bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring approaches for predictive cancer patient digital twins: Opportunities for collaboration and innovation
Authors: Stahlberg Eric A. , Abdel-Rahman Mohamed , Aguilar Boris , Asadpoure Alireza , Beckman Robert A. , Borkon Lynn L. , Bryan Jeffrey N. , Cebulla Colleen M. , Chang Young Hwan , Chatterjee Ansu , Deng Jun , Dolatshahi Sepideh , Gevaert Olivier , Greenspan Emily J. , Hao Wenrui , Hernandez-Boussard Tina , Jackson Pamela R. , Kuijjer Marieke , Lee Adrian , Macklin Paul , Madhavan Subha , McCoy Matthew D. , Mohammad Mirzaei Navid , Razzaghi Talayeh , Rocha Heber L. , Shahriyari Leili , Shmulevich Ilya , Stover Daniel G. , Sun Yi , Syeda-Mahmood Tanveer , Wang Jinhua , Wang Qi , Zervantonakis Ioannis
Published: October 2022

We are rapidly approaching a future in which cancer patient digital twins will reach their potential to predict cancer prevention, diagnosis, and treatment in individual patients. This will be realized based on advances in high performance computing, computational modeling, and an expanding repertoire of observational data across multiple scales and modalities. In 2020, the US National Cancer Institute, and the US Department of Energy, through a trans-disciplinary research community at the intersection of advanced computing and cancer research, initiated team science collaborative projects to explore the development and implementation of predictive Cancer Patient Digital Twins. Several diverse pilot projects were launched to provide key insights into important features of this emerging landscape and to determine the requirements for the development and adoption of cancer patient digital twins. Projects included exploring approaches to using a large cohort of digital twins to perform deep phenotyping and plan treatments at the individual level, prototyping self-learning digital twin platforms, using adaptive digital twin approaches to monitor treatment response and resistance, developing methods to integrate and fuse data and observations across multiple scales, and personalizing treatment based on cancer type. Collectively these efforts have yielded increased insights into the opportunities and challenges facing cancer patient digital twin approaches and helped define a path forward. Given the rapidly growing interest in patient digital twins, this manuscript provides a valuable early progress report of several CPDT pilot projects commenced in common, their overall aims, early progress, lessons learned and future directions that will increasingly involve the broader research community.
Assessments of students’ gains in conceptual understanding and technical skills after using authentic, online learning modules on hydrology and water resources
Authors: Byrd Jenny , Gallagher Melissa A. , Habib Emad
Published: October 2022

The need to adapt quickly to online or remote instruction has been a challenge for instructors during the COVID pandemic. A common issue instructors face is finding high-quality curricular materials that can enhance student learning by engaging them in solving complex, real-world problems. The current study evaluates a set of 15 web-based learning modules that promote the use of authentic, high-cognitive demand tasks. The modules were developed collaboratively by a group of instructors during a HydroLearn hackathon-workshop program. The modules cover various topics in hydrology and water resources, including physical hydrology, hydraulics, climate change, groundwater flow and quality, fluid mechanics, open channel flow, remote sensing, frequency analysis, data science, and evapotranspiration. The study evaluates the impact of the modules on students’ learning in terms of two primary aspects: understanding of fundamental concepts and improving technical skills. The study uses a practical instrument to measure students’ perceived changes in concepts and technical skills known as the Student Assessment of Learning Gains (SALG) survey. The survey was used at two-time points in this study: before the students participated in the module (pre) and at the conclusion of the module (post). The surveys were modified to capture the concepts and skills aligned with the learning objectives of each module. We calculated the learning gains by examining differences in students’ self-reported understanding of concepts and skills from pre- to post-implementation on the SALG using paired samplest-tests. The majority of the findings were statistically at the 0.05 level and practically significant. As measured by effect size, practical significance is a means for identifying the strength of the conclusions about a group of differences or the relationship between variables in a study. The average effect size in educational research isd= 0.4. The effect sizes from this study [0.45, 1.54] suggest that the modules play an important role in supporting students’ gains in conceptual understanding and technical skills. The evidence from this study suggests that these learning modules can be a promising way to deliver complex subjects to students in a timely and effective manner.
Collaboration and communication in blended learning environments
Authors: Johler Minttu
Published: October 2022

