Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Cases of Oculofaciocardiodental (OFCD) Syndrome due to X-Linked BCOR Mutations Presenting with Infantile Hemangiomas: Phenotypic Overlap with PHACE Syndrome

Background Oculofaciocardiodental (OFCD) syndrome is due to mutations in BCOR (BCL-6 corepressor). OFCD has phenotypic overlaps with PHACE syndrome (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac defects, Eye anomalies). Infantile hemangiomas are a key diagnostic criterion for PHACE, but not for OFCD. A previous study reported two cases of infantile hemangiomas in OFCD, but the authors could not exclude chance association. Case Presentation We describe two novel cases of female patients (one initially diagnosed with PHACE syndrome), both of whom had infantile hemangiomas. Ophthalmological findings were consistent with oculofaciocardiodental (OFCD) syndrome. Upon genetic testing, these two females were determined to have X-linked BCOR mutations confirming OFCD syndrome diagnoses. Conclusion These case reports add support to the hypothesis that infantile hemangiomas may be a feature of OFCD. BCOR may potentially be within a pathway of genes involved in PHACE syndrome and/or in infantile hemangioma formation.
Preparation of an Antidanofloxacin Monoclonal Antibody and Development of Immunoassays for Detecting Danofloxacin in Meat

Danofloxacin (DAF), a third-generation fluroquinolone (FQ), is widely used as a broad-spectrum antibacterial drug to prevent diseases in livestock and poultry. In this study, a highly specific and sensitive monoclonal antibody (mAb) against DAF was prepared. Also, the mAb was used for the indirect competitive enzyme-linked immunosorbent assay (icELISA) and immunochromatographic strip for the detection of DAF residues in meat. The IC50 of the icELISA based on this mAb was 1.39 ng/mL, and the limit of detection was 0.2 ng/mL. According to the cross-reactivity (CR) experiment, the ELISA that we developed was highly specific and had low CR with other FQ analogues. Moreover, the cut-off of the immunochromatographic strip developed for detecting DAF in meat was 5 ng/mL. Overall, the developed ELISA and immunochromatographic strip based on the prepared mAb were proved reliable for the rapid detection of DAF in meat and can be considered as effective screening methods for food safety and quality management.
Mental state space visualization for interactive modeling of personalized BCI control strategies

Objective. Numerous studies in the area of BCI are focused on the search for a better experimental paradigm—a set of mental actions that a user can evoke consistently and a machine can discriminate reliably. Examples of such mental activities are motor imagery, mental computations, etc. We propose a technique that instead allows the user to try different mental actions in the search for the ones that will work best. Approach. The system is based on a modification of the self-organizing map (SOM) algorithm and enables interactive communication between the user and the learning system through a visualization of user’s mental state space. During the interaction with the system the user converges on the paradigm that is most efficient and intuitive for that particular user. Main results. Results of the two experiments, one allowing muscular activity, another permitting mental activity only, demonstrate soundness of the proposed method and offer preliminary validation of the performance improvement over the traditional closed-loop feedback approach. Significance. The proposed method allows a user to visually explore their mental state space in real time, opening new opportunities for scientific inquiry. The application of this method to the area of brain–computer interfaces enables more efficient search for the mental states that will allow a user to reliably control a BCI system.
Impaired option generation underpins deficient reasoning in Parkinson’s disease patients with apathy

Abstract Apathy is a debilitating neurological syndrome known to be associated with executive dysfunction, particularly affecting abstract reasoning. However, the underlying cognitive mechanism remains unclear. Recently, it has been proposed that one cognitive process disrupted in apathy is option generation. We investigated whether impaired option generation could explain deficient reasoning in apathy. Data was retrospectively analyzed from patients with Parkinson’s disease (n = 51) who had completed the Lille Apathy Rating Scale and the Brixton Spatial Anticipation Task (Brixton), a measure of inductive reasoning. A hierarchical regression analysis showed that higher levels of apathy predicted poorer Brixton performance. Detailed analysis of Brixton errors was conducted to investigate the cognitive process underlying this relationship. Additional hierarchical regression analyses showed that apathy specifically predicted Brixton errors associated with a failure to generate either correct or incorrect rules. These findings suggest that deficient reasoning in apathy may be underpinned by impaired option generation.
Body mass index and other risk factors for kidney cancer in men: a cohort study in Lithuania.

