Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of Pore Size in Protein G'‐Grafted Mesoporous Silica Nanoparticles as a Serum Pretreatment System for In Vitro Allergy Diagnosis

Particles with the capacity to bind to immunoglobulin G (IgG) can be used for the purification of IgG or to process clinical samples for diagnostic purposes. For in vitro allergy diagnosis, the high IgG levels in serum can interfere with the detection of allergen‐specific IgE, the main diagnostic biomarker. Although commercially available, current materials present a low IgG capture capacity at large IgG concentrations or require complex protocols, preventing their use in the clinic. In this work, mesoporous silica nanoparticles are prepared with different pore sizes, to which IgG‐binding protein G’ is grafted. It is found that for one particular optimal pore size, the IgG capture capacity of the material is greatly enhanced. The capacity of this material to efficiently capture human IgG in a selective way (compared to IgE) is demonstrated in both solutions of known IgG concentrations as well as in complex samples, like serum, from healthy controls and allergic patients using a simple and fast incubation protocol. Interestingly, IgG removal using the best‐performing material enhances in vitro IgE detection in sera from patients allergic to amoxicillin. These results highlight the great translation potential of this strategy to the clinic in the context of in vitro allergy diagnosis.
Estimating resistance surfaces using gradient forest and allelic frequencies.

Understanding landscape connectivity has become a global priority for mitigating the impact of landscape fragmentation on biodiversity. Connectivity methods that use link-based methods traditionally rely on relating pairwise genetic distance between individuals or demes to their landscape distance (e.g., geographic distance, cost distance). In this study, we present an alternative to conventional statistical approaches to refine cost surfaces by adapting the gradient forest approach to produce a resistance surface. Used in community ecology, gradient forest is an extension of random forest, and has been implemented in genomic studies to model species genetic offset under future climatic scenarios. By design, this adapted method, resGF, has the ability to handle multiple environmental predicators and is not subjected to traditional assumptions of linear models such as independence, normality and linearity. Using genetic simulations, resistance Gradient Forest (resGF) performance was compared to other published methods (maximum likelihood population effects model, random forest-based least-cost transect analysis and species distribution model). In univariate scenarios, resGF was able to distinguish the true surface contributing to genetic diversity among competing surfaces better than the compared methods. In multivariate scenarios, the gradient forest approach performed similarly to the other random forest-based approach using least-cost transect analysis but outperformed MLPE-based methods. Additionally, two worked examples are provided using two previously published datasets. This machine learning algorithm has the potential to improve our understanding of landscape connectivity and inform long-term biodiversity conservation strategies.
Towards a real-time release of blends and tablets using NIR and Raman spectroscopy at commercial scales

Abstract Near Infrared and Raman spectroscopy-based Process Analytical Technology tools were used for monitoring blend uniformity (BU) and content uniformity (CU) for solid oral formulations. A quantitative Partial Least Square model was developed to monitor BU as real-time release testing at a commercial scale. The model having the R 2, and root mean square error of 0.9724 and 2.2047, respectively can predict the target concentration of 100% with a 95% confidence interval of 101.85–102.68% even after one year. The tablets from the same blends were investigated for CU using NIR and Raman techniques both in reflection and transmission mode. Raman reflection technique was found to be the best and the PLS model was developed using tablets compressed at different concentrations, hardness, and speed. The model with R 2 and RMSE of 0.9766 and 1.9259, respectively was used for the quantification of CU. Both the BU and CU models were validated for accuracy, precision, specificity, linearity, and robustness. The accuracy was proved against the HPLC method with a relative standard deviation of less than 3%. The equivalency for BU by NIR and CU by Raman was evaluated using Schuirmann’s Two One-sided tests and found equivalent to HPLC within a 2% acceptable limit. Graphical Abstract
Distinct responses and range shifts of lizard populations across an elevational gradient under climate change

Ongoing climate change has profoundly affected global biodiversity, but its impacts on populations across elevations remain understudied. Using mechanistic niche models incorporating species traits, we predicted ecophysiological responses (activity times, oxygen consumption and evaporative water loss) for lizard populations at high‐elevation (<3600 m asl) and extra‐high‐elevation (≥3600 m asl) under recent (1970–2000) and future (2081–2100) climates. Compared with their high‐elevation counterparts, lizards from extra‐high‐elevation are predicted to experience a greater increase in activity time and oxygen consumption. By integrating these ecophysiological responses into hybrid species distribution models (HSDMs), we were able to make the following predictions under two warming scenarios (SSP1‐2.6, SSP5‐8.5). By 2081–2100, we predict that lizards at both high‐ and extra‐high‐elevation will shift upslope; lizards at extra‐high‐elevation will gain more and lose less habitat than will their high‐elevation congeners. We therefore advocate the conservation of high‐elevation species in the context of climate change, especially for those populations living close to their lower elevational range limits. In addition, by comparing the results from HSDMs and traditional species distribution models, we highlight the importance of considering intraspecific variation and local adaptation in physiological traits along elevational gradients when forecasting species' future distributions under climate change.
Involvement and possible role of transglutaminases 1 and 2 in mediating fibrotic signalling, collagen cross-linking and cell proliferation in neonatal rat ventricular fibroblasts

