Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Dietary-SCFA on Microbial Protein Synthesis and Urinal Urea-N Excretion Are Related to Microbiota Diversity in Rumen

Two experiments were performed in this study. In Experiment 1, twenty goats were fed with an isonitrogenous diet, containing 28% Non-Fiber Carbohydrate (MNFC group, n = 10) or 14% NFC (LNFC group, n = 10). In the MNFC group, the ruminal concentration of Short Chain Fatty Acids (SCFA) increased, and pH declined. Compared with those in the LNFC group, the microbial protein synthesis in rumen and mRNA abundance of urea transporter B (UT-B) in rumen epithelium increased in the MNFC group, although serum urea-N (SUN) did not differ significantly between groups. Simultaneously, urinal urea-N excretion was reduced in the MNFC group. Significant correlations were found between rumen SCFA and UT-B and between UT-B and urinal urea-N excretion. Furthermore, the abundances of SCFA receptor of GPR41 and GPR43 increased in the rumen epithelium of the MNFC group. These results suggest that increases of SUN transported into the rumen and incorporated into microbial protein and decreases of urinal urea-N excretion are related to ruminal SCFA. This is supported by data from our previous study in which added SCFA on the mucosal side caused increases of urea transport rate (flux Jsm urea) from the blood to the ruminal lumen side. In Experiment 2, we used 16S rRNA Amplicon Sequencing to analyze the structure of the ruminal microbiota community in relation to SCFA. An additional eight goats were assigned into the MNFC (n = 4) and LNFC (n = 4) groups. The dietary ingredients, chemical composition, and feeding regimes were the same as those in Experiment 1. Constrained correspondence analysis (CCA analysis) revealed NFC promoted the expansion of microbiota diversity, particularly of SCFA-producing microbes. The function prediction of 19 upregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog groups showed an NFC-induced increase of the types and abundances of genes coding for enzymes catalyzing N and fatty acid metabolism. Based on our present and previous investigations, our results indicate that, in goats consuming a MNFC diet, the facilitated urea transport in the rumen and improved urea N salvage are triggered by an expansion of ruminal microbiota diversity and are signaled by ruminal SCFA. This study thus provides new insights into the microbiota involved in the dietary modulation of urea-N salvage in ruminant animals.
Therapeutic drug monitoring (TDM) during maintenance phase treatment at a community mental health centre

Objective: To assess the extent to which therapeutic drug monitoring during maintenance phase treatment with lithium and clozapine was performed according to an agreed protocol and to identify strategies that may support monitoring. Methods: Data concerning the prescribing and monitoring patterns of lithium for 31 patients and clozapine for 53 patients were collected retrospectively over a period of 2 years. Results: Adherence to clozapine monitoring throughout the study period was 90.5%, while the monitoring of lithium was less likely at 58.1% (P < 0.001). While those prescribed lithium were less likely to adhere to prescribed dosing than those prescribed clozapine (P < 0.007), they were also more likely to have a change of medication (P < 0.005) and require admission to inpatient care (P < 0.002). Conclusions: Despite the initiatives established to improve adherence to monitoring, there was a significantly lower level of lithium monitoring compared to that of clozapine. Strategies that are likely to support monitoring include the use of labels to clarify tests required, the use of a database to keep track of those requiring pathology tests and allocation of time each week for a nurse to work with medical staff and case managers to support monitoring.
Proteomic analysis of Rhizobium favelukesii LPU83 in response to acid stress.

Acid soils constitute a severe problem for leguminous crops mainly through a disturbance in rhizobium-legume interactions. Rhizobium favelukesii-an acid-tolerant rhizobium able to nodulate alfalfa-is highly competitive for nodule occupation under acid conditions, but inefficient for biologic nitrogen fixation. In this work, we obtained a general description of the acid-stress response of R. favelukesii LPU83 by means of proteomics by comparing the total proteome profiles in the presence or absence of acid stress by nanoflow ultrahigh-performance liquid chromatography coupled to mass spectrometry. Thus, a total of 336 proteins were identified with a significant differential expression, 136 of which species were significantly overexpressed and 200 underexpressed in acidity. An in-silico functional characterization with those respective proteins revealed a complex and pleiotropic response by these rhizobia involving components of oxidative phosphorylation, glutamate metabolism, and peptidoglycan biosynthesis, among other pathways. Furthermore, a lower permeability was evidenced in the acid-stressed cells along with several overexpressed proteins related to γ-aminobutyric-acid metabolism, such as the gene product of livK, which gene was mutated. This mutant exhibited an acid-sensitive phenotype in agreement with the proteomics results. We conclude that both γ-aminobutyric-acid metabolism and a modified cellular envelope could be relevant to acid tolerance in R. favelukesii.
Sphingolipid Synthesis Inhibition by Myriocin Administration Enhances Lipid Consumption and Ameliorates Lipid Response to Myocardial Ischemia Reperfusion Injury

