bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Beef Cattle Production: Safety and Effectiveness of New Immunocastration Vaccine
Authors: Siel Daniela , Huenchullán Paula R. , Vidal Sonia , Valdés Andrea , Sáenz Leonardo
Published: September 2024

Reproductive control in mammals, particularly in beef production systems, is crucial for managing behaviors driven by sex steroids, which can cause biosecurity issues, reduced weight gain, and decreased meat quality. Additionally, controlling sexual activity in females prevents unwanted pregnancies when both sexes are housed together for fattening. Surgical castration in cattle, commonly performed under field conditions, is associated with significant welfare concerns due to pain and infection risks. Furthermore, castrating female cattle in the field is often impractically expensive. Hence, new reproductive control methods that prioritize animal welfare and are suitable for both sexes are essential. Immunocastration (IC), which involves vaccination against the GnRH-I hormone, has emerged as a promising alternative, demonstrating efficacy and safety in various species. Immunocastration has proven to be an effective alternative to surgical castration in controlling reproduction and promoting animal welfare in several species. This study aims to evaluate the safety, immunogenicity, immunocastration effect, and productive impact of a novel IC vaccine developed in Chile for female cattle. Two consecutive trials were conducted, the first under controlled conditions and the second under field conditions. The results demonstrated that the new vaccine is safe and effective for use in beef cattle, inducing specific immunity against GnRH-I, reducing gonadal functionality, and improving productive parameters. These findings suggest that this new IC vaccine can significantly benefit the beef cattle industry by providing a welfare-friendly and efficient method of reproductive control.
Discrete Homogeneous and Non-Homogeneous Markov Chains Enhance Predictive Modelling for Dairy Cow Diseases
Authors: Saro Jan , Ducháček Jaromir , Brožová Helena , Stádník Luděk , Bláhová Petra , Horáková Tereza , Hlavatý Robert
Published: September 2024

Modelling and predicting dairy cow diseases empowers farmers with valuable information for herd health management, thereby decreasing costs and increasing profits. For this purpose, predictive models were developed based on machine learning algorithms. However, machine-learning based approaches require the development of a specific model for each disease, and their consistency is limited by low farm data availability. To overcome this lack of complete and accurate data, we developed a predictive model based on discrete Homogeneous and Non-homogeneous Markov chains. After aggregating data into categories, we developed a method for defining the adequate number of Markov chain states. Subsequently, we selected the best prediction model through Chebyshev distance minimization. For 14 of 19 diseases, less than 15% maximum differences were measured between the last month of actual and predicted disease data. This model can be easily implemented in low-tech dairy farms to project costs with antibiotics and other treatments. Furthermore, the model’s adaptability allows it to be extended to other disease types or conditions with minimal adjustments. Therefore, including this predictive model for dairy cow diseases in decision support systems may enhance herd health management and streamline the design of evidence-based farming strategies.
Functional Characterization of 11 Tentative Microneme Proteins in Type I RH Strain of Toxoplasma gondii Using the CRISPR-Cas9 System
Authors: Ma Zhi-Ya , Wu Xiao-Jing , Li Chuan , Gao Jin , Kou Yong-Jie , Wang Meng , Zhu Xing-Quan , Zheng Xiao-Nan
Published: September 2024

Toxoplasma gondii, a pathogenic apicomplexan parasite, infects approximately one third of the world’s population and poses a serious threat to global public health. Microneme proteins (MICs) secreted by the microneme, an apical secretory organelle of T. gondii, play important roles in the invasion, motility, and intracellular survival of T. gondii. In this study, we selected 11 genes of interest (GOIs) of T. gondii, tentative MICs predicted to be localized in micronemes, and we used the CRISPR-Cas9 system to construct epitope tagging strains and gene knockout strains to explore the localization and function of these 11 tentative MICs. Immunofluorescence assay showed that nine tentative MICs (TGME49_243930, TGME49_200270, TGME49_273320, TGME49_287040, TGME49_261710, TGME49_205680, TGME49_304490, TGME49_245485, and TGME49_224620) were localized or partially localized in the microneme, consistent with the prediction. However, TGME49_272380 and TGME49_243790 showed different localizations from the prediction, being localized in the endoplasmic reticulum and the dense granule, respectively. Further functional characterization of the 11 RHΔGOI strains revealed that deletion of these 11 GOIs had no significant effect on plaque formation, intracellular replication, egress, invasion ability, and virulence of T. gondii. Although these 11 GOIs are not essential genes for the growth and virulence of tachyzoites of type I RH strain, they may have potential roles in other developmental stages or other genotypes of T. gondii. Thus, further research should be performed to explore the possible role of the nine mics and the other two GOIs in other life cycle stages and other genotypes of T. gondii.
Effects of Social Group Housing on the Behavioral and Physiological Responses of Captive Sub-Adult Giant Pandas
Authors: Yuan Bo , Fu Qin , Wang Xue-Ying , Zhang Xiao-Hui , Liu Yu-Liang , Hou Rong , Zhang Ming-Yue
Published: September 2024

