bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Efficiency of Nitrogen Fertilization Levels in Two Sorghum Hybrids for Bioenergy Production
Authors: Cabrera-Ariza Antonio M. , Aguilera-Peralta Miguel , Santelices-Moya Rómulo
Published: September 2024

To achieve sustainable and profitable production of sorghum for energy purposes, it is crucial to ensure the efficient use of the nutrients necessary for its growth and development. This research investigates the influence of diverse management practices on biomass production, nutrient use efficiency, and nitrogen balance in two sorghum hybrids cultivated for bioenergy applications. A comprehensive field study was conducted over two growing seasons, evaluating the effects of fertilization methods and crop rotation strategies. Results indicate that high nitrogen (HN) fertilization increased dry biomass production (up to 20.7 Mg ha−1) and nutrient removal (up to 343.5 kg K ha−1) in both sorghum hybrids. The H128 hybrid showed higher nutrient use efficiency, especially for phosphorus, while the nitrogen balance was positive under HN but varied under low nitrogen (LN), with the H133 hybrid experiencing a net nitrogen loss at LN. These findings contribute valuable insights into sustainable sorghum cultivation for bioenergy production, highlighting the importance of tailored management practices in achieving optimal crop performance.
Effects of Dietary Lipid Levels on the Growth, Muscle Fatty Acid and Amino Acid Composition, Antioxidant Capacity, and Lipid Deposition in Mirror Carp (Cyprinus carpio)
Authors: Jiang Xiaona , Song Zhenguo , Li Chitao , Hu Xuesong , Ge Yanlong , Cheng Lei , Shi Xiaodan , Jia Zhiying
Published: September 2024

In fish, increasing the crude lipid level of feed can save protein and improve feed utilization. Mirror carp (Cyprinus carpio) is one of the most widely farmed fish species in the world. In this study, mirror carp larvae were fed isonitrogenous diets with different lipid levels (3%, 5%, 7%, 9%, 11%, and 13%). The rearing trial lasted for eight weeks. The results revealed that when the fat content was 9%, the AWGR, WGR, and FCR were highest, whereas FCR was lowest. The AWGR was correlated with the dietary lipid level, and the regression equation was y = −2.312x2 + 45.01x + 214.49. Compared with those in the control group, the T-CHO and TG contents were significantly greater in the 13% lipid content groups and significantly lower in the 9% lipid content groups (p < 0.05). In terms of muscle quality, the contents of MUFAs, PUFAs, and DHA + EPA were significantly greater than those in the other experimental groups (p < 0.05). Oil red O staining revealed a lipid content of 13% with severe fat deposition. In addition, the results of the analysis of antioxidant enzyme activity revealed that the activities of GSH, CAT and T-AOC were significantly greater at the 9% lipid content, and that the MDA content was significantly greater at the 13% lipid content (p < 0.05). Similarly, the mRNA levels of GH, IGF-I, FAS, and LPL were significantly highest at a lipid level of 9% (p < 0.05). The above results revealed that the optimal dietary lipid requirement for the fast growth of mirror carp (6.86 ± 0.95 g) was 9.74% on the basis of nonlinear regression analysis of the AWGR. The dietary lipid level (9%) improved the growth, stress resistance, and lipid utilization of mirror carp to a certain extent.
Prevalence of Aleutian Mink Disease Virus (AMDV) in Free-Ranging American Mink from Biebrza and Narew National Parks (Poland)—An Epidemiological Concern
Authors: Przywara Konrad , Siemionek Jan , Jakubowski Tadeusz , Konczyk-Kmiecik Klaudia , Szczerba-Turek Anna
Published: September 2024

Aleutian Mink Disease Virus (AMDV) is the causative agent of Aleutian disease (AD). This progressive and chronic disorder significantly impacts the mink breeding industry, affecting farmed and free-ranging American and European mink. This study investigated AMDV variants isolated from free-ranging American mink in northeastern Poland. Between 2018 and 2019, 26 spleen samples were collected from mink in Narew National Park (NNP) and Biebrza National Park (BNP). DNA was extracted and subjected to PCR to amplify the NS1 gene, followed by sequencing and phylogenetic analysis. The NS1 gene was detected in 50% of samples from NNP minks and in 30% of samples from BNP minks, with an overall prevalence of 42.31%; these findings align with global data and indicate serious ecological and health concerns. Ten closely related AMDV variants and one distinct variant were identified. The grouped variants exhibited high genetic homogeneity, closely related to strains found in mink from the USA, Germany, Greece, Latvia, and Poland; meanwhile, the distinct variant showed similarities to strains found in mink from Finland, Denmark, China, Poland, and Latvia, suggesting multiple infection sources. These findings, consistent with data from Polish mink farms, indicate significant genetic similarity between farmed and wild mink strains, suggesting potential bidirectional transmission. This underscores the importance of a One Health approach, emphasizing the interconnectedness of human, animal, and environmental health. Continuous surveillance and genetic studies are crucial for understanding AMDV dynamics and mitigating their impacts. Measures to reduce transmission between farmed and wild mink populations are vital for maintaining mink health and ecosystem stability.
UID-Dual Transcriptome Sequencing Analysis of the Molecular Interactions between Streptococcus agalactiae ATCC 27956 and Mammary Epithelial Cells
Authors: Gong Jishang , Li Taotao , Li Yuanfei , Xiong Xinwei , Xu Jiguo , Chai Xuewen , Ma Youji
Published: September 2024

