Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

Background/Aims: Caffeic acid (CA) is known to possess multiple biological activities including anti-cancer activities. However, the molecular mechanisms underlying these activities in non-small-cell lung cancer (NSCLC) cells are not fully understood. We attempted to clarify whether CA could enhance paclitaxel (PTX)-induced cytotoxicity in H1299 cells. Methods: First, we tested the cytotoxic effects in both H1299 cells and normal human Bease-2b cells by cell proliferation experiments. Next, we use Annexin V/propidium iodide apoptosis analysis and flow cytometric analysis to investigate apoptosis and cell cycle arrest under the treatments mentioned above. To further pinpoint changes in apoptosis, we tested the caspase-associated apoptotic pathway, which involves the activities of caspase-3 and caspase-9. Moreover, apoptosis-related proteins and MAPK pathway proteins were examined by western blot. An H1299 xenograft nude mice model was used to further evaluate the tumor-suppressing effects of CA and PTX in vivo. Results: Combination treatment with low-dose CA and PTX decreased the proliferation of NSCLC H1299 cells but not normal Beas-2b cells. Flow cytometry showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. Caspase-3 and caspase-9 activities were both increased after CA treatment. Furthermore, CA increased the PTX-induced activation of Bax, Bid, and downstream cleaved PARP, and phosphorylation of extracellular signal regulated kinase1/2 and c-Jun NH2-terminal protein kinase1/2. An in vivo tumor-suppression assay demonstrated that CA and PTX combined treatment exerted a more effective suppressive effect on tumor growth in H1299 xenografts without causing significant adverse effects. Conclusions: Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.
Factors that impact the cloud portability of legacy Web applications

The technological dependency of products or services provided by a particular cloud platform or provider (i.e. cloud vendor lock-in) leaves cloud users unprotected against service failures and providers going out of business, and unable to modernise their software applications by exploiting new technologies and cheaper services from alternative clouds. High portability is key to ensure a smooth migration of software applications between clouds, reducing the risk of vendor lock-in. This research identifies and models key factors that impact the portability of legacy web applications in cloud computing. Unlike existing cloud portability studies, we use a combination of techniques from empirical software engineering, software quality and areas related to cloud, including service-oriented computing and distributed systems, to carry out a rigorous experimental study of four factors impacting on cloud application portability. In addition, we exploit established methods for software effort prediction to build regression models for predicting the effort required to increase cloud application portability. Our results show that software coupling, authentication technology, cloud platform and service are statistically significant and scientifically relevant factors for cloud application portability in the experiments undertaken. Furthermore, the experimental data enabled the development of fair (mean magnitude of relative error, MMRE, between 0.493 and 0.875), good (MMRE between 0.386 and 0.493) and excellent (MMRE not exceeding 0.368) regression models for predicting the effort of increasing the portability of legacy cloud applications. By providing empirical evidence of factors that impact cloud application portability and building effort prediction models, our research contributes to improving decision making when migrating legacy applications between clouds, and to mitigating the risks associated with cloud vendor lock-in.
Influences for Gender Disparity in the Radiology Societies in North America.

OBJECTIVE The objective of our study was to outline the gender distribution in leadership positions in the North American radiology societies. MATERIALS AND METHODS A review of North American radiology societies was conducted to identify committee members and those holding leadership positions. The Scopus database was queried for research productivity metrics of these individuals. Gender, university affiliation, and academic rank were identified from departmental websites. The chi-square test was used to assess for differences in gender distribution, and nonparametric analyses were applied to determine gender differences in continuous variables. RESULTS Of 2826 radiology society committee members, men outnumbered women 67.4% (n = 1906) to 32.6% (n = 920). There were 696 society leadership positions, of which men held 501 (72.0%) and women held 195 (28.0%) (p < 0.003). Additionally, 26.3% of all men held leadership positions compared with 21.2% of all women (p = 0.0032). Overall, men had a higher median h-index (14 [range, 0-113] vs 11 [range, 0-73]), number of publications (52 [range, 2-1264] vs 35 [range, 2-428]), and number of citations (880 [range, 0-54,813] vs 483.5 [range, 0-17,332]) than women (p < 0.001). Across university academic ranks of assistant and associate professor, research productivity metrics were similar between genders, but interestingly, female representation decreased with increasing academic rank. A higher proportion of men held a university rank of professor than women (39.5% vs 33.4%; p = 0.0017) with parity at the levels of assistant and associate professors. CONCLUSION Gender disparity exists in the leadership positions in North American radiology societies. We have attempted to study the relationship between gender, academic rank, and h-index with leadership roles in these societies.
Moxibustion treatment modulates the gut microbiota and immune function in a dextran sulphate sodium-induced colitis rat model.