Wild giant pandas are inherently solitary creatures, however, the ex-situ conservation efforts significantly alter the living circumstances of their captive counterparts. Following the breeding period, giant pandas in captivity may be maintained in social groups. Currently, there is a lack of research on the effects of group housing on the physiology, behavior, and gut microbiota of captive giant pandas. This study divided six captive giant pandas into two groups following the breeding period. By comparing the behavior, physiology, and microorganisms of the two groups, we aim to investigate the behavioral responses and physiological adaptation mechanisms exhibited by captive giant pandas in a “group living” state. Our findings indicate that sub-adult giant pandas housed in group settings exhibit a significantly longer duration of playing behavior (including interactive and non-interactive play) compared to their counterparts housed separately (p < 0.001) while also demonstrating a significantly lower duration of stereotyped behavior than their separately housed counterparts. Additionally, an analysis of urine cortisol and heart rate variability between the two groups revealed no significant differences. Simultaneously, the group housing strategy markedly elevated the β diversity of gut microbiota in sub-adult giant pandas. In conclusion, the group-rearing model during the sub-adult stage has been shown to significantly alter the behavioral patterns of captive giant pandas. In conclusion, within the present captive setting, the group-rearing approach during the sub-adult stage proved to be less distressing for adult captive giant pandas.
Assessment of Thoracic Radiographic Alterations in Dogs with Heartworm and Their Correlation with Pulmonary Hypertension, Pre- and Post-Adulticide Treatment
Authors: Falcón-Cordón Soraya , Falcón-Cordón Yaiza , Costa-Rodríguez Noelia , Matos Jorge Isidoro , Montoya-Alonso José Alberto , Carretón Elena
Published: September 2024

Pulmonary hypertension (PH) is a prevalent and severe complication in dogs infected with Dirofilaria immitis. This study aimed to elucidate the progression of PH by analyzing radiographic parameters and the Right Pulmonary Artery Distensibility (RPAD) Index at three key time points: diagnosis (day 0), discharge (day 90), and six months post-discharge (day 270). Fifty-two heartworm-infected dogs were divided into two groups: non-hypertensive and hypertensive. Radiographic measurements, including Vertebral Heart Size (VHS), CrPA/R4 ratio, and CdPA/R9 ratio, along with the RPAD Index, were assessed on Days 0, 90, and 270. Results indicated that, in Group A, the RPAD Index improved significantly from 42% on Day 0 to 43.16% on Day 90, with no significant change by Day 270 (42%). In contrast, hypertensive dogs exhibited a persistently low RPAD Index, averaging 17% throughout this study (p < 0.001). Radiographic parameters in hypertensive dogs showed continuous elevation compared to non-hypertensive dogs, with significant increases in VHS, CrPA/R4, and CdPA/R9 ratios on day 270 compared to day 0 (p < 0.05). The results confirmed that PH persisted in dogs with D. immitis after adulticide treatment, highlighting the importance of regular radiographic monitoring for assessing and managing long-term outcomes in dogs with PH during and after adulticide treatment. Continuous surveillance is thus essential for the effective post-treatment management of PH in dogs.
Cattle Body Size Measurement Based on DUOS–PointNet++
Authors: Weng Zhi , Lin Wenzhi , Zheng Zhiqiang
Published: September 2024

The common non-contact, automatic body size measurement methods based on the whole livestock point cloud are complex and prone to errors. Therefore, a cattle body measuring system is proposed. The system includes a new algorithm called dynamic unbalanced octree grouping (DUOS), based on PointNet++, and an efficient method of body size measurement based on segmentation results. This system is suitable for livestock body feature sampling. The network divides the cow into seven parts, including the body and legs. Moreover, the key points of body size are located in the different parts. It combines density measurement, point cloud slicing, contour extraction, point cloud repair, etc. A total of 137 items of cattle data are collected. Compared with some of the other models, the DUOS algorithm improves the accuracy of the segmentation task and mean intersection by 0.53% and 1.21%, respectively. Moreover, compared with the manual measurement results, the relative errors of the experimental measurement results are as follows: withers height, 1.18%; hip height, 1.34%; body length, 2.52%; thoracic circumference, 2.12%; abdominal circumference, 2.26%; and cannon circumference, 2.78%. In summary, the model is proven to have a good segmentation effect on cattle bodies and is suitable for cattle body size measurement.
Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids
Authors: Arroyo Almenas Francisco , Törő Gábor , Szaniszlo Peter , Maskey Manjit , Thanki Ketan K. , Koltun Walter A. , Yochum Gregory S. , Pinchuk Irina V. , Chao Celia , Hellmich Mark R. , Módis Katalin
Published: September 2024

