bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing knee osteoarthritis diagnosis with DMS: a novel dense multi-scale convolutional neural network approach
Authors: Zhang Di , Dong Yuting , Xu Yao , Qian Junhui , Ye Miaoyu , Yuan Qiang , Luo Jian 
Published: December 2024

Abstract
Background
Osteoarthritis (OA) of the knee is a prevalent chronic degenerative joint condition that is having a growing impact on a global scale., posing a challenge in diagnosis which is often reliant on time-consuming and error-prone visual analysis by physicians. There is a critical need for an automated, efficient, and accurate diagnostic method to improve early detection and treatment.

Methods
We developed a novel Convolutional Neural Network (CNN) module, Dense Multi-Scale (DMS), an advancement over Multi-Scale Convolution (MSC). This module utilizes dense connections in convolutions of varying sizes (1 × 1, 3 × 3, 5 × 5) and across layers, enhancing feature reuse and complexity recognition, thereby improving recognition capabilities. Dense connections also facilitate deeper network architecture and mitigate gradient vanishing problems. We compared our model with a standard baseline model and validated it using an unseen-data test set.

Results
The DMS model exhibited exceptional performance in unseen-data tests, achieving 73.00% average accuracy (ACC) and 92.73% area under the curve (AUC), surpassing the baseline model’s (DenseNet) 63.52% ACC and 88.76% AUC. This highlights the DMS model’s superior predictive capability for knee OA.

Conclusion
The DMS model presents a significant advancement in predicting and grading knee OA, holding substantial clinical importance. It promises to aid radiologists in accurate diagnosis and grading, and in choosing appropriate treatments, thereby reducing misdiagnosis and patient burden.
Zhishi Xiebai Guizhi Decoction modulates hypoxia and lipid toxicity to alleviate pulmonary vascular remodeling of pulmonary hypertension in rats
Authors: Fu Min , Li Yuan , Liu Jingjing , Liu Junjie , Wei Jiaoxia , Qiao Yuxin , Zhong Hanxin , Han Dongyang , Lu Haitao , Yao Li 
Published: December 2024

Abstract
Background
Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.

Methods
We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this.

Results
Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl-l-carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH.

Conclusion
Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs.

Graphical Abstract
Crafting inclusive parenting programs– considerations for deaf families: a qualitative study
Authors: Ikwara Asher Emmanuel , Nabagesera Rebecca , Isiko Isaac 
Published: December 2024

Abstract
Background
The parenting of children by deaf parents has many challenges that require a barrier-breaking approach to ensure inclusivity and accessibility. Therefore, this study explored pathways for crafting inclusive parenting programs, fostering a future where every family thrives, regardless of hearing ability.

Methods
This was a qualitative study that employed in-depth interviews with 20 deaf parents and utilized thematic content analysis. This study was carried out at events organized by the Uganda National Association of the Deaf (UNAD) at Makerere College School. Deaf parents were purposively selected from attendees at events organised by the Uganda National Association of the Deaf (UNAD) during the specified celebrations.

Results
An analysis of interviews with deaf parents identified six crucial themes for inclusive parenting programs. Language education was highlighted for strengthening family bonds. Communication and relationship building emphasized equal treatment and love for deaf children. Cultural sensitivity and education were deemed essential, as visual tools and district associations were used. Tailoring content for deaf children emphasized playful and educational materials, such as sign language videos. The utilization of technology for accessible programs and the promotion of community involvement are recognized as critical components.

Conclusion
This study emphasized the unique experiences of deaf parents, highlighting the need for sign language education, cultural sensitivity, and technology while addressing challenges like limited resources, stigma, and advocacy gaps in parenting programs.
Pathogenic mitochondrial DNA variants are associated with response to anti-VEGF therapy in ovarian cancer PDX models
Authors: Boso Daniele , Piga Ilaria , Trento Chiara , Minuzzo Sonia , Angi Eleonora , Iommarini Luisa , Lazzarini Elisabetta , Caporali Leonardo , Fiorini Claudio , D’Angelo Luigi , De Luise Monica , Kurelac Ivana , Fassan Matteo , Porcelli Anna Maria , Navaglia Filippo , Billato Ilaria , Esposito Giovanni , Gasparre Giuseppe , Romualdi Chiara , Indraccolo Stefano 
Published: December 2024

