bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hip Joint Articulotrochanteric Distance Measurements in Children: Articulotrochanteric Distance in Children Aged 5 to 14 Years Does Not Increase With Age
Authors: Yang Di , Haiping Ouyang , Wang Zhongliang 
Published: January 2025

Background:
The articulotrochanteric distance (ATD) has universally been utilized to assess greater trochanter overgrowth in pediatric orthopaedic diseases. However, its overgrowth cannot be detected in a timely manner due to the absence of a normal ATD value. This study is to determine the ATD normal value in hip radiographs of children under the age of 14 and to establish the threshold for overgrowth of the greater trochanter.

Methods:
A retrospective analysis of 1787 hip radiographs was conducted, measuring ATD, trochanter-to-trochanter distance (TTD), lesser trochanter-to-articular surface distance (LTA), epiphysis height (EH), and femoral head epiphyseal plate-to-lesser trochanter distance (ELD). The differences in TTD and ELD between adjacent age groups were denoted as ΔTTD and ΔELD, respectively. Data with normal distribution were analyzed using independent sample (tow-tailed student t test) t tests and One﻿-way ANOVA, while data with non-normal distribution were analyzed through nonparametric tests. The range defined by the 95% measurement values (mean±2SD) was considered the normal range.

Results:
Among 5-14 year-olds, the mean ATD (mean±2SD) was 23.5±10.0 mm for males and 21.2±9.6 mm (mean±2SD) for females, statistically significant differences in the ATD were observed between sexes (P<0.05), whereas no significant differences were noted among age subgroups within the same sex (P>0.05). The normal range for males was 13.5 to 33.5 mm, while for females it was 11.6 to 30.8 mm. In addition, no significant distinction (P>0.05) was noted in the EH between males and females within this age range. Furthermore, the analysis revealed no significant difference (P>0.05) between the changes in ΔTTD and ΔELD among the hips.

Conclusions:
Our findings revealed that in hip radiographs, ATD values of children aged 5 to 14 years differ significantly between males and females, although within each sex group, there was no notable variation across different age groups. We proposed that ATD <13.5 mm in males and <11.6 mm in females might indicate an overgrowth of the greater trochanter, and in such patients, prophylactic greater trochanteric epiphysiodesis may be beneficial. In addition, we believed that the growth rates of the femoral neck and greater trochanter were approximately similar.

Level of Evidence:
Level IV—diagnostic studies.
Challenges in standardizing preimplantation kidney biopsy assessments and the potential of AI-Driven solutions
Authors: Wellekens Karolien , Koshy Priyanka , Naesens Maarten 
Published: January 2025

Purpose of review
This review explores the variability in preimplantation kidney biopsy processing methods, emphasizing their impact on histological interpretation and allocation decisions driven by biopsy findings. With the increasing use of artificial intelligence (AI) in digital pathology, it is timely to evaluate whether these advancements can overcome current challenges and improve organ allocation amidst a growing organ shortage.

Recent findings
Significant inconsistencies exist in biopsy methodologies, including core versus wedge sampling, frozen versus paraffin-embedded processing, and variability in pathologist expertise. These differences complicate study comparisons and limit the reproducibility of histological assessments. Emerging AI-driven tools and digital pathology show potential for standardizing assessments, enhancing reproducibility, and reducing dependence on expert pathologists. However, few studies have validated their clinical utility or demonstrated their predictive performance for long-term outcomes.

Summary
Novel AI-driven tools hold promise for improving the standardization and accuracy of preimplantation kidney biopsy assessments. However, their clinical application remains limited due to a lack of proven associations with posttransplant outcomes and insufficient evaluation of predictive performance metrics. Future research should prioritize longitudinal studies using large-scale datasets, rigorous validation, and comprehensive assessments of predictive performance for both short- and long-term outcomes to fully establish their clinical utility.
Can Sleep Predict Conversion to Mild Cognitive Impairment and Dementia? Results From the Hellenic Longitudinal Investigation of Aging and Diet Study
Authors: Bairami Styliani , Scarmeas Nikolaos , Yannakoulia Mary , Dardiotis Efthimios , Sakka Paraskevi , Hadjigeorgiou Georgios , Tsapanou Angeliki , Kosmidis Mary H. 
Published: January 2025

Objective:
Sleep disturbance is considered a risk factor for cognitive decline in elderly individuals. Our aim in the current study was to investigate whether baseline sleep parameters can predict the conversion from normal cognition to mild cognitive impairment or dementia at follow-up. The Hellenic Longitudinal Investigation of Aging and Diet is a longitudinal population-based study designed to estimate the prevalence and incidence of cognitive decline and dementia in the older Greek population.

