bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of METTL14‐Mediated m6A Modification in Promoting Iron Overload‐Induced Lipid Peroxidative Damage in Vascular Endothelial Cells to Aggravate Atherosclerosis
Authors: Min Xiao‐li , Lin Si‐xian , Zhao Xiao‐hong , Zhao Qing , Li Yun‐fei , Li Xu‐hui , Liu Xiao‐yong , Cao Yi , Sun Yu‐long , Zeng Yong 
Published: November 2024

ABSTRACTAtherosclerosis (AS) is a chronic multifactorial disease with damage to vascular endothelial cells (VECs). This study sought to delve into the mechanism of methyltransferase‐like 14 (METTL14) in iron overload‐induced lipid peroxidative damage in AS. AS mouse model and cell model were established. Levels of METTL14/circRNA coded by the Arhgap12 (circARHGAP12)/Aspartate β‐hydroxylase (ASPH) were determined. AS plaque area/lipid deposition/lipid metabolism in AS mice and iron overload in VECs were evaluated. N6‐methyladenosine (m6A) level and METTL14 enrichment and human antigen R (HuR) in circARHGAP12 or ASPH were measured. The mRNA stability of circARHGAP12 or ASPH was analyzed. We observed that METTL14 was upregulated in AS mice. METTL14 downregulation reduced plaque area/lipid deposition/iron overload/peroxidative damage in AS mice. In cell models, METTL14 downregulation could VEC injury/iron overload/lipid peroxidative damage. Mechanically, METTL14 increased the stability and expression of circARHGAP12 through m6A modification, further stabilized ASPH mRNA, and promoted ASPH transcription by binding to HuR. Overexpression of circARHGAP12 or inhibition of ASPH averted the protective role of METTL14 downregulation against iron overload‐induced peroxidative damage in AS. In conclusion, METTL14‐mediated m6A modification upregulated circARHGAP12 and ASPH to aggravate overload‐induced lipid peroxidative damage and facilitate AS progression.
Embryonic Flubendiamide Exposure Alters Expression of OTX2 and Other Early Regulators in Domestic Chick Leading to Congenital Eye Defects
Authors: Danes Dhanush , Parmar Bhaval , Vaishnav Juhi , Umar Shweta , Sharma Shashikant , Balakrishnan Suresh 
Published: November 2024

ABSTRACTFlubendiamide, a phthalic acid diamide insecticide, has been implicated in potential teratogenic effects on non‐target organisms, especially during embryonic development. This study examines the impact of flubendiamide on eye development in chick embryos, a well‐established model for vertebrate development. Exposure to 0.5 µg/µL of flubendiamide significantly impaired early ocular morphogenesis, resulting in severe defects such as underdeveloped optic cups and the absence of lens and corneal structures. Histopathological analysis demonstrated disrupted optic cup differentiation, while in silico docking studies revealed strong interactions between flubendiamide and key oculogenic proteins, including OTX2, PAX6, and SOX2. These interactions were associated with altered expression patterns of these critical regulators, alongside overexpression of SHH and downregulation of BMP4, BMP7, and FGF8, which are essential for optic vesicle formation and lens differentiation. Additionally, increased CASPASE‐3 expression indicated enhanced apoptosis, contributing to the observed ocular anomalies. These findings suggest that flubendiamide disrupts key signaling pathways necessary for proper eye development, potentially leading to congenital eye defects. The study highlights the need for a thorough evaluation of the molecular mechanisms driving flubendiamide‐induced teratogenicity to ensure safer pesticide use and protect environmental and human health.
CCL2‐CCR2 Axis Inhibition in Osteosarcoma Cell Model: The Impact of Oxygen Level on Cell Phenotype
Authors: Petrosiute Agne , Musvicaitė Justina , Petroška Donatas , Ščerbavičienė Alvilė , Arnold Sascha , Matulienė Jurgita , Žvirblienė Aurelija , Matulis Daumantas , Lučiūnaitė Asta 
Published: November 2024