Blended learning environments have become increasingly common during the past few years, and frequent access to digital technologies has influenced many areas of learning and classroom interaction. This paper investigates teacher-pupil and pupil-pupil communication and collaboration practices in a leading-edge Norwegian primary school. In this small-scale case study, seven teachers were interviewed individually and in their respective grade level teams, and two grade levels were observed for a 4-week period to find out how teachers in technology-rich classrooms utilize and consider the role of digital technologies in everyday communication and collaborative processes. Teachers’ overall perception in this study was that digital technologies are useful in communication and collaboration and thus, digital elements were frequently incorporated in their everyday classroom practices. However, the results also imply that while blended learning environments have opened new avenues for collaboration and communication happening parallel in physical and digital learning arenas, there is a lot of variation in how teachers guide their pupils in collaboration and communication and how digital technologies are utilized in such contexts. Particularly the comparison between proactive and reactive approaches to instruction regarding communication and collaboration indicates that explicit guidance in such processes can have a positive influence on the pupils’ group dynamics and effectiveness. Meanwhile, some of the benefits of supporting the act of collaboration and communication among pupils in a blended learning environment remained unexploited.
Kinetic energy harvesting based sensing and IoT systems: A review
Authors: Chen Zijie , Gao Fei , Liang Junrui
Published: October 2022

The rapid advance of the Internet of Things (IoT) has attracted growing interest in academia and industry toward pervasive sensing and everlasting IoT. As the IoT nodes exponentially increase, replacing and recharging their batteries proves an incredible waste of labor and resources. Kinetic energy harvesting (KEH), converting the wasted ambient kinetic energy into usable electrical energy, is an emerging research field where various working mechanisms and designs have been developed for improved performance. Leveraging the KEH technologies, many motion-powered sensors, where changes in the external environment are directly converted into corresponding self-generated electrical signals, are developed and prove promising for multiple self-sensing applications. Furthermore, some recent studies focus on utilizing the generated energy to power a whole IoT sensing system. These systems comprehensively consider the mechanical, electrical, and cyber parts, which lead a further step to truly self-sustaining and maintenance-free IoT systems. Here, this review starts with a brief introduction of KEH from the ambient environment and human motion. Furthermore, the cutting-edge KEH-based sensors are reviewed in detail. Subsequently, divided into two aspects, KEH-based battery-free sensing systems toward IoT are highlighted. Moreover, there are remarks in every chapter for summarizing. The concept of self-powered sensing is clarified, and advanced studies of KEH-based sensing in different fields are introduced. It is expected that this review can provide valuable references for future pervasive sensing and ubiquitous IoT.
Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis
Authors: Juan Juan , Sun Yiying , Wei Yumei , Wang Shuang , Song Geng , Yan Jie , Zhou Pengxiang , Yang Huixia
Published: October 2022

Background

To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria.

Methods

Systematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I2 statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg’s and Egger’s tests.

Results

This meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias.

Conclusions

Women with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776)
Dynamics of MHD second-grade nanofluid flow with activation energy across a curved stretching surface
Authors: Reddy Srinivas C. , Asogwa Kanayo Kenneth , Yassen Mansour F. , Adnan  , Iqbal Zahoor , M-Eldin Sayed , Ali Bagh , KM Swarnalatha
Published: October 2022

This analysis addresses the influence of activation energy on the MHD flow of second-grade nanoliquid over a convectively heated curved stretched surface. The impact of heat generation/absorption, thermophoresis, and Brownian motion are also incorporated. This current study in addendum reveals the solution narrating the nanofluid flow behaviour of the stretched curve to better the performance of the system. Hence, the mathematical construction of governing partial differential equations (PDEs) is transmitted into nonlinear ODEs by employing appropriate transformations. The attained ODEs are conducted numericallyviaND-Solve. It is consequential to report that fluid velocity and temperature fields significantly rise with concurrent enhancing values of the fluid parameter and curvature parameter. Moreover, the concentration field enhances considering the energy activation variable and suppresses with the reaction rate constant while thermophoresis escalates the temperature distribution as the Nusselt number lowers with a stronger internal heat source parameter Q.
Research on the coupling coordination and prediction of industrial convergence and ecological environment in rural of China
Authors: Gu Jing , Zheng Jiyuan , Zhang Jing
Published: October 2022

Coordination of rural industrial convergence and ecological environment is an important issue in rural social and economic development. This study aims to introduce a comprehensive evaluation index system and construct an integrated approach to evaluate and predict the coupling coordination between rural industrial convergence and ecological environment. Firstly, an index system including 40 indexes is developed for evaluating the two subsystems, and then entropy weight method is applied to determine the weights. Finally, a coupling coordination model and a grey prediction model are developed using provincial panel data from 2017 to 2021 for 29 provinces in China. There are three main findings: 1) penetration of new technologies and agricultural industrialization are the main driving factors of rural industrial convergence. In the three dimensions of ecological environment, environmental pressure has been the smallest contributor, implying that environmental pressure in rural China still needs attention in the next decade. 2) the coupling coordination between rural industrial convergence and ecological environment shows a fluctuating upward trend in China during the studied period and will continue to rise in the next 12 years. Among the 29 provinces studied, only 4 eastern developed provinces have reached primary coordination. The forecast data suggests that coordination with ecological environment will promote the development of rural industrial convergence. 3) the spatial differences of the coupling coordination are related to the level of economic and cultural development, application of agricultural technology, convergence of information technology, energy consumption structure and stock of natural resources. In conclusion, the research develops a rational index system and an effective approach to measure and predict the coupling coordination between rural industrial convergence and ecological environment, providing a theoretical basis for the environmental considerations in the rural industrial convergence policy-making.
Modelling the sustainable agriculture management adaptation practices: Using adaptive capacity as a mediator
Authors: Masud Muhammad Mehedi , Akhtar Rulia , Al Mamun Abdullah , Uddin Md. Sayed , Siyu Long , Yang Qing
Published: October 2022

