bluuebunny/crossref_metadata_2025 huggingface dataset:
Student performance in online learning higher education: A preliminary research
Authors: Prabowo Hartiwi , Ikhsan Ridho Bramulya , Yuniarty Yuniarty
Published: November 2022

The impact of student performance is the focus of online learning because it can determine the success of students and higher education institutions to get good ratings and public trust. This study explores comprehensively the factors that can affect the impact of student performance in online learning. An empirical model of the impact of student performance has been developed from the literature review and previous research. The test of reliability and validity of the empirical model was evaluated through linguist reviews and statistically tested with construct reliability coefficients and confirmatory factor analysis (CFA). Overall, the results of this study prove that the structural model with second-order measurements produces a good fit, while the structural model with first-order measurements shows a poor fit.
A 5-year follow-up study on the efficacy and safety of ultrasound-guided laser ablation in elderly patients with papillary thyroid microcarcinoma: A retrospective, single-center study from China
Authors: Juan Zhang , Yongping Liang , Han Xiaochen , Wang Zhiwu , Liu Jingping , Zhao Yongfeng , Liu Wengang , Zhou Ping
Published: November 2022

Objective

The aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC).

Methods

From September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients’ symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions.

Result

The ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60–78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P < 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected.

Conclusion

Ultrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.
A multi-center study on glucometabolic response to bariatric surgery for different subtypes of obesity
Authors: Liu Yao , Sheng Chunjun , Feng Wenhuan , Sun Fang , Zhang Jingjing , Chen Ying , Su Lili , Liu Jia , Du Lei , Jia Xuyang , You Hui , Huang Xiu , Wu Shandong , Lin Ziwei , Qu Shen
Published: November 2022

Objectives

To assess the benefit of a bariatric surgery in four artificial intelligence-identified metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism and the remission of diabetes and hyperinsulinemia.

Methods

This multicenter retrospective study prospectively collected data from five hospitals in China from 2010 to 2021. At baseline 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into the four AIM subtypes. Baseline and follow-up data (506 and 359 patients at 3- and 12-month post-surgery) were collected for longitudinal effect analysis.

Results

Out of the four AIM subgroups, hypometabolic obesity (LMO) group was characterized by decompensated insulin secretion and high incidence of diabetes (99.2%) pre-surgery. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three subgroups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%). The hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) pre-surgery, which had been greatly alleviated post-surgery. For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups who showed a relatively healthy glucometabolism pre-surgery, rate of glucometabolic comorbidities improved moderately post-surgery.

Conclusion

In terms of glucometabolism, the four AIM subtypes of patients benefited differently from a bariatric surgery, which significantly relieved hyperglycemia and hyperinsulinemia for the LMO and HMO-I patients, respectively. The AIM-based subtypes may help better inform clinical decisions on bariatric surgery and patient counseling pertaining to post-surgery outcomes.
The impact of agricultural machinery services on cultivated land productivity and its mechanisms: A case study of Handan city in the North China plain
Authors: Liu Yan , Shi Xiaoping , Gao Fugang
Published: November 2022

Studying the impact of agricultural machinery services (AMS) on cultivated land productivity is conducive to scientifically improving agricultural production and has far-reaching significance for ensuring food security. Taking Handan City in the North China Plain as the research context and using a surveyed sample of 1918 farming households, this paper examines the effect of AMS on the productivity of cultivated land using OLS estimation and estimates the average treatment effect on the treated (ATT) using the propensity score matching (PSM) method. The research findings are as follows. 1) AMS has a significantly positive impact on cultivated land productivity, and a heterogeneity analysis finds that the effects are larger for farmers with relatively less cultivated land and the marginal effects decrease as the adoption of AMS increases. 2) In various planting activities, AMS adoption in basic activities (e.g., ploughing, seeding, and harvesting) has positive effects on cultivated land productivity, while AMS adoption in management activities (e.g., fertilizing, irrigation, and pesticide spraying), has no obvious effect on cultivated land productivity. 3) According to the results of ATT, the conversion of non-adopting farmers to adopting AMS would increase cultivated land productivity by 7.6%–12.1%. 4) A mechanism analysis reveals that AMS adoption relieves financial constraints, improves technical efficiency, and increases smallholders’ crop yields. These results suggest that AMS has a positive effect on cultivated land productivity and therefore have valuable policy implications for increasing smallholders’ access to various types of AMS to improve the productivity of cultivated land in regions dominated by smallholders.
Impact of land use change on habitat quality and regional biodiversity capacity: Temporal and spatial evolution and prediction analysis
Authors: Li Zhijie , Ma Ziyi , Zhou Guoyan
Published: November 2022

