Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNA-20a in human faeces as a non-invasive biomarker for colorectal cancer

Objective Detection of microRNA (miRNA) aberrations in human faeces is a new approach for colorectal cancer (CRC) screening. The aim of this study was to characterise miR-20a in faeces as a non-invasive biomarker for diagnosis of CRC. Results miR-20a expression was significantly higher in the 40 CRC tumours compared to their respective adjacent normal tissues (P = 0.0065). Levels of miR-20a were also significantly higher in faecal samples from CRC patients (P < 0.0001). The area under receiver operating characteristic (AUROC) curve for miR-20a was 0.73, with a sensitivity of 55% and specificity of 82% for CRC patients compared with controls. No significant difference in the level of miR-20a was found between patients with proximal, distal, and rectal cancer. The use of antibiotics did not influence faecal miR-20a levels. Patients and Methods miR-20a was selected from an expression microarray containing 667 miRNAs. Further verification of miR-20a was performed in 40 pairs of primary CRC tissues, as well as 595 faecal samples (198 CRCs, 199 adenomas, and 198 healthy controls) using TaqMan probe based quantitative Real-Time PCR (qRT-PCR). Conclusions Faecal-based miR-20a can be utilised as a potential non-invasive biomarker for CRC screening.
Transarterial Embolization for Hepatocellular Carcinoma: A Comparison between Nonspherical PVA and Microspheres

Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (P = 0.679) or tumoral response (P = 0.369) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.
Extracellular Acidification Inhibits the ROS-Dependent Formation of Neutrophil Extracellular Traps

The inflammatory microenvironment is commonly characterized by extracellular acidosis (pH < 7.35). Sensitivity to pH, CO2 or bicarbonate concentrations allows neutrophils to react to changes in their environment and to detect inflamed areas in the tissue. One important antimicrobial effector mechanism is the production of neutrophil extracellular traps (NETs), which are released during a programmed reactive oxygen species (ROS)-dependent cell death, the so-called NETosis. Although several functions of neutrophils have been analyzed under acidic conditions, the effect of extracellular acidosis on NETosis remains mainly unexplored and the available experimental results are contradictory. We performed a comprehensive study with the aim to elucidate the effect of extracellular acidosis on ROS-dependent NETosis of primary human neutrophils and to identify the underlying mechanisms. The study was performed in parallel in a CO2–bicabonate-buffered culture medium, which mimics in vivo conditions, and under HEPES-buffered conditions to verify the effect of pH independent of CO2 or bicarbonate. We could clearly show that extracellular acidosis (pH 6.5, 6.0, and 5.5) and intracellular acidification inhibit the release of ROS-dependent NETs upon stimulation of neutrophils with phorbol myristate acetate and immobilized immune complexes. Moreover, our findings suggest that the diminished NET release is a consequence of reduced ROS production and diminished glycolysis of neutrophils under acidic conditions. It was suggested previously that neutrophils can sense the border of inflamed tissue by the pH gradient and that a drop in pH serves as an indicator for the progress of inflammation. Following this hypothesis, our data indicate that an acidic inflammatory environment results in inhibition of extracellular operating effector mechanisms of neutrophils such as release of ROS and NETs. This way the release of toxic components and tissue damage can be avoided. However, we observed that major antimicrobial effector mechanisms such as phagocytosis and the killing of pathogens by neutrophils remain functional under acidic conditions.
The effect of telephone support groups on costs of care for veterans with dementia.

PURPOSE Few studies have addressed the effects of caregiver interventions on the costs of care for the care recipient. This study evaluated the effects of a caregiver education and support group delivered via the telephone on care recipient health care utilization and cost. DESIGN AND METHODS The Telehealth Education Program (TEP) is a manualized program of education and support designed for caregivers of veterans with moderate-to-severe dementia. One hundred fifty-eight spousal caregivers were randomly assigned to either the ten 1-hr sessions of TEP or the usual care (UC). Health care utilization and cost data were extracted from veterans Information System Technology Architecture databases and included outpatient, inpatient, and nursing home data within the VA. RESULTS Total health care cost data showed a significant (p = .039) average cost savings of $2,768 per patient at 6 months for TEP as compared with UC, but these were not maintained at 1 year. All costs included in the total costs measure contributed to this difference. Inpatient, outpatient, and nursing home costs were all assessed separately, but only nursing home costs reached significance (p = .009), with a savings of $1,057 per patient at 6 months. IMPLICATIONS The TEP caregiver intervention resulted in short-term cost savings for veteran care recipients. Future studies of caregiver interventions should examine their effects on costs of care for the care recipients in addition to their effects on caregiver outcomes.
Demyelination Causes Adult CNS Progenitors to Revert to an Immature State and Express Immune Cues That Support Their Migration

