Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity

Significance Increasing evidence suggests a role for the gut microbiome in autoimmune diseases, including multiple sclerosis. However, the impact of natural genetic variation in the mammalian host and other underlying mechanisms has been largely overlooked. We used a mouse model of natural genetic diversity to explore interactions between the host and the microbiome. Our results demonstrate a complex interplay between host genotype and gut microbiota in autoimmune disease, and identify a single commensal species capable of modifying disease susceptibility in a genetically susceptible host. Our studies underscore the need to consider host genetics and baseline gut microbiota composition in autoimmunity. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. The etiology of MS is multifactorial, with disease risk determined by genetics and environmental factors. An emerging risk factor for immune-mediated diseases is an imbalance in the gut microbiome. However, the identity of gut microbes associated with disease risk, their mechanisms of action, and the interactions with host genetics remain obscure. To address these questions, we utilized the principal autoimmune model of MS, experimental autoimmune encephalomyelitis (EAE), together with a genetically diverse mouse model representing 29 unique host genotypes, interrogated by microbiome sequencing and targeted microbiome manipulation. We identified specific gut bacteria and their metabolic functions associated with EAE susceptibility, implicating short-chain fatty acid metabolism as a key element conserved across multiple host genotypes. In parallel, we used a reductionist approach focused on two of the most disparate phenotypes identified in our screen. Manipulation of the gut microbiome by transplantation and cohousing demonstrated that transfer of these microbiomes into genetically identical hosts was sufficient to modulate EAE susceptibility and systemic metabolite profiles. Parallel bioinformatic approaches identified Lactobacillus reuteri as a commensal species unexpectedly associated with exacerbation of EAE in a genetically susceptible host, which was functionally confirmed by bacterial isolation and commensal colonization studies. These results reveal complex interactions between host genetics and gut microbiota modulating susceptibility to CNS autoimmunity, providing insights into microbiome-directed strategies aimed at lowering the risk for autoimmune disease and underscoring the need to consider host genetics and baseline gut microbiome composition.
Prevalence of metabolic syndrome among adult population in India: A systematic review and meta-analysis

Objective This review was done to determine the prevalence of metabolic syndrome (MS) among adult general population in India. We also wanted to find the gender, setting, and region-wide distribution of MS in India. Methods We conducted systematic searches in various databases including Medline, ScienceDirect, Cochrane library and Google Scholar from inception until August 2019. We included studies conducted in India reporting the prevalence of MS among adults aged 18 years or more. We used the Newcastle Ottawa scale to assess the quality of included studies. We carried out a meta-analysis with random-effects model and reported pooled prevalence with 95% confidence intervals (CIs). We used the Funnel plot to assess publication biases. Results In total, we analysed 113 data from 111 studies with 133,926 participants. Majority of the included studies (76 out of 111) had low risk of bias. We found significant heterogeneity among the included studies (p<0.001). We also found a symmetrical funnel plot indicating an absence of publication bias. The prevalence of MS among adult population in India was 30% (95%CI: 28%-33%). There was a steady increase in the burden across the age groups from 13% (18–29 years group) to 50% (50–59 years). We also found that people living in urban areas (32%; 95%CI: 29%-36%) had higher prevalence when compared to tribal (28%; 95%CI: 21%-36%) or rural adults (22%; 95%CI: 20%-25%). Gender distribution of MS showed that the females had higher prevalence (35%; 95%CI: 31%-38%) when compared to males 26% (95%CI: 22%-29%). Conclusion Almost one in three adults in India suffer from MS. Females, people living in urban areas and in northeast region had higher prevalence of MS. Development and implementation of policies and protocols for the screening of MS would enable us in early diagnosis and treatment with special focus towards the vulnerable and high-risk groups.
Management of Young Athletes with Asymptomatic Preexcitation—A Review of the Literature