The ecological stability of a region and the promotion of its coordinated environmental and economic development depend on habitat quality, which is a key indicator of the territory’s biodiversity capacity. A case study is done in Suzhou City, Jiangsu Province, to determine how land use changes affect habitat quality. The types of land use in 2030 are simulated based on 2000, 2010, and 2020. The InVEST and CA-Markov models analyze and predict how land use will change in Suzhou. Spatial analysis methods, such as the standard deviation ellipse, the center of gravity analysis, spatial autocorrelation, and random forest models, were used to reveal the spatial and temporal variation characteristics of habitat quality and to analyze its influencing factors. The bare land, building lands, and non-construction lands significantly increased in Suzhou city’s land use types between 2000 and 2030 due to land use changes, while the water bodies and forests gradually decreased. Most of the high-quality habitats in this region are found in the water bodies and the mountains. In contrast, the poor habitat quality in this area is mainly concentrated in urban construction lands. The habitat quality gradually declined over time, and its center of gravity followed the migration path from northeast to southwest. The temporal and spatial distribution of habitat degradation in Suzhou reveals a trend of habitat degradation from downtown to suburban areas. This degradation is most common in mountainous and forest areas where the landscape is highly fragmented. Habitat quality in Suzhou city has changed over time and space due to spatial patterns, socioeconomic factors, land use, and the natural environment, with land use having the most significant impact.
The application of biochar mitigated the negative effects of freeze-thaw on soil and nutrient loss in the restored soil of the alpine mining area
Authors: Li Fayong , Wang Desheng , You Yongjun , Li Guoyu , Eltohamy Kamel Mohamed , Khan Sangar , Riaz Luqman
Published: November 2022

Mining operations accelerate ecological damage in alpine mountain locations by contributing to soil erosion and nutrient loss in the freeze-thaw (FT) climate. However, limited studies have been conducted to reduce the soil erosion and nutrient loss in FT climate. This study’s goal was to determine how biochar effected soil erosion in the restored soil of the alpine mining region under FT circumstances. Rainfall simulation and FT cycles (FTCs; three and 5) were used to investigate the effects of 500 and 1,000 kg hm−2biochar application rates (BARs) on runoff, soil loss, and runoff loss of ammonia nitrogen (AN), nitrate nitrogen (NN), total phosphorus (TP), and dissolved phosphorus (DP). Soil residual AN, NN, and DP concentrations after FTCs were also evaluated. Biochar application significantly reduced the runoff, soil loss rate, AN and NN loss rates, but increased the runoff NN concentration and decreased the total AN and NN loss under FTCs condition. Reductions in AN (37.2%–52.2%) and NN (14.3%–27.1%) runoff loss can be differentially attributed to the adsorption effect of biochar and decrease in total runoff. The runoff P concentrations, rates, and magnitudes for soils subjected to FTCs significantly decreased with biochar addition, owing to the particulate P loss decrease in soil and increased adsorption effect of soil DP. Biochar addition increased soil residual AN, NN, and DP concentrations. However, the increase in FTCs weakened the inhibitory effects of biochar on soil erosion. This study suggested the important role of biochar application for the recovery of low-nutrient eroded soils in alpine mining areas.
Runnels mitigate marsh drowning in microtidal salt marshes
Authors: Watson Elizabeth B. , Ferguson Wenley , Champlin Lena K. , White Jennifer D. , Ernst Nick , Sylla Habibata A. , Wilburn Brittany P. , Wigand Cathleen
Published: November 2022

As a symptom of accelerated sea level rise and historic impacts to tidal hydrology from agricultural and mosquito control activities, coastal marshes in the Northeastern U.S. are experiencing conversion to open water through edge loss, widening and headward erosion of tidal channels, and the formation and expansion of interior ponds. These interior ponds often form in high elevation marsh, confounding the notion applied in predictive modeling that salt marshes convert to open water when elevation falls below a critical surface inundation threshold. The installation of tidal channel extension features, or runnels, is a technique that has been implemented to reduce water levels and permit vegetation reestablishment in drowning coastal marshes, although there are limited data available to recommend its advisability. We report on 5 years of vegetation and hydrologic monitoring of two locations where a total of 600-m of shallow (0.15–0.30-m in diameter and depth) runnels were installed in 2015 and 2016 to enhance drainage, in the Pettaquamscutt River Estuary, in southern Rhode Island, United States. Results from this Before-After Control-Impact (BACI) designed study found that runnel installation successfully promoted plant recolonization, although runnels did not consistently promote increases in high marsh species presence or diversity. Runnels reduced the groundwater table (by 0.07–0.12 m), and at one location, the groundwater table experienced a 2-fold increase in the fraction of the in-channel tidal range that was observed in the marsh water table. We suggest that restoration of tidal hydrology through runnel installation holds promise as a tool to encourage revegetation and extend the lifespan of drowning coastal marshes where interior ponds are expanding. In addition, our study highlights the importance of considering the rising groundwater table as an important factor in marsh drowning due to expanding interior ponds found on the marsh platform.
Eco-environmental constraints, economic incentives, and spatiotemporal variations of construction land use efficiency in regional China
Authors: Wu Jiawei , Liu Chonggang , Sun Wei
Published: November 2022

