bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients
Authors: Morrison Holly A. , Hoyt Kacie J. , Mounzer Christina , Ivester Hannah M. , Barnes Barrett H. , Sauer Bryan , McGowan Emily C. , Allen Irving C. 
Published: August 2023

IntroductionEosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development.MethodsWe used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity.ResultsGlobal transcriptomic analysis revealed differential expression of several genes previously reported in EoE (CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports.DiscussionOur findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC, that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.
Nanostructured Ti-13Nb-13Zr alloy for implant application—material scientific, technological, and biological aspects
Authors: Klinge Lina , Kluy Lukas , Spiegel Christopher , Siemers Carsten , Groche Peter , Coraça-Huber Débora 
Published: August 2023

In dentistry, the most commonly used implant materials are CP-Titanium Grade 4 and Ti-6Al-4V ELI, possessing comparably high Young’s modulus (&gt;100 GPa). In the present study, the second-generation titanium alloy Ti-13Nb-13Zr is investigated with respect to the production of advanced dental implant systems. This should be achieved by the fabrication of long semi-finished bars with high strength and sufficient ductility to allow the automated production of small implants at low Young’s modulus (&lt;80 GPa) to minimize stress shielding, bone resorption, and gap formation between the bone and implant. In addition, bacterial colonization is to be reduced, and bone adhesion is to be enhanced by adjusting the microstructure. To do so, a dedicated thermo-mechanical treatment for Ti-13Nb-13Zr has been developed. This includes the adaption of equal channel angular swaging, a modern process of severe plastic deformation to continuously manufacture nanostructured materials, to Ti-13Nb-13Zr and short-time recrystallization and ageing treatments. In particular, two-pass equal channel angular swaging at a deformation temperature of 150°C and a counterpressure of 8 MPa has successfully been used to avoid shear band formation during deformation and to produce long Ti-13Nb-13Zr bars of 8 mm diameter. During recrystallization treatment at 700°C for 10 min followed by water quenching, a sub-micron-size primary α-phase in a matrix of α″-phase was developed. Subsequent ageing at 500°C for 1 h leads to martensite decomposition and, thus, to a homogeneously nanostructured microstructure of α- and β-phase with substructures smaller than 200 nm. The resulting mechanical properties, especially the ultimate tensile strength of more than 990 MPa, fulfill the requirements of ASTM F1713 at Young’s modulus of 73 GPa. Biological investigations show promising results in reducing bacterial biofilm formation and increased cell proliferation of osteoblasts compared to CP-Titanium Grade 4 and Ti-6Al-4V ELI, especially, if etched surfaces are applied.
Foraging strategies of fungal mycelial networks: responses to quantity and distance of new resources
Authors: Fukasawa Yu , Ishii Kaho 
Published: August 2023

Fungal mycelial networks are essential for translocating and storing water, nutrients, and carbon in forest ecosystems. In particular, wood decay fungi form mycelial networks that connect various woody debris on the forest floor. Understanding their foraging strategies is crucial for complehending the role of mycelium in carbon and nutrient cycling in forests. Previous studies have shown that mycelial networks initiate migration from the original woody resource (inoculum) to a new woody resource (bait) if the latter is sufficiently large but not if it is small. However, the impact of energetic costs during foraging, such as the distance to the bait, has not been considered. In the present study, we conducted full-factorial experiments with two factors, bait size (4 and 8 cm3) and distance from the inoculum (1 and 15 cm). An inoculum wood block, colonized by the wood decay fungus Phanerochaete velutina, was placed in one corner of a bioassay dish (24 cm × 24 cm) filled with unsterilized soil. Once the mycelium grew onto the soil to a distance &gt;15 cm from the inoculum, a sterilized new bait wood block (of either size) was placed on the soil at one of the two distances to be colonized by the mycelia from the inoculum. After 50 days of incubation, the baits were harvested, and their dried weight was measured to calculate the absolute weight loss during incubation. The inoculum wood blocks were retrieved and placed on a new soil dish to determine whether the mycelium would grow out onto the soil again. If no growth occurred within 8 days of additional incubation, we concluded that the mycelium had migrated from the inoculum to the bait. The results showed that mycelia in inocula coupled with baits positioned 1 cm away migrated to the baits more frequently than those with baits positioned 15 cm away. A structural equation model revealed that bait weight loss (energy gain) and hyphal coverage on the soil (foraging cost) significantly influenced mycelial migration decisions. These findings suggest that fungal mycelia may employ their own foraging strategies based on energetic benefits.
Evaluation of methods for assigning causes of death from verbal autopsies in India
Authors: Benara Sudhir K. , Sharma Saurabh , Juneja Atul , Nair Saritha , Gulati B. K. , Singh Kh. Jitenkumar , Singh Lucky , Yadav Ved Prakash , Rao Chalapati , Rao M. Vishnu Vardhana 
Published: August 2023