ABSTRACTTreatment of osteosarcoma is hampered by tumor hypoxia and requires alternative approaches. Although the CCL2‐CCR2 axis is indispensable in tumor‐induced inflammation and angiogenesis, its blockade has not been effective to date. This study aimed to characterize how CCR2 inhibition affects the crosstalk of osteosarcoma cells with immune cells to better delineate tumor resistance mechanisms that help withstand such treatment. In this study, 143B cells were exposed to healthy donor PBMC supernatants in a transwell assay lacking direct cell‐to‐cell contact and subjected to different oxygen concentrations. In addition, mice bearing orthotopic 143B tumors were subjected to CCR2 antagonist treatment. Our findings show that hypoxic conditions alter cytokine and cancer‐ related protein expression on cells and impair CCR2 antagonist effects in the experimental osteosarcoma model. CCL2‐CCR2 axis blockade in the 143B xenografts, which are positive for hypoxia marker CAIX, did not slow 143B tumor growth or metastasis but altered tumor microenvironment by VEGFR downregulation and shift in the CD44‐positive cell population towards high CD44 expression. This study highlights differential responses of tumor cells to CCR2 antagonists in the presence of different oxygen saturations and expands our knowledge of compensatory mechanisms leading to CCL2‐CCR2 treatment resistance.
Using RZWQM2‐P to capture tile drainage phosphorus dynamics in Ohio
Authors: Grewal Harmanpreet Singh , Qi Zhiming , Shedekar Vinayak , King Kevin 
Published: November 2024

AbstractPhosphorus (P) loading from tile‐drained agricultural lands is linked to water quality and aquatic ecosystem degradation. The RZWQM2‐P model was developed to simulate the fate and transport of P in soil‐water‐plant systems, especially in tile‐drained croplands. Comprehensive evaluation and application of RZWQM2‐P, however, remains limited. This study evaluates RZWQM2‐P in simulating P dynamics using extensive data and assesses the potential of management practices for mitigating P losses. Subsurface drainage and surface runoff flows were monitored at a tile‐drained site from 2017 to 2020 in Ohio, and the water flow and P loss data were summarized on a daily basis. RZWQM2‐P was calibrated and validated using those observed data and was subsequently used to assess the effectiveness of controlled drainage (CD) and winter cover crops (CC) in reducing P losses. The model satisfactorily simulated dissolved reactive P (DRP) loss from tile drainage on daily and monthly bases (Nash–Sutcliffe efficiency [NSE] = 0.50, R2 = 0.52, index of agreement [IoA] = 0.84 for daily; NSE = 0.73, R2 = 0.78, IoA = 0.94 for monthly) and total P (TP) loss on a monthly basis (NSE = 0.64, R2 = 0.65, IoA = 0.88), but the daily TP simulation was less accurate (NSE = 0.30, R2 = 0.30, IoA = 0.59). Simulations showed that winter rye CC reduced DRP by 16% and TP by 4% compared to the base scenario, whereas CD increased DRP (60%–129%) and TP (5%–17%) losses at three tested outlet elevations compared to free drainage. RZWQM2‐P can capture P dynamics in tile‐drained cropland and is a promising tool for effective P management.
Differential Gene Expression and Transcriptomics Reveal High M‐Gene Expression in JN.1 and KP.1/2 Omicron Sub‐Variants of SARS‐CoV‐2: Implications for Developing More Sensitive Diagnostic Tests
Authors: Siddique Aktarul Islam , Sarmah Neelanjana , Bali Nargis K. , Nausch Norman , Borkakoty Biswajyoti 
Published: November 2024

ABSTRACTSARS‐CoV‐2, a positive‐strand RNA virus, utilizes both genomic replication and subgenomic mRNA transcription. Whole genome sequencing (WGS) from clinical samples can estimate viral gene expression levels. WGS was conducted on 529 SARS‐CoV‐2 positive clinical samples from Assam and northeastern India to track viral emergence and assess gene expression patterns. The results reveal differential expression across structural, non‐structural, and accessory genes, with notable upregulation of the M gene, especially in the Omicron variant, followed by E and ORF6. The mean transcript per million (TPM) expression levels of the M gene were significantly higher in Omicron variants (175 611 ± 46 921), peaking in the KP.1/KP.2 sublineage (220 493 ± 34 917), compared to the Delta variant (129 717 ± 33 773). The relative fold change of M gene expression between Delta and Omicron 2024 subvariants showed a 1.6‐fold change. Variant‐wise gene expression analysis suggests a correlation between gene expression and viral mutation, impacting replication. As anticipated, the expression levels of genes surge with the increase in the virus mutation. The Chi‐square trend for average substitution count versus average TPM of the M gene was highly significant (72.78., p < 0.0001). The M gene's high expression and low mutation rate make it an ideal target for designing a real‐time RT‐PCR kit assay. These findings highlight the need for continuous surveillance and understanding of viral gene expression dynamics for effective COVID‐19 management. Further studies are necessary to elucidate the significance of these observations in viral pathogenesis and transmission dynamics.
Human Astrovirus Infection and Outbreaks in Japanese Children Before and After the Emergence of COVID‐19 Pandemic
Authors: Ushijima Hiroshi , Pham Ngan Thi Kim , Nishimura Shuichi , Kobayashi Masaaki , Sugita Kumiko , Hoque Sheikh Ariful , Kumthip Kattareeya , Kotaki Tomohiro , Onda‐Shimizu Yuko , Okitsu Shoko , Komoto Satoshi , Kobayashi Takeshi , Komine‐Aizawa Shihoko , Hayakawa Satoshi , Maneekarn Niwat , Khamrin Pattara 
Published: November 2024

