Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteoarthritis-Related Degeneration Alters the Biomechanical Properties of Human Menisci Before the Articular Cartilage

An exact understanding of the interplay between the articulating tissues of the knee joint in relation to the osteoarthritis (OA)-related degeneration process is of considerable interest. Therefore, the aim of the present study was to characterize the biomechanical properties of mildly and severely degenerated human knee joints, including their menisci and tibial and femoral articular cartilage (AC) surfaces. A spatial biomechanical mapping of the articulating knee joint surfaces of 12 mildly and 12 severely degenerated human cadaveric knee joints was assessed using a multiaxial mechanical testing machine. To do so, indentation stress relaxation tests were combined with thickness and water content measurements at the lateral and medial menisci and the AC of the tibial plateau and femoral condyles to calculate the instantaneous modulus (IM), relaxation modulus, relaxation percentage, maximum applied force during the indentation, and the water content. With progressing joint degeneration, we found an increase in the lateral and the medial meniscal instantaneous moduli (p < 0.02), relaxation moduli (p < 0.01), and maximum applied forces (p < 0.01), while for the underlying tibial AC, the IM (p = 0.01) and maximum applied force (p < 0.01) decreased only at the medial compartment. Degeneration had no influence on the relaxation percentage of the soft tissues. While the water content of the menisci did not change with progressing degeneration, the severely degenerated tibial AC contained more water (p < 0.04) compared to the mildly degenerated tibial cartilage. The results of this study indicate that degeneration-related (bio-)mechanical changes seem likely to be first detectable in the menisci before the articular knee joint cartilage is affected. Should these findings be further reinforced by structural and imaging analyses, the treatment and diagnostic paradigms of OA might be modified, focusing on the early detection of meniscal degeneration and its respective treatment, with the final aim to delay osteoarthritis onset.
Acid Ceramidase Protects Against Hepatic Ischemia/Reperfusion Injury by Modulating Sphingolipid Metabolism and Reducing Inflammation and Oxidative Stress

Ceramide is a bioactive signaling lipid involved in the pathogenesis of numerous diseases. It also plays an important role in ischemia reperfusion (IR) injury via activation of inflammatory/oxidative stress-stimulated signaling pathways, resulting in tissue damage. Acid ceramidase is a lipid hydrolase that modulates the levels of ceramide, and as such has a potential therapeutic role in many human diseases where ceramide has been implicated. Here we investigated the therapeutic potential of recombinant acid ceramidase in a murine model of hepatic IR injury. Serum ALT, AST, and LDH activities, as well as oxidative stress (MDA) and inflammatory (MCP-1) markers, were increased in mice subjected to IR compared to a sham group. In contrast, these elevations were significantly lower in an IR group pretreated with a single injection of acid ceramidase. Histological examination by two different assessment criteria also revealed that acid ceramidase pretreatment alleviated IR-induced hepatocyte damage, including reduced evidence of cell death and necrosis. In addition, elevated ceramide and sphingosine levels were observed in the IR group compared to sham, and were markedly reduced when pretreated with acid ceramidase. In contrast, the levels of the protective signaling lipid, sphingosine-1-phosphate (S1P), were reduced following IR and elevated in response to acid ceramidase pretreatment. These changes in sphingolipid levels could be correlated with changes in the activities of several sphingolipid-metabolizing enzymes. Overall, these results indicated that sphingolipid changes were an important pathologic component of hepatic IR injury, and that acid ceramidase administration ameliorated these lipid changes and other downstream pathologic changes.
BTOB: Extending the Biased GWAS to Bivariate GWAS