The purpose of this research is to investigate the mediating role of farmers’ adaptive capacity between adaptation practices and economic, social, natural, technological, and institutional limitations. A survey questionnaire was employed to collect data, which was subsequently analysed using PLS-Structural Equation Modelling Structural equation modelling. The entire population was stratified into 27 Pertubuhan Peladang Kawasan out of which 500 targeted respondents were randomly selected from seven strata for data collection. The findings revealed that only 67% of farmers are aware of adaptation practices, while 33% are uninformed. The study also revealed that economic, social, natural, technological, and institutional barriers affect farmers’ adaptive capacity levels and ultimately hamper their adaptation practices. This result further affirms the influence of farmers’ adaptive capacity level on their adaptation behaviour. Adaptation strategies are essential to mitigate the negative effects of climate change. However, the success of these strategies is contingent upon the farmers’ adaptive capacity level, which is strained by several barriers. The findings contribute to the development of a national adaptation plan in a bid to aid the implementation of the 2011–2020 National Agri-Food Policy (NAP) to increase the competitiveness and production capacity of the entire agri-food industry value chain and ensure food security in Malaysia. This study will help policymakers come up with a good policy framework to get rid of the problems that get in the way of adapting to climate change.
Does compensatory mitigation restore food webs in coastal wetlands? A terrestrial arthropod case study on the Upper Texas Coast
Authors: Armitage Anna R. , Goeke Janelle A. , Ho Chuan-Kai
Published: October 2022

Compensatory wetland restoration is a critical component of holistic, ecosystem-level oil spill response strategies. An important goal of restoration is to rehabilitate food webs in impacted areas, but faunal assemblages and trophic dynamics are rarely included in post-restoration monitoring or assessments of success. Different approaches to wetland restoration, including variations in construction technique, may influence faunal recovery and trophic interactions. To explore these dynamics, we compared emergent plant communities, terrestrial arthropod assemblages, and trophic interactions in restored emergent marshes that were constructed in terrace and mound configurations and in reference areas in the Lower Neches Wildlife Management Area (Texas, United States). Plant community composition differed among all habitat types, with higher diversity on terraces and in reference marshes. Terrestrial arthropod abundance was similar among habitat types, but species composition was distinctly different among habitat types, especially at the herbivore level, where four of the eight herbivore species were found in either reference or restored sites, but not in both habitat types. Herbivores (primarily beetles and planthoppers) were more abundant than detritivores (midges and flies) in all habitat types. Predator (web-building and hunting spiders) abundance and species identity were similar among habitat types. Based on stable isotope analysis, trophic relationships differed among mounds, terraces, and reference areas. Herbivore diets were more variable at the reference sites than in either restored habitat type, aligning with higher plant diversity in reference areas. In contrast, detritivore diets were more variable at restored sites, where they were likely consuming food sources such as benthic algae or sediment organic matter. Predator diets were primarily comprised of herbivores in reference areas and detritivores in restored habitats. Overall, the restoration approaches supported abundant terrestrial arthropod assemblages, but species composition was different. In addition, trophic relationships differed between restored and reference areas, in part due to unique plant species assemblages at restored and reference sites. These results suggest that ecosystem restoration strategies that introduce geomorphological heterogeneity and plant diversity are more likely to support a diverse array of species and functions.
High genetic connectivity among large populations of Pteronotus gymnonotus in bat caves in Brazil and its implications for conservation
Authors: Ito Fernanda , Lilley Thomas , Twort Victoria G. , Bernard Enrico
Published: October 2022

