bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous prediction of multiple physical parameters using gated recurrent neural network: Porosity, water saturation, shale content
Authors: Zhang Jiajia , Liu Zhuofan , Zhang Guangzhi , Yan Bin , Ni Xuebin , Xie Tian
Published: August 2022

Reservoir parameter prediction is of significant value to oil and gas exploration and development. Artificial intelligence models are developing rapidly in reservoir parameter prediction. Unfortunately, current research has focused on multi-input single-output prediction models. Meaning, these models use a large amount of logging or seismic data to predict the petrophysical properties of a single reservoir. Another prominent problem is that most mechanistic learning studies have focused on using logging data (e.g., gamma ray and resistivity) to make predictions of reservoir parameters. Although these studies have yielded promising accuracy, a great shortcoming is the inability to obtain such data in logs by seismic inversion. The value of our research work is to achieve a complete description of the reservoir using the elastic parameters from the seismic inversion. We developed a deep learning method based on gated recurrent neural network (GRNN) suitable for simultaneous prediction of porosity, saturation and shale content in the reservoir. GRNN is based on Gated Recurrent Unit (GRU), which can automatically update and reset the hidden state. The input parameters to the model are compressive wave velocity, shear wave velocity and density. The model is trained to fit nonlinear relationships between input parameters and multiple physical parameters. We employed two wells: one for testing and the other for training. 20% of the data in the training wells were used as the validation set. In preprocessing, we performed z-score whitening on the input data. During the training phase, the model hyperparameters were optimized based on the mean absolute error (MAE) box plots of the validation set. Experiments on the test data show that the model has superior robustness and accuracy compared to the conventional recurrent neural network (RNN). In the GRNN prediction results of the test set, the MAE is 0.4889 and the mean squared error (MSE) is 0.5283. Due to the difference in input parameters, our prediction is weaker than the research method using logging data. However, our proposed method has higher practical value in exploration work.
Development of a Model Predicting the Outcome of In Vitro Fertilization Cycles by a Robust Decision Tree Method
Authors: Fu Kaiyou , Li Yanrui , Lv Houyi , Wu Wei , Song Jianyuan , Xu Jian
Published: August 2022

Introduction

Infertility is a worldwide problem. To evaluate the outcome of in vitro fertilization (IVF) treatment for infertility, many indicators need to be considered and the relation among indicators need to be studied.

Objectives

To construct an IVF predicting model by a robust decision tree method and find important factors and their interrelation.

Methods

IVF and intracytoplasmic sperm injection (ICSI) cycles between January 2010 and December 2020 in a women’s hospital were collected. Comprehensive evaluation and examination of patients, specific therapy strategy and the outcome of treatment were recorded. Variables were selected through the significance of 1-way analysis between the clinical pregnant group and the nonpregnant group and then were discretized. Then, gradient boosting decision tree (GBDT) was used to construct the model to compute the score for predicting the rate of clinical pregnancy.

Result

Thirty-eight variables with significant difference were selected for binning and thirty of them in which the pregnancy rate varied in different categories were chosen to construct the model. The final score computed by model predicted the clinical pregnancy rate well with the Area Under Curve (AUC) value achieving 0.704 and the consistency reaching 98.1%. Number of two-pronuclear embryo (2PN), age of women, AMH level, number of oocytes retrieved and endometrial thickness were important factors related to IVF outcome. Moreover, some interrelations among factors were found from model, which may assist clinicians in making decisions.

Conclusion

This study constructed a model predicting the outcome of IVF cycles through a robust decision tree method and achieved satisfactory prediction performance. Important factors related to IVF outcome and some interrelations among factors were found.
Research progress on the mechanism by which skin macrophage dysfunction mediates chronic inflammatory injury in diabetic skin
Authors: Huang Jiali , Zhang Shili , Ding Xinyi , Li Shuxian , Luo Xiangrong , Cao Ying , Gao Fang , Zou Mengchen
Published: August 2022

Macrophages, the main immune cells in the skin, form an innate immune barrier. Under physiological conditions, skin maintains immune barrier function through macrophage phagocytosis and antigen presentation. Parenchymal and stromal cell regeneration plays an important role in skin injury repair and uses macrophage plasticity to influence and stabilize the skin microenvironment. Diabetic skin lesions are the most common diabetes complication and are involved in the early pathophysiology of diabetic foot. Therefore, studying the initial link in diabetic skin lesions is a research hot spot in the early pathogenesis of diabetic foot. Skin inflammation caused by hyperglycaemia, oxidative stress and other injuries is an important feature, but the specific mechanism is unknown. Recent studies have suggested that chronic inflammatory injury is widely involved in a variety of skin diseases, and whether it plays an important role in diabetic skin lesions is unclear. In this review, current research hotspots were combined with the pathogenesis of diabetic skin lesions and analysed from the perspectives of the physiological function of skin macrophages, the impairment of skin macrophages in diabetes, and the mechanism of chronic inflammatory injury in macrophages to provide a theoretical basis for early screening and evaluation of diabetic foot.
Toll-like receptor signaling pathway triggered by inhibition of serpin A1 stimulates production of inflammatory cytokines by endometrial stromal cells
Authors: Kusama Kazuya , Satoyoshi Ayaka , Azumi Mana , Yoshie Mikihiro , Kojima Junya , Mizuno Yumi , Ono Masanori , Nishi Hirotaka , Kajihara Takeshi , Tamura Kazuhiro
Published: August 2022

