Miracle-dz/UniFAR-FTUs huggingface dataset:
Cohort Analysis of 67 Charcot-Marie-Tooth Italian Patients: Identification of New Mutations and Broadening of Phenotype Expression Produced by Rare Variants

Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited motor sensory neuropathy, which clusters a clinically and genetically heterogeneous group of disorders with more than 90 genes associated with different phenotypes. The goal of this study is to identify the genetic features in the recruited cohort of patients, highlighting the role of rare variants in the genotype-phenotype correlation. We enrolled 67 patients and applied a diagnostic protocol including multiple ligation-dependent probe amplification for copy number variation (CNV) detection of PMP22 locus, and next-generation sequencing (NGS) for sequencing of 47 genes known to be associated with CMT and routinely screened in medical genetics. This approach allowed the identification of 26 patients carrying a whole gene CNV of PMP22. In the remaining 41 patients, NGS identified the causative variants in eight patients in the genes HSPB1, MFN2, KIF1A, GDAP1, MTMR2, SH3TC2, KIF5A, and MPZ (five new vs. three previously reported variants; three sporadic vs. five familial variants). Familial segregation analysis allowed to correctly interpret two variants, initially reported as “variants of uncertain significance” but re-classified as pathological. In this cohort is reported a patient carrying a novel familial mutation in the tail domain of KIF5A [a protein domain previously associated with familial amyotrophic lateral sclerosis (ALS)], and a CMT patient carrying a HSPB1 mutation, previously reported in ALS. These data indicate that combined tools for gene association in medical genetics allow dissecting unexpected phenotypes associated with previously known or unknown genotypes, thus broadening the phenotype expression produced by either pathogenic or undefined variants. Clinical trial registration: ClinicalTrials.gov (NCT03084224).
Cortical Thinning and Abnormal Structural Covariance Network After Three Hours Sleep Restriction

Sleep loss leads to serious health problems, impaired attention, and emotional processing. It has been suggested that the abnormal neurobehavioral performance after sleep deprivation was involved in dysfunction of specific functional connectivity between brain areas. However, to the best of our knowledge, there was no study investigating the structural connectivity mechanisms underlying the dysfunction at network level. Surface morphological analysis and graph theoretical analysis were employed to investigate changes in cortical thickness following 3 h sleep restriction, and test whether the topological properties of structural covariance network was affected by sleep restriction. We found that sleep restriction significantly decreased cortical thickness in the right parieto-occipital cortex (Brodmann area 19). In addition, graph theoretical analysis revealed significantly enhanced global properties of structural covariance network including clustering coefficient and local efficiency, and increased nodal properties of the left insula cortex including nodal efficiency and betweenness, after 3 h sleep restriction. These results provided insights into understanding structural mechanisms of dysfunction of large-scale functional networks after sleep restriction.
Variants in LAMC3 Causes Occipital Cortical Malformation

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the LAMC3 gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.470G > A and c.4030 + 1G > A) of the LAMC3 gene in a Chinese female with childhood-onset seizures. Cranial magnetic resonance imaging was normal. Functional experiments confirmed that both variant sites caused premature truncation of the laminin γ3 chain. Bioinformatics analysis predicted 10 genes interacted with LAMC3 with an interaction score of 0.4 (P value = 1.0e–16). The proteins encoded by these genes were mainly located in the basement membrane and extracellular matrix component. Furthermore, the biological processes and molecular functions from gene ontology analysis indicated that laminin γ3 chain and related proteins played an important role in structural support and cellular processes through protein-containing complex binding and signaling receptor binding. KEGG pathway enrichment predicted that the LAMC3 gene variant was most likely to participate in the occurrence and development of OCCM through extracellular matrix receptor interaction and PI3K-Akt signaling pathway.
Sustainability, Spread, and Shift: Developing a Professional Learning Program for Out-of-School Educators With Scale-Up in Mind

This case study describes the iterative process used to develop a virtual coaching program for out-of-school-time (OST) educators, particularly those who work in afterschool and library settings. The program, called ACRES (Afterschool Coaching for Reflective Educators in STEM), used a design-based implementation research (DBIR) approach to consider issues related to scale-up. Afterschool and library settings are complex systems that include supports and barriers that require adaptation for implementation. Throughout the design process, program developers worked to identify the essential elements of the program that should be maintained across contexts, while attending to the diverse needs of individual OST settings. Survey and interview data were collected from the full range of stakeholders throughout the implementation process to verify the importance of the essential elements to the professional learning model, and to gather early indicators of the program’s potential related to three key concepts for successful scale-up of programs: sustainability, spread, and shift. Conclusions are shared in relation to how these types of results support the scale-up of programs, and the strengths and gaps in the process used to apply the DBIR approach in our work.
Assessment of Language Functions in Patients With Disorders of Consciousness Using an Alternative Communication Tool