Bat caves in the Neotropical region harbor exceptional bat populations (> 100,000 individuals). These populations play a wider role in ecological interactions, are vulnerable due to their restriction to caves, and have a disproportionate conservation value. Current knowledge of bat caves in Brazil is still small. However, systematic monitoring of some bat caves in northeastern Brazil shows that they experience strong population fluctuations over short periods of time, suggesting large-scale movements between roosts and a much broader use of the landscape than previously considered. Spatio-temporal reproductive connectivity between distant populations would change our understanding of the use of roosts among bat species in Brazil, and important gaps in knowledge of long-distance bat movements in the country would be filled. Here, we used ddRADseq data to analyze the genetic structure of Pteronotus gymnonotus across nine bat caves over 700 km. Our results indicate the lack of a clear geographic structure with gene flow among all the caves analyzed, suggesting that P. gymnonotus uses a network of bat caves geographically segregated hundreds of kilometers apart. Facing strong anthropogenic impacts and an underrepresentation of caves in conservation action plans worldwide, the genetic connectivity demonstrated here confirms that bat caves are priority sites for bat and speleological conservation in Brazil and elsewhere. Moreover, our results demonstrate a warning call: the applied aspects of the environmental licensing process of the mining sector and its impact must be reviewed, not only in Brazil, but wherever this licensing process affects caves having exceptional bat populations.
Environmental and socio-economic impacts of new plant breeding technologies: A case study of root chicory for inulin production
Authors: Hingsamer Maria , Kulmer Veronika , de Roode Matthew , Kernitzkyi Michael
Published: October 2022

In Europe, root chicory and other plants are cultivated for their prebiotic food fiber, inulin, which boosts the growth of beneficial gut bacteria and stimulates the human immune system. CHIC, a H2020 project, develops new chicory variants which produce more and reported to be healthier inulin as well as medicinal terpenes. This paper presents an environmental and socio-economic assessment of the whole value chain of the new chicory variants and their derived products using a case study based in the Netherlands. Two scenarios based on new chicory variants using new plant breeding technologies (NPBT) are analyzed and impacts thereof are compared to the reference scenario; the current commercial inulin process from conventional chicory. Both scenarios show higher inulin content, but the inulin adsorption process differs. While one aims to optimize inulin yield, the other one explores the potential of a multipurpose use, yielding inulin and health beneficial terpenes. Methodologically, we employ multi-regional input-output (MRIO) analysis to estimate additional economic benefits, added value and job creation, while by means of life cycle assessment (LCA) effects on greenhouse gas (GHG) emissions and primary energy demand are derived. Both methods, MRIO and LCA, are well suited to analyze the raised issues and draw on the same data. Generally, the results highlight the importance of inulin production at a national and EU-level in the reference scenario. In case of the two scenarios, we find that the related socio-economic impacts are much higher than in the reference scenario and thus highlight their ability to boost economic activity and increase competiveness of the EU, i.e. over 80% of the generated value added stays in the EU. In terms of environmental impacts, the two scenarios show lower GHG emissions and primary energy demand due to the higher efficiencies of the process in the scenarios compared to the reference inulin process. Additionally, regarding the goal of climate neutral production, we find that the majority of GHG emissions stem from the electricity mix and natural gas demand. Replacing these sources of energy with more renewable ones will contribute to this goal.
Association between CILP and IL-1α polymorphisms and phenotype-dependent intervertebral disc degeneration susceptibility: A meta-analysis
Authors: Liu Jiachen , Chen Yunxia , Shan Xiuqi , Wang Huan
Published: October 2022

Background: The relationship between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and intervertebral disc degeneration (IDD) have been explored in several studies but the results were conflicting. The aim of the study was to evaluate and synthesize the currently available data on the association between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and susceptibility of phenotype-dependent radiologic IDD (RIDD) and symptomatic intervertebral disk herniation (SIDH).

Methods: A computerized literature search was in PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure database, and Web of Science. The pooled results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Moreover, the false-positive report probability (FPRP) test and trial sequential analysis (TSA) were applied to estimate the significant results.

Results: Our evidence demonstrated that IL-1α(+889C/T) was significant associated with RIDD (allele model: OR = 1.34, 95%CI 1.03–1.74, p = 0.029) and SIDH (allele model: OR = 1.28, 95% CI 1.03–1.60, p = 0.028). However, the results were not noteworthy under the FPRP test and TSA analysis. Additionally, CILP (1184T>C) polymorphism was significantly associated with RIDD with adequate evidence (allele model: OR = 1.27, 95% CI 1.09–1.48, p = 0.002) instead of SIDH.

Conclusion: The current meta-analysis illustrated firm evidence that CILP (1184T>C) polymorphism was significantly associated with the susceptibility of RIDD. However, the significant associations between IL-1α(+889C/T) and RIDD and SIDH were less credible. Thus, more multi-center studies with diverse populations were required to verify the results.
DNA methylation regulator-mediated modification pattern defines tumor microenvironment immune infiltration landscape in colon cancer
Authors: Yuan Shijin , Gao Yuzhen , Xia Yan , Wang Zhuo , Wang Xian
Published: October 2022