Endometriosis is characterized by the presence of inflamed and fibrotic endometrial tissue outside the uterine cavity. Previously, we found decreased SERPINA1 (alpha-1 antitrypsin) expression in endometriosis-like lesions in a mouse model of endometriosis, suggesting that it exacerbated inflammation in these lesions. However, the molecular mechanism(s) by which SERPINA1 affects expression of inflammatory factors and development of endometriotic lesions have not been fully characterized. To investigate the role of intracellular SERPINA1 in endometrial stromal cells (ESCs), we performed RNA sequence analysis using RNA extracted from ESCs in which SERPINA1 was knocked down. The analysis identified several toll-like receptor (TLR)-related factors as being upregulated. Silencing of SERPINA1 increased expression of TLR3 and TLR4 in ESCs, as well as several TLR signaling pathway components, including MYD88, IRAK1/4, interleukin (IL)-1β, and interferon (IFN)-β. TLR3 or TLR4 agonists increased expression of inflammatory factors in SERPINA1-knockdown ESCs, whereas TLR3 or TLR4 inhibitors decreased expression. In addition, treatment with recombinant IL-1β or IFN-β increased expression of MYD88 and inflammatory factors in ESCs. Immunohistochemical analysis of endometriotic tissues showed that TLR3, TLR4, and MYD88 were localized in endometriosis lesions. Taken together, the data suggest that reduced expression of SERPINA1 induces expression of inflammatory factors by ESCs, which in turn are associated with TLR3/4, IL-1β, and IFN-β signaling. Regulation of intracellular SERPINA1 levels in ESCs may be a strategy to inhibit inflammatory responses in endometriotic lesions.
Type 1 diabetes-related autoimmune antibodies in women with gestational diabetes mellitus and the long-term risk for glucose intolerance
Authors: Beunen Kaat , Vercauter Lies , Van Crombrugge Paul , Moyson Carolien , Verhaeghe Johan , Vandeginste Sofie , Verlaenen Hilde , Vercammen Chris , Maes Toon , Dufraimont Els , Roggen Nele , De Block Christophe , Jacquemyn Yves , Mekahli Farah , De Clippel Katrien , Van Den Bruel Annick , Loccufier Anne , Laenen Annouschka , Devlieger Roland , Mathieu Chantal , Benhalima Katrien
Published: August 2022

Aims

To characterize women with gestational diabetes mellitus (GDM) positive for type 1 diabetes-related autoimmune antibodies (T1D-related autoantibodies) in pregnancy and to evaluate their risk for long-term glucose intolerance.

Methods

In a multi-centric prospective cohort study with 1843 women receiving universal screening for GDM with a 75 g oral glucose tolerance test (OGTT), autoantibodies were measured in women with GDM: insulin autoantibodies (IAA), islet cell antibodies (ICA), insulinoma-associated protein-2 antibodies (IA-2A) and glutamic acid decarboxylase antibodies (GADA). Long-term follow-up ( ± 4.6 years after delivery) with a 75 g OGTT and re-measurement of autoantibodies was done in women with a history of GDM and autoantibody positivity in pregnancy.

Results

Of all women with GDM (231), 80.5% (186) received autoantibody measurement at a mean of 26.2 weeks in pregnancy, of which 8.1% (15) had one positive antibody (seven with IAA, two with ICA, four with IA-2A and two with GADA). Characteristics in pregnancy were similar but compared to women without autoantibodies, women with autoantibodies had more often gestational hypertension [33.3% (5) vs. 1.7% (3), p<0.001] and more often neonatal hypoglycemia [40.0% (6) vs. 12.5% (19), p=0.012]. Among 14 of the 15 autoantibody positive women with an early postpartum OGTT, two had impaired fasting glucose (IFG). Of the 12 women with long-term follow-up data, four tested again positive for T1D-related autoantibodies (three positive for IA-2A and one positive for ICA and IAA). Five women were glucose intolerant at the long-term follow-up of which two had IA-2A (one had IFG and one had T1D) and three without autoantibodies. There were no significant differences in long-term characteristics between women with and without autoantibodies postpartum.

