Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in patients with type 2 diabetes

Background MicroRNAs (miRNAs) are small non-coding RNAs participating in post-transcriptional regulation of genes. Their key role in modulating the susceptibility to human diseases is now widely recognized, in particular in the context of cardiometabolic disorders. The aim of the present study was to identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods A next-generation sequencing-based miRNA profiling was performed in a case-control study for DN in plasma samples of 23 T2D patients with DN (cases) and 23 T2D without (controls). The main associations were confirmed using quantitative reverse transcription-polymerase chain reaction and tested for replication in an independent case-control collection of 100 T2D patients, 50 with DN and 50 without. Results From the 381 known mature miRNAs that were found highly expressed in the discovery samples, we observed and replicated an association between increased plasma levels of hsa-miR-152-3p and DN (P = 4.03 × 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were further found to be positively correlated (P = 0.003) to plasma osmolarity, a surrogate marker for solute carrier net activity, whose regulation is controlled by several genes including SLC5A3, one of the predicted targets of hsa-miR-152-3p. Conclusions We observed strong evidence for the association of hsa-miR-152-3p plasma levels and DN in patients with T2D, confirming an association previously observed in patients with type 1 diabetes.
Association of Pneumococcal Protein Antigen Serology With Age and Antigenic Profile of Colonizing Isolates

Background Several Streptococcus pneumoniae proteins play a role in pathogenesis and are being investigated as vaccine targets. It is largely unknown whether naturally acquired antibodies reduce the risk of colonization with strains expressing a particular antigenic variant. Methods Serum immunoglobulin G (IgG) titers to 28 pneumococcal protein antigens were measured among 242 individuals aged <6 months-78 years in Native American communities between 2007 and 2009. Nasopharyngeal swabs were collected >- 30 days after serum collection, and the antigen variant in each pneumococcal isolate was determined using genomic data. We assessed the association between preexisting variant-specific antibody titers and subsequent carriage of pneumococcus expressing a particular antigen variant. Results Antibody titers often increased across pediatric groups before decreasing among adults. Individuals with low titers against group 3 pneumococcal surface protein C (PspC) variants were more likely to be colonized with pneumococci expressing those variants. For other antigens, variant-specific IgG titers do not predict colonization. Conclusion We observed an inverse association between variant-specific antibody concentration and homologous pneumococcal colonization for only 1 protein. Further assessment of antibody repertoires may elucidate the nature of antipneumococcal antibody-mediated mucosal immunity while informing vaccine development.
A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk

Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC. We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ2-based Q statistic test Begg's funnel plot or Egger's test, respectively. Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106-1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results.
The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain

Up to 15% of acute myeloid leukemias (AMLs) are characterized by the abnormal expression of the eight-twenty-one (ETO) transcriptional corepressor within an AML1-ETO fusion protein. The t(8;21) chromosomal translocation serves not only to disrupt WT AML1 function but also to introduce ETO activity during hematopoiesis. AML1-ETO was recently shown to inhibit E protein transactivation by physically displacing WT coactivator proteins in an interaction mediated by ETO. Here, we present the 3D solution structure of the human ETO TAFH (eTAFH) domain implicated in AML1-ETO:E protein interactions and report an unexpected fold similarity to paired amphipathic helix domains from the transcriptional corepressor Sin3. We identify and characterize a conserved surface on eTAFH that is essential for ETO:E protein recognition and show that the mutation of key conserved residues at this site alleviates ETO-based silencing of E protein transactivation. Our results address uncharacterized aspects of the corepression mechanism of ETO and suggest that eTAFH may serve to recruit ETO (or AML1-ETO) to DNA-bound transcription factors. Together, these findings imply that a cofactor exchange mechanism, analogous to that described for E protein inhibition, may represent a common mode of action for ETO.
Comparison of Urine 4-(Methylnitrosamino)-1-(3)Pyridyl-1-Butanol and Cotinine for Assessment of Active and Passive Smoke Exposure in Urban Adolescents

