Miracle-dz/UniFAR-FTUs huggingface dataset:
Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study

Abstract Introduction FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line. Methods The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs. NuProtect was a prospective, multinational, open-label, non-controlled, phase III study. PUPs with severe haemophilia A (FVIII:C <1%) of any age and ethnicity were treated with simoctocog alfa for 100 exposure days or a maximum of 5 years. Patients were true PUPs without prior exposure to FVIII concentrates or blood components. Inhibitor titres were measured with the Nijmegen-modified Bethesda assay; cut-off for positivity was 0.6 BU mL−1 (≥0.6 to <5 low-titre, ≥5 high titre). Results A total of 108 PUPs with a median age at first treatment of 12.0 months (interquartile range: 8.0–23.5) were treated with simoctocog alfa. F8 mutation type was known for 102 patients (94.4%) of whom 90 (88.2%) had null F8 mutations and 12 (11.8%) had non-null mutations. Of 105 PUPs evaluable for inhibitor development, 28 (26.7%) developed inhibitors; 17 high titre (16.2%) and 11 low titre (10.5%). No PUPs with non-null F8 mutations developed inhibitors. Conclusion In the NuProtect study, the rate of inhibitor development in PUPs with severe haemophilia A treated with simoctocog alfa was lower than the rate reported for hamster-cell-derived recombinant factor VIII products in other recent clinical trials. No inhibitors were reported in PUPs with non-null F8 mutations.
Pollen morphology of different species of Iris barbata and its systematic significance with scanning electron microscopy methods

Forty‐eight cultivars of Iris barbata were used as research materials, and observations of their pollen morphologies were made using scanning electron microscopy (SEM). The pollen of I. barbata consisted of a single grain, which was subspheroidal or subprolate and boat‐shaped in equatorial view and oval or nearly round in polar view. The pollen was symmetrical or radially symmetrical on both sides, and there were five types of germination furrows: monocolpate, dicolpate, monocolpate‐colpoidal, 2‐syncolpate, and parasyncolpate. The exine ornamentation was mostly crass‐reticulate and occasionally verrucate or pilate. Variation in the equatorial axis length of I. barbata pollen was the lowest, and variation in pollen morphology was stable. Q‐type cluster analysis was conducted using seven indexes: polar axis length (P), equatorial axis length (E), P/E, mesh diameter (D), net ridge width (W), D/W, and germination furrow width (WG). The 48 cultivars were divided into three groups. Three dwarf cultivars were clustered in one group, and the degree of evolution of this group was higher than that of the other two groups. This paper systematically describes the characteristics of I. barbata for the first time, and thus provides important palynological insights into the classification and cross‐breeding of I. barbata.
Effect of Ozone on Removal of Dissolved Organic Matter and its Biodegradability and Adsorbability in Biotreated Textile Effluents

A study was conducted on the efficacy of ozonation in removing dissolved organic matter (DOM) in biotreated textile effluents and effects on its biodegradability and adsorbability. Results showed the efficient removal of color and fluorescence compounds were achieved through ozonation, due to increasing hydrophilicity and lowering molecular weight of DOM. A significant biodegradability improvement was also observed, and DOM adsorbability on activated carbon was highly dependent on ozone dosage. As the key parameter, consumed 3.8 g O3/ g TOC0 was the optimal dosage in the hybrid process combining ozonation with biological activated carbon (BAC) for wastewater reclamation.
Status of free radicals in Indian monsooned coffee beans γ-irradiated for disinfestation

Free radicals in two cultivars of Indian monsooned coffee beans, gamma-irradiated for hygienic and quarantine purposes, were examined by entrapping the small amount of samples in potassium chloride powder in ESR quartz tubes. In contrast to a prominent free radical signal at g = 2.002, observed in spermoderm (silver skin) and cotyledon (whole seed without skin) parts of normal coffee beans, the same was not discernible in monsooned coffee bean parts of both cultivars. The ESR signal was found to be more prominent in the spermoderm than in the whole seed portion of the normal coffee beans. Common practices of roasting and powdering were found to generate quantitatively more free radicals in coffee beans than gamma-irradiation alone. Phenols, contributing maximally to observed free radical signals in coffee beans, were significantly different in normal and monsooned coffee beans. These observations on insignificant free radical population in irradiated monsooned coffee beans may be attributed to their inherent possession of high water activity, favoring decay of free radicals produced. Textural studies with monsooned coffee beans, before and after mild heat treatments, supported these findings.
TFAP2A-induced SLC2A1-AS1 promotes cancer cell proliferation

