bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic optimization elucidates optimal higher-level pathogenicity strategies of Pseudomonas aeruginosa
Authors: Dimitriew Wassili , Schuster Stefan 
Published: June 2024

Abstract

Pseudomonas aeruginosa is a robust pathogen and possesses many virulence components, including the ability to survive inside macrophages. A minimal model is proposed to study the interaction of P. aeruginosa and the human host in terms of nested defence, in which the host and pathogen counter each other in a back-and-forth interaction. In particular, the pathogen attacks the host, macrophages of the host engulf the pathogen and reduce its access to glucose, the pathogen activates the glyoxylate shunt which is started by an enzyme isocitrate lyase (Icl), the host inhibits it by itaconic acid, and the pathogen metabolizes itaconic acid using the enzyme succinyl-CoA:itaconate CoA transferase (Ict). Therefore, the pathogen needs to allocate its limited protein resource between the enzymes Icl and Ict in order to maximize the time integral of a flux through the enzyme Icl. We use both random search and dynamic optimization and analyze three different scenarios of the interaction. We identify the enzyme Ict as a cost-effective means of counter-counter-counter defence and as a possible drug target.
A study on factors influencing dynamic response of thin-walled box-girder railway bridge subjected to high speed train load through regression modelling
Authors: Verma Virajan , Wani Khair Ul Faisal , Dhiman Sahil 
Published: June 2024

Abstract

The issue of evaluating the dynamic characteristics of a bridge due to the presence of rapidly moving vehicles has considerable importance. The objective of this study is to conduct a comprehensive study on the variables that influence the dynamic behavior of a thin-walled box-girder bridge exposed to high-speed train loads using regression analysis. The high-speed train is mathematically represented by a system with 38 degrees of freedom, while the sub-track system utilizes China's Railway Track System slab track. The numerical modeling of the bridge is accomplished using computationally efficient finite elements that represent thin-walled box-beams. The rail's imperfections are also accounted for, and they are represented using a power spectral density function. The dynamic response of the bridge is calculated using the Newmark Beta technique, considering several degrees of freedom and stress resultants. A thorough parametric analysis on the factors affecting dynamic response of the bridge is conducted and a regression model has been proposed. The regression equation yields an excellent fit for shear force, distortional moment, and distortional bi-moment, with an R2 value near to one. It has been alsp been observed that the range of the coefficient R2 in case of bending moment, torsion, torsional bi-moment, and vertical deflection typically falls between 0.82 and 0.9. R2 value near to 1 indicates that it is quite accurate in forecasting the dynamic influence of high speed trains on bridge’s response.
An Exploration of the Influence of ZnO NPs Treatment on Germination of Radish Seeds under Salt Stress based on the YOLOv8-R Lightweight Model
Authors: Ouyang Zhiqian , Fu Xiuqing , Zhong Zhibo , Bai Ruxiao , Cheng Qianzhe , Gao Ge , Li Meng , Zhang Haolun , Zhang Yaben 
Published: June 2024

Abstract

Background
Since traditional germination test methods have drawbacks such as slow efficiency, proneness to error, and damage to seeds, a non-destructive testing method is proposed for full-process germination of radish seeds, which improves the monitoring efficiency of seed quality.
Results
Based on YOLOv8n, a lightweight test model YOLOv8-R is proposed, where the number of parameters, the amount of calculation, and size of weights are significantly reduced by replacing the backbone network with PP-LCNet, the neck part with cross-scale feature fusion module CCFM, the original C2f of the neck part with OREPA, and the original SPPF with FocalModulation. The ablation test and comparative test prove the performance of the model. With adoption of germination rate, germination index, and germination potential as the three vitality indicators, the seed germination phenotype collection system and YOLOv8-R model are used to analyze the full time-series sequence effects of different ZnO NPs concentrations on germination of radish seeds under varying degrees of salt stress.
Conclusions
The results show that salt stress inhibits the germination of radish seeds and that the inhibition effect is more obvious with the increased concentration of NaCl solution; in cultivation with deionized water, the germination rate of radish seeds does not change significantly with increased concentration of ZnO NPs, but the germination index and germination potential increase initially and then decline; in cultivation with NaCl solution, the germination rate, germination potential and germination index of radish seeds first increase and then decline with increased concentration of ZnO NPs.
Increased sensitivity to the aromatic antibiotic novobiocin in Acinetobacter baumannii by vanillic acid
Authors: Sariyer Ayşegül Saral , Sariyer Emrah 
Published: June 2024

