bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyaniline on Stainless Steel Fiber Felt as Anodes for Bioelectrodegradation of Acid Blue 29 in Microbial Fuel Cells
Authors: Khan Mohammad Danish , Tabraiz Shamas , Thimmappa Ravikumar , Li Da , Anwer Abdul Hakeem , Scott Keith , Khan Mohammad Zain , Yu Eileen Hao
Published: April 2022

This study investigated the advantages of using low-cost polyaniline-fabricated stainless steel fiber felt anode-based microbial fuel cells (PANI-SSFF-MFCs) for azo dye acid blue 29 (AB29) containing wastewater treatment integrated with an aerobic bioreactor. The findings of electrochemical impedance spectroscopy (EIS) and polarization studies showed that the PANI–SSFF anode considerably decreased the MFC internal resistance. The highest power density of 103 ± 3.6 mW m−2was achieved by PANI-SSFF-MFCs with a decolorization efficiency of 93 ± 3.1% and a start-up time of 13 days. The final chemical oxygen demand (COD) removal efficiencies for integrated PANI–SSFF–MFC–bioreactor and SSFF–MFC–bioreactor set-ups were 92.5 ± 2% and 80 ± 2%, respectively. Based on 16S rRNA gene sequencing, a substantial microbial community change was observed in MFCs. The majority of sequences were from theProteobacteriaphylum, accounting for 72% and 55% in PANI–SSFF–anodic biofilm and suspension, respectively, and 58 and 45% in SSFF–anodic biofilm and suspension, respectively. The relative abundance of the seven most abundant genera (Pseudomonas, Acinetobacter,Stenotrophomonas, Geothrix,Dysgonomonas, Shinella, andRhizobiales) was higher in PANI–SSFF–MFCs (46.1% in biofilm and 55.4% in suspension) as compared to SSFF–MFC (43% in biofilm and 40.8% in suspension) which predominantly contributed to the decolorization of AB29 and/or electron transfer. We demonstrate in this work that microbial consortia acclimated to the MFC environment and PANI-fabricated anodes are capable of high decolorization rates with enhanced electricity production. A combined single-chamber MFC (SMFC)-aerobic bioreactor operation was also performed in this study for the efficient biodegradation of AB29.
Inhibitors of SARS-CoV-2 PLpro
Authors: Calleja Dale J. , Lessene Guillaume , Komander David
Published: April 2022

The emergence of SARS-CoV-2 causing the COVID-19 pandemic, has highlighted how a combination of urgency, collaboration and building on existing research can enable rapid vaccine development to fight disease outbreaks. However, even countries with high vaccination rates still see surges in case numbers and high numbers of hospitalized patients. The development of antiviral treatments hence remains a top priority in preventing hospitalization and death of COVID-19 patients, and eventually bringing an end to the SARS-CoV-2 pandemic. The SARS-CoV-2 proteome contains several essential enzymatic activities embedded within its non-structural proteins (nsps). We here focus on nsp3, that harbours an essential papain-like protease (PLpro) domain responsible for cleaving the viral polyprotein as part of viral processing. Moreover, nsp3/PLpro also cleaves ubiquitin and ISG15 modifications within the host cell, derailing innate immune responses. Small molecule inhibition of the PLpro protease domain significantly reduces viral loads in SARS-CoV-2 infection models, suggesting that PLpro is an excellent drug target for next generation antivirals. In this review we discuss the conserved structure and function of PLpro and the ongoing efforts to design small molecule PLpro inhibitors that exploit this knowledge. We first discuss the many drug repurposing attempts, concluding that it is unlikely that PLpro-targeting drugs already exist. We next discuss the wealth of structural information on SARS-CoV-2 PLpro inhibition, for which there are now ∼30 distinct crystal structures with small molecule inhibitors bound in a surprising number of distinct crystallographic settings. We focus on optimisation of an existing compound class, based on SARS-CoV PLpro inhibitor GRL-0617, and recapitulate how new GRL-0617 derivatives exploit different features of PLpro, to overcome some compound liabilities.
CsPOM1, a DYRK Family Kinase, Plays Diverse Roles in Fungal Development, Virulence, and Stress Tolerance in the Anthracnose Pathogen Colletotrichum scovillei
Authors: Shin Jong-Hwan , Kim Hee-Yeong , Fu Teng , Lee Kwang-Ho , Kim Kyoung Su
Published: April 2022

