bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternations in gut microbiota and host transcriptome of patients with coronary artery disease
Authors: Chen Liuying , Mou Xuanting , Li Jingjing , Li Miaofu , Ye Caijie , Gao Xiaofei , Liu Xiaohua , Ma Yunlong , Xu Yizhou , Zhong Yigang
Published: August 2023

Background
Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.
Results
Herein, we collected 54 fecal and 54 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that 10 bacteria biomarkers can distinguish CAD patients from health controls with a high performance (AUC = 0.939). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbe genus Fusicatenibacter was associated with expression of CAD-risk genes, such as GBP2, MLKL, and CPR65. In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genus Blautia, Eubacterium, Fusicatenibacter, and Monoglobus.
Conclusions
Our results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.
Promotion of Hydrogen Evolution from Seawater via Poly(aniline-co-4- Nitroaniline) combined with 3D Nickel Nanoparticles
Authors: Moradi-Alavian Saleh , Kazempour Amir , Mirzaei-Saatlo Meysam , Ashassi-Sorkhabi Habib , Mehrdad Abbas , Asghari Elnaz , Lamb Jacob J. , Pollet Bruno G.
Published: August 2023

This work reports the synthesis of poly (aniline-co-4-nitroaniline) deposited on a three-dimensional nanostructured nickel (3D-Ni) film, where both layers were fabricated via potentiostatic electrodeposition. The obtained electrocatalyst exhibited excellent electrochemical activity for the Hydrogen Evolution Reaction (HER) with small overpotentials of + 195 and + 325 mV at + 10 and + 100 mAcm− 2, respectively, and a low Tafel slope of 53.3 mV dec− 1 in seawater. Additionally, the electrocatalyst exhibited good stability after 72 h operation under a constant potential of -1.9 V vs. RHE. The efficient HER performance of the as-prepared catalyst was found to originate from the synergy between the conducting polymer and three-dimensional nickel nanoparticles with a large electrochemical active surface area. Moreover, the results obtained from electrochemical impedance spectroscopy (EIS) measurements revealed that the presence of 3D-Ni layer improved the kinetics of HER by reducing the charge transfer resistance for the electrocatalyst.
Cetuximab inhibits colorectal cancer development through inactivating the Wnt/β-catenin pathway and modulating PLCB3 expression
Authors: Cheng Xun , Zhou Wenming , Wu Chenqu , Feng Li
Published: August 2023

Background
Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigates the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment.
Methods
We extracted differentially expressed genes (DEGs) from the GSE140973 and identified the overlapping genes combined with 151 Wnt/β-Catenin signaling pathway-related genes. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene and scrutinized the impact of cetuximab and the hub gene on CRC cellular progression through cell experimental.
Results
Our study identified 26 overlapping genes. High expression of 8 genes (AXIN1, CACYBP, FBXW11, FZD2, MAPK9, PLCB3, NCOA3, RHOA) correlated with poorer prognosis, whereas high expression of TCF7L2 indicated better prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both β-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings reveal PLCB3 promotes cetuximab inhibition on Wnt/β-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion.
Conclusion
Our study emphasizes the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppresses Wnt/β-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offers fresh perspectives on cetuximab mechanism in CRC.
Discovery of novel diagnostic biomarkers of hepatocellular carcinoma associated with immune infiltration
Authors: Liu Qiang , Zhang Hua , Xiao Heng , Ren Ao , Wu Zhongjun , Yu Huarong , Huang Zuotian
Published: August 2023

Objective
The diagnosis of hepatocellular carcinoma (HCC) remains challenging for clinicians. Machine learning approaches and big data analysis are viable strategies to identify HCC diagnostic markers.
Materials and methods
For this study, we downloaded mRNA expression profiles of HCC from the GEO database and used random forest and machine learning algorithms such as Lasso to screen for reliable diagnostic genes. DO, KEGG, GSEA enrichment analysis for exploring differential gene function, disease pathways. CIBERSORT was performed to calculate the immune cell infiltration of HCC and to calculate the correlation of diagnostic genes with immune cells.
Results
The results indicated that ECM1, NPC1L1, and RSPO3 were downregulated in HCC compared with the normal group (P < 0.05), and furthermore, ECM1, NPC1L1, and RSPO3 had a high diagnostic value for HCC in both the training and test cohorts (AUC > 0.75). Immuno-infiltration analysis revealed that ECM1 and RSPO3 were highly positively correlated with neutrophil and macrophage M2, whereas they were negatively correlated with Tregs.
Conclusion
The present study identifies ECM1, NPC1L1, and RSPO3 as new diagnostic biomarkers for HCC based on normal and disease samples from HCC and correlated with immune cell infiltration.
Competing mechanisms govern the thermal rectification behavior in semi-stochastic polycrystalline graphene with graded grain-density distribution
Authors: Lahkar Simanta , Ranganathan Raghavan
Published: August 2023

