Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes

We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A1c (HbA1c), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time PCR was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miRNAs replicated in both panels and 4 with high statistical significance. The strongest positive correlations with HbA1c were found with miR-125b-5p (rs = 0.40, P = 6.0 × 10−5) and miR-365a-3p (rs = 0.35, P = 5.9 × 10−4). The strongest negative correlations were found with miR-5190 (rs = –0.30, P = 0.003) and miR-770-5p (rs = –0.27, P = 0.008). Pathway analysis revealed that 50 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched by genes targeted by these four miRNAs. The axon guidance signaling pathway was enriched (P < 1 × 10−7) by genes targeted by all four miRNAs. In addition, three other pathways (Rap1 signaling, focal adhesion, and neurotrophin signaling) were also significantly enriched but with genes targeted by only by three of the identified miRNAs. In conclusion, our study identified four circulating miRNAs that were influenced by variation in hyperglycemia. Dysregulation of these miRNAs, which are associated with hyperglycemia in patients with T1D, may contribute to the development of diabetes complications. However, there are multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of diabetes complications.
A New Label-Free Technique for Analysing Evaporation Induced Self-Assembly of Viral Nanoparticles Based on Enhanced Dark-Field Optical Imaging

Nanoparticle self-assembly is a complex phenomenon, the control of which is complicated by the lack of appropriate tools and techniques for monitoring the phenomenon with adequate resolution in real-time. In this work, a label-free technique based on dark-field microscopy was developed to investigate the self-assembly of nanoparticles. A bio-nanoparticle with complex shape (T4 bacteriophage) that self-assembles on glass substrates upon drying was developed. The fluid flow regime during the drying process, as well as the final self-assembled structures, were studied using dark-field microscopy, while phage diffusion was analysed by tracking of the phage nanoparticles in the bulk solutions. The concentrations of T4 phage nanoparticles and salt ions were identified as the main parameters influencing the fluid flow, particle motion and, consequently, the resulting self-assembled structure. This work demonstrates the utility of enhanced dark-field microscopy as a label-free technique for the observation of drying-induced self-assembly of bacteriophage T4. This technique provides the ability to track the nano-sized particles in different matrices and serves as a strong tool for monitoring self-assembled structures and bottom-up assembly of nano-sized building blocks in real-time.
An Overview of Physical Layer Security With Finite-Alphabet Signaling

Providing secure communications over the physical layer with the objective of achieving secrecy without requiring a secret key has been receiving growing attention within the past decade. The vast majority of the existing studies in the area of physical layer security focus exclusively on the scenarios where the channel inputs are Gaussian distributed. However, in practice, the signals employed for transmission are drawn from discrete signal constellations such as phase shift keying and quadrature amplitude modulation. Hence, understanding the impact of the finite-alphabet input constraints and designing secure transmission schemes under this assumption is a mandatory step toward a practical implementation of physical layer security. With this motivation, this paper reviews recent developments on physical layer security with finite-alphabet inputs. We explore transmit signal design algorithms for single-antenna as well as multi-antenna wiretap channels under different assumptions on the channel state information at the transmitter. Moreover, we present a review of the recent results on secure transmission with discrete signaling for various scenarios including multi-carrier transmission systems, broadcast channels with confidential messages, cognitive multiple access and relay networks. Throughout the article, we stress the important behavioral differences of discrete versus Gaussian inputs in the context of the physical layer security. We also present an overview of practical code construction over Gaussian and fading wiretap channels, and discuss some open problems and directions for future research.
Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action

Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three‐dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A‐FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A‐FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning.
Automated Identification of Cryptographic Primitives in Binary Code with Data Flow Graph Isomorphism

Softwares use cryptographic algorithms to secure their communications and to protect their internal data. However the algorithm choice, its implementation design and the generation methods of its input parameters may have dramatic consequences on the security of the data it was initially supposed to protect. Therefore to assess the security of a binary program involving cryptography, analysts need to check that none of these points will cause a system vulnerability. It implies, as a first step, to precisely identify and locate the cryptographic code in the binary program. Since binary analysis is a difficult and cumbersome task, it is interesting to devise a method to automatically retrieve cryptographic primitives and their parameters. In this paper, we present a novel approach to automatically identify symmetric cryptographic algorithms and their parameters inside binary code. Our approach is static and based on DFG isomorphism. To cope with binary codes produced from different source codes and by different compilers and options, the DFG is normalized using code rewrite mechanisms. Our approach differs from previous works, that either use statistical criteria leading to imprecise results, or rely on heavy dynamic instrumentation. To validate our approach, we present experimental results on a set of synthetic samples including several cryptographic algorithms, binary code of well-known cryptographic libraries and reference source implementation compiled using different compilers and options.
Spatial Characteristics of Wireless Channel in Tunnel with Imperfect Walls