Introduction: The management of young athletes with asymptomatic preexcitation remains a challenge, regardless of the progress we have made in understanding the basis of condition and developing catheter ablation procedures. The risk of sudden death, however small, yet definite, being the first symptom is determining our approach. The aim of the study was to establish the current state of knowledge regarding the management of young athletes diagnosed with asymptomatic preexcitation, by conducting a literature review. Material and methods: A comprehensive literature review was completed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to English language publications using the following search terms: “asymptomatic” or “incidental” and “pre-excitation” or “Wolff–Parkinson–White” or “delta wave” and “athlete” or “sport”. The search was supplemented by hand review of the bibliographies of previous relevant systematic reviews. Results: The search resulted in 85 of abstracts, and the manual search of the bibliographies resulted in 24 additional papers. After careful analysis 10 publications were included in the review. In all but one of the presented papers, the authors used non-invasive methods and then either trans-esophageal or invasive EPS as a way to risk stratify asymptomatic patients. Evidence of rapid conduction through the accessory pathway was considered high risk and prompted sport disqualification. In the analysed reports there were combined: 142 episodes of the life-threatening events (LTE)/sudden death (SCD), of which 56 were reported to occur at rest, 61 during activity and no data were available for 25. Conclusions: athletic activity may impose an increased risk of life-threatening arrhythmias in patients with asymptomatic preexcitation; hence, a separate approach could be considered, especially in patients willing to engage in high-intensity, endurance and competitive sports.
Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Simple Summary Antibody Drug Conjugates are an emerging class of biopharmaceuticals that have seen an impressive increase of attention in the field of cancer therapy. Here, we describe the therapeutic activity of 1959-sss/DM3, a non-internalizing ADC targeting LGALS3BP, a secreted, extracellular vesicles-associated protein expressed by the majority of human cancers, including neuroblastoma. We show that 1959-sss/DM3 treatment can cure mice with established neuroblastoma tumours in pseudometastatic, orthotopic and Patient Derived Xenograft models. Abstract Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy. LGALS3BP is a highly glycosylated protein involved in tumor growth and progression. Studies have shown that LGALS3BP is enriched in extracellular vesicles (EV)s derived by most neuroblastoma cells, where it plays a critical role in preparing a favorable tumor microenvironment (TME) through direct cross talk between cancer and stroma cells. Here, we describe the development of a non-internalizing LGALS3BP ADC, named 1959-sss/DM3, which selectively targets LGALS3BP expressing neuroblastoma. 1959-sss/DM3 mediated potent therapeutic activity in different types of neuroblastoma models. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative. These results offer preclinical proof-of-concept for an ADC targeting exosomal LGALS3BP approach for neuroblastomas.
Timing of maternal and neonatal mortality and morbidity in healthy women and newborns during the postnatal period: a systematic review protocol.

OBJECTIVE To determine the timing of overall and cause-specific maternal and neonatal mortality and severe morbidity in healthy women and newborns during the postnatal period. INTRODUCTION Despite significant focus on improving maternal and neonatal outcomes, many women and newborns continue to die or suffer negative health outcomes within the postnatal period. While the maternal and neonatal mortality and morbidity rates and causes are regularly updated, less is known on when they occur during the postnatal period. INCLUSION CRITERIA This review will consider studies that include healthy women and newborns after birth to six weeks' and four weeks' postnatally, respectively, and includes data regarding time to death or complications. Studies that report solely on high risk women (eg, antenatal complications) or preterm or high-risk newborns will not be included in this review. METHODS The search strategy will aim to locate both published and unpublished studies. After the initial search and removal of duplicates, titles and abstracts of all retrieved studies will be screened and the full text of selected reports will be assessed against the eligibility criteria. The reference list of all studies selected for critical appraisal will be screened for additional relevant studies/reports. Screening, critical appraisal, and data extraction will be completed by two independent reviewers. Findings from the studies/reports will be pooled in statistical meta-analysis or presented in narrative form including tables and figures. SYSTEMATIC REVIEW REGISTRATION NUMBER (FOR PROTOCOLS ONLY) PROSPERO CRD:42020187341.
Dose-Response Effect of Fluoride Dentifrices on De-/Remineralization of Root Dentine in situ

