns given a number of known predictors. The variation in wolf responses can be used to assess the degree to which results can be generalized to areas where GPS studies are not feasible, e.g., for predicting the range of likely wolf behaviors, assessing the likelihood of wolf-human encounters, and complementing existing tools for evaluating reports of bold wolves. Showing how wolves respond to human encounters should help demystify the behavior of wild wolves toward humans in their shared habitat.
The Role of Rare Avian Species for Spatial Resilience of Shifting Biomes in the Great Plains of North America
Authors: Angeler David G. , Roberts Caleb P. , Twidwell Dirac , Allen Craig R.
Published: April 2022

Human activity causes biome shifts that alter biodiversity and spatial resilience patterns. Rare species, often considered vulnerable to change and endangered, can be a critical element of resilience by providing adaptive capacity in response to disturbances. However, little is known about changes in rarity patterns of communities once a biome transitions into a novel spatial regime. We used time series modeling to identify rare avian species in an expanding terrestrial (southern) spatial regime in the North American Great Plains and another (northern) regime that will become encroached by the southern regime in the near future. In this time-explicit approach, presumably rare species show stochastic dynamics in relative abundance – this is because they occur only rarely throughout the study period, may largely be absent but show occasional abundance peaks or show a combination of these patterns. We specifically assessed how stochastic/rare species of the northern spatial regime influence aspects of ecological resilience once it has been encroached by the southern regime. Using 47 years (1968–2014) of breeding bird survey data and a space-for-time substitution, we found that the overall contribution of stochastic/rare species to the avian community of the southern regime was low. Also, none of these species were of conservation concern, suggesting limited need for revised species conservation action in the novel spatial regime. From a systemic perspective, our results preliminarily suggest that stochastic/rare species only marginally contribute to resilience in a new spatial regime after fundamental ecological changes have occurred.
The Chromosomes of Zeugodacus tau and Zeugodacus cucurbitae: A Comparative Analysis
Authors: Gouvi G. , Gariou-Papalexiou A. , Augustinos Antonios A. , Drosopoulou E. , Tsiamis George , Bourtzis Kostas , Zacharopoulou A.
Published: April 2022

Availability of polytene chromosomes and development of polytene chromosome maps have greatly facilitated genetic analysis in Diptera and understanding of chromosomal organization. In tephritids, following the first polytene chromosome maps constructed for the Mediterranean fruit fly,Ceratitis capitata, additional maps have been developed for only few species belonging to the main genera of agricultural importance that are Anastrepha, Bactrocera, Ceratitis, Dacus, Rhagoletis, and Zeugodacus. Comparison of the polytene chromosomes of these species has pointed to the presence of chromosomal rearrangements that can, at least partially, shed light to the chromosomal evolution in this family. Up to now, polytene chromosome maps are available only for one Zeugodacus species, that isZeugodacus cucurbitae.Here we report the cytogenetic analysis of the mitotic and polytene chromosomes of the pumpkin fly,Zeugodacus tau, along with a comparative analysis with polytene chromosomes ofZeugodacus cucurbitaeas well as other tephritids.In situhybridization experiments resulting to chromosomal localization of selected genes in both species are also presented. The genes used as markers arehsp70, hsp83, scarlet and white pupae. The established homologies presented in this study verify that the two Zeugodacus species are genetically close and support the current taxonomic placement of the Zeugodacus genus. The differences in polytene chromosome level, in combination with results ofin situhybridization experiments, reveal the presence of chromosomal rearrangements, mainly inversions, to both closely and distantly related species, which could potentially be a useful diagnostic tool.
Forensic Feature Exploration and Comprehensive Genetic Insights Into Yugu Ethnic Minority and Northern Han Population via a Novel NGS-Based Marker Set
Authors: Lan Qiong , Zhao Congying , Chen Chong , Xu Hui , Fang Yating , Yao Hongbing , Zhu Bofeng
Published: April 2022