This study aimed to describe the percentage of tasks involving language functions that were completed by patients diagnosed with disorders of consciousness, as observed during neurorehabilitation conducted for different periods of time using an alternative communication tool. The project involved six participants, who were observed for 1 month, 6 months, and 1 year. The patients were asked to solve tasks involving language functions with the use of an eye-controlled device. The language functions were evaluated on the basis of the average number of tasks performed by the patients, which was 70.45% for the whole subject group. It is not entirely clear what determined the changes in language functions during the research. It is crucial that patients performed the presented tasks even though their state of consciousness, as confirmed through medical documentation (unresponsive wakefulness syndrome), did not suggest the possibility of establishing any contact with them.
Recent Advances and Challenges in the Development of Radiofrequency HTS Coil for MRI

Radiofrequency (RF) coils fashioned from high-temperature superconductor (HTS) have the potential to increase the sensitivity of the magnetic resonance imaging (MRI) experiment by more than a dozen times compared to conventional copper coils. Progress, however, has been slow due to a series of technological hurdles. In this article, we present the developments that recently led to new perspectives for HTS coil in MRI, and challenges that still need to be solved. First, we recall the motivations for the implementations of HTS coils in MRI by presenting the limits of cooled copper coil technology, such as the anomalous skin effect limiting the decrease of the electric resistance of normal conductors at low temperature. Then, we address the progress made in the development of MRI compatible cryostats. New commercially available low-noise pulsed-tube cryocoolers and new materials removed the need for liquid nitrogen-based systems, allowing the design of cryogen-free and more user-friendly cryostats. Another recent advance was the understanding of how to mitigate the imaging artifacts induced by HTS diamagnetism through field cooling or temperature control of the HTS coil. Furthermore, artifacts can also originate from the RF field coupling between the transmission coil and the HTS reception coil. Here, we present the results of an experiment implementing a decoupling strategy exploiting nonlinearities in the electric response of HTS materials. Finally, we discuss the potential applications of HTS coils in bio-imaging and its prospects for further improvements. These include making the technology more user-friendly, implementing the HTS coils as coil arrays, and proposing solutions for the ongoing issue of decoupling. HTS coil still faces several challenges ahead, but the significant increase in sensitivity it offers lends it the prospect of being ultimately disruptive.
Evolution of Frequency and Intensity of Concurrent Heavy Precipitation and Storm Surge at the Global Scale: Implications for Compound Floods

Compound flood raised from the concurrent heavy precipitation and storm surge receives increasing attention because of its potential threat to coastal areas. Analyzing the past changes in the characteristics of compound flood events is critical to understand the changing flood risks associated with the combination of multiple drivers/hazards. Here, we examined the evolution of the compound flood days (defined as days of concurrent extreme precipitation and extreme storm surge exceeding the 90th percentiles) based on the observed precipitation and storm surge data across the globe. Results show that the annual number of compound flood days increased significantly by 1–4 per decade (α = 0.1) on the east coast of the US and northern Europe, while the annual number of compound flood days decreased significantly in southern Europe and Japan. The increasing trends in precipitation under extreme storm surge and storm surge under extreme precipitation were found extensively across the world except in Japan, suggesting that more intense precipitation appeared when extreme storm surges occurred, and higher storm surge emerged when extreme precipitation occurred. Comparatively, the global fractional contributions of storm surge (i.e., 65%) on changes in compound flood days were higher than that of precipitation (i.e., 35%), demonstrating that storm surge was more likely to dominate the changes in the number of compound flood days. This study presents the spatial and temporal characteristics of the compound flood events at the global scale, which helps better understanding the compound floods and provides scientific references for flood risk management and an indispensable foundation for further studies.
Parietal Lobe Reorganization and Widespread Functional Connectivity Integration in Upper-Limb Amputees: A rs-fMRI Study

