Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Conventional Molecular and Whole-Genome Sequencing Methods for Differentiating Salmonella enterica Serovar Schwarzengrund Isolates Obtained from Food and Animal Sources

Over the last decade, Salmonella enterica serovar Schwarzengrund has become more prevalent in Asia, Europe, and the US with the simultaneous emergence of multidrug-resistant isolates. As these pathogens are responsible for many sporadic illnesses and chronic complications, as well as outbreaks over many countries, improved surveillance is urgently needed. For 20 years, pulsed-field gel electrophoresis (PFGE) has been the gold standard for determining bacterial relatedness by targeting genome-wide restriction enzyme polymorphisms. Despite its utility, recent studies have reported that PFGE results correlate poorly with that of closely related outbreak strains and clonally dominant endemic strains. Due to these concerns, alternative amplification-based molecular methods for bacterial strain typing have been developed, including clustered regular interspaced short palindromic repeats (CRISPR) and multilocus sequence typing (MLST). Furthermore, as the cost of sequencing continues to decrease, whole genome sequencing (WGS) is poised to replace other molecular strain typing methods. In this study, we assessed the discriminatory power of PFGE, CRISPR, MLST, and WGS methods to differentiate between 23 epidemiologically unrelated S. enterica serovar Schwarzengrund isolates collected over an 18-year period from distinct locations in Taiwan. The discriminatory index (DI) of each method for different isolates was calculated, resulting in values between 0 (not discriminatory) and 1 (highly discriminatory). Our results showed that WGS has the greatest resolution (DI = 0.982) compared to PFGE (DI = 0.938), CRISPR (DI = 0.906), and MLST (DI = 0.463) methods. In conclusion, the WGS typing approach was shown to be the most sensitive for S. enterica serovar Schwarzengrund fingerprinting.
COVAX and the rise of the ‘super public private partnership’ for global health

ABSTRACT COVAX, the vaccines pillar of the Access to Covid-19 Tools Accelerator (ACT-A), has been promoted as ‘the only global solution' to vaccine equity and ending the Covid-19 pandemic. ACT-A and COVAX build on the public-private partnership (PPP) model that dominates global health governance, but take it to a new level, constituting an experimental form that we call the ‘super-PPP'. Based on an analysis of COVAX's governance structure and its difficulties in achieving its aims, we identify several features of the super-PPP model. First, it aims to coordinate the fragmented global health field by bringing together existing PPPs in an extraordinarily complex Russian Matryoshka doll-like structure. Second, it attempts to scale up a governance model designed for donor-dependent countries to tackle a health crisis affecting the entire world, pitting it against the self-interest of its wealthiest government partners. Third, the super-PPP's structural complexity obscures the vast differences between constituent partners, giving pharmaceutical corporations substantial power and making public representation, transparency, and accountability elusive. As a super-PPP, COVAX reproduces and amplifies challenges associated with the established PPPs it incorporates. COVAX's limited success has sparked a crisis of legitimacy for the voluntary, charity-based partnership model in global health, raising questions about its future.
Processing of Al2O3-AlN Ceramics and Their Structural, Mechanical, and Tribological Characterization

The aim of this study is to present a novel, lower sintering temperature preparation, processing, structural, mechanical, and tribological testing of the AlN-Al2O3 ceramics. The precursor powder of AlN was subjected to oxidation in ambient environment at 900 °C for 3, 10, and 20 h, respectively. These oxidized powders were characterized by SEM and XRD to reveal their morphology, phase, and crystal structure. The SEM results showed coarse powder particles and the presence of aluminum oxide (Al2O3) phase at the surface of aluminum nitride (AlN). The XRD analysis has shown increasing aluminum-oxy-nitride conversion of aluminum nitride as the holding time of oxidation increased. The highest percentage of conversion of AlN powder to AlN-Al2O3 was observed after 10 h. Simultaneously the powders were compacted and sintered using the hot isostatic pressing (HIP) under inert environment (N2 gas) at 1700 °C, 20 MPa for 5 h. This led to the compaction and increase in density of the final samples. Mechanical tests, such as bending test and tribology tests, were carried out on the samples. The mechanical properties of the samples were observed to improve in the oxidized samples compared to the precursor AlN. Moreover, applying longer oxidation time, the mechanical properties of the sintered samples enhanced significantly. Optimum qualitative (microstructure, oxide percentage) and quantitative (tribology, hardness, and bending tests) properties were observed in samples with 10-h oxidation time.
Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

