Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Nanoparticle Intestinal Transport Using an In Vitro Co-Culture Model

We aimed to obtain a tunable intestinal model and study the transport of different types of nanoparticles. Caco-2/HT29-MTX co-cultures of different seeding ratios (7:3 and 5:5), cultured on Transwell® systems, were exposed to non-cytotoxic concentration levels (20 μg/mL) of silicon quantum dots and iron oxide (α-Fe2O3) nanoparticles. Transepithelial electric resistance was measured before and after exposure, and permeability was assessed via the paracellular marker Lucifer Yellow. At regular intervals during the 3 h transport study, samples were collected from the basolateral compartments for the detection and quantitative testing of nanoparticles. Cell morphology characterization was done using phalloidin-FITC/DAPI labeling, and Alcian Blue/eosin staining was performed on insert cross-sections in order to compare the intestinal models and evaluate the production of mucins. Morphological alterations of the Caco-2/HT29-MTX (7:3 ratio) co-cultures were observed at the end of the transport study compared with the controls. The nanoparticle suspensions tested did not diffuse across the intestinal model and were not detected in the receiving compartments, probably due to their tendency to precipitate at the monolayer surface level and form visible aggregates. These preliminary results indicate the need for further nanoparticle functionalization in order to appropriately assess intestinal absorption in vitro.
Linear Birefringent Films of Cellulose Nanocrystals Produced by Dip-Coating

Transparent films of cellulose nanocrystals (CNC) are prepared by dip-coating on glass substrates from aqueous suspensions of hydrolyzed filter paper. Dragging forces acting during films’ deposition promote a preferential alignment of the rod-shaped CNC. Films that are 2.8 and 6.0 µm in thickness show retardance effects, as evidenced by placing them between a linearly polarized light source and a linear polarizer sheet in the extinction configuration. Transmission Mueller matrix spectroscopic ellipsometry measurements at normal incidence as a function of sample rotation were used to characterize polarization properties. A differential decomposition of the Mueller matrix reveals linear birefringence as the unique polarization parameter. These results show a promising way for obtaining CNC birefringent films by a simple and controllable method.
Effect of time taken in injecting subcutaneous heparin injection with reference to site pain and bruising among patients receiving heparin therapy

: The local side effects associated with subcutaneous heparin, namely pain at the injection site and bruising may be the direct result of faulty injection administration techniques. Various administration variables have been studied, such as needle gauze, injectate volume and syringe size, in an effort to minimize these side effects. One of the variables is the time taken for administering subcutaneous heparin at the injection site. Literature reports that subcutaneous heparin be administered over 10 seconds. In the present study a two group design was used among cardiac patients undergoing heparin therapy. In the control group, the time taken for administering subcutaneous heparin in the routine practice was noted, while in the experimental group 30 seconds injection technique’ was utilized. All other steps of injection administration were kept same in both the groups. A total of 100 injection sites were taken in each group and assessed for pain at 0, 24, 48,60hrs and for bruise at 24, 48 and 60 hrs. It was observed that, in the control group nurses gave the injections over 4-10 seconds. Results show that there was no significant difference in the perceived site pain in both groups. However, when mean bruise sizes were compared, it was observed that they were significantly less in the subjects receiving subcutaneous heparin injection through the 30 second injection duration technique (p<0.05).
Genome‐wide variation in nucleotides and retrotransposons in alpine populations of Arabis alpina (Brassicaceae)

