bluuebunny/crossref_metadata_2025 huggingface dataset:
Using of modern foreign experience of communications in the system of public administration
Authors: Malinovska O.
Published: August 2022

The article summarizes the results of research on the use of modern foreign communications experience in the public administration system. It was determined that the basis of communication between the authorities and society is based on the synthesis of the interaction of these two opponents, which has recently been formed precisely through social networks, as a result — electronic governance. It is important not to investigate the significance of communication at the current stage, because communication links are traced in many spheres of life. The study of communication is important in various sciences, including public administration, economics, political science, law, sociology, and others. It is substantiated that the effectiveness of communication between authorities is largely determined by feedback mechanisms between citizens and authorities. Feedback in the public administration system is the influence of the results of the functioning of the public administration system on the nature of this functioning. It was determined that in the system of public administration it seems possible to distinguish two types of feedback: object and subject. Object feedback reflects the level, depth, and adequacy of perception by objects of management of the management influences of the subject of state administration. It has been proven that the main trends in the modernization of public administration in foreign countries are: the use of advanced information and communication technologies in the field of public administration; increasing control over the activities of state authorities; improvement of the mechanism.
ARTIFICIAL INTELLIGENCE IN MARKETING
Authors: Sakib S M Nazmuz
Published: August 2022

Artificial Intelligence is the computer industry that focuses on devising and developing computer systems that replicate features of human activities to indicate leveled rudimentary brainpower (Škavić, 2019). “According to John McCarthy, it is the Science and Methodology of Creating Engine Understanding" (Dick, 2019). On the other hand, marketing can be defined as a management process involving delivering goods and services to customers. It is founded on business strategy from the perspective of client needs and satisfaction as a philosophy. Artificial intelligence is an intersection point among disciplines such as computer science, cognitive science, philosophy, neuroscience, linguistically, and engineering scientists, aiming at replicating intelligence comprising of factors that supports reasoning, knowledge acquisition, and response to environmental changes. Artificial intelligence is usually applied to special-purpose machines or computers.
System dynamics modeling for traumatic brain injury: Mini-review of applications
Authors: Kenzie Erin S. , Parks Elle L. , Carney Nancy , Wakeland Wayne
Published: August 2022

Traumatic brain injury (TBI) is a highly complex phenomenon involving a cascade of disruptions across biomechanical, neurochemical, neurological, cognitive, emotional, and social systems. Researchers and clinicians urgently need a rigorous conceptualization of brain injury that encompasses nonlinear and mutually causal relations among the factors involved, as well as sources of individual variation in recovery trajectories. System dynamics, an approach from systems science, has been used for decades in fields such as management and ecology to model nonlinear feedback dynamics in complex systems. In this mini-review, we summarize some recent uses of this approach to better understand acute injury mechanisms, recovery dynamics, and care delivery for TBI. We conclude that diagram-based approaches like causal-loop diagramming have the potential to support the development of a shared paradigm of TBI that incorporates social support aspects of recovery. When developed using adequate data from large-scale studies, simulation modeling presents opportunities for improving individualized treatment and care delivery.
Could building replacements significantly contribute to seismic vulnerability mitigation at urban scale? Case studies of two typical swiss cities
Authors: Lestuzzi Pierino
Published: August 2022

This paper contains an investigation on the potential decrease of seismic vulnerability related to building replacements for the cities of Sion and Martigny in Switzerland. Those two cities were identified for the present research based on the accuracy of the corresponding available information. Seismic assessment at urban scale was recently achieved for both cities and new buildings are systematically indexed according to the construction regulation of the canton of Wallis (Valais). Sion and Martigny belong to the largest cities of the canton of Wallis and this region is characterized by the highest seismicity within Switzerland. The investigation focuses on a 4-year period between 2016 and 2019. Cases for which an existing building is demolished and replaced by a new one were identified and checked. Those cases do not represent general practice. The majority of new buildings are built on free land. Consequently, the building replacement rate is too low to lead to a significant decrease of the seismic vulnerability at urban scale. In addition to the systematic appropriate seismic design of new buildings, retrofitting of existing buildings therefore remains the adequate strategy for seismic vulnerability mitigation. In case of replacement, low-rise buildings are generally replaced by mid-rise buildings. Moreover, unreinforced masonry buildings are usually replaced by reinforced concrete shear-wall buildings. This slightly impacts the building stock distributions but the seismic vulnerability is not significantly changed, since the demolished buildings are not the most vulnerable ones. Nevertheless, few obvious isolated vulnerability decreases occurred with respect to the demolition of soft-story buildings for instance. By contrast, seismic vulnerability may also be increased in the case where a new building is built against an existing one with a different story level and without an adequate seismic separation joint.
The regulation of the cell wall by glycosylphosphatidylinositol-anchored proteins in Arabidopsis
Authors: Zhou Ke
Published: August 2022

