Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Flavomycin and Colistin Sulfate Pre-Treatment on Ileal Bacterial Community Composition, the Response to Salmonella typhimurium and Host Gene Expression in Broiler Chickens

The composition of the bacterial community affects the intestinal health and growth performance of broiler chickens. The main purpose of this study was to explore the effects of flavomycin and colistin sulfate on the resistance to Salmonella typhimurium infection, ileal bacteria and intestinal health. In total, 396 1-day-old broiler chickens were randomly divided into six groups. Two groups were fed each one of the diets—the control diet (CON), the flavomycin at 10 mg/kg diet (AntiG+), and the colistin sulfate at 40 mg/kg diet (AntiG−), for 5 days. Then, one of each of the two groups was challenged with S. typhimurium on the 8th day; these were named CONS, AntiG+S and AntiG−S, respectively. The results showed that S. typhimurium significantly reduced the feed intake and body weight gain, and increased the feed conversion ratio (p < 0.05). It also increased the inflammatory expressions of NF-κB and MyD88 genes (p < 0.05); and reduced the expressions of claudin-1, occludin and mucin-2 (p < 0.05) tight junction genes in the intestines. S. typhimurium significantly reduced ileal bacterial diversity indexes of observed-species, chao1 and Shannon (p < 0.05). Compared with AntiG+S group, AntiG−S group increased the body weight gain of broiler chickens (p < 0.05), reduced the expression of inflammatory genes (p < 0.05) and intestinal permeability to fluorescein isothiocyanate (p < 0.05). AntiG-S group also improved the ileal bacterial diversity indexes of observed-species and Shannon (p < 0.05). There were many significant correlations between intestinal bacteria, intestinal gene expressions and intestinal morphology (p < 0.05). This study indicated that pre-constructed AntiG− bacteria could against a S. typhimurium infection by inhibiting the expressions of intestinal inflammation genes and increasing the diversity of intestinal bacteria.
An Implantable Cranial Window Using a Collagen Membrane for Chronic Voltage-Sensitive Dye Imaging

Incorporating optical methods into implantable neural sensing devices is a challenging approach for brain–machine interfacing. Specifically, voltage-sensitive dye (VSD) imaging is a powerful tool enabling visualization of the network activity of thousands of neurons at high spatiotemporal resolution. However, VSD imaging usually requires removal of the dura mater for dye staining, and thereafter the exposed cortex needs to be protected using an optically transparent artificial dura. This is a major disadvantage that limits repeated VSD imaging over the long term. To address this issue, we propose to use an atelocollagen membrane as the dura substitute. We fabricated a small cranial chamber device, which is a tubular structure equipped with a collagen membrane at one end of the tube. We implanted the device into rats and monitored neural activity in the frontal cortex 1 week following surgery. The results indicate that the collagen membrane was chemically transparent, allowing VSD staining across the membrane material. The membrane was also optically transparent enough to pass light; forelimb-evoked neural activity was successfully visualized through the artificial dura. Because of its ideal chemical and optical manipulation capability, this collagen membrane may be widely applicable in various implantable neural sensors.
Left ventricular mass normalization for body size in children based on an allometrically adjusted ratio is as accurate as normalization based on the centile curves method

Background Normalization for body size is required for reliable left ventricular mass (LVM) evaluation, especially in children due to the large variability of body size. In clinical practice, the allometrically adjusted ratio of LVM to height raised to the power of 2.7 is often used. However, studies presenting normative LVM data for children recommend centile curves as optimal for the development of normative data. This study aimed to assess whether the allometrically adjusted LVM-to-height ratio can reliably reproduce the results of LVM normalization for height based on the centile curves method. Methods Left ventricular mass was computed for 464 boys and 327 girls, 5–18 years old, based on echocardiographic examination. Normalized data representing LVM for height were developed using the centile curves construction method and two variants of the allometrically adjusted ratio method: one variant with the allometric exponents specific to the study groups, and one variant with the universal exponent of 2.7. The agreement between the allometric methods and the centile curves method was analyzed using the concordance correlation coefficient, sensitivity, and specificity. Results For both the specific allometric variant and the universal variant, the analysis of concordance has indicated high reproducibility compared to the centile curves method. The respective coefficient values were 0.9917 and 0.9916 for girls, and 0.9886 and 0.9869 for boys. The sensitivity and specificity test has also shown high agreement. However, for girls, the sensitivity was higher for the specific variant (100% vs. 90.9%). Conclusion The results of the study show that allometric scaling of LVM for height can very reliably reproduce the results of LVM normalization for height based on the centile curves method. However, the analysis of sensitivity and specificity indicates greater agreement for the allometric normalization with the group-specific allometric exponents.
A Multi-Domain and Multi-Modal Representation Disentangler for Cross-Domain Image Manipulation and Classification