In recent years, a number of literatures published large-scale genome-wide association studies (GWASs) for human diseases or traits while adjusting for other heritable covariate. However, it is known that these GWASs are biased, which may lead to biased genetic estimates or even false positives. In this study, we provide a method called “BTOB” which extends the biased GWAS to bivariate GWAS by integrating the summary association statistics from the biased GWAS and the GWAS for the adjusted heritable covariate. We employ the proposed BTOB method to analyze the summary association statistics from the large scale meta-GWASs for waist-to-hip ratio (WHR) and body mass index (BMI), and show that the proposed approach can help identify more susceptible genes compared with the corresponding univariate GWASs. Theoretical results and simulations also confirm the validity and efficiency of the proposed BTOB method.
Effects of White Matter Hyperintensities on Verbal Fluency in Healthy Older Adults and MCI/AD

Background White matter hyperintensities (WMHs) are markers for cerebrovascular pathology, which are frequently seen in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Verbal fluency is often impaired especially in AD, but little research has been conducted concerning the specific effects of WMH on verbal fluency in MCI and AD. Objective Our aim was to examine the relationship between WMH and verbal fluency in healthy old age and pathological aging (MCI/AD) using quantified MRI data. Methods Measures for semantic and phonemic fluency as well as quantified MRI imaging data from a sample of 42 cognitively healthy older adults and 44 patients with MCI/AD (total n = 86) were utilized. Analyses were performed both using the total sample that contained seven left-handed/ambidextrous participants, as well with a sample containing only right-handed participants (n = 79) in order to guard against possible confounding effects regarding language lateralization. Results After controlling for age and education and adjusting for multiple correction, WMH in the bilateral frontal and parieto-occipital areas as well as the right temporal area were associated with semantic fluency in cognitively healthy and MCI/AD patients but only in the models containing solely right-handed participants. Conclusion The results indicate that white matter pathology in both frontal and parieto-occipital cerebral areas may have associations with impaired semantic fluency in right-handed older adults. However, elevated levels of WMH do not seem to be associated with cumulative effects on verbal fluency impairment in patients with MCI or AD. Further studies on the subject are needed.
Mitochondrial Morphology and Mitophagy in Heart Diseases: Qualitative and Quantitative Analyses Using Transmission Electron Microscopy

Transmission electron microscopy (TEM) has long been an important technique, capable of high degree resolution and visualization of subcellular structures and organization. Over the last 20 years, TEM has gained popularity in the cardiovascular field to visualize changes at the nanometer scale in cardiac ultrastructure during cardiovascular development, aging, and a broad range of pathologies. Recently, the cardiovascular TEM enabled the studying of several signaling processes impacting mitochondrial function, such as mitochondrial fission/fusion, autophagy, mitophagy, lysosomal degradation, and lipophagy. The goals of this review are to provide an overview of the current usage of TEM to study cardiac ultrastructural changes; to understand how TEM aided the visualization of mitochondria, autophagy, and mitophagy under normal and cardiovascular disease conditions; and to discuss the overall advantages and disadvantages of TEM and potential future capabilities and advancements in the field.
Student Self-Efficacy and Aptitude to Participate in Relation to Perceived Functioning and Achievement in Students in Secondary School With and Without Disabilities

School-based Physical Education (PE) is important, especially to students with disabilities whose participation in physical activities out of school is limited. The development over time of participation-related constructs in relation to students’ perceived functioning and achievement is explored. Students in mainstream inclusive secondary school self-rated their PE-specific self-efficacy, general school self-efficacy, aptitude to participate in PE, and perceived physical and socio-cognitive functional skills at two timepoints, year 7 and year 9. Results were compared between three groups of students with: disabilities (n = 28), high grades (n = 47), or low grades (n = 30) in PE. Over time, perceived physical skills of students with disabilities became strongly associated with self-efficacy and aptitude to participate. Perceived socio-cognitive skills in the study sample improved and had a positive effect on PE-specific self-efficacy. Efforts should be made to limit the accelerated negative impact of perceived restricted functioning of students with disabilities. Grading criteria need to be developed to comply with standards adapted to fit abilities of students with disabilities. Meaningful learning experiences appear to be created when participation is promoted and capacity beliefs (PE-specific self-efficacy) are boosted. Allocating resources to support the development of students’ socio-cognitive skills seem to have potential for overall positive school outcome.
Implementation of deep neural networks for classifying electroencephalogram signal using fractional S‐transform for epileptic seizure detection