Colletotrichum scovillei is the major anthracnose fungus of sweet pepper and chili pepper (Capsicum annuum L.), causing significant losses in the yield and quality of the pepper fruits. Molecular mechanisms governing development and pathogenicity have been widely studied in many foliar fungal pathogens, but the information on fruit diseases is still limited. In this study, we determined the functional roles of the dual-specificity tyrosine phosphorylation-regulated kinase CsPOM1 in C. scovillei. Knockout mutant for CsPOM1 gene was obtained via homology-dependent gene replacement. The ΔCspom1 mutant exhibited a reduction in vegetative growth on osmotic stress, surface hydrophobicity, and conidiation compared with wild-type. Conidia of the ΔCspom1 mutant were already two-celled before inoculation on an induction surface, indicating that CsPOM1 negatively regulates conidial cell division. The ΔCspom1 mutant, similar to wild-type, formed appressoria on the plant surface, but was significantly reduced on hydrophobic coverslips, probably due to a defect in the recognition of surface hydrophobicity. Treatment of conidia with cutin monomers restored appressorium formation on hydrophobic coverslips in the ΔCspom1 mutant. On pepper fruits, the ΔCspom1 mutant exhibited delayed penetration and invasive growth, leading to significantly reduced virulence. Collectively, the results showed that CsPOM1 is important for stress tolerance, conidiation, surface hydrophobicity, appressorium formation, and virulence in C. scovillei.
Peptide of Trichinella spiralis Infective Larval Extract That Harnesses Growth of Human Hepatoma Cells
Authors: Ruenchit Pichet , Reamtong Onrapak , Khowawisetsut Ladawan , Adisakwattana Poom , Chulanetra Monrat , Kulkeaw Kasem , Chaicumpa Wanpen
Published: April 2022

Trichinella spiralis, a tissue-dwelling helminth, causes human trichinellosis through ingestion of undercooked meat containing the parasite’s infective larvae. However, benefits from T. spiralis infection have been documented: reduction of allergic diseases, inhibition of collagen-induced arthritis, delay of type 1 diabetes progression, and suppression of cancer cell proliferation. Since conventional cancer treatments have limited and unreliable efficacies with adverse side effects, novel adjunctive therapeutic agents and strategies are needed to enhance the overall treatment outcomes. This study aimed to validate the antitumor activity of T. spiralis infective larval extract (LE) and extricate the parasite-derived antitumor peptide. Extracts of T. spiralis infective larvae harvested from striated muscles of infected mice were prepared and tested for antitumor activity against three types of carcinoma cells: hepatocellular carcinoma HepG2, ovarian cancer SK-OV-3, and lung adenocarcinoma A549. The results showed that LE exerted the greatest antitumor effect on HepG2 cells. Proteomic analysis of the LE revealed 270 proteins. They were classified as cellular components, proteins involved in metabolic processes, and proteins with diverse biological functions. STRING analysis showed that most LE proteins were interconnected and played pivotal roles in various metabolic processes. In silico analysis of anticancer peptides identified three candidates. Antitumor peptide 2 matched the hypothetical protein T01_4238 of T. spiralis and showed a dose-dependent anti-HepG2 effect, not by causing apoptosis or necrosis but by inducing ROS accumulation, leading to inhibition of cell proliferation. The data indicate the potential application of LE-derived antitumor peptide as a complementary agent for human hepatoma treatment.
What Makes Interactive Art Engaging?
Authors: Krzyzaniak Michael , Erdem Çağri , Glette Kyrre
Published: April 2022

Interactive art requires people to engage with it, and some works of interactive art are more intrinsically engaging than others. This article asks what properties of a work of interactive art promote engagement. More specifically, it examines four properties: (1) the number of controllable parameters in the interaction, (2) the use of fantasy in the work, (3) the timescale on which the work responds, and (4) the amount agency ascribed to the work. Each of these is hypothesized to promote engagement, and each hypothesis is tested with a controlled user study in an ecologically valid setting on the Internet. In these studies, we found that more controllable parameters increases engagement; the use of fantasy increases engagement for some users and not others; the timescale surprisingly has no significant on engagement but may relate to the style of interaction; and more ascribed agency is correlated with greater engagement although the direction of causation is not known. This is not intended to be an exhaustive list of all properties that may promote engagement, but rather a starting point for more studies of this kind.
Geodynamic Characteristics in the Southwest Margin of South China Sea
Authors: Yao Yongjian , Zhang Jian , Dong Miao , Zhu Rongwei , Xu Zhiying , Yang Xiaodong , Liu Hailing
Published: April 2022

The strike-slip fault system in the southwestern margin of South China Sea (SCS) lies on the transition zone between the continental shelf and slope of SCS, which is an important ocean–continent boundary. By using submarine heat flow data, a seismic shear wave tomography model, and gravity potential field data, this paper investigates the distribution of submarine heat flow in the southwestern margin of SCS, the thermal–rheological structure of the crust and mantle, the temperature–viscosity characteristics of the upper mantle Vs low-velocity layer, the tangential stress field of the rheological boundary layer at the lithosphere base, and the convective velocity structure of the mantle asthenosphere. Our new results show that the deep geothermal activity in the southwestern margin of SCS is intense, and the high heat flow area of the mantle with Qm/Qs >70% is distributed along an NNE-trending strip. Moreover, both the east and west sides of the strike–slip fault zone correspond to two low-value areas with a viscosity coefficient of 1021–1022 Pa⋅s at Moho depth, and beneath the Nansha Block are strong and cold blocks with a viscosity coefficient of 1024–1025 Pa⋅s. The northward and eastward shear stress components τN and τE of the rheological boundary layer at the base of the lithosphere mantle decrease with depth. At 65-km depth, both τN and τE are greater than 5.5 × 108 N/m2. At 100-km depth, both τN and τE are less than 1 × 108 N/m2. The calculation results based on the seismic shear wave model of the upper mantle and the gravimetric geoid model indicate that the depth of 120–250 km is the low-velocity layer, and the average temperature of the mantle at 180-km depth can be up to 1,300°C. Moreover, the average effective viscosity coefficient is close to 1018 Pa⋅s, which satisfies the temperature and viscosity conditions for partial melting or convective migration of mantle material. The mantle convection calculation results show that the average flow rate is 8.5 cm/a at 200-km depth and 2.2 cm/a at 400-km depth.
Enhancing Early Childhood Educators’ Skills in Co-regulating Children’s Emotions: A Collaborative Learning Program
Authors: Mänty Kristiina , Kinnunen Susanna , Rinta-Homi Outi , Koivuniemi Marika
Published: April 2022