A polysaccharides-based cell wall covers the plant cell, shaping it and protecting it from the harsh environment. Cellulose microfibrils constitute the cell wall backbone and are embedded in a matrix of pectic and hemicellulosic polysaccharides and glycoproteins. Various environmental and developmental cues can regulate the plant cell wall, and diverse glycosylphosphatidylinositol (GPI)-anchored proteins participate in these regulations. GPI is a common lipid modification on eukaryotic proteins, which covalently tethers the proteins to the membrane lipid bilayer. Catalyzed by a series of enzymic complexes, protein precursors are post-translationally modified at their hydrophobic carboxyl-terminus in the endomembrane system and anchored to the lipid bilayer through an oligosaccharidic GPI modification. Ultimately, mature proteins reach the plasma membrane via the secretory pathway facing toward the apoplast and cell wall in plants. In Arabidopsis, more than three hundred GPI-anchored proteins (GPI-APs) have been predicted, and many are reported to be involved in diverse regulations of the cell wall. In this review, we summarize GPI-APs involved in cell wall regulation. GPI-APs are proposed to act as structural components of the cell wall, organize cellulose microfibrils at the cell surface, and during cell wall integrity signaling transduction. Besides regulating protein trafficking, the GPI modification is potentially governed by a GPI shedding system that cleaves and releases the GPI-anchored proteins from the plasma membrane into the cell wall.
Virtual spherical-shaped multicellular platform for simulating the morphogenetic processes of spider-like body axis formation
Authors: Fujiwara Motohiro , Akiyama-Oda Yasuko , Oda Hiroki
Published: August 2022

Remodeling of multicellular architecture is a critical developmental process for shaping the axis of a bilaterally symmetric animal body and involves coordinated cell–cell interactions and cell rearrangement. In arthropods, the early embryonic process that leads to the segmented body axis varies at the cellular and molecular levels depending on the species. Developmental studies using insect and spider model species have provided specific examples of these diversified mechanisms that regulate axis formation and segmentation in arthropod embryos. However, there are few theoretical models for how diversity in the early embryonic process occurred during evolution, in part because of a limited computational infrastructure. We developed a virtual spherical-shaped multicellular platform to reproduce body axis-forming processes. Each virtual cell behaves according to the cell vertex model, with the computational program organized in a hierarchical order from cells and tissues to whole embryos. Using an initial set of two different mechanical states for cell differentiation and global directional signals that are linked to the planar polarity of each cell, the virtual cell assembly exhibited morphogenetic processes similar to those observed in spider embryos. We found that the development of an elongating body axis is achieved through implementation of an interactive cell polarity parameter associated with edge tension at the cell–cell adhesion interface, with no local control of the cell division rate and direction. We also showed that modifying the settings can cause variation in morphogenetic processes. This platform also can embed a gene network that generates waves of gene expression in a virtual dynamic multicellular field. This study provides a computational platform for testing the development and evolution of animal body patterns.
Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity
Authors: Mauch Renan Marrichi , Jensen Peter Østrup , Qvist Tavs , Kolpen Mette , Moser Claus , Pressler Tacjana , Nolasco da Silva Marcos Tadeu , Høiby Niels ,   The Copenhagen Study Group on Mycobacterial Infections in Cystic Fibrosis
Published: August 2022

Background

We aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels.

Methods

In this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood.

Results

All CF/MABSC patients had increased CD3+ and CD19+ lymphoblast formation upon PBMC stimulation with MABSC lysate. There was a higher rate of CD3+ than CD19+ lymphoblasts, predominance of CD4+ over CD8+ lymphoblasts, IFN-γ, TNF-α and IL-2 production, low production of the Th17-associated IL-17, and discrete or no production of Th2/B cell-associated cytokines soluble CD40 ligand (CD40L), IL-4 and IL-5, indicating a Th1-dominated phenotype and infection restricted to the lungs. A similar pattern was seen in C/BCG+ controls, and CF/MAC patients, pointing to cross-reactivity. MABSC-IgG levels were higher in CF/MABSC patients than in both control groups, but not CF/NTM- patients, most of whom also had CD3+ and/or CD19+ lymphoblast formation upon PBMC stimulation, indicating previous exposure, subclinical or latent infection with MABSC or other NTM.