Streptococcus agalactiae ATCC 27956 is a highly contagious Gram-positive bacterium that causes mastitis, has a high infectivity for mammary epithelial cells, and becomes challenging to treat. However, the molecular interactions between it and mammary epithelial cells remain poorly understood. This study analyzed differential gene expression in mammary epithelial cells with varying levels of S. agalactiae infection using UID-Dual transcriptome sequencing and bioinformatics tools. This study identified 211 differentially expressed mRNAs (DEmRNAs) and 452 differentially expressed lncRNAs (DElncRNAs) in host cells, primarily enriched in anti-inflammatory responses, immune responses, and cancer-related processes. Additionally, 854 pathogen differentially expressed mRNAs (pDEmRNAs) were identified, mainly enriched in protein metabolism, gene expression, and biosynthesis processes. Mammary epithelial cells activate pathways, such as the ERK1/2 pathway, to produce reactive oxygen species (ROS) to eliminate bacteria. The bacteria disrupt the host’s innate immune mechanisms by interfering with the alternative splicing processes of mammary epithelial cells. Specifically, the bacterial genes of tsf, prfB, and infC can interfere with lncRNAs targeting RUNX1 and BCL2L11 in mammary epithelial cells, affecting the alternative splicing of target genes and altering normal molecular regulation.
Therapeutic Drug Monitoring of Infliximab and Adalimumab through Concentration and Anti-Drug Antibodies Assessment; Comparison of Sanquin Diagnostics and Theradiag Assays
Authors: Vroemen Wim H. M. , Agata Shakira S. , van Beers Joyce J. B. C. , Damoiseaux Jan G. M. C.
Published: September 2024

Background: Therapeutic drug monitoring of biological Tumor Necrosis Factor (TNF)-alpha inhibitors is of critical importance. In this study, the performance of practically advantageous chemiluminescent immunoassays of Theradiag, assessing Infliximab and Adalimumab serum concentrations and anti-drug antibodies (ADA) against these biologics, were compared to the Enzyme-Linked Immuno-Sorbent Assays (ELISAs) from Sanquin Diagnostics. Methods: Leftover serum samples (n = 80 for each parameter) from patients treated with Infliximab or Adalimumab were collected. Correlation and agreement analyses for serum concentration and ADAs, respectively, were performed. Both Theradiag ADA assays, an assay targeting both free and bound ADAs and an assay targeting solely free ADAs, were investigated and compared to the Sanquin Diagnostics ADA assay, targeting both free and bound ADAs. Results: Strong positive correlations were observed between the biologic concentration assessment of Infliximab (Spearman’s Rho = 0.91) and Adalimumab (Spearman’s Rho = 0.94). However, there appeared to be significant bias in the Theradiag assay when compared to Sanquin (Infliximab median (Confidence Interval (CI)) = 2.1 (1.7–2.6) µg/mL; Adalimumab median (CI) = 0.8 (0.5–0.9) µg/mL). Agreement analyses showed moderate to good agreement for the Theradiag and Sanquin Diagnostics ADA assays, when detecting both free and bound ADAs, for Infliximab (Cohen’s k = 0.717) and Adalimumab (Cohen’s k = 0.802). In contrast, the Theradiag ADA assay detecting solely free ADAs had zero to poor agreement for Infliximab (Cohen’s k = 0.458) and Adalimumab (Cohen’s k = 0.119), respectively. Conclusions: This study demonstrated strong correlations and good agreement between the Theradiag and Sanquin Diagnostics assays measuring Infliximab and Adalimumab serum concentrations and ADAs, both free and bound, against these biologics. Discordance analyses showed significantly decreased drug concentrations in the solely free assays, indicating that the combined detection of free and bound ADAs better aligns with drug levels.
The Effectiveness of Taurolidine Antimicrobial Locks in Preventing Catheter-Related Bloodstream Infections (CRBSIs) in Children Receiving Parenteral Nutrition: A Case Series
Authors: Ling Galina , Ben-Shimol Shalom , Elamour Siham , Nassar Raouf , Kristal Eyal , Shalev Rotem , Howard Gadi , Yerushalmi Baruch , Kogan Slava , Shmueli Moshe
Published: September 2024