The successful design and application of the physical layer techniques of the wireless network, including MIMO, adaptive OFDM, and mining antenna, to name a few, need the detailed knowledge of the spatial characteristics of the transmitted signals. This paper provides a modal approach to quantify the spatial distribution of the waves in tunnels in detail. We develop the modal theory for propagation in a tunnel with imperfect walls, which are lossy, rough, and tilted. And then, we discuss the transmission power of the antenna as a function of the angles of departure (AOD). On this basis, we take the half-wave dipole antenna as an example to analyse by simulations. The theoretical results show that the angular power distribution in the rectangular tunnel follows Gaussian distribution. The angle spread (AS) of the waves can be influenced by the tunnel walls. The roughness of the wall surface is most important in small tunnels and at low frequencies, whereas the wall tilt is most important in large tunnels and at high frequencies.
Substituting physicians with nurse practitioners, physician assistants or nurses in nursing homes: protocol for a realist evaluation case study

Introduction In developed countries, substituting physicians with nurse practitioners, physician assistants and nurses (physician substitution) occurs in nursing homes as an answer to the challenges related to the ageing population and the shortage of staff, as well as to guarantee the quality of nursing home care. However, there is great diversity in how physician substitution in nursing homes is modelled and it is unknown how it can best contribute to the quality of healthcare. This study aims to gain insight into how physician substitution is modelled and whether it contributes to perceived quality of healthcare. Second, this study aims to provide insight into the elements of physician substitution that contribute to quality of healthcare. Methods and analysis This study will use a multiple-case study design that draws upon realist evaluation principles. The realist evaluation is based on four concepts for explaining and understanding interventions: context, mechanism, outcome and context–mechanism–outcome configuration. The following steps will be taken: (1) developing a theory, (2) conducting seven case studies, (3) analysing outcome patterns after each case and a cross-case analysis at the end and (4) revising the initial theory. Ethics and dissemination The research ethics committee of the region Arnhem Nijmegen in the Netherlands concluded that this study does not fall within the scope of the Dutch Medical Research Involving Human Subjects Act (WMO) (registration number 2015/1914). Before the start of the study, the Board of Directors of the nursing home organisations will be informed verbally and by letter and will also be asked for informed consent. In addition, all participants will be informed verbally and by letter and will be asked for informed consent. Findings will be disseminated by publication in a peer-reviewed journal, international and national conferences, national professional associations and policy partners in national government.
Measuring mental workload: ocular astigmatism aberration as a novel objective index

Abstract This study assessed the effect of two perceptually matched mental tasks with different levels of mental demand on ocular aberrations in a group of young adults. We measured ocular aberration with a wavefront sensor, and total, internal and corneal RMS (root mean square) aberrations were calculated from Zernike coefficients, considering natural and scaled pupils (5, 4.5, and 4 mm). We found that total, internal and corneal astigmatism RMS showed significant differences between mental tasks with natural pupils (p < .05), and this effect was maintained with 5 mm scaled pupils (total RMS astigmatism, p < .05). Consistently, pupil size, intraocular pressure, perceived mental load and cognitive performance were influenced by the level of mental complexity (p < .05 for all). The findings suggest that ocular astigmatism aberration, mediated by intraocular pressure, could be an objective, valid reliable index to evaluate the impact of cognitive processing in conjunction with others physiological markers in real world contexts. Practitioner Summary: The search continues for a valid, reliable, convenient method of measuring mental workload. In this study we found ocular astigmatism aberration is sensitive to the cumulative effect of mental effort. It shows promise of being a novel ocular index which may help to assess mental workload in real situations.
ARF-GAP–mediated interaction between the ER-Golgi v-SNAREs and the COPI coat