Conclusions

Systematic screening for T1D-related autoantibodies in GDM does not seem warranted since the low positivity rate for autoantibodies in pregnancy and postpartum. At 4.6 years postpartum, five out of 12 women were glucose intolerant but only two still had autoantibodies. In women with clinically significant increased autoantibody levels during pregnancy, postpartum autoantibody re-measurement seems useful since the high risk for further increase of autoantibody levels.
Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age
Authors: Patti Giuseppa , Malerba Federica , Calevo Maria Grazia , Schiavone Maurizio , Scaglione Marco , Casalini Emilio , Russo Silvia , Fava Daniela , Bassi Marta , Napoli Flavia , Allegri Anna Elsa Maria , D’Annunzio Giuseppe , Gastaldi Roberto , Maghnie Mohamad , Di Iorgi Natascia
Published: August 2022

Context

Data on pubertal timing in Silver Russell syndrome (SRS) are limited.

Design and methods

Retrospective observational study including twenty-three SRS patients [11p15 loss of methylation, (11p15 LOM, n=10) and maternal uniparental disomy of chromosome 7 (mUPD7, n=13)] and 21 small for gestational age (SGA). Clinical (thelarche in females; testis volume ≥ 4 ml in males; pubarche), BMI SD trend from the age of 5 to 9 years to the time of puberty, biochemical parameters of puberty onset [Luteinizing hormone (LH), 17-β-estradiol, testosterone], and bone age progression were evaluated

Results

Pubertal onset and pubarche occurred significantly earlier in children with SRS than in SGA (p 0.03 and p 0.001, respectively) and clinical signs of puberty onset occurred earlier in mUPD7 than in 11p15LOM group (p 0.003). Five SRS children experienced central precocious puberty and LH, 17-β-estradiol, testosterone were detected earlier in SRS than in SGA (p 0.01; p 0.0001). Bone age delay in SRS children was followed by rapid advancement; the delta between bone age and chronological age in SRS group became significantly higher than in SGA group at the age of 9-11 years (p 0.007). 11p15LOM patients were underweight at the age of 5 years and showed a progressive normalization of BMI that was significantly higher than in mUPD7 (p 0.04) and SGA groups (p 0.03) at puberty onset.

Conclusion

Timing of puberty is affected in SRS and occurred earlier in mUPD7 compared to 11p15LOM. The impact of early puberty on adult height and metabolic status deserves long-term evaluation.
Negative emission power plants: Techno-economic analysis of a biomass-based integrated gasification solid oxide fuel cell/gas turbine system for power, heat, and biochar co-production—part 2
Authors: Jaiganesh N. , Kuo Po-Chih , Champatan Vipin , Gopi Girigan , Kumar R. Ajith , Aravind P.V.
Published: August 2022

In our previous work (Part I), we evaluated the thermodynamic models of the biomass-fed integrated gasification solid oxide fuel cell system with a carbon capture and storage (BIGFC/CCS) unit. In this work (Part II), the techno-economic analysis of the proposed negative emission power plants is carried out. Levelized cost of electricity, net present value (NPV), payback period, internal rate of return (IRR), and levelized cost of negative carbon (LCNC) are the key economic parameters evaluated. The results of a series of sensitivity analysis show the impact of gasification agents and stepwise increase in biochar co-production on the performance of the system. The total overnight cost is estimated to be 6197 $/kW and 5567 $/kW for the air and steam-oxygen gasification BIGFC/CCS systems, respectively. Steam-oxygen gasification is found to be more economically beneficial than air gasification one for all of the cases studied. Economically viable biochar co-production cases are identified to ascertain the influence of capital cost, operating cost, biomass cost, plant capacity factor, and tax. Moreover, the effect of the carbon credit scenario on the economic indicators is also reported. The results show that the most effective economic performance from the steam-oxygen gasification case reported an NPV of 3542 M$, an IRR of 24.2%, and a payback period of 3.3 years, with an LCNC of -322.5$/t of CO2. Compiling the results from Part I and Part II shows that it is easier to achieve negative emission using the steam-oxygen gasification of a BIGFC/CCS system. These results are expected to be helpful for stakeholders in identifying appealing negative emissions power plant projects for near and long-term future investments.
Applications and challenges of porous carbon with different dimensions in supercapacitors—a mini review
Authors: Liu Yong , Chen Hongyu , Li Liqing
Published: August 2022

The rapid development of modern electronic technology is in urgent need of further breakthroughs to actualize high-energy, high-power, and long cycling energy storage equipment. Carbon-based supercapacitors (CSs) are potential high-power devices that can stock electrical energy at the electrode–electrolyte interface rather than by diffusing ions inside electrodes. However, the commercial CSs using active carbon (AC) suffer from restricted energy densities on account of relatively small specific surface area, poor porosity, and low electrochemical activity. In recent years, various tactics have been applied to enhance the electrochemical properties of carbon-based electrode, and fruitful successes have been achieved. This mini review first introduces the concerned charge storage mechanisms of CSs, which is followed by a straightforward summary of the pivotal factors affecting the electrochemical performance. Then, the novel fabrication strategies of porous carbon at different dimensions are exemplified and summarized to prepare large-capacitance electrodes. The current challenges and promising future research for exploiting the state-of-the-art supercapacitors are also discussed.
Experimental investigation of the mechanism of supercritical CO2 interaction with tight sandstone
Authors: Peng Huan , Yang Jian , Peng Junliang , Pu Junhong , Liu Qiang , Su Jun , Liu Jin
Published: August 2022

