Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations

Background The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. Methods 1599 individuals (mean age 64 years [min-max 29–96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010–2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. Results Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. Conclusions Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a “missing heritability” in early-onset CAD warrants more research.
Multi-GPU Based Parallel Design of the Ant Colony Optimization Algorithm for Endmember Extraction from Hyperspectral Images

Spectral unmixing is a vital procedure in hyperspectral remote sensing image exploitation. The linear mixture model has been widely utilized to unmix hyperspectral images by extracting a set of pure spectral signatures, called endmembers in hyperspectral jargon, and estimating their respective fractional abundances in each pixel of the scene. Many algorithms have been proposed to extract endmembers automatically, which is a critical step in the spectral unmixing chain. In recent years, the ant colony optimization (ACO) algorithm has been developed for endmember extraction from hyperspectral data, which was regarded as a combinatorial optimization problem. Although the ACO for endmember extraction (ACOEE) can acquire accurate endmember results, its high computational complexity has limited its application in the hyperspectral data analysis. The GPUs parallel computing technique can be utilized to improve the computational performance of ACOEE, but the architecture of GPUs determines that the ACOEE should be redesigned to take full advantage of computing resources on GPUs. In this paper, a multiple sub-ant-colony-based parallel design of ACOEE was proposed, in which an innovative mechanism of local pheromone for sub-ant-colonies is utilized to enable ACOEE to be preferably executed on the multi-GPU system. The proposed method can avoid much synchronization among different GPUs to affect the computational performance improvement. The experiments on two real hyperspectral datasets demonstrated that the computational performance of ACOEE significantly benefited from the proposed methods.
Extended-Family Talk about Sex and Teen Sexual Behavior

Research shows that family communication about sexuality can protect against teens’ risky sexual behavior. However, few studies assess talk with extended family about sex or how this communication relates to teens’ sexual behavior. The current study includes cross-sectional survey data from 952 adolescents. Structural equation modeling (SEM) was used to assess associations between teens’ sexual risk behaviors and communication with extended family about protection methods, risks of sex and relational approaches to sex, defined as talk about sex within a close relationship. For sexually active teens, talk about protection methods was associated with fewer sexual partners and talk about risks of sex was associated with more sexual partners regardless of teen gender and the generation of extended family with whom teens talk. Results suggest that extended-family talk about sex may influence teens’ sexual behavior independent of effects of teen–parent communication. However, the direction of the effect depends on the content of the conversations. These findings suggest the need to explore whether and how extended family could be included in health prevention and intervention programs, because programs which include family largely focus on parents.
Visual mismatch negativity to disappearing parts of objects and textures

Visual mismatch negativity (vMMN), an event-related signature of automatic detection of events violating sequential regularities is traditionally investigated to the onset of frequent (standard) and rare (deviant) events. In a previous study [4] we obtained vMMN to vanishing parts of continuously presented objects (diamonds with diagonals), and we concluded that the offset-related vMMN is a model of sensitivity to irregular partial occlusion of objects. In the present study we replicated the previous results, but to test the object-related interpretation we applied a new condition with a set of separate visual stimuli: a texture of bars with two orientations. In the texture condition (offset of bars with irregular vs. regular orientation) we obtained vMMN, showing that the continuous presence of objects is unnecessary for offset-related vMMN. However, unlike in the object-related condition, reappearance of the previously vanishing lines also elicited vMMN. In a formal way reappearance of the stimuli is an event with probability 1.0, and according to the results, object condition reappearance is an expected event. However, offset and onset of texture elements seems to be treated separately by the system underlying vMMN. As an advantage of the present method, the whole stimulus set during the inter-stimulus interval saturates the visual structures sensitive to stimulus input. Accordingly, the offset-related vMMN is less sensitive to low-level adaptation difference between the deviant and standard stimuli.
The Nrf2/HO-1 axis can be a prognostic factor in clear cell renal cell carcinoma