Abstract Long non-coding RNAs (lncRNAs) are involved in the occurrence and development of human cancers including lung adenocarcinoma (LUAD). SLC2A1-AS1 is a novel lncRNA that has been reported to be exceptionally expressed in several cancer types. However, the expression and role of SLC2A1-AS1 in cancer remains largely unclear. In this study, it was revealed that lncRNA SLC2A1-AS1 was notably over-expressed in LUAD and was closely correlated with patients’ overall survival (OS). Knockdown of SLC2A1-AS1 could significantly restrain cell proliferation of LUAD in vitro, while over-expression of SLC2A1-AS1 had the accelerative effect. SLC2A1-AS1 enriched in the cytoplasm of LUAD cells could directly bind to miR-508-5p and negatively regulate its level. The inhibitory effect of miR-508-5p on LUAD cell proliferation was in part abrogated by SLC2A1-AS1 manipulation. Moreover, the transcription factor activating enhancer binding protein 2 α (TFAP2A) was highly expressed in LUAD and predicted worse patients’ OS. TFAP2A could directly bind to the promoter region of SLC2A1-AS1 encoding gene and positively regulate the transcription of SLC2A1-AS1 in LUAD cells. Furthermore, TFAP2A-induced SLC2A1-AS1 promoted cell proliferation of lung squamous cell carcinoma (LUSC) and pancreatic adenocarcinoma (PAAD). Collectively, these findings suggest that TFAP2A-mediated lncRNA SLC2A1-AS1 works as an oncogene to drive cancer cell proliferation.
Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the non-HLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory T cell function, and specific autoantibodies such as anti-PsA peptide, anti-LL-37, and anti-ADAMTSL5 are the immunopathological findings suggestive of autoimmunity. These were supported by clinical observations of autoimmune multimorbidity and treatment response to calcineurin/mTOR and co-stimulation inhibition.
Xingbi Gel Ameliorates Allergic Rhinitis by Regulating IFN-γ Gene Promoter Methylation in CD4+ T Cells via the ERK-DNMT Pathway

Allergic rhinitis (AR) is a common, non-infectious, chronic nasal mucosal disease primarily mediated by immunoglobulin E (IgE) following allergen exposure. Currently, studies on AR mainly focus on cytokines, IgE and its receptors, basophils, eosinophils, mast cells, and related genes. Among these, an imbalance between T helper (Th) 1 and Th2 cells is considered an important mechanism underlying AR pathogenesis. The most important cytokines in AR are interleukin (Il)-4 and interferon gamma (IFN-γ) which are secreted by Th2 and Th1 cells, respectively. Il-4 and IFN-γ are antagonistic to each other in regulating IgE synthesis. In this study, the expression of extracellular signal-regulated protein kinase (ERK) 1/2 and its phosphorylation from p-ERK1/2, were significantly increased in a cluster of differentiation of 4+ T cells of AR mice, suggesting that the ERK signaling pathway in these cells is involved in the occurrence and development of AR. This result also implies an enhanced expression of deoxyribonucleic acid methyltransferases (DNMTs). To verify the relationship between ERK signaling and DNMT expression, AR mice were treated with PD98059, a specific inhibitor of the ERK1/2 signaling pathway. The results revealed that perturbations in ERK signaling were significantly positively correlated with the downregulation of DNMT1 expression. Pharmacological intervention is key to treating AR. This study demonstrated that Xingbi gel intervention affected both serum IgE levels and AR behavior scores in mice. Based on its effects on IFN-γ gene expression, the regulation of Th1/Th2 balance, and the ERK signaling pathway, research on the effects of Xingbi gel on AR may provide new avenues in its prevention and treatment.
Imaging Mass Spectrometry and Lectin Analysis of N-Linked Glycans in Carbohydrate Antigen–Defined Pancreatic Cancer Tissues

Abstract The early detection of pancreatic ductal adenocarcinoma (PDAC) is a complex clinical obstacle yet is key to improving the overall likelihood of patient survival. Current and prospective carbohydrate biomarkers carbohydrate antigen 19-9 (CA19-9) and sialylated tumor-related antigen (sTRA) are sufficient for surveilling disease progression yet are not approved for delineating PDAC from other abdominal cancers and noncancerous pancreatic pathologies. To further understand these glycan epitopes, an imaging mass spectrometry (IMS) approach was used to assess the N-glycome of the human pancreas and pancreatic cancer in a cohort of patients with PDAC represented by tissue microarrays and whole-tissue sections. Orthogonally, these same tissues were characterized by multiround immunofluorescence that defined expression of CA19-9 and sTRA as well as other lectins toward carbohydrate epitopes with the potential to improve PDAC diagnosis. These analyses revealed distinct differences not only in N-glycan spatial localization across both healthy and diseased tissues but importantly between different biomarker-categorized tissue samples. Unique sulfated biantennary N-glycans were detected specifically in normal pancreatic islets. N-glycans from CA19-9–expressing tissues tended to be biantennary, triantennary, and tetra-antennary structures with both core and terminal fucose residues and bisecting GlcNAc. These N-glycans were detected in less abundance in sTRA-expressing tumor tissues, which favored triantennary and tetra-antennary structures with polylactosamine extensions. Increased sialylation of N-glycans was detected in all tumor tissues. A candidate new biomarker derived from IMS was further explored by fluorescence staining with selected lectins on the same tissues. The lectins confirmed the expression of the epitopes in cancer cells and revealed different tumor-associated staining patterns between glycans with bisecting GlcNAc and those with terminal GlcNAc. Thus, the combination of lectin-immunohistochemistry and lectin-IMS techniques produces more complete information for tumor classification than the individual analyses alone. These findings potentiate the development of early assessment technologies to rapidly and specifically identify PDAC in the clinic that may directly impact patient outcomes.
Detection of Cephalosporin and Fluoroquinolone Resistance Genes via Novel Multiplex qPCR in Fecal Salmonella Isolates From Northern Californian Dairy Cattle, 2002–2016