Introduction: We assessed the efficacy of taurolidine lock (TL) in preventing catheter-related bloodstream infections (CRBSIs) and related hospitalizations in children with parenteral nutrition (PN) in the home setting. Methods: This study is a retrospective case series study. All children with intestinal failure in a single center in southern Israel who were administered PN and treated with TL between 2017 and 2024 were included. The rates of CRBSI episodes, related hospitalizations and pathogen distribution in the pre-TL and post-TL periods were compared. Results: Overall, 14 patients were included. The median pre-TL and post-TL periods were 990 and 1260 days, respectively. The rate of CRBSI episodes due to bacterial infection per 1000 days declined by 45%, from 6.2 to 3.7, with p = 0.0008, while fungal CRBSI rates were low (<10% of all positive cultures) and did not decline significantly. Similarly, the hospitalization episode rate per 1000 days declined by 41%, from 7.6 to 4.5, with p = 0.001. Conclusions: Taurolidine lock treatment for children with central-line PN resulted in a substantial decrease in CRBSI episodes and related hospitalizations.
Fiber Monitoring System Applied to Railway Bridge Structures in a Near-Fault Region
Authors: Su Hsiao-Chen , Hsu Tseng-Hsing , Lee Yu-Lin , Hsu Wen-Kuei , Yang Nien-Tsu , Chang Ning-Hsuan
Published: September 2024

Bridges are widely used for train transportation. Some bridges must be constructed close to geologic faults or across them due to the constraints of travel route alignment and the geographical environment. Taiwan is located at the junction of the Eurasian Plate and the Philippine Plate, where geological joints are present and earthquakes are frequent. In Taiwan, the monitoring and early warning of structural displacements is increasingly important, especially in the mutual control and monitoring of bridges and railways. This study utilizes fiber as a continuous sensor to monitor the safety of railway bridges in a near-fault region. This research builds upon the theory of Brillouin frequency shift (BFS) and applies it to a practical scenario of a fault-crossing railway bridge. BFS is related to the strain and temperature change in a single-mode fiber. Distributed fiber optic sensing (DFOS) systems enable us to detect shifts in frequency on the sensing fiber. A systemic approach to installing DFOS systems will be discussed. Data from a DFOS system are collected, and through data processing, they are converted into strain with regard to the deformations (bending, tension, compression) of a box girder bridge. Changes in the geometric structure of the box girder bridge throughout the year are measured and processed into graphical data. This system can be effectively applied to the structural safety monitoring of railway bridges. Through this research, several functions have been achieved, including continuous displacement, automatic monitoring, and real-time automatic alarm functions, without the need for human intervention.
Vital Views into Drone-Based GPR Application: Precise Mapping of Soil-to-Rock Boundaries and Ground Water Level for Foundation Engineering and Site-Specific Response
Authors: Frid Michael , Frid Vladimir
Published: September 2024

The primary objective of this case study is to evaluate the effectiveness of drone-based ground penetrating radar (GPR) in detecting and mapping underground water levels and soil-to-rock boundaries. This knowledge is crucial for accurate structural engineering analyses, including foundation engineering and site-specific response evaluations. The paper also considers drone-based GPR to overcome common urban obstacles, topographic variations, and environmental factors by simply flying over them, offering a promising solution to these challenges. The research utilized drone-based GPR equipped with an unshielded 150 MHz dipole antenna and employed filtering procedures to diminish the effect of above-ground obstacles on the interpretation of our results. The study unequivocally demonstrated the feasibility and effectiveness of drone-based GPR in these applications, reassuring the civil engineering community. The findings of this study significantly advance our understanding of drone-based GPR technology for mapping disturbed soil boundaries and water table levels in foundation engineering and site response applications and provide valuable recommendations for optimizing its performance in complicated terrains, thereby inspiring and guiding future research and practice in this field.
A Secure Median Implementation for the Federated Secure Computing Architecture
Authors: Goelz Christian , Vieluf Solveig , Ballhausen Hendrik
Published: September 2024

In Secure Multiparty Computation (MPC or SMPC), functions are evaluated in encrypted peer-to-peer networks without revealing the private inputs of the participating parties. The median is a non-trivial computation in MPC and is particularly relevant in fields like medicine and economics. Here, we provide an MPC implementation of the median for the Federated Secure Computing (FSC) framework. It is tested on synthetic datasets with varying sizes (N=102 to N=107) and number of participants (M=2 to M=10) across different network environments and hardware configurations. Using minimal networking and computational resources on a commercial hyperscaler, we evaluated real-world performance with breast cancer (N=569) and heart disease (N=920) datasets. Our results showed effective scaling up to N=106 entries with runtime between 1 and 4 s, but runtime exceeded 15 s for 107 entries. The runtime increased linearly with the number of parties, remaining below one minute for up to M=10 parties. Tests with real-world medical data highlight significant network overhead, with runtime increasing from 16 to 17 s locally to over 800 s across hyperscaler regions, emphasizing the need to minimize latency for practical deployment.
Numerical Evaluation of Hot Air Recirculation in Server Rack
Authors: Madihlaba Nelson Bafana , Kunene Thokozani Justin
Published: September 2024