The right parietal lobe plays an important role in body image, and disorders of body image emerge after lesions in the parietal lobe or with parietal lobe epilepsy. Body image disorder also often accompanies upper-limb amputation, in which the patient misperceives that their missing limb is still part of their body. Cortical reorganization is known to occur after upper-limb amputation, but it is not clear how widespread and to what degree functional connectivity (FC) is reorganized post-amputation, nor whether such changes might be related to misperceptions of body image. Twenty-four subjects who had a traumatically upper-limb amputees (ULAs) and 24 age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Regions of interest (ROIs) in the right superior parietal gyrus (SPG_R) and right inferior parietal lobule (IPL_R) were defined using BrainNet Viewer. We calculated the amplitude of low-frequency fluctuations (ALFF) in ROIs and correlated the ROI mean amplitude of low-frequency fluctuations (mALFF) and mean scores on the phantom limb sensation (PLS) scale and beck depression index (BDI). We also calculated ROIs and whole-brain FC. Compared to the HC group, we observed significantly increased activation (mALFF) in ROIs of the ULA group. Moreover, correlation analyses revealed a significant positive correlation between ROI mALFF and scores on the PLS. There was a significant negative correlation between the SPG_R mALFF and BDI scores. Seed-based, whole-brain FC analysis revealed that FC in the ULA group significantly decreased in many brain regions across the entire brain. The right parietal lobe appears to be involved in some aspect of body awareness and depression in amputation patients. Upper-limb amputation results not only in reorganization in the local brain area formerly representing the missing limb, but also results in more widespread reorganization through FC changes in whole brain.
Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents

Objectives A novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation. Methods VEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs. Results The average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was −13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated. Conclusion Nano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.
At the Intersection of Major and Minor Spliceosomes: Crosstalk Mechanisms and Their Impact on Gene Expression

Many eukaryotic species contain two separate molecular machineries for removing non-coding intron sequences from pre-mRNA molecules. The majority of introns (more than 99.5% in humans) are recognized and excised by the major spliceosome, which utilizes relatively poorly conserved sequence elements at the 5′ and 3′ ends of the intron that are used for intron recognition and in subsequent catalysis. In contrast, the minor spliceosome targets a rare group of introns (approximately 0.5% in humans) with highly conserved sequences at the 5′ and 3′ ends of the intron. Minor introns coexist in the same genes with major introns and while the two intron types are spliced by separate spliceosomes, the two splicing machineries can interact with one another to shape mRNA processing events in genes containing minor introns. Here, we review known cooperative and competitive interactions between the two spliceosomes and discuss the mechanistic basis of the spliceosome crosstalk, its regulatory significance, and impact on spliceosome diseases.
Viability Status-Dependent Effect of Bifidobacterium longum ssp. longum CCM 7952 on Prevention of Allergic Inflammation in Mouse Model

The classical definition of probiotics states that bacteria must be alive to be beneficial for human organism. However, recent reports show that inactivated bacteria or their effector molecules can also possess such properties. In this study, we investigated the physical and immunomodulatory properties of four Bifidobacterium strains in the heat-treated (HT) and untreated (UN) forms. We showed that temperature treatment of bacteria changes their size and charge, which affects their interaction with epithelial and immune cells. Based on the in vitro assays, we observed that all tested strains reduced the level of OVA-induced IL-4, IL-5, and IL-13 in the spleen culture of OVA-sensitized mice. We selected Bifidobacterium longum ssp. longum CCM 7952 (Bl 7952) for further analysis. In vivo experiments confirmed that untreated Bl 7952 exhibited allergy-reducing properties when administered intranasally to OVA-sensitized mice, which manifested in significant suppression of airway inflammation. Untreated Bl 7952 decreased local and systemic levels of Th2 related cytokines, OVA-specific IgE antibodies and simultaneously inhibited airway eosinophilia. In contrast, heat-treated Bl 7952 was only able to reduce IL-4 levels in the lungs and eosinophils in bronchoalveolar lavage, but increased neutrophil and macrophage numbers. We demonstrated that the viability status of Bl 7952 is a prerequisite for the beneficial effects of bacteria, and that heat treatment reduces but does not completely abolish these properties. Further research on bacterial effector molecules to elucidate the beneficial effects of probiotics in the prevention of allergic diseases is warranted.
Emergence and Clonal Spread of CTX-M-65-Producing Escherichia coli From Retail Meat in Portugal