Thermal rectifiers are devices that have different thermal conductivities in opposing directions of heat flow. The realization of practical thermal rectifiers relies significantly on a sound understanding of the underlying mechanisms of asymmetric heat transport, and two-dimensional materials offer a promising opportunity in this regard owing to their simplistic structures together with a vast possibility of tunable imperfections. However, the in-plane thermal rectification mechanisms in 2D materials like graphene having directional gradients of grain sizes have remained elusive. In fact, understanding the heat transport mechanisms in polycrystalline graphene, which are more practical to synthesize than large-scale single-crystal graphene, could potentially allow a unique opportunity, in principle, to combine with other defects and designs for effective optimization of thermal rectification. In this work, we investigate the thermal rectification behavior in periodic atomistic models of polycrystalline graphene whose grain arrangements were generated semi-stochastically to have different gradient grain-density distributions along the in-plane heat flow direction. We employ the centroidal Voronoi tessellation technique to generate realistic grain boundary structures for graphene, and the non-equilibrium molecular dynamics simulations method is used to calculate the thermal conductivities and rectification values. Additionally, detailed phonon characteristics and propagating phonon spatial energy densities are analyzed based on the fluctuation-dissipation theory to elucidate the competitive interplay between two underlying mechanisms, namely, (i) propagating phonon coupling and (ii) temperature-dependence of thermal conductivity that determines the degree of asymmetric heat flow in graded polycrystalline graphene.
Large voltage-controlled magnetic anisotropy effect in magnetic tunnel junctions prepared by deposition at cryogenic temperatures
Authors: Nozaki Takayuki , Ichinose Tomohiro , Uzuhashi Jun , Yamamoto Tatsuya , Konoto Makoto , Yakushiji Kay , Ohkubo Tadakatsu , Yuasa Shinji
Published: August 2023

We investigated the influence of the buffer material and a cryogenic temperature deposition process on the voltage-controlled magnetic anisotropy effect for an ultrathin CoFeB layer in bottom-free type MgO-based magnetic tunnel junctions prepared by a mass production sputtering process. We used Ta and TaB buffers and compared the differences between them. The TaB buffer enabled us to form a flat and less-contaminated CoFeB/MgO interface by suppressing the diffusion of Ta with maintaining a stable amorphous phase. Furthermore, the introduction of cryogenic temperature deposition for the ultrathin CoFeB layer on the TaB buffer improved the efficiency of the voltage-controlled magnetic anisotropy effect and its annealing tolerance. Combining this with interface engineering employing an Ir layer for doping and a CoFe termination layer, a large VCMA coefficient of -138±3 fJ/Vm was achieved. The developed techniques for the growth of ultrathin ferromagnet and oxide thin films using cryogenic temperature deposition will contribute to the development of high-performance spintronic devices, such as voltage-controlled magnetoresistive random access memories.
Structural Equation Models to Interpret Multi-Trait Genome-Wide Association Studies for Morphological and Productive Traits in Soybean [Glycine max (L.) Merr.]
Authors: Suela Matheus Massariol , Azevedo Camila Ferreira , Nascimento Ana Carolina Campana , Morota Gota , Silva Felipe Lopes da , Malone Gaspar , Giasson Nizio Fernando , Nascimento Moysés
Published: August 2023

Understanding the relationship between multiple traits is fundamental in soybean breeding programs because their primary goal is to maximize multiple traits simultaneously, either directly or indirectly. Typically, multi-trait studies are conducted using a multi-trait version of a genome-wide association study (GWAS). However, this approach does not account for phenotypic interrelationships between traits. Therefore, we applied structural equation modeling (SEM) to explore the interrelationship between traits related to morphology (pod thickness - PT) and yield traits (number of pods - NP, number of grains - NG, and hundred grains weight - HGW). We used a dataset containing 96 soybean individuals genotyped with 4,070 single nucleotide polymorphism (SNP) markers. The phenotypic network was modeled using the hill-climbing algorithm, and the structural coefficients were estimated using the SEM approach. According to the sign of the structural coefficient, we identified positive or negative phenotypic interrelationships. We found negative interrelationships between NG and HGW, positive interrelationships between NP and NG, and between HGW and PT. Among these traits, NG, HGW and PT showed indirect SNP effects. In the SEM-GWAS study, we found quantitative trait loci that jointly controlled some and all of the traits. We identified nine candidate genes (i. serine-threonine kinase; ii. protein DA1-related 2; iii. β-1,3-glucanase-like; iv. MYB-like DNA-binding; v. amino acid transporter; vi. Leucine-rich repeat; vii. squamosa promoter-binding-like; viii. monothiol glutaredoxin-s14, and ix. dynamin) that simultaneously acted in the traits. In summary, the SEM-GWAS approach revealed novel relationships among soybean traits, such as PT, thus contributing to soybean breeding programs.
Electron Acceletaion by Laser Driven Electron Plasma Wave in Plasma with Density Ramp: Cosh Gaussian Laser Beam
Authors: Gupta Naveen , Johari Rohit , K Alex A , Choudhry Suman , Kumar Sanjeev , Bhardwaj S. B.
Published: August 2023