Conclusion

The anti-MABSC immune response is Th1-skewed and underlines the cross-reactivity in the anti-mycobacterial immune response. The results, together with published clinical observations, indicate that BCG vaccination may cross-react against NTM in CF patients, and this should be investigated. Due to cross-reactivity, it would also be interesting to investigate whether a combination of MABSC-induced cytokine production by blood cells and anti-MABSC IgG measurement can be useful for identifying latent or subclinical infection both with MABSC and other NTM in CF patients.
Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis
Authors: Zhou Xiaoying , Jin Shengchun , Pan Jingyi , Lin Qingyi , Yang Shaopeng , Ambe Peter C. , Basharat Zarrin , Zimmer Vincent , Wang Wei , Hong Wandong
Published: August 2022

Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than a century. With additional studies into the pathogenesis of AP, new mechanisms have been explored. Among them, the role of immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential role in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach great importance to the immune defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, and modulate inflammation. In this review, we discuss the latest advances in understanding the pathological role of DAMPs and NETs in AP and shed light on the flexible crosstalk between these vital inflammatory mediators. We, then highlight the potentially promising treatment for AP targeting DAMPs and NETs, with a focus on novel insights into the mechanism, diagnosis, and management of AP.
Platelet function changes in patients undergoing endovascular aortic aneurysm repair: Review of the literature
Authors: Burban Anna , Idzik Aleksandra , Gelo Agata , Filipiak Krzysztof J. , Jakimowicz Tomasz , Jama Katarzyna , Grabowski Marcin , Gasecka Aleksandra , Siniarski Aleksander
Published: August 2022

Patients with abdominal aortic aneurysm (AAA) have a higher risk of cardiovascular (CV) events, which seems to be associated with disturbed platelet (PLT) function. Endovascular aneurysm repair (EVAR) is an emerging, less-invasive treatment alternative to surgical AAA repair. Both platelet function abnormalities in patients with AAA and the effect of EVAR on platelet function are poorly understood. In this review, we aim to fill the gap regarding the effect of EVAR on PLT function in AAA patients by discussing PLT function disturbances in patients with AAA, PLT function changes after EVAR, evidence from clinical studies regarding PLT function before and after EVAR, and antiplatelet or and antithrombotic treatment in patients undergoing EVAR. The goal of our review is to summarize the contemporary knowledge and initiate further studies to better understand PLT function changes in patients undergoing EVAR, optimize the pharmacotherapy before and after EVAR and further improve outcomes in this group of patients.
Challenges and innovation: Disease modeling using human-induced pluripotent stem cell-derived cardiomyocytes
Authors: Reilly Louise , Munawar Saba , Zhang Jianhua , Crone Wendy C. , Eckhardt Lee L.
Published: August 2022

Disease modeling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has both challenges and promise. While patient-derived iPSC-CMs provide a unique opportunity for disease modeling with isogenic cells, the challenge is that these cells still demonstrate distinct properties which make it functionally less akin to adult cardiomyocytes. In response to this challenge, numerous innovations in differentiation and modification of hiPSC-CMs and culture techniques have been developed. Here, we provide a focused commentary on hiPSC-CMs for use in disease modeling, the progress made in generating electrically and metabolically mature hiPSC-CMs and enabling investigative platforms. The solutions are bringing us closer to the promise of modeling heart disease using human cells in vitro.
Energy fluxes, mass balance, and climate sensitivity of the Sutri Dhaka Glacier in the western Himalaya
Authors: Oulkar Sunil N. , Thamban Meloth , Sharma Parmanand , Pratap Bhanu , Singh Ajit T. , Patel Lavkush Kumar , Pramanik Ankit , Ravichandran M.
Published: August 2022

Various regional climatic factors influence glacier mass balance and thus control the water budget of the Himalayan rivers. However, the scarcity of observational data hinders a detailed understanding of the processes governing glacier mass balances in the Himalaya. Here we analyze the mass balance of the Sutri Dhaka Glacier, a debris-free glacier in the Chandra basin (western Himalaya) combining field observations and a physically based model to understand the drivers of mass balance variability. The modeled energy flux showed that net shortwave radiation contributed 56% to the total surface energy fluxes, followed by net longwave radiation (27%), sensible heat (8%), latent heat (5%), and ground heat flux (4%). However, over the ablation zone, inward fluxes account for most of the total heat flux, resulting in strong summertime melting. The model estimated glacier mass balance was −1.09 ± 0.31 and −0.62 ± 0.19 m w.e. during 2015/16 and 2016/17, which matches well with the in situ glaciological mass balance of −1.16 ± 0.33 and −0.67 ± 0.33 m w.e., respectively. A sensitivity analysis demonstrates that the mass balance of the glacier is affected by both air temperature (−0.21 m w.e. a−1 °C−1) and precipitation (0.19 m w.e. a−1 (10%)−1) changes. Our study suggests that, the mass balance of the Sutri Dhaka Glacier is less sensitive to changes in the partitioning of precipitation into snow and rain because the majority of precipitation falls as snow during the winter when the temperature is well below 0°C.
"Double Frozen Transfer" Could Influence the Perinatal and Children's Growth: A Nested Case-Control Study of 6705 Live Birth Cycles
Authors: Gao Jie , Zhang Yiyuan , Cui Linlin , Zhang Tao , Wu Bingjie , Gao Shanshan , Chen Zi-Jiang
Published: August 2022

Objective

This study aims to evaluate neonatal and children growth outcomes of cryotransfer of embryos developed from frozen gametes [double frozen transfer (DFT)].