The aim of this article is to introduce a research-based work-integrated collaborative learning program that focuses on early childhood education and care (ECEC) professionals’ skills in co-regulation of emotions. The collaborative learning program draws on the theoretical framework that acknowledges the situated and socially shared nature of regulated learning and emotion regulation as well as years of research highlighting the importance of versatile and sensitive adults in supporting children’s learning of regulation skills during their early years. The program aims to improve professionals’ shared awareness of children’s emotion regulation development and abilities to identify and develop practices that support children in learning these skills, so that professionals can provide conscious and consistent co-regulation of emotions for children in everyday interactions. The design of the program has been developed by considering the aspects of effective collaborative and professional learning. This paper focuses on describing the theoretical grounding and implementation of a 32-week long collaborative learning program for ECEC professionals in Northern Finland (N = 450). Also, the development of a video-stimulated questionnaire (VSQ) for assessment of professionals’ learning during the program will be described. VSQ measures professionals’ abilities to identify and interpret everyday ECEC interactions from the point of view of (co-)regulation of emotions. Developing research-based collaborative programs that increase systematic support for children to learn regulation skills is essential, as these skills affect children’s lives well into adulthood. They set a basis for children’s learning and social skills and general wellbeing.
Toward an Ecosystem Framework for Advancing Women’s Entrepreneurship in Yemen
Authors: Alshebami Ali Saleh , Alzain Elham
Published: April 2022

Women’s entrepreneurship is critical to an economy’s growth and development, yet it faces a variety of difficulties. This study aims to conduct a theoretical assessment of women’s entrepreneurship in Yemen and examine the problems it faces in its development. The findings show that women entrepreneurs in Yemen face numerous hurdles, including social, cultural, and institutional barriers; financial constraints; a lack of entrepreneurial education and knowledge; and a deficiency in training and incubation support. Consequently, it is suggested that a complete ecosystem for women’s entrepreneurship be developed, involving various stakeholders and comprising different types of facilities capable of assisting women entrepreneurs and ensuring their optimum advantage.
Optimization of Metro Central Air Conditioning Cold Source System Based on PCA-ANN Data Model
Authors: Zhou Ying , Li Xinmei , Yang Dongfang
Published: April 2022

Due to the unique features of metro central air conditioning systems’ architectural design and application scenarios, systems demand a greater degree of energy-savings than standard buildings. The central air conditioning system is the major energy user in metro stations, with the cooling source system accounting for a substantial portion. As a consequence, enhancing the energy efficiency of the cold source system is critical for optimizing the energy efficiency of the central air conditioning system. After analyzing the potential for energy-savings, we propose an energy-saving control technique for cold source systems based on the PCA-ANN data model. Firstly, an operating condition simulation was performed using operational data and cold source system equipment specifications. The effective operating data in the operational data-base was then filtered using the simulation data. Additionally, principal component analysis was used to examine the chosen dates. Finally, the fitted and calibrated data model was utilized to optimize the functioning of the cold source system. August’s revised approach resulted in a 10.5 percent decrease in system energy consumption. In comparison to using non-optimized energy parameters, the suggested technique provides a variety of energy efficiency advantages.
Research on EV Scheduling Optimization Strategy Based on Monte Carlo and AntLion Optimizer
Authors: Peng Daogang , Li Chenxi , Zhao Huirong , Yin Shen
Published: April 2022

As environmental problems become more serious, the trend of “carbon peaking and carbon neutral” has become necessary. However, the disorderly entry of large-scale EVs into the grid has threatened the security of the grid. The purpose of this paper is to study the optimization strategy of EVs to improve the economy and stability of distributed energy. Firstly, the EV user behavior model is constructed to study the charging and discharging behavior influencing factors, and the EV charging and discharging loads are simulated using Monte Carlo simulation. Secondly, we build a hierarchical scheduling optimization strategy based on EV user satisfaction using an improved AntLion optimizer, finally, the load peaks of the distributed energy system are suppressed and the satisfaction of EV customers is significantly improved; in the process of EV scheduling optimization at the source storage layer, EVs fully consume renewable energy output and the comprehensive operating costs of the distributed energy system are reduced. The conclusions are verified and the system is optimized, resulting in improved user satisfaction and optimized system economy and stability.
Heat Transfer Evaluation in MgZn6Zr/C8H18 [(Magnesium–Zinc–Zirconium)/Engine Oil] With Non-linear Solar Thermal Radiations and Modified Slip Boundaries Over a 3-Dimensional Convectively Heated Surface
Authors: Adnan  , Khan Umar , Ahmed Naveed , Khan Ilyas , Mohamed Abdullah , Mehrez Sadok
Published: April 2022