The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult CNS, to obtain a comprehensive picture of how they become activated after demyelination and how this enables them to contribute to remyelination. We find that adult OPCs have a transcriptome more similar to that of oligodendrocytes than to neonatal OPCs, but revert to a neonatal-like transcriptome when activated. Part of the activation response involves increased expression of two genes of the innate immune system, IL1β and CCL2, which enhance the mobilization of OPCs. Our results add a new dimension to the role of the innate immune system in CNS regeneration, revealing how OPCs themselves contribute to the postinjury inflammatory milieu by producing cytokines that directly enhance their repopulation of areas of demyelination and hence their ability to contribute to remyelination.
Deletion of Kv4.2 Gene Eliminates Dendritic A-Type K+ Current and Enhances Induction of Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons

Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.
RHETORICAL STRUCTURE AND GRAPHIC ORGANIZERS: EFFECTS ON LEARNING FROM A HISTORY TEXT

This paper describes the effects of different methods to enhance students’ understanding and learning from a text. We compared the efficiency of a text revision procedure (“from the text”) and inferential activity engagement (“toward the text”) in the comprehension and recall of a History text. A total of 338 undergraduate students (aged 19-20) participated in the study. We wrote five versions of the same expository text, showing different rhetorical structures: Causation, antecedent-consequent; Causation, consequent-antecedent; Collection; Problem-solution; and Comparison. The first version, clarifying the causal structure and the temporal order of the events, had a significant effect in the delayed recall of the subjects. The task of filling an incomplete causal diagram also showed significant differences. This inferential activity, which involves the reader in the causal representation of the events, could be more useful than providing a previously elaborated graphic representation. Implications for educational practice and relevant related issues are discussed.
Assessing Violent Couples

In clinical assessment of violence between members of a couple, the practitioner's focus is expanded from the abusive incident and crisis stage to a view of couple dynamics during nonviolent periods. Often, couples view the noncrisis period as the norm and true state of the marriage, and violence is seen as an aberration. Issues such as emotional dependency, fear of rejection and abandonment, and shifting power balance between partners need to be addressed. The complexities of interaction and meaning surrounding the violence as well as the role of violence in the couple system allow for selective, differential use of an array of interventions.
Innate Immune Receptors in Human Airway Smooth Muscle Cells: Activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 Agonists

Background Pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs), recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs). Methods Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. Results HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C), LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C) also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C), down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. Conclusion Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.
The Building the Bridge survey for z =3 Lyα emitting galaxies I. Method and first results

We present the first results of an observational programme at the ESO Very Large Telescope aimed at detecting a large sample of high-redshift galaxies fainter than the current spectroscopic limit of $R=25.5$ for Lyman-Break galaxies. In this paper, we describe the results of deep narrow and broad-band imaging and subsequent follow-up multi-object spectroscopy of faint high-redshift galaxies in the fields of the QSOs BRI 1346-0322 and Q 2138-4427. These QSOs have intervening high neutral hydrogen column density absorbers, at redshifts $z=2.85$ and $z=3.15$ respectively, for which redshifted Ly α emission falls within less than a few A from the central wavelengths of existing VLT (~60 A-wide) narrow-band filters. We selected 37 and 27 candidate emission-line galaxies in the two fields respectively. Most (~85%) of the candidates have R -band magnitudes fainter than $R=25.5$. The first spectroscopic follow-up of a sub-sample of the candidates resulted in 41 confirmed candidates and 4 foreground emission line galaxies (three [$\ion{O}{ii}$] emitters and one $\ion{C}{iv}$ emitter). The confirmation rate for Ly α emitters is 82% and 68% in the field of BRI 1346-0322 and Q 2138-4427 respectively. In addition, we serendipitously detect a number of other emission-line sources on some of the slitlets not used for candidates. Of these, 9 are also most likely Ly α emitters with redshifts ranging from 1.98 to 3.47. The redshift distribution of confirmed candidates in the field of BRI 1346-0322 is consistent with being drawn from a uniform distribution weighted by the filter response curve, whereas the galaxies in the field of Q 2138-4427 have redshifts clustering very close to the redshift of the damped Ly α absorber. This latter fact indicates the existence of a large “pancake”-like structure confirming the earlier suggestions of Francis & Hewitt ([CITE]).
A Simple Method for Analyzing Exome Sequencing Data Shows Distinct Levels of Nonsynonymous Variation for Human Immune and Nervous System Genes

To measure the strength of natural selection that acts upon single nucleotide variants (SNVs) in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs) per nonsynonymous site and synonymous SNVs (sSNVs) per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv) in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs), nervous system genes (NSGs), randomly sampled genes (RSGs), and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30–40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system.
SPINAL STENOSIS AND INTERVERTEBRAL DISC DISEASE