In air-cooled data centers, hot aisle containment is used to separate hot and cold air from mixing to improve cooling effectiveness. However, this creates a significant pressure imbalance between the cold and hot aisles, with the latter being high. The hot aisle high pressure creates bac pressure that pushes against the server-unit fan system, which subsequently results in hot recirculation and insufficient server-unit cooling. This study examines the application of series-configured server fans with the intention of increasing the system pressure head to overcome the hot aisle containment back pressure and eliminate server hot air recirculation. A detailed computational fluid dynamics model for the Dell 2950 2U server is calibrated and validated using existing experimental test results. Furthermore, the impact of changing the server fan system to a series configuration by adding four or more server fans is investigated under different hot-aisle pressure conditions. It was found that changing the server fan system configuration from parallel to series arrangement positively improved the available system static pressure, but it did not result in the elimination of hot air recirculation. The server with the series-configured fan system experienced an average inlet air temperature increase of 9% when compared to the original server under similar conditions. This study serves as a base for integrating liquid and air-cooling systems to form hybrid cooling systems for high-density racks in legacy data centers.
Method of Predicting Dynamic Deformation of Mining Areas Based on Synthetic Aperture Radar Interferometry (InSAR) Time Series Boltzmann Function
Authors: Chi Shenshen , Yu Xuexiang , Wang Lei
Published: September 2024

The movement and deformation of rock strata and the ground surface is a dynamic deformation process that occurs as underground mining progresses. Therefore, the dynamic prediction of three-dimensional surface deformation caused by underground mining is of great significance for assessing potential geological disasters. Synthetic aperture radar interferometry (InSAR) has been introduced into the field of mine deformation monitoring as a new mapping technology, but it is affected by many factors, and it cannot monitor the surface deformation value over the entire mining period, making it impossible to accurately predict the spatiotemporal evolution characteristics of the surface. To overcome this limitation, we propose a new dynamic prediction method (InSAR-DIB) based on a combination of InSAR and an improved Boltzmann (IB) function model. Theoretically, the InSAR-DIB model can use information on small dynamic deformation during mining to obtain surface prediction parameters and further realize a dynamic prediction of the surface. The method was applied to the 1613 (1) working face in the Huainan mining area. The results showed that the estimated mean error of the predicted surface deformation during mining was between 80.2 and 112.5 mm, and the estimated accuracy met the requirements for mining subsidence monitoring. The relevant research results are of great significance, and they support expanding the application of InSAR in mining areas with large deformation gradients.
Mechanical Responses and Fracture Evolution of Marble Samples Containing Stepped Fissures under Increasing-Amplitude Cyclic Loading
Authors: Yu Yongchun , Wang Yu , Yi Xuefeng , Chen Zhenzhen
Published: September 2024

This work aims to reveal the effect of rock bridge length (RBL), i.e., 10, 20, 30, or 40 mm, on the fatigue mechanical responses and fracture evolution of marble samples containing stepped fissures under multilevel cyclic loading paths. Comprehensive investigations were conducted on fatigue strength, deformation, damping evolution, and damage propagation. The test results demonstrate that fatigue strength, volumetric deformation, and fatigue lifetime increase as rock bridge length increases. The energy dissipation reflected by the damping ratio indicates that much energy is consumed to drive crack propagation, especially for rock with larger rock bridge segments at the final cyclic loading stage (CLS). An index of strain incremental rate is proposed to predict rock failure development. It is found that volumetric strain rate is a better early warning sign than axial strain rate. Warning time decreases with increasing rock bridge length; it is suggested that rock with large segments has good ability to resist external fatigue loading.
Fast and Nondestructive Proximate Analysis of Coal from Hyperspectral Images with Machine Learning and Combined Spectra-Texture Features
Authors: Mao Jihua , Zhao Hengqian , Xie Yu , Wang Mengmeng , Wang Pan , Shi Yaning , Zhao Yusen
Published: September 2024