Cystathionine gamma-lyase (CSE) and TNF-α are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated by CSE and TNF-α are poorly understood. In the present study, we investigated these interactions in normal colonocytes and an organoid model of the healthy human colon using CSE-specific pharmacological inhibitors and siRNA-mediated transient gene silencing in analytical and functional assays in vitro. We demonstrated that CSE and TNF-α mutually regulated each other’s functions in colonic epithelial cells. TNF-α treatment stimulated CSE activity within minutes and upregulated CSE expression after 24 h, increasing endogenous CSE-derived H2S production. In turn, CSE activity promoted TNF-α-induced NF-ĸB and ERK1/2 activation but did not affect the p38 MAPK signaling pathway. Inhibition of CSE activity completely abolished the TNF-α-induced increase in transepithelial permeability and wound healing. Our data suggest that CSE activity may be essential for effective TNF-α-mediated intestinal injury response. Furthermore, CSE regulation of TNF-α-controlled intracellular signaling pathways could provide new therapeutic targets in diseases of the colon associated with impaired epithelial wound healing.
Modulation of Antioxidant Enzyme Expression of In Vitro Culture-Derived Reticulocytes
Authors: Langlands Hannah D. , Shoemark Deborah K. , Toye Ashley M.
Published: September 2024

The regulation of reactive oxygen species (ROS) in red blood cells (RBCs) is crucial for maintaining functionality and lifespan. Indeed, dysregulated ROS occurs in haematological diseases such as sickle cell disease and β-thalassaemia. In order to combat this, RBCs possess high levels of protective antioxidant enzymes. We aimed to further boost RBC antioxidant capacity by overexpressing peroxiredoxin (Prxs) and glutathione peroxidase (GPxs) enzymes. Multiple antioxidant enzyme cDNAs were individually overexpressed in expanding immortalised erythroblasts using lentivirus, including Prx isoforms 1, 2, and 6 and GPx isoforms 1 and 4. Enhancing Prx protein expression proved straightforward, but GPx overexpression required modifications. For GPx4, these modifications included adding a SECIS element in the 3’UTR, the removal of a mitochondrial-targeting sequence, and removing putative ubiquitination sites. Culture-derived reticulocytes exhibiting enhanced levels of Prx and GPx antioxidant proteins were successfully engineered, demonstrating a novel approach to improve RBC resilience to oxidative stress. Further work is needed to explore the activity of these proteins and their impact on RBC metabolism, but this strategy shows promise for improving RBC function in physiological and pathological contexts and during storage for transfusion. Enhancing the antioxidant capacity of reticulocytes has exciting promise for developing culture-derived RBCs with enhanced resistance to oxidative damage and offers new therapeutic interventions in diseases with elevated oxidative stress.
Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients
Authors: Magallón María , Castillo-Corullón Silvia , Bañuls Lucía , Romero Teresa , Pellicer Daniel , Herrejón Alberto , Navarro-García María Mercedes , González Cruz , Dasí Francisco
Published: September 2024

Background: Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Methods: Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Results: Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Conclusions: Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.
Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia
Authors: Silva-Llanes Ignacio , Martín-Baquero Raquel , Berrojo-Armisen Alicia , Rodríguez-Cueto Carmen , Fernández-Ruiz Javier , De Lago Eva , Lastres-Becker Isabel
Published: September 2024

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital in limiting neurodegeneration, with its activation shown to mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects in a TAU-dependent FTD mouse model, reducing neurodegeneration and inflammation. This suggests DMF repositioning potential for FTD treatment. Until now, no trial had been conducted to analyze the effect of DMF on TDP-43-dependent FTD. In this study, we aimed to determine the potential therapeutic efficacy of DMF in a TDP-43-related FTD mouse model that exhibits early cognitive impairment. Mice received oral DMF treatment every other day from presymptomatic to symptomatic stages. By post-natal day (PND) 60, an improvement in cognitive function is already evident, becoming even more pronounced by PND90. This cognitive enhancement correlates with the neuroprotection observed in the dentate gyrus and a reduction in astrogliosis in the stratum lacunosum-moleculare zone. At the prefrontal cortex (PFC) level, a neuroprotective effect of DMF is also observed, accompanied by a reduction in astrogliosis. Collectively, our results suggest a potential therapeutic application of DMF for patients with TDP-43-dependent FTD.
A Machine Walks into an Exhibit: A Technical Analysis of Art Curation
Authors: von Davier Thomas Şerban , Herman Laura M. , Moruzzi Caterina
Published: September 2024