Urinary tract infections (UTIs) are quite common and mainly caused by bacteria such as Escherichia coli. However, when patients have urinary catheters, fungal infections comprise up to 15% of these types of infections. Moreover, fungal UTIs have a high mortality, due to rapid spreading of the fungi to the kidneys. Most fungal UTIs are caused by Candida species, among which Candida albicans and Candida glabrata are the most common. C. glabrata is an opportunistic pathogenic yeast, phylogenetically quite close to Saccharomyces cerevisiae. Even though it is commonly isolated from the urinary tract and rapidly acquires resistance to antifungals, its pathogenesis has not been studied extensively in vivo. In vivo studies require high numbers of animals, which can be overcome by the use of non-invasive imaging tools. One such tool, bioluminescence imaging, has been used successfully to study different types of C. albicans infections. For C. glabrata, only biofilms on subcutaneously implanted catheters have been imaged using this tool. In this work, we investigated the progression of C. glabrata UTIs from the bladder to the kidneys and the spleen. Furthermore, we optimized expression of a red-shifted firefly luciferase in C. glabrata for in vivo use. We propose the first animal model using bioluminescence imaging to visualize C. glabrata in mouse tissues. Additionally, this UTI model can be used to monitor antifungal activity in vivo over time.
A Presurgical Study of Curcumin Combined with Anthocyanin Supplements in Patients with Colorectal Adenomatous Polyps

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51–1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50–1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.
Development and Validation of a Short Food Frequency Questionnaire to Measure Dietary Intake of a Selection of Immune-Modulating Nutrients in Patients with Established Peripheral Arterial Disease

Nutrients with the ability to modulate the immune system (immune-modulating nutrients; IMN) may help prevent the development and progression of atherosclerosis, the main disease process underlying peripheral artery disease (PAD). Currently, no screening tool exists to measure IMN intake; therefore, the aim of this project is to develop and validate a short food frequency questionnaire (FFQ) that measures dietary intake of 14 nutrients with proposed immune-modulating effects, identified by the literature (copper, iron and zinc, vitamins A, C, D and E, alpha linolenic acid, total long-chain omega-3 fatty acids, arginine, glutamic acid, isoleucine, leucine and valine) in patients with established PAD. A 21-item FFQ was developed to measure average daily intake of IMNs over the past 12 months. Participants (n = 106) were recruited from Flinders Medical Centre, where they completed the FFQ followed by the reference method, a diet history reflecting usual intake over the past week. The mean age of participants was 72 years, with 83% being male (n = 88). Bland–Altman analysis resulted in a statistically non-significant p-value (p-value > 0.05) for 12 out of 14 nutrients, demonstrating good agreement between the two methods. Additionally, over 50% of nutrients had a sensitivity or specificity >70%. Consequently, the novel 21-item FFQ was determined to be a promising measure of dietary intake of 14 IMNs in patients with PAD when compared to the reference method of a diet history, and it is recommended that further investigations of the utility against biomarkers be explored in the future.
Transcriptome and Proteome Conjoint Analysis Revealed That Exogenous Sulfur Regulates Glucosinolate Synthesis in Cabbage