The MPS technology has expanded the potential applications of DNA markers and increased the discrimination power of the targeted loci by taking variations in their flanking regions into consideration. Here, a collection of nuclear and extranuclear DNA markers (totally six kinds of nuclear genetic markers and mtDNA hypervariable region variations) were comprehensively and systematically assessed for polymorphism detections, further employed to dissect the population backgrounds in the Yugu ethnic group from Gansu province (Yugu) and Han population from the Inner Mongolia Autonomous Region (NMH) of China. The elevated efficiencies of the marker set in separating full sibling and challenging half sibling determination cases in parentage tests (iiSNPs), as well as predicting ancestry origins of unknown individuals from at least four continental populations (aiSNPs) and providing informative characteristic-related clues for Chinese populations (piSNPs) are highlighted in the present study. To sum up, different sets of DNA markers revealed sufficient effciencies to serve as promising tools in forensic applications. Genetic insights from the perspectives of autosomal DNA, Y chromosomal DNA, and mtDNA variations yielded that the Yugu ethnic group was genetically close related to the Han populations of the northern region. But we admit that more reference populations (like Mongolian, Tibetan, Hui, and Tu) should be incorporated to gain a refined genetic background landscape of the Yugu group in future studies.
Gene Expression Profiling of Glioblastoma to Recognize Potential Biomarker Candidates
Authors: Li Qiang , Aishwarya S. , Li Ji-Ping , Pan Dong-Xiao , Shi Jia-Pei
Published: April 2022

Glioblastoma is an aggressive malignant tumor of the brain and spinal cord. Due to the blood–brain barrier, the accessibility of its treatments still remains significantly challenging. Unfortunately, the recurrence rates of glioblastoma upon surgery are very high too. Hence, understanding the molecular drivers of disease progression is valuable. In this study, we aimed to investigate the molecular drivers responsible for glioblastoma progression and identify valid biomarkers. Three microarray expression profiles GSE90604, GSE50601, and GSE134470 containing healthy and glioblastoma-affected samples revealed overlapping differentially expressed genes (DEGs). The interrelational pathway enrichment analysis elucidated the halt of cell cycle checkpoints and activation of signaling pathways and led to the identification of 6 predominant hub genes. Validation of hub genes in comparison with The Cancer Genome Atlas datasets identified the potential biomarkers of glioblastoma. The study evaluated two significantly upregulated genes, SPARC (secreted protein acidic and rich in cysteine) and VIM (vimentin) for glioblastoma. The genes CACNA1E (calcium voltage-gated channel subunit alpha1 e), SH3GL2 (SH3 domain-containing GRB2-like 2, endophilin A1), and DDN (dendrin) were identified as under-expressed genes as compared to the normal and pan-cancer tissues along with prominent putative prognostic biomarker potentials. The genes DDN and SH3GL2 were found to be upregulated in the proneural subtype, while CACNA1E in the mesenchymal subtype of glioblastoma exhibits good prognostic potential. The mutational analysis also revealed the benign, possibly, and probably damaging substitution mutations. The correlation between the DEG and survival in glioblastoma was evaluated using the Kaplan–Meier plots, and VIM had a greater life expectancy of 60.25 months. Overall, this study identified key candidate genes that might serve as predictive biomarkers for glioblastoma.
Combinatorial and Machine Learning Approaches for Improved Somatic Variant Calling From Formalin-Fixed Paraffin-Embedded Genome Sequence Data
Authors: Dodani Dollina D. , Nguyen Matthew H. , Morin Ryan D. , Marra Marco A. , Corbett Richard D.
Published: April 2022

Formalin fixation of paraffin-embedded tissue samples is a well-established method for preserving tissue and is routinely used in clinical settings. Although formalin-fixed, paraffin-embedded (FFPE) tissues are deemed crucial for research and clinical applications, the fixation process results in molecular damage to nucleic acids, thus confounding their use in genome sequence analysis. Methods to improve genomic data quality from FFPE tissues have emerged, but there remains significant room for improvement. Here, we use whole-genome sequencing (WGS) data from matched Fresh Frozen (FF) and FFPE tissue samples to optimize a sensitive and precise FFPE single nucleotide variant (SNV) calling approach. We present methods to reduce the prevalence of false-positive SNVs by applying combinatorial techniques to five publicly available variant callers. We also introduce FFPolish, a novel variant classification method that efficiently classifies FFPE-specific false-positive variants. Our combinatorial and statistical techniques improve precision and F1 scores compared to the results of publicly available tools when tested individually.
Prognostic Characteristics and Immune Effects of N6-Methyladenosine and 5-Methylcytosine-Related Regulatory Factors in Clear Cell Renal Cell Carcinoma
Authors: Li Lei , Tao Zijia , Zhao Yiqiao , Li Mingyang , Zheng Jianyi , Li Zeyu , Chen Xiaonan
Published: April 2022