Transglutaminase (TG) isoforms control diverse normal and pathophysiologic processes through their capacity to cross-link extracellular matrix (ECM) proteins. Their functional and signalling roles in cardiac fibrosis remain poorly understood, despite some evidence of TG2 involvement in abnormal ECM remodelling in heart diseases. In this study, we investigated the role of TG1 and TG2 in mediating fibrotic signalling, collagen cross-linking, and cell proliferation in healthy fibroblasts by siRNA-mediated knockdown. siRNA for TG1, TG2 or negative control was transfected into cultured neonatal rat ventricular fibroblasts and cardiomyocytes. mRNA expression of TGs and profibrotic, proliferation and apoptotic markers was assessed by qPCR. Cell proliferation and soluble and insoluble collagen were determined by ELISA and LC-MS/MS, respectively. TG1 and TG2 were both expressed in neonatal rat cardiomyocytes and fibroblasts before transfection. Other TGs were not detected before and after transfection. TG2 was predominantly expressed and more effectively silenced than TG1. Knocking down TG1 or TG2 significantly modified profibrotic markers mRNA expression in fibroblasts, decreasing connective tissue growth factor (CTGF) and increasing transforming growth factor-β1 compared to the negative siRNA control. Reduced expression of collagen 3A1 was found upon TG1 knockdown, while TG2 knockdown raised α-smooth muscle actin expression. TG2 knockdown further increased fibroblast proliferation and the expression of proliferation marker cyclin D1. Lower insoluble collagen content and collagen cross-linking were evidenced upon silencing TG1 or TG2. Transcript levels of collagen 1A1, fibronectin 1, matrix metalloproteinase-2, cyclin E2, and BCL-2-associated X protein/B-cell lymphoma 2 ratio were strongly correlated with TG1 mRNA expression, whereas TG2 expression correlated strongly with CTGF mRNA abundance. These findings support a functional and signalling role for TG1 and TG2 from fibroblasts in regulating key processes underlying myocardial ECM homeostasis and dysregulation, suggesting that these isoforms could be potential and promising targets for the development of cardiac fibrosis therapies.
Transporting monovalent rotavirus vaccine efficacy estimates to an external target population: a secondary analysis of data from a randomised controlled trial in Malawi

Abstract Oral rotavirus vaccine efficacy estimates from randomised controlled trials are highly variable across settings. Although the randomised study design increases the likelihood of internal validity of findings, results from trials may not always apply outside the context of the study due to differences between trial participants and the target population. Here, we used a weight-based method to transport results from a monovalent rotavirus vaccine clinical trial conducted in Malawi between 2005 and 2008 to a target population of all trial-eligible children in Malawi, represented by data from the 2015–2016 Malawi Demographic and Health Survey (DHS). We reweighted trial participants to reflect the population characteristics described by the Malawi DHS. Vaccine efficacy was estimated for 1008 trial participants after applying these weights such that they represented trial-eligible children in Malawi. We also conducted subgroup analyses to examine the heterogeneous treatment effects by stunting and tuberculosis vaccination status at enrolment. In the original trial, the estimates of one-year vaccine efficacy against severe rotavirus gastroenteritis and any-severity rotavirus gastroenteritis in Malawi were 49.2% (95% CI 15.6%–70.3%) and 32.1% (95% CI 2.5%–53.1%), respectively. After weighting trial participants to represent all trial-eligible children in Malawi, vaccine efficacy increased to 62.2% (95% CI 35.5%–79.0%) against severe rotavirus gastroenteritis and 38.9% (95% CI 11.4%–58.5%) against any-severity rotavirus gastroenteritis. Rotavirus vaccine efficacy may differ between trial participants and target populations when these two populations differ. Differences in tuberculosis vaccination status between the trial sample and DHS population contributed to varying trial and target population vaccine efficacy estimates.
Certainty equivalence-based robust sliding mode control strategy and its application to uncertain PMSG-WECS