This analysis is concerned about the thermal performance of [(MgZn6Zr)/C8H18]nfby incorporating the essential concept of non-linear thermal radiations. The flow is configured over a 3D stretchable surface which is heated convectively and the surface boundaries updated with slip effects; uniform suction is applied. The proper mathematical modeling is performed by exercising the nanofluids’ empirical correlations and similarity equations. Thereafter, the RK scheme is utilized to execute the problem solution. The influences of imperative flow constraints are furnished and discussed deeply. The results revealed that [(MgZn6Zr)/C8H18]nfmotion decays against suction (R1) and slip effects (γ1). The investigation of the results disclosed that the induction of non-linear thermal radiations in the model boosted the internal energy of the fluid, and hence, the nanofluid thermal efficiency improved. Moreover, convection provided from the surface (Binumber) was also of paramount interest regarding the heat transport in [(MgZn6Zr)/C8H18]nf. Furthermore, significant contribution of the temperature ratio parameterβwis examined in thermal enhancement. Optimum shear stress trends are investigated due to suction from the surface. Finally, we hoped that the problem would be beneficial in the field of applied thermal engineering, more specifically in the heat transport models.
Optimization and Comparison of Biodiesel Production Process by Electric Heating and Microwave-Assisted Heating Transesterification for Waste Cooking Oil via One-Way Experiments and ANOVA
Authors: Li Wenjing , Li Guangming , Wang Fan , Zhu Haochen , He Wenzhi , Huang Juwen
Published: April 2022

Base-catalyzed transesterification of waste cooking oils (WCOs) into biodiesel is a widely used renewable fuel production technology. The traditional heating method for this process is electric heating (EH), while microwave-assisted heating (MW) has also received extensive attention in recent years. This study compares the two reaction processes in detail by one-way experiments and ANOVA. Catalyst content, reaction temperature (average temperature), and alcohol–oil molar ratio are key factors for these two transesterification processes. The maximum FAME yield of both EH and MW processes appeared at 1.0% catalyst concentration, with the reaction temperature around 60°C, while the MW process called for more methanol. It is speculated that the acid value of WCOs may be closely related to the time required for transesterification as well. The MW process can improve the transesterification efficiency, which is shown in kinetics as much larger than the reaction constant of the EH process and about one-tenth of the activation energy.
Job-Exposure Matrix: A Useful Tool for Incorporating Workplace Exposure Data Into Population Health Research and Practice
Authors: Descatha Alexis , Fadel Marc , Sembajwe Grace , Peters Susan , Evanoff Bradley A.
Published: April 2022

Workplace exposures to physical, chemical, and psychosocial factors account for a large burden of chronic diseases. Obtaining useful estimates of current and past workplace exposures is challenging, particularly in large general population studies. Job-exposure matrices (JEMs) are a useful tool for exposure assessment, particularly when no individual level exposure data are available. A JEM provides a cross-tabulation of job titles (sometimes combined with industry) and estimated exposures to workers carrying out these jobs during different time periods. The major limitation of JEMs is that they do not account for individual variation in exposures within the same job. This limitation is offset by the advantages of low cost, wide applicability, lack of bias from self-reporting, and the ability to estimate exposures based on job titles when no other exposure data exist. There is growing use of JEMs in research examining the role of workplace exposures in the development of chronic diseases, and interest in their application to public health practice. This paper provides a scoping review of JEM use, some examples of JEMs, and brief guidance for the application of JEMs in epidemiological research. In conclusion, JEMs provide a useful tool for researchers and public health practitioners to estimate occupational exposures in large scale epidemiological studies relevant to many health conditions.
Spatiotemporal Regulation of CRISPR/Cas9 Enables Efficient, Precise, and Heritable Edits in Plant Genomes
Authors: Rahman Farhanur , Mishra Apurva , Gupta Archit , Sharma Rita
Published: April 2022

CRISPR/Cas-mediated editing has revolutionized crop engineering. Due to the broad scope and potential of this technology, many studies have been carried out in the past decade towards optimizing genome editing constructs. Clearly, the choice of the promoter used to drive gRNA and Cas9 expression is critical to achieving high editing efficiency, precision, and heritability. While some important considerations for choosing a promoter include the number and nature of targets, host organism, mode of transformation and goal of the experiment, spatiotemporal regulation of Cas9 expression using tissue-specific or inducible promoters enables higher heritability and efficiency of targeted mutagenesis with reduced off-target effects. In this review, we discuss specific studies that highlight the prospects and trade-offs associated with the choice of promoters on genome editing and emphasize the need for inductive exploration and discovery to further advance this area of research in crop plants.
Genome-Wide Estimates of Runs of Homozygosity, Heterozygosity, and Genetic Load in Two Chinese Indigenous Goat Breeds
Authors: Li Guixin , Tang Jianhong , Huang Jinyan , Jiang Yongchuang , Fan Yin , Wang Xiaopeng , Ren Jun
Published: April 2022