Objective To study the protein expression level of Nrf2/HO-1 in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissue and to explore its relationship with clinicopathological characteristics and prognosis in ccRCC patients. Materials and methods In total, 152 ccRCC patients with available follow-up and clinical data were enrolled, and sample microarrays were prepared for immunohistochemistry studies. The human ccRCC cell lines 786-O, OS-RC-2, A498, and ACHN were cultured for immunofluorescence. The protein concentrations of five ccRCC patients’ tumor and adjacent normal renal tissues were prepared for Western blotting. Chi-squared tests, Fisher’s exact test, Kaplan–Meier analyses, log-rank tests, and Cox regression were performed for statistical analyses. Results The immunoreactivity results showed that the Nrf2 and HO-1 proteins were found in consistent locations in vitro and were expressed both in ccRCC and adjacent normal tissues. The two proteins were localized in the cytoplasm and nucleus of RCC tumor cells and in adjacent normal tissue cells. The expression levels of Nrf2 and HO-1 were significantly higher in ccRCC tissues than in the adjacent normal tissues. The Nrf2 protein level was found to be significantly correlated with the tumor size. Additionally, higher protein expression levels of Nrf2 and HO-1 were also correlated with worse overall survival outcomes and could potentially be used to predict the prognosis of ccRCC patients. Conclusion Our study provides an important theoretical basis for evaluating the clinical prognosis of ccRCC patients, which implies that the Nrf2/HO-1 axis can be a prognostic factor in ccRCC.
Single-Walled Carbon Nanotubes as Enhancing Substrates for PNA-Based Amperometric Genosensors

A new amperometric sandwich-format genosensor has been implemented on single-walled carbon nanotubes screen printed electrodes (SWCNT-SPEs) and compared in terms of performance with analogous genoassays developed using the same methodology on non-nanostructured glassy carbon platforms (GC-SPE). The working principle of the genosensors is based on the covalent immobilization of Peptide Nucleic Acid (PNA) capture probes (CP) on the electrode surface, carried out through the carboxylic functions present on SWCNT-SPEs (carboxylated SWCNT) or electrochemically induced on GC-SPEs. The sequence of the CP was complementary to a 20-mer portion of the target DNA; a second biotin-tagged PNA signalling probe (SP), with sequence complementary to a different contiguous portion of the target DNA, was used to obtain a sandwich hybrid with an Alkaline Phosphatase-streptavidin conjugate (ALP-Strp). Comparison of the responses obtained from the SWCNT-SPEs with those produced from the non-nanostructured substrates evidenced the remarkable enhancement effect given by the nanostructured electrode platforms, achieved both in terms of loading capability of PNA probes and amplification of the electron transfer phenomena exploited for the signal transduction, giving rise to more than four-fold higher sensitivity when using SWCNT-SPEs. The nanostructured substrate allowed to reach limit of detection (LOD) of 71 pM and limit of quantitation (LOQ) of 256 pM, while the corresponding values obtained with GC-SPEs were 430 pM and 1.43 nM, respectively.
The Association between Lead and Attention-Deficit/Hyperactivity Disorder: A Systematic Review

The etiology of Attention-Deficit/Hyperactivity Disorder (ADHD) is complex and multifactorial. Although the development of ADHD symptoms remains to be elucidated, in recent years, epigenetic processes have emerged as candidate mechanisms. Lead is one of the most dangerous environmental pollutants, and it is suspected to be associated with ADHD. The aim of the present study was to review the epidemiological literature currently available on the relation between lead exposure and the diagnosis of ADHD. The PubMed and EMBASE databases were searched from 1 July 2018 up to 31 July 2018. The authors included observational studies (cohort, case–control and cross-sectional studies) published in English carried out on children within the last 5 years, measuring lead exposure and health outcomes related to ADHD. Seventeen studies met the inclusion criteria: 5 of these studies found no association between lead exposure and ADHD whereas the remaining 12 studies showed positive associations, even though not all of them were homogeneous in terms of exposure periods considered or ADHD diagnosis. To conclude, the evidence from the studies allowed us to establish that there is an association between lead and ADHD and that even low levels of lead raise the risk. However, there is still a lack of longitudinal studies about the relationship between lead exposure and the development of ADHD. Given the potential importance for public health, further research that includes the entire potential risk factors for ADHD in children must be encouraged.
Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review

Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.
α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