One of the important technologies for combating global climate change is CCUS (Carbon Capture, Utilization, and Storage), which aims to address the issue of “greenhouse effect” generated by a significant amount of greenhouse gas emissions. Supercritical CO2, a new type of anhydrous fracturing fluid with broad application prospects in low-pressure tight sandstone gas reservoirs, has several advantages over traditional water-based fracturing fluids, including quick flowback, minimal damage to the reservoir, and the ability to realize in-situ storage of greenhouse gases. The tight sandstone cores from the Jinqiu Gas field in the Sichuan Basin were used in an experimental investigation on the interaction mechanism between supercritical CO2 and tight sandstone to examine the viability of supercritical CO2 fracturing with tight sandstone, and analysis of the samples’ post-reaction samples’ mineral composition, microstructure, mass change, and total salinity change. The interaction of tight sandstone with supercritical CO2 results in an increase in quartz content, a decrease in clay mineral content, the formation of new minerals, and partial mineral dissolution on the surface of the sample. Since the degree of mineral dissolution of sandstone samples increases with time, CO2 can be stored in tight sandstone as carbonate minerals. This study evaluates how supercritical CO2 interacts with tight sandstone and can offer a solid theoretical foundation and experimental evidence in favor of CO2in-situ storage in tight sandstone gas reservoir.
Farm-scale water-energy-food-waste nexus analysis for a closed-loop dairy system
Authors: Muell Jordan D. , Mohtar Rabi H. , Kan Eun Sung , Assi Amjad T. , Pappa Valentini
Published: August 2022

Largely due to manure management, intensive livestock production is known to negatively impact air, water, and soil quality. Excessive manure is often applied to soil as fertilizer or stored in lagoon. However, some thermo-chemical methods, such as gasification and pyrolysis, can transform manure from waste into a valuable resource. The closed-loop dairy concept employs these methods to create biochar derived from cow manure for use as a soil amendment and a water filtration medium. This closed-loop concept has the potential to produce syngas and bio-oil for production of electricity, and to reduce excessive nutrients in liquid manure irrigation by filtering manure slurry stored in lagoons. It replaces solid manure with biochar in land applications to further reduce nutrient runoff and increase soil resilience against erosion. In this study, a Water-Energy-Food-Waste nexus-based analysis and resource allocation tool was developed to evaluate the economic, environmental, and social feasibility of the closed-loop dairy system. The tool utilizes several levers to simulate a user-specified dairy operation, such as number of livestock, acres farmed, quantity of effluent irrigation, distribution of manure and biochar products, and type of biomass conversions. Financial estimates from central Texas in 2018 were used to evaluate the profitability of these practices against the costs of a dairy and hay operation. The study showed that the closed-loop dairy system, while case dependent, could be profitable and, based on operational costs, a small dairy of approximately 200 cows could break even. Results also indicate that the benefits of biomass conversions to produce energy byproducts should increase with scale. This study can help many dairy farms that are considering the economic and environmental sustainability of the industry, which has been under scrutiny.
Modelling the Significance of Value-Belief-Norm Theory in Predicting Solid Waste Management Intention and Behavior
Authors: Al Mamun Abdullah , Hayat Naeem , Masud Muhammad Mehedi , Makhbul Zafir Khan Mohamed , Jannat Taslima , Salleh Mohd Fairuz Md.
Published: August 2022

Urbanization and rapid use of natural resources worldwide led to a massive increase in the solid waste produced daily. The processing of solid waste is significantly lower than solid waste production. Sustainable solid waste processing requires collective efforts and a change in the general public mindset to reduce and effectively process solid waste. The current work aims to interpret the intention and behavior to mitigate the climatic issue of solid waste management among Malaysian adults under the value-belief-norm framework, which was extended with social norms. This study adopted a cross-sectional design and collected quantitative data through an online survey from 1571 household heads in Malaysia. Data were analyzed with the partial least square-structure equation modelling (PLS-SEM) technique given that the data were non-normal. Other relevant common method bias analyses were conducted to evaluate the influence of common method variance. The analyses demonstrated that the biospheric and altruistic values were essential for promoting the ecological worldview among the individuals. Following the VBN framework, the ecological worldview promotes the awareness of consequences, which facilitates the ascription of responsibility to perform corrective actions for the climate. Moreover, ecological worldview, awareness of consequences, and ascription of responsibility result in the personal norms towards the pro-climate behaviors. The social and personal norms effectively nurture the intention to engage in solid waste management practices. The VBN framework provides a guideline to promote the intention and behavior to adopt effective solid waste management practices, while education and public policy could harness public beliefs and norms to engage in pro-climatic behaviors.
Abrupt emission reduction during COVID-19 intensified the spring 2020 rainfall over India
Authors: Asutosh A. , Fadnavis S. , Chavan Prashant , Sabin T. P. , Müller Rolf
Published: August 2022