In recent years, methylation modification regulators have been found to have essential roles in various tumor mechanisms. However, the relationships between N6-methyladenosine (m6A) and 5-methylcytosine (m5C) regulators and clear cell renal cell carcinoma (ccRCC) remain unknown. This study investigated these relationships using the data from The Cancer Genome Atlas database. We calculated risk scores using a Lasso regression analysis and divided the patient samples into two risk groups (tumor vs. normal tissues). Furthermore, we used univariate and multivariate Cox analyses to determine independent prognostic indicators and explore correlations between the regulatory factors and immune infiltrating cell characteristics. Finally, quantitative reverse transcriptase–polymerase chain reaction (PCR) and The Human Protein Atlas were used to verify signature-related gene expression in clinical samples. We identified expression differences in 35 regulatory factors between the tumor and normal tissue groups. Next, we constructed a five-gene risk score signature (NOP2 nucleolar protein [NOP2], methyltransferase 14, N6-adenosine-methyltransferase subunit [METTL14], NOP2/Sun RNA methyltransferase 5 [NSUN5], heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1], and zinc finger CCCH-type containing 13 [ZC3H13]) using the screening criteria (p < 0.01), and then divided the cases into high- and low-risk groups based on their median risk score. We also screened for independent prognostic factors related to age, tumor grade, and risk score. Furthermore, we constructed a Norman diagram prognostic model by combining two clinicopathological characteristics, which demonstrated good prediction efficiency with prognostic markers. Then, we used a single-sample gene set enrichment analysis and the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method to evaluate the tumor microenvironment of the regulatory factor prognostic characteristics. Moreover, we evaluated five risk subgroups with different genetic signatures for personalized prognoses. Finally, we analyzed the immunotherapy and immune infiltration response and demonstrated that the high-risk group was more sensitive to immunotherapy than the low-risk group. The PCR results showed that NSUN5 and HNRNPA2B1 expression was higher in tumor tissues than in normal tissues. In conclusion, we identified five m6A and m5C regulatory factors that might be promising biomarkers for future research.
Genome-wide Exploration of a Pyroptosis-Related Long Non-Coding RNA Signature Associated With the Prognosis and Immune Response in Patients With Bladder Cancer
Authors: Gao Xin , Cai Jianping
Published: April 2022

Background: Bladder cancer (BLCA) is a malignant tumor with a complex molecular mechanism and high recurrence rate in the urinary system. Studies have shown that pyroptosis regulates tumor cell proliferation and metastasis and affects the prognosis of cancer patients. However, the role of pyroptosis-related (PR) genes or long non-coding RNAs (lncRNAs) in BLCA development is not fully understood.

Methods: We comprehensively analyzed the molecular biological characteristics of PR genes in BLCA, including copy number variation, mutations, expression and prognostic value based on TCGA database. We then identified PR lncRNAs with prognostic value based on the expression of PR genes and performed a consistent clustering analysis of 407 BLCA patients according to the expression of prognosis-related PR lncRNAs and identified two clusters. The least absolute shrinkage and selection operator (LASSO) regression was used to establish a PR lncRNA signature and calculate the risk score associated with the prognosis of patients with BLCA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were used to evaluate the possible functions of PR lncRNA signature. We also evaluated the relationship between the risk score and tumor immune microenvironment (TIME).

Results: A total of 33 PR genes were obtained in our study and 194 prognosis-related PR lncRNAs were identified. We also constructed a signature consisting of eight-PR-lncRNAs and divided patients into high- and low-risk groups. The overall survival rate of patients with a high risk was significantly lower than patients with a low risk. The risk score was significantly correlated with the degree of infiltration of multiple immune cell subtypes and positively correlated with multiple immune checkpoint genes expression in BLCA. Enrichment analyses showed that these lncRNAs are involved in human immune regulatory functions and immune-related pathways.