Abstract
Background
Mitochondrial DNA (mtDNA) pathogenic variants have been reported in several solid tumors including ovarian cancer (OC), the most lethal gynecologic malignancy, and raised interest as they potentially induce mitochondrial dysfunction and rewiring of cellular metabolism. Despite advances in recent years, functional characterization of mtDNA variants in cancer and their possible modulation of drug response remain largely uncharted.

Methods
Here, we characterized mtDNA variants in OC patient derived xenografts (PDX) and investigated their impact on cancer cells at multiple levels.

Results
Genetic analysis revealed that mtDNA variants predicted as pathogenic, mainly involving complex I and IV genes, were present in all but one PDX (n = 20) at different levels of heteroplasmy, including 7 PDXs with homoplasmic variants. Functional analyses demonstrated that pathogenic mtDNA variants impacted on respiratory complexes activity and subunits abundance as well as on mitochondrial morphology. Moreover, PDX cells bearing homoplasmic mtDNA variants behaved as glucose-addicted and could barely survive glucose starvation in vitro. RNA-seq analysis indicated that mtDNA mutated (heteroplasmy > 50%) PDXs were endowed with upregulated glycolysis and other pathways connected with cancer metabolism. These findings led us to investigate whether pathogenic mtDNA variants correlated with response to anti-VEGF therapy, since the latter was shown to reduce glucose availability in tumors. Strikingly, PDXs bearing homoplasmic pathogenic mtDNA variants associated with improved survival upon anti-VEGF treatment in mice, compared with mtDNA wild type or low heteroplasmy PDXs.

Conclusions
These results hint at mtDNA variants as potential biomarkers of response to antiangiogenic drugs.
SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2/p-EphA2 Axis
Authors: E Haoran , Zhang Lei , Yang Zhenhua , Xu Long , Wang Tao , Guo Junhong , Xia Lang , Yu Juemin , Wang Heyong , She Yunlang , Wu Junqi , Zhao Yue , Chen Chang , Zhao Deping 
Published: December 2024

Abstract
Background
Thymic epithelial tumors (TETs) are infrequent malignancies that arise from the anterior mediastinum. Therapeutic options for TETs, especially thymic carcinoma (TC), remain relatively constrained. This study aims to investigate the oncogenic hub gene and its underlying mechanisms in TETs, as well as to identify potential therapeutic targets.

Methods
Weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis were utilized to identify significant oncogenes using The Cancer Genome Atlas (TCGA) database. LASSO logistic regression analysis was performed to assess the association between hub genes and clinical parameters. The influence of the hub gene on promoting epithelial-mesenchymal transition (EMT), tumor progression, and regulating cancer stem cell-like properties was assessed both in vitro and in vivo. Single-cell RNA sequencing (scRNA-seq) was utilized to analyze the alterations in the tumor and its microenvironment following the administration of the hub gene’s inhibitor. Multiplex immunohistochemistry (mIHC) was employed to validate the results. The potential mechanism was further elucidated through the utilization of Cleavage Under Targets and Tagmentation (CUT&Tag), RNA-sequencing, chromatin immunoprecipitation (ChIP), CUT&RUN, luciferase reporter assay, co-immunoprecipitation (Co-IP), mass spectrometry (MS) and phosphoproteomic assays.

Results
SNAI1 was identified as a hub transcription factor for TETs, and its positive correlation with the invasiveness of the disease was confirmed. Subsequent experiments revealed that the upregulation of SNAI1 augmented the migration, invasion, and EMT of TET cell lines. Furthermore, we observed that the overexpression of SNAI1 sustained cancer stem cell-like properties. ScRNA-seq demonstrated that the use of a SNAI1 inhibitor inhibited the transition of macrophages from M1 to M2 phenotype, a finding further validated by multiplex immunohistochemistry (mIHC). Phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) was identified as one of the downstream targets of SNAI1 through CUT&Tag and RNA-sequencing, a finding validated by ChIP-qPCR, CUT&RUN-qPCR, luciferase reporter and immunofluorescence assays. Co-IP, MS and phosphoproteomic assays further confirmed that PIK3R2 directly interacted with phosphorylated EphA2 (p-EphA2), facilitating downstream GSK3β/β-catenin signaling pathway.

