Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Interictal Epileptiform Discharges in Mesial Temporal Lobe Epilepsy Using Quantitative EEG and Neuroimaging

Objective: Investigate areas of correlation between gray matter volumes by MRI and interictal EEG source maps in subtypes of mesial temporal lobe epilepsy (MTLE). Method: 71 patients and 36 controls underwent 3T MRI and and routine EEG was performed. Voxel-based morphometry (VBM) was used for gray matter analysis and analysis of interictal discharge sources for quantitative EEG. Voxel-wise correlation analysis was conducted between the gray matter and EEG source maps in MTLE subtypes. Results: The claustrum was the main structure involved in the individual source analysis. Twelve patients had bilateral HA, VBM showed bilateral hippocampal. Twenty-one patients had right HA, VBM showed right hippocampal and thalamic atrophy and negatively correlated involving the right inferior frontal gyrus and insula. Twenty-two patients had left HA, VBM showed left hippocampal atrophy and negatively correlated involving the left temporal lobe and insula. Sixteen patients had MTLE without HA, VBM showed middle cingulate gyrus atrophy and were negatively correlated involving extra-temporal regions, the main one located in postcentral gyrus. Conclusions: Negative correlations between gray matter volumes and EEG source imaging. Neuroanatomical generators of interictal discharges are heterogeneous and vary according to MTLE subtype. Significance: These findings suggest different pathophysiological mechanisms among patients with different subtypes of MTLE.
Effects and Moderators of Computer-Based Training on Children's Executive Functions: A Systematic Review and Meta-Analysis

Computer-based training has attracted increasing attention from researchers in recent years. Several studies have found that computer-based training resulted in improved executive functions (EFs) in adults. However, it remains controversial whether children can benefit from computer-based training and what moderator could influence the training effects. The focus of the present meta-analysis was to examine the effects of computer-based training on EFs in children: working memory, cognitive flexibility, and inhibitory control. A thorough search of published work yielded a sample of 36 studies with 216 effect sizes. The results indicated that computer-based training showed moderate training effects on improving EFs in children (g = 0.35, k = 36, p < 0.001), while training effects of working memory were significantly higher. Furthermore, we found near-transfer effects were marginally significantly higher than far-transfer effects. The standard training method was significantly more effective than training with game elements. In computer-based training, typically developing children had significantly better training effects than atypically developing children. Some additional factors, such as the number of training sessions and age, also modulated the training effects. In conclusion, the present study investigated the effects and moderators of computer-based training for children's EFs. The results provided evidence that computer-based training (especially standard training) may serve as an efficient way to improve EFs in children (especially typically developing individuals). We also discussed some directions for future computer-based training studies.
Association of Odor Identification Ability With Amyloid-β and Tau Burden: A Systematic Review and Meta-Analysis

Background: The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear. Objective: This meta-analysis aimed to examine the associations between OI and Aβ and tau burden. Methods: Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aβ or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups. Results: Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aβ PET, one involved tau PET (N = 26), and four involved CSF Aβ or tau (N = 345). OI was negatively associated with Aβ PET in the mixed (r = −0.25, P = 0.008) and cognitively normal groups (r = −0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aβ42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET. Conclusion: The associations between OI ability and Aβ and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.
Beneficial Effect of Systemic Allogeneic Adipose Derived Mesenchymal Cells on the Clinical, Inflammatory and Immunologic Status of a Patient With Recessive Dystrophic Epidermolysis Bullosa: A Case Report

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable inherited mucocutaneous fragility disorder characterized by recurrent blisters, erosions, and wounds. Continuous blistering triggers overlapping cycles of never-ending healing and scarring commonly evolving to chronic systemic inflammation and fibrosis. The systemic treatment with allogeneic mesenchymal cells (MSC) from bone marrow has previously shown benefits in RDEB. MSC from adipose tissue (ADMSC) are easier to isolate. This is the first report on the use of systemic allogeneic ADMSC, correlating the clinical, inflammatory, and immunologic outcomes in RDEB indicating long-lasting benefits. We present the case of an RDEB patient harboring heterozygous biallelic COL7A1 gene mutations and with a diminished expression of C7. The patient presented with long-lasting refractory and painful oral ulcers distressing her quality of life. Histamine receptor antagonists, opioid analgesics, proton-pump inhibitors, and low-dose tricyclic antidepressants barely improved gastric symptoms, pain, and pruritus. Concomitantly, allogeneic ADMSC were provided as three separate intravenous injections of 106 cells/kg every 21 days. ADMSC treatment was well-tolerated. Improvements in wound healing, itch, pain and quality of life were observed, maximally at 6–9 months post-treatment, with the relief of symptoms still noticeable for up to 2 years. Remarkably, significant modifications in PBL participating in both the innate and adaptive responses, alongside regulation of levels of profibrotic factors, MCP-1/CCL2 and TGF-β, correlated with the health improvement. This treatment might represent an alternative for non-responding patients to conventional management. It seems critical to elucidate the paracrine modulation of the immune system by MSC for their rational use in regenerative/immunoregulatory therapies.
The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.
Gilles de la Tourette Syndrome—A Disorder of Action-Perception Integration

