Miracle-dz/UniFAR-FTUs huggingface dataset:
New Polymers for Needleless Electrospinning from Low-Toxic Solvents

Electrospinning is a new technology whose scope is gradually being developed. For this reason, the number of known polymer–solvent combinations for electrospinning is still very low despite the enormous variety of substances that are potentially available. In particular, electrospinning from low-toxic solvents, such as the use of dimethyl sulfoxide (DMSO) in medical technology, is rare in the relevant scientific literature. Therefore, we present in this work a series of new polymers that are applicable for electrospinning from DMSO. From a wide range of synthetic polymers tested, poly(vinyl alcohol) (PVOH), poly(2ethyl2oxazolene) (PEOZ), and poly(vinylpyrrolidone) (PVP) as water-soluble polymers and poly(styrene-co-acrylonitrile) (SAN), poly(vinyl alcohol-co-ethylene) (EVOH), and acrylonitrile butadiene styrene (ABS) as water-insoluble polymers were found to be suitable for the production of nanofibers. Furthermore, the influence of acetone as a volatile solvent additive in DMSO on the fiber morphology of these polymers was investigated. Analyses of the fiber morphology by helium ion microscopy (HIM) showed significantly different fiber diameters for different polymers and a reduction in beads and branches with increasing acetone content.
Characterization of platelet factor 4 amino acids that bind pathogenic antibodies in heparin‐induced thrombocytopenia

Essentials Many patients produce antibodies but few lead to heparin‐induced thrombocytopenia (HIT). Pathogenic epitopes are difficult to identify as HIT antibodies are polyclonal and polyspecific. KKO binding to platelet factor 4 (PF4) depends on 13 amino acids, three of which are newly observed. Five amino acids in PF4 can help distinguish pathogenic from non‐pathogenic antibodies.
m6A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins

The control of gene expression is a multi-layered process occurring at the level of DNA, RNA, and proteins. With the emergence of highly sensitive techniques, new aspects of RNA regulation have been uncovered leading to the emerging field of epitranscriptomics dealing with RNA modifications. Among those post-transcriptional modifications, N6-methyladenosine (m6A) is the most prevalent in messenger RNAs (mRNAs). This mark can either prevent or stimulate the formation of RNA-protein complexes, thereby influencing mRNA-related mechanisms and cellular processes. This review focuses on proteins containing a YTH domain (for YT521-B Homology), a small building block, that selectively detects the m6A nucleotide embedded within a consensus motif. Thereby, it contributes to the recruitment of various effectors involved in the control of mRNA fates through adjacent regions present in the different YTH-containing proteins.
The Use of Student Consulting Projects as an Active Learning Pedagogy: A Case Study in a Production/Operations Management Course

Active learning has attracted considerable attention in higher education in response to concerns about how and what students are learning. There are many different forms of active learning, yet most of them are classroom based. We propose an alternative to active learning in the classroom through active learning outside of the classroom in the form of student consulting projects. While the literature on student consulting has largely focused on projects to assist small business owners, this research demonstrates the potential for using student-consulting projects in the Production/Operations Management course. We use a case study to describe the use of a student-consulting project as an alternative to the other types of active learning described in the Operations Management education literature.
Gene expression effects of lithium and valproic acid in a serotonergic cell line

Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e. odds ratio of ≥ 2, at FDR <5%), but only two genes (Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B) and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix (ECM) remodelling, cell adhesion and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into the therapeutic action of the commonly used mood stabilizer drugs.
“Vitamin D” as a Profile Marker for Cardiovascular Diseases

