bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH RETURN ON EQUITY DAN DEBT TO EQUITY RATIO TERHADAP NILAI PERUSAHAAN DENGAN KEBIJAKAN DIVIDEN SEBAGAI VARIABEL MODERASI
Authors: Pinandita Candra Pramula
Published: April 2024

The purpose of this research was to know the influence of the financial performance of firm value with dividend policy as moderating variables. The variables used were Return On Equity, Debt to Equity Ratio as independent variable, Firm Value as dependent variable and Dividend Policy as  moderating variable. Sampling method used purposive sampling in manufacturing companies listed LQ-45 index from 2011-2015 and it was obtained 10 companies of them are used as the samples. This study used secondary data with documentation as collect data method. This study used simple regression and absolute residual as data analysis. The result showed that ROE had significant positive effect on PBV, DPR had significant positive effect on relationship between ROE and PBV, DER had significant positive effect on PBV, DPR had significant positive effect on relationship between ROE and PBV. The results of this research are expected to help management consider investment opportunities company in the future
An Extensive Review of Various Optimization Techniques for Electric Discharge Machining
Authors: Singh Abhishek , Garg Rajiv Kumar , Sachdeva Anish
Published: April 2024

In this paper, an investigation of wire and electric discharge machining has been provided. Wider possibilities for the creation of composites and sophisticated materials were made possible by advances in machining science. As research in this area continues, more materials with complicated meteorological structures and strong mechanical resistance capabilities are emerging. Because of the exceptional strength, toughness, and hardness of these materials, advanced machining techniques are replacing traditional machining techniques in this industry. One unique type of advanced machining technique used in this research is electrical discharge machining. It has also been discussed how these machining methods might develop in the future. This paper serves as both a research tool and a step in that direction. The best settings for the processes outlined above will aid in boosting diverse sectors' output. The research on non-conventional machining processes with diverse optimisation strategies is presented in this review. The optimisation techniques taken into account for the current work were Taguchi's, artificial neural networks, particle swarm optimisation, response surface approach, grey connection analysis, and genetic algorithm.
Case Report of a Hidden Intruder—Extremely Rare Presentation of Hydatidosis as a Nuchal Tumoural Mass
Authors: Voicu Dragoș F. , Popazu Constantin , Râșnoveanu Delia Mihaela , Mihalache Daniela , Toma Alexandra
Published: April 2024

Introduction: The parasitic tapeworm impersonated by the larvae of Echinococcus granulosus represents the aetiology of the hydatid pathology. The predilect site of invasion is the liver, but there are other cases of different localization all over the body, regardless of the type of invaded tissue. Soft tissue hydatidosis can be a real challenge for the clinician in terms of the diagnosis, and it might generate various complications such as anaphylactic shock. The aim of the present work is to illustrate a unique case of primary hydatidosis located in the nuchal region.

Case Report: We report the case of a 68-year-old male patient, a zootechnic, who presented at the hospital with a tumoural mass (dimension: about 12/10 cm) located in the nuchal region. The complex approach needed consisted of surgical therapy along with histopathological confirmation of the diagnostic and antiparasitic medication, which led to a complete recovery with a low probability of recurrence.

Discussion: Encounters with patients with primary soft tissue hydatidosis are exceptionally rare, but the surgeon must take into consideration this clinical diagnosis, especially for patients located in an endemic region with occupations that might have exposed the patient to this type of parasite.
A mini-review on data science approaches in crop yield and disease detection
Authors: Valleggi Lorenzo , Stefanini Federico Mattia
Published: April 2024

Agriculture constitutes a sector with a considerable environmental impact, a concern that is poised to increase with the projected growth in population, thereby amplifying implications for public health. Effectively mitigating and managing this impact demands the implementation of intelligent technologies and data-driven methodologies collectively called precision agriculture. While certain methodologies enjoy widespread acknowledgement, others, despite their lesser prominence, contribute meaningfully. This mini-review report discusses the prevalent AI technologies within precision agriculture over the preceding five years, with a specific emphasis on crop yield prediction and disease detection domains extensively studied within the current literature. The primary objective is to give a comprehensive overview of AI applications in agriculture, spanning machine learning, deep learning, and statistical methods. This approach aims to address a notable gap wherein existing reviews predominantly focus on singular aspects rather than presenting a unified and inclusive perspective.
Prediction of polyspecificity from antibody sequence data by machine learning
Authors: Éliás Szabolcs , Wrzodek Clemens , Deane Charlotte M. , Tissot Alain C. , Klostermann Stefan , Ros Francesca
Published: April 2024