Methods

This nested case-control study included 6,705 women who had a singleton live birth after embryo transfer at the Center for Reproductive Medicine, Shandong University, from 2008 to 2020. Of these, 745 women underwent frozen embryo transfer (FET) using embryos developed from frozen gametes (DFT). Propensity score methodology was used to balance the two groups by maternal age and body mass index (BMI) before evaluating outcomes. After age and BMI were matched using the propensity score methodology in a ratio of 1:4, the control groups enrolled 2,980 women who underwent fresh embryo transfer (ET) and 2,980 women underwent FET from fresh gametes. The children born were followed to at least 5 years of age, and some were followed up to 10 years. Neonatal outcomes and childhood growth measurements were compared among the three groups.

Results

The average birth weight of the DFT group (3,462 g) was significantly higher than the FET group (3,458 g) and ET group (3,412 g). The rate of large for gestational age (LGA) babies in the DFT and FET group was higher than that for the ET group (30.9% vs. 24.8%; 29.4% vs. 24.8%, respectively). After adjusting for different confounder combinations in the three models, the birth weight and risk of LGA in the DFT and FET groups were still higher than in the ET group, and the values group of P for trend in the models were significant. In multiple linear regression analysis of the children’s development, the height Z-score of children born from the DFT and FET group was higher than that for children from the ET group (β = 0.21, 95% CI 0.07–0.35; b = 0.17, 95% CI 0.05–0.28, respectively). However, childhood growth measurements including body weight Z-score and BMI Z-score were not significantly different among the three groups. In addition, the proportion of male children born from DET was higher than that from ET.

Conclusions

There is an increased risk of LGA babies associated with pregnancies conceived from DFT. Children are inclined to be taller in the future in this group than after FET. The related etiology and pathophysiology mechanisms still need to be revealed. In the future, well-designed, observational studies with in-depth collection of patients’ characteristics may shed more light on this issue.
Resilient cooperative control for optimal current sharing and voltage regulation of microgrid-based distribution network under FDI attacks
Authors: Wang Biheng
Published: August 2022

In this study, the security secondary control problems are considered for optimal current sharing and voltage restoration of a microgrid distribution network under false data injection (FDI) attacks. To solve these problems, a resilient secondary control method is provided. Specifically, a resilient secondary controller is designed by introducing an adaptive parameter based on the adaptive technique. Then, a theoretical analysis method is provided to show that the designed resilient secondary controller can ensure optimal current sharing and voltage regulation under FDI attacks.
Remaining useful life prediction of lithium-ion batteries based on wavelet denoising and transformer neural network
Authors: Hu Wangyang , Zhao Shaishai
Published: August 2022

It is imperative to accurately predict the remaining useful life (RUL) of lithium-ion batteries to ensure the reliability and safety of related industries and facilities. In view of the noise sequence embedded in the measured aging data of lithium-ion batteries and the strong nonlinear characteristics of the aging process, this study proposes a method for predicting lithium-ion batteries’ RUL based on the wavelet threshold denoising and transformer model. To specify, firstly, the wavelet threshold denoising method is adopted to preprocess the measured discharging capacity data of lithium-ion batteries to eliminate some noise signals. Second, based on the denoised data, the transformer model output’s full connection layer is applied to replace the decoder layer for establishing the RUL prediction model of lithium-ion batteries. Finally, the discharging capacity of each charging–discharging cycle is predicted iteratively, and then the RUL of lithium-ion batteries can be calculated eventually. Two groups of lithium-ion batteries’ aging data from the Center for Advanced Life Cycle Engineering (CALCE) at the University of Maryland and the laboratory at Anqing Normal University (AQNU) are employed to verify the proposed method, individually. The experimental results demonstrate that this method can overcome the impacts of data measurement noise, effectively predict the RUL of lithium-ion batteries, and present a sound generalization ability and high accuracy.
Balancing future renewable energy infrastructure siting and associated habitat loss for migrating whooping cranes
Authors: Ellis Kristen S. , Pearse Aaron T. , Brandt David A. , Bidwell Mark T. , Harrell Wade , Butler Matthew J. , Post van der Burg Max
Published: August 2022