Methods:
A total of 955 cognitively normal older adults (aged ≥65 y) were drawn from the Hellenic Longitudinal Investigation of Aging and Diet study. A comprehensive neurological and neuropsychological assessment was conducted at baseline and a mean of 3.1 (SD = 0.85) years later, resulting in 160 individuals diagnosed with mild cognitive impairment and 34 with dementia at follow-up, whereas 761 remained cognitively normal.

Results:
Using Cox regression analyses, no sleep parameters increased the risk of conversion status adjusting for demographics and clinical factors. Napping, however, decreased this risk by 19.3% (P < 0.001).

Conclusions:
As several previous studies have proposed, napping constitutes a protective factor against cognitive decline. Thus, clinicians should encourage their elderly patients to adopt this healthy habit.
Hsa-MiR-483 -3p Regulates the Extracellular Matrix Proteins via TGFβ2/SMAD4 Signaling in the Glucocorticoid-responsive Human Trabecular Meshwork Cells
Authors: Haribalaganesh Ravinarayanan , Sharmila Rajendrababu , Krishnadas Ramasamy , Willoughby Colin E. , Senthilkumari Srinivasan 
Published: January 2025

AbstractPurposeTo investigate the role of hsa-miR-483-3p on the regulation of extracellular matrix (ECM) in cultured human trabecular meshwork (HTM) cells with known steroid response.MethodsPrimary cultures of HTM cells with known steroid responsiveness [GC-responder (GC-R) and GC-Non-responder (GC-NR) cells] were grown on coverslip in 12-well plate until 80% confluence and treated with 100 nM dexamethasone (DEX) for 24 h and transfected with different concentrations of synthetic miRNA 483-3p mimic or inhibitor. After 24 h or 72 h post transfection, the cells were harvest for the following experiments: (i) percentage transfection efficiency (ii) RNA isolation for qPCR analysis and (iii) immunofluorescence staining, (iv) protein isolation for Western blotting respectively. All experiments were performed in triplicate with three biological samples (n□=□3).ResultsGC-R HTM cells showed significantly higher expression of SMAD4 as compared to GC-NR HTM cells. Similarly, DEX treatment up-regulated the SMAD4-dependent ECM proteins. The presence of a miR-483-3p mimic down-regulated SMAD4 expression and SMAD4-dependent ECM production in a dose-dependent manner by negatively down- regulating SMAD4/TGF-β2 signalling. The inhibition of SMAD4-dependent ECM production by miR-483-3p was more pronounced in GC-R HTM cells as compared to GC- NR cells.ConclusionThe down-regulation in ECM production by miR-483-3p is SMAD4 dependent and may play a protective role in mitigating steroid response in GC-R HTM cells. Using miR-483-3p mimics demonstrates therapeutic potential for the management of steroid induced ocular hypertension and glaucoma.
Timelapse and volumetric imaging of mitochondrial networking using NAD(P)H autofluorescence via 2-photon microscopy
Authors: ter Hofstede Blanche , Walsh Alex J. 
Published: January 2025

AbstractSignificanceMitochondria are dynamic organelles that play a key role in energy production and maintaining cellular homeostasis. The regulation of mitochondrial dynamics, involving both fission and fusion, is vital for maintaining a healthy population of mitochondria within the cell. Alterations in mitochondrial dynamics have been associated with various disease states, such as metabolic and neurodegenerative diseases and cancer.AimWe describe a protocol for imaging and analyzing NAD(P)H intensity to visualize the movement of mitochondria over time and in 3D to visualize the distribution of the mitochondrial network within the cell.ApproachA multiphoton (MP) laser scanning microscope was used to image NAD(P)H autofluorescence signal of MDA-MB-231 cells at 750 nm excitation. A mitochondrial fluorescent dye, MitoSpy Orange, was used to validate the signal. Laser power, image size, dwell time, interval time, and imaging duration were optimized for timelapse and 3D imaging to minimize photodamage and maximize autofluorescence signal.ResultsThe NAD(P)H signal in 2D was imaged with a frame rate of 0.4 frames per second (FPS) allowing for visualization of mitochondria movement. 3D imaging was performed with a frame rate of 0.5 FPS for a single cell with a thickness of approximately 15 microns that allowed for visualization of the mitochondria network within the cell.ConclusionsThis protocol motivates using label-free imaging techniques to study mitochondrial dynamics in a non- destructive manner, suitable for drug screening and understanding the effects of mitochondrial dynamic alterations in disease.
BIND: Large-Scale Biological Interaction Network Discovery through Knowledge Graph-Driven Machine Learning
Authors: Aamer Naafey , Asim Muhammad Nabeel , Bhatti Aamer Iqbal , Dengel Andreas 
Published: January 2025