Abstract

This paper focuses on in vitro analysis of the ability of vanillic acid to potentiate representative antibiotics, which are substrates of pumps responsible for antibiotic resistance in Acinetobacter baumannii. To investigate whether vanillic acid can potentiate antibiotics in cells overexpressing the AdeABC, AdeFGH, and AdeIJK efflux pumps, a minimum potentiation concentration determination (MPC4) experiment was performed. Vanillic acid potentiates novobiocin (8-fold) in Acinetobacter baumannii overexpressing AdeIJK. RNA-seq analysis was used to examine the gene-level effects of vanillic acid in AdeIJK-overexpressing cells treated with a sub-MIC concentration of novobiocin. AdeIJK overexpressing cells were cultivated at a sub-MIC concentration of novobiocin alone (1.5625 µg/ml) and at a sub-MIC concentration of novobiocin (1.5625 µg/ml) and vanillic acid (50 µg/ml) together in order to ascertain the effect of vanillic acid at the transcriptional level. DEG results revealed the upregulation of genes involved in the degradation and transport of aromatic compounds, along with alcohol metabolism. From the results of the present study, the upregulation of genes related to the degradation of aromatic compounds is regulated by vanillic acid, which is not surprising, and this may also make it possible to increase novobiocin sensitivity, aligning with existing literature. However, it is crucial to validate these findings through experimental studies in the future. In conclusion, our study highlights the potential regulatory role of vanillic acid, warranting further investigation.
A machine learning approach to population pharmacokinetic modelling automation
Authors: Richardson Samuel , Arana Itziar Irurzun , Nowojewski Andrzej , Zhou Diansong , Leander Jacob , Tang Weifeng , Dearden Richard , Gibbs Megan 
Published: June 2024

Abstract

Population pharmacokinetic (PopPK) models are vital for decision making across the drug development lifecycle; however, conventional model development is labour-intensive and time-consuming. In this paper, we present an approach to automatically develop popPK model structures for extravascularly administered drugs using optimisation algorithms. We propose a generic parameter space for generating model structures and a penalty function for selecting the optimal configurations. Across four clinical datasets we observed the reproducible discovery of models comparable with those manually developed with an average search time under 48 hours. These results demonstrate that a single penalty function and model space can be used within an optimisation framework to automatically identify model structures for a diverse range of drugs. Adoption of automatic model search can accelerate popPK analysis, improve model quality, increase reproducibility, and reduce manual effort for modellers.
New insights into the management of hardwater using bentonite: Studying the mechanism via experiments and statistical physics treatment
Authors: Mostafa Hemmat , Zaher Amal , Seliem Moaaz K. , Shehata Nabila 
Published: June 2024

Abstract

Hard water is related to some health issues owned to numerous diseases and economic challenges associated with the calcification of industrial water. Hence, in the present research, the treatment of hard groundwater via adsorption of polyvalent Ca+ 2 and Mg+ 2 ions at different initial concentration using bentonite was investigated. Full characterization of the adsorbent was carried out using different techniques. At all solution temperatures, the formation of a monolayer of these ions was caused by the Ca2+ and Mg2+ hardness–bentonite interaction, and the adsorption process was ascribed to active sites with a homogenous characteristic of the bentonite since Langmuir model fit the Ca2+ and Mg2+ adsorption data (R2 = 0.99). The statistical physics treatment indicated that the advanced monolayer model fitted Ca+ 2 and Mg+ 2 adsorption data at all temperatures. Based on this statical model, mixed (parallel and non-parallel orientations) adsorption geometry was recognized. The density of bentonite active sites (the steric NM parameter) rose from 688 to 1019 mg g− 1 within 25° to 50 ºC and this factor was the main variable influencing the bentonite adsorption capacity. Overall, bentonite is recommended by the current study as a cost-effective and environmentally safe adsorbent to remove TH from groundwater.
Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates
Authors: Lalagkas Panagiotis N. , Melamed Rachel D. 
Published: June 2024

Abstract

Background
Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drug targets, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drug repurposing, but also to highlight shared etiology explaining repurposing.
Methods
We compile breast cancer's predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways, and similarly for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer.
Results
We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 76 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher’s exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing.
Conclusions
Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known risk factors. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.
A quantitative experimental study on sand production from unconsolidated sandstone reservoir and gravel-pack plugging performance
Authors: Wei Na , Qiao Yi , Cai Meng , Li Junliang , Kvamme Bjørn 
Published: June 2024