Conclusion
The tumorigenic role of SNAI1 through the PIK3R2/p-EphA2 axis was preliminarily validated in TETs. A potential therapeutic strategy for TETs may involve the inhibition of SNAI1.
Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment
Authors: Raaijmakers Kris T. P. M. , Adema Gosse J. , Bussink Johan , Ansems Marleen 
Published: December 2024

AbstractCancer-associated fibroblasts (CAFs) represent a group of genotypically non-malignant stromal cells in the tumor micro-environment (TME) of solid tumors that encompasses up to 80% of the tumor volume. Even though the phenotypic diversity and plasticity of CAFs complicates research, it is well-established that CAFs can affect many aspects of tumor progression, including growth, invasion and therapy resistance. Although anti-tumorigenic properties of CAFs have been reported, the majority of research demonstrates a pro-tumorigenic role for CAFs via (in)direct signaling to cancer cells, immunomodulation and extracellular matrix (ECM) remodeling. Following harsh therapeutic approaches such as radio- and/or chemotherapy, CAFs do not die but rather become senescent. Upon conversion towards senescence, many pro-tumorigenic characteristics of CAFs are preserved or even amplified. Senescent CAFs continue to promote tumor cell therapy resistance, modulate the ECM, stimulate epithelial-to-mesenchymal transition (EMT) and induce immunosuppression. Consequently, CAFs play a significant role in tumor cell survival, relapse and potentially malignant transformation of surviving cancer cells following therapy. Modulating CAF functioning in the TME therefore is a critical area of research. Proposed strategies to enhance therapeutic efficacy include reverting senescent CAFs towards a quiescent phenotype or selectively targeting (non-)senescent CAFs. In this review, we discuss CAF functioning in the TME before and during therapy, with a strong focus on radiotherapy. In the future, CAF functioning in the therapeutic TME should be taken into account when designing treatment plans and new therapeutic approaches.
Metformin protects prepubertal mice ovarian reserve against cyclophosphamide via regulation of the PI3K/Akt/mTOR signaling pathway and Yap-1
Authors: Zatalian Negin , Dalman Azam , Afsharian Parvaneh , Hezavehei Maryam , Gourabi Hamid 
Published: December 2024

Abstract
Background
Cyclophosphamide is a widely utilized chemotherapeutic agent for pediatric cancers, known to elicit adverse effects, including perturbation of the PI3K/Akt/mTOR and Hippo signaling pathways, thereby diminishing ovarian reserve and fertility potential in females. Consequently, this investigation delves into the mitigative effects of metformin on cyclophosphamide-induced ovarian impairment in prepubertal mice.

Methods
Twenty-four 14-day-old NMRI female mice were distributed into four groups: Control (Cont), Cyclophosphamide (Cyc), Metformin (Met), and Metformin plus Cyclophosphamide (Met-Cyc). The Met-Cyc group was given daily doses of 150 mg/kg metformin for 11 consecutive days and in parallel 3 intermittent doses of 65 mg/kg cyclophosphamide once every three days. The Met and Cyc groups were given identical doses of Met or Cyc alone. The control group received normal saline treatment. On the 12th day, mice were sacrificed for analysis. Stereological methods were employed to measure the overall volume of the ovaries, including the medulla, cortex, and follicles, along with measuring anti-Müllerian hormone (AMH) levels using an ELISA kit. Furthermore, qRT-PCR was utilized to quantify the expression levels of genes, including P53, Bax, Bcl-2, Rad-51, Pten, Mtor, and Yap-1.