The expansion of human infrastructure has contributed to novel risks and disturbance regimes in most ecosystems, leading to considerable uncertainty about how species will respond to altered landscapes. A recent assessment revealed that whooping cranes (Grus americana), an endangered migratory waterbird species, avoid wind-energy infrastructure during migration. However, uncertainties regarding collective impacts of other types of human infrastructure, such as power lines, variable drought conditions, and continued construction of wind energy infrastructure may compromise ongoing recovery efforts for whooping cranes. Droughts are increasing in frequency and severity throughout the whooping crane migration corridor, and the impacts of drought on stopover habitat use are largely unknown. Moreover, decision-based analyses are increasingly advocated to guide recovery planning for endangered species, yet applications remain rare. Using GPS locations from 57 whooping cranes from 2010 through 2016 in the United States Great Plains, we assessed habitat selection and avoidance of potential disturbances during migration relative to drought conditions, and we used these results in an optimization analysis to select potential sites for new wind energy developments that minimize relative habitat loss for whooping cranes and maximize wind energy potential. Drought occurrence and severity varied spatially and temporally across the migration corridor during our study period. Whooping cranes rarely used areas <5 km from human settlements and wind energy infrastructure under both drought and non-drought conditions, and <2 km from power lines during non-drought conditions, with the lowest likelihood of use near wind energy infrastructure. Whooping cranes differed in their selection of wetland and cropland land cover types depending on drought or non-drought conditions. We identified scenarios for wind energy expansion across the migration corridor and in select states, which are robust to uncertain drought conditions, where future loss of highly selected stopover habitats could be minimized under a common strategy. Our approach was to estimate functional habitat loss while integrating current disturbances, potential future disturbances, and uncertainty in drought conditions. Therefore, dynamic models describing potential costs associated with risk-averse behaviors resulting from future developments can inform proactive conservation before population impacts occur.
The Causal Evidence of Birth Weight and Female-Related Traits and Diseases: A Two-Sample Mendelian Randomization Analysis
Authors: He Renke , Liu Rui , Wu Haiyan , Yu Jiaen , Jiang Zhaoying , Huang Hefeng
Published: August 2022

Objectives: A large meta-analysis indicated a more pronounced association between lower birth weight (BW) and diseases in women but less concern about the causality between BW and female-related phenotypes and diseases.

Methods: Mendelian randomization (MR) analysis was used to estimate the causal relationship between two traits or diseases using summary datasets from genome-wide association studies. Exposure instrumental variables are variants that are strongly associated with traits and are tested using four different statistical methods, including the inverse variance weighting, MR-Egger, weighted median, and weighted mode in MR analysis. Next, sensitivity analysis and horizontal pleiotropy were assessed using leave-one-out and MR-PRESSO packages.

Results: The body mass index (BMI) in adulthood was determined by BW (corrected β = 0.071, p = 3.19E-03). Lower BW could decrease the adult sex hormone-binding globulin (SHBG) level (β = −0.081, p = 2.08E-06), but it resulted in increased levels of bioavailable testosterone (bio-T) (β = 0.105, p = 1.25E-05). A potential inverse effect was observed between BW and menarche (corrected β = −0.048, p = 4.75E-03), and no causal association was confirmed between BW and the risk of endometriosis, leiomyoma, and polycystic ovary syndrome.

Conclusion: Our results suggest that BW may play an important role and demonstrates a significant direct influence on female BMI, SHBG and bio-T levels, and menarche.
Next-generation sequencing reveals a case of Norrie disease in a child with bilateral ocular malformation
Authors: Li Haijun , Li Zhiming , Wang Degang , Chen Chuanming , Chen Zhiqiang , Wang Jinhua , Xu Chenxia , Dong Xingsheng
Published: August 2022

A Norrie disease protein gene (NDP) variant, c.174 + 1G > A, was found in a Chinese family through next-generation sequencing and verified with Sanger sequencing. A case of Norrie disease was reported in the first child, and the symptoms were consistent with the results of gene sequencing. The child’s mother, who was pregnant at the time, was found to be a carrier of the identified pathogenic variant. To determine if the fetus carried the same disease-causing variant, prenatal examination and prenatal diagnosis were conducted. The fetus had biocular vitreous abnormalities and complete retinal abnormalities. Genetic testing showed that the fetus had maternally inherited the NDP gene variant found in the proband. It was concurrently confirmed that the NDP gene variant led to the deletion of 246 bp at the 3′ end of exon 2, resulting in the deletion of the initiation codon and the occurrence of disease. Our study suggests that the diagnosis of rare diseases through next-generation sequencing, combined with prenatal ultrasound and prenatal diagnosis, can help families with known familial genetic diseases. Furthermore, the findings of this study broaden the known genetic spectrum of Norrie disease.
Comprehensive Analysis of Molecular Subtypes and Hub Genes of Sepsis by Gene Expression Profiles
Authors: Lai Yongxing , Lin Chunjin , Lin Xing , Wu Lijuan , Zhao Yinan , Shao Tingfang , Lin Fan
Published: August 2022

Background: Sepsis is a systemic inflammatory response syndrome (SIRS) with heterogeneity of clinical symptoms. Studies further exploring the molecular subtypes of sepsis and elucidating its probable mechanisms are urgently needed.

