Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncostatic treatment effect of triple negative breast cancer cell line with copper (I)‐nicotinate complex

The treatment of triple‐negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)‐nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC‐1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein‐1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme‐linked immunosorbent assay technique was used for the detection of phospho‐Chk1 at ser 317 and caspase‐3. Moreover, the gene expression of survivin was identified by real‐time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC‐1806 cells treated with CNC was decreased in a dose‐dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase‐3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis‐mediated mechanism. However, one cannot neglect the abundance of cell necrosis–mediated death of cells via CNC, especially at higher concentrations.
RNA Sequencing-Based Whole-Transcriptome Analysis of Friesian Cattle Fed with Grape Pomace-Supplemented Diet

Simple Summary Grape pomace (GPO) is an important source of polyphenols which are known to have antioxidant properties. In the past decade, GPO has received some attention as a bioactive dietary component in farm animals’ diet. In this study, we have analyzed the whole-transcriptome of Friesian calves fed with a GPO-supplemented diet using RNA-sequencing. We noted that the most affected pathway was the cholesterol lipid biosynthesis and this effect was consistent with a reduction in both serum cholesterol and lipid oxidation in the carcasses. This study provides evidence on the antioxidant property of GPO-supplemented diet, from a molecular biology standpoint. Abstract Grape pomace (GPO), the main by-product of the wine making process, is a rich source of polyphenols with potent antioxidant properties. Recently, GPO has emerged as a potential feed additive in livestock nutrition, with several reports describing its beneficial effects on animals’ overall health status or production traits. However, little is known about it from a molecular biology standpoint. In the present study, we report the first RNA sequencing-based whole-transcriptome profiling of Friesian calves fed with a GPO-supplemented diet. We identified 367 differentially expressed genes (p < 0.05) in the GPO-supplemented calves (n = 5), when compared with unsupplemented control group (n = 5). The pathway analysis showed that ‘cholesterol lipid biosynthesis’ was the most negatively-enriched (p < 0.001) pathway in the GPO-supplemented animals. In specific terms, five important genes coding for cholesterol biosynthesis enzymes, namely the Farnesyl-diphosphate Farnesyltransferase 1 (FDFT-1), Squalene Epoxidase (SQLE), NAD(P)-dependent Steroid Dehydrogenase-like (NSDHL), Methylsterol Monooxygenase (MSMO)-1, and Sterol-C5-desaturase (SC5D), two major transcription factors (the Sterol Regulatory Element-binding Transcription Factor 1 and 2), as well as the Low-Density Lipoprotein Receptor (LDLR), were all downregulated following GPO supplementation. Such an effect was mirrored by a reduction of blood cholesterol levels (p = 0.07) and a lowered (p < 0.001) Malondialdehyde (lipid oxidation marker) level in carcasses. We provide evidence on the effects of GPO-supplemented diets on the whole-transcriptome signature in veal calves, which mainly reflects an antioxidant activity.
A Data-Driven Approach for Identifying Medicinal Combinations of Natural Products

Combinations of natural products have been used as important sources of disease treatments. Existing databases contain information about prescriptions, herbs, and compounds and their relationships with phenotypes, but they do not have information on the use of combinations of natural product compounds. In this paper, we identified large-scale associations between natural product combinations and phenotypes by applying an association rule mining technique to integrated information on herbal medicine, combination drugs, functional foods, molecular compounds, and target genes. The rationale behind this approach is that natural products commonly found in medicinal multicomponent mixtures have statistically significant associations with the therapeutic effects of the multicomponent mixtures. Based on a molecular network analysis and an external literature validation, we show that the inferred associations are valuable information for identifying medicinal combinations of natural products since they have statistically significant closeness proximity in the molecular layer and have much experimental evidence. All results are available through the workbench site at http://biosoft.kaist. ac.kr/coconut to facilitate the investigation of the medicinal use of natural products and their combinations.
Ten‐year recurrence rates for breast cancer subtypes in the Netherlands: A large population‐based study