Contemporary art consumption is predominantly online, driven by algorithmic recommendation systems that dictate artwork visibility. Despite not being designed for curation, these algorithms’ machinic ways of seeing play a pivotal role in shaping visual culture, influencing artistic creation, visibility, and associated social and financial benefits. The Algorithmic Pedestal was a gallery, practice-based research project that reported gallerygoers’ perceptions of a human’s curation and curation achieved by Instagram’s algorithm. This paper presents a technical analysis of the same exhibit using computer vision code, offering insights into machines’ perception of visual art. The computer vision code assigned values on various metrics to each image, allowing statistical comparisons to identify differences between the collections of images selected by the human and the algorithmic system. The analysis reveals statistically significant differences between the exhibited images and the broader Metropolitan Museum of Art digital collection. However, the analysis found minimal distinctions between human-curated and Instagram-curated images. This study contributes insights into the perceived value of the curation process, shedding light on how audiences perceive artworks differently from machines using computer vision.
Impact of El Niño-Southern Oscillation on Dust Variability during the Spring Season over the Arabian Peninsula
Authors: Alsubhi Yazeed , Ali Gohar
Published: September 2024

This study investigates the dust aerosol optical depth (DAOD) variability over the Arabian Peninsula (AP) in the spring season, a region profoundly affected by dust activity due to its desert terrain. Employing the MERRA-2 DAOD reanalysis dataset for the period 1981–2022, a significant trend in DAOD is noted in the spring season compared to the other seasons. The leading Empirical Orthogonal Function (EOF) explains 67% of the total DAOD variance during the spring season, particularly over the central and northeastern parts of AP. The analysis reveals the strengthening of upper-level divergence over the western Pacific, favoring mid-tropospheric positive geopotential height anomalies over the AP, leading to warm and drier surface conditions and increased DAOD. A statistically significant negative relationship (correlation = −0.32, at 95% confidence level) is noted between DAOD over AP and the El Niño-Southern Oscillation (ENSO), suggesting that La Niña conditions may favor higher dust concentrations over the AP region and vice versa during El Niño phase. The high (low) DAOD over the region corresponds to mid-tropospheric positive (negative) geopotential height anomalies through strengthening (weakening) of the upper-level divergence (convergence) over the western Pacific during the La Niña (El Niño) phase. This study shows that ENSO could be a possible precursor to predicting dust variability on a seasonal time scale.
The Quantum-Inspired Evolutionary Algorithm in the Parametric Optimization of Lithium-Ion Battery Housing in the Multiple-Drop Test
Authors: Rurański Adam , Kuś Wacław
Published: September 2024

Recent developments in lithium-ion batteries have improved their capacity, which allows them to be used in more applications like power tools. However, they also carry higher risks, such as thermal runaway, which can happen if they are damaged. To make these batteries safer, it is important to improve the design of their housings subjected to multiple drops during their use. This article introduces a new method for optimizing the design of lithium-ion battery housings using a Quantum-Inspired Evolutionary Algorithm (QEA). Previously used mainly in theoretical settings, the authors have adapted QEA for practical engineering tasks. Multiple-drop test simulations were performed, and QEA was used to identify the best housing designs that minimize damage. To support this, a program was developed that automates all drop tests and rebuilds the model. The damage is obtained on the basis of the finite element method (FEM) analyses. The findings show that the algorithm successfully identified designs with the least damage during these tests. This research helps make battery housings safer and explores new uses for QEA in mechanical engineering.
Stress and Strain Characterization for Evaluating Mechanical Safety of Lithium-Ion Pouch Batteries under Static and Dynamic Loadings
Authors: Akbari Edris , Voyiadjis George Z.
Published: September 2024

The crashworthiness of electric vehicles depends on the response of lithium-ion cells to significant deformation and high strain rates. This study thoroughly explores the mechanical behavior due to damage of lithium-ion battery (LIB) cells, focusing on Lithium Nickel Manganese Cobalt Oxide (NMC) and Lithium Iron Phosphate (LFP) types during both quasi-static indentation and dynamic high-velocity penetration tests. Employing a novel approach, a hemispherical indenter addresses gaps in stress–strain data for pouch cells, considering crucial factors like strain rate/load rate and battery cell type. In the finite element method (FEM) analysis, the mechanical response is investigated in two stages. First, a viscoplastic model is developed in Abaqus/Standard to predict the indentation test. Subsequently, a thermomechanical model is formulated to predict the high-speed-impact penetration test. Considering the high plastic strain rate of the LIB cell, adiabatic heating effects are incorporated into this model, eliminating heat conduction between elements. Addressing a notable discrepancy from prior research, this work explores the substantial reduction in force observed when transitioning from a single cell to a stack of two cells. The study aims to unveil the underlying reasons and provide insights into the mechanical behavior of stacked cells.
A Trusted Supervision Paradigm for Autonomous Driving Based on Multimodal Data Authentication
Authors: Shi Tianyi , Wu Ruixiao , Zhou Chuantian , Zheng Siyang , Meng Zhu , Cui Zhe , Huang Jin , Ren Changrui , Zhao Zhicheng
Published: September 2024