Construction land expansion and use efficiency are tied to the promotion of sustainable cities and communities. This article explores how and why the spatiotemporal variation of construction land use efficiency (CLUE) evolved in the Yangtze River Delta (YRD), China between 2000 and 2020. Our descriptive results show that county-level regions with higher CLUE are concentrated in major cities in the core YRD, as well as ecologically sensitive regions in the peripheral YRD. Although CLUE improvement in peripheral regions has been more remarkable since the early 2010s, the efficiency gap in construction land use between the core YRD (central cities) and the peripheral YRD (suburban counties) has doubled. The modeling results indicate the temporally and spatially heterogeneous impacts of various factors related to economic incentives and eco-environmental constraints on the uneven CLUE. Economic level and ecological sensitivity are positively associated with regional CLUE. The continuing growth of service industries and the spatial agglomeration of knowledge-intensive and foreign-invested firms are increasingly vital for CLUE improvement in the core YRD, while the prosperity of manufacturing industries is more important for the peripheral YRD. The “crowding out effect” of environmental pollution on CLUE could be proved in the peripheral rather than the core YRD. Our findings suggest that proper policies should be tailored to specific places to coordinate construction land use, economic growth, and eco-environmental sustainability.
Synergistic influence on microbial communities ascribed to copper and tetracycline during aerobic composting: Insights into bacterial and fungal structures
Authors: Cui Hu , Wang Lixia , Zhang Jian
Published: November 2022

There are a considerable number of discussions aimed at analyzing microbial communities and their functions during the composting process. However, microbial succession under copper (Cu) and tetracycline (TCH)-stressed conditions has received less attention. Thus, this work analyzed the bacterial and fungal structures with high-throughput sequencing in Cu/TCH-amended composting (Cu: 0, 100, and 500 mg/kg; TCH: 0, 50, and 300 mg/kg), and the dominating controls on microbial diversity were identified using redundancy analysis (RDA) and structural equation models (SEMs). Low-concentration Cu increased the peak temperature (57°C) at the thermophilic phase. Composting phase-derived changes in bacterial and fungal communities were significant, while Cu and TCH showed a remarkable influence on fungi but not on bacteria. Cu and TCH inhibited Firmicutes' activity while promoting Actinobacteriota growth. Low-concentration Cu and TCH had a negative effect on Basidiomycota in the thermophilic phase and a positive influence on Chytridiomycota in the mature phase. TOC and TN were primary controls on the changes in microbial communities. NH4+-N and NO3--N were more beneficial to fungi with a contribution proportion of 42.13 and 16.85%, respectively. These findings could provide theoretical guidance for the directional research on microbial inoculants.
An enigmatic beetle with affinity to Lamingtoniidae in mid-Cretaceous amber from northern Myanmar (Coleoptera: Cucujoidea)
Authors: Li Yan-Da , Leschen Richard A. B. , Liu Zhen-Hua , Huang Di-Ying , Cai Chen-Yang
Published: November 2022

An enigmatic cucujiform beetle, Alloterocucus atratus Li, Leschen, Liu, and Cai gen. et sp. nov., is reported from mid-Cretaceous Burmese amber. The character combination of the new fossil is not completely consistent with any of the known cucujoid or erotyloid families. Based on our phylogenetic analyses, Alloterocucus is assigned to Cucujoidea and may be allied to Lamingtoniidae, which contains a single Australasian genus in the extant fauna. Alloterocucus shares with Lamingtoniidae a similar habitus and a series of characters, including the absence of postocular constriction, 3-segmented antennal club, externally open procoxal cavities, laterally open mesocoxal cavities, exposed pro- and mesotrochantins, and the absence of epipleural fovea and pronotal setose cavities, but differs from extant Lamingtoniidae in its apically truncate terminal maxillary palpomeres, 5-5-4 tarsi in male and absence of distinct dorsal punctation.

