Miracle-dz/UniFAR-FTUs huggingface dataset:
IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption

Objective Autoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption. Methods Anti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption. Results NET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts. Conclusion IgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies.
Comprehensive Analysis of the SBP Family in Blueberry and Their Regulatory Mechanism Controlling Chlorophyll Accumulation

SQUAMOSA Promoter Binding Protein (SBP) family genes act as central players to regulate plant growth and development with functional redundancy and specificity. Addressing the diversity of the SBP family in crops is of great significance to precisely utilize them to improve agronomic traits. Blueberry is an important economic berry crop. However, the SBP family has not been described in blueberry. In the present study, twenty VcSBP genes were identified through data mining against blueberry transcriptome databases. These VcSBPs could be clustered into eight groups, and the gene structures and motif compositions are divergent among the groups and similar within each group. The VcSBPs were differentially expressed in various tissues. Intriguingly, 10 VcSBPs were highly expressed at green fruit stages and dramatically decreased at the onset of fruit ripening, implying that they are important regulators during early fruit development. Computational analysis showed that 10 VcSBPs were targeted by miR156, and four of them were further verified by degradome sequencing. Moreover, their functional diversity was studied in Arabidopsis. Noticeably, three VcSBPs significantly increased chlorophyll accumulation, and qRT-PCR analysis indicated that VcSBP13a in Arabidopsis enhanced the expression of chlorophyll biosynthetic genes such as AtDVR, AtPORA, AtPORB, AtPORC, and AtCAO. Finally, the targets of VcSBPs were computationally identified in blueberry, and the Y1H assay showed that VcSBP13a could physically bind to the promoter region of the chlorophyll-associated gene VcLHCB1. Our findings provided an overall framework for individually understanding the characteristics and functions of the SBP family in blueberry.
Habitat, Snow-Cover and Soil pH, Affect the Distribution and Diversity of Mortierellaceae Species and Their Associations to Bacteria

Mortierellaceae species are among the most frequent and globally distributed soil fungi. However, the factors shaping their diversity and distribution remain obscure. Several species have been reported to be associated to bacteria, but the kind and frequency of such associations were not addressed up to now. We hypothesized that such associations could be important for Mortierellaceae ecology. Therefore, our aim was to understand the driving factors responsible for the Mortierellaceae diversity, community composition and bacterial associations in alpine and subalpine habitats. For answering our question, we collected both snow-free and snow-covered soil at sampling sites from different habitats: bare alpine soil in a glacier forefield, alpine dwarf-willow habitats, and high-altitude Pinus cembra forests. The isolations were carried out by direct cultivation without any antibiotics to the isolation media. Altogether, we obtained 389 Mortierellaceae isolates representing 29 operational taxonomic units (OTUs). Many OTUs could be placed to the genera Mortierella sensu stricto, Dissophora, Entomortierella, Gamsiella, Linnemannia, and Podila, but others could not unambiguously be assigned to a genus. Our results demonstrate that both, the distribution as well as the diversity of the Mortierellaceae species, were significantly influenced by habitat, soil pH, and snow-cover. We noticed that >30% of our isolates were associated to a non-contaminant bacterium. The bacteria associated to our Mortierellaceae isolates belonged to seven different genera. Pseudomonas was the most frequently detected genus associated to the isolated Mortierellaceae species and it was found to be species-specific. Mortierellaceae–bacteria pairs, including those with Pseudomonas, were influenced by location, habitat, and snow-cover. The majority of the fungus–bacterium associations were potentially epihyphal, but we also detected potential endohyphal bacterial species belonging to Mycoavidus, Burkholderiaceae, and Paraburkholderia. Taken together, the non-random associations we detected suggest that fungus–bacterium associations are ecologically meaningful – an interesting path that needs to be investigated further.
Sap Flow Disruption in Grapevine Is the Early Signal Predicting the Structural, Functional, and Genetic Responses to Esca Disease