OBJECTIVES Previous studies have observed notable unexplained geographic differences in incidence of kidney cancer in Europe. Lithuania is among the countries with the highest incidence and mortality. Our objective was to investigate the effect of different lifestyle, anthropometric and biological factors on the risk of kidney cancer in Lithuanian men. METHODS This population-based cohort study included 6,849 men initially free from cancer. During the follow-up (1978-2008), 79 incident cases of kidney cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). RESULTS Risk of kidney cancer was significantly associated with increasing body mass index (BMI), the adjusted HR for ≥ 35 vs. < 25 kg/m2 was 3.00, 95% CI 1.10-8.19 and the HR per 1 unit increment of BMI was 1.07, 95% CI 1.01-1.14. In overweight men (BMI ≥ 25 kg/m2), the HRs for kidney cancer per 10 mmHg increment of systolic or diastolic blood pressure were 1.10, 95% CI 0.96-1.25 and 1.26, 95% CI 1.01-1.56, respectively. We found no significant association between smoking, alcohol consumption or total serum cholesterol level and kidney cancer risk. CONCLUSIONS This study supports a link between increased BMI and the development of kidney cancer among men in Lithuania. Hypertension appears to be associated with risk of kidney cancer in overweight men, although the assessment was limited by the lack of statistical power.
Effects of Daily Low-Dose Date Consumption on Glycemic Control, Lipid Profile, and Quality of Life in Adults with Pre- and Type 2 Diabetes: A Randomized Controlled Trial

Dates have a low glycemic index and are a source of antioxidants but, nevertheless, contain more than 70% sugar. This study aims to assess the effects of date consumption (three dates daily) on glycemic profile (HbA1c), body mass index (BMI), quality of life, and lipid profile, including total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) in terms of safety for type 2 diabetic mellitus (T2DM) subjects. A randomized controlled trial was conducted with a sample of 100 T2DM subjects (39 male and 61 female) randomly assigned in two groups. The first group received three dates daily for 16 weeks, and the control group avoided date consumption. After a 16-week follow-up period, the study results showed an improvement of lipid profile with a statistically significant decrease in total cholesterol of ∆ = −0.209 mmol/L (confidence interval (CI) 95% −0.358, −0.059; p < 0.05) and in LDL of ∆ = −0.171 mmol/L (CI 95% −0.358, 0.016) in the group receiving three dates daily. Intra-group mean differences of BMI were not statistically different in both groups after 16 weeks of date consumption. Even HbA1c did not change, both within and between groups after date consumption (∆ = 0.087%; CI 95% −0.086, 0.261). Between groups, mean difference changes (intervention minus control) showed a statistically significant improvement of quality of life index of ∆ = ± 30.66 points (CI 95% 12.45, 48.23) due to the consequent improvement in mental health. Although the definitive effect of dose/intake response of date consumption on Hb1Ac, lipid profile, and BMI in T2DM subjects is still to be established, the study suggests that dates could potentially have a beneficial effect on lipid profile, especially in reducing total cholesterol and elevating HDL, because of its high polyphenolic content. In addition, a low–moderate consumption of dates did not impact glucose levels because of dates’ low glycemic index.
Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China