The objectives of this study were to evaluate the prevalence of extended spectrum β-lactamase (ESBL) genes, AmpC-type β-lactamase (ACBL) genes, and plasmid mediated quinolone resistance (PMQR) genes in Salmonella isolated at a Veterinary Medical Teaching Hospital microbiology laboratory, examine trends in presence of these resistance genes, and to explore the correlation between phenotypic resistance and presence of specific genes. The presence of ESBL, ACBL, and PMQR genes were detected using a single, novel multiplex qPCR. Only the genes blaCMY–2 and blaTEM were detected in the 110 Salmonella isolates tested. PMQR genes were not detected in isolates screened. Of 94 third-generation cephalosporin resistant isolates, representing eight serotypes, 48% (n = 45) were positive for blaCMY–2 only and 50% (n = 47) were simultaneously positive for blaCMY–2 and blaTEM. Two third-generation cephalosporin resistant isolates were tested negative for all β-lactamase genes in our qPCR assay and likely house ESBL genes not screened for by our qPCR assay. A logistic regression model revealed that for serotype Dublin isolates (n = 38) the odds ratio for testing positive for blaTEM when compared to all other serotypes was 51.6 (95% CI: 4.01–664.03, p = 0.0029). For serotype Typhimurium (n = 9) the odds ratio for testing positive for blaTEM when compared to all other serotypes was 43.3 (95% CI: 1.76–1000, p = 0.0216). Overall, our results suggest that the prevalence of resistance to cephalosporins and fluoroquinolones due to ESBLs, ACBLs, and PMQR genes present in bovine nontyphoidal Salmonella enterica isolates has remained relatively constant in the isolates screened over a 14-year period.
“Can you help me move this over there?”: training children with ASD to joint action through tangible interaction and virtual agent

New technologies for autism focus on the training of either social skills or motor skills, but not both. Such a dichotomy omits a wide range of joint action tasks that require the coordination of two persons (e.g. moving a heavy furniture). The training of these physical tasks performed in dyad has great potential to foster inclusiveness while having an impact on both social and motor skills. In this paper, we present the design of a tangible and virtual interactive system for the training of children with Autism Spectrum Disorder (ASD) in performing joint actions. The proposed system is composed of a virtual character projected onto a surface on which a tangible object is magnetized: both the user and the virtual character hold the object, thus simulating a joint action. We report and discuss preliminary results of a field training study, which shows the potential of the interactive system.
VirtualWire: Supporting Rapid Prototyping with Instant Reconfigurations of Wires in Breadboarded Circuits

Assembling circuits is a challenging and time consuming activity for novice makers, frequently resulting in incorrect placements of wires and components into breadboards. This results in errors that are difficult to identify and debug, and delays that hinder creating, exploring or reconfiguring circuit layouts. This paper presents VirtualWire, a tool that allows users to rapidly design and modify circuits in software and have these changes instantiated in real-time as electrical connections on a physical breadboard. To achieve this, VirtualWire dynamically translates circuit design files into physical connections inside a hardware switching matrix, which handles wiring across breadboard rows and to/from an embedded Arduino. The user can interactively test, tune, and share different circuit layouts for an Arduino shield, and once satisfied, can fabricate the circuit on a permanent substrate. Quantitative and qualitative user studies demonstrate that VirtualWire significantly reduces the time taken for (by 37%), and the number of errors made during (by 53%) circuit assembly, while also supporting users in creating readable, space-efficient and flexible layouts.
Coarse-Grained Simulation of Mechanical Properties of Single Microtubules With Micrometer Length

Microtubules are one of the most important components in the cytoskeleton and play a vital role in maintaining the shape and function of cells. Because single microtubules are some micrometers long, it is difficult to simulate such a large system using an all-atom model. In this work, we use the newly developed convolutional and K-means coarse-graining (CK-CG) method to establish an ultra-coarse-grained (UCG) model of a single microtubule, on the basis of the low electron microscopy density data of microtubules. We discuss the rationale of the micro-coarse-grained microtubule models of different resolutions and explore microtubule models up to 12-micron length. We use the devised microtubule model to quantify mechanical properties of microtubules of different lengths. Our model allows mesoscopic simulations of micrometer-level biomaterials and can be further used to study important biological processes related to microtubule function.
Learning earth system models from observations: machine learning or data assimilation?