Gilles de la Tourette syndrome is a multifaceted and complex neuropsychiatric disorder. Given that tics as motor phenomena are the defining and cardinal feature of Tourette syndrome, it has long been conceptualized as a motor/movement disorder. However, considering premonitory urges preceding tics, hypersensitivity to external stimuli and abnormalities in sensorimotor integration perceptual processes also seem to be relevant in the pathophysiology of Tourette syndrome. In addition, tic expression depends on attention and tics can, at least partly and transiently, be controlled, so that cognitive processes need to be considered as well. Against this background, explanatory concepts should encompass not only the motor phenomenon tic but also perceptual and cognitive processes. Representing a comprehensive theory of the processing of perceptions and actions paying particular attention to their interdependency and the role of cognitive control, the Theory of Event Coding seems to be a suitable conceptual framework for the understanding of Tourette syndrome. In fact, recent data suggests that addressing the relation between actions (i.e., tics) and perceptions (i.e., sensory phenomena like premonitory urges) in the context of event coding allows to gaining relevant insights into perception-action coding in Tourette syndrome indicating that perception action binding is abnormally strong in this disorder.
Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches

Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of Eryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Both in-vitro and in-vivo assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of E. caeruleum (Ec.Cr) and its sub-fractions [i.e., n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50 of 437 μg/ml in comparison to the standard acarbose (IC50 25 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50 values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and H2O2 respectively. Based on the in-vitro potential of Ec.Chf, this was subjected to the in-vivo model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that Eryngium caeruleum is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of Eryngium caeruleum into active sites of the homology model of α-glucosidase.
Identification of Aedes (Diptera: Culicidae) Species and Arboviruses Circulating in Arauca, Eastern Colombia

The identification of vector species and their natural infection with arboviruses results in important data for the control of their transmission. However, for the eastern region of Colombia, this information is limited. Therefore, this study morphologically and molecularly identified species of the genus Aedes and the detection of arboviruses (Dengue, Chikungunya, Zika, and Mayaro) in female mosquitoes (individually) present in three municipalities (Saravena, Arauquita, and Tame) by amplifying the genetic material using RT-PCR (reverse transcriptase polymerase chain reaction) in the department of Arauca, eastern Colombia. Inconsistencies between morphological and molecular identification were detected in 13 individuals with Aedes albopictus initially determined as Aedes aegypti based on morphology (n = 13). Molecular identification showed the simultaneous presence of A. aegypti (n = 111) and A. albopictus (n = 58) in the urban municipalities of Saravena and Arauquita. These individuals were naturally infected with Dengue virus type 1 (DENV-1) and Chikungunya virus (CHIKV). The most frequent arbovirus was DENV-1 with an infection rate of 40.7% (11/27) for A. aegypti and 39.7% (23/58) for A. albopictus, which was followed by CHIKV with an infection rate of 1.8% for A. aegypti (2/111) and 6.9% for A. albopictus (4/58). Additionally, a mixed infection of DENV-1 and CHIKV was obtained in 4.5% of A. aegypti (5/111). Zika virus (ZIKV) and Mayaro virus (MAYV) infections were not detected. This study found that barcoding (fragment gene COI) is a successful method for identifying Aedes species. Additionally, we recommend the individual processing of insects as a more accurate strategy for arboviruses detection since the infection rate is obtained and co-infection between DENV-1 and CHIKV is also possible.
Cadmium and Copper Removal From Aqueous Solutions Using Chitosan-Coated Gasifier Biochar

Gasifier Biochar (GBC) and Chitosan-Coated Gasifier Biochar (CGBC) derived from pine wood was used to remove Cu2+ and Cd2+ from water. Chitosan-Coated Gasifier Biochar was made by mixing GBC with aqueous acetic acid chitosan solution followed by treatment with NaOH. Both CGBC and GBC were characterized using FT-IR, scanning electron microscopy, surface area measurement (BET), elemental analysis, thermogravimetric analysis, and point of zero charge. Chitosan accounts for 25% of the weight of the CGBC. Thermogravimetric analysis showed chitosan decomposes sharply at 225–270°C and then more slowly thereafter. The BET surface areas of GBC and CGBC were 34.1 and 4.61 m2/g, respectively. Batch adsorption studies performed at pH values of 2–5 followed Cu2+ and Cd2+ adsorption quantitatively using atomic absorption spectrophotometry. Sorption was evaluated using the Freundlich, Langmuir, and Sips isotherm models. Cu2+ adsorption on CGBC fit best the Sips model (capacity 111.5 mg/g) and Cd2+ with the Langmuir model (capacity 85.8 mg/g). Langmuir adsorption capacities on GBC were 83.7 and 68.6 mg/g for Cu2+ and Cd2+ respectively. CGBC removed more Cu2+(25.8 mg/g) and Cd2+(17.2 mg/g) than GBC because chitosan modification generates amine coordination sites that enhance metal adsorption. Adsorption on CGBC and GBC of both metal ions followed pseudo-second order kinetics.
Health, Wellness, and Place Attachment During and Post Health Pandemics