Here we report for the first time the relation between breast cancer subtypes and 10‐year recurrence rates and mortality in the Netherlands. All operated women diagnosed with invasive non‐metastatic breast cancer in 2005 in the Netherlands were included. Patients were classified into breast cancer subtypes according to ER, PR, HER2 status and grade: luminal A, luminal B, HER2 positive and triple negative. Percentages and hazards of recurrence were compared among subtypes. Adjusted 10‐year overall (OS) and recurrence‐free survival (RFS) were calculated using multivariable Cox regression. Of 8,062 patients, 4,482 (56%) were luminal A, 2,090 (26%) luminal B, 504 (6%) HER2 positive and 986 (12%) triple negative. Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively). Regional recurrences were most often diagnosed in triple negative disease (5.2%), and the least often in luminal A (1.7%). HER2 positive and triple negative subtypes had the highest recurrence rates in the second year, while luminal A and B showed a more continuous pattern over time, with lobular tumours recurring more often. After adjustment for differences in baseline characteristics, triple negative disease showed worse 10‐year OS and triple negative and HER2 positive disease had the lowest 10‐year RFS. In the Netherlands, breast cancer subtypes are important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes, in combination with other prognostic factors, can support patient‐tailored treatment and individualised follow‐up.
Longitudinal Associations Between Inflammation and Depressive Symptoms in Chronic Dialysis Patients

Objective Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients. Methods Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1&bgr;, IL-6, IL-10, and tumor necrosis factor &agr;) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses. Results A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (&bgr; = 0.9, confidence interval [CI] = 0.4–1.4) and 6-month follow-up (&bgr; = 1.1, CI = 0.3–2.0), and between IL-1&bgr; and depressive symptoms at 6-month follow-up (&bgr; = 1.3, CI = 0.8–1.8) and 12-month follow-up (&bgr; = 1.2, CI = 0.4–1.9). Inflammation makers (HsCRP, IL-6, IL-1&bgr;, IL-10, and tumor necrosis factor &agr;) at baseline were not associated with depressive symptoms at follow-up and vice versa. Conclusions We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.
COL‑3 enhances the anti‑proliferative and pro‑apoptotic effects of paclitaxel in breast cancer cells.

Paclitaxel, a chemotherapeutic agent used in the treatment of breast cancer and other solid tumor types, including ovarian and lung, causes a dose‑dependent neuropathic pain, which limits its use. Chemically modified tetracycline‑3 (COL‑3) has anticancer properties and was previously reported to inhibit neuroinflammation and protect against paclitaxel‑induced neuropathic pain (PINP) in mice models. However, it is not known whether it affects the anticancer activities of paclitaxel. Thus, the aim of the present study was to evaluate the effect of COL‑3 on the anticancer activity of paclitaxel on the breast cancer cell lines MCF‑7 (estrogen receptor‑positive), pII [estrogen receptor‑negative (ER‑ve)] and MDA‑MB‑231 (ER‑ve). Cell proliferation, apoptosis and cell cycle stage were determined using an MTT assay, Annexin V/7‑aminoactinomycin D and flow cytometry. The expression of various signaling molecules was determined with ELISA‑based proteome profiling and western blotting. Additionally, the degree of cell invasion was determined with a Matrigel assay and caspase‑3 activity was determined with a colorimetric assay. Treatment with paclitaxel or COL‑3 alone inhibited cell proliferation in a concentration‑dependent manner in all cell lines. The anti‑proliferative effects of paclitaxel and COL‑3 in combination varied from synergism against MDA‑MB‑231 and pII cells to notably additive and slight antagonism against MCF‑7 cells. In the highly proliferative and invasive pII cells, the observed synergistic anti‑proliferative effect was partially through the induction of apoptosis via modulation of caspase‑3 levels and activity, and P70S6K phosphorylation, but not cell cycle arrest. COL‑3 inhibited the invasion of pII cells in a concentration‑dependent manner partially through inhibiting total matrix metalloproteinase activity. The combination regimen significantly inhibited the expression of two proteases, ADAM metallopeptidase with thrombospondin type 1 motif 1 and proteinase 3. In conclusion, the combination of paclitaxel and COL‑3 indicated additive to synergistic anti‑proliferative effects on breast cancer cells mediated partially via the induction of apoptosis. The combination regimen could further inhibit invasion and metastasis. Thus, COL‑3 could be a beneficial adjunct to a paclitaxel‑based anticancer regimen to improve therapeutic outcome and reduce the adverse effects of paclitaxel, primarily PINP.
Prognostic Value of Biventricular Strain in Risk Stratifying in Patients With Acute Heart Failure