Antibodies are generated with great diversity in nature resulting in a set of molecules, each optimized to bind a specific target. Taking advantage of their diversity and specificity, antibodies make up for a large part of recently developed biologic drugs. For therapeutic use antibodies need to fulfill several criteria to be safe and efficient. Polyspecific antibodies can bind structurally unrelated molecules in addition to their main target, which can lead to side effects and decreased efficacy in a therapeutic setting, for example via reduction of effective drug levels. Therefore, we created a neural-network-based model to predict polyspecificity of antibodies using the heavy chain variable region sequence as input. We devised a strategy for enriching antibodies from an immunization campaign either for antigen-specific or polyspecific binding properties, followed by generation of a large sequencing data set for training and cross-validation of the model. We identified important physico-chemical features influencing polyspecificity by investigating the behaviour of this model. This work is a machine-learning-based approach to polyspecificity prediction and, besides increasing our understanding of polyspecificity, it might contribute to therapeutic antibody development.
Rethinking running biomechanics: a critical review of ground reaction forces, tibial bone loading, and the role of wearable sensors
Authors: Xiang Liangliang , Gao Zixiang , Wang Alan , Shim Vickie , Fekete Gusztáv , Gu Yaodong , Fernandez Justin
Published: April 2024

This study presents a comprehensive review of the correlation between tibial acceleration (TA), ground reaction forces (GRF), and tibial bone loading, emphasizing the critical role of wearable sensor technology in accurately measuring these biomechanical forces in the context of running. This systematic review and meta-analysis searched various electronic databases (PubMed, SPORTDiscus, Scopus, IEEE Xplore, and ScienceDirect) to identify relevant studies. It critically evaluates existing research on GRF and tibial acceleration (TA) as indicators of running-related injuries, revealing mixed findings. Intriguingly, recent empirical data indicate only a marginal link between GRF, TA, and tibial bone stress, thus challenging the conventional understanding in this field. The study also highlights the limitations of current biomechanical models and methodologies, proposing a paradigm shift towards more holistic and integrated approaches. The study underscores wearable sensors’ potential, enhanced by machine learning, in transforming the monitoring, prevention, and rehabilitation of running-related injuries.
Characterization of polyamine metabolism predicts prognosis, immune profile, and therapeutic efficacy in lung adenocarcinoma patients
Authors: Li Zhouhua , Wu Yue , Yang Weichang , Wang Wenjun , Li Jinbo , Huang Xiaotian , Yang Yanqiang , Zhang Xinyi , Ye Xiaoqun
Published: April 2024

Background

Polyamine modification patterns in lung adenocarcinoma (LUAD) and their impact on prognosis, immune infiltration, and anti-tumor efficacy have not been systematically explored.

Methods

Patients from The Cancer Genome Atlas (TCGA) were classified into subtypes according to polyamine metabolism-related genes using the consensus clustering method, and the survival outcomes and immune profile were compared. Meanwhile, the geneCluster was constructed according to the differentially expressed genes (DEGs) of the subtypes. Subsequently, the polyamine metabolism-related score (PMRS) system was established using the least absolute shrinkage and selection operator (LASSO) multivariate regression analysis in the TCGA training cohort (n = 245), which can be applied to characterize the prognosis. To verify the predictive performance of the PMRS, the internal cohort (n = 245) and the external cohort (n = 244) were recruited. The relationship between the PMRS and immune infiltration and antitumor responses was investigated.

Results

Two distinct patterns (C1 and C2) were identified, in which the C1 subtype presented an adverse prognosis, high CD8+ T cell infiltration, tumor mutational burden (TMB), immune checkpoint, and low tumor immune dysfunction and exclusion (TIDE). Furthermore, two geneClusters were established, and similar findings were observed. The PMRS, including three genes (SMS, SMOX, and PSMC6), was then constructed to characterize the polyamine metabolic patterns, and the patients were divided into high- and low-PMRS groups. As confirmed by the validation cohort, the high-PMRS group possessed a poor prognosis. Moreover, external samples and immunohistochemistry confirmed that the three genes were highly expressed in tumor samples. Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC50) values.