Background: Many adolescents are exposed to tobacco smoke, from either active smoking (CS) or secondhand smoke (SHS) exposure. Tobacco-specific biomarkers of exposure include cotinine (detects use in past 2–4 days) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; detects use for a month or longer). NNAL is expected to detect more intermittent tobacco exposure. We compared NNAL and cotinine as biomarkers of exposure to tobacco in urban adolescents and determined the optimal NNAL cutoff point to distinguish CS from SHS exposure. Methods: Surplus urine samples, collected from 466 adolescents attending pediatric well or urgent care visits at Zuckerberg San Francisco General Hospital in 2013 to 2014, were assayed for cotinine and NNAL. Results: Ninety-four percent of adolescents had measurable levels of NNAL compared with 87% for cotinine. The optimal NNAL cutoff point to distinguish CS from SHS was 9.6 pg/mL by latent class or 14.4 pg/mL by receiver-operating characteristic analysis. Cotinine and NNAL were strongly correlated, but the correlation slopes differed for active versus SHS-exposed adolescents. Among nonsmokers, NNAL levels were significantly higher in African American (median, 3.3 pg/mL) compared with other groups (0.9–1.9 pg/mL), suggesting greater exposure to SHS. Conclusions: Urine NNAL screening finds a large majority (94%) of urban adolescents are exposed to tobacco. African Americans are exposed to higher levels of SHS than other ethnic/racial groups. Impact: SHS is associated with significant medical morbidity in adolescents. Routine biochemical screening with NNAL or cotinine detects high prevalence of SHS exposure and should be considered as a tool to reduce SHS exposure in high-risk populations. Cancer Epidemiol Biomarkers Prev; 27(3); 254–61. ©2018 AACR.
Social comparisons in adults with type 2 diabetes: Patients’ reasons for target selection

Objective: To examine reasons for selecting a social comparison target (i.e. a specific other for relative self-evaluation), and their influence on affect and motivation for self-care, in type 2 diabetes (T2DM). Design: Adults with T2DM (n = 180, MA1c = 7.6%) chose to read about one of four targets. Participants rated five reasons for their choice (strongly disagree – strongly agree), and rated affect and self-care motivation before and after reading. Results: To boost confidence in my ability to manage diabetes was rated highest overall (ps < 0.01), though choosing worse-off (vs. better-off) targets was associated with to gain useful information about how to improve (p = 0.04, = 0.05). Selection in order to feel better worked for those who chose better-off targets; choosing worse-off targets for this purpose worsened mood and stress (ps < 0.04, s = 0.02). Choosing worse-off targets to learn about similar others reduced self-care motivation (p < 0.01, = 0.05). Selection in order to boost confidence showed increased motivation only among those who chose better-off targets (p = 0.01). Conclusions: Patients’ reasons for a particular comparison are associated with short-term changes in affect and self-care motivation, and warrant greater empirical and clinical attention.
Euploidy rates in donor egg cycles significantly differ between fertility centers