Proximate analysis, including ash, volatile matter, moisture, fixed carbon, and calorific value, is a fundamental aspect of fuel testing and serves as the primary method for evaluating coal quality, which is critical for the processing and utilization of coal. The traditional analytical methods involve time-consuming and costly combustion processes, particularly when applied to large volumes of coal that need to be sampled in massive batches. Hyperspectral imaging is promising for the rapid and nondestructive determination of coal quality indices. In this study, a fast and nondestructive coal proximate analysis method with combined spectral-spatial features was developed using a hyperspectral imaging system in the 450–2500 nm range. The processed spectra were evaluated using PLSR, with the most effective MSC spectra selected. To reduce the spectral redundancy and improve the accuracy, the SPA, Boruta, iVISSA, and CARS algorithms were adopted to extract the characteristic wavelengths, and 16 prediction models were constructed and optimized based on the PLSR, RF, BPNN, and LSSVR algorithms within the Optuna framework for each quality indicator. For spatial information, the histogram statistics, gray-level covariance matrix, and Gabor filters were employed to extract the texture features within the characteristic wavelengths. The texture feature-based and combined spectral-texture feature-based prediction models were constructed by applying the spectral modeling strategy, respectively. Compared with the models based on spectral or texture features only, the LSSVR models with combined spectral-texture features achieved the highest prediction accuracy in all quality metrics, with Rp2 values of 0.993, 0.989, 0.979, 0.948, and 0.994 for Ash, VM, MC, FC, and CV, respectively. This study provides a technical reference for hyperspectral imaging technology as a new method for the rapid, nondestructive proximate analysis and quality assessment of coal.
An IoT Healthcare System Based on Fog Computing and Data Mining: A Diabetic Use Case
Authors: Karimi Azin , Razi Nazila , Rezazadeh Javad
Published: September 2024

The advent of the Internet of Things (IoT) has revolutionized numerous sectors, with healthcare being particularly significant. Despite extensive studies addressing healthcare challenges, two persist: (1) the need for the swift detection of abnormalities in patients under medical care and timely notifications to patients or caregivers and (2) the accurate diagnosis of abnormalities tailored to the patient’s condition. Addressing these challenges, numerous studies have focused on developing healthcare systems, leveraging technologies like edge computing, which plays a pivotal role in enhancing system efficiency. Fog computing, situated at the edge of network hierarchies, leverages multiple nodes to expedite system processes. Furthermore, the wealth of data generated by sensors connected to patients presents invaluable insights for optimizing medical care. Data mining techniques, in this context, offer a means to enhance healthcare system performance by refining abnormality notifications and disease analysis. In this study, we present a system utilizing the K-Nearest Neighbor (KNN) algorithm and Raspberry Pi microcomputer within the fog layer for a diabetic patient data analysis. The KNN algorithm, trained on historical patient data, facilitates the real-time assessment of patient conditions based on past vital signs. A simulation using an IBM SPSS dataset and real-world testing on a diabetic patient demonstrate the system’s efficacy. The results manifest in prompt alerts or normal notifications, illustrating the system’s potential for enhancing patient care in healthcare settings.
Weighted Secrecy Sum Rate Optimization for Simultaneously Transmitting and Reflecting Reconfigurable Intelligent Surface-Assisted Multiple-Input Single-Output Systems
Authors: Wu Baoliang , Wu Yue
Published: September 2024

The study investigates the effectiveness of a novel Simultaneously Transmitting and Reflecting Reconfigurable Intelligent Surface (STAR-RIS) technology in enhancing the physical layer security of Multiple-Input Single-Output (MISO) systems. To address the complexity of the security challenge, we examine two distinct phase shift strategies, namely, the coupled phase scheme and the independent phase scheme. The coupled paradigm focuses on optimizing weighted sum secrecy rate (WSSR) through a customized Block Coordinate Descent (BCD) approach integrated with path tracking, aiming to achieve a balanced security enhancement. Furthermore, for the independent phase shift paradigm, an optimization algorithm based on the Concave–Convex Procedure (CCCP) is explored to provide a flexible security solution. The numerical results validate the superior performance of STAR-RIS, confirming its potential as a robust security enhancer for MISO systems.
Activity Enhancement Study of Xinjiang Silica-Alumina Volcanic Rock Powder through Different Activation Processes
Authors: Yang Shuhong , Wu Yingjie , Wang Huaiyi , Yang Guiquan , Ding Xiangyi , Xia Zhaoxuan
Published: September 2024