Iron toxicity is associated with organ injury and has been reported in various clinical conditions, such as hemochromatosis, thalassemia major, and myelodysplastic syndromes. Therefore, iron chelation therapy represents a pivotal therapy for these patients during their lifetime. The aim of the present study was to assess the iron chelating properties of α-lipoic acid (ALA) and how such an effect impacts on iron overload mediated toxicity. Human mesenchymal stem cells (HS-5) and animals (zebrafish, n = 10 for each group) were treated for 24 h with ferric ammonium citrate (FAC, 120 µg/mL) in the presence or absence of ALA (20 µg/mL). Oxidative stress was evaluated by reduced glutathione content, reactive oxygen species formation, mitochondrial dysfunction, and gene expression of heme oxygenase-1b and mitochondrial superoxide dismutase; organ injury, iron accumulation, and autophagy were measured by microscopical, cytofluorimetric analyses, and inductively coupled plasma‒optical mission Spectrometer (ICP-OES). Our results showed that FAC results in a significant increase of tissue iron accumulation, oxidative stress, and autophagy and such detrimental effects were reversed by ALA treatment. In conclusion, ALA possesses excellent iron chelating properties that may be exploited in a clinical setting for organ preservation, as well as exhibiting a good safety profile and low cost for the national health system.
Kv2 channels create endoplasmic reticulum / plasma membrane junctions: a brief history of Kv2 channel subcellular localization

ABSTRACT The potassium channels Kv2.1 and Kv2.2 are widely expressed throughout the mammalian brain. Kv2.1 provides the majority of delayed rectifying current in rat hippocampus while both channels are differentially expressed in cortex. Particularly unusual is their neuronal surface localization pattern: while half the channel population is freely-diffusive on the plasma membrane as expected from the generalized Singer & Nicolson fluid mosaic model, the other half localizes into micron-sized clusters on the soma, dendrites, and axon initial segment. These clusters contain hundreds of channels, which for Kv2.1, are largely non-conducting. Competing theories of the mechanism underlying Kv2.1 clustering have included static tethering to being corralled by an actin fence. Now, recent work has demonstrated channel clustering is due to formation of endoplasmic reticulum/plasma membrane (ER/PM) junctions through interaction with ER-resident VAMP-associated proteins (VAPs). Interaction between surface Kv2 channels and ER VAPs groups channels together in clusters. ER/PM junctions play important roles in inter-organelle communication: they regulate ion flux, are involved in lipid transfer, and are sites of endo- and exocytosis. Kv2-induced ER/PM junctions are regulated through phosphorylation of the channel C-terminus which in turn regulates VAP binding, providing a rapid means to create or dismantle these microdomains. In addition, insults such as hypoxia or ischemia disrupt this interaction resulting in ER/PM junction disassembly. Kv2 channels are the only known plasma membrane protein to form regulated, injury sensitive junctions in this manner. Furthermore, it is likely that concentrated VAPs at these microdomains sequester additional interactors whose functions are not yet fully understood.
Systematic review and meta-analysis of prognostic microRNA biomarkers for survival outcome in nasopharyngeal carcinoma

Background Nasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient survival. Therefore, this systematic review and meta-analysis is aimed to evaluate the potential prognostic value of miRNAs as prognostic biomarkers in NPC. Methods PRISMA guidelines were used to conduct this systematic review and meta-analysis study. Permutations of multiple “search key-words” were used for the search strategy, which was limited to articles published between January 2012 and March 2018. The retrieved articles were meticulously searched with multi-level screening by two reviewers and confirmed by other reviewers. Meta-analysis was performed using Hazard Ratios (HR) and associated 95% Confidence Interval (CI) of survival obtained from previously published studies. Publication bias was assessed by Egger’s bias indicator test and funnel plot symmetry. Results A total of 5069 patients across 21 studies were considered eligible for inclusion in the systematic review, with 65 miRNAs being evaluated in the subsequent meta-analysis. Most articles included in this study originated from China and one study from North Africa. The forest plot was generated using cumulated survival data, resulting in a pooled HR value of 1.196 (95% CI: 0.893–1.601) indicating that the upregulated miRNAs increased the likelihood of death of NPC patients by 19%. Conclusion To our knowledge, this is the first meta-analysis that examines the prognostic effectiveness of miRNAs as biomarkers in NPC patients. We noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival. However, further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results.
A Notch-mediated, temporal asymmetry in BMP pathway activation promotes photoreceptor subtype diversification