Results
The findings demonstrate that metformin ameliorates cyclophosphamide-induced ovarian toxicity by increasing AMH levels and attenuating the excessive activation of primordial follicles, the ratio of growing to quiescent follicles, and follicular atresia. This protective effect is mediated by the downregulation of apoptosis-related genes, upregulation of the gene involved in a reparative pathway, and modulation of the PI3K/Akt/mTOR pathway evidenced by increased expression of Pten, Mtor and Hippo pathway by Yap-1 expression.

Conclusions
Our results advocate for the potential of metformin as a viable therapeutic option for preserving ovarian function in cyclophosphamide-treated adolescent girls, given its favorable side effect profile and ability to improve cyclophosphamide-induced ovarian damage.
HGVS Nomenclature 2024: improvements to community engagement, usability, and computability
Authors: Hart Reece K. , Fokkema Ivo F. A. C. , DiStefano Marina , Hastings Ros , Laros Jeroen F. J. , Taylor Rachel , Wagner Alex H. , den Dunnen Johan T. 
Published: December 2024

Abstract
Background
The Human Genome Variation Society (HGVS) Nomenclature is the global standard for describing and communicating variants in DNA, RNA, and protein sequences in clinical and research genomics. This manuscript details recent updates to the HGVS Nomenclature, highlighting improvements in governance, community engagement, website functionality, and underlying implementation of the standard.

Methods
The HGVS Variant Nomenclature Committee (HVNC) now operates under the Human Genome Organization (HUGO), facilitating broader community feedback and collaboration with related standards organizations. The website has been redesigned using modern documentation tools and practices. The specification was updated to include guidance for transcript selection and to align with recent cross-consortia recommendations for the representation of gene fusions. A formal computational grammar was introduced to improve the precision and consistency of variant descriptions.

Results
Major improvements in HGVS Nomenclature v. 21.1 include a redesigned website with enhanced navigation, search functionality, and mobile responsiveness; a new versioning policy aligned with software management practices; formal mechanisms for community feedback and change proposals; and adoption of Extended Backus-Naur Form (EBNF) for defining syntax. The specification now recommends MANE Select transcripts where appropriate and includes updated guidance for representing adjoined transcripts and gene fusions. All content is freely available under permissive licenses at hgvs-nomenclature.org.

Conclusions
These advancements establish a more sustainable foundation for maintaining and evolving the HGVS Nomenclature while improving its accessibility and utility. The introduction of formal computational grammar marks a crucial step toward unambiguous variant descriptions that can be reliably processed by both humans and machines. Combined with enhanced community engagement mechanisms and improved guidance, these changes position the HGVS Nomenclature to better serve the evolving needs of clinical and research genomics while maintaining the stability that users require.
ITC-MNP: a diverse dataset for image file fragment classification
Authors: Tavassoli Behnam , Naghshbandi Zhino , Teimouri Mehdi 
Published: December 2024

Abstract
Objectives
Image file fragment classification is a critical area of study in digital forensics. However, many publicly available datasets in this field are derived from a single source, often lacking consideration of the diversity in image settings and content. To demonstrate the effectiveness of a given methodology, it is essential to evaluate it using datasets that are sampled from varied data sources. Therefore, providing a sufficiently diverse dataset is crucial to enable a realistic assessment of any proposed method.

Data description
The dataset includes image file fragments of 4096 bytes from five formats (JPG, BMP, GIF, PNG, and TIFF), each processed with different conversion settings. The source images are categorized into three content types: Nature, People, and Medical. In total, the dataset contains 501,000 fragments. These fragments consist of file headers and incomplete end-of-file fragments, completed with random bytes to approximate how operating systems handle data when file sizes are not multiples of the sector size. This approach aims to simulate typical scenarios where fragments are recovered from a hard drive, though it may not capture all real-world complexities such as data corruption and complex file structures.
‘QuickDASH’ to find unique genes and biological processes associated with shoulder osteoarthritis: a prospective case–control study
Authors: Lynskey Samuel J. , Gill Stephen D. , McGee Sean L. , Ziemann Mark , Page Richard S. 
Published: December 2024