Genetic factors have been implicated to play a role in both degenerative lumbar spinal stenosis (LSS) and intervertebral disc disease (IDD). Sequence variations in the genes coding for collagen IX and inflammatory mediators have been indicated as risk factors for IDD. Nine genes coding for intervertebral disc (IVD) collagens I, II, IX and XI and aggrecan (AGC1) were analyzed for sequence variations in 29 Finnish individuals with LSS. In addition, two polymorphisms in the vitamin D receptor gene and one in the matrix metalloproteinase-3 gene were studied. Study subjects were analyzed both clinically and radiologically. Results indicated an association between the COL11A2 IVS6-4 a to t polymorphism and LSS (p = 0.0016). Moreover, the t/t genotype was found more often in the patient group compared to controls (p = 0.0011). A novel splicing mutation, likely resulting in the synthesis of a truncated protein, was identified in COL9A2. Eight hundred four Chinese individuals were screened for the presence of the Trp2 and Trp3 alleles. The Trp2 allele was found in 20% of the individuals compared to the previously reported 5% in Finnish patients with IDD characterized by sciatica. The Trp2 allele was found to predispose to IVD degeneration and end plate herniations, increasing the risk by 2.4-fold from 40 to 49 years of age. In addition, the degeneration was worse in individuals with the Trp2 allele. The risk for annular tears was 4-fold greater in study subjects from 30 to 39 years of age who were Trp2 positive. Surprisingly, the Trp3 allele was absent even though it was found in about 9% of Finnish individuals. One hundred fifty-five Finnish individuals with IDD characterized by sciatica were analyzed for sequence variations in four genes coding for inflammatory mediators IL1A, IL1B, IL6, and TNFA. In addition, sixteen polymorphisms in inflammatory mediator genes were analyzed. The results identified an association between sciatica and the E5+15T>A polymorphism in IL6 (p = 0.007). A significant association was also seen in the IL6 haplotype analysis (-597 g>a, -572 g>c, -174 g>c and E5+15T>A). The association of the GGGA haplotype with the disease was highly significant
Operative exploration and reduction of syndesmosis in Weber type C ankle injury

OBJECTIVE: To investigate the surgical methods in treating Weber type C ankle injury and estimate the necessity of syndesmosis operative exploration. METHODS: Forty three patients of Weber type C ankle injury were treated with open reduction and internal fixation from October 2004 to December 2009. Twenty nine patients were treated with routine procedure by open reduction and internal fixation, syndesmosis exploration and repair were performed in addition in the others. Thirty four patients were followed during an average time of 31.2 months (range 18 to 50 months), amomg them 22 patients were treated with routine procedures and 12 were treated with additional syndesmosis surgical exploration. RESULTS: All the fractures were reunited in an average time of 13.1 weeks (range 10 to 18 weeks) and full weight bearing began. The mean ankle and hindfoot scale of the American Orthopaedic Foot and Ankle Society (AOFAS) score was 79.86(range 65 to 98) in the routine procedures group and 86.67 (range 78 to 100) in the syndesmosis exploration group and Olerud-Molander score was 77.27 (range 55 to 100) and 86.67 (range 75 to 100) respectively. Statistically significant difference was found between the two groups (P<0.05). CONCLUSION: Syndesmosis surgical exploration is an essential treatment in some Weber type C ankle injuries, which make debridement and direct reduction of the syndesmosis possible, providing thus a more stabilized ankle joint. Level of Evidence III, Retrospective Comparative Study
How does knowledge management influence innovation and competitiveness?

Is concerned with human value management, examines the relationships between organizations’ competitiveness, innovation advancements, and knowledge management and presents a set of considerations regarding how these relationships affect strategic management and the formulation of competitive strategies. By considering how knowledge development is related with personal characteristics and personal development, this article attempts to provide useful insights on the linkages between innovation and competitiveness. These considerations point out the importance of knowledge development and the role of knowledge management in order to assure competitiveness. This work proposes also a conceptual model, with special focus on the relationships between knowledge management, competitiveness, and innovation. The major factors are presented and directions for future research are suggested according to the proposed model.
Statistical count models for prognosis the risk factors of hepatitis C

Aim The aim of this study was to compare alternatives methods for analysis of zero inflated count data and compare them with simple count models that are used by researchers frequently for such zero inflated data. Background Analysis of viral load and risk factors could predict likelihood of achieving sustain virological response (SVR). This information is useful to protect a person from acquiring Hepatitis C virus (HCV) infection. The distribution of viral load contains a large proportion of excess zeros (HCV-RNA under 100), that can lead to over-dispersion. Patients and methods This data belonged to a longitudinal study conducted between 2005 and 2010. The response variable was the viral load of each HCV patient 6 months after the end of treatment. Poisson regression (PR), negative binomial regression (NB), zero inflated Poisson regression (ZIP) and zero inflated negative binomial regression (ZINB) models were carried out to the data respectively. Log likelihood, Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) were used to compare performance of the models. Results According to all criterions, ZINB was the best model for analyzing this data. Age, having risk factors genotype 3 and protocol of treatment were being significant. Conclusion Zero inflated negative binomial regression models fit the viral load data better than the Poisson, negative binomial and zero inflated Poisson models.
Competitive On‐line Statistics

A radically new approach to statistical modelling, which combines mathematical techniques of Bayesian statistics with the philosophy of the theory of competitive on‐line algorithms, has arisen over the last decade in computer science (to a large degree, under the influence of Dawid's prequential statistics). In this approach, which we call “competitive on‐line statistics”, it is not assumed that data are generated by some stochastic mechanism; the bounds derived for the performance of competitive on‐line statistical procedures are guaranteed to hold (and not just hold with high probability or on the average). This paper reviews some results in this area; the new material in it includes the proofs for the performance of the Aggregating Algorithm in the problem of linear regression with square loss.