Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole Exome Sequencing Identifies Novel De Novo Variants Interacting with Six Gene Networks in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a highly heritable condition caused by a combination of environmental and genetic factors such as de novo and inherited variants, as well as rare or common variants among hundreds of related genes. Previous genome-wide association studies have identified susceptibility genes; however, most ASD-associated genes remain undiscovered. This study aimed to examine rare de novo variants to identify genetic risk factors of ASD using whole exome sequencing (WES), functional characterization, and genetic network analyses of identified variants using Korean familial dataset. We recruited children with ASD and their biological parents. The clinical best estimate diagnosis of ASD was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5TM), using comprehensive diagnostic instruments. The final analyses included a total of 151 individuals from 51 families. Variants were identified and filtered using the GATK Best Practices for bioinformatics analysis, followed by genome alignments and annotation to the reference genome assembly GRCh37 (liftover to GRCh38), and further annotated using dbSNP 154 build databases. To evaluate allele frequencies of de novo variants, we used the dbSNP, gnomAD exome v2.1. 1, and genome v3.0. We used Ingenuity Pathway Analysis (IPA, Qiagen) software to construct networks using all identified de novo variants with known autism-related genes to find probable relationships. We identified 36 de novo variants with potential relations to ASD; 27 missense, two silent, one nonsense, one splice region, one splice site, one 5′ UTR, and one intronic SNV and two frameshift deletions. We identified six networks with functional relationships. Among the interactions between de novo variants, the IPA assay found that the NF-κB signaling pathway and its interacting genes were commonly observed at two networks. The relatively small cohort size may affect the results of novel ASD genes with de novo variants described in our findings. We did not conduct functional experiments in this study. Because of the diversity and heterogeneity of ASD, the primary purpose of this study was to investigate probable causative relationships between novel de novo variants and known autism genes. Additionally, we based functional relationships with known genes on network analysis rather than on statistical analysis. We identified new variants that may underlie genetic factors contributing to ASD in Korean families using WES and genetic network analyses. We observed novel de novo variants that might be functionally linked to ASD, of which the variants interact with six genetic networks.
X-ray Absorption Spectroscopy (XAS) Study of the Hydration Structure of Yttrium(III) Cations in Liquid and Glassy States:??? Eight or Nine-Fold Coordination?

An extensive X-ray absorption spectroscopy study has been carried out on 0.005 to 2.0 molal YBr3·6H2O aqueous solutions in liquid and glassy states to determine the solvation structure of the yttrium(III) cations in aqueous dilute and concentrate solutions. The existence of a symmetric polyhedron of water molecules around yttrium(III) cations at 2.35 A, as well as the absence of contact Y−Br ion pairs, in all of the investigated solutions was deduced from the EXAFS analysis. The existence of a multiple electron transition of nonnegligible intensity within the EXAFS region of the spectra has been proven. This transition induces an overestimation in the coordination numbers derived from the EXAFS analysis so that we have extended our study to the XANES part of the spectra. We have performed detailed computations of the XANES spectra by using a one-electron full-multiple-scattering code. This analysis shows unambiguously that the eight water molecules surround yttrium(III) cations at 2.35 A forming a symmetr.
Bimetallic Ni-Based Catalysts for CO2 Methanation: A Review

CO2 methanation has recently emerged as a process that targets the reduction in anthropogenic CO2 emissions, via the conversion of CO2 captured from point and mobile sources, as well as H2 produced from renewables into CH4. Ni, among the early transition metals, as well as Ru and Rh, among the noble metals, have been known to be among the most active methanation catalysts, with Ni being favoured due to its low cost and high natural abundance. However, insufficient low-temperature activity, low dispersion and reducibility, as well as nanoparticle sintering are some of the main drawbacks when using Ni-based catalysts. Such problems can be partly overcome via the introduction of a second transition metal (e.g., Fe, Co) or a noble metal (e.g., Ru, Rh, Pt, Pd and Re) in Ni-based catalysts. Through Ni-M alloy formation, or the intricate synergy between two adjacent metallic phases, new high-performing and low-cost methanation catalysts can be obtained. This review summarizes and critically discusses recent progress made in the field of bimetallic Ni-M (M = Fe, Co, Cu, Ru, Rh, Pt, Pd, Re)-based catalyst development for the CO2 methanation reaction.
Chest Expansion and Lung Function for Healthy Subjects and Individuals With Pulmonary Disease