Neural progenitors produce neurons whose identities can vary as a function of the time that specification occurs. Here, we describe the heterochronic specification of two photoreceptor (PhR) subtypes in the zebrafish pineal gland. We find that accelerating PhR specification by impairing Notch signaling favors the early fate at the expense of the later fate. Using in vivo lineage tracing, we show that most pineal PhRs are born from a fate-restricted progenitor. Furthermore, sister cells derived from the division of PhR-restricted progenitors activate the bone morphogenetic protein (BMP) signaling pathway at different times after division, and this heterochrony requires Notch activity. Finally, we demonstrate that PhR identity is established as a function of when the BMP pathway is activated. We propose a novel model in which division of a progenitor with restricted potential generates sister cells with distinct identities via a temporal asymmetry in the activation of a signaling pathway.
Molecular Mechanisms Underlying Increase in Lysine Content of Waxy Maize through the Introgression of the opaque2 Allele

The opaque2 (o2) mutation in maize is associated with high lysine content in endosperm and good nutritional value. To improve the nutritional quality of waxy maize, the o2 allele was introgressed into the wxwx line using marker-assisted backcrossing selection technology. The lysine content of o2o2wxwx lines was higher than that of the wxwx line. To reveal the mechanism of increasing lysine content through introgression of the o2 in waxy maize, the transcriptome on kernels (18th day after pollination) of the o2o2wxwx and parent lines was analyzed using RNA-sequencing (RNA-Seq). The RNA-Seq analysis revealed 49 differentially expressed genes (DEGs). Functional analysis showed that these DEGs were mostly related to the catalytic activity and metabolic processes. The O2 gene regulated multiple metabolic pathways related to biological processes (BP) and molecular function (MP) during waxy maize endosperm development. In particular, in the o2o2wxwx lines, the two genes that encode the EF-1α and LHT1 were up-regulated, but the gene that encodes sulfur-rich proteins was down-regulated, raising the grain lysine content. These findings are of great importance for understanding the molecular mechanism underlying the lysine content increase due to o2 allele introgression into waxy maize.
Empowering innovative improvements through creative construction procurement

The heightened state of flux in the construction industry in general and construction procurement strategies in particular, provides welcome opportunities to inject innovative improvements. While some improvements are generated from within the construction industry itself, these evolve sluggishly along prolonged learning curves. These are compared with lessons to be learnt and examples to be drawn from manufacturing in the development of a marketable product. A product development focus is thus advocated in re‐integrating segregated groups and in empowering and inspiring the innovations that are needed to achieve the dramatic productivity gains now demanded from the construction industry.
Developmental regulation of DNA cytosine methylation at the immunoglobulin heavy chain constant locus

DNA cytosine methylation is involved in the regulation of gene expression during development and its deregulation is often associated with disease. Mammalian genomes are predominantly methylated at CpG dinucleotides. Unmethylated CpGs are often associated with active regulatory sequences while methylated CpGs are often linked to transcriptional silencing. Previous studies on CpG methylation led to the notion that transcription initiation is more sensitive to CpG methylation than transcriptional elongation. The immunoglobulin heavy chain (IgH) constant locus comprises multiple inducible constant genes and is expressed exclusively in B lymphocytes. The developmental B cell stage at which methylation patterns of the IgH constant genes are established, and the role of CpG methylation in their expression, are unknown. Here, we find that methylation patterns at most cis-acting elements of the IgH constant genes are established and maintained independently of B cell activation or promoter activity. Moreover, one of the promoters, but not the enhancers, is hypomethylated in sperm and early embryonic cells, and is targeted by different demethylation pathways, including AID, UNG, and ATM pathways. Combined, the data suggest that, rather than being prominently involved in the regulation of the IgH constant locus expression, DNA methylation may primarily contribute to its epigenetic pre-marking.
Picking Towels in Point Clouds

Picking clothing has always been a great challenge in laundry or textile industry automation, especially when some clothes are of the same colors, material and entangled with each other. In order to solve the problem, we present a grasp pose determination method to pick towels placed in a laundry basket or on a table. In our method, it is not needed to segment towels into independent items and the target towels are not necessarily distinguishable in color. The proposed algorithm firstly segments point clouds into several convex wrinkles, and then selects the appropriate grasp point on the candidate convex wrinkle. Moreover, we plan the grasp orientation with respect to the wrinkle which can effectively reduce the grasp failure caused by the inappropriate grasp direction. We evaluate our method on picking white towels and square towels, respectively, and achieved an average success rate of about 80%.