Emerging evidence implies a non-negligible role of DNA methylation in tumor immunity, however, its comprehensive impact on tumor microenvironment (TME) formation and immune activation remains unclear. In this study, we integrated 24 DNA methylation regulators among 754 colon cancer patients to distinguish different modification patterns via an unsupervised clustering method, and explore their TME immune characteristics. Three DNA methylation modification patterns with distinct prognosis and biological behaviors were identified, consistent with three known phenotypes of immune-inflamed, immune-excluded, and immune-desert. We then determined a DNA methylation gene signature and constructed a DNA methylation score (DMS) to quantify modification patterns individually through principal component analysis algorithms. DMS-low group had characteristics of specific molecular subtypes, including microsatellite instability, CpG island methylator phenotype positive, and mutant BRAF, presented by increased mutation burden, activation of DNA damage repair and immune-related pathways, highly TME immune cells infiltration, and hence, a preferable prognosis. Further, low DMS was also demonstrated to be correlated to better response and prolonged survival of anti-PD-L1 antibody, indicating that DMS could be considered as an effective predictive tool for immunotherapy. In conclusion, our work presented a landscape of different DNA methylation modification patterns, and their vital role in the formation of TME diversity and complexity, which could help to enhance understanding of TME immune infiltration characteristics and more importantly, guide immunotherapy strategies more effectively and personalized.
Comprehensive analysis of key m5C modification-related genes in type 2 diabetes
Authors: Song Yaxian , Jiang Yan , Shi Li , He Chen , Zhang Wenhua , Xu Zhao , Yang Mengshi , Xu Yushan
Published: October 2022

Background: 5-methylcytosine (m5C) RNA methylation plays a significant role in several human diseases. However, the functional role of m5C in type 2 diabetes (T2D) remains unclear.

Methods: The merged gene expression profiles from two Gene Expression Omnibus (GEO) datasets were used to identify m5C-related genes and T2D-related differentially expressed genes (DEGs). Least-absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify optimal predictors of T2D. After LASSO regression, we constructed a diagnostic model and validated its accuracy. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to confirm the biological functions of DEGs. Gene Set Enrichment Analysis (GSEA) was used to determine the functional enrichment of molecular subtypes. Weighted gene co-expression network analysis (WGCNA) was used to select the module that correlated with the most pyroptosis-related genes. Protein-protein interaction (PPI) network was established using the STRING database, and hub genes were identified using Cytoscape software. The competitive endogenous RNA (ceRNA) interaction network of the hub genes was obtained. The CIBERSORT algorithm was applied to analyze the interactions between hub gene expression and immune infiltration.

Results: m5C-related genes were significantly differentially expressed in T2D and correlated with most T2D-related DEGs. LASSO regression showed that ZBTB4 could be a predictive gene for T2D. GO, KEGG, and GSEA indicated that the enriched modules and pathways were closely related to metabolism-related biological processes and cell death. The top five genes were identified as hub genes in the PPI network. In addition, a ceRNA interaction network of hub genes was obtained. Moreover, the expression levels of the hub genes were significantly correlated with the abundance of various immune cells.

Conclusion: Our findings may provide insights into the molecular mechanisms underlying T2D based on its pathophysiology and suggest potential biomarkers and therapeutic targets for T2D.
The genetics of occupational asthma development among workers exposed to diisocyanates: A systematic literature review with meta-analysis
Authors: Word Laura J. , McAden Emily P. , Poole Charles , Nylander-French Leena A.
Published: October 2022

Diisocyanates are widely used compounds that pose a safety concern for workers in occupations within the spray-paint, spray-foam insulation, and furniture varnish industries. Epidemiological studies show that only a subset of workers exposed to diisocyanates develop diisocyanate-induced occupational asthma (diisocyanate asthma, DA), indicating that genetic susceptibility may play a role. The purpose of this systematic literature review was to compile and meta-analyze the reported data on genetic susceptibility markers for DA. Three databases (Embase, Pubmed, and Scopus) were searched and 169 non-duplicate publications were identified, of which 22 relevant occupational studies were included in this review. Researchers reported prevalence odds ratios (PORs) for 943 comparisons in 82 different genes/serotypes. Protein network functions for the DA-associated genes from this review include: antigen processing, lymphocyte activation, cytokine production regulation, and response to oxidative stress. Meta-analysis of comparisons between workers with DA and controls was conducted for 23 genetic markers within: CTNNA3, GSTM1, GSTP1, GSTT1, HLA-C, HLA-DQB1, HLA-DR1, HLA-DR3, HLA-DR4, HLA-DR7, and HLA-DR8. These genes code for proteins that are involved in cell-cell adhesions (CTNNA3), glutathione conjugation for xenobiotic metabolism (GST gene family), and immune system response (HLA gene family). The most compelling pooled PORs were for two studies on CTNNA3 (increased DA risk: rs10762058 GG, rs7088181 GG, rs4378283 TT; PORs 4.38–4.97) and three studies on HLA-DR1 (decreased DA risk, POR 0.24). Bioinformatics of the predicted protein pathways for DA shows overlap with biomarker-associated pathways in workers before development of asthma, suggesting overlap in toxicokinetic and toxicodynamic pathways of diisocyanates. The control groups were also compared against each other and differences were negligible. Suggestions for improving future research are also presented. Of the highest importance, the literature was found to be profoundly publication-biased, in which researchers need to report the data for all studied markers regardless of the statistical significance level. We demonstrate the utility of evaluating the overlap in predicted protein pathway functions for identifying more consistency across the reported literature including for asthma research, biomarker research, and in vitro studies. This will serve as an important resource for researchers to use when generating new hypothesis-driven research about diisocyanate toxicology.
Integrative study reveals the prognostic and immunotherapeutic value of CD274 and PDCD1LG2 in pan-cancer
Authors: Zhou Xuan , Wang Yu , Zheng Jianwei , Wang Sinan , Liu Chao , Yao Xiaofeng , Ren Yu , Wang Xudong
Published: October 2022