Recent progress in machine learning (ML) inspires the idea of improving (or learning) earth system models directly from the observations. Earth sciences already use data assimilation (DA), which underpins decades of progress in weather forecasting. DA and ML have many similarities: they are both inverse methods that can be united under a Bayesian (probabilistic) framework. ML could benefit from approaches used in DA, which has evolved to deal with real observations—these are uncertain, sparsely sampled, and only indirectly sensitive to the processes of interest. DA could also become more like ML and start learning improved models of the earth system, using parameter estimation, or by directly incorporating machine-learnable models. DA follows the Bayesian approach more exactly in terms of representing uncertainty, and in retaining existing physical knowledge, which helps to better constrain the learnt aspects of models. This article makes equivalences between DA and ML in the unifying framework of Bayesian networks. These help illustrate the equivalences between four-dimensional variational (4D-Var) DA and a recurrent neural network (RNN), for example. More broadly, Bayesian networks are graphical representations of the knowledge and processes embodied in earth system models, giving a framework for organising modelling components and knowledge, whether coming from physical equations or learnt from observations. Their full Bayesian solution is not computationally feasible but these networks can be solved with approximate methods already used in DA and ML, so they could provide a practical framework for the unification of the two. Development of all these approaches could address the grand challenge of making better use of observations to improve physical models of earth system processes. This article is part of the theme issue ‘Machine learning for weather and climate modelling’.
SARS CoV-2 Spike Protein in silico Interaction With ACE2 Receptors From Wild and Domestic Species

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization (WHO), and since its first report, it has become a major public health concern. SARS-CoV-2 is closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been described to use angiotensin-converting enzyme 2 (ACE2) as a receptor. Natural SARS-CoV-2 infection in domestic and wildlife animals, measured by RT-qPCR, has been confirmed in different countries, especially from the Felidae family. In silico analysis of the interaction between the SARS-CoV-2 spike protein and the cellular receptor ACE2 in various animal species has suggested that wild felids and domestic cats could be susceptible to SARS-CoV-2 based on this interaction. Here, we performed a protein-protein molecular docking analysis of SARS-CoV-2 spike protein with the ACE2 receptor from different animals to elucidate the potential of those species as intermediate hosts or susceptible animals for SARS-CoV-2 infection. Compared to human ACE2, we found that ACE2 receptors from domestic cats and tigers could efficiently interact with RBD of SARS CoV-2 Spike protein. However, dog, ferret, and hamster ACE2 receptor interaction with SARS-CoV-2 S protein RBD was not predicted as favorable, demonstrating a potential differentiated susceptibility in the evaluated species.
The Efficacy, Safety, and Tolerability of Probiotics on Depression: Clinical Results From an Open-Label Pilot Study

Background: A growing body of research has shown that consumption of probiotics can improve symptoms associated with mood and anxiety disorders through activity of the gut-brain axis. However, the effects of probiotics have yet to be tested in a clinical sample of treatment-naïve patients diagnosed with Major Depressive Disorder (MDD). The aim of this 8-week, open-label pilot study is to examine changes in depressive symptoms before and after the introduction of a probiotic supplement in 10 treatment-naïve MDD patients and to provide data on the feasibility of conducting a larger double-blind, randomized, placebo-controlled trial in the same patient population. Here we report on the clinical outcome measures of the study. Methods: Participants recruited from the community in Kingston, Ontario, Canada consumed a probiotic supplement containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (CEREBIOME®) at a dose of 3 × 109 CFU once per day for 8 weeks. Clinical symptoms of depression were measured using a validated battery of clinical scales and self-report questionnaires (CAN-BIND protocol). Data was collected at baseline, week 4, and week 8. Results: Significant improvements in affective clinical symptoms were observed at week 4 and were sustained at week 8. Significant improvements in subjective sleep quality were observed by week 8. No side effects or adverse effects associated with the probiotic supplement were observed. Conclusions: The findings from this study support the existing evidence in this emerging field for probiotics having a role in alleviating symptoms of depression in treatment-naïve, moderately depressed patients and indicate that the probiotic supplement is safe and well-tolerated in this population. However, further comprehensive studies are required to draw conclusions.