Conclusion

We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.
Economy of scale for green hydrogen-derived fuel production in Nepal
Authors: Thapa Biraj Singh , Pandey Bishnu , Ghimire Rahul
Published: April 2024

Opportunity for future green hydrogen development in Nepal comes with end-use infrastructural challenges. The heavy reliance of industries on fossil fuels (63.4%) despite the abundance of hydroelectricity poses an additional challenge to the green transition of Nepal. The presented work aims to study the possibility of storing and utilizing spilled hydroelectricity due to runoff rivers as a compatible alternative to imported petroleum fuels. This is achieved by converting green hydrogen from water electrolysis and carbon dioxide from carbon capture of hard-to-abate industries into synthetic methane for heating applications via the Sabatier process. An economy-of-scale study was conducted to identify the optimal scale for the reference case (Industries in Makwanpur District Nepal) for establishing the Synthetic Natural Gas (SNG) production industry. The techno-economic assessment was carried out for pilot scale and reference scale production unit individually. Uncertainty and sensitivity analyses were performed to study the project profitability and the sensitivity of the parameters influencing the feasibility of the production plant. The reference scale for the production of Synthetic Natural Gas was determined to be 40 Tons Per Day (TPD), with a total capital investment of around 72.15 Million USD. Electricity was identified as the most sensitive parameter affecting the levelized cost of production (LCOP). The 40 TPD plant was found to be price competitive to LPG when electricity price is subsidized below 3.55 NPR/unit (2.7 c/unit) from 12 NPR/unit (9.2 c/unit). In the case of the 2 TPD plant, for it to be profitable, the price of electricity must be subsidized to well below 2 NPR/kWh. The study concludes that the possibility of SNG production in Nepal is profitable and price-competitive at large scales and at the same time limited by the low round efficiency due to conversion losses. Additionally, it was observed that highly favorable conditions driven by government policies would be required for the pilot-scale SNG project to be feasible.
Single-cell RNA sequencing and ATAC sequencing identify novel biomarkers for bicuspid aortic valve-associated thoracic aortic aneurysm
Authors: Liu Xu-Wen , Wang Pei , Zhang Li , Zhu Yu , Zhai Jun-Yu , Wang Chang-Nan , Li Jun , Xiao Jian
Published: April 2024

Introduction

Bicuspid aortic valve (BAV) is the most prevalent congenital cardiovascular defect and known to cause thoracic aortic aneurysms (TAAs). To improve our understanding of BAV pathogenesis, we characterized the cellular composition of BAV tissues and identified molecular changes in each cell population.

Methods

Tissue samples from two patients with BAV and two heart transplant donors were analyzed using single-cell RNA sequencing, assay for transposase-accessible chromatin using sequencing, and weighted gene coexpression network analysis for differential gene analysis. TAA-related changes were evaluated by comparing the proportion of each cell type and gene expression profiles between TAA and control tissues. Further, by combining our single-cell RNA sequencing data with publicly available data from genome-wide association studies, we determined critical genes for BAV.

Results

We found 20 cell subpopulations in TAA tissues, including multiple subtypes of smooth muscle cells, fibroblasts, macrophages, and T lymphocytes. This result suggested that these cells play multiple functional roles in BAV development. Several differentially expressed genes, including CD9, FHL1y, HSP90AA1, GAS6, PALLD, and ACTA2, were identified.

Discussion

We believe that this comprehensive assessment of the cellular composition of TAA tissues and the insights into altered gene expression patterns can facilitate identification of novel diagnostic biomarkers and therapeutic targets for BAV-associated TAA.
The mechanics of congenital heart disease: from a morphological trait to the functional echocardiographic evaluation
Authors: Avesani Martina , Sabatino Jolanda , Borrelli Nunzia , Cattapan Irene , Leo Isabella , Pelaia Giulia , Moscatelli Sara , Bianco Francesco , Bassareo PierPaolo , Martino Francesco , Leonardi Benedetta , Oreto Lilia , Guccione Paolo , Di Salvo Giovanni
Published: April 2024

Advances in pediatric cardiac surgery have resulted in a recent growing epidemic of children and young adults with congenital heart diseases (CHDs). In these patients, congenital defects themselves, surgical operations and remaining lesions may alter cardiac anatomy and impact the mechanical performance of both ventricles. Cardiac function significantly influences outcomes in CHDs, necessitating regular patient follow-up to detect clinical changes and relevant risk factors. Echocardiography remains the primary imaging method for CHDs, but clinicians must understand patients' unique anatomies as different CHDs exhibit distinct anatomical characteristics affecting cardiac mechanics. Additionally, the use of myocardial deformation imaging and 3D echocardiography has gained popularity for enhanced assessment of cardiac function and anatomy. This paper discusses the role of echocardiography in evaluating cardiac mechanics in most significant CHDs, particularly its ability to accommodate and interpret the inherent anatomical substrate in these conditions.
Methane gas flares in the forearc basin of the Andaman-Nicobar subduction zone
Authors: Ankush  , Dewangan P. , Sriram G.
Published: April 2024