This paper presents a theoretical investigation into the nonlinear propagation of a Cosh-Gaussian (ChG) laser beam through plasma with axial inhomogeneity. The study takes into consideration the relativistic mass nonlinearity of plasma electrons in response to the laser beam. Additionally, the research explores the influence of self-focusing on the excitation of electron plasma waves (EPWs). The analysis employs variational theory to derive semi-analytical solutions for the nonlinear wave equations governing the laser beam and EPWs. Furthermore, the study examines the acceleration of electrons trapped within the excited EPWs. The results obtained from numerical analysis indicate a more pronounced self-focusing effect of the Cosh-Gaussian laser beam when optimal values of the decentered parameter are utilized. This finding is beneficial for generating high-amplitude EPWs, enabling electron acceleration by extending the interaction length.
Legal Determinants That Impact Economic Growth: Panel Data Evidence
Authors: Hajdari Arton , Hajdini Artan , Hadzimustafa Shenaj
Published: August 2023

Economic growth, as a leading macroeconomic objective, is supposed to be determined by different types of variables and indicators, including legal ones. Therefore, through panel data analysis of the 20 EU countries for 2013-2021 years, this research article came across legal determinants that impact economic growth. Data covered in the examination were from secondary sources, i.e. from two credible international institutions, the World Justice Project and the World Bank. This study, conducted through a quantitative scientific approach, i.e. the robust Fixed Effects model of regression analysis, found the following six legal determinants that impact economic growth: no. 1) Effectiveness of keeping crime under control; no. 2) Effectiveness of enforcement of civil justice; no. 3) People do not use violence to redress personal grievances; no. 4) Laws and government data are publicized properly (transparency); no. 5) Government officials in the judicial branch do not utilize their office for personal gain. no. 6) Civil justice is accessed and afforded by people. Of course, the robust Fixed Effects model was not a subjective choice, but a decision made through the respective tests of Pooled OLS, Random Effects and Fixed Effects.
Combined Analysis of Root Transcriptome, Metabolome and physiology on the mechanism of rapid growth recovery for rice seedlings after low temperature stress
Authors: Fu Xiaoquan , Zhong Lei , Wang Hui , He Haohua , Chen Xiaorong
Published: August 2023

Background
Late spring cold is a disastrous weather phenomenon that often occurs during the early rice seedling stage in southern China, which poses a significant threat to open direct seeding of early rice seedlings. We found the differences in growth recovery performance between rice varieties after low temperature stress, but the differences in recovery between roots and stems/leaves are still unclear. 12 ℃ low temperature treatment of 4 days was set to investigate the growth phenotype and physiological changes of rice seedling roots during rewarming, as well as Transcriptome and metabolome were analyzed.
Results
Root growth was significantly inhibited after low temperature stress. During the rewarming process, the root length recovered the fastest, followed by the number of main roots. The fastest growth recovery period was in the first 3 days of rewarming; overall, the growth rate of B116 was higher than that of B811. The content of H2O2 and MDA in the root system of B116 decreased faster than that of B811 during the recovery process. The activities of POD and SOD showed an initial increase followed by a decrease, and returned to the control level after 6 days for the two varieties; Transcriptome analysis showed that the differential genes were mainly enriched in plant endogenous signal transduction, MAPK signal pathway, nitrogen metabolism and other biological pathways; The differential metabolites mainly included organic acids and their derivatives, organic oxygen compounds, and lipids and lipid molecules. Correlation analysis between Transcriptome and metabolome showed that plant endogenous signal transduction, starch and sucrose metabolism were the main metabolic pathways, and the differential expression of auxin response factors AUX/IAA, ARF and sucrose synthase SUS4, SPS1 was related to root growth.
Conclusion
The recovery of rice seedling growth after low temperature stress is related to the rapid clearance of ROS, utilization of auxin, and rapid metabolism of sucrose. The root system recovers growth earlier than the aboveground part, and the root system should be the main response to the harm of late spring cold in production.
Genetic analysis of patients with triple positive primary antiphospholipid syndrome
Authors: GUFFROY Aurélien , Jacquel Lea , Seeleuthner Yoann , Nicodème Paul , Poindron Vincent , Martin Thierry , Maurier François , Delannoy Valerie , Voegeli Anne-Claire , Zhang Peng , Nespola Benoit , Molitor Anne , Apithy Marie-Joëlle , Soulas-Sprauel Pauline , Voll Reinhard , Bahram Seiamak , Vincent Gies , Casanova Jean-Laurent , Cobat Aurélie , Boisson Bertrand , Carapito Raphaël , Korganow Anne-Sophie
Published: August 2023