Human infections with avian influenza viruses including H5, H7 and H9 hemagglutinin subtypes occur at a low rate. Among human infections with H7 viruses, regional outbreaks with H7N2, H7N3, H7N7 and H7N9 have been documented. Early in 2018, a human infection with a novel H7N4 avian influenza virus was reported in Jiangsu, China. This study is aimed at understanding the probable origin and molecular features of this emerging H7N4 virus. Genomic segments encoding hemagglutinin (HA) and neuraminidase (NA) of H7Nx and HxN4 viruses were compared with this H7N4 strain by alignment and phylogenetic tree analysis. Phylogenetic analysis indicated that the human H7N4 virus probably originated from multiple reassortments of avian H7N7 and H8N4 viruses for its HA and NA, respectively, and likely a regional uncharacterized virus for its internal segments. Our data excluded that circulating avian H9N2 viruses were the origin of the H7N4 internal segments, unlike the human H5N1 and H7N9 viruses that both had H9N2 backbones. This index case provided a unique opportunity to examine viral mutations by directly comparing the human isolate with its closest viral relatives isolated from avian species from the patient’s farm, which may suggest critical mutations required for viral adaptation in humans. Whole-genome scanning was performed and the sequences of the human and related avian H7N4 isolates were compared. Mutations in PB2 (E627K), PB2 (K683T), PB1-F2 (N47S), HA (N283D), HA(K321E), NA(A137V), NA(K296R) and M2 (C19Y) were identified in the human isolate while no mutations were found in PB1, NP, NS1, and NS2 of the human H7N4 compared to the avian H7N4 viruses. Our data in this report provide further evidence for the genesis of this novel H7N4 virus with a multi-reassortment model and show molecular changes that might be responsible for the transmission of this virus from chickens or ducks to and subsequent replication in humans.
Low-Concentration Ammonia Gas Sensors Manufactured Using the CMOS–MEMS Technique

This study describes the fabrication of an ammonia gas sensor (AGS) using a complementary metal oxide semiconductor (CMOS)–microelectromechanical system (MEMS) technique. The structure of the AGS features interdigitated electrodes (IDEs) and a sensing material on a silicon substrate. The IDEs are the stacked aluminum layers that are made using the CMOS process. The sensing material; polypyrrole/reduced graphene oxide (PPy/RGO), is synthesized using the oxidation–reduction method; and the material is characterized using an electron spectroscope for chemical analysis (ESCA), a scanning electron microscope (SEM), and high-resolution X-ray diffraction (XRD). After the CMOS process; the AGS needs post-processing to etch an oxide layer and to deposit the sensing material. The resistance of the AGS changes when it is exposed to ammonia. A non-inverting amplifier circuit converts the resistance of the AGS into a voltage signal. The AGS operates at room temperature. Experiments show that the AGS response is 4.5% at a concentration of 1 ppm NH3; and it exhibits good repeatability. The lowest concentration that the AGS can detect is 0.1 ppm NH3
Comparison of the myometrial transcriptome from singleton and twin pregnancies by RNA-Seq

Preterm birth is recognized as the primary cause of infant mortality worldwide. Twin pregnancies are significantly more at risk of preterm birth than singleton pregnancies. A greater understanding of why this is and better modes of treatment and prevention are needed. Key to this is determining the differing pathophysiological mechanisms of preterm birth in twins, including the role of the myometrium and premature uterine contraction. We performed RNA sequencing (RNA-Seq) of human myometrium from singleton and twin pregnancies at term (> 37+0 weeks) and preterm (< 37+0 weeks), collected during pre-labour Caesarean Section. RNA-Seq libraries were prepared from polyA-selected RNA and sequenced on the Illumina HiSeq 4000 platform. Differentially expressed genes (DEGs), GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment were conducted using R software. Significance was determined with a false discovery rate–adjusted P value of <0.05. Only 3 DEGs were identified between gestational age-matched singleton and twin myometrium and only 1 DEG identified between singleton term and twin preterm tissues. Comparison of singleton preterm myometrium with twin term myometrium however, revealed 75 down-regulated and 24 up-regulated genes in twin myometrium. This included genes associated with inflammation and immune response, T cell maturation and differentiation and steroid biosynthesis. GO and KEGG enrichment analyses for biologically relevant processes and functions also revealed several terms related to inflammation and immune response, as well as cytokine-cytokine receptor interaction and chemokine receptor signalling. Data indicate that little or no differences exist in the transcriptome of singleton and twin myometrium when matched for gestational age. The significant up- and down-regulation of genes identified between preterm singleton and twin myometrium at term may point to transcriptome changes associated with the chronic levels of uterine stretch in twin pregnancy or genes associated with the myometrium transitioning to labour onset.
Maintenance of hindgut reabsorption during cold exposure is a key adaptation for Drosophila cold tolerance