Zoobank registration

[https://zoobank.org/], identifier [111CE15E-5B49-4154-9E4A-7B3A738C6D2A].
Approach for machine learning based design of experiments for occupant simulation
Authors: Schneider Bernd , Kofler Desiree , D'Addetta Gian Antonio , Freienstein Heiko , Wolkenstein Maja , Klug Corina
Published: November 2022

The complexity of crash scenarios in the context of vehicle safety is steadily increasing. This is especially the case on the way to mixed traffic challenges with non-automated and automated driving vehicles. The number of simulations required to design a robust restraint system is thus also increasing. The vast range of possible scenarios here is causing a huge parameter space. Simultaneously biofidelic simulation models are resulting in very high computational costs and therefore the number of simulations should be limited to a feasible operational range. In this study, a machine-learning based design of experiments algorithm is developed, which specifically addresses the issues when designing a safety system with a limited number of simulation samples taking diversity of the occupant and accident scenario into account. In contrast to an optimization task, where the aim is to meet a target function, our job has been to find the critical load case combinations to make sure that these are addressed and not missed. A combination of a space-filling approach and a metamodel has been established to find the critical scenarios in order to improve the system for those cases. It focuses specifically on the areas that are difficult to predict by the metamodel. The developed method was applied to iteratively generate a simulation matrix of a total of 208 simulations with a generic interior model and a detailed FE human body model. Kinematic and strain-based injury metrics were used as simulation output. These were used to train the metamodels after each iteration and derive the simulation matrix for the next iteration. In this paper we present a method that allows the training of a robust metamodel for the prediction of injury criteria, considering both varying load cases and varying restraint system parameters for individual anthropometries and seating postures. Based on that, restraint systems or metamodels can be optimized to achieve the best overall performance for a huge variety of possible scenarios with a specific focus on critical scenarios.
Association mapping for important agronomic traits in wild and cultivated Vigna species using cross-species and cross-genera simple sequence repeat markers
Authors: Kumari Gita , Shanmugavadivel P. S. , Lavanya G. Roopa , Tiwari Pravin , Singh Dharmpal , Gore P. G. , Tripathi Kuldeep , Madhavan Nair Ramakrishnan , Gupta Sanjeev , Pratap Aditya
Published: November 2022

The genus Vigna is an agronomically important taxon, with many of its species inhabiting a wide range of environments and offering numerous useful genes for the improvement of the cultivated types. The present study aimed to detect the genomic regions associated with yield-attributing traits by genome-wide association mapping. A diverse panel of 98 wild and cultivated Vigna accessions (acc.) belonging to 13 different species was evaluated for yield and related traits during the kharif season of 2017 and 2018. The panel was also genotyped using 92 cross-genera and cross-species simple sequence repeat markers to study the population genetic structure and useful market-trait associations. The PCA and trait correlation established relationships amongst the traits during both seasons while 100-seed weight (HSW) had a positive correlation with pod length (PL), and days to first flowering (DFF) with days to maturity (DM). The population genetic structure analysis grouped different acc. into three genetically distinct sub-populations with SP-1 comprising 34 acc., SP-2 (24 acc.), and SP-3 (33 acc.) and one admixture group (7 acc.). Mixed linear model analysis revealed an association of 13 markers, namely, VR018, VR039, VR022, CEDG033, GMES0337, MBSSR008, CEDG220, VM27, CP1225, CP08695, CEDG100, CEDG008, and CEDG096A with nine traits. Seven of the aforementioned markers, namely, VR018 for plant height (PH) and terminal leaflet length (TLL), VR022 for HSW and pod length (PL), CEDG033 for DFF and DM, MBSSR008 for DFF and DM, CP1225 for CC at 30 days (CC30), DFF and DM, CEDG100 for PH and terminal leaflet length (TLL), and CEDG096A for CC30 and chlorophyll content at 45 days were associated with multiple traits. The marker CEDG100, associated with HSW, PH, and TLL, is co-localized in gene-encoding histone–lysine N-methyltransferase ATX5. Similarly, VR22, associated with PL and HSW, is co-located in gene-encoding SHOOT GRAVITROPISM 5 in mungbean. These associations may be highly useful for marker-assisted genetic improvement of mungbean and other related Vigna species.
Evolutionary genetics of malaria
Authors: Schneider Kristan Alexander , Salas Carola Janette
Published: November 2022

Many standard-textbook population-genetic results apply to a wide range of species. Sometimes, however, population-genetic models and principles need to be tailored to a particular species. This is particularly true for malaria, which next to tuberculosis and HIV/AIDS ranks among the economically most relevant infectious diseases. Importantly, malaria is not one disease—five human-pathogenic species of Plasmodium exist. P. falciparum is not only the most severe form of human malaria, but it also causes the majority of infections. The second most relevant species, P. vivax, is already considered a neglected disease in several endemic areas. All human-pathogenic species have distinct characteristics that are not only crucial for control and eradication efforts, but also for the population-genetics of the disease. This is particularly true in the context of selection. Namely, fitness is determined by so-called fitness components, which are determined by the parasites live-history, which differs between malaria species. The presence of hypnozoites, i.e., dormant liver-stage parasites, which can cause disease relapses, is a distinct feature of P. vivax and P. ovale sp. In P. malariae inactivated blood-stage parasites can cause a recrudescence years after the infection was clinically cured. To properly describe population-genetic processes, such as the spread of anti-malarial drug resistance, these features must be accounted for appropriately. Here, we introduce and extend a population-genetic framework for the evolutionary dynamics of malaria, which applies to all human-pathogenic malaria species. The model focuses on, but is not limited to, the spread of drug resistance. The framework elucidates how the presence of dormant liver stage or inactivated blood stage parasites that act like seed banks delay evolutionary processes. It is shown that, contrary to standard population-genetic theory, the process of selection and recombination cannot be decoupled in malaria. Furthermore, we discuss the connection between haplotype frequencies, haplotype prevalence, transmission dynamics, and relapses or recrudescence in malaria.
Phylogenomics as an effective approach to untangle cross-species hybridization event: A case study in the family Nymphaeaceae
Authors: Cheng Lin , Han Qunwei , Chen Fei , Li Mengge , Balbuena Tiago Santana , Zhao Yiyong
Published: November 2022