This work focuses on maximum power extraction via certainty equivalence-based robust sliding mode control protocols for an uncertain Permanent Magnet Synchronous Generator-based Wind Energy Conversion System (PMSG-WECS). The considered system is subjected to both structured and unstructured disturbances, which may occur through the input channel. Initially, the PMSG-WECS system is transformed into a Bronwsky form, i.e., controllable canonical form, which is composed of both internal and visible dynamics. The internal dynamics are proved stable, i.e., the system is in the minimum phase. However, the control of visible dynamics, to track the desired trajectory, is the main concern. To carry out this task, the certainty equivalence-based control strategies, i.e., conventional sliding mode control, terminal sliding mode control and integral sliding mode control are designed. Consequently, a chattering phenomenon is suppressed by the employment of equivalent estimated disturbances, which also enhance the robustness of the proposed control strategies. Eventually, a comprehensive stability analysis of the proposed control techniques is presented. All the theoretical claims are verified via computer simulations, which are performed in MATLAB/Simulink.
Bacillus thuringiensis toxins divert progenitor cells toward enteroendocrine fate by decreasing cell adhesion with intestinal stem cells in Drosophila

Bacillus thuringiensis subsp. kurstaki (Btk) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, Btk and its toxins are used worldwide as microbial insecticide and in genetically modified crops, respectively, to fight crop pests. However, Btk belongs to the B. cereus group, some strains of which are well known human opportunistic pathogens. Therefore, ingestion of Btk along with food may threaten organisms not susceptible to Btk infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of Drosophila melanogaster, an organism non-susceptible to Btk. Surprisingly, a high proportion of the ISC daughter cells differentiate into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins weaken the E-Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, although not lethal to non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and endocrine functions.
Capsid structure of a fungal dsRNA megabirnavirus reveals its previously unidentified surface architecture

Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 Å resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Compared with other non-enveloped icosahedral dsRNA viruses, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus.
Elucidation of the Late Steps during Hexacosalactone A Biosynthesis in Streptomyces samsunensis OUCT16-12

In this study, we elucidate the post-PKS tailoring steps during the biosynthesis of compound 1 and demonstrate that both C5N and 15-OMe groups are critical for the antibacterial activities of compound 1, paving the way for generation of hexacosalactone derivatives via synthetic biology strategy. In addition, mining of HexABC homologs from the GenBank database revealed their wide distribution across the bacterial world, facilitating the discovery of other bioactive natural products with C5N moiety. ABSTRACT Hexacosalactone A (1) is a polyene macrolide compound featuring a 2-amino-3-hydroxycyclopent-2-enone (C5N)-fumaryl moiety. While compound 1 has been proposed to be assembled via a type I modular polyketide synthase (PKS) system, most of the putative biosynthetic steps lack experimental evidence. In this study, we elucidated the post-PKS tailoring steps of compound 1 through in vivo gene inactivation and in vitro biochemical assays. We demonstrated that the amide synthetase HexB and O-methyltransferase HexF are responsible for the installations of the C5N moiety and the methyl group at 15-OH of compound 1, respectively; two new hexacosalactone analogs, named hexacosalactones B (4) and C (5), were purified and structurally characterized, followed by anti-multidrug resistance (anti-MDR) bacterial assays, revealing that the C5N ring and the methyl group are necessary for the antibacterial bioactivities. Through database mining of C5N-forming proteins HexABC, six uncharacterized biosynthetic gene clusters (BGCs), putatively encoding compounds with different types of backbones, were identified, providing potentials to discover novel bioactive compounds with C5N moiety. IMPORTANCE In this study, we elucidate the post-PKS tailoring steps during the biosynthesis of compound 1 and demonstrate that both C5N and 15-OMe groups are critical for the antibacterial activities of compound 1, paving the way for generation of hexacosalactone derivatives via synthetic biology strategy. In addition, mining of HexABC homologs from the GenBank database revealed their wide distribution across the bacterial world, facilitating the discovery of other bioactive natural products with C5N moiety.
The neutral gas in the environs of the Wolf Rayet stars in the Circinus OB1 association