Learning interpretable data representation has been an active research topic in deep learning and computer vision. While representation disentanglement is an effective technique for addressing this task, existing works cannot easily handle the problems in which manipulating and recognizing data across multiple domains are desirable. In this paper, we present a unified network architecture of Multi-domain and Multi-modal Representation Disentangler ( $M^{2}RD$ ), with the goal of learning domain-invariant content representation with the associated domain-specific representation observed. By advancing adversarial learning and disentanglement techniques, the proposed model is able to perform continuous image manipulation across data domains with multiple modalities. More importantly, the resulting domain-invariant feature representation can be applied for unsupervised domain adaptation. Finally, our quantitative and qualitative results would confirm the effectiveness and robustness of the proposed model over state-of-the-art methods on the above tasks.
Fabrication of a Large-Area, Fused Polymer Micromold Based on Electric-Field-Driven (EFD) μ-3D Printing

An electric-field-driven (EFD), μ-3D printed, fused polymer technique has been developed for the fabrication of large-area microscale prototype molds using typical polymer materials, including microcrystalline wax (MC-wax), polycaprolactone (PCL), and polymathic methacrylate (PMMA). This work proposes an alternative for large area microscale modes and overcomes the limitation of high cost in the traditional mold manufacturing industry. The EFD principle enables printing of fused polymers materials more than one order of magnitude lower than the nozzle diameter, contributing to the necking effect of the Taylor cone jet, which is the key factor to achieve the microscale manufacturing. Numerical simulation of electric field distribution between the meniscus and substrate was carried out to elucidate the dependence of electric field distribution on the meniscus condition of three types of polymers under printable voltage, and the electrical field parameters for the EFD μ-3D printing were determined. A number of experiments were printed successfully using a large range of viscosity materials, ranging from tens of mPa·s to hundreds of thousands of mPa·s of PCL and PMMA. The differences in parameters of different materials, such as viscosity, tensile properties, and surface energy, were studied to assess their use in different fields. Using proper process parameters and a nozzle with an inner diameter of 200 μm, three different application cases were completed, including a Wax microarray and microchannel with a minimum dot diameter of 20 μm, a PCL mesh structure with a minimum line width of 5 μm, and a PMMA large-area mold with a maximum aspect ratio of 0.8. Results show that the EFD μ-3D printing has the outstanding advantages of high printing resolution and polymer material universality.
Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells

Significance Hematopoietic stem cells (HSCs) are rare cells with the unique ability to self-renew and produce all blood cells throughout life. HSCs are functionally heterogeneous, and studies have shown that HSCs can differ in their contribution to major blood lineages. We found that the surface marker Neogenin-1, when combined with the reporter gene for long-term repopulating HSCs, Hoxb5, can stratify HSCs into 2 subpopulations—one that is more active and biased toward producing myeloid cells and another that is more dormant and capable of producing all blood lineages equally. Neogenin-1 reveals the diversity and hierarchical relationship of HSCs in the mouse bone marrow, enables the prospective isolation of myeloid-biased and balanced HSCs, and opens opportunities to do the same in humans. Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs expand with age and respond to myeloablative stress in young mice while NEO1−Hoxb5+ LT-HSCs exhibit no significant change in number. Furthermore, NEO1+Hoxb5+ LT-HSCs are more often in the G2/S cell cycle phase compared to NEO1−Hoxb5+ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution while NEO1−Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1+ fraction and association of quiescence and self-renewal–related transcription factors with NEO1− LT-HSCs. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1−Hoxb5+ LT-HSCs while NEO1−Hoxb5+ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced NEO1−Hoxb5+ LT-HSCs can hierarchically precede active, myeloid-biased NEO1+Hoxb5+ LT-HSCs.
Mitochondrial Arginase-2 is a cell autonomous regulator of CD8+ T cell function and anti-tumor efficacy.

As sufficient extracellular arginine is crucial for T cell function, depletion of extracellular arginine by elevated Arginase 1 (Arg1) activity has emerged as a hallmark immunosuppressive mechanism. However, the potential cell-autonomous roles of arginases in T cells have remained unexplored. Here we show that the arginase isoform expressed by T cells, the mitochondrial Arginase 2 (Arg2), is a cell-intrinsic regulator of CD8+ T cell activity. Both germ-line Arg2 deletion and adoptive transfer of Arg2-/- CD8+ T cells significantly reduced tumor growth in preclinical cancer models by enhancing CD8+ T cell activation, effector function and persistence. Transcriptomic, proteomic and high-dimensional flow cytometry characterization revealed a CD8+ T cell-intrinsic role of Arg2 in modulating T cell activation, anti-tumor cytoxicity and memory formation, independently of extracellular arginine availability. Furthermore, specific deletion of Arg2 in CD8+ T cells strongly synergized with PD-1 blockade for the control of tumor growth and animal survival. These observations coupled with the finding that pharmacologic arginase inhibition accelerates activation of ex vivo human T cells unveil Arg2 as a new therapeutic target for T cell-based cancer therapies.
Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration with Wuzhi capsule