Objective: A growing body of research indicates that there exists a correlation between Vit D deficiency and cardiovascular diseases (CVD). In addition to being genetically determined, it is strongly influenced by lifestyle factors. In this study, Vit D and its interrelated factors have been studied as profile marker for identifying the risk of CVD in patients. Methods: The present study includes comparison of a total 200 adults CVD patients with the healthy patients as control, by measuring their serum lipid levels and Vit D concentrations with other CVD risk factors. Results: The average serum Vit D in CVD patients and controls are found to be 22.55±6.2 ng/ml and 37.62±3.2 ng/ml respectively, showing that 63% of CVD patients and 35% of controls are Vit D deficient. Serum lipids levels were considered as marker for patients having CVD which include high levels of total cholesterol, triglycerides, and low-density lipoprotein-cholesterol while low levels of high-density lipoproteins-cholesterol levels. Other risk factors like hypertension, lifestyle, smoking, dietary factors and nutritional status shows significantly correlation for CVD patients compared to controls. Conclusion: Literature supports the relationship between lipid profile and Vit D level by using this as a profile marker for CVD patients. Our study also suggests the same that vitamin D can be used as profile marker for cardiovascular diseases.
Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids

Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder (GB) total lipids and the mol% (mole percent) of bile acids (BAs), cholesterol, and phospholipids (PLs). Whereas CSI indicates GS risk, we hypothesized that additional comparisons of GB lipid mol% data are inappropriate to identify why CSI is increased in GS disease. We anticipated that GB lipid mmol/l (millimole per liter) levels should instead identify that, and therefore retrieved GB mmol/l data for BAs, cholesterol, and PLs from a study on 145 GS and 87 GS-free patients and compared them with the corresponding mol% data. BA and PL mmol/l levels were 33% and 31% lower in GS patients, while cholesterol was unaltered. CSI was higher in GS patients and correlated inversely with GB levels of BAs and PLs, but not with cholesterol. A literature search confirmed, in 13 studies from 11 countries, that GB BA levels and, to a certain extent, PLs are strongly reduced in GS patients, while cholesterol levels are not elevated. Our findings show that a shortage of BAs is a major reason why GB bile is supersaturated with cholesterol in GS patients. These results are sustainable because they are also valid from a global perspective.
MLML2R: an R package for maximum likelihood estimation of DNA methylation and hydroxymethylation proportions

Abstract Accurately measuring epigenetic marks such as 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) at the single-nucleotide level, requires combining data from DNA processing methods including traditional (BS), oxidative (oxBS) or Tet-Assisted (TAB) bisulfite conversion. We introduce the R package MLML2R, which provides maximum likelihood estimates (MLE) of 5-mC and 5-hmC proportions. While all other available R packages provide 5-mC and 5-hmC MLEs only for the oxBS+BS combination, MLML2R also provides MLE for TAB combinations. For combinations of any two of the methods, we derived the pool-adjacent-violators algorithm (PAVA) exact constrained MLE in analytical form. For the three methods combination, we implemented both the iterative method by Qu et al. [Qu, J., M. Zhou, Q. Song, E. E. Hong and A. D. Smith (2013): “Mlml: consistent simultaneous estimates of dna methylation and hydroxymethylation,” Bioinformatics, 29, 2645–2646. ], and also a novel non iterative approximation using Lagrange multipliers. The newly proposed non iterative solutions greatly decrease computational time, common bottlenecks when processing high-throughput data. The MLML2R package is flexible as it takes as input both, preprocessed intensities from Infinium Methylation arrays and counts from Next Generation Sequencing technologies. The MLML2R package is freely available at https://CRAN.R-project.org/package=MLML2R.
Discovery of an Unusual Fatty Acid Amide from the ndgRyo Gene Mutant of Marine-Derived Streptomyces youssoufiensis

NdgRyo, an IclR-like regulator, was selected as the target gene to activate new secondary metabolites in the marine-derived Streptomyces youssoufiensis OUC6819. Inactivation of the ndgRyo gene in S. youssoufiensis OUC6819 led to the accumulation of a new fatty acid amide (1), with an unusual 3-amino-butyl acid as the amine component. Moreover, its parent fatty acid (2) was also discovered both in the wild-type and ΔndgRyo mutant strains, which was for the first time isolated from a natural source. The structures of compounds 1 and 2 were elucidated by combination of LC-MS and NMR spectroscopic analyses. This study demonstrated that the ndgRyo homologs might serve as a target for new compound activation in Streptomyces strains.
Arsenic species uptake and translocation in Elodea canadensis