Abstract

In order to understand the sand production law of unconsolidated sandstone reservoirs and the plugging performance of packed gravel comprehensively. In this study, the “Multi-Injection and One-Production” (MIOP) sand production simulation experimental system designed and developed independently was used to conduct experimental research on the sand production law of unconsolidated sandstone reservoirs and the plugging performance of packed gravel under different pressure differences and different fluid properties. And two standards of sand production intensity(Is) and sand production concentration(Cs) were put forward to evaluate the sand production severity of formation and the sand plugging performance of gravel-pack. The results show that: The sand production law of the reservoir shows that the sand production is loose sand and free sand under low pressure difference and low viscosity, which leads to pore throat blockage. With the continuous increase of pressure difference and viscosity, the reopening of pore throat and the peeling of skeleton sand lead to the increase of sand production. At the same time, the critical sand production pressure difference of the target reservoir is 1.9MPa and the critical sand production viscosity is 65-70mPa s. When the packed gravel is 0.425-0.8mm quartz sand, the minimum invaded depth of the gravel-pack is 3.3mm and the Is and Cs under different conditions are slight sand production, which indicates that the best packed gravel suitable for the target reservoir is 0.425-0.8mm quartz sand. In addition, the experimental results show that the plugging performance of quartz sand is better than that of ceramsite sand under the condition of the same particle diameter. This study has a certain engineering guiding significance for clarifying the sand production mechanism of sandstone reservoir and the design of gravel-pack control scheme.
Consanguinity in the Lebanese Population: Knowledge, Attitude and Practice
Authors: Chouery Eliane , Ibrahim José-Noel , Deeb Mary , Sobh Ali , Ghanem Mohamad , Sobh Jeanine , Choueiry Francesca El , Rashwan Ramy , Swaidan Dana , Abdelrazzak Aya , Massaad Christian , Fouani Adam El , Mehawej Cybel , Megarbane Andre 
Published: June 2024

Abstract

Background:
Consanguinity, defined as marriage between individuals sharing a common ancestor, has been associated with an increased risk of autosomal recessive diseases. The practice of consanguinity varies globally, with high prevalence in Middle Eastern countries. Understanding the prevalence and societal attitudes towards consanguineous marriages, particularly in regions where it is prevalent, is crucial for public health interventions.
This study evaluates the current prevalence of consanguinity in Lebanon and its contributing risk factors. It also assesses the knowledge of the Lebanese population towards this practice and premarital genetic screening. Moreover, the attitude of the participants regards consanguinity and genetic counseling is ascertained.
Methods:
A cross-sectional study was conducted among 984 Lebanese individuals aged 18 to 65 using an online self-administered questionnaire that included data on participants’ sociodemographic variables, knowledge level of consanguinity and premarital genetic screening, as well as questions assessing the attitudes towards consanguinity and genetic counseling.
Results:
The prevalence of consanguinity in Lebanon was found to be 24.5%, with first-cousin marriages comprising 46.5% of these unions; place of residence was the only independent factors affecting consanguinity prevalence among our sample. Most participants had a good understanding of consanguinity but misconceptions about specific genetic risks persisted. Attitudes varied, with participants from consanguineous backgrounds showing greater acceptance of the practice. Logistic regression identified gender, education, occupational status, and age as independent predictors of consanguinity while insufficient income, having consanguineous parents, and having a poor knowledge were associated with a positive attitude towards consanguinity.
Conclusion:
While the consanguinity rate remains high and consistent over time, societal beliefs and cultural practices continue to influence this phenomenon. Public health interventions should focus on raising awareness and disseminating accurate information about the implications of consanguinity and the importance of genetic counseling, particularly among communities with high rates of consanguinity.
Control of spiral waves in myocardial tissue by optogenetics and temperature
Authors: Hu Yipeng , Ding Qianming , Wu Yong , Jia Ya , Li Tianyu , Yu Dong , Zhan Xuan 
Published: June 2024