Advances in high‐throughput sequencing have promoted the collection of reference genomes and genome‐wide diversity. However, the assessment of genomic variation among populations has hitherto mainly been surveyed through single‐nucleotide polymorphisms (SNPs) and largely ignored the often major fraction of genomes represented by transposable elements (TEs). Despite accumulating evidence supporting the evolutionary significance of TEs, comprehensive surveys remain scarce. Here, we sequenced the full genomes of 304 individuals of Arabis alpina sampled from four nearby natural populations to genotype SNPs as well as polymorphic long terminal repeat retrotransposons (polymorphic TEs; i.e., presence/absence of TE insertions at specific loci). We identified 291,396 SNPs and 20,548 polymorphic TEs, comparing their contributions to genomic diversity and divergence across populations. Few SNPs were shared among populations and overall showed high population‐specific variation, whereas most polymorphic TEs segregated among populations. The genomic context of these two classes of variants further highlighted candidate adaptive loci having a putative impact on functional genes. In particular, 4.96% of the SNPs were identified as nonsynonymous or affecting start/stop codons. In contrast, 43% of the polymorphic TEs were present next to Arabis genes enriched in functional categories related to the regulation of reproduction and responses to biotic as well as abiotic stresses. This unprecedented data set, mapping variation gained from SNPs and complementary polymorphic TEs within and among populations, will serve as a rich resource for addressing microevolutionary processes shaping genome variation.
Impact of cochlear tonotopy on electrically evoked compound action potentials (ECAPs)

Abstract Background: A wide range of cochlear implant electrode designs exists. Lateral wall electrodes may be favored for their potential to preserve residual hearing by virtue of being thin and delicate; whereas perimodiolar electrodes may have advantages in case of profound hearing loss, due to electrode positioning in close proximity to the auditory nerve fibers. Aim: The aim of this study was to investigate the impact of these two array designs on the interaction between electrodes and the auditory nerve in different tonotopic regions of the cochlea. Patients and methods: A retrospective study of both adult and pediatric cochlear implant recipients (CI24RE/CI512 or CI422, Cochlear®) was undertaken. The differences of threshold Neural Response Telemetry (tNRT) acquired 12 months after surgery were analyzed with respect to the tonotopic location. Results: The results of 168 implants showed that perimodiolar arrays had lowest thresholds in the basal region whereas straight arrays had lowest thresholds in the apex. Highest thresholds for both array types were encountered in the medial parts. Conclusions and Significance: tNRTs differ depending on electrode type and location inside the cochlea. This should be considered pre implantation when choosing the electrode array type and post-implantation when mapping the CI program.
Peri-arterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling

ABSTRACT Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using pdgfrb and abcc9 reporters, we show that the onset of expression of abcc9, a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in pdgfrb expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naïve pdgfrblow mesenchymal cells. The emergence of peri-arterial pdgfrbhigh MCs required Notch signaling. We found that pdgfrb-positive cells express notch2 in addition to notch3, and although depletion of notch2 or notch3 failed to block MC emergence, embryos depleted of both notch2 and notch3 lost mesoderm- as well as neural crest-derived pdgfrbhigh MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into pdgfrbhigh MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification. Summary: Live imaging of mural cell development in zebrafish uncovers the fact that specification into mural cells is positively regulated by Notch signaling.
Impact of screening programme using the faecal immunochemical test on stage of colorectal cancer: Results from the IMPATTO study

To evaluate the impact of faecal immunochemical test (FIT) screening on stage distribution at diagnosis, and to estimate relative incidence rates by stage in screened at first and subsequent rounds vs. unscreened. We included all incident cases occurring in 2000–2008 in 50‐ to 71‐year‐olds residing in areas with an FIT‐screening programme. Multinomial logistic models were computed to estimate the relative risk ratio (RRR) of stages I and IV, compared to stage II + III, adjusting for age, sex, geographical area, and incidence year. Proportions were then used to estimate incidence rate ratios (IRR) by stage for screened subjects at the first and at subsequent rounds vs. unscreened subjects, applying the expected changes in overall incidence during screening phases. 11,663 cancers were included: 5965 in not‐invited and 5,698 in invited subjects, 3,425 of whom attendees. Compared to not‐invited, invited subjects had RRR 2.04 (95% CI: 1.84; 2.46) of stage I and RRR 0.77 (95% CI: 0.69; 0.87) of stage IV. Differences were stronger comparing attendees vs. nonattendees. Interval cancers were more frequently stage I compared to non‐invited (RRR 1.54; 95% CI: 1.15; 2.04), but there was no difference for stage IV. IRRs in screened at first round vs. unscreened were 4.6 (95% CI: 4.2; 5.1), 1.4 (95% CI: 1.3; 1.5) and 0.7 (95% CI: 0.6; 0.9) for stages I, II + III and IV, respectively; in the following rounds the IRRs of screened vs. unscreened were 1.4 (95% CI: 1.2; 1.6), 0.8 (95% CI: 0.7; 0.9) and 0.3 (95% CI: 0.1; 0.4) for stages I, II + III and IV, respectively. FIT screening reduces the incidence of metastatic cancers by about 70% after the first round.
Mechanical performance, intracellular Ca²⁺ handling and ventricular repolarisation in isolated hearts from rabbits with heart failure