Runs of homozygosity (ROH) and heterozygosity (ROHet) are windows into population demographic history and adaptive evolution. Numerous studies have shown that deleterious mutations are enriched in the ROH of humans, pigs, cattle, and chickens. However, the relationship of deleterious variants to ROH and the pattern of ROHet in goats have been largely understudied. Here, 240 Guangfeng and Ganxi goats from Jiangxi Province, China, were genotyped using the Illumina GoatSNP50 BeadChip and genome-wide ROH, ROHet, and genetic load analyses were performed in the context of 32 global goat breeds. The classes with the highest percentage of ROH and ROHet were 0.5–2 Mb and 0.5–1 Mb, respectively. The results of inbreeding coefficients (based on SNP and ROH) and ROHet measurements showed that Guangfeng goats had higher genetic variability than most Chinese goats, while Ganxi goats had a high degree of inbreeding, even exceeding that of commercial goat breeds. Next, the predicted damaging homozygotes were more enriched in long ROHs, especially in Guangfeng goats. Therefore, we suggest that information on damaging alleles should also be incorporated into the design of breeding and conservation programs. A list of genes related to fecundity, growth, and environmental adaptation were identified in the ROH hotspots of two Jiangxi goats. A sense-related ROH hotspot (chromosome 12: 50.55–50.81 Mb) was shared across global goat breeds and may have undergone selection prior to goat domestication. Furthermore, an identical ROHet hotspot (chromosome 1: 132.21–132.54 Mb) containing two genes associated with embryonic development (STAG1 and PCCB) was detected in domestic goat breeds worldwide. Tajima’s D and BetaScan2 statistics indicated that this region may be caused by long-term balancing selection. These findings not only provide guidance for the design of conservation strategies for Jiangxi goat breeds but also enrich our understanding of the adaptive evolution of goats.
Precision Medicine Needs to Think Outside the Box
Authors: Martschenko Daphne O. , Young Jennifer L.
Published: April 2022

Precision medicine offers a precious opportunity to change clinical practice and disrupt medicine’s reliance on crude racial, ethnic, or ancestral categories by focusing on an individual’s unique genetic, environmental, and lifestyle characteristics. However, precision medicine and the genomic studies that are its cornerstone have thus far failed to account for human diversity. This failure is made clearer when looking at individuals who encapsulate a mosaic of different genetic ancestries and do not fit neatly into existing population labels. This piece argues that precision medicine continues to rely on the same forms of crude categorization it seeks to unsettle. Until the scientific community creates inclusive solutions for individuals who fall outside or between our existing population labels, precision medicine will continue to fall short in its aims.
The Prognostic Significance and Potential Mechanism of Ferroptosis-Related Genes in Hepatocellular Carcinoma
Authors: Li Wenli , Liu Jun , Zhang Dangui , Gu Liming , Zhao Hetong
Published: April 2022

Ferroptosis exerts a pivotal role in the formation and dissemination processes of hepatocellular carcinoma (HCC). The heterogeneity of ferroptosis and the link between ferroptosis and immune responses have remained elusive. Based on ferroptosis-related genes (FRGs) and HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) cohorts, we comprehensively explored the heterogeneous ferroptosis subtypes. The genetic alterations, consensus clustering and survival analysis, immune infiltration, pathway enrichment analysis, integrated signature development, and nomogram building were further investigated. Kaplan–Meier plotter confirmed statistically differential probabilities of survival among the three subclusters. Immune infiltration analysis showed there were clear differences among the types of immune cell infiltration, the expression of PD-L1, and the distribution of TP53 mutations among the three clusters. Univariate Cox regression analysis, random survival forest, and multivariate Cox analysis were used to identify the prognostic integrated signature, including MED8, PIGU, PPM1G, RAN, and SNRPB. Kaplan–Meier analysis and time-dependent receiver operating characteristic (ROC) curves revealed the satisfactory predictive potential of the five-gene model. Subsequently, a nomogram was established, which combined the signature with clinical factors. The nomogram including the ferroptosis-based signature was conducted and showed some clinical net benefits. These results facilitated an understanding of ferroptosis and immune responses for HCC.
Novel Prognostic Signature for Acute Myeloid Leukemia: Bioinformatics Analysis of Combined CNV-Driven and Ferroptosis-Related Genes
Authors: Han Chunjiao , Zheng Jiafeng , Li Fangfang , Guo Wei , Cai Chunquan
Published: April 2022

Background: Acute myeloid leukemia (AML), which has a difficult prognosis, is the most common hematologic malignancy. The role of copy number variations (CNVs) and ferroptosis in the tumor process is becoming increasingly prominent. We aimed to identify specific CNV-driven ferroptosis-related genes (FRGs) and establish a prognostic model for AML.