Epilepsy is one of the most common neurological diseases of the human brain. It affects the nervous system of brain which shows the impact on an individual's life because of its repetitious occurrences of seizure. Epileptic detection using automatic learning is essential to reduce the substantial work on reviewing continuous electroencephalogram (EEG) signal in spatial and temporal dimensions. A novel methodology is implemented on EEG signals for the detection of epileptic seizure with the combination of fractional S‐transform (FST) and entropies along with deep convolutional neural networks (CNN). The original EEG signals are preprocessed with discrete wavelet transform to generate Daubechies‐4 (Db4) wavelets. FST is enacted on every segment of the preprocessed signal for time‐frequency representation and the features are obtained through entropies. Afterwards, a 15‐layer deep CNN with dropout layer and soft‐max is used for classification. The experimental results showed that the singular value decomposition entropy are more stable and deep CNN models always performed better for this entropy. A specificity of 98.70%, sensitivity of 97.71%, and accuracy of 99.70% are achieved for the multichannel segment.
SYNTHESE ET CARACTERISATION DE POLY(ε-CAPROLACTONE) A PARTIR D'ε-CAPROLACTONE ET DIFFERENTS DIACIDES

La e-caprolactone (CL) a ete polymerisee sous atmosphere d'azote a 130°C en presence d'acide succinique (AS), acide adipique (AD) et acide sebacique (ASB) respectivement. L'Infra-Rouge, les RMN 1 H et 13 C, la titration des groupes carboxyles terminaux et les poids moleculaires CES montrent que les polycaprolactones (PCL) obtenus possedent deux groupes carboxyles terminaux. Leurs poids moleculaires augmentent au cours de polymerisation.
Crossbill: an open access single objective light-sheet microscopy platform

We present an open access scanned oblique plane microscopy platform Crossbill. It combines a new optical configuration, open hardware assembly, a systematic alignment protocol, and dedicated control software to provide a compact, versatile, high resolution single objective light-sheet microscopy platform. The demonstrated configuration yields the most affordable sub-micron resolution oblique plane microscopy system to date. We add galvanometer enabled tilt-invariant lateral scan for multi-plane, multi-Hz volumetric imaging capability. A precision translation stage extends stitched field of view to centimeter scale. The accompanying open software is optimized for Crossbill and can be easily extended to include alternative configurations. Using Crossbill, we demonstrate large volume structural fluorescence imaging with sub-micron lateral resolution in zebrafish and mouse brain sections. Crossbill is also capable of multiplane functional imaging, and time-lapse imaging. We suggest multiple alternative configurations to extend Crossbill to diverse microscopy applications.
Principled Decision-Making Workflow with Hierarchical Bayesian Models of High-Throughput Dose-Response Measurements

We present a case study applying hierarchical Bayesian estimation on high throughput protein melting point data measured across the tree of life. We show that the model is able to impute reasonable melting temperatures even in the face of unreasonably noisy data. Additionally, we demonstrate how to use the variance in melting temperature posterior distribution estimates to enable principled decision-making in common high throughput measurement tasks, and contrast the decision-making workflow against simple maximum-likelihood curve fitting. We conclude with a discussion of the relative merits of each workflow.
Transcriptome analyses reveal tau isoform-driven changes in transposable element and gene expression