ABSTRACTHuman astroviruses (HAstVs) were examined in 1625 stool samples collected from outpatient children with diarrhea who visited clinics in 4–6 prefectures in Japan. The study was conducted over a period of 4 years from July 2018 to June 2022, spanning the period before and after the emergence of COVID‐19. The HAstV and other diarrheal viruses including group A rotavirus, norovirus and sapovirus were screened by RT‐PCR. Of these, HAstV was detected in 140 out of 1625 (8.6%). When the stool samples were categorized by the year of collection, HAstV was detected in 2018–2019, 2019–2020, 2020–2021, and 2021–2022 with the prevalences of 3.1%, 6.6%, 3.0%, and 20.1%, respectively. Among 140 HAstV positive cases, HAstV1, MLB1, MLB2, HAstV3, MLB3, and VA2 were detected in 77, 46, 10, 3, 2, and 2 samples, respectively. High infection rate was found in children 1–3 years of age (95/140; 67.9%). Severity of the disease increased with the co‐infection with norovirus. During the surveillance of 2021–2022, two outbreaks of HAstV were detected, one was an outbreak of HAstV1 and MLB2 in September, 2021 in Kyoto, the second was an outbreak of HAstV1 and MLB1 in December, 2021 in Kyoto and Shizuoka. It was interesting to observe that mixed‐infection of astroviruses between HAstV1 and MLB1 was reported for the first time in this study. Characterization of the subgenotypes in HAstV1 and HAstV3 indicated that most HAstV1 circulating in Japan belonged to HAstV1a and only a single strain was HAstV1b, whereas all HAstV3 was identified as the HAstV3c subgenotype. In conclusion, several HAstV genotypes, including classic HAstV, novel MLB, and VA genotypes, were detected in this study. The incidence of astrovirus outbreaks was also reported after the pandemic of COVID‐19 in 2021–2022.
45° helical plates are a valid alternative to straight plates for treatment of proximal humeral shaft fractures
Authors: Pastor Tatjana , Zderic Ivan , Beeres Frank J. P. , Helmy Nader , Richards R. Geoff , Kriechling Philipp , Drenchev Ludmil , Skulev Hristo K. , Gueorguiev Boyko , Pastor Torsten 
Published: November 2024

AbstractHelical plates used for proximal humeral shaft fracture fixation avoid the radial nerve distally as compared to straight plates. To investigate in a human cadaveric model the biomechanical competence of straight lateral plates versus 45° helical plates used for fixation of proximal comminuted humeral shaft fractures, eight pairs of human cadaveric humeri were instrumented using either a long straight PHILOS plate (Group 1) or a 45° helical plate (Group 2) for treatment of an unstable proximal humeral shaft fracture. All specimens were tested under non‐destructive quasi‐static loading in axial compression, internal and external rotation, and bending in four directions. Subsequently, progressively increasing cyclic loading in internal rotation was applied until failure and interfragmentary movements were monitored by motion tracking. Axial displacement (mm) was 3.13 ± 0.31 in Group 1 and 2.60 ± 0.42 in Group 2, p = 0.015. Flexion/extension deformation (°) in Group 1 and Group 2 was 0.56 ± 0.42 and 0.43 ± 0.23, p = 0.551. Varus/valgus deformation (°) was 6.39 ± 0.44 in Group 1 and 5.13 ± 0.87 in Group 2, p = 0.012. Shear (mm) and torsional (°) displacement were 5.36 ± 0.76 and 17.75 ± 1.06 in Group 1, and 5.03 ± 0.46 and 16.79 ± 1.36 in Group 2, p ≥ 0.090. Cycles to catastrophic failure were 10000 ± 1401 in Group 1 and 9082 ± 1933 in Group 2, p = 0.708. From a biomechanical perspective, 45° helical plating is associated with lower axial and varus/valgus displacement under axial loading and demonstrates comparable resistance to failure versus straight plating. Therefore, 45° helical plates can be considered as a valid alternative to straight plates for treatment of proximal humeral shaft fractures.
Coacervate Droplets as Biomimetic Models for Designing Cell‐Like Microreactors
Authors: Ivanov Tsvetomir , Doan‐Nguyen Thao. P. , Belahouane Mohammed Amin , Dai Zhen , Cao Shoupeng , Landfester Katharina , Caire da Silva Lucas 
Published: November 2024