AbstractThe complex interactions between biological entities provide valuable insights into fundamental life processes, which pave the way to a deeper understanding of disease mechanisms for the development of innovative therapeutic strategies. To enable large-scale predictions of biological interactions, multifarious AI-driven predictors have been developed. However, most of these are developed by leveraging information from only a limited subset of interaction types, and the broader interaction types landscape could facilitate AI algorithms to learn more informative patterns to predict unknown interactions. To address the need of a robust and precise interaction predictor, we introduce BIND (Biological Interaction Network Discovery), a predictor that leverages simultaneous learning across 10 biological entities and 30 interaction types. To develop BIND, we first evaluate 11 distinct Knowledge Graph Embedding Methods on the largest public biomedical interaction dataset namely PrimeKG. For each relation type, we extracted entity embeddings from the top 5 performing Knowledge Graph Embedding Models (KGEMs) and input them into 7 distinct machine learning classifiers. Rigorous evaluation of 1,050 predictive pipelines demonstrated that specific combinations of KGEMs and classifiers achieved F1 scores of 90% to 99% across various interaction types. Comprehensive evaluation across each relation type identified the top-performing predictive pipelines, which became the foundation of the BIND web application. To reveal the practical utility of our web application in identifying novel biological interactions, we conducted a case study on drug-phenotype interactions. The application gave 1,355 high confidence predictions, from which potential interactions were subsequently validated by scientific evidence found within the existing literature (Table 5). We believeBIND’s web application’s public accesswill serve as a valuable tool for biologists to identify unknown interactions that can be subsequently validated through wet-lab experiments.
JIND-Multi: Leveraging Multiple Labeled Datasets for Automated Annotation of Single-Cell RNA and ATAC Data
Authors: Sancho Joseba , Kanhirodan Akash , Garrote Xabier , Gevaert Olivier , Hernaez Mikel , Serrano Guillermo , Ochoa Idoia 
Published: January 2025

AbstractBackgroundThe creation of single-cell atlases is essential for understanding cellular diversity and heterogeneity. However, assembling these atlases is challenging due to batch effects and the need for accurate cell annotation. Current methods for single-cell RNA and ATAC sequencing, while effective for integration, are not optimized for cell annotation. Additionally, many annotation tools rely on external databases or reference scRNA-Seq datasets, which may limit their adaptability to specific study needs, especially for rare cell-types or scATAC-Seq data.ResultsWe introduce JIND-Multi, an extended version of the JIND framework, designed to transfer cell-type labels across multiple annotated datasets. JIND-Multi significantly reduces the proportion of unclassified cells in single-cell RNA sequencing (scRNA-Seq) data while maintaining the accuracy and performance of the original JIND model. Furthermore, JIND-Multi demonstrates robust and precise annotation results in its inaugural application to scATAC-Seq data, proving its versatility and effectiveness across different single-cell sequencing technologies.ConclusionsJIND-Multi represents an improvement in cell annotation, reducing unassigned cells and offering a reliable solution for both scRNA-Seq and scATAC-Seq data. Its ability to handle multiple labeled datasets enhances the precision of annotations, making it a valuable tool for the single-cell research community. JIND-Multi is publicly available at:https://github.com/ML4BM-Lab/JIND-Multi.git.
Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter
Authors: Pérez Carrillo Victor Hugo , Di Cesare Margot , Rose-Sperling Dania , Javed Waqas , Neuweiler Hannes , Marcoux Julien , Orelle Cédric , Jault Jean-Michel , Hellmich Ute A. 
Published: January 2025