Abstract
Objective
Osteoarthritis (OA) is a disease impacting the synovial joint complex, yet transcriptional changes specific to shoulder OA remain underexplored. This study aims to profile transcriptomic changes in periarticular tissues from patients undergoing shoulder replacement for OA. By correlating these profiles with QuickDASH scores—a validated measure of worsening shoulder function—this research seeks to understand the gene expression changes associated with clinical decline. Capsular tissue biopsies from shoulder OA patients were compared with those from a control group undergoing shoulder stabilization for recurrent instability. This investigation forms part of a larger transcriptomic analysis of painful shoulder conditions which will address the current gap in knowledge regarding the molecular and genetic underpinnings of shoulder OA, rotator cuff tears and cuff-tear arthropathy.

Results
The analysis revealed that genes most strongly associated with increasing QuickDASH scores across tissues were linked to inflammation and stress response. Key pathways involved interleukins, chemokines, complement components, nuclear response factors, and immediate early response genes, reflecting a balance between pro- and anti-inflammatory signalling. Additionally, this study identified unique gene expression patterns in shoulder OA not previously observed in hip and knee OA, along with novel genes implicated in shoulder OA, highlighting areas for future targeted investigation.
Trial registration This investigation has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registered on the 26th of March 2018, registration number: 12618000431224, accessible from: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374665&isReview=true
Deep learning for opportunistic, end-to-end automated assessment of epicardial adipose tissue in pre-interventional, ECG-gated spiral computed tomography
Authors: Theis Maike , Garajová Laura , Salam Babak , Nowak Sebastian , Block Wolfgang , Attenberger Ulrike I. , Kütting Daniel , Luetkens Julian A. , Sprinkart Alois M. 
Published: December 2024

Abstract
Objectives
Recently, epicardial adipose tissue (EAT) assessed by CT was identified as an independent mortality predictor in patients with various cardiac diseases. Our goal was to develop a deep learning pipeline for robust automatic EAT assessment in CT.

Methods
Contrast-enhanced ECG-gated cardiac and thoraco-abdominal spiral CT imaging from 1502 patients undergoing transcatheter aortic valve replacement (TAVR) was included. Slice selection at aortic valve (AV)-level and EAT segmentation were performed manually as ground truth. For slice extraction, two approaches were compared: A regression model with a 2D convolutional neural network (CNN) and a 3D CNN utilizing reinforcement learning (RL). Performance evaluation was based on mean absolute z-deviation to the manually selected AV-level (Δz). For tissue segmentation, a 2D U-Net was trained on single-slice images at AV-level and compared to the open-source body and organ analysis (BOA) framework using Dice score. Superior methods were selected for end-to-end evaluation, where mean absolute difference (MAD) of EAT area and tissue density were compared. 95% confidence intervals (CI) were assessed for all metrics.

Results
Slice extraction using RL was slightly more precise (Δz: RL 1.8 mm (95% CI: [1.6, 2.0]), 2D CNN 2.0 mm (95% CI: [1.8, 2.3])). For EAT segmentation at AV-level, the 2D U-Net outperformed BOA significantly (Dice score: 2D U-Net 91.3% (95% CI: [90.7, 91.8]), BOA 85.6% (95% CI: [84.7, 86.5])). The end-to-end evaluation revealed high agreement between automatic and manual measurements of EAT (MAD area: 1.1 cm2 (95% CI: [1.0, 1.3]), MAD density: 2.2 Hounsfield units (95% CI: [2.0, 2.5])).

Conclusions
We propose a method for robust automatic EAT assessment in spiral CT scans enabling opportunistic evaluation in clinical routine.

Critical relevance statement
Since inflammatory changes in epicardial adipose tissue (EAT) are associated with an increased risk of cardiac diseases, automated evaluation can serve as a basis for developing automated cardiac risk assessment tools, which are essential for efficient, large-scale assessment in opportunistic settings.

Key Points

Deep learning methods for automatic assessment of epicardial adipose tissue (EAT) have great potential.

A 2-step approach with slice extraction and tissue segmentation enables robust automated evaluation of EAT.

End-to-end automation enables large-scale research on the value of EAT for outcome analysis.

Graphical Abstract