Glucosinolates (GLS) are important anionic secondary metabolites that are rich in thiocyanin in cabbage, Brassica oleracea L. var. capitata. GLS are important in food flavor, plant antimicrobial activity, insect resistance, disease resistance, and human anti-cancer effects. Sulfur is an important raw material of GLS, directly affecting their synthesis. However, the mechanism of sulfur regulation of GLS biosynthesis in cabbage is unclear. In the present study, cabbage was treated with sulfur-free Hoagland nutrient solution (control; −S), and normal Hoagland nutrient solution (treatment; +S). Through joint transcriptomic and proteomic analyses, the effect of exogenous S on GLS synthesis was explored. S application induced GLS accumulation; especially, indole glycosides. Transcriptome analysis showed that +S treatment correlated positively with differentially expressed genes and proteins involved in amino acid biosynthesis, carbon metabolism, and plant hormone signal transduction. Compared with −S treatment, the mRNA expression of GLS synthesis genes (CYP, GSTU, UGT, and FMO) and those encoding transcription factors (RLK, MYB, AP2, bHLH, AUX/IAA, and WRKY) were upregulated significantly in the +S group. Combined transcriptome and proteome analysis suggested that the main pathway influenced by S during GLS synthesis in cabbage is amino acid biosynthesis. Moreover, S treatment activated GLS synthesis and accumulation.
Protocols for Characterization of Cdk5 Kinase Activity

Cyclin‐dependent kinases (Cdks) are generally known to be involved in controlling the cell cycle, but Cdk5 is a unique member of this protein family for being most active in post‐mitotic neurons. Cdk5 is developmentally important in regulating neuronal migration, neurite outgrowth, and axon guidance. Cdk5 is enriched in synaptic membranes and is known to modulate synaptic activity. Postnatally, Cdk5 can also affect neuronal processes such as dopaminergic signaling and pain sensitivity. Dysregulated Cdk5, in contrast, has been linked to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Despite primarily being implicated in neuronal development and activity, Cdk5 has lately been linked to non‐neuronal functions including cancer cell growth, immune responses, and diabetes. Since Cdk5 activity is tightly regulated, a method for measuring its kinase activity is needed to fully understand the precise role of Cdk5 in developmental and disease processes. This article includes methods for detecting Cdk5 kinase activity in cultured cells or tissues, identifying new substrates, and screening for new kinase inhibitors. Furthermore, since Cdk5 shares homology and substrate specificity with Cdk1 and Cdk2, the Cdk5 kinase assay can be used, with modification, to measure the activity of other Cdks as well. © 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Mercury Chloride Impacts on the Development of Erythrocytes and Megakaryocytes in Mice

Inorganic mercury (Hg2+) is a highly toxic heavy metal. The aim of this study was to investigate the impact of Hg2+ on the development of erythrocytes and megakaryocytes. B10.S mice (H-2s) and DBA/2 mice (H-2d) were administrated with 10 μM HgCl2 or 50 μM HgCl2 via drinking water for four weeks, and erythro-megakaryopoiesis was evaluated thereafter. The administration of 50 μM HgCl2 increased the number of erythrocytes and platelets in B10.S mice, which was not due to a reduced clearance for mature erythrocytes. The administration of 50 μM HgCl2, but not 10 μM HgCl2, increased the number of progenitors for erythrocytes and megakaryocytes in the bone marrow (BM) of B10.S mice, including erythroid-megakaryocyte progenitors (EMPs), burst-forming unit-erythroid progenitors (BFU-Es), colony-forming unit-erythroid progenitors (CFU-Es), and megakaryocyte progenitors (MkPs). Moreover, 50 μM HgCl2 caused EMPs to be more proliferative and possess an increased potential for differentiation into committed progenies in B10.S mice. Mechanistically, 50 μM HgCl2 increased the expression of the erythropoietin receptor (EPOR) in EMPs, thus enhancing the Jak2/STAT5 signaling pathway to promote erythro-megakaryopoiesis in B10.S mice. Conversely, 50 μM HgCl2 did not impact erythro-megakaryopoiesis in DBA/2 mice. This study may extend our current understanding for hematopoietic toxicology of Hg.
Risk Factors for Gut Dysbiosis in Early Life