AbstractATP-binding cassette (ABC) transporters use ATP to transport substrates across cellular membranes. In type IV ABC transporters, including many multidrug resistance (MDR) pumps, communication between the nucleotide-binding domains (NBDs) and transmembrane domains (TMDs) occurs via intracellular coupling helices. However, the precise mechanism of interdomain crosstalk and coordination between the ATP and substrate binding sites remain unclear. Combining nuclear magnetic resonance (NMR) spectroscopy, Hydrogen-Deuterium eXchange Mass Spectrometry (HDX-MS), photo-induced electron-transfer fluorescence correlation spectroscopy (PET-FCS) and functional assays, we identified a conserved cluster of residues at the NBD/TMD interface of the bacterial MDR transporter BmrA. This cluster is crucial for transporter function and relays nucleotide and substrate binding between the two domains via coupling helix 2. Mutations impact both local and global transporter dynamics. Our findings reveal a novel interdomain communication pathway in type IV ABC transporters, shedding light on the intricate coupling mechanisms that enable the coordination of these molecular machines.
Development of a High-throughput Morphological Assay for Evaluating Mesenchymal Stromal Cell-derived Extracellular Vesicle Modulation of Brain Pericyte Secretory Phenotype
Authors: Campagna Courtney E. , Larey Andrew M. , Daga Kanupriya R. , Roos Morgan , Ghosh Sneha , Grimsey Neil , Han Jin , Marklein Ross A. 
Published: January 2025

ABSTRACTMesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising therapeutic tool for treating many neurodegenerative diseases. Neuroinflammation plays a major role in many of these conditions through an orchestration of interdependent processes that lead to the breakdown of the blood-brain barrier (BBB), infiltration of immune cells and neuronal death. MSC-EVs have shown preliminary evidence of modulating neuroinflammation, but their mechanisms of action are still unknown. Therefore, we explored the potential of MSC-EVs in modulating brain pericytes, a cell type that plays a critical role in BBB maintenance but has not been investigated as a therapeutic target for MSC-EVs. Brain pericytes are multifaceted cells that can modulate neuroinflammation through their involvement in BBB homeostasis, as well as the innate and adaptive immune response. Pericyte morphology has been shown to change in response to inflammatory stimuliin vivo, hence, we used this behavior to develop a quantitative morphological profiling approach to assess the immunomodulatory function of MSC-EVs in a high-throughput, low-cost manner. Using this assay, we were able to demonstrate that MSC-EVs manufactured under various conditions (2D, 3D, and in response to cytokine priming) could induce distinct pericyte morphological responses indicative of changes in secretion of chemokines and cytokines relevant to neuroinflammation.
Propofol Treatment Alters the Metabolic State of MDA-MB-231 Breast Cancer Cells
Authors: Tasmi Tasbassum Ahmed , Holla Shubha , Walsh Alex J. 
Published: January 2025

AbstractThe mechanisms of many anesthetic drugs, such as propofol, are unknown. This study investigates the impact of propofol, a widely used intravenous anesthetic drug, on the metabolic behavior of the human triple-negative breast cancer cell line, MDA-MB 231. Utilizing fluorescence lifetime imaging microscopy (FLIM), we assessed the effect of propofol on cellular metabolism through imaging of the fluorescence lifetimes of NADH and FAD, coenzymes of metabolism reactions. Exposure to propofol-induced significant morphological and metabolic changes of the cells, including substantial cellular shrinkage, which may reveal a metabolic component to propofol’s mechanism.
DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint
Authors: Khan Md Maruf , Roos Wynand P. , Angajala Anusha , Gibbs Denise Y. , Liu Jeffrey C. , Ragin Camille , Sobol Robert W. 
Published: January 2025