Myocardial infarct requires prompt thrombolytic therapy or primary percutaneous coronary intervention to limit the extent of necrosis, but reperfusion creates additional damage. Along with reperfusion, a maladaptive remodeling phase might occur and it is often associated with inflammation, oxidative stress, as well as a reduced ability to recover metabolism homeostasis. Infarcted individuals can exhibit reduced lipid turnover and their accumulation in cardiomyocytes, which is linked to a deregulation of peroxisome proliferator activated receptors (PPARs), controlling fatty acids metabolism, energy production, and the anti-inflammatory response. We previously demonstrated that Myriocin can be effectively used as post-conditioning therapeutic to limit ischemia/reperfusion-induced inflammation, oxidative stress, and infarct size, in a murine model. In this follow-up study, we demonstrate that Myriocin has a critical regulatory role in cardiac remodeling and energy production, by up-regulating the transcriptional factor EB, PPARs nuclear receptors and genes involved in fatty acids metabolism, such as VLDL receptor, Fatp1, CD36, Fabp3, Cpts, and mitochondrial FA dehydrogenases. The overall effects are represented by an increased β–oxidation, together with an improved electron transport chain and energy production. The potent immunomodulatory and metabolism regulatory effects of Myriocin elicit the molecule as a promising pharmacological tool for post-conditioning therapy of myocardial ischemia/reperfusion injury.
A Tool for Visualization and Analysis of Single-Cell RNA-Seq Data Based on Text Mining

Gene expression in individual cells can now be measured for thousands of cells in a single experiment thanks to innovative sample-preparation and sequencing technologies. State-of-the-art computational pipelines for single-cell RNA-sequencing data, however, still employ computational methods that were developed for traditional bulk RNA-sequencing data, thus not accounting for the peculiarities of single-cell data, such as sparseness and zero-inflated counts. Here, we present a ready-to-use pipeline named gf-icf (gene frequency–inverse cell frequency) for normalization of raw counts, feature selection, and dimensionality reduction of scRNA-seq data for their visualization and subsequent analyses. Our work is based on a data transformation model named term frequency–inverse document frequency (TF-IDF), which has been extensively used in the field of text mining where extremely sparse and zero-inflated data are common. Using benchmark scRNA-seq datasets, we show that the gf-icf pipeline outperforms existing state-of-the-art methods in terms of improved visualization and ability to separate and distinguish different cell types.
A Comparative Genome-Wide Analysis of the R2R3-MYB Gene Family Among Four Gossypium Species and Their Sequence Variation and Association With Fiber Quality Traits in an Interspecific G. hirsutum × G. barbadense Population

Cotton (Gossypium spp.) is the most important natural fiber crop in the world. The R2R3-MYB gene family is a large gene family involved in many plant functions including cotton fiber development. Although previous studies have reported its phylogenetic relationships, gene structures, and expression patterns in tetraploid G. hirsutum and diploid G. raimondii, little is known about the sequence variation of the members between G. hirsutum and G. barbadense and their involvement in the natural quantitative variation in fiber quality and yield. In this study, a comprehensive genome-wide comparative analysis was performed among the four Gossypium species using whole genome sequences, i.e., tetraploid G. hirsutum (AD1) and G. barbadense (AD2) as well as their likely ancestral diploid extants G. raimondii (D5) and G. arboreum (A2), leading to the identification of 406, 393, 216, and 213 R2R3-MYB genes, respectively. To elucidate whether the R2R3-MYB genes are genetically associated with fiber quality traits, 86 R2R3-MYB genes were co-localized with quantitative trait loci (QTL) hotspots for fiber quality and yield, including 42 genes localized within the fiber length QTL hotspots, in interspecific G. hirsutum × G. barbadense populations. There were 20 interspecific nonsynonymous single-nucleotide polymorphism (SNP) sites between the two tetraploid cultivated species, of which 16 developed from 11 R2R3-MYB genes were significantly correlated with fiber quality and yield in a backcross inbred population (BIL) of G. hirsutum × G. barbadense in at least one of the four field tests. Taken together, these results indicate that the sequence variation in these 11 R2R3-MYB genes is associated with the natural variation (i.e., QTL) in fiber quality and yield. Moreover, the functional SNPs of five R2R3-MYB allele pairs from the AD1 and AD2 genomes were significantly correlated with the gene expression related to fiber quality in fiber development. The results will be useful in further elucidating the role of the R2R3-MYB genes during fiber development.
Impact of an Antibiotic Stewardship Program on Antibiotic Prescription for Acute Respiratory Tract Infections in Children: A Prospective Before-After Study