Alternative splicing of the gene MAPT produces several isoforms of tau protein. Overexpression of these isoforms is characteristic of tauopathies, which are currently untreatable neurodegenerative diseases. Though non-canonical functions of tau have drawn interest, the role of tau isoforms in these diseases has not been fully examined and may reveal new details of tau-driven pathology. In particular, tau has been shown to promote activation of transposable elements — highly regulated nucleotide sequences that replicate throughout the genome and can promote immunologic responses and cellular stress. This study examined tau isoforms’ roles in promoting cell damage and dysregulation of genes and transposable elements at a family-specific and locus-specific level. We performed immunofluorescence, Western blot and cytotoxicity assays, along with paired-end RNA sequencing on differentiated SH-SY5Y cells infected with lentiviral constructs of tau isoforms and treated with amyloid-beta oligomers. Our transcriptomic findings were validated using publicly available RNA-sequencing data from Alzheimer’s disease, progressive supranuclear palsy and control human samples from the Accelerating Medicine’s Partnership for AD (AMP-AD). Significance for biochemical assays was determined using Wilcoxon ranked-sum tests and false discovery rate. Transcriptome analysis was conducted through DESeq2 and the TEToolkit suite available from the Hammell lab at Cold Spring Harbor Laboratory. Our analyses show overexpression of different tau isoforms and their interactions with amyloid-beta in SH-SY5Y cells result in isoform-specific changes in the transcriptome, with locus-specific transposable element dysregulation patterns paralleling those seen in patients with Alzheimer’s disease and progressive supranuclear palsy. Locus-level transposable element expression showed increased dysregulation of L1 and Alu sites, which have been shown to drive pathology in other neurological diseases. We also demonstrated differences in rates of cell death in SH-SY5Y cells depending on tau isoform overexpression. These results demonstrate the importance of examining tau isoforms’ role in neurodegeneration and of further examining transposable element dysregulation in tauopathies.
Oxidized alkyl phospholipids stimulate sodium transport in proximal tubules via PPARγ-dependent pathway

The pleiotropic effects of oxidized phospholipids (oxPLs) have been identified. 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxPL formed from alkyl phosphatidylcholines, is a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist. Although it has been reported that thiazolidinediones can induce volume expansion by enhancing renal sodium and water retention, the role of azPC, an endogenous PPARγ agonist, in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues. We showed that azPC rapidly stimulated Na+/HCO3- cotransporter 1 activity and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner, at submicromolar concentrations, in isolated PTs from rats and humans. Additionally, the stimulatory effects were completely blocked by a specific PPARγ antagonist, 2-chloro-5-nitro-N-phenylbenzamide (GW9662), and a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor, PD98059. Treatment with an siRNA against PPARγ significantly suppressed the expression of PPARγ mRNA, and it completely blocked the stimulation of both Na+/HCO3- cotransporter 1 and NHE activities by azPC. Moreover, azPC induced extracellular signal-regulated kinase (ERK) phosphorylation in rat and human kidney cortex tissues, and the induced ERK phosphorylation by azPC was completely suppressed by GW9662 and PD98059. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via the PPARγ/MEK/ERK pathway. The stimulatory effects of azPC on PT transport may be partially involved in the development of volume expansion.
Volumetric Semantic Instance Segmentation of the Plasma Membrane of HeLa Cells

In this work, the unsupervised volumetric semantic segmentation of the plasma membrane of HeLa cells as observed with Serial Block Face Scanning Electron Microscopy is described. The resin background of the images was segmented at different slices of a 3D stack of 518 slices with 8, 192 × 8, 192 pixels each. The background was used to create a distance map which helped identify and rank the cells by their size at each slice. The centroids of the cells detected at different slices were linked to identify them as a single cell that spanned a number of slices. A subset of these cells, i.e., largest ones and those not close to the edges were selected for further processing. The selected cells were then automatically cropped to smaller regions of interest of 2, 000 × 2, 000 × 300 voxels that were treated as cell instances. Then, for each of these volumes the nucleus was segmented and the cell was separated from any neighbouring cells through a series of traditional image processing steps that followed the plasma membrane. The segmentation process was repeated for all the regions selected. For one cell for which the ground truth was available, the algorithm provided excellent results in Accuracy (AC) and Jaccard Index (JI): Nucleus: JI = 0.9665, AC= 0.9975, Cell and Nucleus JI = 0.8711, AC = 0.9655, Cell only JI = 0.8094, AC = 0.9629. A limitation of the algorithm for the plasma membrane segmentation was the presence of background, as in cases of tightly packed cells. When tested for these conditions, the segmentation of the nuclear envelope was still possible. All the code and data are released openly through GitHub, Zenodo and EMPIAR.
Multi-animal pose estimation and tracking with DeepLabCut