In this thesis, a rabbit coronary artery ligation model was used to study the cardiac mechanical performance, Ca2+ handling and ventricular activation/repolarisation in heart failure. Significant cardiac dilatation and contractile dysfunction were demonstrated in vivo on echocardiography 7 weeks after the initial myocardial infarct resulting from the coronary artery ligation procedure. In addition, liver, lung and heart weights were increased indicating significant organ congestion, cardiac remodelling and hypertrophy as seen in the human clinical syndrome of heart failure. Impaired mechanical performance was also demonstrated in vitro in the isolated failing hearts both in the working heart configuration and during Langendorff perfusion, with significant systolic and diastolic dysfunction. The Frank-Starling relationship was attenuated in the failing hearts and there was also a blunted slow response to step increase in pre-load, which may partly explain the findings of the Frank-Starling relationship in the failing hearts. Epicardial Ca2+ transients measured from the isolated failing hearts were found to have a prolonged time course. Impaired relaxation was shown to be associated with the prolonged Ca2+ transient durations in the failing hearts and there was an increased variation of Ca2+ transient durations over the left ventricular epicardial surface in the failing hearts. Monophasic Action Potentials (MAPs) measured from the left ventricular epicardial surface of failing hearts also had a prolonged time course and there was also an increased variation of MAP durations. The prolonged Ca2+ transient durations appeared to be associated with prolonged MAP durations in the failing hearts. Finally, delayed ventricular activation with impaired intraventricular conduction was demonstrated in the failing hearts, which may be an additional contributory factor in the mechanical dysfunction in heart failure.
Native mass spectrometry reveals the conformational diversity of the UVR8 photoreceptor

Significance The plant photoreceptor UVR8 absorbs UV-B light to regulate UV protection and photomorphogenic responses in plants. Here we show that UVR8 adopts multiple conformations to generate the signaling active state. The conformational diversity of UVR8 was revealed using a native mass spectrometry approach, where the photoreceptor was photoactivated in the ion source. Our analyses show that not only disordered but also ostensibly well-folded regions of UVR8 can adopt highly extended conformations that are likely to enhance interactions with partner proteins to facilitate signal propagation. The methodology employed could be used to investigate the structural dynamics of other proteins that are activated by light. UVR8 is a plant photoreceptor protein that regulates photomorphogenic and protective responses to UV light. The inactive, homodimeric state absorbs UV-B light, resulting in dissociation into monomers, which are considered to be the active state and comprise a β-propeller core domain and intrinsically disordered N- and C-terminal tails. The C terminus is required for functional binding to signaling partner COP1. To date, however, structural studies have only been conducted with the core domain where the terminal tails have been truncated. Here, we report structural investigations of full-length UVR8 using native ion mobility mass spectrometry adapted for photoactivation. We show that, while truncated UVR8 photoconverts from a single conformation of dimers to a single monomer conformation, the full-length protein exists in numerous conformational families. The full-length dimer adopts both a compact state and an extended state where the C terminus is primed for activation. In the monomer the extended C terminus destabilizes the core domain to produce highly extended yet stable conformations, which we propose are the fully active states that bind COP1. Our results reveal the conformational diversity of full-length UVR8. We also demonstrate the potential power of native mass spectrometry to probe functionally important structural dynamics of photoreceptor proteins throughout nature.
Aryl hydrocarbon receptor‐mediated activity of gas‐phase ambient air derived from passive sampling and an in vitro bioassay