Conclusion: Our study comprehensively studied the molecular biological characteristics of PR genes BLCA, and the eight-PR-lncRNA signature we identified might play a crucial role in tumor immunity and may be able to predict the prognosis of BLCA patients, providing a theoretical basis for an in-depth study of the relationship between the prognosis and TIME.
Case Report: A Novel Homozygous Frameshift Mutation of the SKIV2L Gene in a Trichohepatoenteric Syndrome Patient Presenting With Short Stature, Premature Ovarian Failure, and Osteoporosis
Authors: Yang Minyi , Jiang Yu , Shao Xinyu
Published: April 2022

Background: Trichohepatoenteric syndrome (THES) is a rare Mendelian autosomal recessive genetic disease characterized by intractable diarrhea, woolly hair, facial abnormality, immune dysfunction, and intrauterine growth restriction. THES mutations are found in the TTC37 and SKIV2L genes, which encode two components of the human superkiller (SKI) complex.

Methods and results: We report one case of a 32-year-old woman of Chinese descent with THES, who was born with a low weight (2000 g). She had intractable diarrhea during the neonatal period and was allergic to cow’s milk and condensed milk, but did not require total parenteral nutrition. She experienced menarche at age 12 and amenorrhea at age 28. In May 2019, the patient presented with a left fibular head fracture and was diagnosed with osteoporosis. Genetic testing showed a novel mutation in exon1 [p.E5Afs∗37 (c.12_13del)] of SKIV2L, which is composed of 28 exons. After the diagnosis, hormone replacement therapy was prescribed, in addition to the routine calcium and vitamin D supplements.

Conclusion: This case expands the clinical characteristic and phenotype spectrum of THES, providing further understanding of SKIV2L and its autoimmune influence.
Human Leukocyte Antigens in Pregnancy and Preeclampsia
Authors: Aisagbonhi Omonigho , Morris Gerald P.
Published: April 2022

Preeclampsia is a pregnancy-induced hypertensive disorder, the pathophysiology of which includes underlying maternal cardiovascular disease, deficient spiral artery remodeling during placenta development, and inflammatory immune responses at the maternal-fetal interface. Human leukocyte antigens (HLA) are major histocompatibility complex molecules essential for the recognition of foreign antigens that is central to immune defense against pathogens and critical determinants for the immune system discriminating between self and non-self tissues, such as in transplantation. Pregnancy represents a naturally existing “transplantation”, where the maternal immune system must be immunologically tolerant to the developing fetus which is 50% allogeneic. It is then unsurprising that HLA also influence normal pregnancy and pregnancy complications including preeclampsia. Here we review the role of classical and non-classical HLA molecules in influencing normal physiologic function during pregnancy and describe the association of HLA with pathophysiology in preeclampsia.
Considerations for the Feasibility of Neutralizing Antibodies as a Surrogate Endpoint for COVID-19 Vaccines
Authors: Liu Jianyang , Mao Qunying , Wu Xing , He Qian , Bian Lianlian , Bai Yu , Wang Zhongfang , Wang Qian , Zhang Jialu , Liang Zhenglun , Xu Miao
Published: April 2022

To effectively control and prevent the pandemic of coronavirus disease 2019 (COVID-19), suitable vaccines have been researched and developed rapidly. Currently, 31 COVID-19 vaccines have been approved for emergency use or authorized for conditional marketing, with more than 9.3 billion doses of vaccines being administered globally. However, the continuous emergence of variants with high transmissibility and an ability to escape the immune responses elicited by vaccines poses severe challenges to the effectiveness of approved vaccines. Hundreds of new COVID-19 vaccines based on different technology platforms are in need of a quick evaluation for their efficiencies. Selection and enrollment of a suitable sample of population for conducting these clinical trials is often challenging because the pandemic so widespread and also due to large scale vaccination. To overcome these hurdles, methods of evaluation of vaccine efficiency based on establishment of surrogate endpoints could expedite the further research and development of vaccines. In this review, we have summarized the studies on neutralizing antibody responses and effectiveness of the various COVID-19 vaccines. Using this data we have analyzed the feasibility of establishing surrogate endpoints for evaluating the efficacy of vaccines based on neutralizing antibody titers. The considerations discussed here open up new avenues for devising novel approaches and strategies for the research and develop as well as application of COVID-19 vaccines.
Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good
Authors: Grassi Germana , Notari Stefania , Gili Simona , Bordoni Veronica , Casetti Rita , Cimini Eleonora , Tartaglia Eleonora , Mariotti Davide , Agrati Chiara , Sacchi Alessandra
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- associated molecular patterns (PAMPs). PAMPs give rise to local inflammation, increasing the secretion of pro- inflammatory cytokines and chemokines, which attract immune cells from the blood into the infected lung. In most individuals, lung-recruited cells clear the infection, and the immune response retreats. However, in some cases, a dysfunctional immune response occurs, which triggers a cytokine storm in the lung, leading to acute respiratory distress syndrome (ARDS). Severe COVID-19 is characterized by an impaired innate and adaptive immune response and by a massive expansion of myeloid-derived suppressor cells (MDSCs). MDSCs function as protective regulators of the immune response, protecting the host from over-immunoreactivity and hyper-inflammation. However, under certain conditions, such as chronic inflammation and cancer, MDSCs could exert a detrimental role. Accordingly, the early expansion of MDSCs in COVID-19 is able to predict the fatal outcome of the infection. Here, we review recent data on MDSCs during COVID-19, discussing how they can influence the course of the disease and whether they could be considered as biomarker and possible targets for new therapeutic approaches.
The Era of Cytotoxic CD4 T Cells
Authors: Cenerenti Mara , Saillard Margaux , Romero Pedro , Jandus Camilla
Published: April 2022