Therapeutic landscapes encapsulate healing and recovery notions in natural and built environmental settings. Tourists’ perceptions determine their decision making of health and wellness tourism consumption. Researchers struggle with the conceptualization of the term ‘therapeutic landscapes’ across disciplines. Drawing on extant literature searched in nine databases, this scoping review identifies different dimensions of therapeutic landscapes. Out of identified 178 literature sources, 124 met the inclusion criteria of identified keywords. We review the contribution and the potential of environmental psychology in understanding tourist behavior to promote health and wellness tourism destinations in a post COVID-19 context. We develop and propose a conceptual framework comprising: (1) perceived goodness of therapeutic landscapes, (2) health and wellness consumption, (3) COVID-19 pandemic perceived health and wellness risk, (4) place attachment, and (5) re-visitation. We propose measurement scales and discuss implications and major issues in the immediate and post the COVID-19 pandemic to inform future research.
Nonverbal Immediacy Mediates the Relationship Between Interpersonal Motives and Belongingness

While belongingness is a predictor of mental and physical health, the lack of social bonds is an issue for many people in occidental countries. This issue calls for global and affordable solutions. In this study, we notably investigated (a) the presumed positive relationships between agentic and communal interactional motives and belongingness, and (b) the mediating role of self-reported non-verbal immediacy—an indicator of availability to interact—in these relationships. Cross-sectional and longitudinal data were collected by means of questionnaires to test these hypotheses (NCrossectional = 344; NLongitudinal = 126) using the General Belongingness Scale, the Non-verbal Immediacy Scale, and the Bem Sex Role Inventory. Results supported the hypotheses: Interpersonal motives and non-verbal immediacy are associated cross-sectionally to belongingness, non-verbal immediacy mediates the interpersonal motives—belongingness relationship and positive changes in non-verbal immediacy are also related to increased belongingness. Practical and research implications are discussed.
Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation

The pathobiology of atherosclerotic disease requires further elucidation to discover new approaches to address its high morbidity and mortality. To date, over 17 million cardiovascular-related deaths have been reported annually, despite a multitude of surgical and nonsurgical interventions and advances in medical therapy. Existing strategies to prevent disease progression mainly focus on management of risk factors, such as hypercholesterolemia. Even with optimum current medical therapy, recurrent cardiovascular events are not uncommon in patients with atherosclerosis, and their incidence can reach 10–15% per year. Although treatments targeting inflammation are under investigation and continue to evolve, clinical breakthroughs are possible only if we deepen our understanding of vessel wall pathobiology. Vascular smooth muscle cells (VSMCs) are one of the most abundant cells in vessel walls and have emerged as key players in disease progression. New technologies, including in situ hybridization proximity ligation assays, in vivo cell fate tracing with the CreERT2-loxP system and single-cell sequencing technology with spatial resolution, broaden our understanding of the complex biology of these intriguing cells. Our knowledge of contractile and synthetic VSMC phenotype switching has expanded to include macrophage-like and even osteoblast-like VSMC phenotypes. An increasing body of data suggests that VSMCs have remarkable plasticity and play a key role in cell-to-cell crosstalk with endothelial cells and immune cells during the complex process of inflammation. These are cells that sense, interact with and influence the behavior of other cellular components of the vessel wall. It is now more obvious that VSMC plasticity and the ability to perform nonprofessional phagocytic functions are key phenomena maintaining the inflammatory state and senescent condition and actively interacting with different immune competent cells.
Long-Term Outcomes of a Phase I Study With UV1, a Second Generation Telomerase Based Vaccine, in Patients With Advanced Non-Small Cell Lung Cancer

Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials. Eighteen non-HLA-typed patients with stage III/IV NSCLC with no evidence of progression after prior treatments, were enrolled in a phase I dose-escalation study of UV1 vaccination with GM-CSF as adjuvant, evaluating safety, immune response, and long-term clinical outcome. Treatment with UV1 was well tolerated with no serious adverse events observed. Seventeen patients were evaluable for tumor response; 15 patients had stable disease as best response. The median progression free survival (PFS) was 10.7 months, and the median overall survival (OS) was 28.2 months. The OS at 4 years was 39% (7/18). Five patients are alive (median survival 5.6 years), and none of these are known to have received checkpoint therapy after vaccination. UV1 induced specific T-cell responses in the majority (67%) of patients. Immune responses were dynamic and long lasting. Both immune response (IR) and OS were dose related. More patients in the highest UV1 dosage group (700 μg) developed IRs compared to the other groups, and the IRs were stronger and occurred earlier. Patients in this group had a 4-year OS of 83%. The safety and clinical outcome data favor 700 μg as the preferred UV1 dose in this patient population. These results provide a rationale for further clinical studies in NSCLC with UV1 vaccination in combination with immune checkpoint blockade. Clinical Trial Registration https://www.clinicaltrials. gov, identifier NCT0178909.