Hybridization is common and considered as an important evolutionary force to increase intraspecific genetic diversity. Detecting hybridization events is crucial for understanding the evolutionary history of species and further improving molecular breeding. The studies on identifying hybridization events through the phylogenomic approach are still limited. We proposed the conception and method of identifying allopolyploidy events by phylogenomics. The reconciliation and summary of nuclear multi-labeled gene family trees were adopted to untangle hybridization events from next-generation data in our novel phylogenomic approach. Given horticulturalists’ relatively clear cultivated crossbreeding history, the water lily family is a suitable case for examining recent allopolyploidy events. Here, we reconstructed and confirmed the well-resolved nuclear phylogeny for the Nymphaeales family in the context of geological time as a framework for identifying hybridization signals. We successfully identified two possible allopolyploidy events with the parental lineages for the hybrids in the family Nymphaeaceae based on summarization from multi-labeled gene family trees of Nymphaeales. The lineages where species Nymphaea colorata and Nymphaea caerulea are located may be the progenitors of horticultural cultivated species Nymphaea ‘midnight’ and Nymphaea ‘Woods blue goddess’. The proposed hybridization hypothesis is also supported by horticultural breeding records. Our methodology can be widely applied to identify hybridization events and theoretically facilitate the genome breeding design of hybrid plants.
Mechanisms underlying the therapeutic effects of 4-octyl itaconate in treating sepsis based on network pharmacology and molecular docking
Authors: Chen Maolin , Su Wenxing , Chen Fangling , Lai Tianlun , Liu Yilun , Yu Daojiang
Published: November 2022

Objective: Through network pharmacology and molecular docking technology, the hub genes, biological functions, and signaling pathways of 4-Octyl itaconate (4-OI) against sepsis were revealed.

Methods: Pathological targets of sepsis were screened using GeneCards and GEO databases. Similarly, the pharmacological targets of 4-OI were obtained through Swiss TargetPrediction (STP), Similarity ensemble approach (SEA), and TargetNet databases. Then, all the potential targets of 4-OI anti-sepsis were screened by the online platform Draw Venn diagram, and the hub genes were screened by Cytoscape software. The identified hub genes were analyzed by GO and KEGG enrichment analysis, protein interaction (PPI) network, and molecular and docking technology to verify the reliability of hub gene prediction, further confirming the target and mechanism of 4-OI in the treatment of sepsis.

Results: After the target screening of 4-OI and sepsis, 264 pharmacological targets, 1953 pathological targets, and 72 genes related to 4-OI anti-sepsis were obtained, and eight hub genes were screened, namely MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2, and HSP90AA1. The enrichment analysis results indicated that 4-OI might be involved in regulating inflammatory imbalance, immunosuppression, and oxidative stress in developing sepsis. 4-OI protects multiple organ dysfunction in sepsis by acting on hub genes, and MMP9 is a reliable gene for the prognosis and diagnosis of sepsis. The molecular docking results showed that 4-OI binds well to the hub target of sepsis.

Conclusion: 4-OI plays an antiseptic role by regulating MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2 and HSP90AA1. These Hub genes may provide new insights into follow-up research on the target of sepsis treatment.
LABAMPsGCN: A framework for identifying lactic acid bacteria antimicrobial peptides based on graph convolutional neural network
Authors: Sun Tong-Jie , Bu He-Long , Yan Xin , Sun Zhi-Hong , Zha Mu-Su , Dong Gai-Fang
Published: November 2022