In response to the dilemma of the scarcity of mineral additions and the high cost of long-distance transport in Hotan, Xinjiang, China, this paper presented an activation process study on the feasibility of volcanic rock powders unique to this region as mineral additions. This study explored the activity-enhancing effects of volcanic rock powder via three methods: physical activation process, chemical activation process, and thermal activation process. The results showed that physical grinding improved the particle size distribution and enhanced the ‘microaggregate’ effect. For every 80 m2/kg increase in specific surface area, the particle size decreased by approximately 0.7 μm, and the 28-day activity index increased by up to 4%. In the chemical activation process, the optimal combination scheme of 6% CaO, 2% CaCO3, and 2% CaSO4·2H2O increased the 28-day strength of volcanic rock powder mortar specimens by approximately 20%, achieving an activity index of 82%. Thermal activation studies showed that the low-temperature heat treatment interval of 300 °C to 700 °C increased the 28 d activity index of volcanic rock powders by 12 to 22 percent. However, when the temperature reached the high-temperature interval of 800 °C to 1400 °C, it, rather, inhibited the activity enhancement. A combination of the three activation methods (physical milling with a specific surface area of 560 m2/kg after heat treatment at 600 °C, chemical activation with 6% CaO, 2% CaCO3, and 2% CaSO4·2H2O) resulted in an activity of up to 86% for the volcanic rock powder. The activity enhancement by different activation methods provided a theoretical basis and practical reference for the application of volcanic rock powder as a mineral additions in Hotan, Xinjiang.
Two P or Not Two P: Mendel Random Variables in Combining Fake and Genuine p-Values
Authors: Brilhante M. Fátima , Gomes M. Ivette , Mendonça Sandra , Pestana Dinis , Santos Rui
Published: September 2024

The classical tests for combining p-values use suitable statistics T(P1,…,Pn), which are based on the assumption that the observed p-values are genuine, i.e., under null hypotheses, are observations from independent and identically distributed Uniform(0,1) random variables P1,…,Pn. However, the phenomenon known as publication bias, which generally results from the publication of studies that reject null hypotheses of no effect or no difference, can tempt researchers to replicate their experiments, generally no more than once, with the aim of obtaining “better” p-values and reporting the smallest of the two observed p-values, to increase the chances of their work being published. However, when such “fake p-values” exist, they tamper with the statistic T(P1,…,Pn) because they are observations from a Beta(1,2) distribution. If present, the right model for the random variables Pk is described as a tilted Uniform distribution, also called a Mendel distribution, since it was underlying Fisher’s critique of Mendel’s work. Therefore, methods for combining genuine p-values are reviewed, and it is shown how quantiles of classical combining test statistics, allowing a small number of fake p-values, can be used to make an informed decision when jointly combining fake (from Two P) and genuine (from not Two P) p-values.
Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids
Authors: Shimonosono Masataka , Morimoto Masaki , Hirose Wataru , Tomita Yasuto , Matsuura Norihiro , Flashner Samuel , Ebadi Mesra S. , Okayasu Emilea H. , Lee Christian Y. , Britton William R. , Martin Cecilia , Wuertz Beverly R. , Parikh Anuraag S. , Sachdeva Uma M. , Ondrey Frank G. , Atigadda Venkatram R. , Elmets Craig A. , Abrams Julian A. , Muir Amanda B. , Klein-Szanto Andres J. , Weinberg Kenneth I. , Momen-Heravi Fatemeh , Nakagawa Hiroshi
Published: September 2024

Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco’s Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids. To optimize the ADF-based medium, we evaluated the requirement of exogenous epidermal growth factor (EGF) and inhibition of transforming growth factor-(TGF)-β receptor-mediated signaling, both key regulators of the proliferation of human esophageal keratinocytes. We have modeled human esophageal epithelial pathology by stimulating esophageal 3D organoids with interleukin (IL)-13, an inflammatory cytokine, or UAB30, a novel pharmacological activator of retinoic acid signaling. Results: The formation of normal human esophageal 3D organoids was limited by excessive EGF and intrinsic TGFβ-receptor-mediated signaling. Optimized HOME0 improved normal human esophageal organoid formation. In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. Conclusions: HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media.
Using Large Language Models for Microbiome Findings Reports in Laboratory Diagnostics
Authors: Krause Thomas , Glau Laura , Newels Patrick , Reis Thoralf , Bornschlegl Marco X. , Kramer Michael , Hemmje Matthias L.
Published: September 2024

Background: Advancements in genomic technologies are rapidly evolving, with the potential to transform laboratory diagnostics by enabling high-throughput analysis of complex biological data, such as microbiome data. Large Language Models (LLMs) have shown significant promise in extracting actionable insights from vast datasets, but their application in generating microbiome findings reports with clinical interpretations and lifestyle recommendations has not been explored yet. Methods: This article introduces an innovative framework that utilizes LLMs to automate the generation of findings reports in the context of microbiome diagnostics. The proposed model integrates LLMs within an event-driven, workflow-based architecture, designed to enhance scalability and adaptability in clinical laboratory environments. Special focus is given to aligning the model with clinical standards and regulatory guidelines such as the In-Vitro Diagnostic Regulation (IVDR) and the guidelines published by the High-Level Expert Group on Artificial Intelligence (HLEG AI). The implementation of this model was demonstrated through a prototype called “MicroFlow”. Results: The implementation of MicroFlow indicates the viability of automating findings report generation using LLMs. Initial evaluation by laboratory expert users indicated that the integration of LLMs is promising, with the generated reports being plausible and useful, although further testing on real-world data is necessary to assess the model’s accuracy and reliability. Conclusions: This work presents a potential approach for using LLMs to support the generation of findings reports in microbiome diagnostics. While the initial results seem promising, further evaluation and refinement are needed to ensure the model’s effectiveness and adherence to clinical standards. Future efforts will focus on improvements based on feedback from laboratory experts and comprehensive testing on real patient data.
Tumor Microenvironment Based on Extracellular Matrix Hydrogels for On-Chip Drug Screening
Authors: Liu Xiaoyan , Cheng Jinxiong , Zhao Yingcan
Published: September 2024