In 1986, Mosmann and Coffman identified 2 functionally distinct subsets of activated CD4 T cells, Th1 and Th2 cells, being key in distinct T cell mediated responses. Over the past three decades, our understanding of CD4 T cell differentiation has expanded and the initial paradigm of a dichotomic CD4 T cell family has been revisited to accommodate a constantly growing number of functionally distinct CD4 T helper and regulatory subpopulations. Of note, CD4 T cells with cytotoxic functions have also been described, initially in viral infections, autoimmune disorders and more recently also in cancer settings. Here, we provide an historical overview on the discovery and characterization of cytotoxic CD4 T cells, followed by a description of their mechanisms of cytotoxicity. We emphasize the relevance of these cells in disease conditions, particularly in cancer, and we provide insights on how to exploit these cells in immunotherapy.
Engineering Islets From Stem Cells: The Optimal Solution for the Treatment of Diabetes?
Authors: Du Suya , Li Yanjiao , Geng Zhen , Zhang Qi , Buhler Leo H. , Gonelle-Gispert Carmen , Wang Yi
Published: April 2022

Diabetes is a metabolic disease characterized by insulin deficiency. Bioengineering of stem cells with the aim to restore insulin production and glucose regulation has the potential to cure diabetic patients. In this review, we focus on the recent developments for bioengineering of induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and pancreatic progenitor cells in view of generating insulin producing and glucose regulating cells for β-cell replacement therapies. Recent clinical trials using islet cells derived from stem cells have been initiated for the transplantation into diabetic patients, with crucial bottlenecks of tumorigenesis, post-transplant survival, genetic instability, and immunogenicity that should be further optimized. As a new approach given high expectations, bioengineered islets from stem cells occupies considerable potential for the future clinical application and addressing the treatment dilemma of diabetes.
Dissecting the Role of AXL in Cancer Immune Escape and Resistance to Immune Checkpoint Inhibition
Authors: Engelsen Agnete S. T. , Lotsberg Maria L. , Abou Khouzam Raefa , Thiery Jean-Paul , Lorens James B. , Chouaib Salem , Terry Stéphane
Published: April 2022

The development and implementation of Immune Checkpoint Inhibitors (ICI) in clinical oncology have significantly improved the survival of a subset of cancer patients with metastatic disease previously considered uniformly lethal. However, the low response rates and the low number of patients with durable clinical responses remain major concerns and underscore the limited understanding of mechanisms regulating anti-tumor immunity and tumor immune resistance. There is an urgent unmet need for novel approaches to enhance the efficacy of ICI in the clinic, and for predictive tools that can accurately predict ICI responders based on the composition of their tumor microenvironment. The receptor tyrosine kinase (RTK) AXL has been associated with poor prognosis in numerous malignancies and the emergence of therapy resistance. AXL is a member of the TYRO3-AXL-MERTK (TAM) kinase family. Upon binding to its ligand GAS6, AXL regulates cell signaling cascades and cellular communication between various components of the tumor microenvironment, including cancer cells, endothelial cells, and immune cells. Converging evidence points to AXL as an attractive molecular target to overcome therapy resistance and immunosuppression, supported by the potential of AXL inhibitors to improve ICI efficacy. Here, we review the current literature on the prominent role of AXL in regulating cancer progression, with particular attention to its effects on anti-tumor immune response and resistance to ICI. We discuss future directions with the aim to understand better the complex role of AXL and TAM receptors in cancer and the potential value of this knowledge and targeted inhibition for the benefit of cancer patients.
The Beneficial Effect of Pollen on Varroa Infested Bees Depends on Its Influence on Behavioral Maturation Genes
Authors: Frizzera Davide , Ray Allyson M. , Seffin Elisa , Zanni Virginia , Annoscia Desiderato , Grozinger Christina M. , Nazzi Francesco
Published: April 2022