Lactic acid bacteria antimicrobial peptides (LABAMPs) are a class of active polypeptide produced during the metabolic process of lactic acid bacteria, which can inhibit or kill pathogenic bacteria or spoilage bacteria in food. LABAMPs have broad application in important practical fields closely related to human beings, such as food production, efficient agricultural planting, and so on. However, screening for antimicrobial peptides by biological experiment researchers is time-consuming and laborious. Therefore, it is urgent to develop a model to predict LABAMPs. In this work, we design a graph convolutional neural network framework for identifying of LABAMPs. We build heterogeneous graph based on amino acids, tripeptide and their relationships and learn weights of a graph convolutional network (GCN). Our GCN iteratively completes the learning of embedded words and sequence weights in the graph under the supervision of inputting sequence labels. We applied 10-fold cross-validation experiment to two training datasets and acquired accuracy of 0.9163 and 0.9379 respectively. They are higher that of other machine learning and GNN algorithms. In an independent test dataset, accuracy of two datasets is 0.9130 and 0.9291, which are 1.08% and 1.57% higher than the best methods of other online webservers.
IgG subclass and Fc glycosylation shifts are linked to the transition from pre- to inflammatory autoimmune conditions
Authors: Buhre Jana Sophia , Becker Mareike , Ehlers Marc
Published: November 2022

A crucial factor for the development of inflammatory autoimmune diseases is the occurrence of antibodies directed against self-tissues and structures, which leads to damage and inflammation. While little is known about the cause of the development of mis-directed, disease-specific T and B cells and resulting IgG autoantibody responses, there is increasing evidence that their induction can occur years before disease symptoms appear. However, a certain proportion of healthy individuals express specific IgG autoantibodies without disease symptoms and not all subjects who generate autoantibodies may develop disease symptoms. Thus, the development of inflammatory autoimmune diseases seems to involve two steps. Increasing evidence suggests that harmless self-directed T and B cell and resulting IgG autoantibody responses in the pre-autoimmune disease stage might switch to more inflammatory T and B cell and IgG autoantibody responses that trigger the inflammatory autoimmune disease stage. Here, we summarize findings on the transition from the pre-disease to the disease stage and vice versa, e.g. by pregnancy and treatment, with a focus on low-/anti-inflammatory versus pro-inflammatory IgG autoantibody responses, including IgG subclass and Fc glycosylation features. Characterization of biomarkers that identify the transition from the pre-disease to the disease stage might facilitate recognition of the ideal time point of treatment initiation and the development of therapeutic strategies for re-directing inflammatory autoimmune conditions.
Expanding spectrum, intrafamilial diversity, and therapeutic challenges from 15 patients with heterozygous CARD11-associated diseases: A single center experience
Authors: Urdinez Luciano , Erra Lorenzo , Palma Alejandro M. , Mercogliano María F. , Fernandez Julieta Belén , Prieto Emma , Goris Verónica , Bernasconi Andrea , Sanz Marianela , Villa Mariana , Bouso Carolina , Caputi Lucia , Quesada Belen , Solis Daniel , Aguirre Bruzzo Anabel , Katsicas Maria Martha , Galluzzo Laura , Weyersberg Christian , Bocian Marcela , Bujan Maria Marta , Oleastro Matías , Almejun María B. , Danielian Silvia
Published: November 2022

CARD11-associated diseases are monogenic inborn errors of immunity involving immunodeficiency, predisposition to malignancy and immune dysregulation such as lymphoproliferation, inflammation, atopic and autoimmune manifestations. Defects in CARD11 can present as mutations that confer a complete or a partial loss of function (LOF) or contrarily, a gain of function (GOF) of the affected gene product. We report clinical characteristics, immunophenotypes and genotypes of 15 patients from our center presenting with CARD11-associated diseases. Index cases are pediatric patients followed in our immunology division who had access to next generation sequencing studies. Variant significance was defined by functional analysis in cultured cells transfected with a wild type and/or with mutated hCARD11 constructs. Cytoplasmic aggregation of CARD11 products was evaluated by immunofluorescence. Nine index patients with 9 unique heterozygous CARD11 variants were identified. At the time of the identification, 7 variants previously unreported required functional validation. Altogether, four variants showed a GOF effect as well a spontaneous aggregation in the cytoplasm, leading to B cell expansion with NF-κB and T cell anergy (BENTA) diagnosis. Additional four variants showing a LOF activity were considered as causative of CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS). The remaining variant exhibited a neutral functional assay excluding its carrier from further analysis. Family segregation studies expanded to 15 individuals the number of patients presenting CARD11-associated disease. A thorough clinical, immunophenotypical, and therapeutic management evaluation was performed on these patients (5 BENTA and 10 CADINS). A remarkable variability of disease expression was clearly noted among BENTA as well as in CADINS patients, even within multiplex families. Identification of novel CARD11 variants required functional studies to validate their pathogenic activity. In our cohort BENTA phenotype exhibited a more severe and expanded clinical spectrum than previously reported, e.g., severe hematological and extra hematological autoimmunity and 3 fatal outcomes. The growing number of patients with dysmorphic facial features strengthen the inclusion of extra-immune characteristics as part of the CADINS spectrum. CARD11-associated diseases represent a challenging group of disorders from the diagnostic and therapeutic standpoint, especially BENTA cases that can undergo a more severe progression than previously described.
Differential effects of age, sex and dexamethasone therapy on ACE2/TMPRSS2 expression and susceptibility to SARS-CoV-2 infection
Authors: Shahbaz Shima , Oyegbami Olaide , Saito Suguru , Osman Mohammed , Sligl Wendy , Elahi Shokrollah
Published: November 2022