ABSTRACT Maintaining extracellular osmotic and ionic homeostasis is crucial for organismal function. In insects, hemolymph volume and ion content is regulated by the secretory Malpighian tubules and reabsorptive hindgut. When exposed to stressful cold, homeostasis is gradually disrupted, characterized by a debilitating increase in extracellular K+ concentration (hyperkalemia). Accordingly, studies have found a strong link between species-specific cold tolerance and the ability to maintain ion and water homeostasis at low temperature. This is also true for drosophilids where inter- and intra-specific differences in cold tolerance are linked to the secretory capacity of Malpighian tubules. There is, however, little information on the reabsorptive capacity of the hindgut in Drosophila. To address this, we developed a novel method that permits continuous measurements of hindgut ion and fluid reabsorption in Drosophila. We demonstrate that this assay is temporally stable (∼2 h) and responsive to cAMP stimulation and pharmacological intervention in accordance with the current insect hindgut reabsorption model. We then investigated how cold acclimation or cold adaptation affected hindgut reabsorption at benign (24°C) and low temperature (3°C). Cold-tolerant Drosophila species and cold-acclimated D. melanogaster maintain superior fluid and Na+ reabsorption at low temperature. Furthermore, cold adaptation and acclimation caused a relative reduction in K+ reabsorption at low temperature. These characteristic responses of cold adaptation/acclimation will promote maintenance of ion and water homeostasis at low temperature. Our study of hindgut function therefore provides evidence that adaptations in the osmoregulatory capacity of insects are critical for their ability to tolerate cold. Highlighted Article: A novel assay measuring hindgut ion and fluid reabsorption in Drosophila shows that inter- and intraspecific differences in cold tolerance are linked to maintenance of hindgut osmoregulatory capacity at low temperature.
Omp25‐dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo

The strategies by which intracellular pathogenic bacteria manipulate innate immunity to establish chronicity are poorly understood. Here, we show that Brucella abortus outer membrane protein Omp25 specifically binds the immune cell receptor SLAMF1 in vitro. The Omp25‐dependent engagement of SLAMF1 by B. abortus limits NF‐κB translocation in dendritic cells (DCs) with no impact on Brucella intracellular trafficking and replication. This in turn decreases pro‐inflammatory cytokine secretion and impairs DC activation. The Omp25‐SLAMF1 axis also dampens the immune response without affecting bacterial replication in vivo during the acute phase of Brucella infection in a mouse model. In contrast, at the chronic stage of infection, the Omp25/SLAMF1 engagement is essential for Brucella persistence. Interaction of a specific bacterial protein with an immune cell receptor expressed on the DC surface at the acute stage of infection is thus a powerful mechanism to support microbe settling in its replicative niche and progression to chronicity.
ETV6/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia

Background: The t(12;21)(p13;q22), which fuses ETV6 and RUNX1 genes, is the most common genetic abnormality in children with B-cell precursor acute lymphoblastic leukaemia. The implication of the fusion protein in leukemogenesis seems to be clear. However, its role in the maintenance of the disease continues to be controversial. Methods: Generation of an in vitro ETV6/RUNX1 knock out model using the CRISPR/Cas9 gene editing system. Functional characterization by RNA sequencing, proliferation assays, apoptosis and pharmacologic studies, and generation of edited-cell xenograft model. Results: The expression of ETV6/RUNX1 fusion gene was completely eliminated, thus generating a powerful model on which to study the role of the fusion gene in leukemic cells. The loss of fusion gene expression led to the deregulation of biological processes affecting survival such as apoptosis resistance and cell proliferation capacity. Tumour cells showed higher levels of apoptosis, lower proliferation rate and a greater sensitivity to PI3K inhibitors in vitro along as a decrease in tumour growth in xenografts models after ETV6/RUNX1 fusion gene abrogation. Conclusions: ETV6/RUNX1 fusion protein seems to play an important role in the maintenance of the leukemic phenotype and could thus become a potential therapeutic target.
Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile

Mesenchymal stem cell (MSC) therapy is a promising alternative approach for the treatment of neurodegenerative diseases, according to its neuroprotective and immunomodulatory potential. Despite numerous clinical trials involving autologous MSCs, their outcomes have often been unsuccessful. Several reports have indicated that MSCs from patients have low capacities in terms of the secretion of neurotrophic or anti-inflammatory factors, which might be associated with cell senescence or disease severity. Therefore, a new strategy to improve their capacities is required for optimal efficacy of autologous MSC therapy. In this study, we compared the secretory potential of MSCs among cerebellar ataxia patients (CA-MSCs) and healthy individuals (H-MSCs). Our results, including secretome analysis findings, revealed that CA-MSCs have lower capacities in terms of proliferation, oxidative stress response, motility, and immunomodulatory functions when compared with H-MSCs. The functional differences were validated in a scratch wound healing assay and neuron-glia co-cultures. In addition, the neuroprotective and immunoregulatory protein follistatin-like 1 (FSTL1) was identified as one of the downregulated proteins in the CA-MSC secretome, with suppressive effects on proinflammatory microglial activation. Our study findings suggest that targeting aspects of the downregulated anti-inflammatory secretome, such as FSTL1, might improve the efficacy of autologous MSC therapy for CA.
Reporter Assays for Ebola Virus Nucleoprotein Oligomerization, Virion-Like Particle Budding, and Minigenome Activity Reveal the Importance of Nucleoprotein Amino Acid Position 111

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]). The Ebola virus nucleoprotein (NP) plays multiple essential roles during the viral life cycle, yet few tools exist to study the protein under BSL-2 or equivalent containment. Therefore, we adapted reporter assays to measure NP oligomerization and virion-like particle (VLP) production in live cells and further measured transcription and replication using established minigenome assays. As a proof-of-concept, we examined the NP-R111C substitution, which emerged during the 2013–2016 Western African Ebola virus disease epidemic and rose to high frequency. NP-R111C slightly increased NP oligomerization and VLP budding but slightly decreased transcription and replication. By contrast, a synthetic charge-reversal mutant, NP-R111E, greatly increased oligomerization but abrogated transcription and replication. These results are intriguing in light of recent structures of NP oligomers, which reveal that the neighboring residue, K110, forms a salt bridge with E349 on adjacent NP molecules. By developing and utilizing multiple reporter assays, we find that the NP-111 position mediates a complex interplay between NP’s roles in protein structure, virion budding, and transcription and replication.
Fluorescent Western Blotting: High Sensitivity Detection of Multiple Targets

Western blotting with fluorescence detection offers the possibility of detecting multiple targets simultaneously on a single blot. Primary antibodies are increasingly available from multiple hosts, and there are now a wide variety of dye labels to exploit multiple imaging channels. If primary and secondary antibodies are selected so that individual targets can be discriminated, multiple antigens can be detected and quantified in a single experiment. Current fluorescence imaging instrumentation offers multiple detection channels and gives sensitivity comparable to other methods. The method described in this article allows multiple targets to be quantified simultaneously and reduces the need for stripping and re‐probing. It also allows loading controls to be detected alongside the targets of interest. © 2020 by John Wiley & Sons, Inc.
A Model for Ischaemic Heart Disease and Stroke II: Modelling Obesity

ABSTRACT This is the second in a series of three papers. In the first paper we describe a comprehensive stochastic model of an individual's lifetime that includes diagnosis with ischaemic heart disease and stroke and also the development of the major risk factors for these conditions. The third paper is devoted to some applications of this model. In this paper we discuss the effect of BMI on diabetes, heart disease and mortality and we use data from the Framingham Heart Study and the Health Survey for England to develop stochastic models for changes in an individual's BMI. Some of these models incorporate time trends leading to increasing prevalence of obesity. We then use these models to investigate how future expected lifetime and future expected healthy lifetime depend on BMI. Our conclusions are that if the prevalence of obesity increases, even to an extreme degree, then the prevalence of diabetes and hypertension in the population will increase, possibly to a significant extent, but the prevalence of heart disease and stroke will increase by a much smaller amount and the effect on expected future lifetime will be small.