Study question Do external factors affect euploidy in egg donor cycles? Summary answer The study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic. What is known already Chromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group. Study design, size, duration A total of 1645 donor oocyte cycles and 13 282 blastocyst biopsies from 42 fertility clinics were included in this retrospective cohort study. Samples from donor cycles with PGS attempted between September 2011 and July 2015 were included. Participants/materials, setting, methods PGS cycles from multiple fertility clinics referred to Reprogenetics (Livingston, NJ) that involved only oocyte donation were included in this study. Testing was performed by array comparative genomic hybridization (aCGH). Ploidy data were analyzed using Generalized Linear Mixed Models with logistic regression using a logit link function considering a number of variables that represent fixed and random effects. Main results and the role of chance Euploidy rate was associated with the referring center and independent of almost all the parameters examined except donor age and testing technology. Average euploidy rate per center ranged from 39.5 to 82.5%. The mean expected rate of euploidy was 68.4%, but there are variations in this rate associated with the center effect. Limitations, reasons for caution Data set does not include details of the donor selection process, donor race or ethnic origin, ovarian reserve or ovarian responsiveness. Due to the retrospective nature of the study, associations are apparent, however, causality cannot be established. Discrepancies in regard to completeness and homogeneity of data exist due to data collection from over 40 different clinics. Wider implications of the findings This is the first study to show a strong association between center-specific ART treatment practices and the incidence of chromosome abnormality in human embryos, although the meiotic or mitotic origin of these abnormalities could not be determined using these technologies. Given the widespread applications of ART in both subfertile and fertile populations, our findings should be of interest to the medical community in general as well as the ART community in particular. Study funding/competing interest(s) No external funds were used for this study. S. Munne is a founding principle of Reprogenetics/current employee of Cooper Genomics. M Alikani's spouse is a founding principle of Reprogenetics/current consultant for Cooper Genomics. The remaining authors have no conflicts to declare.
General Unbiased FIR Filter With Applications to GPS-Based Steering of Oscillator Frequency

The general unbiased finite-impulse response (UFIR) filter proposed in this brief has important structural advantages against its basic predecessor. It can be applied to systems with or without the control input. We derive this filter in a batch form and then design its fast iterative Kalman-like algorithm using recursions. The iterative UFIR algorithm proposed is applied to the three-state polynomial model which is basic in clock synchronization. We test it by the global positioning system-based frequency steering of an oven-controlled crystal oscillator. Better robustness and higher accuracy of the UFIR filter against the Kalman filter are shown experimentally.
Chromosomally encoded ESBL genes in Escherichia coli of ST38 from Mongolian wild birds

Objectives ESBL genes in Escherichia coli are mainly plasmid encoded, although recent studies have also shown chromosomal integration, e.g. in clinical E. coli isolates of ST38. As ESBL-producing E. coli are also found in non-clinical settings, we were interested in determining whether chromosomally integrated ESBL genes occur in ST38 isolates from non-clinical habitats, e.g. wildlife. Methods Four ESBL-producing E. coli isolates of ST38 originating from Mongolian birds of prey sampled in 2015 were subjected to a detailed analysis in terms of phenotypic resistance, plasmid profiling and WGS, followed by the determination of genotypic resistance factors including the chromosomal integration of ESBL and carbapenemase genes. Results Results based on phenotypic and genotypic plasmid profiling, contiguous sequence (contig) sizes and PCR analysis of flanking insertion site regions showed that three of four ST38 isolates harboured chromosomally encoded bla CTX-M genes of three different types ( bla CTX-M-14 , bla CTX-M-15 and bla CTX-M-24 ) that were inserted into three different chromosomal locations. A comparison of WGS data with ST38 isolates from a clinical outbreak in the UK indicated only low numbers of core-genome SNPs detected among one Mongolian wild bird isolate and eight clinical isolates from the UK. Conclusions The chromosomal integration of bla CTX-M genes in E. coli isolates of ST38 appears to be common and is likely independent of antimicrobial selective pressure in clinical environments. Our data corroborate the zoonotic potential of environmental isolates of ESBL-producing E. coli , which harbour stably integrated, chromosomally encoded resistance factors.
Impact of CSI Knowledge on the Codebook-Based Hybrid Beamforming in Massive MIMO