Background: Disorders of CD274 and PDCD1LG2 contribute to immune escape in human cancers, and treatment with anti-programmed death receptor 1 (PD-1) has been widely used in recurrent or metastatic tumors. However, integrated studies considering CD274 and PDCD1LG2 across cancers remain limited.

Materials and Methods: Differences in expression levels of CD274 and PDCD1LG2 were analyzed in diverse cancer types using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The clinical information and matched expression profiles of TCGA patients were obtained to determine the prognostic value of CD274 and PDCD1LG2. Moreover, correlations between CD274 and PDCD1LG2 and the immune signature were analyzed by exploring the TIMER2 and TISIDB databases. We also investigated correlations between CD274 and PDCD1LG2 and immunotherapeutic biomarkers, including mismatch repair (MMR), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA methylation.

Results: Expression levels of CD274 and PDCD1LG2 varied across multiple cancer types. CD274 and PDCD1LG2 not only impacted the prognosis of patients with cancer but were associated with clinical characteristics (lymph node metastasis, tumor stage, and sex) in kidney renal papillary cell carcinoma, thyroid carcinoma, and some other cancer types. Typically, CD274 and PDCD1LG2 could be strongly correlated with macrophages, dendritic cells, neutrophils, and CD8+ T-cells. Furthermore, CD274 and PDCD1LG2 expression were associated with various immunosuppressive biomarkers, such as CTLA4, TIGIT, and LAG3. In addition, CD274 and PDCD1LG2 were significantly associated with MMR, TMB, MSI, and DNA methylation. Finally, enrichment analysis confirmed that CD274 and PDCD1LG2 were associated with numerous biological pathways, such as: “Activation of Immune Reactions” and “Epithelial-Mesenchymal Transition,” suggesting that CD274 and PDCD1LG2 play crucial roles in cancer immunity and tumor metastasis.

Conclusion: CD274 and PDCD1LG2 play critical roles in cancer progression and immune response and could serve as effective biomarkers to predict the prognosis and immune signature of cancer.
Rare complications of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: Time to nip them in the bud
Authors: Yang Jinming , Yan Bing
Published: October 2022

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5+ DM) is an infrequent autoimmune disease, which mainly distributes in Asians and females. MDA5+ DM usually presents various skin lesions and positive anti-MDA5 antibody (a myositis-specific autoantibody for itself) with amyopathic or hypomyopathic features. For MDA5+ DM patients, rapidly progressive interstitial lung disease is a common complication with a high-speed deterioration and a poor prognosis. Besides, there are other complications of MDA5+ DM patients, including pneumomediastinum, macrophage activation syndrome and spontaneous intramuscular hemorrhage. These complications were rare but lethal, so it is necessary to explore their diagnosis methods, therapies and potential mechanisms, which are helpful for early diagnoses and timely treatment. To date, several cases and studies have shown distinctive features, diagnoses and treatments of these three rare complications, and there are also some differences among them. In this review, we outlined the characteristics, administration and potential pathogenesis of these rare complications of MDA5+ DM.
The established chemokine-related prognostic gene signature in prostate cancer: Implications for anti-androgen and immunotherapies
Authors: Chen Lei , Zheng Yi , Jiang Changqin , Yang Cheng , Zhang Li , Liang Chaozhao
Published: October 2022

Background

Prostate cancer (PCa) was one of the most common malignancies among men, while the prognosis for PCa patients was poor, especially for patients with recurrent and advanced diseases.

Materials and methods

Five PCa cohorts were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and the biochemical recurrence (BCR)-related chemokine genes were identified by LASSO-Cox regression. The chemokine-related prognostic gene signature (CRPGS) was established, and its association with PCa patients’ clinical, pathological and immune characteristics was analyzed. The association between CRPGS and PCa patients’ responses to androgen deprivation therapy (ADT) and immunotherapy was analyzed. The CRPGS was compared with other previously published molecular signatures, and the CRPGS was externally validated in our real-world AHMU-PC cohort.