We assessed the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescriptions for acute respiratory tract infection (ARTI) in a medical school. Our ASP included delivering an antibiotic use guideline via e-mail and LINE (an instant messaging app) to faculty staff, fellows, and residents, and posting of the guideline in examination rooms. Medical records of pediatric patients diagnosed with ARTI were reviewed to assess the appropriateness of antibiotic prescription. ASP could increase the rate of appropriateness from 78% (1979 out of 2553 visits) to 83.4% (2449 out of 2935 visits; P < .001). The baseline of appropriateness was higher in residents (95%) compared with fellows (82%) and faculty staff (75%). The ASP significantly increased the appropriateness only in faculty staff, especially in semiprivate clinics (75% to 83%, P < .001). In conclusion, our ASP increased appropriateness of antibiotic prescriptions for ARTI, with the greatest impact among faculty staff in semiprivate clinics.
Integrating multi-omics longitudinal data to reconstruct networks underlying lung development.

A comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. To construct such a model, we profiled mRNA, microRNA, DNA methylation, and proteomics of developing murine alveoli isolated by laser capture microdissection at 14 predetermined time points. We developed a detailed comprehensive and interactive model that provides information about the major expression trajectories, the regulators of specific key events, and the impact of epigenetic changes. Intersecting the model with single cell RNAseq (scRNA-Seq) data led to the identification of active pathways in multiple or individual cell types. We then constructed a similar model for human lung development by profiling time series human omics datasets. Several key pathways and regulators are shared between the reconstructed models. We experimentally validated the activity of a number of predicted regulators leading to new insights about the regulation of innate immunity during lung development.
Glycogen synthase kinase-3 beta inhibitors protectagainst the acute lung injuries resulting from acute necrotizing pancreatitis 1

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.
Model-Based Inference of Synaptic Transmission

Synaptic computation is believed to underlie many forms of animal behavior. A correct identification of synaptic transmission properties is thus crucial for a better understanding of how the brain processes information, stores memories and learns. Recently, a number of new statistical methods for inferring synaptic transmission parameters have been introduced. Here we review and contrast these developments, with a focus on methods aimed at inferring both synaptic release statistics and synaptic dynamics. Furthermore, based on recent proposals we discuss how such methods can be applied to data across different levels of investigation: from intracellular paired experiments to in vivo network-wide recordings. Overall, these developments open the window to reliably estimating synaptic parameters in behaving animals.
MicroRNAs as Therapeutic Targets in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin that is prone to local invasion and early distant metastasis. Although concurrent chemotherapy and radiotherapy improves the 5-year survival outcomes, persistent or recurrent disease still occurs. Therefore, novel therapeutic targets are needed for NPC patients. MicroRNAs (miRNAs) play important roles in normal cell homeostasis, and dysregulations of miRNA expression have been implicated in human cancers. In NPC, studies have revealed that miRNAs are dysregulated and involved in tumorigenesis, metastasis, invasion, resistance to chemo- and radiotherapy, and other disease- and treatment-related processes. The advantage of miRNA-based treatment approaches is that miRNAs can concurrently target multiple effectors of pathways involved in tumor cell differentiation and proliferation. Thus, miRNA-based cancer treatments, alone or combined with standard chemotherapy and/or radiotherapy, hold promise to improve treatment response and cure rates. In this review, we will summarize the dysregulation of miRNAs in NPC initiation, progression, and treatment as well as NPC-related signaling pathways, and we will discuss the potential applications of miRNAs as biomarkers and therapeutic targets in NPC patients. We conclude that miRNAs might be potential promising therapeutic targets in nasopharyngeal carcinoma.
Fluorescein Application in Cranial and Spinal Tumors Enhancing at Preoperative MRI and Operated With a Dedicated Filter on the Surgical Microscope: Preliminary Results in 279 Patients Enrolled in the FLUOCERTUM Prospective Study