BackgroundPhysician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (COD) in countries where medical certification of death is low. Computer-coded verbal autopsy (CCVA), an alternative method to PCVA for assigning the COD is considered to be efficient and cost-effective. However, the performance of CCVA as compared to PCVA is yet to be established in the Indian context.MethodsWe evaluated the performance of PCVA and three CCVA methods i.e., InterVA 5, InSilico, and Tariff 2.0 on verbal autopsies done using the WHO 2016 VA tool on 2,120 reference standard cases developed from five tertiary care hospitals of Delhi. PCVA methodology involved dual independent review with adjudication, where required. Metrics to assess performance were Cause Specific Mortality Fraction (CSMF), sensitivity, positive predictive value (PPV), CSMF Accuracy, and Kappa statistic.ResultsIn terms of the measures of the overall performance of COD assignment methods, for CSMF Accuracy, the PCVA method achieved the highest score of 0.79, followed by 0.67 for Tariff_2.0, 0.66 for Inter-VA and 0.62 for InSilicoVA. The PCVA method also achieved the highest agreement (57%) and Kappa scores (0.54). The PCVA method showed the highest sensitivity for 15 out of 20 causes of death.ConclusionOur study found that the PCVA method had the best performance out of all the four COD assignment methods that were tested in our study sample. In order to improve the performance of CCVA methods, multicentric studies with larger sample sizes need to be conducted using the WHO VA tool.
Association between soluble α-klotho and mortality risk in middle-aged and older adults
Authors: Chuang Min-Hsiang , Wang Hung-Wei , Huang Yun-Ting , Jiang Ming-Yan 
Published: August 2023

IntroductionStudies on association of α-klotho levels with mortality risk in general population are relatively scarce and inconclusive. Therefore, we conducted a population-based cohort study to investigate the relationship between soluble α-klotho and all-cause mortality in a nationally representative sample of middle-aged and older adults in the United States (U.S.).MethodsThe study population was 2007-2016 National Health and Nutrition Examination Survey (NHANES) participants, totaling 13,583 adults aged 40-79 years. Participants were divided into 7 groups by septile of α-klotho levels. We linked the NHANES data to the National Death Index to determine participants’ survival status. End of follow-up was participants’ death date or December 31, 2019.ResultsWe observed that males, current smokers, older age, higher body mass index, and lower estimated glomerular filtration rate correlated to lower α-klotho levels, while hepatitis C virus infection correlated to higher α-klotho. The population mortality rate was 11.8 per 10,000 person-months (1,490 deaths); group 1 (the first septile) had higher mortality risk compared with group 2 through group 7. By weighted Cox regression with adjustment for potential confounders, we found that group 2 through group 6, but not group 7, were associated with 25% to 35% lower risk of all-cause mortality compared with group 1. When compared with group 4, we observed that both group 1 (HR: 1.46, 95% CI 1.13-1.88) and group 7 (HR: 1.38, 95% CI 1.09-1.74) were associated with higher mortality risk.ConclusionIn summary, among middle-aged and older U.S. adults, we observed a non-linear association between soluble α-klotho and all-cause mortality, with individuals at the two extremes at increased risk of death.
Prenatal diagnosis and outcomes in 320 fetuses with nasal bone anomalies
Authors: Li Hui , Yao Yanyi , Zhang Chengcheng , Qin Yayun , Zeng Ling , Song Jieping , Lu Li , Wang Wei , Liu Lijun 
Published: August 2023