Abstract

Optogenetics as an emerging technology can eliminate spiral waves in myocardial tissue. The heat generated during illumination of myocardial tissue is an overlooked influence. Even small fluctuations in temperature may affect the action potentials of cardiomyocyte. In this paper, a minimal ventricular model and a simplified model of optogenetics are employed to study the effects of heat generation by illumination on elimination of spiral waves. The Luo-Rudy model and Channelrhodospin-2 light-sensitive ion channel model are used to validate our conclusions. Weinduce drift of spiral waves through inhomogeneities generated by discrete gradients of illumination. The inhomogeneity of temperature caused by gradient illumination can inhibit the elimination of spiral waves. Spiral waves in the myocardial medium can be induced to drift more efficiently by controlling temperature changes in the myocardial medium during illumination. We emphasized the importance of temperature factors in optogenetic experiments, hoping that our results could provide guidance for its clinical applications.
The association of Helicobacter pylori with adverse pregnancy outcomes in three European birth cohorts
Authors: GALAN Raquel , PEMBREY Lucy , BUSTAMANTE Mariona , AGUILAR Ruth , MANSON Dan , VIDAL Marta , BAÑULS Marc , ROUMELIOTAKI Theano , DELGADO-SABORIT Juana MARI , MARIN Natalia , VRIJHEID Martine , BEMPI Vicky , MONCUNILL Gemma , DOBAÑO Carlota , KOGEVINAS Manolis , KARACHALIOU Marianna 
Published: June 2024

Abstract

Background
Helicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women.
Objective
This study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations.
Study design
Multiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity.
Results
Helicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). H.pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06–1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62–2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10–8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29–8.74), p-value 0.03].
Conclusion
Our study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the specific antibody responses against OMP, GroEL and NapA seem to determine disease associations.
Optimization of hydrofoils for a bidirectional tidal stream turbine
Authors: Giljarhus Knut Erik Teigen 
Published: June 2024

Abstract

Tidal stream turbines present an appealing approach for consistent renewable energy generation. Capitalizing on the periodic nature of tidal streams, these turbines can be designed to function bidirectionally, eliminating the need for a yaw control system. Although airfoils and hydrofoils in general have been extensively studied, there is less work available on bidirectional designs. Through the use of optimization methods, this work introduces bidirectional hydrofoils of varying thicknesses with improved performance compared to elliptic profiles. The optimization was performed using the hydrodynamic efficiency as the objective function, with simulations performed using 2D computational fluid dynamics. The optimized hydrofoil was then used in a turbine design, which is simulated using blade element momentum theory. The hydrofoils showed an improvement in hydrodynamic efficiency of up to 10 %. In the turbine design, this resulted in an improvement of 5.3 % in power coefficient and a reduction in thrust coefficient of 13.2 %. The new line of hydrofoils are promising for use in cost-effective and reliable tidal stream turbine designs.
Evaluation of Glucosyltransferase B and secretory immunoglobulin A in relation to dental caries in saliva of electronic cigarette smokers
Authors: alyaseen Haneen A. , Aldhaher Zainab A. 
Published: June 2024

Abstract

Electronic cigarettes (vape) are actively used, and their use is growing globally. With e-cigarettes, users may get their recommended nicotine intake without burning tobacco. Research indicates that, compared to traditional cigarettes, electronic cigarettes offer a more effective nicotine delivery system and have fewer adverse effects on oral and general health. However, e-cigarettes are considered a good strategy to reduce the harmful effects of conventional cigarettes. Saliva contains many types of proteins, such as glucosyltransferase B, a bacterial-derived enzyme, and secretory immunoglobulin A, which play roles in immune responses that might be affected by electronic cigarettes. The goal of this study was to evaluate glucosyltransferase B and secretory immunoglobulin A in relation to dental caries in the saliva of electronic cigarette users ,and to study the impact of E.C. on oral health. Ninety active males were divided into two groups: 45 electronic-cigarette smokers in addition to 45 non-electronic-cigarette smokers as a control group. An oral examination was performed on the studied groups, and decayed missing filling tooth surfaces (DMFS) were documented. Additionally, unstimulated saliva was collected to evaluate salivary glucosyltransferase B and secretory immunoglobulin A by using a sandwich enzyme-linked immune-sorbent assay (ELISA). The obtained outcomes showed that decayed, missing, and filled Surfaces values(DMFS), salivary glucosyltransferase B, and salivary secretory immunoglobulin A were greater in the study group than in control group, and additionally, a correlation between glucosyltransferase B, secretory immunoglobulin A, and DMFS was positive and significant. It was concluded that e-cigarettes may have an effect on saliva components and dental caries.