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown.
We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti b2 glycoprotein1 autoantibodies. We performed whole exome sequencing. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort.
We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity.
These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous cohort of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.
Biomechanical analysis of detachable duet screw to resist intraoperative screw loosening.
Authors: Zhang Zhong , Hu Zheng-Jun , Zhao Deng , Gao Ting , Zhong Rui , Huang Hua-Qiang , Jiang Deng-Xu , Wang Fei , Liang Yi-Jian
Published: August 2023

Purpose
Pedicle screws are widely used in spinal fusion surgery, while screw loosening frequently occurs during spinal deformity correction. The aim of this study was to evaluate whether detachable duet screw can resist cutting or breach of pedicle walls under tensile test.
Methods
In this study, a novel duet screw was designed and developed for the purpose of spinal deformity correction. Eight spine specimens from goats were used and divided into two groups: group A (traditional insertion) and group B (combination of two detachable duet screws). Prior to biomechanical testing, the average density of the vertebrae was determined using quantitative computed tomography (QCT). To simulate the distraction or compression process during spinal deformity correction, loading was applied to the side of the screw through the rod, which was perpendicular to the pedicle screw axis. The process from initiation to the breach of the pedicle was assessed in order to determine the effectiveness of the duet screw.
Results
The quantitative computed tomography (QCT) analysis revealed that the average bone density of the entire goat population was 500.63 ± 37.88 mg/cm3. In group A and group B, the mean maximum failure load (MFL) was determined to be 1052.38 N and 1762.25 N, respectively. Notably, the average MFL exhibited a significant increase in group B compared to group A (P < 0.05).
Conclusion
The implementation of detachable duet screws exhibits the potential to enhance the resistance against screw loosening by connecting two screws under tensile force. This investigation offers valuable preclinical evidence for future clinical applications.
Exploring Plasmodium falciparum genetic diversity’s influence on antimalarial drugs resistance in endemic setting of Burkina Faso
Authors: Nikiema Moustapha , Gneme Awa , Quaye Charles , Ilboudo Hamidou , Nikiema Seni , Kabore Justine , Soulama Issiaka , Nebie Eric , Dah Clarisse , Sie Ali , Badolo Athanase
Published: August 2023

The diversity of Plasmodium genotypes characterizes the dynamics of malaria transmission and is thought to be one of the factors hampering malaria control efforts The aim of the present study was to explore the influence of Plasmodium falciparum genetic polymorphism on antimalarial drug resistance molecular markers in two endemic settings in Burkina Faso.
Blood blots from malaria-positive samples were processed with molecular tools for Plasmodium falciparum genetic polymorphism alleles detection and markers associated with antimalarial drug resistance. The chi2 analysis and ANOVA were used to compare allelic frequencies, mean multiplicity of infection (mMOI) and prevalence of mutant pfcrt, pfmdr, dhfr/dhps genes.
Out of the 285 samples positive for Plasmodium falciparum, 279 were successfully genotyped for markers associated with antimalarial drug resistance and genetic polymorphism. Significant positive correlations were found between mean multiplicity of infection (mMOI) and pfcrt76, dhfr51 and dhps437 mutant prevalence. No significant variation was found between msp1/ msp2 alleles and the prevalence of pfcrt, pfmdr, dhfr, and dhps mutants. Monoclonal msp1 infections harbored high prevalence mutation in pfcrt76, dhfr51 and dhps437 genes.
Overall, this study showed a negligible correlation between genetic diversity of Plasmodium falciparum and antimalarial mutant genes. Competition between different strains (polyclonality) of the parasite within the host would be to the disadvantage of mutant strains.
Rainfall Variability and Deciduous-Evergreen Coexistence in Tropical Forests
Authors: Muehleisen Andrew J. , Schwartz Naomi B. , Stump Simon M. , Staver A. Carla
Published: August 2023