Dysbiosis refers to a reduction in microbial diversity, combined with a loss of beneficial taxa, and an increase in pathogenic microorganisms. Dysbiosis of the intestinal microbiota can have a substantial effect on the nervous and immune systems, contributing to the onset of several inflammatory diseases. Epidemiological studies provided insight in how changes in the living environment have contributed to an overall loss of diversity and key taxa in the gut microbiome, coinciding with increased reports of atopy and allergic diseases. The gut microbiome begins development at birth, with major transition periods occurring around the commencement of breastfeeding, and the introduction of solid foods. As such, the development of the gut microbiome remains highly plastic and easily influenced by environmental factors until around three years of age. Developing a diverse and rich gut microbiome during this sensitive period is crucial to setting up a stable gut microbiome into adulthood and to prevent gut dysbiosis. Currently, the delivery route, antibiotic exposure, and diet are the best studied drivers of gut microbiome development, as well as risk factors of gut dysbiosis during infancy. This review focuses on recent evidence regarding key environmental factors that contribute to promoting gut dysbiosis.
Investigation of the Occurrence of Cyanotoxins in Lake Karaoun (Lebanon) by Mass Spectrometry, Bioassays and Molecular Methods

Lake Karaoun is the largest artificial lake in Lebanon and serves multiple purposes. Recently, intensive cyanobacterial blooms have been reported in the lake, raising safety and aesthetic concerns related to the presence of cyanotoxins and cyanobacterial taste and odor (T&O) compounds, respectively. Here, we communicate for the first time results from a recent investigation by LC-MS/MS covering multiple cyanotoxins (microcystins (MCs), anatoxin-a, cylindrospermopsin, nodularin) in water and fish collected between 2019 and 2020. Eleven MCs were identified reaching concentrations of 211 and 199 μg/L for MC-LR and MC-YR, respectively. Cylindrospermopsin, anatoxin-a and nodularin were not detected. The determination of the total MCs was also carried out by ELISA and Protein Phosphatase Inhibition Assay yielding comparable results. Molecular detection of cyanobacteria (16S rRNA) and biosynthetic genes of toxins were carried out by qPCR. Untargeted screening analysis by GC-MS showed the presence of T&O compounds, such as β-cyclocitral, β-ionone, nonanal and dimethylsulfides that contribute to unpleasant odors in water. The determination of volatile organic compounds (VOCs) showed the presence of anthropogenic pollutants, mostly dichloromethane and toluene. The findings are important to develop future monitoring schemes in order to assess the risks from cyanobacterial blooms with regard to the lake’s ecosystem and its uses.
Phase Lag Entropy as a Surrogate Measurement of Hypnotic Depth during Sevoflurane Anesthesia

Background and Objectives: Phase lag entropy, an electroencephalographic monitor, evaluates the variety in temporal patterns of phase relationship between frontal and prefrontal brain region. Phase lag entropy can reflect the depth of anesthesia induced by propofol, but the association between sevoflurane and phase lag entropy has not been elucidated. This study examined the effect of sevoflurane on phase lag entropy during induction of general anesthesia. We also explored the pharmacodynamic model between end-tidal anesthetic concentration and electroencephalographic monitor. Materials and Methods: A total of 20 patients were enrolled. General anesthesia was produced by escalating the sevoflurane (1 vol% up to 8 vol%). The relationship between phase lag entropy and end-tidal anesthetic concentration was analyzed. A non-linear mixed-effects model was used to get the relationship of pharmacodynamics between the end-tidal sevoflurane concentration and phase lag entropy. Mean blood pressure, heart rate, and the modified observer’s assessment of alertness/sedation scale were also recorded during sevoflurane anesthesia. Results: As level of sedation increased, phase lag entropy decreased. A significant correlation was showed between phase lag entropy and end-tidal sevoflurane concentration (r = −0.759, p < 0.001). The correlation coefficient between the modified observer’s assessment of alertness/sedation scale and phase lag entropy was 0.731 (p < 0.001). The pharmacodynamic factors assessed by the sigmoid Emax model were E0 = 84.9, Emax = 42, Ce50 = 1.81, γ = 4.78, and ke0 = 0.692. The prediction probability of phase-lag entropy for measuring the modified observer’s assessment of alertness/sedation scale and end-tidal sevoflurane concentration were 0.764 and 0.789, respectively. With the increasing concentration of sevoflurane, mean blood pressure decreased, but heart rate did not change. Conclusions: The continuing escalation in end-tidal sevoflurane concentration caused a decline in phase lag entropy. Phase lag entropy can serve as an indicator of hypnotic depth in patients receiving sevoflurane anesthesia.
Tuning the Cytotoxicity of Bis-Phosphino-Amines Ruthenium(II) Para-Cymene Complexes for Clinical Development in Breast Cancer