Abstract The capacity of Elodea canadensis to phytofiltrate arsenic species from water was evaluated. Plants were adapted to tap water and supplemented with 15 and 250 µg L−1 of As. Inorganic arsenic species (As III, As V), and organic arsenic compounds: monomethylarsonate (MMA) and dimethylarsinate (DMA) were analyzed. Sampling was carried out at different times after exposure in culture water and plant organs. Plants exposed to 15 µg L−1 of As concentration showed no significant difference on As concentration (95% confidence level) in their organs compared to controls. When plants were exposed to 250 µg L−1 of As concentration, a significant increase of As concentration in plant organs was observed. After 1 h exposure, plants reduce 63.16% the As concentration in the culture water, with a bioaccumulation factor (BF) of 4.3. Under these conditions, E. canadensis accumulate As V in roots and do not translocate it to stems (transfer factor <1). MMA was determined in stems and leaves. E. canadensis effectively phytofiltrate As from tap water of a city located in an arsenic endemic area from concentrations of 36 µg L−1 to undetectable levels (10 ng L−1).
Effect of exposure of osteoblast-like cells to low-dose silver nanoparticles: uptake, retention and osteogenic activity

Abstract Objective Silver nanoparticles (AgNPs) are widely used in orthopaedic implants because of their excellent antimicrobial properties. However, the effects of AgNPs on bone cells and osteogenic activity are still poorly understood. Method Here, we investigated the effect of AgNPs on the cell viability, uptake, and osteogenic activity of osteoblast-like cells (MG-63 cells) at low concentrations. Results Our results showed that uptake and retention of AgNPs reduced the cell viability and increased cell membrane penetrability even after termination of exposure of MG-63 cells to AgNPs. In addition, AgNPs induced cell shrinkage, reduced the expressions of ALP, COL-I, OCN and OPG, and enhanced the expressions of Runx2 and RANKL. Conclusion Collectively, our work demonstrated that the cytotoxic effects of low-dose AgNPs on MG-63 cells persisted even after termination of exposure. AgNPs may interfere with bone formation. More attention should be paid to the toxicity of AgNPs during the design of future orthopaedic implants.
An ultra-high frequency radio frequency identification system for studying individual feeding and drinking behaviors of group-housed broilers

Radio frequency identification (RFID) technology offers a real-time solution to monitor behavioral responses of individual animals to various stimuli, which provides crucial implications on farm management and animal well-being. The objectives of this study were to (1) develop and describe an ultra-high frequency radio frequency identification (UHF-RFID) system for continuously monitoring feeding and drinking behaviors of individual broilers in group settings; and (2) validate the performance of the UHF-RFID system against video analysis in determining the instantaneous bird number (IBN) and time spent (TS) at feeder and drinker. The UHF-RFID system consisted of cable-tie tags, antennas, a reader and a data acquisition (DAQ) system. The antennas generated electromagnetic fields where tags were detected and registered by the DAQ system. Electromagnetic fields of the antennas were modified to cover areas of concern (i.e. tube feeders and nipple drinkers) through a series of system evaluations and customizations including tag sensitivity test, power adjustment, radio wave shielding, and assessment of interference by add-ons (e.g. plastic wraps for protecting antennas and an empty carton box for zoning out broilers) and feed/feeder. System validation was performed in two experimental rooms, each with 60 tagged broilers. The results showed that the max reading distances of tags with an identical manufacturer’s specification were markedly different, indicating large variations in sensitivity among the tags. Desired electromagnetic fields could be achieved by adjusting the power supplied to antennas and by partially shielding antennas with customized stainless steel sheets. The protection materials and fully loaded feeder had little effect on electromagnetic fields of the antennas. The accuracies of the UHF-RFID system for determining IBN and TS were, respectively, 92.5±4.2% and 99.0±1.2% by the feeder antennas and 94.7±4.2% and 93.7±6.9% by the drinker antennas. It is concluded that the UHF-RIFD system can accurately detect and record feeding and drinking behaviors of individual broilers in group settings and thus is a useful tool for investigating impacts of resource allocations and management practices on these behaviors.
Longer lifespan in the Rpd3 and Loco signaling results from the reduced catabolism in young age with noncoding RNA