In tropical forests, deciduous and evergreen leaf habits represent contrasting tree adaptations to precipitation seasonality. Both rainfall seasonality and interannual variation in rainfall are determinants of forest deciduousness, but their relative influence is not well understood. In this study, we evaluate the extent of deciduous-evergreen coexistence in tropical forests and develop a simple model of competition for water between leaf habits. Using this model, we formalize two mechanisms representing rainfall variability across time scales that may explain their stable coexistence: the temporal storage effect via interannual variability in rainfall vs. rainfall partitioning via evergreen access to dry-season rainfall. In our model, both mechanisms resulted in coexistence, but coexistence was more robust via resource partitioning. Empirically, remotely sensed deciduousness increased with precipitation seasonality, but effects of interannual rainfall variability on deciduousness were minor. We hypothesize that dry-season rainfall may prove a stronger influence on coexistence between leaf habits, and that changes in rainfall seasonality will have a greater impact on forest deciduousness than changes in the interannual variability of rainfall.
Investigating the relationship between thyroid hormones with the risk level screening tests in the first trimester of pregnancy in hypothyroid women: A case-control study
Authors: Rezavand Negin , Darvishi Somayeh , Hematti Maryam , Rezaei Mansour , Nemati Houshang , Seyedzadeh Seyed mohammad Saleh , Kamravamanesh Alireza , Seyedzadeh Saydeh Saba , Kamravamanesh Mastaneh
Published: August 2023

Background
The aim of this study was to assess the association between T3, T4, FT3, FT4, TSH, Anti TPO, Free BhCG, B-MOM, P-MOM, and NT-MOM with the risk level of screening tests in the first trimester of pregnancy in hypothyroid and control women.
Methods
In this case-control study, 82 pregnant women were enrolled. The ELISA method was performed to evaluate the serum levels of T3, free T3, T4, free T4, TSH, and Anti TPO, and the first stage of fetal screening tests including Free BhCG, B-MOM, P-MOM, NT-MOM were done by Electro-chemiluminescent (ECL) method., and finally data analysis was performed with SPSS statistical software.
Results
The average levels of TSH (p-value = 0.001), TPO (p-value = 0.006), trisomy 21 (p-value < 0.001), and trisomy 13/18 (p-value < 0.001) in the intervention group were significantly higher and PAPP-A was significantly (p-value < 0.001) lower than control group; However, there was no statistical difference between the intervention and control groups in terms of the mean levels of beta-hCG (p-value = 0.297), B-MoM (p-value = 0.202), and NT-MoM (p-value = 0.221). Also, in the intervention with levothyroxine group, the mean serum TSH level was significantly higher in the screen positive group and the medium risk group of DS than the negative screen group (p-value = 0.014).
Conclusion:
It is suggested to identify hypothyroid pregnant mothers early and make it mandatory to perform timely fetal health screening tests in the first trimester of pregnancy in this group of mothers, with the aim of identifying fetuses at risk of developing chromosomal disorders. This should be the priority of maternal health policy makers.
Accurate Identification of Micro-scale Urban Functional Zones from the Perspective of Dialectical Materialism
Authors: Zhang Changfan
Published: August 2023

With the advancement of global urbanization, accurate identification of urban functional zones has become a crucial task for the high-quality development of cities. Traditional methods that rely on POI data are insufficient to accurately identify micro-scale urban functional zones. Thus, this study proposes a novel method for identifying urban functional zones based on VOI (Volume of Interest) data and applies it to a small region in Hong Kong for comparative research. Subsequently, the identification accuracy of the two methods is assessed using a confusion matrix and the Kappa Coefficient. The results show that the VOI data contains richer and more comprehensive urban spatial information compared to POI data, enabling a superior representation of connections and influences among different zones within cities. The study can be applied to analyse micro-scale urban functional zones in other cities, providing a new perspective for the in-depth research.
Machine learning-based pathomics model to predict the infiltration of regulatory T cells and prognosis in isocitrate dehydrogenase-wild- type glioblastoma
Authors: Peng Shaoli , Wang Xuezhen , Chen Jinyang , Yang Minghuan , Lan Hailin , Hong Jinsheng , Zhang Mingwei
Published: August 2023

Purpose
Regulatory T cells (Tregs) have been highlighted as prognostic factors in isocitrate dehydrogenase (IDH)-wild-type (wt) glioblastoma (GBM). However, conventional detection of Tregs with immunohistochemistry is limited for practical application in clinical settings. The aim of this study was to construct a pathomics model to predict Treg infiltration in IDH-wt GBM and explore the related biological processes.
Methods
Using the Pyradiomics package, pathomics features were extracted from hematoxylin and eosin-stained biopsy images of patients from The Cancer Genome Atlas. The proportion of Tregs was confirmed in orthotopic glioblastoma mouse model via flow cytometry. The pathomics model was constructed using a gradient-boosting machine-learning approach, and the pathomics score (PS) was determined with the minimal redundancy-maximal relevance and relief algorithms. Cox proportional hazard regression analysis was employed to access the association between PS and overall survival (OS). Transcriptomic data were analyzed through GSEA set enrichment, differential gene expression, and correlation analyses.
Results
PS was positively correlated with high Treg expression. Patients with a high PS had significantly worse overall survival than did those with a low PS. A high PS independently served as a prognostic risk factor for patients with IDH-wt GBM. Gene set enrichment analysis revealed significant associations between PS and the Notch and IL-6/JAK/STAT3 signaling pathways. A high PS was also significantly correlated with elevated RAD50 expression.
Conclusion
The developed pathomics model based on machine-learning algorithms can offer an alternative non-invasive method to predict Treg infiltration and prognosis in patients with IDH-wt GBM, further suggesting potential targets for immunotherapy.
Evaluation of Quantitative IgG and Interferon-Gamma Responses After Different Booster Strategies of CoronaVac and BNT162b2 Vaccines in Turkey
Authors: Ocakli Aylin Irem , Kurtcu Seyma Aybuke Ozyar , Uzun Mertcan , Cavdar Merve Kasikci , Dizman Gulcin Telli , Metan Gokhan , Akova Murat , Saribas Zeynep , Sener Burcin
Published: August 2023