Despite some limitations such as long-term side effects or the potential presence of intrinsic or acquired resistance, platinum compounds are key therapeutic components for the treatment of several solid tumors. To overcome these limitations, maintaining the same efficacy, organometallic ruthenium(II) compounds have been proposed as a viable alternative to platinum agents as they have a more favorable toxicity profile and represent an ideal template for both, high-throughput and rational drug design. To support the preclinical development of bis-phoshino-amine ruthenium compounds in the treatment of breast cancer, we carried out chemical modifications in the structure of these derivatives with the aim of designing less toxic and more efficient therapeutic agents. We report new bis-phoshino-amine ligands and the synthesis of their ruthenium counterparts. The novel ligands and compounds were fully characterized, water stability analyzed, and their in vitro cytotoxicity against a panel of tumor cell lines representative of different breast cancer subtypes was evaluated. The mechanism of action of the lead compound of the series was explored. In vivo toxicity was also assessed. The results obtained in this article might pave the way for the clinical development of these compounds in breast cancer therapy.
DAKS1, a Kunitz Scaffold Peptide from the Venom Gland of Deinagkistrodon acutus Prevents Carotid-Artery and Middle-Cerebral-Artery Thrombosis via Targeting Factor XIa

Scaffold-based peptides (SBPs) are fragments of large proteins that are characterized by potent bioactivity, high thermostability, and low immunogenicity. Some SBPs have been approved by the FDA for human use. In the present study, we developed SBPs from the venom gland of Deinagkistrodon acutus (D. acutus) by combining transcriptome sequencing and Pfam annotation. To that end, 10 Kunitz peptides were discovered from the venom gland of D. acutus, and most of which peptides exhibited Factor XIa (FXIa) inhibitory activity. One of those, DAKS1, exhibiting strongest inhibitory activity against FXIa, was further evaluated for its anticoagulant and antithrombotic activity. DAKS1 prolonged twofold APTT at a concentration of 15 μM in vitro. DAKS1 potently inhibited thrombosis in a ferric chloride-induced carotid-artery injury model in mice at a dose of 1.3 mg/kg. Furthermore, DAKS1 prevented stroke in a transient middle cerebral-artery occlusion (tMCAO) model in mice at a dose of 2.6 mg/kg. Additionally, DAKS1 did not show significant bleeding risk at a dose of 6.5 mg/kg. Together, our results indicated that DAKS1 is a promising candidate for drug development for the treatment of thrombosis and stroke disorders.
Effect of the Elongational Flow on the Morphology and Properties of Polymer Systems: A Brief Review

Polymer-processing operations with dominating elongational flow have a great relevance, especially in several relevant industrial applications. Film blowing, fiber spinning and foaming are some examples in which the polymer melt is subjected to elongational flow during processing. To gain a thorough knowledge of the material-processing behavior, the evaluation of the rheological properties of the polymers experiencing this kind of flow is fundamental. This paper reviews the main achievements regarding the processing-structure-properties relationships of polymer-based materials processed through different operations with dominating elongational flow. In particular, after a brief discussion on the theoretical features associated with the elongational flow and the differences with other flow regimes, the attention is focused on the rheological properties in elongation of the most industrially relevant polymers. Finally, the evolution of the morphology of homogeneous polymers, as well as of multiphase polymer-based systems, such as blends and micro- and nano-composites, subjected to the elongational flow is discussed, highlighting the potential and the unique characteristics of the processing operations based on elongation flow, as compared to their shear-dominated counterparts.