Object: To investigate the chromosome abnormalities associated with absent or hypoplastic fetal nasal bone.Methods: Patients with fetal nasal bone anomalies (NBA) referred to our center for prenatal diagnosis between 2017 and 2021 were retrospectively evaluated. All these patients underwent chromosomal microarray and/or karyotyping and received genetic counseling before and after testing.Results: Among 320 fetuses with NBA, chromosomal abnormalities were diagnosed in 89 (27.8%) cases, including 53 cases of trisomy 21, which was the most common type of chromosomal aneuploidy, accounting for 59.6% of all detected abnormalities. In addition to aneuploidies, 29 cases of copy number variants (CNVs) were detected. In cases of isolated NBA with low-risk screening results and without other risk factors, the incidence of fetal chromosomal aneuploidies and pathogenic CNVs is 5.3% (7 in 132 cases).Conclusion: This study suggests that parents of fetuses should be informed about the possibility of fetal aneuploidy and pathogenic CNVs and that discussion with the parents is also recommended, providing data support and reference for clinical counseling.
Mendelian randomization shows depression increases the risk of type 2 diabetes
Authors: Jin Heejin , Lee Sanghun , Won Sungho 
Published: August 2023

Introduction: Type 2 diabetes (T2D) is associated with severe mental illnesses (SMIs), such as schizophrenia, bipolar disorder, and depression. However, causal relationships between SMIs and T2D remain unclear owing to potential bias in observational studies. We aimed to characterize the causal effect of SMI liability on T2D using two-sample Mendelian randomization (MR).Methods: The causality between liability to SMI and T2D was investigated using the inverse-variance weighted (IVW), MREgger, MR-Egger with a simulation extrapolation, weighted median, and the MR pleiotropy residual sum and outlier method. Similarly, we performed additional MR which can detect the reverse causation effect by switching exposure and outcome for T2D liability for SMI. To further consider pleiotropic effects between SMIs, multivariable MR analysis was performed after accounting for the other traits.Results: In the univariable IVW method, depression showed a causal effect on T2D (odds ratio [OR]: 1.128, 95% confidence interval [CI]: 1.024–1.245, p = 0.014). Multinomial MR more strongly supported these results (IVW OR: 1.197, 95% CI: 1.069, 1.340, p = 0.002; MR-Egger OR: 1.198, 95% CI: 1.062, 1.349, p = 0.003). Bidirectional MR showed absence of reversecausality between depression and T2D. However, causal relationship of bipolar and schizophrenia on T2D was not detected.Discussion: Careful attention is needed for patients with depression regarding T2D prevention and treatment.
Sperm quality parameters, fertilizing potential, metabolites, and DNA methylation in cold-stored and cryopreserved milt from Atlantic salmon (Salmo salar L.)
Authors: Narud Birgitte , Khezri Abdolrahman , Zeremichael Teklu T. , Eriksen Anne-Lene , Grevle Inger S. , Nordborg Anna , Klinkenberg Geir , Wilson Robert C. , Kommisrud Elisabeth 
Published: August 2023