Recent advances in three-dimensional (3D) culturing and nanotechnology offer promising pathways to overcome the limitations of drug screening, particularly for tumors like neuroblastoma. In this study, we develop a high-throughput microfluidic chip that integrates a concentration gradient generator (CGG) with a 3D co-culture system, constructing the vascularized microenvironment in tumors by co-culturing neuroblastoma (SY5Y cell line) and human brain microvascular endothelial cells (HBMVECs) within a decellularized extracellular matrix (dECM) hydrogels. The automated platform enhances the simulation of the tumor microenvironment and allows for the precise control of the concentrations of nanomedicines, which is crucial for evaluating therapeutic efficacy. The findings demonstrate that the high-throughput platform can significantly accelerate drug discovery. It efficiently screens and analyzes drug interactions in a biologically relevant setting, potentially revolutionizing the drug screening process.
Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases
Authors: Ore Adaleiz , Angelastro James M. , Giulivi Cecilia
Published: September 2024

The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and Huntington’s diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell–derived secretions, and extracellular vesicles. Mesenchymal stem cell–mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.
Emerging Trends of Safe Working Conditions in the Construction Industry: A Bibliometric Approach
Authors: Alejo Ayodele Oluwole , Aigbavboa Clinton Ohis , Aghimien Douglas Omoregie
Published: September 2024

The construction industry has been slow to implement safe working conditions, even though it could reduce the risks and dangers that the industry’s operations pose to human health and safety. More research and development in this area is clearly needed to increase the acceptance of safety in the execution of engineering projects, as previous study has demonstrated. Therefore, this study will analyse safe working conditions in construction-related professions in order to determine the focal area of previous studies. However, there has not been much effort put into mapping international studies on safe working environments in the construction industry. This research evaluates safety for the construction industry in order to discover new research trends. This indicates the ongoing challenges in the sector. For this study, comprehensive bibliometric methodology was applied, and data were extracted from the Scopus database. Using keywords like “safe”, “working condition”, “construction industry” or “built environment”, “health and safety”, and “technology”, publications from the database were extracted. Based on the collected bibliographic information, a co-authorship and co-occurrence map was created using VOSviewer. Research on occupational health and safety in the building industry, safety management and risk factors in the construction industry, ethical considerations in human experimentation, and safety and work environment revealed an emerging trend in safe working conditions in the construction industry.
Molecular Insights into the Anticancer Activity of Withaferin-A: The Inhibition of Survivin Signaling
Authors: Wadhwa Renu , Wang Jia , Shefrin Seyad , Zhang Huayue , Sundar Durai , Kaul Sunil C.
Published: September 2024

Survivin, a member of the IAP family, functions as a homodimer and inhibits caspases, the key enzymes involved in apoptosis. Several Survivin inhibitors, including YM-155, Debio1143, EM1421, LQZ-7I, and TL32711, have emerged as potential anticancer drugs awaiting validation in clinical trials. Due to the high cost and adverse side effects of synthetic drugs, natural compounds with similar activity have also been in demand. In this study, we conducted molecular docking assays to evaluate the ability of Wi-A and Wi-N to block Survivin dimerization. We found that Wi-A, but not Wi-N, can bind to and prevent the homodimerization of Survivin, similar to YM-155. Therefore, we prepared a Wi-A-rich extract from Ashwagandha leaves (Wi-AREAL). Experimental analyses of human cervical carcinoma cells (HeLa and ME-180) treated with Wi-AREAL (0.05–0.1%) included assessments of viability, apoptosis, cell cycle, migration, invasion, and the expression levels (mRNA and protein) of molecular markers associated with these phenotypes. We found that Wi-AREAL led to growth arrest mediated by the upregulation of p21WAF1 and the downregulation of several proteins (CDK1, Cyclin B, pRb) involved in cell cycle progression. Furthermore, Wi-AREAL treatment activated apoptosis signaling, as evidenced by reduced PARP-1 and Bcl-2 levels, increased procaspase-3, and elevated Cytochrome C. Additionally, treating cells with a nontoxic low concentration (0.01%) of Wi-AREAL inhibited migration and invasion, as well as EMT (epithelial–mesenchymal transition) signaling. By combining computational and experimental approaches, we demonstrate the potential of Wi-A and Wi-AREAL as natural inhibitors of Survivin, which may be helpful in cancer treatment.
A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses
Authors: Hobbs Kallie J. , Bayless Rosemary , Sheats M. Katie
Published: September 2024