The present study aimed to evaluate the effect of fluoride (F) dentifrice with different F concentrations on root dentine de-/remineralization. Ten healthy volunteers took part in this randomized, double-blinded, cross-over, and split-mouth in situ experimental study. During 4 phases of 7 days, they wore a palatal appliance containing 4 bovine dentine blocks (2 sound and 2 with caries) of 4 × 4 × 2 mm. Treatments were performed with silica-based dentifrices containing 0, 700, 1,300, and 5,000 µg F/g (F as NaF). To provide a cariogenic challenge, a 20% sucrose solution was dripped 3 and 8 times daily on the carious-like and sound blocks, respectively. After each experimental phase, the percentage of surface hardness loss (%SHL) or recovery (%SHR) was calculated and the fluoride concentration in the biofilm was determined. The statistical analysis was performed using ANOVA and the Tukey post hoc test with p at 5%. The relationship between variables was analyzed by linear regression. The results showed a lower %SHL when 5,000 µg F/g dentifrice was used but without a statistically significant difference from the conventional one (1,300 µg F/g). Regarding remineralization and F in biofilms, the high-fluoride dentifrice was expressively superior in mineral replacement on the surface and in the F concentration in the biofilms, respectively, compared to the other 3 products (p < 0.05). Also, a significant linear fit between mineral loss/gain, F in biofilms, and fluoride concentration in the dentifrices could be observed. In conclusion, a dose-response F effect was observed, and the high-fluoride dentifrice was effective in enhancing root dentine remineralization in this short-term in situ study.
In Vitro Activity Analysis of a New Polymyxin, SPR741, Tested in Combination with Antimicrobial Agents against a Challenge Set of Enterobacteriaceae, Including Molecularly Characterized Strains

The activities of azithromycin, fusidic acid, vancomycin, doxycycline, and minocycline were evaluated alone and in combination with SPR741. A total of 202 Escherichia coli and 221 Klebsiella pneumoniae isolates were selected, and they included a genome-sequenced subset (n = 267), which was screened in silico for β-lactamase, macrolide-lincosamide-streptogramin (MLS), and tetracycline (tet) genes. Azithromycin (>16 mg/liter), fusidic acid (>64 mg/liter), vancomycin (>16 mg/liter), and SPR741 (>8 mg/liter) showed off-scale MICs when each was tested alone against all isolates. ABSTRACT The activities of azithromycin, fusidic acid, vancomycin, doxycycline, and minocycline were evaluated alone and in combination with SPR741. A total of 202 Escherichia coli and 221 Klebsiella pneumoniae isolates were selected, and they included a genome-sequenced subset (n = 267), which was screened in silico for β-lactamase, macrolide-lincosamide-streptogramin (MLS), and tetracycline (tet) genes. Azithromycin (>16 mg/liter), fusidic acid (>64 mg/liter), vancomycin (>16 mg/liter), and SPR741 (>8 mg/liter) showed off-scale MICs when each was tested alone against all isolates. MIC50/90 results of 0.5/8 mg/liter, 4/>32 mg/liter, 16/>16 mg/liter, 2/32 mg/liter, and 0.25/4 mg/liter were obtained for azithromycin-SPR741, fusidic acid-SPR741, vancomycin-SPR741, doxycycline-SPR741 and minocycline-SPR741, respectively, against all isolates. Overall, azithromycin-SPR741 (MIC90, 2 to 4 mg/liter) and minocycline-SPR741 (MIC90, 0.5 to 2 mg/liter) showed the lowest MIC90 values against different subsets of E. coli isolates, except for azithromycin-SPR741 (MIC90, 16 mg/liter) against the AmpC and metallo-β-lactamase subsets. In general, minocycline-SPR741 (MIC90, 2 to 8 mg/liter) had the lowest MIC90 against K. pneumoniae isolates producing different groups of β-lactamases. The azithromycin-SPR741 MIC (MIC50/90, 2/32 mg/liter) was affected by MLS genes (MIC50/90 of 0.25/2 mg/liter against isolates without MLS genes), whereas doxycycline-SPR741 (MIC50/90, 0.5/2 versus 8/32 mg/liter) and minocycline-SPR741 (MIC50/90, 0.25/1 versus 1/8 mg/liter) MIC results were affected when tested against isolates carrying tet genes in general. However, minocycline-SPR741 inhibited 88.2 to 92.9% of tet-positive isolates regardless of the tet gene. The azithromycin-SPR741 MIC results (MIC50/90, 1/16 mg/liter) against isolates with enzymatic MLS mechanisms were lower than against those with ribosomal protection (MIC50/90, 16/>32 mg/liter). SPR741 increased the in vitro activity of tested codrugs at different levels and seemed to be dependent on the species and resistance mechanisms of the respective codrug.
Anti-inflammatory and atheroprotective properties of glucagon