The high level of aerosol pollution in South Asia has a measurable impact on clouds, radiation, and precipitation. Here, exploring multiple observational data sets and simulations of the state-of-the-art ECHAM6-HAMMOZ chemistry-climate model, we report that the reduction in anthropogenic emissions during the COVID-19 lockdown period has enhanced precipitation by 5–25% over India. This precipitation enhancement is the result of the combined effect of an enhancement in cloud cover, a reduction in aerosol induced cloud invigoration and dynamical changes. We observed that the increase in cloud cover was associated with a reduction in cloud base height and an increase in the effective radius of cloud particles which led to an increase in cloud water content. In response to sudden emission reduction, an anomalous northward moisture transport was observed adding convection and precipitation over the Indian region. Importantly, we show that there is an advantage of anthropogenic pollution reduction for water availability in addition to benefits of air quality, human health, and crop yield.
Mercury biomagnification in a coastal Louisiana food web following the 2010 Deepwater Horizon oil spill
Authors: Lamb Katelyn J. , Midway Stephen R. , Brasso Rebecka L. , López-Duarte Paola C. , Kimball Matthew E. , Polito Michael J.
Published: August 2022

The estuarine environments surrounding coastal Louisiana create favorable conditions for microbially mediated mercury (Hg) methylation and subsequent bioaccumulation by biota. In 2010, the Deepwater Horizon (DWH) oil spill released large amounts of oil which, despite having low Hg concentrations, had the potential to influence methylmercury (MeHg) bioavailability in the coastal zone. To explore this possibility, we assessed Hg concentrations and trophodynamics in the coastal Louisiana food web prior to and immediately following the DWH oil spill and compared these metrics with an adjacent coastal ecosystem in the northern Gulf of Mexico. We found no differences in MeHg concentrations between oysters collected in years prior to the spill (1986–2007) and those collected during or in the months immediately after the spill (May to December 2010). When comparing tissue MeHg concentrations and carbon and nitrogen stable isotope values across 13 species of bivalves, shrimp, crabs, fishes, and birds we found evidence of significant biomagnification within the coastal Louisiana food web driven by species’ trophic position and their use of differing basal carbon sources. In addition, Hg trophodynamics also differed between two adjacent coastal ecosystems, post-spill coastal Louisiana (2010) and pre-spill coastal Alabama (2008–2009). While there was a higher trophic magnification factor in coastal Louisiana relative to coastal Alabama, food web baseline MeHg concentrations were higher in coastal Alabama. The high degree of biomagnification in coastal Louisiana, and significant regional variation, underscores the need to monitor Hg trophodynamics over space and time to better evaluate the short and long-term ecological consequences of events like the DWH oil spill.
Vegetation and vantage point influence visibility across diverse ecosystems: Implications for animal ecology
Authors: Stein Rachel M. , Lecigne Bastien , Eitel Jan U. H. , Johnson Timothy R. , McGowan Craig , Rachlow Janet L.
Published: August 2022

Visual information can influence animal behavior and habitat use in diverse ways. Visibility is the property that relates 3D habitat structure to accessibility of visual information. Despite the importance of visibility in animal ecology, this property remains largely unstudied. Our objective was to assess how habitat structure from diverse environments and animal position within that structure can influence visibility. We gathered terrestrial lidar data (1 cm at 10 m) in four ecosystems (forest, shrub-steppe, prairie, and desert) to characterize viewsheds (i.e., estimates of visibility based on spatially explicit sightlines) from multiple vantage points. Both ecosystem-specific structure and animal position influenced potential viewsheds. Generally, as height of the vantage point above the ground increased, viewshed extent also increased, but the relationships were not linear. In low-structure ecosystems (prairie, shrub-steppe, and desert), variability in viewsheds decreased as vantage points increased to heights above the vegetation canopy. In the forest, however, variation in viewsheds was highest at intermediate heights, and markedly lower at the lowest and highest vantage points. These patterns are likely linked to the amount, heterogeneity, and distribution of vegetation structure occluding sightlines. Our work is the first to apply a new method that can be used to estimate viewshed properties relevant to animals (i.e., viewshed extent and variability). We demonstrate that these properties differ across terrestrial landscapes in complex ways that likely influence many facets of animal ecology and behavior.
Genome-wide association mapping for root traits associated with frost tolerance in faba beans using KASP-SNP markers
Authors: Sallam Ahmed , Moursi Yasser S. , Martsch Regina , Eltaher Shamseldeen
Published: August 2022