Methods: Microarray datasets of peripheral blood in sepsis were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) analysis was conducted to screen key module genes. Consensus clustering analysis was carried out to identify distinct sepsis molecular subtypes. Subtype-specific pathways were explored using gene set variation analysis (GSVA). Afterward, we intersected subtype-related, dramatically expressed and module-specific genes to screen consensus DEGs (co-DEGs). Enrichment analysis was carried out to identify key pathways. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for screen potential diagnostic biomarkers.

Results: Patients with sepsis were classified into three clusters. GSVA showed these DEGs among different clusters in sepsis were assigned to metabolism, oxidative phosphorylation, autophagy regulation, and VEGF pathways, etc. In addition, we identified 40 co-DEGs and several dysregulated pathways. A diagnostic model with 25-gene signature was proven to be of high value for the diagnosis of sepsis. Genes in the diagnostic model with AUC values more than 0.95 in external datasets were screened as key genes for the diagnosis of sepsis. Finally, ANKRD22, GPR84, GYG1, BLOC1S1, CARD11, NOG, and LRG1 were recognized as critical genes associated with sepsis molecular subtypes.

Conclusion: There are remarkable differences in and enriched pathways among different molecular subgroups of sepsis, which may be the key factors leading to heterogeneity of clinical symptoms and prognosis in patients with sepsis. Our current study provides novel diagnostic and therapeutic biomarkers for sepsis molecular subtypes.
Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer
Authors: Chen Minhua , Chen Zhang , Lin Zongbin , Ding Xiang , Liang Tianyu
Published: August 2022

Background: Increasing evidences show a clinical significance in the interaction between hypoxia and prostate cancer. However, reliable prognostic signatures based on hypoxia have not been established yet.

Methods: We screened hypoxia-related gene modules by weighted gene co-expression network analysis (WGCNA) and established a hypoxia-related prognostic risk score (HPRS) model by univariate Cox and LASSO-Cox analyses. In addition, enriched pathways, genomic mutations, and tumor-infiltrating immune cells in HPRS subgroups were analyzed and compared. HPRS was also estimated to predict immune checkpoint blockade (ICB) therapy response.

Results: A hypoxia-related 22-gene prognostic model was established. Furthermore, three independent validation cohorts showed moderate performance in predicting biochemical recurrence-free (BCR-free) survival. HPRS could be a useful tool in selecting patients who can benefit from ICB therapy. The CIBERSORT results in our study demonstrated that hypoxia might act on multiple T cells, activated NK cells, and macrophages M1 in various ways, suggesting that hypoxia might exert its anti-tumor effects by suppressing T cells and NK cells.

Conclusion: Hypoxia plays an important role in the progression of prostate cancer. The hypoxia-derived signatures are promising biomarkers to predict biochemical recurrence-free survival and ICB therapy responses in patients with prostate cancer.
Screening seven hub genes associated with prognosis and immune infiltration in glioblastoma
Authors: Zhang Yesen , Fan Huasheng , Zou Chun , Wei Feng , Sun Jiwei , Shang Yuchun , Chen Liechun , Wang Xiangyu , Hu Beiquan
Published: August 2022

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Diagnostic and therapeutic challenges have been raised because of poor prognosis. Gene expression profiles of GBM and normal brain tissue samples from GSE68848, GSE16011, GSE7696, and The Cancer Genome Atlas (TCGA) were downloaded. We identified differentially expressed genes (DEGs) by differential expression analysis and obtained 3,800 intersected DEGs from all datasets. Enrichment analysis revealed that the intersected DEGs were involved in the MAPK and cAMP signaling pathways. We identified seven different modules and 2,856 module genes based on the co-expression analysis. Module genes were used to perform Cox and Kaplan-Meier analysis in TCGA to obtain 91 prognosis-related genes. Subsequently, we constructed a random survival forest model and a multivariate Cox model to identify seven hub genes (KDELR2, DLEU1, PTPRN, SRBD1, CRNDE, HPCAL1, and POLR1E). The seven hub genes were subjected to the risk score and survival analyses. Among these, CRNDE may be a key gene in GBM. A network of prognosis-related genes and the top three differentially expressed microRNAs with the largest fold-change was constructed. Moreover, we found a high infiltration of plasmacytoid dendritic cells and T helper 17 cells in GBM. In conclusion, the seven hub genes were speculated to be potential prognostic biomarkers for guiding immunotherapy and may have significant implications for the diagnosis and treatment of GBM.
ADD1 Single Nucleotide Polymorphisms Are Associated With Essential Hypertension Among Han and Mongolian Population in Inner Mongolia Area
Authors: Zhang Yi , Chang Peiye , Liu Zhiyue
Published: August 2022