Gas hydrates deposits in the Andaman forearc basin are inferred from seismic data and confirmed by drilling/coring during the NGHP-01 expedition. We present new evidence of gas flares in the Andaman forearc basin, detected through water column image (WCI), subbottom profiling, and high-resolution seismic data acquired onboard RV Sindhu Sadhana (SSD-085) in November-December 2021. The gas flares are located over an elongated sedimentary ridge, featuring two prominent mounds (M1 and M2) with distinct geological features. Compressional tectonics induced by the Diligent fault (DLF) formed the ridge with varying slopes and elevations. Gas flares observed above the mound M1 in WCI and sub-bottom profiler data. Seafloor samples reveal carbonate rocks with visible pores, indicating gas/fluid migration or burrows. The regional seismic profile delineates three sedimentary sequences: folded and faulted strata, mass transport deposits, and horizontal-to-sub-horizontal sedimentary layers. Additionally, we observed a bottom simulating reflector (BSR), indicating potential subsurface gas hydrate deposits. Detailed high-resolution seismic data revealed complex fault systems near bathymetry mounds (M1 and M2), which may serve as pathways for vertical fluid/gas migration.
The application of the game theory combination weighting-normal cloud model to the quality evaluation of surrounding rocks
Authors: Zhao Bing , Shao Yang-Bing , Yang Chao , Zhao Chao
Published: April 2024

The status of surrounding rocks dramatically influences the safety of construction workers, so the quality assessment of surrounding rocks has great significance. The uniaxial saturated compressive strength of rock (X1), the quality index of surrounding rock (X2), the frictional coefficient of the structural surface (X3), the joint spacing (X4), the state of groundwater(X5), and the integrity coefficient (X6) are selected as the initial evaluation index. Then, the game theory combination weighting-normal cloud model is introduced. Second, the certainty degree matrix of each index is established, and the weight coefficients of assessment indexes are determined based on the game theory combination weighting method. Finally, the quality level of surrounding rocks is judged. Compared with the traditional methods, the proposed model solves the fuzziness and randomness of different indexes, improves the reliability of the assessment process, and enhances the predictive accuracy of assessment results. In addition, it can provide a solution scheme for the evaluation indicators, which are difficult to quantify, and reduce the influence of human factors. The results obtained from the suggested model are consistent with the current specification. Its accuracy approaches 100%, and the method is feasible for the quality level assessment of surrounding rocks, providing a new technique and approach to assessing the risk level of surrounding rocks.
Endocrine, auxological and metabolic profile in children and adolescents with Down syndrome: from infancy to the first steps into adult life
Authors: Molinari Silvia , Fossati Chiara , Nicolosi Maria Laura , Di Marco Santo , Faraguna Martha Caterina , Limido Francesca , Ocello Laura , Pellegrinelli Claudia , Lattuada Martina , Gazzarri Alessandra , Lazzerotti Alessandra , Sala Debora , Vimercati Chiara , Capitoli Giulia , Daolio Cecilia , Biondi Andrea , Balduzzi Adriana , Cattoni Alessandro
Published: April 2024

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.
Low-carbon optimal operation of the integrated energy system considering integrated demand response and oxygen-rich combustion capture technology
Authors: Ji Xiu , Li Meng , Li Meiyue , Han Huanhuan
Published: April 2024

In view of the current operating constraints and environmental pollution problems of traditional units, in this article, oxygen-rich combustion capture technology is introduced to transform gas-fired units, demand response technology is used on the load side, the energy conversion equipment such as power-to-gas equipment is combined to form an integrated energy system, and then, a low-carbon optimization approach of the integrated energy system is proposed. First, the system architecture is constructed, and a model with an oxygen-rich combustion unit and integrated demand response is established. Second, a power-to-gas equipment model considering reaction waste heat utilization and oxygen recovery is established. Finally, a stepped carbon trading mechanism is introduced to establish a low-carbon economic scheduling model for the integrated energy system with the goal of minimizing the operating cost of the integrated energy system. The simulation results show that the total cost and carbon emissions of the integrated energy system are reduced by 6.44% and 44.24%, respectively, under this model. At the same time, the operation adjustment capability and the oxygen production efficiency of the internal units of the system are improved.
Deep learning-based correlation analysis for probabilistic power flow considering renewable energy and energy storage
Authors: Xia Xiaotian , Xiao Liye , Ye Hua
Published: April 2024