Background
The global effort to combat the COVID-19 pandemic requires a comprehensive assessment of vaccine efficacy, humoral and cellular immune responses. The current study aimed to determine the effects of CoronaVac and BNT162b2 boosters on quantitative IgG and interferon-gamma (IFN-γ) responses of individuals primed with two doses of CoronaVac in Turkey. This prospective cohort study included 48 participants aged 18–59 years, without any comorbidities and were not under drug therapy, with no clinical history of COVID-19. The study was conducted in three groups: Group 1 was composed of individuals immunized with three doses of CoronaVac; Group 2 two doses of CoronaVac and one dose of BNT162b2; Group 3 two doses of CoronaVac plus two doses of BNT162b2. Humoral immunity was assessed by the determination of the IgG levels against the spike RBD protein of SARS-CoV-2 and cellular immunity by the IFN-γ release assay.
Results
When the 6–12 month post-vaccination period was considered, the lowest quantitative IgG levels were detected in group 1 in which the booster was applied as CoronaVac. IgG levels were higher in the two groups with BNT162b2 boosters, group 3 (two BNT boosters) revealed the highest levels. The highest IFN-γ response was observed in the group with two BNT162b2 booster applications. Although the difference between the IFN-γ levels was not statistically significant for the three groups, the individuals boosted with the mRNA vaccine revealed two- and three-fold higher levels in comparison to the homologous boosted individuals. No significant gender difference was found for IgG and IFN-γ values in the three groups. The IgG and IFN-γ median values of the younger participants were significantly higher than those of the older participants in Group 3.
Conclusions
We conclude that although both homologous and heterologous boosting in inactivated vaccine-primed individuals provided effective humoral and cellular immunity, boosting with two doses of BNT162b2 should be prioritized, particularly in people with a higher risk of infection with SARS-CoV-2, since it exhibited a clearly positive impact on both humoral and cellular immunity.
Opsin 5 mediates violet light-induced early growth response-1 expression in the mouse retina
Authors: Jeong Heonuk , Lee Deokho , Jiang Xiaoyan , Negishi Kazuno , Tsubota Kazuo , Kurihara Toshihide
Published: August 2023

Myopia is an abnormal vision condition characterized by difficulties in seeing distant objects. Myopia has become a public health issue not only in Asian countries but also in Western countries. Previously, we found that violet light (VL, 360–400 nm wavelength) exposure effectively suppressed myopia progression in experimental chick and mice models of myopia. The inhibitory effects of VL on myopia progression are reduced in retina-specific opsin 5 (Opn5) knockout (KO) mice. Furthermore, VL exposure upregulated early growth response-1 (Egr-1) expression in the chorioretinal tissues of chicks. However, the expression of EGR-1 and role of OPN5 in mice following VL exposure remain unclear. In this study, we examined whether VL exposure-induced EGR-1 upregulation depends on Opn5 expression in the mouse retina. EGR-1 mRNA and protein expressions increased in the mouse retina and mouse retinal 661W cells following VL exposure. These increases were consistently reduced in retina specific Opn5 conditional KO mice and Opn5 KO 661W cells. Our results suggest that OPN5 mediates VL-induced EGR-1 upregulation in mice. These molecular targets could be considered for the prevention and treatment of myopia.
Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures
Authors: Ren Yuanfang , Li Yanjun , Loftus Tyler J. , Balch Jeremy , Abbott Kenneth L. , Ruppert Matthew M. , Guan Ziyuan , Shickel Benjamin , Rashidi Parisa , Ozrazgat-Baslanti Tezcan , Bihorac Azra
Published: August 2023