Fungal species involved in Esca cause the formation of grapevine wood necroses. It results in the deterioration of vascular network transport capacity and the disturbance of the physiological processes, leading to gradual or sudden grapevine death. Herein, for two consecutive growing seasons, a detailed analysis of the structural (wood necrosis and leaf discoloration) and physiological parameters related to the water use of healthy and esca-symptomatic grapevines was conducted. Measurements were carried out on 17-year-old grapevines that expressed, or not, Esca-leaf symptoms in a vineyard of the Bordeaux region (France). Whole-plant transpiration was recorded continuously from pre-veraison to harvest, using noninvasive sap flow sensors. Whole-plant transpiration was systematically about 40–50% lower in Esca-diseased grapevines compared with controls, and this difference can be observed around 2 weeks before the first Esca-foliar symptoms appeared in the vineyard. Unlike grapevine sap flow disruption, structural (e.g., leaf discolorations), functional (e.g., stomatal conductance, photosynthetic activity, phenolic compounds), and genetic (e.g., expression of leaf-targeted genes) plant responses were only significantly impacted by Esca at the onset and during leaf symptoms development. We conclude that sap flow dynamic, which was related to a high level of a white-rot necrosis, provides a useful tool to predict plant disorders due to Esca-grapevine disease.
Lower Funneling Pathways in Scedosporium Species

Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this molecule by microorganisms still remains largely misunderstood. Extracellular oxidative degradation is followed by intracellular metabolic degradation of conserved aromatic intermediate compounds (protocatechuate, catechol, hydroxyquinol, and gentisic acid) that are used as carbon and energy sources. The lower funneling pathways are characterized by the opening of the aromatic ring of these molecules through dioxygenases, leading to degradation products that finally enter into the tricarboxylic acid (TCA) cycle. In order to better understand the adaptation mechanisms of Scedosporium species to their environment, these specific catabolism pathways were studied. Genes encoding ring-cleaving dioxygenases were identified in Scedosporium genomes by sequence homology, and a bioinformatic analysis of the organization of the corresponding gene clusters was performed. In addition, these predictions were confirmed by evaluation of the expression level of the genes of the gentisic acid cluster. When the fungus was cultivated in the presence of lignin or gentisic acid as sole carbon source, experiments revealed that the genes of the gentisic acid cluster were markedly overexpressed in the two Scedosporium species analyzed (Scedosporium apiospermum and Scedosporium aurantiacum). Only the gene encoding a membrane transporter was not overexpressed in the gentisic acid-containing medium. Together, these data suggest the involvement of the lower funneling pathways in Scedosporium adaptation to their environment.
Finding One's Footing When Everyone Has an Opinion. Negotiating an Acceptable Identity After Sexual Assault

Identities used to describe oneself after trauma may influence recovery, and searches for acceptable identities after sexual assault can be challenging. Fifteen Norwegian female survivors of sexual assault were recruited at a clinical center, and were individually interviewed about post-assault discussions with others. Our focus was on the experiences of non-blaming and believing interactions with others, and how these interactions can be understood as a process of searching for acceptable identities after sexual assault. A reflexive thematic analysis resulted in four themes: navigating between other people's stories and one's own; realizing the seriousness of the assault without drowning in the upset of others; finding a place between too much closeness and too much distance; and being more than a victim. We discuss the importance of participants retaining agency in post-assault interactions. We suggest that being a survivor of sexual assault increases the probability, even in believing and non-blaming interactions, of being cast in a subject–object relationship with less freedom and agency than before. Navigating toward acceptable identities may mean working one's way back to being a subject in a subject–subject relationship again.
Deep Shape Features for Predicting Future Intracranial Aneurysm Growth

Introduction: Intracranial aneurysms (IAs) are a common vascular pathology and are associated with a risk of rupture, which is often fatal. Aneurysm growth is considered a surrogate of rupture risk; therefore, the study aimed to develop and evaluate prediction models of future artificial intelligence (AI) growth based on baseline aneurysm morphology as a computer-aided treatment decision support. Materials and methods: Follow-up CT angiography (CTA) and magnetic resonance angiography (MRA) angiograms of 39 patients with 44 IAs were classified by an expert as growing and stable (25/19). From the angiograms vascular surface meshes were extracted and the aneurysm shape was characterized by established morphologic features and novel deep shape features. The features corresponding to the baseline aneurysms were used to predict future aneurysm growth using univariate thresholding, multivariate random forest and multi-layer perceptron (MLP) learning, and deep shape learning based on the PointNet++ model. Results: The proposed deep shape feature learning method achieved an accuracy of 0.82 (sensitivity = 0.96, specificity = 0.63), while the multivariate learning and univariate thresholding methods were inferior with an accuracy of up to 0.68 and 0.63, respectively. Conclusion: High-performing classification of future growing IAs renders the proposed deep shape features learning approach as the key enabling tool to manage rupture risk in the “no treatment” paradigm of patient follow-up imaging.
Reshaping of Gut Microbiota in Gilthead Sea Bream Fed Microbial and Processed Animal Proteins as the Main Dietary Protein Source