Hybrid beamforming, which consists of an RF precoder and a baseband precoder, has been proposed to reduce the number of RF chains at the massive multiple input multiple output (MIMO) base station (BS). This paper studies the impact of channel state information (CSI) on the capacity of massive MIMO systems with codebook-based hybrid beamforming , where the RF precoder is selected from a finite size codebook. Two types of CSI at the BS (CSIT) are commonly assumed: full instantaneous CSIT and hybrid CSIT (channel statistics plus the low-dimensional effective channel matrix). With full instantaneous CSIT, both the RF and baseband precoders are adaptive to the full instantaneous CSI at the fast timescale. With hybrid CSIT, the RF precoder is adaptive to channel statistics only, and the baseband precoder is adaptive to the instantaneous effective channel, yielding lower implementation complexity by sacrificing some capacity. We derive asymptotic sum capacity expressions under these two types of CSIT. We find that, in codebook-based hybrid beamforming systems, exploiting the full instantaneous CSIT can only achieve a marginal SNR gain and hybrid CSIT is sufficient to achieve the first-order gain provided by the massive MIMO for most of the cases. We also propose fast and slow timescale RF precoding algorithms, which asymptotically achieve the capacity under full instantaneous CSIT and hybrid CSIT, respectively.
Bionanocomposite materials from layered double hydroxide/N-trimellitylimido-l-isoleucine hybrid and poly(vinyl alcohol)

Nanocomposites (NCs) of poly(vinyl alcohol) (PVA) with chiral-modified magnesium–aluminum-layered double hydroxides (LDHs) were prepared by solution intercalation method. A novel chiral organomodified LDH was synthesized from the coprecipitation reaction of the aluminum (III) nitrate nonahydrate, magnesium (II) nitrate hexahydrate, and bioactive N-trimellitylimido-l-isoleucine amino acid in aqueous solution via simple, fast, and green method under ultrasound irradiation for the first time. The morphology and structure of the obtained material are examined by X-ray diffraction (XRD), Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and field-emission SEM techniques. The TEM and XRD structure study revealed a coexistence of exfoliated and intercalated modified LDH in PVA matrix. The effects of modified LDH contents on the thermal property of PVA films were investigated by thermogravimetric analysis method, and the results show that by the addition of the modified LDH into the PVA causes an increase in the thermal decomposition temperatures of the novel NC materials.
Deep Dirichlet Multinomial Regression

Dirichlet Multinomial Regression (DMR) and other supervised topic models can incorporate arbitrary document-level features to inform topic priors. However, their ability to model corpora are limited by the representation and selection of these features – a choice the topic modeler must make. Instead, we seek models that can learn the feature representations upon which to condition topic selection. We present deep Dirichlet Multinomial Regression (dDMR), a generative topic model that simultaneously learns document feature representations and topics. We evaluate dDMR on three datasets: New York Times articles with fine-grained tags, Amazon product reviews with product images, and Reddit posts with subreddit identity. dDMR learns representations that outperform DMR and LDA according to heldout perplexity and are more effective at downstream predictive tasks as the number of topics grows. Additionally, human subjects judge dDMR topics as being more representative of associated document features. Finally, we find that supervision leads to faster convergence as compared to an LDA baseline and that dDMR’s model fit is less sensitive to training parameters than DMR.
Identification of distinct biological functions for four 3′-5′ RNA polymerases

The superfamily of 3′-5′ polymerases synthesize RNA in the opposite direction to all other DNA/RNA polymerases, and its members include eukaryotic tRNAHis guanylyltransferase (Thg1), as well as Thg1-like proteins (TLPs) of unknown function that are broadly distributed, with family members in all three domains of life. Dictyostelium discoideum encodes one Thg1 and three TLPs (DdiTLP2, DdiTLP3 and DdiTLP4). Here, we demonstrate that depletion of each of the genes results in a significant growth defect, and that each protein catalyzes a unique biological reaction, taking advantage of specialized biochemical properties. DdiTLP2 catalyzes a mitochondria-specific tRNAHis maturation reaction, which is distinct from the tRNAHis maturation reaction typically catalyzed by Thg1 enzymes on cytosolic tRNA. DdiTLP3 catalyzes tRNA repair during mitochondrial tRNA 5′-editing in vivo and in vitro, establishing template-dependent 3′-5′ polymerase activity of TLPs as a bona fide biological activity for the first time since its unexpected discovery more than a decade ago. DdiTLP4 is cytosolic and, surprisingly, catalyzes robust 3′-5′ polymerase activity on non-tRNA substrates, strongly implying further roles for TLP 3′-5′ polymerases in eukaryotes.
Two Novel MicroRNA Biomarkers Related to &bgr;-Cell Damage and Their Potential Values for Early Diagnosis of Type 1 Diabetes