Downregulation of Rpd3 (histone deacetylase) or Loco (regulator of G-protein signaling protein) extends Drosophila lifespan with higher stress resistance. We found rpd3-downregulated long-lived flies genetically interact with loco-upregulated short-lived flies in stress resistance and lifespan. Gene expression profiles between those flies revealed that they regulate common target genes in metabolic enzymes and signaling pathways, showing an opposite expression pattern in their contrasting lifespans. Functional analyses of more significantly changed genes indicated that the activities of catabolic enzymes and uptake/storage proteins are reduced in long-lived flies with Rpd3 downregulation. This reduced catabolism exhibited from a young age is considered to be necessary for the resultant longer lifespan of the Rpd3- and Loco-downregulated old flies, which mimics the dietary restriction (DR) effect that extends lifespan in the several species. Inversely, those catabolic activities that break down carbohydrates, lipids, and peptides were high in the short lifespan of Loco-upregulated flies. Long noncoding gene, dntRL (CR45923), was also found as a putative target modulated by Rpd3 and Loco for the longevity. Interestingly, this dntRL could affect stress resistance and lifespan, suggesting that the dntRL lncRNA may be involved in the metabolic mechanism of Rpd3 and Loco signaling.
Elevated Vitamin B12 Levels and Cancer Risk in UK Primary Care: A THIN Database Cohort Study

Background: Elevated vitamin B12 levels (B12) are associated with increased short-term cancer risk. However, the implications for early cancer detection in primary care have not been assessed. Methods: Individuals with plasma B12 measurements were sampled from The Health Improvement Network primary care database, UK. Persons with low B12 levels were excluded together with persons with cancer or B12 treatment before date of B12 measurement. Incident cancer was the outcome of interest and was identified through Read codes. Individuals were disaggregated according to plasma B12 levels (unit: pmol/L): 150–600 (reference range values), 601–800, 801–1,000, and >1,000. Results: Among the 757,185 persons who met the inclusion criteria, we identified 33,367 incident cancers during 2,874,059 years of follow-up. We found a higher 1-year cancer risk among the 25,783 (3.4%) persons with elevated B12 levels compared with those with normal B12 levels. After multivariable adjustment for lifestyle factors and social deprivation, persons with B12 >1,000 pmol/L had a 1-year incidence rate ratio of 4.72 (95% confidence interval: 3.99–5.58). The association showed a nonlinear dose–response pattern, and it remained robust in stratified analyses, including when reducing the risk of confounding by indication in subanalyses. The risks were particularly elevated for liver cancer, pancreas cancer, and myeloid malignancies among persons with elevated B12 levels. Conclusions: Elevated plasma B12 levels were associated with a higher 1-year cancer risk than normal B12 levels among persons seen in UK primary care, suggesting that some cancers may affect B12 metabolism. Impact: Elevated B12 may mark occult cancer.
Differences in the rate of nicotine metabolism among smokers with and without HIV.