Results

Four recurrence-free survival (RFS)-related chemokine genes (CXCL14, CCL20, CCL24, and CCL26) were identified, and the CRPGS was established based on the four identified chemokine genes, and TCGA-PRAD patients with high riskscores exhibited poorer RFS, which was validated in the GSE70768 cohort. The CRPGS was associated with the clinical, pathological, and immune characteristics of PCa patients. Low-risk PCa patients were predicted to respond better to ADT and immunotherapy. By comparing with other molecular signatures, the CRPGS could classify PCa patients into two risk groups well, and the CRPGS was associated with the m6A level, as well as TP53 and SPOP mutation status of PCa patients. In the AHMU-PC cohort, the CRPGS was associated with the advanced pathology stage and Gleason score.

Conclusions

The identified chemokine genes and CRPGS were associated with the prognosis of PCa, which could predict PCa patients’ responses to anti-androgen and immunotherapies.
Molecular subtypes based on Wnt-signaling gene expression predict prognosis and tumor microenvironment in hepatocellular carcinoma
Authors: Xu Weifeng , Nie Caiyun , Lv Huifang , Chen BeiBei , Wang Jianzheng , Wang Saiqi , Zhao Jing , He Yunduan , Chen Xiaobing
Published: October 2022

Based on increasing research evidence, hepatocellular carcinoma (HCC) is heterogeneous, and genetic profiling has led to the identification of multiple subtypes of this disease. To advance our knowledge and the ability to use individualized medicine in the treatment of HCC, it is essential to perform a complete and methodical characterization of various molecular subtypes. The canonical Wnt/β-catenin pathway is an evolutionarily conserved complicated signaling mechanism that plays a role in carcinogenesis and progression of HCC. In this study, we acquired RNA sequencing, somatic mutation, and clinical data from 701 patients from The Cancer Genome Atlas and Gene Expression Omnibus databases and stratified patients into two subgroups: WNT-high and WNT-low. In general, the WNT-high subtype is associated with an immunosuppressive microenvironment, poor prognosis, cancer-related pathways, and a low response to immune checkpoint therapy. We also found that WNT3 is negatively linked to CD8+ T-cell infiltration using multiple immunofluorescence assays. Finally, we developed a WNT-related prognostic model to predict the survival time of patients with HCC. In summary, we developed a new classification scheme for HCC based on Wnt signaling signatures. This classification produced substantial clinical effects, both in terms of assessing patient prognosis and immunotherapy administered to patients with HCC.
Phenotypic spectrum in recessive STING-associated vasculopathy with onset in infancy: Four novel cases and analysis of previously reported cases
Authors: Wan Rensheng , Fänder Johannes , Zakaraia Ia , Lee-Kirsch Min Ae , Wolf Christine , Lucas Nadja , Olfe Lisa Isabel , Hendrich Corinna , Jonigk Danny , Holzinger Dirk , Steindor Mathis , Schmidt Gunnar , Davenport Claudia , Klemann Christian , Schwerk Nicolaus , Griese Matthias , Schlegelberger Brigitte , Stehling Florian , Happle Christine , Auber Bernd , Steinemann Doris , Wetzke Martin , von Hardenberg Sandra
Published: October 2022

Gain-of-function variants in the stimulator of interferon response cGAMP interactor 1 (STING1) gene cause STING-Associated Vasculopathy with onset in Infancy (SAVI). Previously, only heterozygous and mostly de novo STING1 variants have been reported to cause SAVI. Interestingly, one variant that only leads to SAVI when homozygous, namely c.841C>T p.(Arg281Trp), has recently been described. However, there are no entries in public databases regarding an autosomal recessive pattern of inheritance. Here, we report four additional unrelated SAVI patients carrying c.841C>T in homozygous state. All patients had interstitial lung disease and displayed typical interferon activation patterns. Only one child displayed cutaneous vasculitis, while three other patients presented with a relatively mild SAVI phenotype. Steroid and baricitinib treatment had a mitigating effect on the disease phenotype in two cases, but failed to halt disease progression. Heterozygous c.841C>T carriers in our analysis were healthy and showed normal interferon activation. Literature review identified eight additional cases with autosomal recessive SAVI caused by c.841C>T homozygosity. In summary, we present four novel and eight historic cases of autosomal recessive SAVI. We provide comprehensive clinical data and show treatment regimens and clinical responses. To date, SAVI has been listed as an exclusively autosomal dominant inherited trait in relevant databases. With this report, we aim to raise awareness for autosomal recessive inheritance in this rare, severe disease which may aid in early diagnosis and development of optimized treatment strategies.
Severe COVID-19 patients display hyper-activated NK cells and NK cell-platelet aggregates
Authors: Malengier-Devlies Bert , Filtjens Jessica , Ahmadzadeh Kourosh , Boeckx Bram , Vandenhaute Jessica , De Visscher Amber , Bernaerts Eline , Mitera Tania , Jacobs Cato , Vanderbeke Lore , Van Mol Pierre , Van Herck Yannick , Hermans Greet , Meersseman Philippe , Wilmer Alexander , Gouwy Mieke , Garg Abhishek D. , Humblet-Baron Stephanie , De Smet Frederik , Martinod Kimberly , Wauters Els , Proost Paul , Wouters Carine , Leclercq Georges , Lambrechts Diether , Wauters Joost , Matthys Patrick
Published: October 2022