Frost is an abiotic stress factor that threatens plant development and crop productivity not only in cold regions but also in temperate zones. Roots play an important role in plant growth during frost stress. Therefore, variation in root characteristics could be studied to improve frost tolerance in winter faba bean. The present study aimed to identify the genomic regions that control frost tolerance in a winter faba bean population by focusing on root-related traits. A set of 185 genotypes were tested for frost tolerance under artificial frost growth conditions at −16°C, −18°C, and −19°C in a growth chamber. Frost stress reduced the root-related parameters in all genotypes, with a wide variation among genotypes. A genome-wide association study identified nine novel single-nucleotide polymorphisms that are associated with the root-related traits. The most frost-tolerant genotypes were identified; two genotypes, S_028 and S_220, exhibited remarkable performance under frost stress. Moreover, they harbored all four of the alleles favorable for frost tolerance. Remarkably, two markers showed genetic pleiotropic effects with positive allele effects on root fresh matter and root dry matter. Thus, both genotypes can be implemented in a breeding program to provide the alleles for healthier roots under frost conditions to develop more frost-tolerant varieties, and the two markers can be used to screen large collections to select for frost tolerance. These results may provide novel insights for improving frost tolerance in faba beans and in other legume crops.
Evolutionary selection identifies critical immune-relevant genes in lung cancer subtypes
Authors: Luddy Kimberly A. , Teer Jamie K. , Freischel Audrey , O’Farrelly Cliona , Gatenby Robert
Published: August 2022

In an evolving population, proliferation is dependent on fitness so that a numerically dominant population typically possesses the most well adapted phenotype. In contrast, the evolutionary “losers” typically disappear from the population so that their genetic record is lost. Historically, cancer research has focused on observed genetic mutations in the dominant tumor cell populations which presumably increase fitness. Negative selection, i.e., removal of deleterious mutations from a population, is not observable but can provide critical information regarding genes involved in essential cellular processes. Similar to immunoediting, “evolutionary triage” eliminates mutations in tumor cells that increase susceptibility to the host immune response while mutations that shield them from immune attack increase proliferation and are readily observable (e.g., B2M mutations). These dynamics permit an “inverse problem” analysis linking the fitness consequences of a mutation to its prevalence in a tumor cohort. This is evident in “driver mutations” but, equally important, can identify essential genes in which mutations are seen significantly less than expected by chance. Here we utilized this new approach to investigate evolutionary triage in immune-related genes from TCGA lung adenocarcinoma cohorts. Negative selection differs between the two cohorts and is observed in endoplasmic reticulum aminopeptidase genes, ERAP1 and ERAP2 genes, and DNAM-1/TIGIT ligands. Targeting genes or molecular pathways under positive or negative evolutionary selection may permit new treatment options and increase the efficacy of current immunotherapy.
Nine-gene signature and nomogram for predicting survival in patients with head and neck squamous cell carcinoma
Authors: Yang Fan , Zhou Liu-qing , Yang Hui-wen , Wang Yan-jun
Published: August 2022

Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients’ prognosis and provide guidance to the personalized treatment.

Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan–Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results.

Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades.

Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.
Elevated insulin-like growth factor 2 mRNA binding protein 1 levels predict a poor prognosis in patients with breast carcinoma using an integrated multi-omics data analysis
Authors: Li Shiqi , Jiang Meixiu
Published: August 2022

Background: Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) controls the cytoplasmic fate of certain mRNAs and is hypothesized to predict a poor patient prognosis in several malignant tumors. However, the prognostic relevance of IGF2BP1 in breast cancer remains debatable.

Methods: We interrogated large publicly available datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and cBioportal databases to analyze the genetic alterations in the expression levels of IGF2BP1 in patients with invasive breast carcinoma (BRCA), and to discern the prognostic value of IGF2BP1 in BRCA. We applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genome (KEGG), and gene set enrichment analysis (GSEA) to uncover a functional association between IGF2BP1 and BRCA using differentially expressed genes (DEGs), and we screened genes and proteins related to BRCA.

Results: We determined that both genetic alterations in IGF2BP1 (approximately 10%) and an increase in IGF2BP1 mRNA levels were related to certain cancer subtypes and an unfavorable prognosis in BRCA patients, and we then established an OS nomogram upon our multivariate regression model. The DEGs and IGF2BP1-correlated genes/proteins that implied the involvement of cornification, keratinization, drug/xenobiotic metabolism by cytochrome P450, chemical carcinogenesis, cell interactions, and cell adhesion to the extracellular matrix (ECM) pathways with respect to the prognostic relevance of IGF2BP1.