Aldosterone synthase (CYP11B2) and α-adducing (ADD1) are candidate genes that play key roles during essential hypertension (EH) incidence. However, the association between their genetic mutations and the risk of EH is unclear. The present study investigated specific single nucleotide polymorphisms (SNPs) from CYP11B2 and ADD1, and their potential role as risk factors for EH based on 423 Mongolian and 410 Han people in Inner Mongolia province. In the allelic model, people with ADD1 rs2239728-A presented a 0.74-fold risk than rs2239728-C, whereas the ADD1 rs4961-T was associated with a 1.37-fold higher risk than allele G in the Han population. The genetic model reported that the rs2239728-A carrier (AA + AC) was 0.59-fold lower than the CC carrier, whereas the rs4961-G carrier (GG + GT) was 0.59-fold lower than the TT carrier in the dominant model. After gender adjustment, people with rs2239728-A was a 0.63-fold risk than –C in EH, but the rs4961-T carrier was associated with a 1.63-times higher risk than –G in females. Haplotype analysis showed that GCCT was associated with essential hypertension in the Han population, and it was a risk factor for EH. Our identification reported novel SNPs of ADD1 with protective significance for EH among females in the Chinese Han population, together with its haplotype GCCT as a risk factor for EH.
Identification of Novel Compound Heterozygous Variants of MMP9 in Fetus With Metaphyseal Anadysplasia Type 2
Authors: Cheng Lin , Yang Fan , Chen Xinlin , Kang Jiawei , Li Jiafu , Zhang Yuanzhen , Liu Juan , Li Jin , Ma Jianhong , Duan Jie
Published: August 2022

Matrix metalloproteinase 9 (MMP9) is an important member of the matrix metalloproteinase family and plays a key role in balancing extracellular matrix proteins. Studies have shown that the homozygous mutations in MMP9 can lead to metaphyseal anadysplasia type 2 (MANDP2, OMIM#613073). The clinical phenotype of this disease is limited and there were only five reported cases of MANDP2 associated with homozygous MMP9 mutations from three families. In this study, we described a case of a fetus with skeletal system malformation. The main clinical manifestations include the short bilateral femur, absence of right fibula, and curved ipsilateral tibia with short length. Importantly, two novel compound heterozygous variants of the MMP9 gene (NM_004,994.3: c.151C > T and c.929del) were found through the trio whole exome sequencing and Sanger sequencing. This is the first report that identified the compound heterozygous variants of the MMP9 gene associated with metaphyseal dysplasia type 2.
Comparison of PuraStat self-assembling peptide hydrogel versus mineral-based Hemospray for endoscopic hemostasis of upper and lower gastrointestinal lesions in pigs
Authors: Gil Eun Seok , O’Neill Kate , Aleksi Elton , Budrewicz Jay , Melidone Raffaele , Spirio Lisa
Published: August 2022

Objective

To compare a RADA16-based self-assembling peptide hydrogel versus an inorganic powder-based spray device for controlling postoperative bleeding in upper and lower GI mucosal lesions in pigs.

Methods

Multiple mucosal lesions were endoscopically-created in the stomachs and lower colons of six Yorkshire swine on Day 0. Three animals’ wounds were treated with 2.5% RADA16 solution (PuraStat®), two animals were treated with an aerosolized mineral powder (Hemospray®), and one animal was an untreated control. Primary outcomes were test article applications required to control initial bleeding, time-to-hemostasis, and rebleeding incidence. Secondary outcomes included animal recovery, and clinical pathology at weekly endoscopic evaluations and the 4-week study terminus.

Results

Number of material administrations required and time-to-hemostasis was comparable between PuraStat and Hemospray groups. Rebleeding rates were comparable between treatments. Two of 12 (17%) Hemospray and none of 18 (0%) PuraStat stomach sites experienced rebleeding during the final 4 min of the 10-min observation period. No delayed bleeding was observed during weekly endoscopic follow-ups. Hematology and serology values remained normal in all animals. Histology showed expected healing responses at all PuraStat- and Hemospray-treated defects, with less inflammation than untreated sites. Histomorphological observations were comparable between different groups for both the stomach and colon for test and control materials, with lower inflammation scores than untreated sites. Performance and usability responses were generally good with both systems, although the Ability to Treat Intended Site score was significantly better with PuraStat in upper GI lesions.