Background: While the initial few hours of a hospital admission can significantly impact a patient’s clinical trajectory, early clinical decisions often suffer due to data paucity. By using clustering analysis for patient vital signs that were recorded in the first six hours after hospital admission, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Historically, phenotyping based on these early vital signs has proven challenging, as vital signs are typically sampled sporadically.
Methods: We created a single-center, longitudinal dataset of electronic health record data for 75,762 adult patients admitted to a tertiary care center for at least six hours. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from sparse and irregularly sampled vital sign data and derived distinct patient phenotypes within a training cohort (n=41,502). Model and hyper-parameters were selected based on a validation cohort (n=17,415). A test cohort (n=16,845) was used to analyze reproducibility and correlation with clinical biomarkers.
Results: The three cohorts—training, validation, and testing—had comparable distributions of age (54-55 years), sex (55% female), race, comorbidities, and illness severity. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (three-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B’s favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the various phenotypes’ sequential organ failure assessment scores, the results of the clustering did not simply provide a recapitulation of previous acuity assessments.
Conclusions: Within a heterogeneous cohort of patients in hospitals, four phenotypes with distinct categories of disease and clinical outcomes were identified by using a deep temporal interpolation and clustering network. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.
Specxai - Spectral Interpretability of Deep Learning Models
Authors: Balu Aditya , Druc Stefan , Wooldridge Peter , Krishnamurthy Adarsh , Sarkar Soumik
Published: August 2023

Deep learning is becoming increasingly adopted in almost all sectors of business due to its ability to transform large quantities of data into high-performing models. The power of deep learning is that it can capture non-trivial and non-linear phenomena from data that even humans can find hard to interpret. Despite this, these models are generally regarded as black boxes, which, despite their performance, could hinder their adoption in some industries. Trusting these models for essential engineering applications such as automotive, energy, healthcare, and finance is difficult without any reasoning. In this context, the field of eXplainable AI attempts to develop techniques that temper the impenetrable nature of the models and promote a level of understanding of their behavior. Here, we present a novel framework, SpecXAI, based on the spectral characterization of the entire network. We show how this framework can be used to not only understand the model but also manipulate it into a more interpretable and linear symbolic representation, which is useful for better understanding the model's behavior.
Association between Obstructive sleep apnea and Allergic rhinitis in the United States: NHANES 2005–2006
Authors: Wang Chao , Shi Mengdi , Qin Zhu , Wang Jingyi , Li Wentao , Wang Rui , Xie Liangzhen , Li Yan
Published: August 2023

Exploring whether allergic rhinitis increases the risk of obstructive sleep apnea (OSA). Complete records of allergic rhinitis and sleep about OSA from the 2005–2006 National Health and Nutrition Examination Survey. The American people were divided into two groups: AR, NAR. OSA was assessed by three main signs and symptoms from the questionnaire. Multivariable logistic regression after adjusting for covariates was conducted to investigate the association of OSA with AR or NAR patterns. Among the 4864 participants, the prevalence of OSA was higher among AR participants compared to NAR participants (P < 0.0001).And AR participants also had other sleep problem. Our findings point out the hazard of OSA was once greater in AR affected person than NAR patient. And in contrast with NAR affected person AR affected person additionally have different sleep problem.
Compressive strength prediction of recycled aggregate concrete based on DE-XGBoost algorithm model and explainable machine learning
Authors: Guo Lei , luo Wei , Tian WenFeng , Guo LiXia
Published: August 2023

In the current concrete performance prediction research, common machine learning algorithms include random forest (RF), gradient boosting decision tree (GBDT), LightGBM (Light Gradient Boosting Machine), extreme gradient boosting tree (XGBoost), etc. Based on the compressive strength data of recycled aggregate concrete at different ages under different mixing ratios, this paper establishes a combined model (DE-XGBoost) of differential evolution algorithm (DE) and extreme gradient boosting tree algorithm (XGBoost), using XGBoost, Light GBM, GBDT, RF models as comparisons, and R², RMSE, MSE and MAE as model evaluation indexes. Use interpretability machine learning algorithms (SHAPs) to explore the feature importance of model input features to output results. The results show that: (1) In a single model, the prediction accuracy of XGBoost model (R²=0.9599) is better than that of Light GBM (R²=0.9493), GBDT (R²=0.9459), RF (R²=0.9321) model; (2) The prediction accuracy of the DE-XGBoost combination model is improved by 1.12% compared with the XGBoost model, and the RMSE, MSE and MAE values are reduced by 16.09%, 29.60% and 27.77%, respectively.
Fabrication and investigation of oxidized- β- Cyclodextrin nanoparticle as a novel class pH responsive drug delivery vehicle
Authors: Bergal Ayhan , Andac Muberra
Published: August 2023