Methods: The combined analysis of CNV differential data and differentially expressed genes (DEGs) data from The Cancer Genome Atlas (TCGA) database was performed to identify key CNV-driven FRGs for AML. A risk model was constructed based on univariate and multivariate Cox regression analysis. The Gene Expression Omnibus (GEO) dataset was used to validate the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to clarify the functional roles of DEGs and CNV-driven FRGs.

Results: We identified a total of 6828 AML-related DEGs, which were shown to be significantly associated with cell cycle and immune response processes. After a comprehensive analysis of CNVs and corresponding DEGs and FRGs, six CNV-driven FRGs were identified, and functional enrichment analysis indicated that they were involved in oxidative stress, cell death, and inflammatory response processes. Finally, we screened 2 CNV-driven FRGs (DNAJB6 and HSPB1) to develop a prognostic risk model. The overall survival (OS) of patients in the high-risk group was significantly shorter in both the TCGA and GEO (all p < 0.05) datasets compared to the low-risk group.

Conclusion: A novel signature based on CNV-driven FRGs was established to predict the survival of AML patients and displayed good performance. Our results may provide potential targets and new research ideas for the treatment and early detection of AML.
A Pan-Cancer Analysis of the Oncogenic Role of WD Repeat Domain 74 in Multiple Tumors
Authors: Wu Xiaoxuan , Song Peng , Wang Shun , Qian Zhirong , Ying Jianming , Gao Shugeng , Li Wenbin
Published: April 2022

Although emerging patient-derived samples and cellular-based evidence support the relationship between WDR74 (WD Repeat Domain 74) and carcinogenesis in multiple cancers, no systematic pan-cancer analysis is available. Our preliminary research demonstrated that WDR74 is over-expressed in lung squamous cell carcinoma (LUSC) and related with worse survival. We thus investigated the potential oncogenic roles of WDR74 across 33 tumors based on the database of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). WDR74 is highly expressed in most cancers and correlated with poor prognosis in several cancers (all p < 0.05). Mutation analysis demonstrated that WDR74 is frequently mutated in promoter regions of lung cancer. Moreover, we found that CD8+ T-cells and the fibroblast infiltration level increased in WDR74 over-expressed cancer cells. The GO (Gene Ontology) enrichment analysis of the WDR74 pathway revealed its participation in cellular biogenesis of the RNA metabolism and its critical role in cancer initiation and progression through the tumor cell energy metabolism. Our first pan-cancer study inferred a relatively comprehensive understanding of the oncogenic roles of WDR74 across various cancers.
Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis
Authors: Meng Qingnan , Li Xiaoying , Xiong Xuelian
Published: April 2022

Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers.

Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4).

Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model.

Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder.
A Systematic Screening of ADHD-Susceptible Variants From 25 Chinese Parents–Offspring Trios
Authors: Li Qianqian , Meng Yingying , Wang Jingyang , Xie Yuhang , Li Tian , Sun Wei
Published: April 2022

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and heritable childhood behavioral disorders. Although a number of ADHD-susceptible regions had been identified, details about the variations of genes and their related patterns involved in ADHD are still lacking. In this study, we collected 25 Chinese parents–offspring trios, each of which consisted of a child diagnosed with ADHD and his/her unaffected parents, and analyzed the variations from whole-genome sequencing data. SNVs in reported ADHD-susceptible regions and on the genes whose functions were related to dopamine were screened, and we identified a set of variants with functional annotations which were specifically detected in ADHD children, including most SNVs in the gene coding region that might impair protein functions and a few SNVs in promoter or 3′ untranslated region (3′-UTR) that might affect the regulation of relative gene expression in a transcriptional or posttranscriptional level. All the information may further contribute to the understanding, prediction, prevention, and treatment of ADHD in clinical.
Clinical Prediction of Heart Failure in Hemodialysis Patients: Based on the Extreme Gradient Boosting Method
Authors: Wang Yanfeng , Miao Xisha , Xiao Gang , Huang Chun , Sun Junwei , Wang Ying , Li Panlong , You Xu
Published: April 2022

Background: Heart failure (HF) is the main cause of mortality in hemodialysis (HD) patients. However, it is still a challenge for the prediction of HF in HD patients. Therefore, we aimed to establish and validate a prediction model to predict HF events in HD patients.

Methods: A total of 355 maintenance HD patients from two hospitals were included in this retrospective study. A total of 21 variables, including traditional demographic characteristics, medical history, and blood biochemical indicators, were used. Two classification models were established based on the extreme gradient boosting (XGBoost) algorithm and traditional linear logistic regression. The performance of the two models was evaluated based on calibration curves and area under the receiver operating characteristic curves (AUCs). Feature importance and SHapley Additive exPlanation (SHAP) were used to recognize risk factors from the variables. The Kaplan–Meier curve of each risk factor was constructed and compared with the log-rank test.