BACKGROUND: The purposes of this study were to verify the correlation between chest expansion and lung function within a larger sample of subjects composed of both healthy subjects and subjects affected by pulmonary disease, and to verify the influence of age, body mass index, and gender on chest expansion. METHODS: Adults were recruited prospectively when they visited the lung function lab. Chest expansion was measured with a measuring tape at 2 different levels of the rib cage by 1 blinded examiner. Spirometry was performed for each subject. RESULTS: Data from 251 subjects between 18 and 88 y old were collected and analyzed. Among the analyzed subjects, mean upper and lower chest expansion were 4.82 ± 1.84 cm and 3.99 ± 2.15 cm, respectively. A significant but poor correlation was found between both chest expansion and all lung function parameters (total lung capacity, FVC, and FEV1) (P = .01). Negative significant correlations were found between chest expansion and age as well as body mass index. The difference in upper chest expansion between obese and nonobese subjects was not statistically significant, but the difference in lower chest expansion was significant for these 2 groups. Finally, upper and lower chest expansion were not different between males and females. CONCLUSIONS: Based on these results, one cannot validate the use of chest expansion measurement to define lung function. In centers that have easy access to more precise and complete methods to measure lung function, the measurement of chest expansion for diagnostic purposes seems to be archaic. Additionally, age and body mass index are 2 parameters that can influence chest expansion.
Prunus spinosa Extract Loaded in Biomimetic Nanoparticles Evokes In Vitro Anti-Inflammatory and Wound Healing Activities

Prunus spinosa fruits (PSF) contain different phenolic compounds showing antioxidant and anti-inflammatory activities. Innovative drug delivery systems such as biomimetic nanoparticles could improve the activity of PSF extract by promoting (i) the protection of payload into the lipidic bilayer, (ii) increased accumulation to the diseased tissue due to specific targeting properties, (iii) improved biocompatibility, (iv) low toxicity and increased bioavailability. Using membrane proteins extracted from human monocyte cell line THP-1 cells and a mixture of phospholipids, we formulated two types of PSF-extract-loaded biomimetic vesicles differing from each other for the presence of either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG). The biological activity of free extract (PSF), compared to both types of extract-loaded vesicles (PSF-DOPCs and PSF-DOPGs) and empty vesicles (DOPCs and DOPGs), was evaluated in vitro on HUVEC cells. PSF-DOPCs showed preferential incorporation of the extract. When enriched into the nanovesicles, the extract showed a significantly increased anti-inflammatory activity, and a pronounced wound-healing effect (with PSF-DOPCs more efficient than PSF-DOPGs) compared to free PSF. This innovative drug delivery system, combining nutraceutical active ingredients into a biomimetic formulation, represents a possible adjuvant therapy for the treatment of wound healing. This nanoplatform could be useful for the encapsulation/enrichment of other nutraceutical products with short stability and low bioavailability.
Mobile Technologies to Promote Physical Activity during Cardiac Rehabilitation: A Scoping Review

Promoting regular physical activity (PA) and improving exercise capacity are the primary goals of cardiac rehabilitation (CR). Mobile technologies (mTechs) like smartphones, smartwatches, and fitness trackers might help patients in reaching these goals. This review aimed to scope current scientific literature on mTechs in CR to assess the impact on patients’ exercise capacity and to identify gaps and future directions for research. PubMed, CENTRAL, and CDSR were systematically searched for randomized controlled trials (RCTs). These RCTs had to utilize mTechs to objectively monitor and promote PA of patients during or following CR, aim at improvements in exercise capacity, and be published between December 2014 and December 2019. A total of 964 publications were identified, and 13 studies met all inclusion criteria. Home-based CR with mTechs vs. outpatient CR without mTechs and outpatient CR with mTechs vs. outpatient CR without mTechs did not lead to statistically significant differences in exercise capacity. In contrast, outpatient CR followed by home-based CR with mTechs led to significant improvement in exercise capacity as compared to outpatient CR without further formal CR. Supplying patients with mTechs may improve exercise capacity. To ensure that usage of and compliance with mTechs is optimal, a concentrated effort of CR staff has to be achieved. The COVID-19 pandemic has led to an unprecedented lack of patient support while away from institutional CR. Even though mTechs lend themselves as suitable assistants, evidence is lacking that they can fill this gap.
Anti-Inflammatory and Neuromodulatory Effects Induced by Tanacetum parthenium Water Extract: Results from In Silico, In Vitro and Ex Vivo Studies