The present study aimed to unravel the effects of partial (50%; 50LSAqua) and total (100%; 100LSAqua) replacement of fish meal (FM) by a commercial protein source (LSAqua SusPro) made of bacterial and processed animal proteins (PAP) in farmed juveniles of gilthead sea bream (Sparus aurata). The trial lasted 8 weeks, and the feasibility of replacement was assessed in terms of growth performance, histopathological scoring and composition of mucosal adherent microbiota from anterior intestine (AI). Specific growth rates (SGR) of 50LSAqua fish were undistinguishable from the CTRL group, whereas a slight but significant growth impairment was found with the total replacement. Histological signs of inflammation across the intestine were more evident at the highest level of FM replacement, and the total concentration of short chain fatty acids (SCFA) in stripped feces decreased in a dose dependent manner. Illumina sequencing of gut mucosal microbiota yielded a mean of 130,439 reads per sample assigned to 1,567 OTUs at 97% identity threshold. The bacterial richness was similar in all groups, but a significantly higher Simpson diversity index was found in 100LSAqua fish. At the phylum level, Proteobacteria were the most abundant in all groups, whereas Firmicutes decreased and Actinobacteria increased with the FM replacement. At a closer look, pro-inflammatory Gammaproteobacteria of the genus Psychrobacter, and Acinetobacter decreased with FM replacement, whereas the anti-inflammatory Paracoccus, Arthrobacter, and Actinomycetales increased, with a remarkable presence of the Propioniciclava genus in LSAqua groups. The inferred metagenome analysis suggested that these discriminant bacteria could be implicated in a counter-regulatory anti-inflammatory response. It also pointed to an over-representation of mucosal microbes that can potentially be involved in the natural production of antimicrobials in fish fed the experimental diets.
Report of Eleven Patients of Subcutaneous Panniculitis-Like T-Cell Lymphoma: Clinicopathologic Features, 18F-FDG PET/CT Findings and Outcome

Objectives Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a fairly rare subtype of primary cutaneous lymphoma. This study aims to investigate the clinicopathologic features, 18F-FDG PET/CT findings, and outcome of patients with SPTCL. Methods A retrospective single-center study enrolled 11 patients with SPTCL between August 2010 and March 2020. A total of 26 18F-FDG PET/CT scans were performed, and the initial and follow-up PET/CT imaging features, clinicopathologic and immunohistochemical characteristics, and outcome were analyzed. Results The male-to-female ratio was 1.2. The mean age at diagnosis was 24.2 years (age range: 13–48 years). Histopathological examinations revealed atypical T-lymphocyte rimming of individual subcutaneous adipocytes, mostly with CD2+, CD3+, CD4−, CD5+, CD8+, CD56−, T-cell intracellular antigen-1+, Granzyme B+, and high Ki-67 index. Multiple large skin ulcerations with a maximum diameter of 10 cm were observed in one of the 11 patients (9.1%, 1/11), and hemophagocytic syndrome was found in another one. At initial PET/CT scans, the lesions in all 11 patients showed increased uptake of 18F-FDG with a wide range of maximum standard uptake value (SUVmax) from 2.0 to 14.9. The morphology of the lesions presented as multiple nodules and/or disseminated plaques mainly involving the trunk and/or limbs. Five patients had extracutaneous non-lymph node lesions with SUVmax of 5.6 ± 2.8 on 18F-FDG PET/CT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.19, P > 0.05). Follow-up 18F-FDG PET/CT scans in six patients showed complete remission of the disease in two, partial remission in three, and progressive disease in one. During the follow-up period, there was no death except for the patient with multiple ulcerations who died 4 months after diagnosis of SPTCL. Conclusions SPTCL may be a group of heterogeneous diseases with varying degrees of 18F-FDG uptake. 18F-FDG PET/CT demonstrates its usefulness in detecting disease extent, providing diagnostic work-up, staging, and evaluating treatment response of SPTCL. Multiple large skin ulcerations may be a factor of poor prognosis for patients with SPTCL.
To Combine or Not to Combine Physical Therapy With tDCS for Stroke With Shoulder Pain? Analysis From a Combination Randomized Clinical Trial for Rehabilitation of Painful Shoulder in Stroke

