Miracle-dz/UniFAR-FTUs huggingface dataset:
The Local Topological Reconfiguration in the Brain Network After Targeted Hub Dysfunction Attacks in Patients With Juvenile Myoclonic Epilepsy

The central brain regions of brain networks have been extensively studied in terms of their roles in various diseases. This study provides a direct measure of the brain’s responses to targeted attacks on central regions, revealing the critical role these regions play in patients with juvenile myoclonic epilepsy (JME). The resting-state data of 37 patients with JME and 37 healthy subjects were collected, and brain functional networks were constructed for the two groups of data according to their Pearson correlation coefficients. The left middle cingulate gyrus was defined as the central brain region by the eigenvector centrality algorithm and was attacked by the CLM sequential failure model. The rich-club connection differences between the patients with JME and healthy controls before and after the attacks were compared according to graph theory indices and the number of rich-club connections. We found that the numbers of rich connections in the brain networks of the healthy control group and the group of patients with JME were significantly reduced [p < 0.05, false discovery rate (FDR) correction] before the CLM sequential failure attacks, and no significant differences were observed between the feeder connections and local connections. In the healthy control group, significant rich connection differences were obtained (p < 0.01, FDR correction), and no statistically significant differences were observed regarding the feeder connections and local connections in the brain network before and after CLM failure attacks on the central brain region. No significant differences were obtained between the rich connections, feeder connections, and local connections in patients with JME before and after CLM successive failure attacks on the central brain area. The rich connections, feeder connections, and local connections were not significantly different in the brain networks of the healthy control group and the group of patients with JME after CLM successive failure attacks on the central brain region. We concluded that the damage to the left middle cingulate gyrus is closely linked to various brain disorders, suggesting that this region is of great importance for understanding the pathophysiological basis of myoclonic seizures in patients with JME.
Protein Kinase C Life Cycle: Explained Through Systems Biology Approach

Protein kinase C (PKC) enzymes are a family of kinases that mediate signal transduction originating at the cell surface. Most cell membranes can contain functional PKC enzymes. Aberrations in the PKC life cycle may result in cellular damage and dysfunction. For example, some cancerous cells exhibit alterations in PKC activity. Here, we use a systems biology approach to describe a molecular model of the PKC life cycle. Understanding the PKC life cycle is necessary to identify new drug targets. The PKC life cycle is composed of three key regulatory processes: maturation, activation, and termination. These processes precisely control PKC enzyme levels. This model describes the fate of PKC during de novo synthesis and PKC’s lipid-mediated activation cycle. We utilize a systems biology approach to show the PKC life cycle is controlled by multiple phosphorylation and dephosphorylation events. PKC processing events can be divided into two types: maturation via processing of newly synthesized enzyme and secondary messenger-dependent activation of dormant, but catalytically competent enzyme. Newly synthesized PKC enzyme is constitutively processed through three ordered phosphorylations and stored in the cytosol as a stable, signaling-competent inactive and autoinhibited molecule. Upon extracellular stimulation, diacylglycerol (DAG) and calcium ion (Ca2+) generated at the membrane bind PKC. PKC then undergoes cytosol-to-membrane translocation and subsequent activation. Our model shows that, once activated, PKC is prone to dephosphorylation and subsequent degradation. This model also describes the role of HSP70 in stabilization and re-phosphorylation of dephosphorylated PKC, replenishing the PKC pool. Our model shows how the PKC pool responds to different intensities of extracellular stimuli? We show that blocking PHLPP dephosphorylation replenishes the PKC pool in a dose-dependent manner. This model provides a comprehensive understanding of PKC life cycle regulation.
Investigating the Adipogenic Effects of Different Tissue-Derived Decellularized Matrices

Objective: Decellularized adipose-derived matrix (DAM) can promote adipogenic differentiation and adipose tissue remodeling, but the biological impact of tissue origin on DAM remains unknown. The present study aimed to investigate the effects of tissue origins on the adipogenic capacity of the decellularized matrix by comparing the cellular and tissue responses of DAM versus acellular dermal matrix (ADM). Methods: The in vitro response of adipose-derived stem/stromal cells (ADSCs) to DAM and ADM was characterized by proliferation and differentiation. The in vivo remodeling response was evaluated in the subcutaneous injection model of immunocompromised mice, using histology, protein expression, and transcriptome analysis. Results: Both DAM and ADM exhibited excellent decellularization effects and cytocompatibility. In the absence of exogenous stimuli, DAM could induce adipogenic differentiation of ADSCs compared with ADM. In the animal model, the levels of PDGF, VEGF, and ACRP30 were higher in the DAM groups than in the ADM group, and more neovascularization and extensive adipose tissue remodeling were observed. The mRNA-seq analysis indicated that the DAM implant regulated tissue remodeling by modulating Lat1/2 expression along with Hippo Signaling pathway in the early stage. Conclusion: Tissue origin can influence the biological response of the decellularized matrix. DAM can retain favorable tissue-specific characteristics after the decellularization process and have unique adipogenic effects in vitro and vivo, which can be fully utilized for soft tissue repair and regeneration.
Cyber-Bystander Behavior Among Canadian and Iranian Youth: The Influence of Bystander Type and Relationship to the Perpetrator on Moral Responsibility