Tanacetum parthenium (feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial T. parthenium water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K+ 60 mM Krebs-Ringer buffer and treated with T. parthenium water extract. The prostaglandin E2 (PGE2) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1β gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE2 release and IL-1β gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of T. parthenium water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.
Calming the (Cytokine) Storm: Dimethyl Fumarate as a Therapeutic Candidate for COVID-19

COVID-19 has rapidly spread worldwide and incidences of hospitalisation from respiratory distress are significant. While a vaccine is in the pipeline, there is urgency for therapeutic options to address the immune dysregulation, hyperinflammation and oxidative stress that can lead to death. Given the shared pathogenesis of severe cases of COVID-19 with aspects of multiple sclerosis and psoriasis, we propose dimethyl fumarate as a viable treatment option. Currently approved for multiple sclerosis and psoriasis, dimethyl fumarate is an immunomodulatory, anti-inflammatory and anti-oxidative drug that could be rapidly implemented into the clinic to calm the cytokine storm which drives severe COVID-19.
Quantitative Color Fundus Autofluorescence in Patients with Diabetes Mellitus

A new short wavelength confocal blue-light 450 nm-fundus autofluorescence (color-FAF) allows for visualization of minor fluorophores (e.g., advanced glycation end products, AGEs), besides lipofuscin. The aim of the present pilot study was to quantitatively evaluate color-FAF in patients with diabetes mellitus (DM) and to correlate these data with different stages of retinal disease severity. Optical coherence tomography and color-FAF images of 193 patients/eyes and 18 controls were analyzed using a custom software for quantification of the long (red) and short (green) wavelength components of the emission spectrum (REFC/GEFC). Measurements were performed in nine quadrants of the 6-mm ETDRS macular grid. Foveal GEFC and REFC intensities were higher in patients with DM compared to controls (p = 0.015 and p = 0.006 respectively) and in eyes with center involving diabetic macular edema (DME) compared to eyes without DME (p < 0.001). A positive correlation was found between GEFC and REFC intensities and central retinal thickness, r = 0.37 (p < 0.001) and r = 0.42 (p < 0.001), respectively. No differences were found in color-FAF among different DR severity groups. Quantitative color-FAF could become helpful for the metabolic evaluation of retina in patients with DM and in DME; however, further histologic and immunohistochemical studies on distribution of different retinal fluorophores in DM are needed to better understand its role.
Omega-3 fatty acid supplementation is associated with favorable outcomes in patients with sepsis: an updated meta-analysis

Objectives The efficacy of omega-3 fatty acids in the treatment of sepsis is controversial. We conducted an updated meta-analysis to clarify the efficacy of omega-3 fatty acids in patients with sepsis. Methods PubMed, EMBASE, and the Cochrane Library were searched for randomized clinical trials (RCTs) on omega-3 fatty acid supplementation in adults with sepsis. Results Twenty eligible RCTs involving 1514 patients were included in the meta-analysis. Omega-3 fatty acid supplementation was linked to reductions of mortality (I2 = 0, relative risk [RR] = 0.82, 95% confidence interval [CI] = 0.69–0.97), the duration of mechanical ventilation (DMV; I2 = 74%, weighted mean difference [WMD] = −2.20, 95% CI = −4.00 to −0.40), and intensive care unit (ICU) length of stay (LOS; I2 = 91%, WMD = −3.86, 95% CI = −5.72 to −2.01). Subgroup analysis illustrated that mortality was significantly reduced in patients with sepsis and gastrointestinal dysfunction (RR = 0.5, 95% CI = 0.29–0.86, I2 = 0). Conclusion Omega-3 fatty acid supplementation might be associated with reduced mortality in patients with sepsis, especially those with gastrointestinal dysfunction. Furthermore, omega-3 fatty acid administration could shorten DMV and ICU LOS.
Severity of Experimental Autoimmune Uveitis Is Reduced by Pretreatment with Live Probiotic Escherichia coli Nissle 1917

Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer’s patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut–eye axis.
Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.
Decision Rules Construction: Algorithm Based on EAV Model

In the paper, an approach for decision rules construction is proposed. It is studied from the point of view of the supervised machine learning task, i.e., classification, and from the point of view of knowledge representation. Generated rules provide comparable classification results to the dynamic programming approach for optimization of decision rules relative to length or support. However, the proposed algorithm is based on transformation of decision table into entity–attribute–value (EAV) format. Additionally, standard deviation function for computation of averages’ values of attributes in particular decision classes was introduced. It allows to select from the whole set of attributes only these which provide the highest degree of information about the decision. Construction of decision rules is performed based on idea of partitioning of a decision table into corresponding subtables. In opposite to dynamic programming approach, not all attributes need to be taken into account but only these with the highest values of standard deviation per decision classes. Consequently, the proposed solution is more time efficient because of lower computational complexity. In the framework of experimental results, support and length of decision rules were computed and compared with the values of optimal rules. The classification error for data sets from UCI Machine Learning Repository was also obtained and compared with the ones for dynamic programming approach. Performed experiments show that constructed rules are not far from the optimal ones and classification results are comparable to these obtained in the framework of the dynamic programming extension.
Topical exposure to triclosan inhibits Th1 immune responses and reduces T cells responding to influenza infection in mice

Healthcare workers concurrently may be at a higher risk of developing respiratory infections and allergic disease, such as asthma, than the general public. Increased incidence of allergic diseases is thought to be caused, in part, due to occupational exposure to chemicals that induce or augment Th2 immune responses. However, whether exposure to these chemical antimicrobials can influence immune responses to respiratory pathogens is unknown. Here, we use a BALB/c murine model to test if the Th2-promoting antimicrobial chemical triclosan influences immune responses to influenza A virus. Mice were dermally exposed to 2% triclosan for 7 days prior to infection with a sub-lethal dose of mouse adapted PR8 A(H1N1) virus (50 pfu); triclosan exposure continued until 10 days post infection (dpi). Infected mice exposed to triclosan did not show an increase in morbidity or mortality, and viral titers were unchanged. Assessment of T cell responses at 10 dpi showed a decrease in the number of total and activated (CD44hi) CD4+ and CD8+ T cells at the site of infection (BAL and lung) in triclosan exposed mice compared to controls. Influenza-specific CD4+ and CD8+ T cells were assessed using MHCI and MHCII tetramers, with reduced populations, although not reaching statistical significance at these sites following triclosan exposure. Reductions in the Th1 transcription factor T-bet were seen in both activated and tetramer+ CD4+ and CD8+ T cells in the lungs of triclosan exposed infected mice, indicating reduced Th1 polarization and providing a potential mechanism for numerical reduction in T cells. Overall, these results indicate that the immune environment induced by triclosan exposure has the potential to influence the developing immune response to a respiratory viral infection and may have implications for healthcare workers who may be at an increased risk for developing infectious diseases.
Tracking the Genetic Susceptibility Background of B-Cell Non-Hodgkin’s Lymphomas from Genome-Wide Association Studies

B-cell non-Hodgkin’s lymphoma (NHL) risk associations had been mainly attributed to family history of the disease, inflammation, and immune components including human leukocyte antigen (HLA) genetic variations. Nevertheless, a broad range of genome-wide association studies (GWAS) have shed light into the identification of several genetic variants presumptively associated with B-cell NHL etiologies, survival or shared genetic risk with other diseases. The present review aims to overview HLA structure and diversity and summarize the evidence of genetic variations, by GWAS, on five NHL subtypes (diffuse large B-cell lymphoma DLBCL, follicular lymphoma FL, chronic lymphocytic leukemia CLL, marginal zone lymphoma MZL, and primary central nervous system lymphoma PCNSL). Evidence indicates that the HLA zygosity status in B-cell NHL might promote immune escape and that genome-wide significance variants can give biological insight but also potential therapeutic markers such as WEE1 in DLBCL. However, additional studies are needed, especially for non-DLBCL, to replicate the associations found to date.