At the current stage of autonomous driving, monitoring the behavior of safety stewards (drivers) is crucial to establishing liability in the event of an accident. However, there is currently no method for the quantitative assessment of safety steward behavior that is trusted by multiple stakeholders. In recent years, deep-learning-based methods can automatically detect abnormal behaviors with surveillance video, and blockchain as a decentralized and tamper-resistant distributed ledger technology is very suitable as a tool for providing evidence when determining liability. In this paper, a trusted supervision paradigm for autonomous driving (TSPAD) based on multimodal data authentication is proposed. Specifically, this paradigm consists of a deep learning model for driving abnormal behavior detection based on key frames adaptive selection and a blockchain system for multimodal data on-chaining and certificate storage. First, the deep-learning-based detection model enables the quantification of abnormal driving behavior and the selection of key frames. Second, the key frame selection and image compression coding balance the trade-off between the amount of information and efficiency in multiparty data sharing. Third, the blockchain-based data encryption sharing strategy ensures supervision and mutual trust among the regulatory authority, the logistic platform, and the enterprise in the driving process.
AHEAD: A Novel Technique Combining Anti-Adversarial Hierarchical Ensemble Learning with Multi-Layer Multi-Anomaly Detection for Blockchain Systems
Authors: Kamran Muhammad , Rehan Muhammad Maaz , Nisar Wasif , Rehan Muhammad Waqas
Published: September 2024

Blockchain technology has impacted various sectors and is transforming them through its decentralized, immutable, transparent, smart contracts (automatically executing digital agreements) and traceable attributes. Due to the adoption of blockchain technology in versatile applications, millions of transactions take place globally. These transactions are no exception to adversarial attacks which include data tampering, double spending, data corruption, Sybil attacks, eclipse attacks, DDoS attacks, P2P network partitioning, delay attacks, selfish mining, bribery, fake transactions, fake wallets or phishing, false advertising, malicious smart contracts, and initial coin offering scams. These adversarial attacks result in operational, financial, and reputational losses. Although numerous studies have proposed different blockchain anomaly detection mechanisms, challenges persist. These include detecting anomalies in just a single layer instead of multiple layers, targeting a single anomaly instead of multiple, not encountering adversarial machine learning attacks (for example, poisoning, evasion, and model extraction attacks), and inadequate handling of complex transactional data. The proposed AHEAD model solves the above problems by providing the following: (i) data aggregation transformation to detect transactional and user anomalies at the data and network layers of the blockchain, respectively, (ii) a Three-Layer Hierarchical Ensemble Learning Model (HELM) incorporating stratified random sampling to add resilience against adversarial attacks, and (iii) an advanced preprocessing technique with hybrid feature selection to handle complex transactional data. The performance analysis of the proposed AHEAD model shows that it achieves higher anti-adversarial resistance and detects multiple anomalies at the data and network layers. A comparison of the proposed AHEAD model with other state-of-the-art models shows that it achieves 98.85% accuracy against anomaly detection on data and network layers targeting transaction and user anomalies, along with 95.97% accuracy against adversarial machine learning attacks, which surpassed other models.
A Putative Effector Pst-18220, from Puccinia striiformis f. sp. tritici, Participates in Rust Pathogenicity and Plant Defense Suppression
Authors: Tian Mengfan , Zhang Zhen , Bi Xiaorui , Xue Yan , Zhou Jiahui , Yuan Bo , Feng Zhaozhong , Li Lianwei , Wang Junjuan
Published: September 2024

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), stands out as one of the most devastating epidemics impacting wheat production worldwide. Resistant wheat varieties had swiftly been overcome due to the emergence of new virulent Pst strains. Effectors secreted by Pst interfere with plant immunity, and verification of their biological function is extremely important for controlling wheat stripe rust. In this study, we identified an effector, Pst-18220, from Puccinia striiformis f. sp. tritici (Pst), which was induced during the early infection stage of Pst. Silencing the expression of Pst-18220 through virus-mediated host-induced gene silencing (HIGS) resulted in a decreased number of rust pustules. In Nicotiana benthamiana, it significantly suppressed cell death induced by Pseudomonas syringae pv. tomato (Pto) DC3000. In Arabidopsis, plants with stable overexpression of Pst-18220 showed increased susceptibility to Pto DC3000, accompanied by a decrease in the expression level of pattern-triggered immunity (PTI)/effector-triggered immunity (ETI)-related genes, namely, AtPCRK1, AtPCRK2, and AtBIK1. These results emphasize the significant role of the Pst candidate effector, Pst-18220, in rust pathogenicity and the suppression of plant defense mechanisms. This broadens our understanding of effectors without any known motif.
Bringing Vitamin D and the Vitamin D Receptor into the Limelight
Authors: Sun Jun
Published: September 2024

Classically, vitamin D is known to regulate skeletal and mineral ion homeostasis [...]
Genetics of Female Pelvic Organ Prolapse: Up to Date
Authors: Li Yuting , Li Zihan , Li Yinuo , Gao Xiaofan , Wang Tian , Huang Yibao , Wu Mingfu
Published: September 2024