Context New strategies and biomarkers are needed in the early detection of β-cell damage in the progress of type 1 diabetes mellitus (T1DM). Objective To explore whether serum microRNAs (miRNA) should be served as biomarkers for T1DM. Design, Settings, and Patients The miRNA profile was established with miRNA microarray in discovery phase (six T1DM, six controls). A miRNA-based model for T1DM diagnosis was developed using logistic regression analysis in the training dataset (40 T1DM, 56 controls) and then validated with leave-one-out cross validation and another independent validation dataset (33 T1DM, 29 controls). Main Outcome Measures Quantitative reverse transcription polymerase chain reaction was applied to confirm the differences of candidate miRNAs between T1DM and controls. Area under the receiver-operating characteristic (ROC) curve (AUC) was used to evaluate diagnostic accuracy. INS-1 cells, streptozotocin-treated mice (n = 4), and nonobese diabetic (NOD) mice (n = 12) were used to evaluate the association of miRNAs with β-cell damage. Results A miRNA -based model was established in the training dataset with high diagnostic accuracy for T1DM (AUC = 0.817) based on six candidate differential expressed miRNAs identified in discovery phase. The validation dataset showed the model's satisfactory diagnostic performance (AUC = 0.804). Secretions of miR-1225-5p and miR-320c were significantly increased in streptozotocin-treated mice and INS-1 cells. Noteworthy, the elevation of these two miRNAs was observed before glucose elevation in the progress of diabetes in NOD mice. Conclusions Two miRNA biomarkers (miR-1225-5p and miR-320c) related to β-cell damage were identified in patients with recent-onset T1DM. The miRNA-based model established in this study exhibited a good performance in diagnosis of T1DM.
Formulation design and development of matrix diffusion controlled transdermal drug delivery of glimepiride

Background The present work was conducted to prepare and evaluate transdermal patches with optimization of suitable polymeric blend of poly(meth) acrylates (Eudragit®) (Ammonio Methacrylate Copolymer Ph Eur) for sustained transdermal delivery of glimepiride. Method Polymeric matrix transdermal films were prepared by using Ammonio Methacrylate Copolymer Ph Eur RL 100 and Ammonio Methacrylate Copolymer Ph Eur RS 100 as the film former, and dibutyl phthalate (30% w/w) as the plasticizer. Patches were characterized by physical appearance, thickness, weight variation, folding endurance, percentage erosion, swelling index, moisture content, and moisture uptake capacity. Fourier transform infrared spectroscopic studies and differential scanning calorimetry analysis of physical mixtures of contents were performed to identify any chemical and physical interaction between drug and excipients. Five different enhancers (isopropyl myristate [IPM], Span® 80, Tween® 20, eucalyptus oil, and limonene) were employed at three different concentrations of polymer (2%, 5%, and 10% w/w) in order to enhance permeation through rabbit skin. In vitro drug release studies were performed at pH 7.4, and scanning electron microscopy was conducted to elucidate surface morphology before and after the drug release. In vitro permeation studies through rabbit skin were performed on Franz diffusion cells and permeation kinetics followed the Higuchi model. Results Results of in vitro permeation studies revealed that these enhancers not only increased drug release but also augmented the skin permeation of glimepiride. Conclusion IPM was the most effective enhancer with the highest permeation flux of 51.763 μg/cm2/hr, and the enhancement effect of different enhancers on glimepiride permeation through rabbit skin was in the rank order of IPM > eucalyptus oil > Span® 80 > Tween® 20> limonene.