Oxidized β- cyclodextrin (O-β-CD) nanoparticle was synthesized using oxidation process and Amoxicillin trihydrate (AMOX) model drug was integrated both via Schiff base reaction (C = N bond) as well as inclusion into cavity of O-β-CD to evaluate pH-responsive drug release behavior. The drug loaded nanocarrier (AM-O-β-CD) was characterized and results showed this formation, encapsulation and morphological change with average particle size (398 ± 8.51nm), negative zeta potential values (-25.4 ± 1.54) and high entrapment efficiency (86.1%). The in vitro release behavior of AM-O-β-CD was evaluated in physiological buffer conditions (0.1 M PBS, pH 5.2, at 37°C). It was found that drug-loaded AM-O-β-CD showed sustain, prolonged much higher drug release profile (94.72%) in low pH than that of the pure drug (24.18%) in the same acidic medium. Release kinetics of drug loaded AM-O-β-CD was determined according to well-known mathematical models, revealing that in vitro release profile could be best expressed by Higuchi kinetic model as release data showed the highest linearity (R2 = 0.967) so that drug release takes place due to both dissolution and diffusion as it is expected. As a result, it has been proven that the nanostructure has the potential to be pH sensitive drug carrier, especially for drugs containing NH2 side groups in acidic environments.
A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma
Authors: Samadi Pouria , Shahnazari Mina , Shekari Abolfazl , Maghool Fatemeh , Jalali Akram
Published: August 2023

The HAND2-AS1 (HAND2 Antisense RNA 1) lncRNA has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Long noncoding RNAs (lncRNAs) are rising as essential regulators of gene expression and pivotal contributors to immune modulation. Here, based on the co-expression network analysis and construction of interacting lncRNA-mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1's aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1's engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8 + T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1's potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The heightened HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic stratagem, and a focal point for immunotherapeutic interventions.
A double single-ended resonant inverter for low harmonic line frequency applications
Authors: Daoud Jafar M.
Published: August 2023

Some of the problems with photovoltaic projects for household applications are the cost, efficiency and complexity of the inverter. various inverter topologies are in use but they do not provide a boost and true sinewave voltage without additional complex circuitry. A double-switch resonant inverter with two different capacitor configurations is proposed in this paper. The performance of this topology is verified both by simulation and experimentally. The output voltage of the proposed resonant inverter has a true sinusoidal waveform at no-load, pure capacitive and pure inductive load conditions. At resistive load, the waveform is noticeably near sinusoidal and the THD is nonzero. Formulae for the resonant frequency and the voltage gain are derived and verified. The circuit was tested under different operating conditions and parameters for achieving zero-voltage switching (ZVS). The results show that there are no stability issues with the proposed circuit and that a closed-loop control is not required. The proposed topology is applicable to a wide range of loads and dc voltage sources at power-line frequencies.
Contamination Level, Spatial Distribution, and sources of Potentially Toxic Elements in Indoor Settled Household Dusts in Tehran, Iran
Authors: Khajooee Neda , Modabberi Soroush , Zadeh Behnoush Khoshmanesh , Razavian Fatemeh , Gayà-Caro Nuria , Sierra Jordi , Rovira Joaquim
Published: August 2023

Tehran, the capital city of Iran has been facing air pollution since several decades ago because of rapid urbanization and population growth and improper use of vehicles, and low quality of fuels. In this study, 31 indoor dust samples were collected passively from residential, and commercial buildings located in the central and crowded districts of the city and were analyzed after sample preparation for elements (As, Be, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, Sr, V, Zn). Statistical data analyses were used in comparing their relationship in various uses and variations and source identification. Geochemical indices of Contamination Factor (CF) and Pollution Load Index (PLI) were used to evaluate the degree of contamination.
The mean concentration of Zn, Cu, and Pb (938, 206, and 176 µg g-1), are 6, 5, and 3 times higher than their mean values for worldwide urban soils, respectively and Cd, Mo, and Ni showed about 1.5 times higher concentrations while As, Co, Cr, Mn, and Sr were within the range of reference soils. Be, V, and Sb showed remarkably lower mean values. Building use does not influence element levels in indoor deposited dust except for Pb and Zn. A comparison of indoor concentrations with previously published data for outdoor dusts showed that Mo, Cu, Pb, and Ni are more enriched while As, Cd and Zn are less enriched in street dusts. The CF values indicate the order of Hg>Zn>Cd>Pb>Cu>As>Ni>Cr>Co>V. For Hg, Zn, Pb, Cd, and Cu all or almost all of the samples showed very highly contamination. PLI showed values higher than 1, or contamination in all samples. The multivariate statistical analysis and specific geological location of Tehran indicated that mafic-intermediate volcanic rocks are the main sources for Cr, Cu, Fe, and Ni (PC1). As, Pb and V (PC2) are attributed to fossil fuel combustion in vehicles and residential buildings. Pb is a legacy metal remained from using leaded gasoline, which was phased out in the 1990s. Zn (PC3) is derived from vehicle tires.