We have investigated the neutral hydrogen in the direction of the Circinus OB1 association with particular emphasis in the study of the vicinity of the WR stars WR 65 and WR 67. The HI line data were obtained with the Australia Telescope Compact Array with a synthesized beam of $4\farcm0 \times 2\farcm7$ and a velocity resolution of 1.1 km s -1 . These data led to the discovery of a large cavity surrounded by an almost complete shell in agreement with the locations and distances of the two WR stars. We propose that the HI features constitute an interstellar bubble created by the powerful winds of the WR stars and their progenitors. By assuming a distance of 3 kpc, we calculate for this HI bubble a linear radius of 22 pc, a swept-up mass of 1600 $M_\odot$ and an expansion velocity of more than 7 km s -1 . High angular resolution IRAS infrared data (HIRES) reveal the presence of a ring with good spatial correlation with the HI shell. Eight IRAS protostellar candidates located around the HI cavity suggest that star formation may be taking place in the shell. Further investigation is required to confirm this proposition.
Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia

Objective We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. Methods Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. Results There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. Conclusion In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.
Continuous quality improvement in peritoneal dialysis: Your questions answered

Peritoneal dialysis (PD) uptake around the globe has steadily increased over the last several decades as a viable alternative to haemodialysis. Continued success of this technique for patients is contingent on the application of continuous quality improvement (CQI) principles in PD practice which can improve patient outcomes and in turn lead to more successful PD programmes worldwide. In this installation of ‘Your Questions Answered’, we will outline an approach to quality improvement initiatives and examine the importance of CQI principles in PD practice. We will also highlight common pitfalls and provide strategies to identify potential targets for improvement within your PD programme.
Development of a skin phantom of the epidermis and evaluation by using fluorescence techniques

The aim of this project was to develop a skin phantom that resembles the epidermis including the lipid matrix of the stratum corneum and the dermis. The main intent was to achieve optical properties similar to skin tissue. Therefore, two compartments of the skin, dermis and epidermis, were examined regarding their optical properties. Based on these results, the skin phantom was designed using relevant skin components. The scattering coefficient was measured by using Reflectance-based Confocal Microscopy (RCM) and the fluorescence spectrum was detected via confocal laser-scanning microscopy (CLSM). Prospective, the skin phantom can be used to incorporate various fluorescing chemicals, such as fluorescent dyes and fluorescent-labeled drugs to perform calibration measurements in wide-field and laser-scanning microscopes to provide a basis for the quantification of skin penetration studies.
Cystic echinococcosis in donkeys in eastern Africa

Abstract Abstract Cystic echinococcosis (CE) is endemic in humans and domestic animals in eastern Africa. All the species of the Echinococcus granulosus sensu lato complex have been reported in this region except for E. equinus, possibly due to the small number of studies involving equids. This study reports the frequency of different Echinococcus species in donkeys from eastern Africa. A total of 5961 donkeys were examined during meat inspection in 3 slaughterhouses in Kenya. Identification of Echinococcus spp. was achieved through polymerase chain reaction-restriction fragment-length polymorphism and sequencing of the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 gene. The prevalence of CE was 5.7% (337/5961). The 263 genotyped cysts belonged to E. equinus (n = 163), E. granulosus sensu stricto (n = 70), E. canadensis (G6/7) (n = 26) and E. ortleppi (n = 4). One donkey harboured a metacestode of Spirometra theileri. All E. equinus cases, except 2, originated from southern Ethiopia, whereas the other species were more evenly distributed across the study area. Most of the cysts belonging to E. equinus were fertile (111/163), while those of the other species were non-fertile. This is the first report of Echinococcus spp. in donkeys from sub-Saharan Africa and the first confirmation of E. equinus in East Africa. The frequent fertility of E. equinus cysts in donkeys affirms their suitability as intermediate hosts of this species, while low frequency and cyst fertility suggest a marginal role of donkeys in the transmission of E. granulosus s. s. , E. canadensis (G6/7) and E. ortleppi.
Accurately Assessing Teacher ADHD-Specific Attitudes Using the Scale for ADHD-Specific Attitudes

Objective: The aim of this study is therefore twofold, first to accurately examine the ADHD-specific attitudes of New South Wales Government school in-service teachers using the Scale for ADHD-Specific Attitudes (Authors 2016), and second, to determine if any of their socio-demographic features could predict their attitudes Method: Exploratory factor analysis found a 5-factor structure, and multiple regression analysis was performed to establish the existence of groups of variables with respect to teacher attitudes towards ADHD-type behaviours and any demographic predictors of teacher attitudes. Results: The final regression model found significant predictors of each factor with R2 values ranging from . 007 to . 147. Conclusion: This study illustrated that teachers had generally positive attitudes towards students who display ADHD-type behaviours, however, they found the externalised behaviours of ADHD irritating in the classroom and found teaching students with ADHD-type behaviours difficult, and teachers want more information about ADHD and how to manage it in the classroom.