OBJECTIVE HIV-infected smokers lose more life years to tobacco use than to HIV infection. The nicotine metabolite ratio (NMR), a biomarker of CYP2A6, represents individual variation in the rate at which nicotine is metabolized and is associated with response to smoking cessation treatments. We evaluated whether HIV-infected smokers metabolize nicotine faster than HIV-uninfected smokers, which may contribute to the disproportionate smoking burden and may have important treatment implications. DESIGN We analysed baseline data from two clinical trials (NCT01710137; NCT01314001) to compare the NMR in HIV-infected smokers (N = 131) to HIV-uninfected smokers (N = 199). METHODS Propensity scores were used to match the groups 2 : 1 on characteristics that influence NMR: sex, race, BMI and smoking rate. Nicotine metabolites were assessed via LC-MS methods and the ratio of 3-hydroxycotinine:cotinine was used to compute the NMR. RESULTS HIV-infected smokers had significantly higher NMR (mean = 0.47, SEM = 0.02) and were more likely to be in the highest NMR quartile compared with HIV-uninfected smokers (mean = 0.34, SEM = 0.02; Ps < 0.001). CONCLUSION The higher NMR observed among HIV-infected smokers may partially explain higher smoking rates and lower response to transdermal nicotine therapy. Understanding the mechanisms by which HIV and/or ART contribute to faster nicotine metabolism may guide the use of the NMR to personalize tobacco cessation strategies in this underserved population.
Discorhabdin N, a South African Natural Compound, for Hsp72 and Hsc70 Allosteric Modulation: Combined Study of Molecular Modeling and Dynamic Residue Network Analysis

The human heat shock proteins (Hsps), predominantly Hsp72 and Hsp90, have been strongly implicated in various critical stages of oncogenesis and progression of human cancers. While drug development has extensively focused on Hsp90 as a potential anticancer target, much less effort has been put against Hsp72. This work investigated the therapeutic potential of Hsp72 and its constitutive isoform, Hsc70, via in silico-based screening against the South African Natural Compounds Database (SANCDB). A comparative modeling approach was used to obtain nearly full-length 3D structures of the closed conformation of Hsp72 and Hsc70 proteins. Molecular docking of SANCDB compounds identified one potential allosteric modulator, Discorhabdin N, binding to the allosteric β substrate binding domain (SBDβ) back pocket, with good binding affinities in both cases. This allosteric region was identified in one of our previous studies. Subsequent all-atom molecular dynamics simulations and free energy calculations exhibited promising protein–ligand association characteristics, indicative of strong binding qualities. Further, we utilised dynamic residue network analysis (DRN) to highlight protein regions actively involved in cross-domain communication. Most residues identified agreed with known allosteric signal regulators from literature, and were further investigated for the purpose of deducing meaningful insights into the allosteric modulation properties of Discorhabdin N.
Dealing with Access to Spirometry in Africa: A Commentary on Challenges and Solutions

Spirometry is an important tool in the surveillance, epidemiology, diagnosis, and management of respiratory disease, yet its accessibility is currently limited in Africa where the burden of respiratory diseases is amongst the highest globally. The reasons for limited access to spirometry in Africa include poor access to training and skilled technicians, limited availability of equipment, consumables, and technical support, and lack of human and financial resources. The Pan African Thoracic Society, working together with regional African thoracic societies and key research initiatives in Africa, have made progress in training and education, but a lot of work is still needed to meet the challenges faced. Accurately defining these challenges of access to high quality spirometry, development of local, standardised, and context-specific training and quality assurance tools; development of appropriate reference standards and innovative approaches to addressing the challenges of access to equipment, consumables and technical support are needed. Training and research collaborations that include regional thoracic societies, health system leaders, the Pan African Thoracic Society and international role players in the field are key to maximising available intellectual and financial resources. Hence ensuring that access to high quality spirometry measures that are used effectively in tackling the burden of respiratory disease in Africa.
Incorporation of a spectral model in a convolutional neural network for accelerated spectral fitting

MRSI has shown great promise in the detection and monitoring of neurologic pathologies such as tumor. A necessary component of data processing includes the quantitation of each metabolite, typically done through fitting a model of the spectrum to the data. For high‐resolution volumetric MRSI of the brain, which may have ~10,000 spectra, significant processing time is required for spectral analysis and generation of metabolite maps.