AbstractCoacervates are versatile compartments formed by liquid–liquid phase separation. Their dynamic behavior and molecularly crowded microenvironment make them ideal materials for creating cell‐like systems such as synthetic cells and microreactors. Recently, combinations of synthetic and natural molecules have been exploited via simple or complex coacervation to create compartments that can be used to build hierarchical chemical systems with life‐like properties. This review highlights recent advances in the design of coacervate compartments and their application as biomimetic compartments for the design of cell‐like chemical reactors and cell mimicking systems. It first explores the variety of materials used for coacervation and the influence of their chemical structure on their controlled dynamic behavior. Then, the applications of coacervates as cell‐like systems are reviewed, focusing on how they can be used as cell‐like microreactors through their ability to sequester molecules and provide a distinct and regulatory microenvironment for chemical reactions in aqueous media.
Polyphenols and Functionalized Hydrogels for Osteoporotic Bone Regeneration
Authors: Xv Dejia , Cao Yuming , Hou Yue , Hu Yuelin , Li Minqi , Xie Chaoming , Lu Xiong 
Published: November 2024

AbstractOsteoporosis induces severe oxidative stress and disrupts bone metabolism, complicating the treatment of bone defects. Current therapies often have side effects and require lengthy bone regeneration periods. Hydrogels, known for their flexible mechanical properties and degradability, are promising carriers for drugs and bioactive factors in bone tissue engineering. However, they lack the ability to regulate the local pathological environment of osteoporosis and expedite bone repair. Polyphenols, with antioxidative, anti‐inflammatory, and bone metabolism‐regulating properties, have emerged as a solution. Combining hydrogels and polyphenols, polyphenol‐based hydrogels can regulate local bone metabolism and oxidative stress while providing mechanical support and tissue adhesion, promoting osteoporotic bone regeneration. This review first provides a brief overview of the types of polyphenols and the mechanisms of polyphenols in facilitating adhesion, antioxidant, anti‐inflammatory, and bone metabolism modulation in modulating the pathological environment of osteoporosis. Next, this review examines recent advances in hydrogels for the treatment of osteoporotic bone defects, including their use in angiogenesis, oxidative stress modulation, drug delivery, and stem cell therapy. Finally, it highlights the latest research on polyphenol hydrogels in osteoporotic bone defect regeneration. Overall, this review aims to facilitate the clinical application of polyphenol hydrogels for the treatment of osteoporotic bone defects.
Interpret Gaussian Process Models by Using Integrated Gradients
Authors: Zhang Fan , Ono Naoaki , Kanaya Shigehiko 
Published: November 2024

AbstractGaussian process regression (GPR) is a nonparametric probabilistic model capable of computing not only the predicted mean but also the predicted standard deviation, which represents the confidence level of predictions. It offers great flexibility as it can be non‐linearized by designing the kernel function, made robust against outliers by altering the likelihood function, and extended to classification models. Recently, models combining deep learning with GPR, such as Deep Kernel Learning GPR, have been proposed and reported to achieve higher accuracy than GPR. However, due to its nonparametric nature, GPR is challenging to interpret. While Explainable AI (XAI) methods like LIME or kernel SHAP can interpret the predicted mean, interpreting the predicted standard deviation remains difficult. In this study, we propose a novel method to interpret the prediction of GPR by evaluating the importance of explanatory variables. We have incorporated the GPR model with the Integrated Gradients (IG) method to assess the contribution of each feature to the prediction. By evaluating the standard deviation of the posterior distribution, we show that the IG approach provides a detailed decomposition of the predictive uncertainty, attributing it to the uncertainty in individual feature contributions. This methodology not only highlights the variables that are most influential in the prediction but also provides insights into the reliability of the model by quantifying the uncertainty associated with each feature. Through this, we can obtain a deeper understanding of the model′s behavior and foster trust in its predictions, especially in domains where interpretability is as crucial as accuracy.
Cross‐shaped windows transformer with self‐supervised pretraining for clinically significant prostate cancer detection in bi‐parametric MRI
Authors: Li Yuheng , Wynne Jacob , Wang Jing , Qiu Richard L. J. , Roper Justin , Pan Shaoyan , Jani Ashesh B. , Liu Tian , Patel Pretesh R. , Mao Hui , Yang Xiaofeng 
Published: November 2024