The gaseous fraction of hydrophobic organic contaminants (HOCs) in ambient air appears to be responsible for a significant portion of aryl hydrocarbon receptor (AhR)‐mediated activity, but the majority of compounds contributing to this activity remain unidentified. The present study investigated the use of polyethylene passive samplers to isolate gaseous HOCs from ambient air for use in in vitro bioassays and to improve our understanding of the toxicological relevance of the gaseous fraction of ambient air in urban and residential environments. Concentrations of polycyclic aromatic hydrocarbons (PAHs) and organic flame retardants were measured in polyethylene passive sampler extracts. Extracts were also analyzed using an in vitro bioassay to measure AhR‐mediated activity. Bioassay‐derived benzo[a]pyrene (BaP) equivalents (BaP‐Eqbio), a measure of potency of HOC mixtures, were greatest in the downtown Cleveland area and lowest at rural/residential sites further from the city center. The BaP‐Eqbio was weakly correlated with concentrations of 2‐ring alkyl/substituted PAHs and one organophosphate flame retardant, ethylhexyl diphenyl phosphate. Potency predicted based on literature‐derived induction equivalency factors (IEFs) explained only 2 to 23% of the AhR‐mediated potency observed in bioassay experiments. Our results suggests that health risks of gaseous ambient air pollution predicted using data from targeted chemical analysis may underestimate risks of exposure, most likely due to augmentation of potency by unmonitored chemicals in the mixture, and the lack of relevant IEFs for many targeted analytes. Environ Toxicol Chem 2019;38:748–759. © 2019 SETAC
Factors Contributing to the Shortage of Speech-Language Pathologists in Utah Schools

FACTORS CONTRIBUTING TO THE SHORTAGE OF SPEECH-LANGUAGE PATHOLOGISTS EMPLOYED IN UTAH SCHOOLS Stephanie Harris Department of Counseling Psychology and Special Education Education Specialist in School Psychology This study examined factors contributing to Utah’s critical shortage of school-based speechlanguage pathologists. Specifically, this study focused on the following three constructs: (a) stress levels among professionals currently in the field, (b) attrition and the reasons professionals leave their positions, and (c) factors at the university level. Stress among Utah’s speech-language pathologists was assessed using the Speech-Language Pathologist Stress Inventory (Fimian, Lieberman, & Fasteneau, 1991). Of the 230 potential participants, 97 completed and returned questionnaires. Results indicated that Utah’s school-based speech-language pathologists experience less overall stress than a normative sample of speech-language pathologists throughout the United States; however, Utah’s professionals reported significantly greater stress related to caseload, salary, and use of prescription drugs. However, overall stress was not related to caseload size or the number of service delivery sites. In regard to how various aspects of burnout were related, a weak positive relationship was found between years of experience and Time and Workload Management. Overall, Total Stress appeared to be most strongly related to Lack of Professional Supports. Attrition was investigated by distributing an existing survey to the special education directors of Utah’s 40 school districts, who reported the status of speechlanguage pathologists employed in their respective districts. All 40 of the directors responded to the survey. Based on their report, 67 of the speech-language pathologists left their positions during the 2004-2005 school year, representing 14.5% of Utah’s school-based speech-language pathologists. The top reasons indicated for speech-language pathologists leaving their positions were (a) moved, (b) children/pregnancy, (c) changed district within state, (d) retired, and (e) left education. Finally, the directors of Utah’s three university graduate-level speech-language pathology programs were surveyed to assess factors at the university level that may be contributing to the shortage. All three directors responded to the survey. The mean number of applicants over the three-year period in question was 186 per year, and of these, an average of 111.3 or 60.0% was accepted. From these three combined programs, an average of 67 students graduated each year, and approximately 30 to 40% of these graduates initiated practice in Utah’s schools. Data from one of the three programs, Utah State University, indicated that the addition of an outreach program significantly increased their number of graduates.
Use of the Shared Decision-Making Visit for Lung Cancer Screening Among Medicare Enrollees.