Pelvic organ prolapse (POP) is a benign disease characterized by the descent of pelvic organs due to weakened pelvic floor muscles and fascial tissues. Primarily affecting elderly women, POP can lead to various urinary and gastrointestinal tract symptoms, significantly impacting their quality of life. The pathogenesis of POP predominantly involves nerve–muscle damage and disorders in the extracellular matrix metabolism within the pelvic floor. Recent studies have indicated that genetic factors may play a crucial role in this condition. Focusing on linkage analyses, single-nucleotide polymorphisms, genome-wide association studies, and whole exome sequencing studies, this review consolidates current research on the genetic predisposition to POP. Advances in epigenetics are also summarized and highlighted, aiming to provide theoretical recommendations for risk assessments, diagnoses, and the personalized treatment for patients with POP.
Biochemical Characterisation of the Short Isoform of Histone N-Terminal Acetyltransferase NAA40
Authors: Klavaris Ariel , Kouma Maria , Ozdemir Cem , Nicolaidou Vicky , Miller Kyle M. , Koufaris Costas , Kirmizis Antonis
Published: September 2024

N-alpha-acetyltransferase 40 (NAA40) is an evolutionarily conserved N-terminal acetyltransferase (NAT) linked to oncogenesis and chemoresistance. A recent study reported the generation of a second, shorter NAA40 isoform (NAA40S) through alternative translation, which we proceeded to further characterise. Notably, recombinant NAA40S had a greater in vitro enzymatic activity and affinity towards its histone H2A/H4 substrates compared to full-length NAA40 (NAA40L). Within cells, NAA40S was enzymatically active, based on its ability to suppress the H2A/H4S1Ph antagonistic mark in CRISPR-generated NAA40 knockout cells. Finally, we show that in addition to alternative translation, the NAA40S isoform could be derived from a primate and testis-specific transcript, which may align with the “out-of-testis” origin of recently evolved genes and isoforms. To summarise, our data reveal an even greater functional divergence between the two NAA40 isoforms than had been previously recognised.
Sedative-Hypnotic Effect and Mechanism of Carbon Nanofiber Loaded with Essential Oils of Ligusticum chuanxiong (Ligusticum chuanxiong Hort.) and Finger Citron (Citrus medica L. var. sarcodactylis) on Mice Models of Insomnia
Authors: Hu Yue , He Xiaofang , Wu Yuanyuan , Zhang Wenjie , Feng Huiyi , Liu Haolin , Wu Qianqian , Gao Leying , Long Yu , Li Xiaoqiu , Deng Jie , Ma Yin , Li Nan
Published: September 2024

(1) Background: Insomnia is a neurological illness that poses a significant threat to both physical and mental health. It results in the activation of neuroglial cells, heightened neuroinflammation, oxidative stress, and disruptions in the Hypothalamic–Pituitary–Adrenal (HPA) axis. Ligusticum Chuanxiong (CX) and Finger citron (FC) are frequently utilized botanicals for addressing sleeplessness. Both herbs possess notable anti-inflammatory properties in their volatile oils. However, their effectiveness is hindered by the nasal mucosal irritation and instability they exhibit. (2) Methods: This study involved the preparation of a nanofiber composite system using carbon nanofiber (CNF) suspensions containing essential oils of Ligusticum chuanxiong–Finger citron (CXEO-FCEO-CNF). The effects and mechanisms of these essential oils in improving insomnia were investigated using an insomnia mouse model after encapsulation. (3) Results: The CXEO-FCEO-CNF had an average particle size of 103.19 ± 1.64 nm. The encapsulation rates of essential oils of Ligusticum chuanxiong (CXEO) and essential oils of Finger citron (FCEO) were 44.50% and 46.15%, respectively. This resulted in a considerable improvement in the stability of the essential oils over a period of 30 days. The essential oils effectively decreased the irritation of the nasal mucosa following encapsulation. Furthermore, CXEO-FCEO-CNF enhanced voluntary activity and sleep in mice with insomnia, notably boosted the activity of superoxide dismutase (SOD), reduced the concentration of lipoxidized malondialdehyde (MDA), decreased the levels of hormones associated with the HPA axis, and regulated the levels of neurotransmitters, resulting in a beneficial therapeutic outcome. CXEO-FCEO-CNF contains a total of 23 active ingredients, such as alpha-Asarone, (E)-methyl isoeugenol, and Senkyunolide. These ingredients primarily work by modulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling system to decrease oxidative stress and inflammatory reactions. (4) Conclusions: This study presented initial evidence that the combination of CXEO and FCEO in nanofiber formulations effectively reduces the nasal mucosal irritation and instability of essential oils. Furthermore, it demonstrated the potential anti-neuroinflammatory and therapeutic effects of these formulations in treating insomnia. Overall, this study provides a theoretical foundation for developing new essential oil formulations derived from herbs.
Enhancing Missense Variant Pathogenicity Prediction with MissenseNet: Integrating Structural Insights and ShuffleNet-Based Deep Learning Techniques
Authors: Liu Jing , Chen Yingying , Huang Kai , Guan Xiao
Published: September 2024