ABSTRACTHead and Neck Squamous Cell Carcinoma (HNSCC) imposes a significant health burden, necessitating innovative therapeutic strategies to enhance treatment efficacy. Current treatments such as surgery, radiation, and chemotherapy have limited effectiveness and yield severe side effects, emphasizing the need for targeted therapies. We have focused on DNA polymerase beta (Polβ) and its roles in replication stress, cellular responses to DNA damaging therapies, and DNA damage response modifiers. Our investigations reveal a regulatory role for base excision repair (BER) proteins, including Polβ, in the cellular response to inhibitors of poly(ADP-ribose) glycohydrolase (PARG), an enzyme involved in poly(ADP-ribose) (PAR) degradation. The inhibition of PARG, in HNSCC cells, elicits replication stress. Further, this activates the PAR-induced S-phase/ATR checkpoint, leading to a block to replication, cell cycle arrest, and the onset of apoptosis. However, Polβ overexpression mitigates this response, reducing replication-stress induced PAR foci formation, suggesting a modulation of replication checkpoint activation. We found that PARG inhibitor treatment is ineffective on HNSCC cells that overexpress Polβ, implying that the PARG inhibitor-induced PAR and apoptotic response is dependent on the level of Polβ. Further, ourin vitroexperiments demonstrate that combining PARG and ATR/CHK1 inhibitors overcomes Polβ-mediated treatment resistance in HNSCC cells, producing enhanced effects as compared to the individual treatment conditions. Our findings suggest a possible treatment paradigm for HNSCC, employing ATR or CHK1 inhibitors in combination with PARG inhibitors. This strategy offers a promising path for more effective HNSCC treatments, potentially overcoming Polβ-related resistance.
SOuLMuSiC: A Computational Tool for Predicting the Impact of Mutations on Protein Solubility
Authors: Attanasio Simone , Kwasigroch Jean , Rooman Marianne , Pucci Fabrizio 
Published: January 2025

AbstractProtein solubility problems arise in a wide range of applications, from antibody development to enzyme production, and are linked to several major disorders, including cataracts and Alzheimer’s diseases. To assist scientists in designing proteins with improved solubility and better understand solubility-related diseases, we introduce SOuLMuSiC, a computational tool for the fast and accurate prediction of the impact of mutations on protein solubility. Our model is based on a simple shallow artificial neural network that takes as input a series of features, including biophysical properties of wild-type and mutated residues, energetic values computed using various statistical potentials, and mutational scores derived from protein language models. SOuLMuSiC has been trained on a curated dataset of about seven hundred mutations with known solubility values, collected and manually verified from original literature. It significantly outperforms current state-of-the-art predictors in strict cross-validation and shows good performance on external datasets containing high-throughput enzyme solubility-related data as well as protein aggregation propensities. In summary, SOuLMuSiC is a valuable tool for identifying mutations that impact protein solubility, and can play a major role in the rational design of proteins with improved solubility and in understanding genetic variants’ effect. It is freely available for academic use athttp://babylone.ulb.ac.be/SoulMuSiC/.
Age and Sex-Specific Changes in Mitochondrial Quality Control in Skeletal and Cardiac Muscle
Authors: Springer-Sapp Catherine B. , Ogbara Olayinka , Da Silva Maria Canellas , Liu Yuan , Prior Steven J. , Kuzmiak-Glancy Sarah 
Published: January 2025

AbstractSkeletal and cardiac muscle mitochondria exist in a dynamic reticulum that is maintained by a balance of mitochondrial biogenesis, fusion, fission, and mitophagy. This balance is crucial for adequate ATP production, and alterations in skeletal muscle mitochondria have been implicated in aging-associated declines in mitochondrial function. We sought to determine whether age and biological sex affect mitochondrial content [Complex IV (CIV)], biogenesis (PGC-1ɑ), fusion (MFN2, OPA1), fission (DRP1, FIS1), and mitophagy (Parkin, Pink1) markers in skeletal and cardiac muscle by assessing protein expression in tibialis anterior (TA) and ventricular tissue from 16 young (≤6 months) and 16 old (≥20 months) male and female Sprague-Dawley rats. In the TA, CIV expression was 40% lower in old vs. young rats (p<0.001), indicating lower mitochondrial content, and coincided with higher expression of Parkin (+4-fold, p<0.001). Further, MFN2 expression was higher (+2-fold, p<0.005) and Parkin was lower (-40%, p=0.014) in older rats. In cardiac muscle, mitochondrial content was maintained in old vs. young rats, and this occurred concomitantly with higher expression of both PGC-1ɑ and Parkin. MFN2 and OPA1 expression were also 1.2-5-fold higher in older rats (p<0.05 for all). Largely, protein expression did not differ between male and female rats, with the exception of Pink1 and FIS1 expression in the TA. Collectively, older skeletal and cardiac muscle demonstrated higher expression of fusion and mitophagy proteins, which indicates age alters the balance of biogenesis, fission, fusion, and mitophagy. This may, in turn, affect the ability to provide ATP to these metabolically active tissues.