Purpose: Transcranial Direct Current Stimulation (tDCS) is an intervention that seems to be an ideal tool to enhance the effects of rehabilitation therapies given it facilitates generation of plasticity in the stimulated brain area. In stroke this strategy has been highly utilized; however, the results have been mixed. In this trial we have evaluated the analgesic and functional effects of Transcranial Direct Current Stimulation (tDCS) combined with physiotherapy in stroke survivors with shoulder pain. Methods: Twenty-six stroke surviving adults with shoulder pain received 10 sessions of passive mobilization and performed upper limb exercises using a cycle ergometer, combined with active or sham tDCS. The intensity of pain in the hemiplegic shoulder was measured using the Visual Analog Scale (VAS); secondary outcomes were the level of motor impairment, handgrip strength, range of motion, motor function of the upper limbs, and quality of life (QOL) assessed before and after 10 sessions and 1 month after the end of the treatment. Results: A clinically important pain reduction (3 points) was found in both groups and was maintained at follow-up; there was no significant difference between groups (p = 0.3). Similarly, the shoulder range of motion improved, motor function and quality of life improved showed no significant differences between groups. One result that needs to be underscored is that both groups had a significant effect size toward improvement in all of these outcomes. Conclusions: We discuss in this study that tDCS is not a useful combination strategy when the physical therapy has a large effect by itself and we also review other negative trials of combined therapy under this framework of ceiling effect of the main physical therapy. Trial registry: Trial registration: Brazilian Registry of Clinical Trials, RBR-8F5MNY (http://www.ensaiosclinicos.gov.br/rg/RBR-8f5mny/). Registered on June 2, 2017. Beginning of the recruitment of the volunteers: august, 2017.
The Application of 3D-Printing and Nanotechnology for the Targeted Treatment of Osteosarcoma

Osteosarcoma is a malignant bone neoplasm prevalent in adolescents. Current therapies include chemotherapy and surgery. Surgical resection of osteosarcoma induces a large bone defect which may be overcome by employing scaffolds for bone tissue engineering. This review details the polymers and bioceramics that may be used to fabricate 3D printed scaffolds for bone regeneration and the nanotechnology strategies that may be incorporated into such scaffolds. Natural polymers discussed include chitosan, alginate, collagen, gelatin, and silk fibroin. Synthetic polymers discussed include polycaprolactone, polyurethane, poly(lactic)acid and poly(vinyl) alcohol. Bioceramics that are utilized in bone regeneration such as calcium phosphate, calcium silicate and bioglass are elaborated on. Furthermore, comparison data between different types of 3D printed scaffolds for bone regeneration are presented. A discussion on Photo-responsive and magneto-responsive 3D printed scaffolds that have been fabricated for bone regeneration is included. Research concerning drug-loaded scaffolds as well as the incorporation of nanocarriers into scaffolds for bone regeneration is provided. Chemotherapy utilized in osteosarcoma therapy has severe adverse effects due to being non-selective between healthy cells and tumor cells. A possible way to overcome this is to utilize nanotechnology. Therefore, research detailing other types of nanocarriers that have the potential to be incorporated into 3D printed scaffolds for localized adjuvant therapy is presented.
Distinctive Association of the Functional Connectivity of the Posterior Cingulate Cortex on Memory Performances in Early and Late Amnestic Mild Cognitive Impairment Patients

Background Attempts have been made to explore the biological basis of neurodegeneration in the amnestic mild cognitive impairment (MCI) stage, subdivided by memory performance. However, few studies have evaluated the differential impact of functional connectivity (FC) on memory performances in early- and late-MCI patients. Objective This study aims to explore the difference in FC of the posterior cingulate cortex (PCC) among healthy controls (HC) (n = 37), early-MCI patients (n = 30), and late-MCI patients (n = 35) and to evaluate a group-memory performance interaction against the FC of PCC. Methods The subjects underwent resting-state functional MRI scanning and a battery of neuropsychological tests. Results A significant difference among the three groups was found in FC between the PCC (seed region) and bilateral crus cerebellum, right superior medial frontal gyrus, superior temporal gyrus, and left middle cingulate gyrus (Monte Carlo simulation-corrected p < 0.01; cluster p < 0.05). Additionally, the early-MCI patients displayed higher FC values than the HC and late-MCI patients in the right superior medial frontal gyrus, cerebellum crus 1, and left cerebellum crus 2 (Bonferroni-corrected p < 0.05). Furthermore, there was a significant group-memory performance interaction (HC vs. early MCI vs. late MCI) for the FC between PCC and bilateral crus cerebellum, right superior medial frontal gyrus, superior temporal gyrus, and left middle cingulate gyrus (Bonferroni-corrected p < 0.05). Conclusion These findings contribute to the biological implications of early- and late-MCI stages, categorized by evaluating the impairment of memory performance. Additionally, comprehensively analyzing the structural differences in the subdivided amnestic MCI (aMCI) stages could deepen our understanding of these biological meanings.