ACE2 and TMPRSS2 are crucial for SARS-CoV-2 entry into the cell. Although ACE2 facilitates viral entry, its loss leads to promoting the devastating clinical symptoms of COVID-19 disease. Thus, enhanced ACE2/TMPRSS2 expression is likely to increase predisposition of target cells to SARS-CoV-2 infection. However, little evidence existed about the biological kinetics of these two enzymes and whether dexamethasone treatment modulates their expression. Here, we show that the expression of ACE2 at the protein and mRNA levels was significantly higher in the lung and heart tissues of neonatal compared to adult mice. However, the expression of TMPRSS2 was developmentally regulated. Our results may introduce a novel concept for the reduced susceptibility of the young to SARS-CoV-2 infection. Moreover, ACE2 expression but not TMPRSS2 was upregulated in adult female lungs compared to their male counterparts. Interestingly, the ACE2 and TMPRSS2 expressions were upregulated by dexamethasone treatment in the lung and heart tissues in both neonatal and adult mice. Furthermore, our findings provide a novel mechanism for the observed differential therapeutic effects of dexamethasone in COVID-19 patients. As such, dexamethasone exhibits different therapeutic effects depending on the disease stage. This was supported by increased ACE2/TMPRSS2 expression and subsequently enhanced infection of normal human bronchial epithelial cells (NHBE) and Vero E6 cells with SARS-CoV-2 once pre-treated with dexamethasone. Therefore, our results suggest that individuals who take dexamethasone for other clinical conditions may become more prone to SARS-CoV-2 infection.
Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab
Authors: Dey Agnish , Austin Matthew , Kluger Harriet M. , Trunova Nataliya , Mann Helen , Shire Norah , Morgan Claire , Zhou Diansong , Mugundu Ganesh M.
Published: November 2022

Purpose

Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).

Methods

The analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model.

Results

Patients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41–0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44–0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56–5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment.

Conclusion

Post-hoc exploratory analysis found that the efficacy of immunotherapy was improved in patients who developed on-treatment imAEs. This was independent of severity of imAEs or the need for steroid treatment, which is important in allowing patients to remain on treatment and derive optimal clinical benefit. Further research is warranted to establish the correlation between incidence of imAEs and efficacy in this patient population.
Activation of distinct antiviral T-cell immunity: A comparison of bi- and trispecific T-cell engager antibodies with a chimeric antigen receptor targeting HBV envelope proteins
Authors: Debelec-Butuner Bilge , Quitt Oliver , Schreiber Sophia , Momburg Frank , Wisskirchen Karin , Protzer Ulrike
Published: November 2022

Despite the availability of an effective prophylactic vaccine, 820,000 people die annually of hepatitis B virus (HBV)-related liver disease according to WHO. Since current antiviral therapies do not provide a curative treatment for the 296 million HBV carriers around the globe, novel strategies to cure HBV are urgently needed. A promising approach is the redirection of T cells towards HBV-infected hepatocytes employing chimeric antigen receptors or T-cell engager antibodies. We recently described the effective redirection of T cells employing a second-generation chimeric antigen receptor directed against the envelope protein of hepatitis B virus on the surface of infected cells (S-CAR) as well as bispecific antibodies that engage CD3 or CD28 on T cells employing the identical HBV envelope protein (HBVenv) binder. In this study, we added a trispecific antibody comprising all three moieties to the tool-box. Cytotoxic and non-cytolytic antiviral activities of these bi- and trispecific T-cell engager antibodies were assessed in co-cultures of human PBMC with HBV-positive hepatoma cells, and compared to that of S-CAR-grafted T cells. Activation of T cells via the S-CAR or by either a combination of the CD3- and CD28-targeting bispecific antibodies or the trispecific antibody allowed for specific elimination of HBV-positive target cells. While S-CAR-grafted effector T cells displayed faster killing kinetics, combinatory treatment with the bispecific antibodies or single treatment with the trispecific antibody was associated with a more pronounced cytokine release. Clearance of viral antigens and elimination of the HBV persistence form, the covalently closed circular (ccc) DNA, through cytolytic as well as cytokine-mediated activity was observed in all three settings with the combination of bispecific antibodies showing the strongest non-cytolytic, cytokine-mediated antiviral effect. Taken together, we demonstrate that bi- and trispecific T-cell engager antibodies can serve as a potent, off-the-shelf alternative to S-CAR-grafted T cells to cure HBV.
A broad cuproptosis landscape in inflammatory bowel disease
Authors: Chen Yuan , Li Xinfang , Sun Ran , Ji Jiamin , Yang Fan , Tian Weiliang , Ji Wu , Huang Qian
Published: November 2022

Background

Cuproptosis, a genetic process of copper-dependent cell death linked to mitochondria respiration, demonstrates its correlation with inhibiting tumoral angiogenesis and motility. Recent studies have developed systematic bioinformatics frameworks to identify the association of cuproptosis with tumors but any non-neoplastic diseases. Therefore, against the background of an increased incidence of inflammatory bowel disease (IBD), the landscape of cuproptosis regulation in IBD is a critical need to be investigated.