With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.
Evaluation of Known Markers of Ferroptosis in Semen of Patients with Different Reproductive Pathologies and Fertile Men
Authors: Moretti Elena , Signorini Cinzia , Liguori Laura , Corsaro Roberta , Nerucci Fabiola , Fiorini Marcello , Menchiari Silvia , Collodel Giulia
Published: September 2024

This study aims to investigate the role of ferroptosis, an iron-dependent form of regulated cell death, in male infertility. The motivation behind this research stems from the increasing recognition of oxidative stress and iron metabolism dysregulation as critical factors in male reproductive health. In this study, 28 infertile patients (grouped by the presence of urogenital infections or varicocele) and 19 fertile men were selected. Spermiograms were performed by light microscopy (WHO, 2021). Testosterone, ferritin, transferrin-bound iron, transferrin, and F2-isoprostanes (F2-IsoPs) were detected in seminal plasma. Glutathione peroxidase 4 (GPX4) and acyl coenzyme A synthetase long chain family member 4 (ACSL4) were also assessed in sperm cells using enzyme-linked immunosorbent assays (ELISA). All the variables were correlated (statistically significant Spearman’s rank correlations) in the whole population, and then the comparison between variables of the different groups of men were carried out. Seminal ferritin and transferrin positively correlated with seminal F2-IsoPs, which had positive correlations with ACSL4 detected in sperm cells. Ferritin and ACSL4 negatively correlated with the seminal parameters. No correlation was detected for GPX4. Comparing the variables in the three examined groups, elevated levels of ACSL4 were observed in infertile patients with urogenital infections and varicocele; GPX4 levels were similar in the three groups. These results suggested a mechanism of ferroptosis, identified by increased ACSL4 levels and the occurrence of lipid peroxidation. Such events appear to be GPX4-independent in reproductive pathologies such as varicocele and urogenital infections.
The Relationship between HERV, Interleukin, and Transcription Factor Expression in ZIKV Infected versus Uninfected Trophoblastic Cells
Authors: Costa Anderson Luís da , Prieto-Oliveira Paula , Duarte-Barbosa Márcia , Andreata-Santos Robert , Peter Cristina M. , Prolo de Brito Thamires , Antoneli Fernando , Durães-Carvalho Ricardo , Briones Marcelo R. S. , Maricato Juliana T. , Zanotto Paolo M. A. , Jacob Machado Denis , Janini Luiz M. R.
Published: September 2024

Zika virus (ZIKV) is an arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV triggers an immune defense in the placenta. This immune response counts with the participation of interleukins and transcription factors. Additionally, it has the potential involvement of human endogenous retroviruses (HERVS). Interleukins are immune response regulators that aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. HERVs are remnants of ancient viral infections that integrate into the genome and produce syncytin proteins crucial for placental development. Since ZIKV can infect trophoblast cells, we analyzed the relationship between ZIKV infection, HERV, interleukin, and transcription factor modulations in the placenta. To investigate the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asian–Brazilian) using Taqman and RT2 Profiler PCR Array assays. Our results indicate that early ZIKV infection (24–72 h) does not induce differential interleukins, transcription factors, and HERV expression. However, we show that the expression of a few of these host defense genes appears to be linked independently of ZIKV infection. Future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and transcription factors in the placenta.
Emerging and Biological Concepts in Pediatric High-Grade Gliomas
Authors: Yoel Abigail , Adjumain Shazia , Liang Yuqing , Daniel Paul , Firestein Ron , Tsui Vanessa
Published: September 2024

Primary central nervous system tumors are the most frequent solid tumors in children, accounting for over 40% of all childhood brain tumor deaths, specifically high-grade gliomas. Compared with pediatric low-grade gliomas (pLGGs), pediatric high-grade gliomas (pHGGs) have an abysmal survival rate. The WHO CNS classification identifies four subtypes of pHGGs, including Grade 4 Diffuse midline glioma H3K27-altered, Grade 4 Diffuse hemispheric gliomas H3-G34-mutant, Grade 4 pediatric-type high-grade glioma H3-wildtype and IDH-wildtype, and infant-type hemispheric gliomas. In recent years, we have seen promising advancements in treatment strategies for pediatric high-grade gliomas, including immunotherapy, CAR-T cell therapy, and vaccine approaches, which are currently undergoing clinical trials. These therapies are underscored by the integration of molecular features that further stratify HGG subtypes. Herein, we will discuss the molecular features of pediatric high-grade gliomas and the evolving landscape for treating these challenging tumors.