Tacrolimus, an immunosuppressant, has been used to treat paediatric systemic lupus erythematosus, but the optimal initial regimen is not clear. The purpose of this study was to explore the optimal initial dose of tacrolimus for children with systemic lupus erythematosus using population pharmacokinetics and pharmacogenomics.
Deep Learning Models for Health and Safety Risk Prediction in Power Infrastructure Projects

Inappropriate management of health and safety (H&S) risk in power infrastructure projects can result in occupational accidents and equipment damage. Accidents at work have detrimental effects on workers, company, and the general public. Despite the availability of H&S incident data, utilizing them to mitigate accident occurrence effectively is challenging due to inherent limitations of existing data logging methods. In this study, we used a text‐mining approach for retrieving meaningful terms from data and develop six deep learning (DL) models for H&S risks management in power infrastructure. The DL models include DNNclassify (risk or no risk), DNNreg1 (loss time), DNNreg2 (body injury), DNNreg3 (plant and fleet), DNNreg4 (equipment), and DNNreg5 (environment). An H&S risk database obtained from a leading UK power infrastructure construction company was used in developing the models using the H2O framework of the R language. Performances of DL models were assessed and benchmarked with existing models using test data and appropriate performance metrics. The overall accuracy of the classification model was 0.93. The average R2 value for the five regression models was 0.92, with mean absolute error between 0.91 and 0.94. The presented results, in addition to the developed user‐interface module, will help practitioners obtain a better understanding of H&S challenges, minimize project costs (such as third‐party insurance and equipment repairs), and offer effective strategies to mitigate H&S risk.
The Analysis of the Influence of Threshold on the Dynamic Contact Process of a Fabricated Vertically Driven MEMS Inertial Switch

In this work, to evaluate the influence of the threshold on the dynamic contact process, five models (number 1, 2, 3, 4, 5) with different thresholds were proposed and fabricated with surface micromachining technology. The contact time and response time were used to characterize the dynamic contact performance. The dynamic contact processes of the inertial switches with gradually increasing thresholds were researched using analytical, simulation, and experimental methods. The basic working principle analysis of the inertial switch shows that the contact time of the inertial switch with a low-g value can be extended by using a simply supported beam as the fixed electrode, but the high-G inertial needs more elasticity for fixed electrode. The simulation results indicate that the response time and contact time decrease with the increment in the designed threshold. Prototypes were tested using a dropping hammer system, and the test result indicates that the contact time of the inertial switch with a fixed electrode of the simply supported beam is about 15 and 5 μs when the threshold is about 280 and 580 g, respectively. Meanwhile, the contact time can be extended to 100 μs for the inertial switch using a spring as the fixed electrode when the threshold is about 280 and 580 g. These test results not only prove that the spring fixed electrode can effectively extend the contact time, but also prove that the style of the fixed electrode is the deciding factor affecting the contact time of the high-G inertial switch.
Modelling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation

The accurate clinical interpretation of human sequence variation is foundational to personalized medicine. This remains a pressing challenge, however, as genome sequencing becomes routine and new functionally undefined variants rapidly accumulate. Here, we describe a platform for the rapid generation, characterization and interpretation of genomic variants in haploid cells focusing on Niemann-Pick disease type C (NPC) as an example. NPC is a fatal neurodegenerative disorder characterized by a lysosomal accumulation of unesterified cholesterol and glycolipids. In 95% of cases, NPC is caused by mutations in the NPC1 gene, where over 200 unique disease-causing variants have been reported to date. Furthermore, the majority of patients with NPC are compound heterozygotes that often carry at least one private mutation, presenting a challenge for the characterization and classification of individual variants. Here, we have developed the first haploid cell model of NPC. This haploid cell model recapitulates the primary biochemical and molecular phenotypes typically found in patient-derived fibroblasts, illustrating its utility in modelling NPC. Additionally, we demonstrate the power of CRISPR-Cas9-mediated base editing in quickly and efficiently generating haploid cell models of individual patient variants in NPC. These models provide a platform for understanding the disease mechanisms underlying individual NPC1 variants while allowing for definitive clinical variant interpretation for NPC. While this study has focused on modelling NPC, the outlined approach could be translated widely and applied to a variety of genetic disorders or understanding the pathogenicity of somatic mutations in cancer.
An innovative corticosteroid/long-acting β2-agonist breath-triggered inhaler: facilitating lung delivery of fluticasone propionate/formoterol fumarate for the treatment of asthma