The emergence and dissemination of resistance to third- and fourth-generation cephalosporins among Enterobacteriaceae from different sources impose a global public health threat. Here, we characterized by whole-genome sequencing four Escherichia coli strains harboring the blaCTX–M–65 gene identified among 49 isolates from beef and pork collected at retail. The genomic content was determined using the Center for Genomic Epidemiology web tools. Additionally, the prediction and reconstruction of plasmids were conducted, the genetic platform of the blaCTX–M–65 genes was investigated, and phylogenetic analysis was carried out using 17 other genomes with the same sequence type and harboring the blaCTX–M–65 gene. All strains harbored blaCTX–M–65, blaOXA–1, and blaTEM–1B, and one also carried the blaSHV–12 gene. Other resistance genes, namely, qnrS2, aac(6′)-Ib-c, dfrA14, sul2, tetA, and mphA, were present in all the genomes; the mcr-1.1 gene was identified in the colistin-resistant strains. They belong to sequence type 2179, phylogenetic group B1, and serotype O9:H9 and carried plasmids IncI, IncFIC(FII), and IncFIB. All strains share an identical genetic environment with IS903 and ISEcp1 flanking the blaCTX–M–65 gene. It seems likely that the blaCTX–M–65 gene is located in the chromosome in all isolates based on deep in silico analysis. Our findings showed that the strains are clonally related and belong to two sub-lineages. This study reports the emergence of CTX-M-65-producing E. coli in Portugal in food products of animal origin. The chromosomal location of the blaCTX–M–65 gene may ensure a stable spread of resistance in the absence of selective pressure.
miR-30a-5p Regulates Viability, Migration, and Invasion of Lung Adenocarcinoma Cells via Targeting ECT2

Objective The abnormal expression of epithelial cell transforming sequence 2 (ECT2) is often considered the driving factor for the growth and invasion of tumors. This study was performed to investigate the regulatory effect of miR-30a-5p and ECT2 on lung adenocarcinoma (LUAD), which provides a basis for the effective clinical treatment of LUAD. Methods The mature miRNAs, expression data of mRNAs, and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). The expression levels of ECT2 mRNA and miR-30a-5p in cancer cell lines were detected by qRT-PCR. Western blot was performed to test the expression of ECT2 protein. The targeting relationship between miR-30a-5p and ECT2 was verified by dual-luciferase assay. The CCK-8 method and Transwell assay were conducted to test the viability, migratory, and invasive abilities of cells. Results ECT2 expression was upregulated in LUAD and was significantly correlated with the LUAD clinical stage and pathologic T stage, and the expression of its upstream regulatory gene miR-30a-5p was downregulated. miR-30a-5p targeted ECT2 in LUAD. Downregulation of ECT2 could inhibit the viability, migration, and invasion of LUAD cells, which could be reversed by simultaneously suppressing the expression of miR-30a-5p. Conclusion Our results suggested that miR-30a-5p repressed the malignant progression of LUAD via downregulating ECT2. miR-30a-5p and ECT2 may be effective targets for LUAD patients.
Génération de textes artificiels pour l'expansion de requêtes

RÉSUMÉ. Un moyen d’améliorer les performances de la recherche de documents consiste à étendre la requête de l’utilisateur. Plusieurs approches ont été proposées dans la littérature, et certaines d’entre elles obtiennent des résultats très compétitifs. Dans cet article, nous explorons l’utilisation de la génération de texte pour étendre automatiquement les requêtes. Nous nous appuyons sur un modèle génératif neuronal bien connu, GPT-2, qui est fourni avec des modèles pré-entraînés pour l’anglais mais qui peut également être afﬁné sur des corpus spéciﬁques. À travers différentes expériences, nous montrons que la génération de texte est un moyen très efﬁcace d’améliorer les performances d’un système de RI, avec une marge importante (+10% de gains MAP), et qu’il surpasse des approches état-de-l’art reposant également sur l’expansion des requêtes (LM+RM3). Cette approche conceptuellement simple peut être facilement mise en œuvre sur n’importe quel système de RI grâce à la disponibilité du code et des modèles GPT. ABSTRACT. A well-known way to improve the performance of document retrieval is to expand the user’s query. Several approaches have been proposed in the literature, and some of them are considered as yielding state-of-the-art results. In this paper, we explore the use of text generation to automatically expand the queries. We rely on a well-known neural generative model, GPT-2, that comes with pre-trained models for English but can also be ﬁne-tuned on speciﬁc corpora. Through different experiments, we show that text generation is a very effective way to improve the performance of an IR system, with a large margin (+10% MAP gains), and that it outperforms strong baselines also relying on query expansion (LM+RM3). This conceptually simple approach can easily be implemented on any IR system thanks to the availability of GPT code and models. MOTS-CLÉS