In early 2015, the Centers for Medicare & Medicaid Services (CMS) initiated reimbursement for low-dose computed tomography (LDCT) screening for lung cancer in individuals aged 55 to 77 years with a 30 pack-year or greater smoking history.1 A unique feature of the CMS approval was a requirement for a separate shared decision-making (SDM) session before the LDCT.1 This visit had several required components, including use of a decision aid and counseling on tobacco abstinence. We used Medicare data from January 1,2015, through December 31,2016 to determine the percentage of enrollees who received an LDCT had a visit for SDM.
Effect of the CSF1R inhibitor PLX3397 on remyelination of corpus callosum in a cuprizone‐induced demyelination mouse model

Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). Despite introducing multiple immunomodulatory approaches for MS, there are still major concerns about possible ways for improving remyelination in this disease. Microglia exert essential roles in regulation of myelination processes, and interaction between colony‐stimulating factor 1 (CSF1) with its receptor CSF1R is considered as a key regulator of microglial differentiation and survival. The aim of this study was to investigate possible roles for a CSF1R inhibitor PLX3397 in recovery of central myelination processes. Chronic demyelination was induced in mice by addition of 0.2% cuprizone to the chow for 12 weeks. Next, animals were undergoing a diet containing 290 mg/kg PLX3397 to induce microglial ablation. The PLX3397 treatment caused a significant decrease in the rate of expression for the CSF1/CSF1R axis, and a reduction in the protein expressions for the microglial marker Iba‐1 and for the oligodendrocyte marker Olig‐2. Findings from Luxol fast blue (LFB) staining and transmission electron microscopy (TEM) showed an increase in the rate of myelination for the mice receiving PLX3397. The rate of destruction in the nerve fibers and the extent of the gaps formed between layers of myelin sheaths was also reduced after the treatment with PLX3397. In addition, animals experienced an improvement in recovery of motor deficit after receiving PLX3397 (for all P < 0.05). It could be concluded that PLX3397 could retain myelination in the MS model possibly through regulation of the myelin environment.
Lymph Node Ratio: Is It an Independent Prognostic Factor for Stage III Cutaneous Melanoma?

Objective: Lymph node ratio (LNR) is defined as the ratio of the number of metastatic lymph nodes to the dissected lymph nodes. LNR is a prognostic factor for many tumor types. The present study aimed to evaluate the prognostic value of LNR in melanoma. Methods: This retrospective cohort study was conducted on 123 patients with stage III cutaneous melanoma. Multivariate Cox proportional hazards model was used to evaluate the correlations between LNR and other clinicopathological factors associated with survival. The patients were divided into four groups in terms of the LNR, including groups A (LNR≤0.18), B (0.180.625). Results: Initially, LNR was evaluated as a continuous quantity associated with survival. In the univariate analysis, a significant correlation was observed between LNR, overall survival (OS), and disease free survival (DFS). Meanwhile, the only association observed in the multivariate analysis was between LNR and OS. Increased LNR from group A to group D reduced OS from 46 (±44.09) to 22.5 (±16.33) months (P=0.022). According to the multivariate analysis, prognostic factors in OS were tumor thickness, American joint committee of cancer (AJCC) N stage, interferon administration, and undergoing chemotherapy. Conclusion: According to the results, LNR could be used as an independent prognostic factor for estimating the survival of patients with stage III cutaneous melanoma also designing an effective adjuvant treatment protocol for these patients.