Results: Compared with the traditional linear logistic regression, the XGBoost model had better performance in accuracy (78.5 vs. 74.8%), sensitivity (79.6 vs. 75.6%), specificity (78.1 vs. 74.4%), and AUC (0.814 vs. 0.722). The feature importance and SHAP value of XGBoost indicated that age, hypertension, platelet count (PLT), C-reactive protein (CRP), and white blood cell count (WBC) were risk factors of HF. These results were further confirmed by Kaplan–Meier curves.

Conclusions: The HF prediction model based on XGBoost had a satisfactory performance in predicting HF events, which could prove to be a useful tool for the early prediction of HF in HD.
Child Labor Among Syrian Refugees in Turkey
Authors: Fehr Irina , Rijken Conny
Published: April 2022

Nearly 4 million Syrian refugees, including more than 1.8 million Syrian children, fled to Turkey during the Syrian war, where they face many challenges to rebuild their lives. They are confronted with restrictions on their residence status and access to the labor market, limiting their formal employment opportunities. Poverty and labor exploitation are widespread consequences, and to make ends meet, children are driven into the workforce. In Turkey, child labor among Turkish nationals is also widespread as follows from the Turkish national child labor survey from 2019, creating a fertile ground for Syrian children to take up work. Although child labor among the Syrian refugee population is gaining increasing attention among scholars and humanitarian actors, knowledge about its extent or characteristics remains limited. Drawing on a survey conducted in late 2020, this paper contributes to a deeper and more numerically based understanding of the current situation of Syrian minor workers in Turkey. The quantitative results of our research are compared with the Turkish national child labor survey, highlighting the differences and commonalities between Syrian and Turkish children working in the country and looking into the impact of the lack of permanent residency on the prevalence of child labor. Our findings suggest that Syrian children enter the labor force at a younger age and have less access to education while working very long hours and earning low wages. The study thus demonstrates the specific vulnerabilities of Syrian children to labor exploitation.
Safety and Efficacy of Nemolizumab for Atopic Dermatitis With Pruritus: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials
Authors: Liang Junqin , Hu Fengxia , Dan Maoli , Sang Yingbing , Abulikemu Kailibinuer , Wang Qian , Hong Yongzhen , Kang Xiaojing
Published: April 2022

Background

Nemolizumab is deemed as a promising drug for atopic dermatitis (AD) patients with pruritus.

Objective

This study aimed to evaluate the efficacy of nemolizumab in treating patients with AD and the association between the dosage or regimen of nemolizumab with the improvement in clinical indices.

Methods and Materials

PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) published from inception to August 2021.

Results

A total of 14 cohorts of participants from six randomized controlled studies were included in the meta-analysis. Nemolizumab significantly reduced the pruritus VAS (WMD = −18.86, 95% CI: −27.57 to −10.15, p < 0.001; I2 = 56.2%, pheterogeneity = 0.005) and EASI (WMD = −11.76, 95% CI: −20.55 to −2.96, p = 0.009; I2 = 0%, pheterogeneity = 0.978) scores compared with placebo. No significant difference was observed in the occurrence of any AEs (RR = 1.03, 95% CI: 0.93 to 1.13, p = 0.593; I2 = 0%, pheterogeneity = 0.980) between the two groups. The univariate meta-regression showed that both the dosage and study duration had no association with the change of pruritus VAS score.

Conclusion

Nemolizumab presented a promising effect based on the difference in the average change in pruritus VAS and EASI scores compared with placebo. The results indicated its efficacy in relieving pruritus and the severity of AD and improving patients’ quality of life.
The Role Of BMPs in the Regulation of Osteoclasts Resorption and Bone Remodeling: From Experimental Models to Clinical Applications
Authors: Bordukalo-Nikšić Tatjana , Kufner Vera , Vukičević Slobodan
Published: April 2022

In response to mechanical forces and the aging process, bone in the adult skeleton is continuously remodeled by a process in which old and damaged bone is removed by bone-resorbing osteoclasts and subsequently is replaced by new bone by bone-forming cells, osteoblasts. During this essential process of bone remodeling, osteoclastic resorption is tightly coupled to osteoblastic bone formation. Bone-resorbing cells, multinuclear giant osteoclasts, derive from the monocyte/macrophage hematopoietic lineage and their differentiation is driven by distinct signaling molecules and transcription factors. Critical factors for this process are Macrophage Colony Stimulating Factor (M-CSF) and Receptor Activator Nuclear Factor-κB Ligand (RANKL). Besides their resorption activity, osteoclasts secrete coupling factors which promote recruitment of osteoblast precursors to the bone surface, regulating thus the whole process of bone remodeling. Bone morphogenetic proteins (BMPs), a family of multi-functional growth factors involved in numerous molecular and signaling pathways, have significant role in osteoblast-osteoclast communication and significantly impact bone remodeling. It is well known that BMPs help to maintain healthy bone by stimulating osteoblast mineralization, differentiation and survival. Recently, increasing evidence indicates that BMPs not only help in the anabolic part of bone remodeling process but also significantly influence bone catabolism. The deletion of the BMP receptor type 1A (BMPRIA) in osteoclasts increased osteoblastic bone formation, suggesting that BMPR1A signaling in osteoclasts regulates coupling to osteoblasts by reducing bone-formation activity during bone remodeling. The dual effect of BMPs on bone mineralization and resorption highlights the essential role of BMP signaling in bone homeostasis and they also appear to be involved in pathological processes in inflammatory disorders affecting bones and joints. Certain BMPs (BMP2 and -7) were approved for clinical use; however, increased bone resorption rather than formation were observed in clinical applications, suggesting the role BMPs have in osteoclast activation and subsequent osteolysis. Here, we summarize the current knowledge of BMP signaling in osteoclasts, its role in osteoclast resorption, bone remodeling, and osteoblast–osteoclast coupling. Furthermore, discussion of clinical application of recombinant BMP therapy is based on recent preclinical and clinical studies.
Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release
Authors: Ham Hyoungjun , Medlyn Michael , Billadeau Daniel D.
Published: April 2022