Developing photovoltaic (PV) and wind power is one of the most efficient approaches to reduce carbon emissions. Accumulating the PV and wind energy resources at different geographical locations can minimize total power output variance as injected into the power systems. To some extent, a low degree of the variance amplitude of the renewable resources can reduce the requirement of in-depth regulation and dispatch for the fossil fuel-based thermal power plants. Such an issue can alternatively reduce carbon emissions. Thus, the correlation problem by minimizing the variance of total PV and wind power plays a vital role in power system planning and operation. However, the synergistic effect of power output correlation is mainly considered on the generation side, and it is often neglected for the correlation relationship between the power grid components. To address this problem, this paper proposes a correlation coefficient analysis method for the power grid, which can quantify the relationship between energy storage and the probabilistic power flow (PPF) of the grid. Subsequently, to accelerate the mapping efficiency of power correlation coefficients, a novel deep neural network (DNN) optimized by multi-task learning and attention mechanism (MA-DNN) is developed to predict power flow fluctuations. Finally, the simulation results show that in IEEE 9-bus and IEEE14-bus systems, the strong correlation grouping percentage between the power correlation coefficients and power flow fluctuations reached 92% and 51%, respectively. The percentages of groups indicating weak correlation are 4% and 38%. In the modified IEEE 23-bus system, the computational accuracy of MA-DNN is improved by 37.35% compared to the PPF based on Latin hypercube sampling. Additionally, the MA-DNN regression prediction model exhibits a substantial improvement in assessing power flow fluctuations in the power grid, achieving a speed enhancement of 758.85 times compared to the conventional probability power flow algorithms. These findings provide the rapid selection of the grid access point with the minimum power flow fluctuations.
Communication network robust routing optimization in an integrated energy cyber–physical system based on a random denial-of-service attack
Authors: Fan Hong , Huang Xu , Wang Diwei , Zhou Boyang
Published: April 2024

The integration of power grids and communication networks in smart grids enhances system safety and reliability but also exposes vulnerabilities to network attacks, such as Denial-of-Service (DoS) attacks targeting communication networks. A multi-index evaluation approach is proposed to optimize routing modes in integrated energy cyber-physical systems (IECPS) considering potential failures from attacks. Security and economic service evaluation indexes are incorporated to quantify the significance of information flow routing. An optimization model for electric, heat, and gas routing in worst-case scenarios is formulated and solved using a column and constraint generation algorithm. The optimized routing method effectively circumvents specified attack areas, reducing the correlation degree of communication links within the attack area. Comparison with single-service optimization methods demonstrates the superiority of the proposed approach in mitigating the impact of network attacks on IECPS. The study highlights the importance of considering security and economic factors in optimizing routing modes to enhance the resilience of integrated energy cyber-physical systems against network attacks, particularly DoS attacks on communication networks. The evaluation index approach presented in this study provides a comprehensive method for assessing the importance of communication links in IECPS and optimizing routing modes to improve system robustness and reliability in the face of network attacks.
Expression profiling of ALOG family genes during inflorescence development and abiotic stress responses in rice (Oryza sativa L.)
Authors: Liu Zhiyuan , Fan Zhenjiang , Wang Lei , Zhang Siyue , Xu Weichen , Zhao Sijie , Fang Sijia , Liu Mei , Kofi Sackitey Mark , Zhang Shuangxi , Kang Ningning , Ai Hao , Li Ruining , Feng Tingting , Wei Shuya , Zhao Heming
Published: April 2024

The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.
Gut microbiome, T cell subsets, and cytokine analysis identify differential biomarkers in tuberculosis
Authors: Chai Yinghui , Liu Xin , Bai Guangliang , Zhou Nannan , Liu Danfeng , Zhang Xiaomeng , Li Min , Li Kang , Lei Hong
Published: April 2024

Introduction

The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis.

Methods

According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines.

Results

We showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10.

Conclusion

Diverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB.
Peripheral CD4+ T cells correlate with response and survival in patients with advanced non-small cell lung cancer receiving chemo-immunotherapy
Authors: Yang Xin , Li Qiao , Zeng Tianyang
Published: April 2024

Background

The aim of the present study was to explore the potential of peripheral immune cells in predicting the response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1 immunotherapy and platinum-based chemotherapy.