The classification of missense variant pathogenicity continues to pose significant challenges in human genetics, necessitating precise predictions of functional impacts for effective disease diagnosis and personalized treatment strategies. Traditional methods, often compromised by suboptimal feature selection and limited generalizability, are outpaced by the enhanced classification model, MissenseNet (Missense Classification Network). This model, advancing beyond standard predictive features, incorporates structural insights from AlphaFold2 protein predictions, thus optimizing structural data utilization. MissenseNet, built on the ShuffleNet architecture, incorporates an encoder-decoder framework and a Squeeze-and-Excitation (SE) module designed to adaptively adjust channel weights and enhance feature fusion and interaction. The model’s efficacy in classifying pathogenicity has been validated through superior accuracy compared to conventional methods and by achieving the highest areas under the Receiver Operating Characteristic (ROC) and Precision-Recall (PR) curves (Area Under the Curve and Area Under the Precision-Recall Curve) in an independent test set, thus underscoring its superiority.
Postoperative Atrial Fibrillation: A Review
Authors: Shah Sidra , Chahil Vipanpreet , Battisha Ayman , Haq Syed , Kalra Dinesh K.
Published: September 2024

Atrial fibrillation (AF) in the postoperative phase is a manifestation of numerous factors, including surgical stress, anesthetic effects, and underlying cardiovascular conditions. The resultant cardiac hyperactivity can induce new onset or exacerbate existing AF. A common phenomenon, postoperative atrial fibrillation (POAF) affects nearly 40% of patients and is associated with longer hospitalization stays, and increased mortality, heart failure, stroke, and healthcare costs. Areas of controversy in POAF include whether to anticoagulate patients who have short-lived POAF, especially given their higher bleeding risk in the postoperative period, and the identification of patients who would benefit the most from preventive drug therapy for POAF. This review discusses the pathophysiology and management of POAF, and strategies to reduce its occurrence.
Changes in Mitochondrial Function and Cell Death Patterns in Peripheral Blood Mononuclear Cells during Trastuzumab Treatment Following Doxorubicin Chemotherapy
Authors: Leemasawat Krit , Osataphan Nichanan , Apaijai Nattayaporn , Yanpiset Panat , Phrommintikul Arintaya , Somwangprasert Areewan , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: September 2024

Trastuzumab, a monoclonal antibody which works against human epidermal growth factor receptor 2 (HER2), possibly causes cardiotoxicity through mitochondrial dysfunction. The usefulness of isolated peripheral blood mononuclear cells (PBMCs) in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. This study aimed to determine the temporal changes in mitochondrial function, oxidative stress, and cell death in the isolated PBMCs of HER2-positive breast cancer patients during breast cancer treatment and to compare the changes with HER2-negative breast cancer patients who did not receive trastuzumab therapy. Eighteen newly diagnosed HER2-positive breast cancer women who received sequential doxorubicin and trastuzumab were consecutively recruited. Age- and gender-matched controls with HER2-negative breast cancer were selected. Echocardiography was carried out, and blood samples for the study of cardiac biomarkers and PBMCs were collected periodically during treatment. Only one patient in our cohort developed asymptomatic left ventricular dysfunction during trastuzumab treatment. However, trastuzumab following doxorubicin aggravated subclinical cardiac injury, determined by cardiac troponin and echocardiography. Cellular and mitochondrial oxidative stress in isolated PBMCs remained unchanged throughout breast cancer treatment. Regarding mitochondrial respiration, the maximal respiration and spare respiration capacity was significantly increased in controls after doxorubicin treatment but not in patients who received trastuzumab therapy. Moreover, the percentage of apoptosis and necroptosis in isolated PBMCs was dramatically decreased in the control, compared to patients with trastuzumab treatment. In conclusion, trastuzumab caused subtle myocardial injury and impaired mitochondrial respiration and cell viability in isolated PBMCs.
Concomitant Administration of Psychotropic and Prostate Cancer Drugs: A Pharmacoepidemiologic Study Using Drug–Drug Interaction Databases
Authors: Ungureanu Daniel , Popa Adina , Nemeș Adina , Crișan Cătălina-Angela
Published: September 2024