Although glucagon has been shown to exert pleiotropic actions in various types of cells and organs through the interaction with its receptor, its pathophysiological role in atherosclerotic cardiovascular disease remains unclear. Here, we examined whether and how glucagon could attenuate the progression of atherosclerotic plaques in apolipoprotein E-deficient mice (ApoE−/−), an animal model of atherosclerosis. Glucagon (138 or 413 nmol/kg/day) or vehicle was infused to mice at 16 weeks of age. After 4-week treatment, vascular samples were collected for histological and RT-PCR analyses. Human monocytic THP-1 cells were pre-incubated with or without a glucagon receptor antagonist L-168049, and then treated with or without glucagon for 7 h. Gene and protein expressions were determined by RT-PCR and western blot analyses, respectively. High-dose glucagon infusion significantly decreased aortic plaque area and volume in ApoE−/− mice, both of which were inversely correlated with plasma glucagon levels. Glucagon infusion also reduced the ratio of pro-inflammatory interleukin-1β to anti-inflammatory interleukin-10 gene expression in aortae. Glucagon receptor was expressed in THP-1 cells, and 1 nM glucagon decreased the ratio of interleukin-1β to interleukin-10 gene expression, which was significantly prevented by L-168049. Our present findings suggest that glucagon could exert atheroprotection partly via its anti-inflammatory property.
PyOIF: Computational tool for modelling of multi-cell flows in complex geometries

A user ready, well documented software package PyOIF contains an implementation of a robust validated computational model for cell flow modelling. The software is capable of simulating processes involving biological cells immersed in a fluid. The examples of such processes are flows in microfluidic channels with numerous applications such as cell sorting, rare cell isolation or flow fractionation. Besides the typical usage of such computational model in the design process of microfluidic devices, PyOIF has been used in the computer-aided discovery involving mechanical properties of cell membranes. With this software, single cell, many cell, as well as dense cell suspensions can be simulated. Many cell simulations include cell-cell interactions and analyse their effect on the cells. PyOIF can be used to test the influence of mechanical properties of the membrane in flows and in membrane-membrane interactions. Dense suspensions may be used to study the effect of cell volume fraction on macroscopic phenomena such as cell-free layer, apparent suspension viscosity or cell degradation. The PyOIF module is based on the official ESPResSo distribution with few modifications and is available under the terms of the GNU General Public Licence. PyOIF is based on Python objects representing the cells and on the C++ computational core for fluid and interaction dynamics. The source code is freely available at GitHub repository, runs natively under Linux and MacOS and can be used in Windows Subsystem for Linux. The communication among PyOIF users and developers is maintained using active mailing lists. This work provides a basic background to the underlying computational models and to the implementation of interactions within this framework. We provide the prospective PyOIF users with a practical example of simulation script with reference to our publicly available User Guide.
ERG11 Polymorphism in Voriconazole-Resistant Candida tropicalis: Weak Role of ERG11 Expression, Ergosterol Content, and Membrane Permeability