Honey bees collect nectar and pollen to fulfill their nutritional demands. In particular, pollen can influence longevity, the development of hypopharyngeal glands, and immune-competence of bees. Pollen can also mitigate the deleterious effects caused by the parasitic mite Varroa destructor and related deformed wing virus (DWV) infections. It has been shown that V. destructor accelerates the physiological and behavioral maturation of honey bees by influencing the interaction between two core physiological factors, Vitellogenin and juvenile hormone. In this study, we test the hypothesis that the beneficial effects of pollen on Varroa-infested bees are related to the hormonal control underpinning behavioral maturation. By analyzing the expression of genes associated to behavioral maturation in pollen-fed mite-infested bees, we show that treatment with pollen increases the lifespan of mite-infested bees by reversing the faster maturation induced by the parasite at the gene expression level. As expected, from the different immune-competence of nurse and forager bees, the lifespan extension triggered by pollen is also correlated with a positive influence of antimicrobial peptide gene expression and DWV load, further reinforcing the beneficial effect of pollen. This study lay the groundwork for future analyses of the underlying evolutionary processes and applications to improve bee health.
A New Approach to Measuring Local Properties of Preforms Enhanced for Formability
Authors: Turk Mark A. , Cao Hengli , Thompson Adam J. , Belnoue Jonathan P-H. , Hallett Stephen R. , Ivanov Dmitry S.
Published: April 2022

Forming of dry engineering textiles is a quality-critical operation in composites manufacturing. There are various different defect mitigation strategies that have been developed to ensure that material will not wrinkle or fold when depositing and forming. One promising direction is the modification of textile properties in the regions where a defect is likely to form. This can be achieved by the integration of patches: additional materials, such as reactive thermally-conditioned resins, tufted or stitched yarns, thermoplastic films, locally activated binder, etc. This method is simple and effective for a certain class of forming problems. The success of the forming operation depends on the balance of properties between dry and patched materials. At present, there is no clearly established methodology for the characterisation of these formability enhancements. Patches are local and an isolated coupon often cannot be extracted from a hosting fabric. This paper discusses the feasibility of adapting the conventional bias extension test to extract the shear properties of locally enhanced material. The obtained properties are critical for modelling tools that can inform the optimum patch location and orientation. The suggested approach is practical, simple to implement and proven to provide properties to a reasonable degree of accuracy for non-linear elastic and visco-elastic patch behaviours.
Neuromuscular Blocking Agents and Monitoring in China: A Cross-Sectional Survey of Current Management
Authors: Wu HaoTian , Lin ZengMao , Zhou RuiHao , Huang SuiSui , Chen LingJun , Su Yang , Cheng LuoNa , Zhang Huan
Published: April 2022

Background

Little is known about the recent use of neuromuscular blocking agents (NMBAs) and monitoring in China. This paper presents the results of a nationwide survey conducted to obtain information regarding the current management of NMBAs in China.

Methods

A questionnaire was sent to Chinese anesthesiologists inviting them to participate in the study. The questionnaire was available through the wenjuanxing website, and the link was sent to 1,488 anesthesiologists using the Wechat mini app.

Results

The web-based survey consisted of 28 questions, and data were collected using an online tool. Between May 19, 2021 and June 16, 2021, 637 responses were collected (response rate = 42.8%). Only 10.2% of anesthesiologists reported using neuromuscular function monitors, and 6.59% of respondents reported that they had the relevant monitors in the operating room.

Conclusion

Although PORC is a potential safety issue, the frequency of using reversal agents and monitors remains extremely low in China. Surveys such as this are important to understand the use and application customs of NMBAs in China.