Participants and Methods

We utilized flow cytometry to examine the levels and dynamics of blood immune cells in 79 advanced NSCLC patients treated with the chemoimmunotherapy between December 2019 and January 2022. The pre- and post-treatment blood samples were collected within 3 days prior to the initiation of the first and third cycle of combination treatment, respectively. Progression-free survival (PFS) and overall survival (OS) analyses were conducted using Kaplan-Meier method and Cox regression models.

Results

The pre-treatment CD4+/Total T cells ratio was significantly higher in responders than non-responders (P < 0.05). The levels of pre-treatment total lymphocytes (P = 0.012), total B lymphocytes (P = 0.025), and NK cells (P = 0.022), and post-treatment NK cells (P = 0.011) and NKT cells (P = 0.035) were significantly associated with OS. Post-treatment CD8+/Total T cells ratio was positively correlated with OS (P = 0.038). In multivariate analysis, post-treatment NK cells and post-treatment CD4+CD8+/Total T cells ratio were negatively associated with OS (hazard ratio [HR] = 10.30, P = 0.038) and PFS (HR = 1.95, P = 0.022), respectively. Notably, significantly positive correlations were observed between CD4+/Total T cells ratio and prognosis both before and after treatment (P < 0.05).

Conclusion

To summarize, our finding reveals that high CD4+/total T cells ratio was associated with favorable response and prognosis, highlighting its potential as a predictive biomarker to guide the selection of likely responders to platinum and anti-PD-1 combination therapy.
Ferroptosis in liver cancer: a key role of post-translational modifications
Authors: Xu Ying , Xing Zhiyao , Abdalla Ibrahim Suliman Ruaa , Liu Zichuan , Tang Fengyuan
Published: April 2024

Ferroptosis is an emerging form of regulated cell death in an oxidative stress- and iron-dependent manner, primarily induced by the over-production of reactive oxygen species (ROS). Manipulation of ferroptosis has been considered a promising therapeutic approach to inhibit liver tumor growth. Nevertheless, the development of resistance to ferroptosis in liver cancer poses a significant challenge in cancer treatment. Post-translational modifications (PTMs) are crucial enzymatic catalytic reactions that covalently regulate protein conformation, stability and cellular activities. Additionally, PTMs play pivotal roles in various biological processes and divergent programmed cell death, including ferroptosis. Importantly, key PTMs regulators involved in ferroptosis have been identified as potential targets for cancer therapy. PTMs function of two proteins, SLC7A11, GPX4 involved in ferroptosis resistance have been extensively investigated in recent years. This review will summarize the roles of PTMs in ferroptosis-related proteins in hepatocellular carcinoma (HCC) treatment.
Prognostic value of CD8+T cells related genes and exhaustion regulation of Notch signaling pathway in hepatocellular carcinoma
Authors: Pu Qing , Yu Lihua , Liu Xiaoli , Yan Huiwen , Xie Yuqing , Cai Xue , Wu Yuan , Du Juan , Yang Zhiyun
Published: April 2024

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion—a potential target for future immunotherapeutic interventions.
The molecular mechanism of macrophage-adipocyte crosstalk in maintaining energy homeostasis
Authors: Zhang Yudie , Zhang Bin , Sun Xiaobo
Published: April 2024

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism and obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming of adipocytes, browning, and thermogenesis. Accordingly, investigating the roles of macrophages and adipocytes in the maintenance of energy homeostasis is critical for the development of novel therapeutic approaches specifically targeting macrophages in metabolic disorders such as obesity. Current review outlines macrophage polarization not only regulates the release of central nervous system and inflammatory factors, but controls mitochondrial function, and other factor that induce metabolic reprogramming of adipocytes and maintain energy homeostasis. We also emphasized on how the adipocytes conversely motivate the polarization of macrophage. Exploring the interactions between adipocytes and macrophages may provide new therapeutic strategies for the management of obesity-related metabolic diseases.
Immunomodulatory effects of a probiotic combination treatment to improve the survival of Pacific oyster (Crassostrea gigas) larvae against infection by Vibrio coralliilyticus
Authors: Hesser Jennifer , Mueller Ryan S. , Langdon Chris , Schubiger Carla B.
Published: April 2024

Introduction

The culture of Pacific oysters (Crassostrea gigas) is of significant socio-economic importance in the U.S. Pacific Northwest and other temperate regions worldwide, with disease outbreaks acting as significant bottlenecks to the successful production of healthy seed larvae. Therefore, the current study aims to describe the mechanisms of a probiotic combination in improving the survival of C. gigas larvae. Specifically, we investigate changes in C. gigas larval gene expression in response to V. coralliilyticus infection with or without a pre-treatment of a novel probiotic combination.