AbstractBackgroundBi‐parametric magnetic resonance imaging (bpMRI) has demonstrated promising results in prostate cancer (PCa) detection. Vision transformers have achieved competitive performance compared to convolutional neural network (CNN) in deep learning, but they need abundant annotated data for training. Self‐supervised learning can effectively leverage unlabeled data to extract useful semantic representations without annotation and its associated costs.PurposeThis study proposes a novel self‐supervised learning framework and a transformer model to enhance PCa detection using prostate bpMRI.Methods and materialsWe introduce a novel end‐to‐end Cross‐Shaped windows (CSwin) transformer UNet model, CSwin UNet, to detect clinically significant prostate cancer (csPCa) in prostate bpMRI. We also propose a multitask self‐supervised learning framework to leverage unlabeled data and improve network generalizability. Using a large prostate bpMRI dataset (PI‐CAI) with 1476 patients, we first pretrain CSwin transformer using multitask self‐supervised learning to improve data‐efficiency and network generalizability. We then finetune using lesion annotations to perform csPCa detection. We also test the network generalization using a separate bpMRI dataset with 158 patients (Prostate158).ResultsFive‐fold cross validation shows that self‐supervised CSwin UNet achieves 0.888 ± 0.010 aread under receiver operating characterstics curve (AUC) and 0.545 ± 0.060 Average Precision (AP) on PI‐CAI dataset, significantly outperforming four comparable models (nnFormer, Swin UNETR, DynUNet, Attention UNet, UNet). On model generalizability, self‐supervised CSwin UNet achieves 0.79 AUC and 0.45 AP, still outperforming all other comparable methods and demonstrating good generalization to external data.ConclusionsThis study proposes CSwin UNet, a new transformer‐based model for end‐to‐end detection of csPCa, enhanced by self‐supervised pretraining to enhance network generalizability. We employ an automatic weighted loss (AWL) to unify pretext tasks, improving representation learning. Evaluated on two multi‐institutional public datasets, our method surpasses existing methods in detection metrics and demonstrates good generalization to external data.
Evidence for extirpation of native kokanee in a large impounded watershed following introduction of a conspecific
Authors: Breault Paige W. , Wetklo Mike , Shrimpton J. Mark 
Published: November 2024

Abstract

Objective
Williston Reservoir in north-central British Columbia was stocked with kokanee Oncorhynchus nerka from the Columbia River during the 1990s. A native population of kokanee already existed in the reservoir, but that population has not been found in sampling efforts since 2000. Most of the recent sampling, however, has targeted tributaries, and the stocked Columbia River-type kokanee are stream spawners, whereas Thutade Lake kokanee, from which the native Williston Reservoir kokanee originated, are shore spawners.

Methods
In August 2021, pelagic surveys were conducted in Williston Reservoir by gillnetting and trawling to capture kokanee for subsequent genotyping to assess whether the native Williston Reservoir kokanee have persisted. We used 14 microsatellite loci to genotype 165 samples from the pelagic surveys and compared them to 623 previously genotyped kokanee from four reference populations: native reservoir fish; fish from the source population (Thutade Lake) that naturally colonized the reservoir; fish from isolated lakes in the Williston Reservoir watershed; and Columbia River-type fish that now spawn in tributaries to the reservoir.

Result
Kokanee collected from the pelagic survey conducted in Williston Reservoir were entirely assigned to the Columbia River type by using the Bayesian clustering program STRUCTURE and a discriminant analysis of principal components. We found no evidence of any native Williston Reservoir genotypes.

Conclusion
Formation of Williston Reservoir favored pelagic species, such as kokanee, which have gradually increased in proportion over time—particularly since the introduction of kokanee from the Columbia River. Unfortunately, native Williston Reservoir kokanee appear to have been extirpated from the reservoir and were likely outcompeted by the introduced Columbia River-origin kokanee.