The current study examines how social determinants influence the way youth from Canadian and Iranian contexts evaluate and morally disengage as bystanders of cyberbullying. While Iranian culture differs from other individualistic and collectivist cultures, Iranian youth have become just as technologically acculturated as their global peers. Despite this, less is understood about how Iranian youth respond to cyberbullying in comparison to youth from individualistic societies. Participants from Canada (N = 60) and Iran (N = 59) who were between the ages of 8-to-15 years old (N = 119, M = 11.33 years, SD = 1.63 years) read 6 cyberbullying scenarios that varied according to Bystander Relationship to Perpetrator (Acquaintance or Friend) and Bystander Response (Assists Cyberbully, Does Nothing, Defends Victim). After reading each scenario, participants were asked to evaluate the bystander's behavior. They were also asked how they would feel if they were the bystander. Similar to past research, these responses were coded on a continuous scale ranging from morally disengaged to morally responsible. Overall, Canadians were more critical of passive bystander behaviors and more supportive toward defending behaviors compared to Iranians. Iranians were more supportive of the behaviors of bystanders who were friends of perpetrators than Canadians were, and Iranians were more critical toward acquaintances of perpetrators. Significant interactions were also found between participants' country of origin, the bystander's relationship with the perpetrator and the bystander's behavior. Taken together, these findings highlight the importance of differentiating between negative judgments and moral attributions of bystander responses.
Colletotrichum Spp. Diversity Between Leaf Anthracnose and Crown Rot From the Same Strawberry Plant

Leaf anthracnose (LA) and anthracnose crown rot (ACR) represent serious fungal diseases that pose significant threats to strawberry production. To characterize the pathogen diversity associated with above diseases, 100 strawberry plants, including varieties of “Hongjia,” “Zhangji,” and “Tianxianzui,” were sampled from Jiande and Zhoushan, the primary plantation regions of Zhejiang province, China. A total of 309 Colletotrichum isolates were isolated from crown (150 isolates) and leaves (159 isolates) of affected samples. Among these, 100 isolates obtained from the plants showing both LA and CR symptoms were selected randomly for further characterization. Based on the morphological observations combined with phylogenetic analysis of multiple genes (ACT, ITS, CAL, GAPDH, and CHS), all the 100 tested isolates were identified as C. gloeosporioides species complex, including 91 isolates of C. siamense, 8 isolates of C. fructicola causing both LA and ACR, and one isolate of C. aenigma causing ACR. The phenotypic characteristics of these isolated species were investigated using the BIOLOG phenotype MicroArray (PM) and a total of 950 different metabolic phenotype were tested, showing the characteristics among these isolates and providing the theoretical basis for pathogenic biochemistry and metabolism. The pathogenicity tests showed that even the same Colletotrichum species isolated from different diseased tissues (leaves or crowns) had significantly different pathogenicity toward strawberry leaves and crown. C. siamense isolated from diseased leaves (CSLA) was more aggressive than C. siamense isolated from rotted crown (CSCR) during the infection on “Zhangji” leaves. Additionally, C. fructicola isolated from affected leaf (CFLA) caused more severe symptoms on the leaves of four strawberry varieties compared to C. fructicola isolated from diseased crown (CFCR). For crown rot, the pathogenicity of CSCR was higher than that of CSLA.
NEK1 Variants in a Cohort of Italian Patients With Amyotrophic Lateral Sclerosis

Introduction In the last few years, different studies highlighted a significant enrichment of NEK1 loss of function (LoF) variants in amyotrophic lateral sclerosis (ALS), and an additional role for the p.Arg261His missense variant in the disease susceptibility. Several other missense variants have been described so far, whose pathogenic relevance remains however unclear since many of them have been reported in both patients and controls. This study aimed to investigate the presence of NEK1 variants and their correlation with phenotype in a cohort of Italian patients with ALS. Methods We sequenced a cohort of 350 unrelated Italian patients with ALS by next-generation sequencing (NGS) and then we analyzed the clinical features of NEK1 carriers. Results We detected 20 different NEK1 rare variants (four LoF and 16 missense) in 33 unrelated patients with sporadic ALS (sALS). The four LoF variants (two frameshift and two splice-site variants) were all novel. The p.Arg261His missense variant was enriched in the patients’ cohort (p < 0.001). Excluding this variant from counting, the difference in the frequency of NEK1 rare missense variants between patients and controls was not statistically significant. NEK1 carriers had a higher frequency of flail arm (FA) phenotype compared with the other patients of the cohort (29.2% vs. 6.4%). Nine NEK1 carriers (37.5%) also harbored variants in other ALS-related genes. Conclusion This study confirms that NEK1 LoF and p.Arg261. His missense variants are associated with ALS in an Italian ALS cohort and suggests a correlation between the presence of NEK1 variants and FA phenotype.
Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury

Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced β-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome.
Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.
Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.
Behavioural Responses of a Large, Benthic Elasmobranch to Catch-and-Release Angling

Catch-and-release angling is widespread, but the impacts of this practice for captured individuals are understudied, especially among elasmobranchs. Studies on sub-lethal behavioural impacts are particularly sparse, despite their importance for the interpretation of biologging data and for assessments of species’ tolerance to capture. In this study, the behavioural responses of flapper skate (Dipturus intermedius) to catch-and-release angling were described for the first time, using archival observations (depth and temperature) for 21 tag deployment/retrieval events and five recreational angling events that occurred during tagged individuals’ time at liberty from charter vessels off the west coast of Scotland in 2016–17. During capture (8–50 minutes), the changes in depth and temperature experienced by individuals typically exceeded natural variability. Post-release, behavioural change was apparent from visual inspection, regression and functional data analysis of the time series. Immediately following release, movements into deeper water and short periods of low vertical activity (usually 1–2 hours in duration) were common. However, overall average vertical activity was typically around 38% higher in the 12 hours following release than in undisturbed activity. A small number of individuals (n = 3, 14%) exhibited irregular post-release behaviour in the form of rapid, transient re-ascents towards the surface following release. Collectively, the evidence for limited, short-term behavioural changes suggests that flapper skate behaviour is relatively resilient to catch-and-release angling from charter vessels, but irregular post-release behaviour in 14% of individuals is sufficiently notable to indicate that further research is required on the impacts of this practice. This study clearly demonstrates the value of biologging data and behavioural analyses for examining the impacts of disturbance and separating ‘disturbed’ and ‘undisturbed’ behaviours in studies of animal movement.
The Impact of Frame Running on Quality of Life in Young Athletes With Mobility Limitations

Purpose The para-athletic sport Frame Running is developed for persons with neurological impairments causing severe limitations of walking ability. Participating in sports can contribute to a better quality of life (QoL). It is unknown if participation in Frame Running contributes to QoL in children with mobility limitations. This study aims to explore the changes in QoL in children and youth who started Frame Running. Materials and Methods We conducted a cross-sectional study amongst young Frame Running athletes with mobility limitations due to various underlying causes, aged 6–19 years, who are members of one of the Frame Running groups in the Netherlands. For 62 athletes, parents completed the Psychosocial Impact of Assistive Devices Scale (PIADS) questionnaire (subscales: competence, adaptability, and self-esteem). For six athletes, parents were interviewed to obtain more in-depth insight in the perceived changes in the QoL of their children. Results Parents (of 58% boys, mean age 12 years 4 months; SD 3 years 3 months; 52% supported walkers) reported a significant positive change on all three subscales of the PIADS questionnaire since their children started Frame Running. Most change was experienced in the items performance, the ability to participate, happiness and self-confidence. Quotes of the parents who were interviewed elucidated these changes. Conclusion Frame Running increased QoL in young athletes with a mobility limitation. Frame Running may therefore be advised for these children and youth to improve QoL.
Carotid Endarterectomy for the Treatment of Carotid Near-Occlusion With Recurrent Symptoms

Objective Report our preliminary experience of carotid endarterectomy (CEA) for the treatment of carotid near-occlusion (CNO) with recurrent symptoms. Materials and Methods Retrospectively analyze the demographics, treatment detail, and outcomes data of 122 patients with CNO from 2014 to 2020. According to whether distal full collapse exists, patients were classified into the full collapse group and the non-full collapse group. The incidence of death, myocardial infarction, stroke, and other variables were compared between the two groups. Results A total of 122 patients with CNO and recurrent symptoms were enrolled. The demographics were comparable between the two groups. Thirty-day incidence of primary endpoints was 1.85% in the full collapse group and 4.41% in the non-full collapse group. Twelve-month incidence of primary endpoints was 7.41% in the full collapse group and 4.41% in the non-full collapse group. One re-stenosis occurred in the non-full collapse group 8 months after CEA. Conclusion For patients with CNO with recurrent symptoms, CEA is not worse than the results described in historical control groups, despite whether distal full collapse exists. The shunt is important to avoid intraoperative hypoperfusion and postoperative hyperperfusion. The long-term results should be further evaluated.
Ultrafast Laser Direct-Writing of Self-Organized Microstructures in Ge-Sb-S Chalcogenide Glass

The structuring of mid-IR materials, such as chalcogenide glass (ChG), at the micro and nano scales, is of high interest for the fabrication of photonic devices in general, and for spectroscopy applications in particular. One efficient method for producing regular patterns with a sub-micron to micron length scale is through self-organization processes occurring during femtosecond laser exposure. These processes occur in a broad set of materials, where such self-organized patterns can be found not only on the surface but also within the material volume. This study specifically investigates the case of chalcogenide glass (Ge23Sb7S70) exposed to femtosecond laser pulses, inducing pulse-to-pulse nanostructure formation that is correlated to the glass network structural evolution using Raman spectroscopy as well as morphological and elemental microscopy analysis.