Methods

Treatment groups consisted of replicates of Pacific oyster larvae exposed to a) a combination of four probiotic bacteria at a total concentration of 3.0 x 105 CFU/mL at 18 hours post-fertilization (hpf), b) pathogenic V. coralliilyticus RE22 at a concentration of 6.0 x 103 CFU/mL at 48 hpf, and c) the probiotic combination at 18 hpf and V. coralliilyticus RE22 at 48 hpf. RNA was extracted from washed larvae after 72 hpf, and transcriptome sequencing was used to identify significant differentially expressed genes (DEGs) within each treatment.

Results

Larvae challenged with V. coralliilyticus showed enhanced expression of genes responsible for inhibiting immune signaling (i.e., TNFAIP3, PSMD10) and inducing apoptosis (i.e., CDIP53). However, when pre-treated with the probiotic combination, these genes were no longer differentially expressed relative to untreated control larvae. Additionally, pre-treatment with the probiotic combination increased expression of immune signaling proteins and immune effectors (i.e., IL-17, MyD88). Apparent immunomodulation in response to probiotic treatment corresponds to an increase in the survival of C. gigas larvae infected with V. coralliilyticus by up to 82%.

Discussion

These results indicate that infection with V. coralliilyticus can suppress the larval immune response while also prompting cell death. Furthermore, the results suggest that the probiotic combination treatment negates the deleterious effects of V. coralliilyticus on larval gene expression while stimulating the expression of genes involved in infection defense mechanisms.
Outer membrane vesicles derived from Bordetella pertussis are potent adjuvant that drive Th1-biased response
Authors: Pschunder Bernarda , Locati Lucia , López Oriana , Martin Aispuro Pablo , Zurita Eugenia , Stuible Matthew , Durocher Yves , Hozbor Daniela
Published: April 2024

For several years, we have been committed to exploring the potential of Bordetella pertussis-derived outer membrane vesicles (OMVBp) as a promising third-generation vaccine against the reemerging pertussis disease. The results of our preclinical trials not only confirm its protective capacity against B. pertussis infection but also set the stage for forthcoming human clinical trials. This study delves into the examination of OMVBp as an adjuvant. To accomplish this objective, we implemented a two-dose murine schedule to evaluate the specific immune response induced by formulations containing OMVBp combined with 3 heterologous immunogens: Tetanus toxoid (T), Diphtheria toxoid (D), and the SARS-CoV-2 Spike protein (S). The specific levels of IgG, IgG1, and IgG2a triggered by the different tested formulations were evaluated using ELISA in dose-response assays for OMVBp and the immunogens at varying levels. These assays demonstrated that OMVBp exhibits adjuvant properties even at the low concentration employed (1.5 μg of protein per dose). As this effect was notably enhanced at medium (3 μg) and high concentrations (6 μg), we chose the medium concentration to determine the minimum immunogen dose at which the OMV adjuvant properties are significantly evident. These assays demonstrated that OMVBp exhibits adjuvant properties even at the lowest concentration tested for each immunogen. In the presence of OMVBp, specific IgG levels detected for the lowest amount of antigen tested increased by 2.5 to 10 fold compared to those found in animals immunized with formulations containing adjuvant-free antigens (p<0.0001). When assessing the adjuvant properties of OMVBp compared to the widely recognized adjuvant alum, we detected similar levels of specific IgG against D, T and S for both adjuvants. Experiments with OMVs derived from E. coli (OMVE.coli) reaffirmed that the adjuvant properties of OMVs extend across different bacterial species. Nonetheless, it’s crucial to highlight that OMVBp notably skewed the immune response towards a Th1 profile (p<0.05). These collective findings emphasize the dual role of OMVBp as both an adjuvant and modulator of the immune response, positioning it favorably for incorporation into combined vaccine formulations.
Parameterization scheme of the sea surface drag coefficient considering the influence of wave states and sea spray stress
Authors: Zhao Zeqi , Shi Jian , Wang Hanshi , Yi Zhenhui , Zhang Wenjing , Zhang Xueyan
Published: April 2024