COVID-19 is characterised by a broad spectrum of clinical and pathological features. Natural killer (NK) cells play an important role in innate immune responses to viral infections. Here, we analysed the phenotype and activity of NK cells in the blood of COVID-19 patients using flow cytometry, single-cell RNA-sequencing (scRNA-seq), and a cytotoxic killing assay. In the plasma of patients, we quantified the main cytokines and chemokines. Our cohort comprises COVID-19 patients hospitalised in a low-care ward unit (WARD), patients with severe COVID-19 disease symptoms hospitalised in intensive care units (ICU), and post-COVID-19 patients, who were discharged from hospital six weeks earlier. NK cells from hospitalised COVID-19 patients displayed an activated phenotype with substantial differences between WARD and ICU patients and the timing when samples were taken post-onset of symptoms. While NK cells from COVID-19 patients at an early stage of infection showed increased expression of the cytotoxic molecules perforin and granzyme A and B, NK cells from patients at later stages of COVID-19 presented enhanced levels of IFN-γ and TNF-α which were measuredex vivoin the absence of usualin vitrostimulation. These activated NK cells were phenotyped as CD49a+CD69a+CD107a+cells, and their emergence in patients correlated to the number of neutrophils, and plasma IL-15, a key cytokine in NK cell activation. Despite lower amounts of cytotoxic molecules in NK cells of patients with severe symptoms, majority of COVID-19 patients displayed a normal cytotoxic killing of Raji tumour target cells.In vitrostimulation of patients blood cells by IL-12+IL-18 revealed a defective IFN-γ production in NK cells of ICU patients only, indicative of an exhausted phenotype. ScRNA-seq revealed, predominantly in patients with severe COVID-19 disease symptoms, the emergence of an NK cell subset with a platelet gene signature that we identified by flow and imaging cytometry as aggregates of NK cells with CD42a+CD62P+activated platelets. Post-COVID-19 patients show slow recovery of NK cell frequencies and phenotype. Our study points to substantial changes in NK cell phenotype during COVID-19 disease and forms a basis to explore the contribution of platelet-NK cell aggregates to antiviral immunity against SARS-CoV-2 and disease pathology.
On the role of allergen-specific IgG subclasses for blocking human basophil activation
Authors: Zinkhan Simon , Thoms Franziska , Augusto Gilles , Vogel Monique , Bachmann Martin F.
Published: October 2022

Successful treatment of IgE mediated allergies by allergen-specific immunotherapy (AIT) usually correlates with the induction of allergen-specific IgG4. However, it is not clear whether IgG4 prevents the allergic reaction more efficiently than other IgG subclasses. Here we aimed to compare allergen-specific monoclonal IgG1 and IgG4 antibodies in their capacity to inhibit type I allergic reactions by engaging FcγRIIb. We found that IgG1, which is the dominant subclass induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4 and is comparable at blocking human basophil activation from allergic patients; both by neutralizing the allergen as well as engaging the inhibitory receptor FcγRIIb. Hence, the IgG subclass plays a limited role for the protective efficacy of AIT even if IgG4 is considered the best correlate of protection, most likely simply because it is the dominant subclass induced by classical AITs.
Identification of a six-gene prognostic signature for bladder cancer associated macrophage
Authors: Jiang Yunzhong , Qu Xiaowei , Zhang Mengzhao , Zhang Lu , Yang Tao , Ma Minghai , Jing Minxuan , Zhang Nan , Song Rundong , Zhang Yuanquan , Yang Zezhong , Zhang Yaodong , Pu Yuanchun , Fan Jinhai
Published: October 2022

As major components of the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play an exceedingly complicated role in tumor progression and tumorigenesis. However, few studies have reported the specific TAM gene signature in bladder cancer. Herein, this study focused on developing a TAM-related prognostic model in bladder cancer patients based on The Cancer Genome Atlas (TCGA) data. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key genes related to TAM (M2 macrophage). Gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed the functional categories of the key genes. Simultaneously, we used the Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regressions to establish a TMA-related prognostic model containing six key genes: TBXAS1, GYPC, HPGDS, GAB3, ADORA3, and FOLR2. Subsequently, single-cell sequencing data downloaded from Gene Expression Omnibus (GEO) suggested that the six genes in the prognostic model were expressed in TAM specifically and may be involved in TAM polarization. In summary, our research uncovered six-TAM related genes that may have an effect on risk stratification in bladder cancer patients and could be regarded as potential TAM-related biomarkers.