Mutations in ERG11 were detected by gene sequencing and amino acid alignment in 18 Candida tropicalis strains with different degrees of sensitivity to voriconazole (VRC). ERG11 expression, sterol content, and membrane permeability were also evaluated. We report three missense mutations in ERG11 that resulted in resistance to VRC. The transcriptional levels of ERG11 as well as the ergosterol content and membrane permeability demonstrated no correlation to only a slight correlation with the obtained MIC values, but the data did suggest a tendency toward such a correlation. ABSTRACT Mutations in ERG11 were detected by gene sequencing and amino acid alignment in 18 Candida tropicalis strains with different degrees of sensitivity to voriconazole (VRC). ERG11 expression, sterol content, and membrane permeability were also evaluated. We report three missense mutations in ERG11 that resulted in resistance to VRC. The transcriptional levels of ERG11 as well as the ergosterol content and membrane permeability demonstrated no correlation to only a slight correlation with the obtained MIC values, but the data did suggest a tendency toward such a correlation.
Metallographic Investigation and Solidification-Structure Modelling of Al Micro Castings

Producing micro-castings trough vacuum investment casting is known to be associated with high cooling rates due to small scale of the castings. High cooling rates together with alloy composition might be the main factors affecting the final metallographic structure of castings’ alloys during the solidification process. When using Al-Si-Mg casting alloys, the size of the dendritic structure can be used for a non-destructive test to assess the mechanical properties and overall quality of the castings. Also the ability of the alloys to be structured by different mechanical and energy assisted processes is highly dependant on their metallographic structure. This paper investigates the structural changes occurring when shifting from conventional size castings to micro-castings. An empirical model describing the degree of dendrite cell refinement as a function of micro-castings aspect ratio is proposed. Additionally, the paper reports the changes in porosity and Si particles morphology observed on micro-castings produced with different flask temperatures. MHV measurements were also performed for different aspect ratio of the cast micro-features.
The Challenge for Rapid Detection of High-Structured Circular RNA: Assay of Potato Spindle Tuber Viroid Based on Recombinase Polymerase Amplification and Lateral Flow Tests

An assay was developed to detect the potato spindle tuber viroid (PSTVd), a dangerous plant pathogen that causes crop damage resulting in economic losses in the potato agriculture sector. The assay was based on the reverse transcription and recombinase polymerase amplification (RT-RPA) of PSTVd RNA coupled with amplicon detection via lateral flow assay (LFA). Primers labeled with fluorescein and biotin were designed for RT-RPA for effective recognition of the loop regions in the high-structured circular RNA of PSTVd. The labeled DNA amplicon was detected using lateral flow test strips consisting of a conjugate of gold nanoparticles with antibodies specific to fluorescein and streptavidin in the test zone. The RT-RPA-LFA detected 106 copies of in vitro transcribed PSTVd RNA in reaction or up to 1:107 diluted extracts of infected plant leaves. The assay took 30 min, including the RT-RPA stage and the LFA stage. The testing of healthy and infected potato samples showed full concordance between the developed RT-RPA-LFA and quantitative reverse transcription polymerase chain reaction (RT-qPCR) and the commercial kit. The obtained results proved the feasibility of using the developed assay to detect PSTVd from a natural source.
Pet-Human Gut Microbiome Host Classifier Using Data from Different Studies

(1) Background: microbiome host classification can be used to identify sources of contamination in environmental data. However, there is no ready-to-use host classifier. Here, we aimed to build a model that would be able to discriminate between pet and human microbiomes samples. The challenge of the study was to build a classifier using data solely from publicly available studies that normally contain sequencing data for only one type of host. (2) Results: we have developed a random forest model that distinguishes human microbiota from domestic pet microbiota (cats and dogs) with 97% accuracy. In order to prevent overfitting, samples from several (at least four) different projects were necessary. Feature importance analysis revealed that the model relied on several taxa known to be key components in domestic cat and dog microbiomes (such as Fusobacteriaceae and Peptostreptococcaeae), as well as on some taxa exclusively found in humans (as Akkermansiaceae). (3) Conclusion: we have shown that it is possible to make a reliable pet/human gut microbiome classifier on the basis of the data collected from different studies.