Cold storage and freezing/thawing of milt may affect sperm functionality and the subsequent fertilization ability of milt. This study aimed to investigate sperm quality parameters and fertilization potential of Atlantic salmon milt, stored cold and subsequently cryopreserved, using different storage conditions. The objective was also to assess if analysis of milt metabolites and sperm DNA methylation signatures could be applicable to further elucidate sperm quality and fertilization following preservation. Milt samples were collected from eight mature Atlantic salmon males and stored for 4 days at 2°C and 8°C. Samples were taken on day one of storage at 2°C and on day four of storage at 2°C and 8°C. Storage for 4 days at 8°C is expected to be detrimental to sperm quality, and was included to create contrasts. Correspondingly, aliquots of cold-stored milt were prepared for cryopreservation, resulting in a total of six experimental conditions. Samples from all six experimental conditions were used in fertilization trials and analyzed for sperm viability, motility, ATP content, DNA fragmentation index, and High DNA stainability. In addition, milt samples from four of the males were analyzed for targeted metabolites and DNA methylation signatures by reduced representation bisulfite sequencing. The fertilization trials were performed using sperm:egg ratios of 75 × 103and 500 × 103, respectively. Storage duration, temperature, and cryopreservation of cold-stored milt influenced several sperm quality parameters, metabolites, and DNA methylation signatures. The total motility, progressive motility, ATP, and velocity parameters were the sperm parameters with the strongest correlation to fertilization rates (p&lt; 0.01). Several metabolites were correlated with fertility rates in both cold-stored and cryopreserved samples (p&lt; 0.05). The fertilizing capacity of cold-stored milt was significantly reduced after 4 days of storage at 8°C, while corresponding cryopreserved milt showed reduced fertilization at both storage temperatures (2°C and 8°C) (p&lt; 0.05). The results indicate that cryopreservation of milt stored for 1 day does not compromise either fertilization ability or DNA methylation signatures.
An efficient convolutional neural network-based diagnosis system for citrus fruit diseases
Authors: Huang Zhangcai , Jiang Xiaoxiao , Huang Shaodong , Qin Sheng , Yang Su 
Published: August 2023

Introduction: Fruit diseases have a serious impact on fruit production, causing a significant drop in economic returns from agricultural products. Due to its excellent performance, deep learning is widely used for disease identification and severity diagnosis of crops. This paper focuses on leveraging the high-latitude feature extraction capability of deep convolutional neural networks to improve classification performance.Methods: The proposed neural network is formed by combining the Inception module with the current state-of-the-art EfficientNetV2 for better multi-scale feature extraction and disease identification of citrus fruits. The VGG is used to replace the U-Net backbone to enhance the segmentation performance of the network.Results: Compared to existing networks, the proposed method achieved recognition accuracy of over 95%. In addition, the accuracies of the segmentation models were compared. VGG-U-Net, a network generated by replacing the backbone of U-Net with VGG, is found to have the best segmentation performance with an accuracy of 87.66%. This method is most suitable for diagnosing the severity level of citrus fruit diseases. In the meantime, transfer learning is applied to improve the training cycle of the network model, both in the detection and severity diagnosis phases of the disease.Discussion: The results of the comparison experiments reveal that the proposed method is effective in identifying and diagnosing the severity of citrus fruit diseases identification.
A novel signature constructed by differential genes of muscle-invasive and non-muscle-invasive bladder cancer for the prediction of prognosis in bladder cancer
Authors: Wang Weizhuo , Zhang Xi , Jiang Silin , Xu Peng , Chen Kang , Li Kai , Wang Fei , Le Xiang , Zhang Ke 
Published: August 2023