In eukaryotic cells, secretion is achieved by vesicular transport. Fusion of such vesicles with the correct target compartment relies on SNARE proteins on both vesicle (v-SNARE) and the target membranes (t-SNARE). At present it is not clear how v-SNAREs are incorporated into transport vesicles. Here, we show that binding of ADP-ribosylation factor (ARF)–GTPase-activating protein (GAP) to ER-Golgi v-SNAREs is an essential step for recruitment of Arf1p and coatomer, proteins that together form the COPI coat. ARF-GAP acts catalytically to recruit COPI components. Inclusion of v-SNAREs into COPI vesicles could be mediated by direct interaction with the coat. The mechanisms by which v-SNAREs interact with COPI and COPII coat proteins seem to be different and may play a key role in determining specificity in vesicle budding.
Mechanical Behavior of Fiber-Reinforced Polymer-Wrapped Concrete Columns—Complicating Effects

The present study focuses on the mechanical response of concrete columns confined with fiber-reinforced polymer composites (FRP). Practical columns often deviate from axisymmetric conditions due to noncircular cross section, geometric imperfections, and loading eccentricities. This paper discusses these complicating effects on the mechanical behavior of columns confined with FRP. Experiments have been carried out to examine the effects of geometric and loading imperfections on columns of various shapes. A model originally developed for axisymmetric situations has been extended to include the complicating effects. An analytical study for the corner radius that avoids concentration of stress is carried out. The theoretical models have been verified with the present and published experimental results.
P16(INK4a) immunocytochemistry in liquid-based cytology samples in equivocal Pap smears: added value in management of women with equivocal Pap smear.

OBJECTIVE To test whether p1l6(INK4a) immunocytochemistry (ICC) in liquid-based cytology (LBC) is useful with colposcopy in abnormal Pap smears. STUDY DESIGN A series of 248 women with abnormal Pap smear were analyzed for oncogenic (HR) human papillomavirus (HPV) types using the Hybrid Capture II assay and for p16(INK4a) expression using ICC on cervical samples in PreservCyt liquid media. Colposcopic and loop electrosurgical excision procedure (LEEP) cone biopsy were the gold standard. RESULTS p16(INK4a) ICC did best as predictor of high-grade squamous intraepithelial lesion, with OR 12.18 (2.72-54.57) (p = 0.0001), showing 88.2% sensitivity (SE), 61.9% specificity (SP), 14.6% positive predictive value (PPV) and 98.6% negative predictive value (NPV). In sorting discrepant cases, p16(INK4a) ICC results in 100% SE and 100% NPV in detecting cervical intraepithelial neoplasia (CIN) 2 lesions among Pap+/biopsy- women. In atypical squamous cells undetermined significance (ASCUS) cytology, adding p16(INK4a) ICC improves specificity of colposcopy from 27.3% to 81.8% and PPV from 42.8% to 71.4%. Best performance is obtained with p16(INK4a) ICC and colposcopy: 83.3% SE, 81.8% SP, 71.4% PPV and 90.0% NPV. CONCLUSION p16(INK4a) is useful in sorting clinically relevant discrepant cases, and p16(INK4a) ICC significantly improves SP and PPV of colposcopy in management of ASCUS cytology.
Pharmacists’ Impact on Improving Outcomes in Patients With Type 2 Diabetes Mellitus

Purpose The purpose of this study was to evaluate a diabetes education program that includes a pharmacist as a member of the diabetes management team by assessing the change in hemoglobin A1c (A1C), cholesterol, and blood pressure for patients with type 2 diabetes in outpatient clinics. Methods This was a retrospective study in outpatient clinics at Shands Jacksonville Medical Center. The patients were assigned into either the pharmacist group or the nonpharmacist group, according to the presence or the absence of a pharmacist in the clinic. The primary end point was the absolute change in A1C versus baseline. Secondary end points included change in cholesterol and blood pressure and the number of patients to attain American Diabetes Association goals. End points were recorded to correlate within 3 months of the initial visit and final visit with a provider. Results Compared to the nonpharmacist group, patients in the pharmacist group had more advanced and uncontrolled diabetes at baseline. The pharmacist group showed a greater percent change in A1C and improvement between the initial and final clinic visits, after adjusting for baseline confounders. Despite the statistically significant improvement in A1C in the pharmacist group, there was no difference found between the 2 groups for the end points of cholesterol and blood pressure. Conclusion Including a pharmacist as a part of the diabetes management team may result in lower A1C in patients with more advanced and uncontrolled type 2 diabetes mellitus versus a health care team without a pharmacist.
Outcome of Robotic Radical Prostatectomy in Men Over 74