Estimating the pose of multiple animals is a challenging computer vision problem: frequent interactions cause occlusions and complicate the association of detected keypoints to the correct individuals, as well as having extremely similar looking animals that interact more closely than in typical multi-human scenarios. To take up this challenge, we build on DeepLabCut, a popular open source pose estimation toolbox, and provide high-performance animal assembly and tracking—features required for robust multi-animal scenarios. Furthermore, we integrate the ability to predict an animal’s identity directly to assist tracking (in case of occlusions). We illustrate the power of this framework with four datasets varying in complexity, which we release to serve as a benchmark for future algorithm development.
Glaucoma assessment from color fundus images using convolutional neural network

Early detection and proper screening are essential to prevent vision loss due to glaucoma. In recent years, convolutional neural network (CNN) has been successfully applied to the color fundus images for the automatic detection of glaucoma. Compared to the existing automatic screening methods, CNNs have the ability to extract the distinct features directly from the fundus images. In this paper, a deep learning architecture based on a CNN is designed for the classification of glaucomatous and normal fundus images. An 18–layer CNN is designed and trained to extract the discriminative features from the fundus image. It comprises of four convolutional layers, two max pooling layers, and one fully connected layer. A two–stage tuning approach is proposed for the selection of suitable batch size and initial learning rate. The proposed network is tested on DRISHTI–GS1, ORIGA, RIM–ONE2 (release 2), ACRIMA, and large–scale attention–based glaucoma (LAG) databases. Rotation data augmentation technique is employed to enlarge the dataset. Randomly selected 70% of images are used for training the model and remaining 30% images are used for testing. An overall accuracy of 86.62%, 85.97%, 78.32%, 94.43%, and 96.64% are obtained on DRISHTI–GS1, RIM–ONE2, ORIGA, LAG, and ACRIMA databases, respectively. The proposed method has achieved an accuracy, sensitivity, specificity, and precision of 96.64%, 96.07%, 97.39%, and 97.74%, respectively, for ACRIMA database. Compared to other existing architectures, the proposed method is robust to Gaussian noise and salt–and–pepper noise.
Maternal Piwi Regulates Primordial Germ Cell Development to Ensure the Fertility of Female Progeny in Drosophila

In many animals, germline development is initiated by proteins and RNAs that are expressed maternally. PIWI proteins and their associated small noncoding PIWI-interacting RNAs (piRNAs), which guide PIWI to target RNAs by base-pairing, are among the maternal components deposited into the germline of the early embryo in Drosophila. Piwi has been extensively studied in the adult ovary and testis, where it is required for transposon suppression, germline stem cell self-renewal, and fertility. Consequently, loss of Piwi in the adult ovary using piwi-null alleles or knockdown from early oogenesis results in complete sterility, limiting investigation into possible embryonic functions of maternal Piwi. In this study, we show that the maternal Piwi protein persists in the embryonic germline through gonad coalescence, suggesting that maternal Piwi can regulate germline development beyond early embryogenesis. Using a maternal knockdown strategy, we find that maternal Piwi is required for the fertility and normal gonad morphology of female, but not male, progeny. Following maternal piwi knockdown, transposons were mildly derepressed in the early embryo but were fully repressed in the ovaries of adult progeny. Furthermore, the maternal piRNA pool was diminished, reducing the capacity of the PIWI/piRNA complex to target zygotic genes during embryogenesis. Examination of embryonic germ cell proliferation and ovarian gene expression showed that the germline of female progeny was partially masculinized by maternal piwi knockdown. Our study reveals a novel role for maternal Piwi in the germline development of female progeny and suggests that the PIWI/piRNA pathway is involved in germline sex determination in Drosophila.