BackgroundBladder cancer (BCa) is a malignant tumor that usually forms cancer cells in the inner lining of the bladder. Hundreds of thousands of people worldwide have BCa diagnosed each year. The purpose of this study was to construct a prognostic model by differential expression of genes between muscular and non-muscular invasive BCa, and to investigate the prognosis of BCa patients.MethodsThe data of BCa patients was sourced from the GEO and TCGA database. Single-cell sequencing data was obtained from three patients in the GSE135337 database, and microarray data for verification was obtained from GSE32894. Univariate, Lasso and multivariate cox regression analyses were performed to construct the prognostic model. The prognostic features, immune features and drug sensitivity of the model were further evaluated. Single-cell data and microarray data were used to validate the differential expression of model genes between muscle-invasive and non-muscle-invasive BCa. The invasion and migration of BCa cells were evaluated using the transwell assay and wound-healing assay. The cell proliferation capacity was simultaneously evaluated using Colony formation experiments. The protein expression of the specific gene was detected by western blot analysis.ResultsWe identified 183 differentially expressed muscle-invasive-related differential genes (MIRDGs), among which four were selected to establish a prognostic model. Based on our signature, patients in different groups displayed varying levels of immune infiltration and immunotherapy profiles. Single-cell sequencing data and microarray data confirmed that four invasion-related genes were expressed at higher levels in muscle-invasive BCa. Given the critical role of S100A9 in the progression of BCa, we performed further analysis. The results showed that protein expression of S100A9 was high in muscle-invasive BCa, and S100A9 knockdown could inhibit the proliferation, migration and invasion of BCa.ConclusionThese findings demonstrated that the prognostic model for BCa patients was reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of BCa patients in the future. S100A9 may become a better prognostic marker and potential therapeutic target to further guide clinical treatment decisions.
Impact of age on liver damage, inflammation, and molecular signaling pathways in response to femoral fracture and hemorrhage
Authors: Meng Fanshuai , Zhou Yuzhuo , Wagner Alessa , Bülow Jasmin Maria , Köhler Kernt , Neunaber Claudia , Bundkirchen Katrin , Relja Borna 
Published: August 2023

BackgroundTrauma causes disability and mortality globally, leading to fractures and hemorrhagic shock. This can trigger an irregular inflammatory response that damages remote organs, including liver. Aging increases the susceptibility to dysregulated immune responses following trauma, raising the risk of organ damage, infections, and higher morbidity and mortality in elderly patients. This study investigates how aging affects liver inflammation and damage post-trauma.Methods24 male C57BL/6J mice were randomly divided into four groups. Twelve young (17-26 weeks) and 12 aged (64-72 weeks) mice were included. Mice further underwent either hemorrhagic shock (trauma/hemorrhage, TH), and femoral fracture (osteotomy) with external fixation (Fx) (THFx, n=6) or sham procedures (n=6). After 24 hours, mice were sacrificed. Liver injury and apoptosis were evaluated using hematoxylin-eosin staining and activated caspase-3 immunostaining. CXCL1 and infiltrating polymorphonuclear leukocytes (PMNL) in the liver were assessed by immunostaining, and concentrations of CXCL1, TNF, IL-1β, and IL-10 in the liver tissue were determined by ELISA. Gene expression of Tnf, Cxcl1, Il-1β, and Cxcl2 in the liver tissue was determined by qRT-PCR. Finally, western blot was used to determine protein expression levels of IκBα, Akt, and their phosphorylated forms.ResultsTHFx caused liver damage and increased presence of active caspase-3-positive cells compared to the corresponding sham group. THFx aged group had more severe liver injury than the young group. CXCL1 and PMNL levels were significantly higher in both aged groups, and THFx caused a greater increase in CXCL and PMNL levels in aged compared to the young group. Pro-inflammatory TNF and IL-1β levels were elevated in aged groups, further intensified by THFx. Anti-inflammatory IL-10 levels were lower in aged groups. Tnf and Cxcl1 gene expression was enhanced in the aged sham group. Phosphorylation ratio of IκBα was significantly increased in the aged sham group versus young sham group. THFx-induced IκBα phosphorylation in the young group was significantly reduced in the aged THFx group. Akt phosphorylation was significantly reduced in the THFx aged group compared to the THFx young group.ConclusionThe findings indicate that aging may lead to increased vulnerability to liver injury and inflammation following trauma due to dysregulated immune responses.