Abstract Introduction: We set out to evaluate outcomes in patients over 74 after robotic radical prostatectomy. Materials and Methods: Six hundred forty-seven patients over 74 (≥75) were analyzed for preoperative factors (body mass index [BMI], American Society of Anestesiologists classification [ASA], prostate-specific antigen [PSA], International prostate symptome score [IPSS], International index of erectile function [IIEF]), operative and perioperative characteristics (technique, erythrocyte conc., complications), and histopathological results. After 12 months, following items were assessed: PSA, frequency of urine loss, number of pads used (including safety), incontinence at night, and potency as quantified by IIEF-5. Results: Mean age in the group <75 was 64.8 years (range 46–74 years) and in the group ≥75 76.9 years (75–88). No statistically significant differences could be detected in terms of BMI, ASA score, or preoperative PSA, respectively. IPSS and IIEF were significantly worse in the group ≥75. Major complications (>Clavien-Dindo III) were found in 1.6% vs. 1.3% (≥75) of cases. Minor complications were encountered in 22.8% vs. 26.3% (≥75). There was a remarkably high percentage of locally advanced disease (73.3% vs. 71.0%) in both groups. Patients ≥75 showed a tendency toward more aggressive cancer and more frequent nodal involvement; we found a higher percentage of R1-resections (19.5% vs. 30.4%, p < 0.05) and PSA relapse after 1 year (12.3% vs. 22.8%, p < 0.05). Twelve months pad-free continence rate (69.9% vs. 63.2%) showed no statistically significant difference between both groups as did the preservation rate of erectile function. Conclusion: We could show that robotic prostatectomy can be carried out safely with good functional and histopathological results in patients ≥75. It is therefore questionable if elderly patients can be precluded from curative radical treatment solely because of their age.
CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line

Objective(s): Multidrug resistance (MDR) is a major obstacle in the successful chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR in cancer. The aim of this study was to investigate the efficiency and ability of CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression in adriamycin resistant (A2780/ADR) ovarian cancer cell line and evaluate the sensitivity changes to doxorubicin. Materials and Methods: Three single-guide RNAs (sgRNAs) targeting the fourth and fifth exons of human ABCB1 gene were designed in this study. Expression level of ABCB1 was detected using quantitative real time PCR (qRT-PCR) after co-transfection of all three sgRNAs into A2780/ADR cell line and subsequent antibiotic selection. Drug sensitivity to doxorubicin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The results showed that CRISPR/Cas9 system could significantly reduce the expression of P-gp. The dramatic decline in ABCB1 gene expression was associated with increased sensitivity of cells transfected with sgRNAs to doxorubicin. Conclusion: Based on the results of this study, it is concluded that the CRISPR-based systems, used in the present study, effectively down-regulated the target gene and acted as an ideal and cost-effective tool for gene editing of A2780/ADR cell line resulting in restoration of nonmalignant phenotype.
Utilization of Pyrosequencing to Monitor the Microbiome Dynamics of Probiotic Treated Poultry (Gallus gallus domesticus) during Downstream Poultry Processing

Antibiotic growth promoters that have been historically employed to control pathogens and increase the rate of animal development for human consumption are currently banned in many countries. Probiotics have been proposed as an alternative to control pathogenic bacteria. Traditional culture methods typically used to monitor probiotic effects on pathogens possess significant limitations such as a lack in sensitivity to detect fastidious and non-culturable bacteria, and are both time consuming and costly. Here, we tested next generation pyrosequencing technology as a streamline and economical method to monitor the effects of a probiotic on microbial communities in juvenile poultry (Gallus gallus domesticus) after exposure to several microbiological challenges and litter conditions. Seven days and repeated again at 39 days following hatching, chicks were challenged with either Salmonella enterica serovar Enteritidis, Campylobacter jejuni, or no bacteria in the presence of, or without a probiotic (i.e., Bacillus subtilis) added to the feed. Three days following each of two challenges (i.e., days 10 and 42, respectively) the microbiome distributions of the poultry caecum were characterized based on 16S rDNA analysis. Generated PCR products were analyzed by automated identification of the samples after pooling, multiplexing and sequencing. A bioinformatics pipeline was then employed to identify microbial distributions at the phylum and genus level for the treatments. In conclusion, our results demonstrated that pyrosequencing technology is a rapid, efficient and cost-effective method to monitor the effects of probiotics on the microbiome of poultry propagated in an agricultural setting.