NK cell-mediated cytotoxicity is a critical element of our immune system required for protection from microbial infections and cancer. NK cells bind to and eliminate infected or cancerous cellsviadirect secretion of cytotoxic molecules toward the bound target cells. In this review, we summarize the current understanding of the molecular regulations of NK cell cytotoxicity, focusing on lytic granule development and degranulation processes. NK cells synthesize apoptosis-inducing proteins and package them into specialized organelles known as lytic granules (LGs). Upon activation of NK cells, LGs converge with the microtubule organizing center through dynein-dependent movement along microtubules, ultimately polarizing to the cytotoxic synapse where they subsequently fuse with the NK plasma membrane. From LGs biogenesis to degranulation, NK cells utilize several strategies to protect themselves from their own cytotoxic molecules. Additionally, molecular pathways that enable NK cells to perform serial killing are beginning to be elucidated. These advances in the understanding of the molecular pathways behind NK cell cytotoxicity will be important to not only improve current NK cell-based anti-cancer therapies but also to support the discovery of additional therapeutic opportunities.
Dissecting Intra-Tumoral Changes Following Immune Checkpoint Blockades in Intrahepatic Cholangiocarcinoma via Single-Cell Analysis
Authors: Sun Bao-Ye , Zhou Cheng , Guan Ruo-Yu , Liu Gao , Yang Zhang-Fu , Wang Zhu-Tao , Gan Wei , Zhou Jian , Fan Jia , Yi Yong , Qiu Shuang-Jian
Published: April 2022

Purpose

To dissect the tumor ecosystem following immune checkpoint blockades (ICBs) in intrahepatic cholangiocarcinoma (ICC) at a single-cell level.

Methods

Single-cell RNA sequencing (scRNA-seq) data of 10 ICC patients for the ICB clinical trial were extracted from GSE125449 and systematically reanalyzed. Bulk RNA-seq data of 255 ICC patients were analyzed. Infiltration levels of SPP1+CD68+ tumor-associated macrophages (TAMs) were examined by dual immunofluorescence (IF) staining in 264 resected ICC samples. The correlation between SPP1+ TAMs and clinicopathological features as well as their prognostic significance was evaluated.

Results

Among the 10 patients, five received biopsy at baseline, and others were biopsied at different timings following ICBs. Single-cell transcriptomes for 5,931 cells were obtained. A tighter cellular communication network was observed in ICB-treated ICC. We found a newly emerging VEGF signaling mediated by PGF-VEGFR1 between cancer-associated fibroblasts (CAFs) and endothelial cells in ICC following ICBs. SPP1 expression was dramatically upregulated, and SPP1+ TAM gene signatures were enriched in TAMs receiving ICB therapy. We also identified SPP1+ TAMs as an independent adverse prognostic indicator for survival in ICC.

Conclusion

Our analyses provide an overview of the altered tumor ecosystem in ICC treated with ICBs and highlight the potential role of targeting CAFs and SPP1+TAMs in developing a more rational checkpoint blockade-based therapy for ICC.
The Ins and Outs of Antigen Uptake in B cells
Authors: McShane Adam Nathan , Malinova Dessislava
Published: April 2022

A review of our current knowledge of B cell antigen uptake mechanisms, the relevance of these processes to pathology, and outstanding questions in the field. Specific antigens induce B cell activation through the B cell receptor (BCR) which initiates downstream signaling and undergoes endocytosis. While extensive research has shed light on the signaling pathways in health and disease, the endocytic mechanisms remain largely uncharacterized. Given the importance of BCR-antigen internalization for antigen presentation in initiating adaptive immune responses and its role in autoimmunity and malignancy, understanding the molecular mechanisms represents critical, and largely untapped, potential therapeutics. In this review, we discuss recent advancements in our understanding of BCR endocytic mechanisms and the role of the actin cytoskeleton and post-translational modifications in regulating BCR uptake. We discuss dysregulated BCR endocytosis in the context of B cell malignancies and autoimmune disorders. Finally, we pose several outstanding mechanistic questions which will critically advance our understanding of the coordination between BCR endocytosis and B cell activation.