Conclusion: In summary, our results indicated that both genetic alterations in IGF2BP1 and increased levels of IGF2BP1 mRNA and protein predict a poor patient prognosis in BRCA patients.
Gonadal bacterial community composition is associated with sex-specific differences in swamp eels (Monopterus albus)
Authors: Meng Kaifeng , Lin Xing , Liu Hairong , Chen Huijie , Liu Fei , Xu Zhen , Sun Yonghua , Luo Daji
Published: August 2022

Organisms are colonized by microorganism communities and play a pivotal role in host function by influencing physiology and development. In mammals, bacterial community may alter gonadal maturation and drive sex-specific differences in gene expression and metabolism. However, bacterial microbiota diversity in the gonads of early vertebrates has not been fully elucidated. Here, we focused on the swamp eel (Monopterus albus), which naturally undergoes sex reversal, and systematically analyzed the bacterial microbiota profiles between females and males using 16S rRNA gene sequences. Specifically, the microbial abundance and community diversity of gonads in males were higher than in females. Although Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were characterized as the dominating phyla in ovary and testis, the relative abundance of Firmicutes was significantly higher in males than females. Detailed analysis of the microbial community revealed that Bacilli were the dominant bacteria in ovaries and Clostridium in testes of M. albus. More importantly, we proposed that differences in the microbial composition and distribution between ovaries and testes may be linked to functional categories in M. albus, especially metabolism. These findings represent a unique resource of bacterial community in gonads to facilitate future research about the mechanism of how microbiota influence sex-specific differences and sex reversal in vertebrates.
Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies
Authors: Powell Abigail E. , Xu Duo , Roth Gillie A. , Zhang Kaiming , Chiu Wah , Appel Eric A. , Kim Peter S.
Published: August 2022

Ebola virus (EBOV), a member of the Filoviridae family of viruses and a causative agent of Ebola Virus Disease (EVD), is a highly pathogenic virus that has caused over twenty outbreaks in Central and West Africa since its formal discovery in 1976. The only FDA-licensed vaccine against Ebola virus, rVSV-ZEBOV-GP (Ervebo®), is efficacious against infection following just one dose. However, since this vaccine contains a replicating virus, it requires ultra-low temperature storage which imparts considerable logistical challenges for distribution and access. Additional vaccine candidates could provide expanded protection to mitigate current and future outbreaks. Here, we designed and characterized two multimeric protein nanoparticle subunit vaccines displaying 8 or 20 copies of GPΔmucin, a truncated form of the EBOV surface protein GP. Single-dose immunization of mice with GPΔmucin nanoparticles revealed that neutralizing antibody levels were roughly equivalent to those observed in mice immunized with non-multimerized GPΔmucin trimers. These results suggest that some protein subunit antigens do not elicit enhanced antibody responses when displayed on multivalent scaffolds and can inform next-generation design of stable Ebola virus vaccine candidates.
C5a elevation in convalescents from severe COVID-19 is not associated with early complement activation markers C3bBbP or C4d
Authors: Kowalska Daria , Kuźniewska Alicja , Senent Yaiza , Tavira Beatriz , Inogés Susana , López-Díaz de Cerio Ascensión , Pio Ruben , Okrój Marcin , Yuste José Ramón
Published: August 2022

Numerous publications have underlined the link between complement C5a and the clinical course of COVID-19. We previously reported that levels of C5a remain high in the group of severely ill patients up to 90 days after hospital discharge. We have now evaluated which complement pathway fuels the elevated levels of C5a during hospitalization and follow-up. The alternative pathway (AP) activation marker C3bBbP and the soluble fraction of C4d, a footprint of the classical/lectin (CP/LP) pathway, were assessed by immunoenzymatic assay in a total of 188 serial samples from 49 patients infected with SARS-CoV-2. Unlike C5a, neither C3bBbP nor C4d readouts rose proportionally to the severity of the disease. Detailed correlation analyses in hospitalization and follow-up samples collected from patients of different disease severity showed significant positive correlations of AP and CP/LP markers with C5a in certain groups, except for the follow-up samples of the patients who suffered from highly severe COVID-19 and presented the highest C5a readouts. In conclusion, there is not a clear link between persistently high levels of C5a after hospital discharge and markers of upstream complement activation, suggesting the existence of a non-canonical source of C5a in patients with a severe course of COVID-19.
Immunomodulatory effects of the Bifidobacterium longum BL-10 on lipopolysaccharide-induced intestinal mucosal immune injury
Authors: Dong Jiahuan , Ping Lijun , Cao Ting , Sun Lenan , Liu Deyu , Wang Song , Huo Guicheng , Li Bailiang
Published: August 2022

The intestine is the largest digestive and immune organ in the human body, with an intact intestinal mucosal barrier. Bifidobacterium longum is the specific gut commensals colonized in the human gut for boosting intestinal immunity to defend against intestinal mucosal immune injury. In the LPS-induced intestinal injury model, the Bifidobacterium longum BL-10 was suggested to boost the intestinal immune. Detailly, compared with the LPS-induced mice, the BL10 group significantly reduced intestine (jejunum, ileum, and colon) tissue injury, pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-17, IL-22, and IL-12) levels and myeloperoxidase activities. Moreover, the B. longum BL-10 significantly increased the number of immunocytes (CD4+ T cells, IgA plasma cells) and the expression of tight junction protein (Claudin1 and Occludin). B. longum BL-10 regulated the body’s immune function by regulating the Th1/Th2 and Th17/Treg balance, which showed a greater impact on the Th1/Th2 balance. Moreover, the results also showed that B. longum BL-10 significantly down-regulated the intestinal protein expression of TLR4, p-IκB, and NF-κB p65. The B. longum BL-10 increased the relative abundance of the genera, including Lachnospiraceae_NK4A136_group and Clostridia_UCG-014, which were related to declining the levels of intestinal injury. Overall, these results indicated that the B. longum BL-10 had great functionality in reducing LPS-induced intestinal mucosal immune injury.
Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma
Authors: Gao Qiang , Luo Jing , Pan Jingjing , Zhang Longxiao , Song Dengpan , Zhang Mingchu , Xu Dingkang , Guo Fuyou
Published: August 2022