Background Few studies have shown that right ventricular (RV) function is independently related to adverse events regardless of left ventricular (LV) function in heart failure. We evaluated the prognostic value of global longitudinal strain (GLS) of both ventricles in patients with acute heart failure. Methods and Results We measured biventricular strains in 1824 randomly selected patients (973 men, aged 70±14 years) from a strain registry. A total of 799 patients (43.8%) died during the median follow‐up duration of 31.7 months. In univariate analysis, LVGLS and RVGLS were significantly associated with all‐cause mortality. We classified them into 4 strain groups according to LVGLS (≥9%) and RVGLS (≥12%). On Cox proportional hazards analysis, group 4 (<9% LVGLS and <12% RVGLS) had the worst prognosis, with a hazard ratio (HR) of 1.755 (95% confidence interval [CI], 1.473–2.091; P<0.001) compared with that of group 1 (≥9% LVGLS and ≥12% RVGLS). After multivariate analysis, both LVGLS (per 1% decrease; HR: 1.057; 95% CI, 1.029–1.086; P<0.001) and RVGLS (per 1% decrease; HR: 1.022; 95% CI, 1.004–1.040; P=0.014) were also significant. The HR of RVGLS <12% was higher in patients without pulmonary hypertension (assessed by maximal tricuspid regurgitation ≤2.8 m/s) after the adjustment of LVGLS (HR: 1.40 [95% CI, 1.11–1.77] versus 1.07 [95% CI, 0.88–1.30] with pulmonary hypertension; interaction, P=0.043). Conclusions In the patients with acute heart failure, RVGLS was significantly associated with all‐cause mortality regardless of LVGLS, and those with decreased biventricular GLS showed the worst prognosis. The predictive power of RVGLS was more prominent in the absence of pulmonary hypertension.
Responsiveness of a parent-reported outcome measure to evaluate AAC interventions for children and youth with complex communication needs

Abstract Evaluation of the effectiveness of augmentative and alternative communication (AAC) interventions requires reliable measures that are responsive to change. The aim of this study was to explore the potential of the Family Impact of Assistive Technology Scale for AAC (FIATS-AAC) to detect functional change in children and youth with AAC needs, aged 3–17 years, and their families, 6 and 12 weeks after receiving a graphic-based, speech-generating device (SGD). Parents whose children were awaiting a SGD as part of their regular AAC service participated in the study. In all, 45 parents completed the FIATS-AAC during each of three phone interviews: at the time of device delivery, and then 6 weeks and 12 weeks after receiving the device. Children and youth were aged 3–16 years (M = 7.8, SD = 3.3) and were mostly context-dependent communicators. Paired t-tests indicated statistically significant gains in functioning from baseline to both 6 and 12 weeks after receiving the AAC device. Effect sizes were 0.41 and 0.38, respectively. This study provides initial support for the ability of the FIATS-AAC to detect functional changes in children and youth and their families after receiving a graphic-based SGD.
Possible Insulinotropic Action of Apolipoprotein A–I Through the ABCA1/Cdc42/cAMP/PKA Pathway in MIN6 Cells

Aims/Introduction: We studied the mechanisms for the possible insulinotropic action of apolipoprotein (Apo) A–I in mouse insulinoma (MIN6) cells. Materials and Methods: The effects of ApoA-I on cAMP production and glucose-stimulated insulin secretion (GSIS), and the dose dependency (ApoA-I at 5, 10, 25, and 50 μg/ml) were determined using MIN6 cells. The effects of the small-interference ribonucleic acid (siRNA) of ATP-binding cassette transporter A1(ABCA1) and Cell division control protein 42 homolog (Cdc42) on the insulinotropic action of ApoA-I was studied, as well as mRNA and protein levels of ABCA1 and Cdc42. Then, the influence of cAMP inhibitor SQ22536, and the cAMP-dependent protein kinase inhibitor Rp-cAMPS on ApoA-I action were studied. Results: Addition of ApoA-I produced cAMP and increased insulin secretion, dose-dependently in high glucose concentration (25 mmmol/l). and ABCA1 protein and Cdc42 mRNA and protein were also enhanced. Specific ABCA1 and Cdc42 siRNA significantly decreased the effects of ApoA-I on insulin secretion compared with negative controls. Manifestations of ABCA1 and Cdc42 mRNA and protein were less than that of the negative control group. Both cAMP inhibiror (SQ22536) and protein kinases inhibitor (Rp-cAMPS) strongly inhibited the effects of ApoA-I on insulin secretion. Conclusions: We demonstrated that ApoA-I enhances glucose-stimulated insulin release in high glucose at least partially through the ABCA1/Cdc42/cAMP/ Protein kinase A (PKA) pathway.
Evaluation of Autologous Blood in Pterygium Surgery With Conjunctival Autograft