ABSTRACT Introduction: Incorrect inhaler technique is one reason why the efficacies of inhaled asthma treatments in clinical trials and effectiveness in the real world differ. Inhaler technique is critical for drug delivery to the lungs; incorrect technique negatively impacts asthma control and long-term outcomes. Breath-triggered inhalers (BTIs) can simplify drug administration and are suitable for most patients, including those with reduced inspiratory flow. Until recently, no inhaled corticosteroid/long-acting β2-agonist combination BTI was available in Europe. The flutiform® (fluticasone propionate/formoterol fumarate [FP/FORM]) k-haler® is the first combination BTI now approved in Europe for asthma maintenance treatment. Areas covered: We review studies examining the challenges posed to patients by different inhaler types and explore evidence demonstrating the clinical efficacy of FP/FORM administered via a pressurized metered-dose inhaler. We also review the pharmacokinetic/pharmacodynamic studies supporting FP/FORM k-haler use, and consider data showing high lung deposition with the device. Finally, we review patient experiences using the BTI, device characteristics, and health economic aspects. Expert opinion: Despite the availability of therapies, asthma control levels remain low, and there is a clear need for easy-to-use inhalers. Research to increase our understanding of critical errors with each inhaler and how to overcome them is important for improving care. Abbreviations: AUCt: area under the plasma concentration–time curve from the time of dosing to the last measurable concentration; BDP: beclometasone dipropionate; BTI: breath-triggered inhaler; BUD: budesonide; CI: confidence interval; Cmax: maximum observed plasma concentration; DPI: dry powder inhaler; FDC: fixed-dose combination; FEV1: forced expiratory volume in 1 s; FORM: formoterol fumarate; FP: fluticasone propionate; HCP: health-care professional; ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; OR: odds ratio; PIL: patient information leaflet; pMDI: pressurized metered-dose inhaler; SAL: salmeterol xinafoate
Structural Insights into Escherichia coli Shiga Toxin (Stx) Glycosphingolipid Receptors of Porcine Renal Epithelial Cells and Inhibition of Stx-Mediated Cellular Injury Using Neoglycolipid-Spiked Glycovesicles

Shiga toxin (Stx) producing Escherichia coli (STEC) cause the edema disease in pigs by releasing the swine-pathogenic Stx2e subtype as the key virulence factor. Stx2e targets endothelial cells of animal organs including the kidney harboring the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer). Since the involvement of renal epithelial cells in the edema disease is unknown, in this study, we analyzed the porcine kidney epithelial cell lines, LLC-PK1 and PK-15, regarding the presence of Stx-binding GSLs, their sensitivity towards Stx2e, and the inhibitory potential of Gb3- and Gb4-neoglycolipids, carrying phosphatidylethanolamine (PE) as the lipid anchor, towards Stx2e. Immunochemical and mass spectrometric analysis revealed various Gb3Cer and Gb4Cer lipoforms as the dominant Stx-binding GSLs in both LLC-PK1 and PK-15 cells. A dihexosylceramide with proposed Galα1-4Gal-sequence (Gal2Cer) was detected in PK-15 cells, whereas LLC-PK1 cells lacked this compound. Both cell lines were susceptible towards Stx2e with LLC-PK1 representing an extremely Stx2e-sensitive cell line. Gb3-PE and Gb4-PE applied as glycovesicles significantly reduced the cytotoxic activity of Stx2e towards LLC-PK1 cells, whereas only Gb4-PE exhibited some protection against Stx2e for PK-15 cells. This is the first report identifying Stx2e receptors of porcine kidney epithelial cells and providing first data on their Stx2e-mediated damage suggesting possible involvement in the edema disease.
MiST 3.0: an updated microbial signal transduction database with an emphasis on chemosensory systems

Abstract Bacteria and archaea employ dedicated signal transduction systems that modulate gene expression, second-messenger turnover, quorum sensing, biofilm formation, motility, host-pathogen and beneficial interactions. The updated MiST database provides a comprehensive classification of microbial signal transduction systems. This update is a result of a substantial scaling to accommodate constantly growing microbial genomic data. More than 125 000 genomes, 516 million genes and almost 100 million unique protein sequences are currently stored in the database. For each bacterial and archaeal genome, MiST 3.0 provides a complete signal transduction profile, thus facilitating theoretical and experimental studies on signal transduction and gene regulation. New software infrastructure and distributed pipeline implemented in MiST 3.0 enable regular genome updates based on the NCBI RefSeq database. A novel MiST feature is the integration of unique profile HMMs to link complex chemosensory systems with corresponding chemoreceptors in bacterial and archaeal genomes. The data can be explored online or via RESTful API (freely available at https://mistdb.com).