Prostate cancer (PC) represents the second most common diagnosed cancer in men. The burden of diagnosis and long-term treatment may frequently cause psychiatric disorders in patients, particularly depression. The most common PC treatment option is androgen deprivation therapy (ADT), which may be associated with taxane chemotherapy. In patients with both PC and psychiatric disorders, polypharmacy is frequently present, which increases the risk of drug–drug interactions (DDIs) and drug-related adverse effects. Therefore, this study aimed to conduct a pharmacoepidemiologic study of the concomitant administration of PC drugs and psychotropics using three drug interaction databases (Lexicomp®, drugs.com®, and Medscape®). This study assayed 4320 drug–drug combinations (DDCs) and identified 814 DDIs, out of which 405 (49.63%) were pharmacokinetic (PK) interactions and 411 (50.37%) were pharmacodynamic (PD) interactions. The most common PK interactions were based on CYP3A4 induction (n = 275, 67.90%), while the most common PD interactions were based on additive torsadogenicity (n = 391, 95.13%). Proposed measures for managing the identified DDIs included dose adjustments, drug substitutions, supplementary agents, parameters monitoring, or simply the avoidance of a given DDC. A significant heterogenicity was observed between the selected drug interaction databases, which can be mitigated by cross-referencing multiple databases in clinical practice.
Investigation of Type A Aortic Dissection Using Computational Modelling
Authors: Al-Rawi Mohammad , Belkacemi Djelloul , Lim Eric T. A. , Khashram Manar
Published: September 2024

Aortic dissection is a catastrophic failure of the endothelial wall that could lead to malperfusion or rupture. Computational modelling tools may help detect arterial damage. Technological advancements have led to more sophisticated forms of modelling being made available to low-grade computers. These devices can create 3D models with clinical data, where the clinical blood pressure waveforms’ model can be used to form boundary conditions for assessing hemodynamic parameters, modelling blood flow propagation along the aorta to predict the development of cardiovascular disease. This study presents patient-specific data for a rare case of severe Type A aortic dissection. CT scan images were taken nine months apart, consisting of the artery both before and after dissection. The results for the pre-dissection CT showed that the pressure waveform at the ascending aorta was higher, and the systolic pressure was lagging at the descending aorta. For the post-dissection analysis, we observed the same outcome; however, the amplitude for the waveform (systolic pressure) at the ascending aorta increased in the false lumen by 25% compared to the true lumen by 3%. Also, the waveform peak (systolic) was leading by 0.01 s. The hemodynamic parameter of wall shear stress (WSS) predicted the aneurysm’s existence at the ascending aorta, as well as potential aortic dissection. The high WSS contours were located at the tear location at the peak blood flow of 0.14 s, which shows the potential of this tool for earlier diagnosis of aortic dissection.
Analysis of Peri-Implantitis Photothermal Therapy Effect According to Laser Irradiation Location and Angle: A Numerical Approach
Authors: Kim Donghyuk , Kim Hyunjung , Kim Hee-Sun
Published: September 2024

In recent years, dental implants have become increasingly popular around the world. However, if the implant is not properly managed, inflammation may occur, and the implant itself may need to be removed. Peri-implantitis is a common inflammation that occurs in dental implants, and various laser treatments have recently been studied to eliminate it. In this study, the situation of removing peri-implantitis using photothermal therapy, one of the various laser treatments, was analyzed theoretically and numerically. The temperature distribution in the tissue for various laser irradiation locations, angles, and power was calculated based on heat transfer theory, and the degree of thermal damage to tissue was analyzed using the Arrhenius damage integral. In addition, the thermally damaged region ratio of inflamed and normal tissue was analyzed using the Arrhenius thermal damage ratio and normal tissue Arrhenius thermal damage ratio to confirm the trend of treatment results for each treatment condition. The results of the study showed that if only the thermal damage to the inflamed tissue is considered, the laser should be angled vertically, and the laser should be applied to the center of the inflamed tissue rather than close to the implant. However, if the thermal damage to the surrounding normal tissue is also considered, it was found that the laser should be applied at 1.0 mm from the right end of the inflamed tissue for maximum effect. This will allow for more accurate clinical treatment of peri-implantitis in the future.
The Road Ahead in Pancreatic Cancer: Emerging Trends and Therapeutic Prospects
Authors: Do Chris T. P. , Prochnau Jack Y. , Dominguez Angel , Wang Pei , Rao Manjeet K.
Published: September 2024

This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy for pancreatic cancer. Pancreatic ductal adenocarcinoma, characterized by its dense stromal architecture, presents unique challenges for effective treatment. Recent advancements have emphasized the role of the tumor microenvironment in therapeutic resistance and disease progression. We discuss novel strategies targeting the desmoplastic barrier and immunosuppressive cells to enhance immune cell infiltration and activation. Recent clinical trials, particularly those involving novel immunotherapeutic agents and tumor vaccines, are examined to understand their efficacy and limitations. Our analysis reveals that combining immunotherapy with chemotherapy, radiation therapy, or drugs targeting epigenetic processes shows promise, improving overall survival rates and response to treatment. For instance, trials utilizing checkpoint inhibitors in combination with standard chemotherapies have extended disease-free survival by up to 6 months compared to chemotherapy alone. Importantly, vaccines targeting specific tumor neoantigens have shown the potential to increase patient survival. However, these approaches also face significant challenges, including overcoming the immunosuppressive tumor microenvironment and enhancing the delivery and efficacy of therapeutic agents. By providing an overview of both the promising results and the obstacles encountered, this review aims to highlight ongoing efforts to refine immunotherapy approaches for better patient outcomes.