Conclusions

PuraStat and Hemospray were effective topical hemostats for mild-to-moderate bleeding in upper and lower GI wounds. Rebleeding was observed in two of 12 Hemospray-treated sites and none of 18 PuraStat-treated sites. PuraStat and Hemospray were associated with better wound healing than untreated controls. The ability to treat upper GI lesions was easier with the PuraStat versus Hemospray system.
USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses
Authors: Zhang Na , Wang Fei , Zhang Gaomeng , Zhang Qi , Liu Yuhong , Wang Qiao , Elsharkawy Mohamed Shafey , Zheng Maiqing , Wen Jie , Zhao Guiping , Li Qinghe
Published: August 2022

Toll-like receptors (TLRs) are involved in the sensing of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, unmethylated double-stranded DNA (CpG), single-stranded RNA (ssRNA) and lipoproteins. Myeloid differentiation primary response protein 88 (MyD88) is a canonical adaptor for the Toll-like receptor family which has crucial roles in host defense against infection by microbial pathogens. The dysregulation of MyD88 may also induce autoimmune diseases. Here, we demonstrate that the deubiquitinase USP7 interacts with MyD88 in chicken, with knockdown or overexpression of USP7 leading to the regulation of MyD88 protein in a positive manner. Consequently, USP7 positively regulates the expression of proinflammatory factors upon LPS challenge. Furthermore, we observed USP7-deficient mice to be more susceptible to infection by Salmonella typhimurium. Collectively, our findings demonstrate MyD88 as a bona fide substrate of USP7 and uncover a mechanism by which USP7 regulates innate immune signaling.
Integrative network analysis revealed the molecular function of folic acid on immunological enhancement in a sheep model
Authors: Wang Bing , Li Heqiong , Li Zhen , Wang Bo , Zhang Han , Zhang Boyan , Luo Hailing
Published: August 2022

We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL, and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.
Computational identification of immune-related lncRNA signature for predicting the prognosis and immune landscape of human glioblastoma multiforme
Authors: Shi Dongjie , Zhong Wenjie , Liu Dan , Sun Xiaochuan , Hao Shilei , Yang Yaying , Ao Lei , Zhou Junjie , Xia Yongzhi , Zhou Yudong , Yu Hua , Xia Haijian
Published: August 2022

Emerging evidence shows immune-related long noncoding RNAs (ir-lncRNAs) perform critical roles in tumor progression and prognosis assessment. However, the identification of ir-lncRNAs and their clinical significance in human glioblastoma multiforme (GBM) remain largely unexplored. Here, a designed computational frame based on immune score was used to identify differentially expressed ir-lncRNAs (DEir-lncRNAs) from The Cancer Genome Atlas (TCGA) GBM program. The immune-related lncRNA signature (IRLncSig) composed of prognosis-related DEir-lncRNAs selected by Cox regression analysis and its clinical predictive values were verified, which was further validated by another dataset from the Gene Expression Omnibus database (GEO). Subsequently, the association between IRLncSig and immune cell infiltration, immune checkpoint inhibitor (ICI) biomarkers, O6-methylguanine-DNA methyltransferase (MGMT) gene expression, and biological function were also analyzed. After calculation, five prognosis-related ir-lncRNAs were included in the establishment of IRLncSig. The risk assessment based on IRLncSig indicated that the high-IRLncSig-score group was significantly associated with poor prognosis (p < 0.001), significant aggregation of macrophages (p < 0.05), higher ICI biomarker expression, and MGMT gene expression (p < 0.05). Signature-related lncRNAs may be involved in immune activities in the tumorigenesis and progression of GBM. In summary, the novel IRLncSig shows a promising clinical value in predicting the prognosis and immune landscape of GBM.
Display of receptor-binding domain of SARS-CoV-2 Spike protein variants on the Saccharomyces cerevisiae cell surface
Authors: Xing Hongguan , Zhu Liyan , Wang Pingping , Zhao Guoping , Zhou Zhihua , Yang Yi , Zou Hong , Yan Xing
Published: August 2022

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a significant global human health threat. The most effective way to end the pandemic is through timely vaccination. In this study, the receptor-binding domains (RBDs) of Spike protein of the initial strain of SARS-CoV-2 and its variants, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa), were successfully displayed on the surface of a Saccharomyces cerevisiae strain for development as a vaccine candidate. To rapidly express the recombinant protein and avoid the need for expensive galactose as an inducer, the gal80 gene of S. cerevisiae was knocked out, and the conventional 72-h culture period was thus successfully shortened to 24 h. Mice vaccinated against variant B.1.617.1 showed robust humoral and cellular immune responses. Moreover, the antiserum in the B.1.671.1 group had neutralizing activity against wild-type RBD and high binding titers against RBD mutants of variants B.1.351 and B.1.1.7. Double deglycosylation at N331Q and N343Q resulted in marked reduction of the affinity of RBD binding to angiotensin converting enzyme 2 (ACE2) and escaped antibody neutralization. This study demonstrates that yeast surface display technology can provide an alternative approach to rapid large-scale preparation of promising SARS-CoV-2 vaccine candidates at low cost.