Craniopharyngiomas (CPs) are histologically benign tumors located in the sellar–suprasellar region. Although the transcriptome development in recent years have deepened our knowledge to the tumorigenesis process of adamantinomatous craniopharyngioma (ACP), the peritumoral immune infiltration of tumor is still not well understood. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify different gene modules based on clinical characteristics and gene expression, and then, the protein–protein interaction (PPI) network with the Cytohubba plug-in were performed to screen pivotal genes. In addition, immune cell infiltration (ICI) analysis was used to evaluate the immune microenvironment of ACP patients. In total, 8,568 differential expression genes were identified based on our datasets and two microarray profiles from the public database. The functional enrichment analysis revealed that upregulated genes were mainly enriched in immune-related pathways while downregulated genes were shown in the hormone and transduction of signaling pathways. The WGCNA investigated the most relevant modules, and 1,858 hub genes was detected, from which the PPI network identified 14 pivotal genes, and the Hypoxia-inducible factor 1-alpha (HIF-1α) pathway including four critical genes may be involved in the development of ACP. Moreover, naïve CD4+ and CD8+ T cells were decreased while specific subtypes of T cells were significantly increased in ACP patients according to ICI analysis. Validation by immunofluorescence staining revealed a higher expression of HIF-1α in ACP (ACP vs. control) and adult-subtype (adult vs. children), suggesting a possible state of immune system activation. Notably, children with low HIF-1α scores were related to the hypothalamus involvement and hydrocephalus symptoms. In this study, we successfully identified HIF-1α as a key role in the tumorigenesis and development of ACP through comprehensive integrated analyses and systematically investigated the potential relationship with immune cells in ACP. The results may provide valuable resources for understanding the underlying mechanisms of ACP and strengthen HIF-1α as a potential immunotherapeutic target in clinical application.
Robust pyroptosis risk score guides the treatment options and predicts the prognosis of bladder carcinoma
Authors: Deng Dingshan , Liu Fenglian , Liu Zhi , Wu Zuowei , He Yunbo , Zhang ChunYu , Zu Xiongbin , Ou Zhenyu , Wang Yongjie
Published: August 2022

Background

Bladder carcinoma (BLCA) is a heterogeneous disease that makes it difficult to achieve proper individual treatment and predict prognosis. This study aimed to develop a risk score from a new perspective of pyroptosis and guide accurate treatment and prognosis prediction for BLCA.

Methods

The TCGA-BLCA cohort data were downloaded from The Cancer Genome Atlas database. Two external validation cohorts were collected from the Gene Expression Omnibus. Another independent validation cohort (the Xiangya cohort) was recruited from our hospital. The least absolute shrinkage and selector operation (LASSO) algorithm and Cox regression models were used to establish the pyroptosis risk score. Thereafter, we correlated the pyroptosis risk score with prognosis, tumor microenvironment (TME) immune hallmarks, and multiple treatments, including anticancer immunotherapy, chemotherapy, radiotherapy, and targeted therapy.

Results

The pyroptosis risk score was an independent prognostic predictor of BLCA. We found that the activities of multiple steps of the anticancer immune response cycle, such as the release of cancer cell antigens, CD8 T cell recruitment, and NK cell recruitment, were significantly higher in the high-risk score group than in the low-risk score group. In addition, the infiltration levels of the corresponding tumor-infiltrating immune cells (TIICs), such as CD8 T cells and NK cells, were positively correlated with the pyroptosis risk score. Thus, BLCA with a high-risk score may be associated with inflamed phenotypes. Simultaneously, the expression of multiple immune checkpoints (such as PD-L1, CTLA-4, and PD-1) and enrichment scores of gene signatures positively correlated with immunotherapy response were positively correlated with the pyroptosis risk score. Therefore, patients with a high pyroptosis risk score may be more sensitive to immunotherapy. In addition, patients with high pyroptosis risk scores may be more sensitive to chemotherapeutic drugs, such as cisplatin, docetaxel, and paclitaxel. In addition, the pyroptosis risk score accurately predicted the molecular subtypes of BLCA, which were cross-validated in several independent systems.

Conclusions

This study developed and validated a robust pyroptosis risk score that can predict the clinical outcomes and TME immune phenotypes of BLCA. In summary, the pyroptosis risk score helps drive precision therapy in patients with BLCA.