Methods

The differentially expressed cuproptosis-related genes (DECRGs) were identified with human sequencing profiles for four inflammatory digestive disorders. Another four independent IBD datasets from GEO were used as a validation cohort. And experimental mice model provides another validation method. Using single sample gene set enrichment analysis (ssGSEA), receiver operating characteristic (ROC) curve, CIBERSORT, and consensus clustering algorithms, we explored the association between immune score and cuproptosis-related genes, as well as the diagnostic value of these genes. Molecular docking screened potential interaction of IBD drugs with the structural regulator by Autodock Vina.

Results

Cuproptosis-related regulators exhibited extensive differential expression in Crohn’s Disease (CD), Ulcerative Colitis (UC), Celiac Disease (CEL), and IBD-induced cancer (IBD-CA) that share common differential genes (PDHA1, DBT, DLAT, LIAS). The differential expression of DECRGs was reverified in the validated cohort and immunohistochemistry assay. Moreover, the cell signaling pathways and ontology mainly focused on the mitochondrial respiratory function, which was highly enriched in Gene set enrichment analysis (GSEA). According to ssGSEA and ROC, when considering the four regulators, which showed robust association with immune infiltration in IBD, the area under the ROC (AUC) was 0.743. In addition, two clusters of consensus clustering based on the four regulators exhibit different immune phenotypes. According to molecular docking results, methotrexate gained the highest binding affinity to the main chain of key cuproptosis-related regulators compared with the remaining ten drugs.

Conclusion

Cuproptosis-related regulators were widely linked to risk variants, immune cells, immune function, and drug efficacy in IBD. Regulation of cuproptosis may deeply influence the occurrence and development of patients with IBD.
The role of NLRP3 inflammasome in inflammation-related skeletal muscle atrophy
Authors: Liu Yukun , Wang Dongfang , Li Tianyu , Yang Fan , Li Zhanfei , Bai Xiangjun , Wang Yuchang
Published: November 2022

Skeletal muscle atrophy is a common complication in survivors of sepsis, which affects the respiratory and motor functions of patients, thus severely impacting their quality of life and long-term survival. Although several advances have been made in investigations on the pathogenetic mechanism of sepsis-induced skeletal muscle atrophy, the underlying mechanisms remain unclear. Findings from recent studies suggest that the nucleotide-binding and oligomerisation domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a regulator of inflammation, may be crucial in the development of skeletal muscle atrophy. NLRP3 inhibitors contribute to the inhibition of catabolic processes, skeletal muscle atrophy and cachexia-induced inflammation. Here, we review the mechanisms by which NLRP3 mediates these responses and analyse how NLRP3 affects muscle wasting during inflammation.
Targeted drug delivery system for ovarian cancer microenvironment: Improving the effects of immunotherapy
Authors: Peng Hongling , He Xiang , Wang Qiao
Published: November 2022

Immunotherapies have shown modest benefits in the current clinical trials for ovarian cancer. The tumor microenvironment (TME) in an immunosuppressive phenotype contributes to this “failure” of immunotherapy in ovarian cancer. Many stromal cell types in the TME (e.g., tumor-associated macrophages and fibroblasts) have been identified as having plasticity in pro- and antitumor activities and are responsible for suppressing the antitumor immune response. Thus, the TME is an extremely valuable target for adjuvant interventions to improve the effects of immunotherapy. The current strategies targeting the TME include: 1) eliminating immunosuppressive cells or transforming them into immunostimulatory phenotypes and 2) inhibiting their immunosuppressive or pro-tumor production. Most of the effective agents used in the above strategies are genetic materials (e.g., cDNA, mRNA, or miRNA), proteins, or other small molecules (e.g., peptides), which are limited in their target and instability. Various formulations of drug delivery system (DDS) have been designed to realize the controlled release and targeting delivery of these agents to the tumor sites. Nanoparticles and liposomes are the most frequently exploited materials. Based on current evidence from preclinical and clinical studies, the future of the DDS is promising in cancer immunotherapy since the combination of agents with a DDS has shown increased efficacy and decreased toxicities compared with free agents. In the future, more efforts are needed to further identify the hallmarks and biomarkers in the ovarian TME, which is crucial for the development of more effective, safe, and personalized DDSs.