Purpose: Autologous blood has been used exploratively with conjunctival autograft in pterygium surgery. However, it is controversial whether autologous blood performed better than other fixation methods, including fibrin glue and sutures. This meta-analysis was conducted to evaluate the effectiveness of using autologous blood in pterygium surgery with conjunctival autograft. Methods: The study was conducted according to the PRISMA guidelines. The MEDLINE, Cochrane library, and Embase databases were systematically searched from their establishment until April 1, 2018. Randomized controlled trials comparing autologous blood with fibrin glue/suture in pterygium surgery with conjunctival autograft were included. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Outcome measurements were recurrence, graft displacement, graft retraction, and surgical duration. Review Manager 5.3 (Cochrane Community, Cochrane Collaboration, London, UK) was used to perform the statistical analysis. When I2 < 50%, statistical heterogeneity was considered acceptable, and a fixed-effects model was adopted; alternatively, the random-effects model was used. Results: Seven randomized controlled trials including 516 patients were finally included in the meta-analysis. Four studies with 379 patients compared autologous blood and fibrin glue. Autologous blood was inferior to fibrin glue with respect to surgical duration, graft retraction, and graft displacement. However, there was no statistical difference between the 2 groups in terms of the recurrence rate. Four studies with 152 patients compared autologous blood and traditional suturing. Autologous blood was superior to sutures in terms of surgical duration and inferior to sutures in terms of graft retraction. No difference was detected in terms of graft displacement and recurrence rate. Conclusions: In conclusion, autologous blood is an appropriate method for graft fixation in pterygium surgery. Current research suggests that autologous blood derivatives may be a promising approach after pterygium excision. However, this requires further confirmation.
Socioeconomic environment and disparities in cancer survival for 19 solid tumor sites: An analysis of the French Network of Cancer Registries (FRANCIM) data

Social inequalities are concerning along the cancer continuum. In France, social gradient in health is particularly marked but little is known about social gradient in cancer survival. We aimed to investigate the influence of socioeconomic environment on cancer survival, for all cancers reported in the French Network of Cancer Registries. We analyzed 189,657 solid tumors diagnosed between 2006 and 2009, recorded in 18 registries. The European Deprivation Index (EDI), an ecological index measuring relative poverty in small geographic areas, assessed social environment. The EDI was categorized into quintiles of the national distribution. One‐ and five‐year age‐standardized net survival (ASNS) were estimated for each solid tumor site and deprivation quintile, among men and among women. We found that 5‐year ASNS was lower among patients living in the most deprived areas compared to those living in the least deprived ones for 14/16 cancers among men and 16/18 cancers among women. The extent of cancer survival disparities according to deprivation varied substantially across the cancer sites. The reduction in ASNS between the least and the most deprived quintile reached 34% for liver cancer among men and 59% for bile duct cancer among women. For pancreas, stomach and esophagus cancer (among men), and ovary and stomach cancer (among women), deprivation gaps were larger at 1‐year than 5‐year survival. In conclusion, survival was worse in the most deprived areas for almost all cancers. Our results from population‐based cancer registries data highlight the need for implementing actions to reduce social inequalities in cancer survival in France.
Semi-Supervised Translation with MMD Networks

This work aims to improve semi-supervised learning in a neural network architecture by introducing a hybrid supervised and unsupervised cost function. The unsupervised component is trained using a differentiable estimator of the Maximum Mean Discrepancy (MMD) distance between the network output and the target dataset. We introduce the notion of an $n$-channel network and several methods to improve performance of these nets based on supervised pre-initialization, and multi-scale kernels. This work investigates the effectiveness of these methods on language translation where very few quality translations are known \textit{a priori}. We also present a thorough investigation of the hyper-parameter space of this method on both synthetic data.
Altered expression patterns of circular RNAs between implantation sites and interimplantation sites in early pregnant mice

Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have been found to play important roles in regulating gene expression and participate in several biological processes. However, their specific roles in embryo implantation remain unclear. This study aims to investigate the roles of circRNAs in embryo implantation. In the current study, we screened the expression profiles of circRNAs between implantation sites and interimplantation sites in the endometrial tissue of early pregnant mice on Day 5 using microarray assay. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of four dysregulated circRNAs was performed to validate the microarray results. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and circRNA–microRNA (miRNA)–messenger RNA (mRNA) negative correlation network analyses were performed. The microarray results showed 101 upregulated and 75 downregulated circRNAs (fold change [FC] ≥ 1.5 and p value < 0.05) at implantation sites compared with interimplantation sites. Four randomly selected circRNAs were successfully verified by qRT‐PCR. The GO and KEGG analyses revealed some meaningful terms. Moreover, based on circRNAs microarray data and the miRNA and mRNA high‐throughput data previously published by our groups, differently expressed circRNAs, miRNAs, and mRNAs were performed to conjoint analysis. Then circRNA–miRNA–mRNA negative correlation networks were constructed and 21 downregulated circRNAs, 14 upregulated miRNAs, and 79 downregulated mRNAs were involved in the networks. The findings of this study may provide a novel perspective on circRNAs and lay a foundation for future research into the potential roles of circRNAs in embryo implantation.