Objective: Sodium fluorescein, a green, water soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier (BBB) disruption. The authors report the preliminary results of a prospective observational study regarding the use of fluorescein-guided technique for the resection of suspected malignant neoplasms of the central nervous system (CNS), contrast enhancing at preoperative magnetic resonance imaging (MRI), using a dedicated filter on the surgical microscope. Methods: In March 2016 the authors started a prospective, observational trial to evaluate intraoperative fluorescence's characteristics of CNS tumors, the percentage of extent of resection thanks to fluorescein aid and side effects related to fluorescein administration. This report is based on a preliminary analysis of the results of first 279 enrolled patients. Fluorescein was intravenously injected after intubation or immediately at the entrance in the operating room for awake procedures; the tumor was removed using a dedicated filter on the surgical microscope in an inside-out fashion until all fluorescent tissue was removed, as considered feasible by the surgeon. Results: The 279 patients finally enrolled in the trial, both firstly diagnosed and recurrent, were categorized according to WHO pathological classification and there were 212 neuroepithelial tumors, 25 brain metastases, 10 cerebral lymphomas, 7 hemangioblastomas, or hemangioendotheliomas and 25 other tumors and conditions. No adverse reaction related to the administration of fluorescein or to the combined use of fluorescein with other fluorophores was registered. Fluorescein accumulated in cerebral regions where the BBB was damaged, representing a significant surgical aid in most of the CNS tumors with contrast enhancement. In cases of complete removal of all fluorescent tissue, as intraoperatively judged by the surgeon, postoperative MRI revealed a gross total resection in 181/198 patients (91.4%). Conclusions: Based on these preliminary results, fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration.
Accuracy of Individuals Post-hemiparetic Stroke in Matching Torques Between Arms Depends on the Arm Referenced

Background: Prior work indicates that 50–75% of individuals post-hemiparetic stroke have upper-extremity weakness and, in turn, inaccurately judge the relative torques that their arms generate during a bimanual task. Recent findings also reveal that these individuals judge the relative torques their arms generate differently depending on whether they reference their paretic vs. non-paretic arm. Objective: Our goal was to determine whether individuals with hemiparetic stroke inaccurately matched torques between arms, regardless of the arm that they referenced. Methods: Fifteen participants with hemiparetic stroke and 10 right-hand dominant controls matched torques between arms. Participants performed this task with their right arm referencing their left arm, and vice versa. Participants generated (1) 5 Nm and (2) 25% of their reference elbow's maximum voluntary torque (MVT) in flexion and extension using their reference arm while receiving audiovisual feedback. Then, participants matched the reference torque using their opposite arm without receiving feedback on their matching performance. Results: Participants with stroke had greater magnitudes of error in matching torques than controls when referencing their paretic arm (p < 0.050), yet not when referencing their non-paretic arm (p > 0.050). The mean magnitude of error when participants with stroke referenced their paretic and non-paretic arm and controls referenced their dominant and non-dominant arm to generate 5 Nm in flexion was 9.4, 2.6, 4.2, and 2.5 Nm, respectively, and in extension was 5.3, 2.8, 2.5, and 2.3 Nm, respectively. However, when the torques generated at each arm were normalized by the corresponding MVT, no differences were found in matching errors regardless of the arm participants referenced (p > 0.050). Conclusions: Results demonstrate the importance of the arm referenced, i.e., paretic vs. non-paretic, on how accurately individuals post-hemiparetic stroke judge their torques during a bimanual task. Results also indicate that individuals with hemiparetic stroke judge torques primarily based on their perceived effort. Finally, findings support the notion that training individuals post-hemiparetic stroke to accurately perceive their self-generated torques, with a focus of their non-paretic arm in relation to their paretic arm, may lead to an improved ability to perform bimanual activities of daily living.
A Swarm Optimization Solver Based on Ferroelectric Spiking Neural Networks

As computational models inspired by the biological neural system, spiking neural networks (SNN) continue to demonstrate great potential in the landscape of artificial intelligence, particularly in tasks such as recognition, inference, and learning. While SNN focuses on achieving high-level intelligence of individual creatures, Swarm Intelligence (SI) is another type of bio-inspired models that mimic the collective intelligence of biological swarms, i.e., bird flocks, fish school and ant colonies. SI algorithms provide efficient and practical solutions to many difficult optimization problems through multi-agent metaheuristic search. Bridging these two distinct subfields of artificial intelligence has the potential to harness collective behavior and learning ability of biological systems. In this work, we explore the feasibility of connecting these two models by implementing a generalized SI model on SNN. In the proposed computing paradigm, we use SNNs to represent agents in the swarm and encode problem solutions with the spike firing rate and with spike timing. The coupled neurons communicate and modulate each other's action potentials through event-driven spikes and synchronize their dynamics around the states of optimal solutions. We demonstrate that such an SI-SNN model is capable of efficiently solving optimization problems, such as parameter optimization of continuous functions and a ubiquitous combinatorial optimization problem, namely, the traveling salesman problem with near-optimal solutions. Furthermore, we demonstrate an efficient implementation of such neural dynamics on an emerging hardware platform, namely ferroelectric field-effect transistor (FeFET) based spiking neurons. Such an emerging in-silico neuron is composed of a compact 1T-1FeFET structure with both excitatory and inhibitory inputs. We show that the designed neuromorphic system can serve as an optimization solver with high-performance and high energy-efficiency.