The drag coefficient of the sea surface is crucial for the exchange of momentum between the ocean and atmosphere. The wave state significantly influences the variability of the drag coefficient. In the past, researchers commonly employed single-parameterization methods to describe this influence. However, the influence of wave conditions on drag coefficient is complex and variable, and it is difficult to accurately describe it with a single parameter alone. Wave age represents the ability of wind-induced waves to input energy, while wave steepness reflects the stability of the waves. By simultaneously considering wave age and wave steepness, a more accurate characterization of the dynamic nature of waves can be achieved. Additionally, the presence of sea spray profoundly impacts the distribution of the momentum flux between the ocean and atmosphere, thereby influencing the drag coefficient of the sea surface. In this study, we established a novel sea spray generation function that bases on both the wind speed and wave states (wave steepness and wave age). Considering this function, the momentum flux of sea spray droplets was analyzed under different wave states. Moreover, with increasing wave age or wave steepness, the effective sea surface drag coefficient is attenuated at low to moderate wind speeds. Considering the challenge of simultaneously obtaining wave age and wave steepness data, this paper proposes a relationship equation between the two wave state parameters. When the wave age is greater than 0.4, the correlation between the wave age and the wave steepness is strong. As the wind speed increases from low to high, there is a noticeable decrease in the effective sea surface drag coefficient with the corresponding increase in wave age. When the wave age is less than 0.4, the wave steepness reaches a maximum value, and the effective sea surface drag coefficient increases with the increase of the wave age at medium and low wind speed. With further increases in wind speed, the momentum flux derived from the air also increases. Simultaneously, the effective sea surface drag coefficient exhibits a decrease as wave age increases.
Bioavailability and remineralization rates of sediment-derived dissolved organic carbon from a Baltic Sea depositional area
Authors: Lengier Monika , Koziorowska-Makuch Katarzyna , Szymczycha Beata , Kuliński Karol
Published: April 2024

This pilot study investigated the bioavailability and remineralization kinetics of the sediment-derived dissolved organic carbon (DOC) from the Gdańsk Deep, a depositional area in the Baltic Sea. This was assessed in the long-lasting (126 d) incubation experiment, in which the mixture of DOC from sediment pore water and bottom water was exposed to oxic microbial respiration with incubation of bottom water as a control run. The obtained decay curves allowed us to distinguish three DOC fractions: labile (DOCL), semi-labile (DOCSL), and refractory (DOCR). In bottom water, the refractory fraction was predominant and amounted to almost 85% of total DOC, whereas about 15% of DOC was bioavailable: 6% labile and 9% semi-labile. In contrast, DOC from pore water was much more bioavailable DOC (~55% of total DOC) and contained 11% DOCL and 44% DOCSL. The remineralization rate constants recalculated to the in situ temperature of 6°C for labile and semi-labile DOC in pore water were 0.025 d−1 and 0.002 d−1, respectively, whereas, in bottom water, 0.026 d−1 and 0.004 d−1. The half-life times for DOCL were comparable for both bottom water and pore water and amounted to 26.2 d and 27.6 d, respectively. For DOCSL, the half-life time was shorter for bottom water (165.5 d) than for pore water (322.9 d).
Shaping ability of ProTaper Ultimate and BlueShaper in mandibular molars: a micro-CT evaluation
Authors: Greco Katia , Iacono Francesco , Montagna Francesco , Esposito Corcione Carola , Paolone Gaetano , Gherlone Enrico , Cantatore Giuseppe
Published: April 2024

Aim: The study aimed to evaluate the shaping characteristics of ProTaper Ultimate (Dentsply Sirona) and BlueShaper (Zarc4Endo) using microcomputed tomographic imaging technology (micro-CT).

Methods: Thirty mesial and distal canals of extracted second mandibular molars with similar anatomy were selected and scanned pre- and postoperatively by micro-CT scanning (SkyScan 1172, Bruker micro-CT) with a voxel size of 11 μm and shaped with two different procedures: ProTaper Ultimate (Group 1: n = 15) and BlueShaper (Group 2: n = 15) were used following the manufacturer’s recommendations up to final 30 apical size. Irrigation was ensured in all groups with 5.25% NaOCl and 10% EDTA during instrumentation. Canal transportation, the volume of removed dentin, and area of untreated surface were matched with preoperative values with Bruker CT Analyser (Bruker micro-CT). Data were statistically analyzed using Student’s t-test.

Results: No significant differences were observed between Group 1 and Group 2 in terms of canal transportation, volume of removed dentin, and untreated surfaces. A significant difference (p < 0.05) in the amount of untreated surfaces was found between the mesial and distal canals in both groups.

Conclusion: Shaping procedures with both ProTaper Ultimate and BlueShaper demonstrated similar canal enlargement volumes and similar canal transportation without evidence of significant preparation errors. Nevertheless, a high amount of untreated surface was reported for both systems, particularly in distal canals.