AIM To investigate the effect and mechanism of moxibustion in rats with ulcerative colitis. METHODS A rat colitis model was established by administering 4% dextran sulphate sodium solution. Seventy male rats were randomly divided into seven groups: Healthy controls (HC), ulcerative colitis model group (UC), UC with 7 d of moxibustion (UC-7), UC with 14 d of moxibustion (UC-14), UC with mesalazine gavage (UC-W), HC with 7 d of moxibustion (HC-7), HC with 14 d of moxibustion (HC-14). Moxibustion was applied to the bilateral Tianshu (ST25). Gut microbiome profiling was conducted by 16S rRNA amplicon sequencing, and PCR and ELISA determined the expression of inflammatory cytokines in colon mucosa and serum, respectively. RESULTS Moxibustion treatment restored the colonic mucosa and decreased submucosal inflammatory cell infiltration in colitis rats. Rats treated with moxibustion and mesalazine had significantly lower levels of the dominant phyla Proteobacteria and the genera Saccharibacteria, Sphingomonas and Barnesiella than colitis rats, and they could restore the microbiome to levels similar to those observed in healthy rats. UC rats had reduced alpha diversity, which could be alleviated by moxibustion therapy, and UC-7 had a higher alpha diversity than UC-14. This finding suggests that short-term (7 d) but no longer term (14 d) moxibustion treatment may significantly affect the gut microbiome. The potential bacterial functions affected by moxibustion may be ascorbate and aldarate metabolism, and amino acid metabolism. Compared with HC group, the levels of the cytokines interleukin-12 (IL-12) (P < 0.05) and IL-6, IL-17, IL-23, interferon-γ, lipopolysaccharide, IgA, tumour necrosis factor-α and its receptors 1 (TNFR1) and TNFR2 (P < 0.01) were all increased, whereas anti-inflammatory cytokine IL-2 and IL-10 (P < 0.01) and transforming growth factor-β (P < 0.05) were decreased in UC rats. These changes were reversed by moxibustion. CONCLUSION Our findings suggest that moxibustion exerts its therapeutic effect by repairing mucosal tissue damage and modulating the gut microbiome and intestinal mucosal immunity.
Changes in Temperature Management of Cardiac Arrest Patients Following Publication of the Target Temperature Management Trial*

Objectives: To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial. Design: Retrospective cohort study (January 2005 to December 2016). Setting: The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs. Patients: Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest. Interventions: The primary exposure of interest was admission before versus after publication of the target temperature management trial. Measurements and Main Results: The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± SD lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89–1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, –1.8 to –0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, –1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, –0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16–1.57]). Conclusions: The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.
Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype

Rationale: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. Objectives: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. Methods: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV1 and weight and height z‐scores). Measurements and Main Results: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV1 and weight and height z‐scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV1 and weight and height z‐scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], −1.11 [0.48] percent predicted/yr; P = 0.02). Conclusions: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects.
Extracellular matrix promotes proliferation, migration and adhesion of airway smooth muscle cells in a rat model of chronic obstructive pulmonary disease via upregulation of the PI3K/AKT signaling pathway

Extracellular matrix (ECM) creates the tissue microenvironment and serves a role in airway wall remodeling in chronic obstructive pulmonary disease (COPD). However, the biological function of ECM in COPD remains to be elucidated. In the present study, 24 healthy Sprague Dawley rats were randomized to normal and COPD groups. COPD was established by intratracheal injection with lipopolysaccharide over 30 days. Subsequently, airway smooth muscle cells (ASMCs) were isolated from rats and served as a model to assess the effects of three ECM components, including collagen type I, laminin and collagen type III (COL-3). Functional analysis in vitro, using cell counting kit-8, flow cytometry, wound healing and cell adhesion assays indicated that the ECM components could promote cell proliferation, cell cycle progression, migration and adhesion ability, respectively. Furthermore, as demonstrated by ELISA, treatment with ECM components increased levels of C-X-C motif chemokine ligand 1 (CXCL1), CXCL8 and interleukin-6 in ASMCs. Expression of transforming growth factor β1 (TGFβ1), fibroblast growth factor-1 (FGF-1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was increased, and expression of matrix metalloproteinase-9 (MMP-9) was decreased following treatment with ECM components, as demonstrated by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Additionally, specific activation of phosphoinositide 3-kinase (PI3K) signaling, using insulin-like growth factor-1 (IGF-1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF-1, PI3K, AKT, phospho-AKT, serine/threonine-protein kinase mTOR (mTOR), phospho-mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP-9 in cells from COPD rats. Consistently, PI3K inhibitor LY294002 exerted the opposite effect to IGF-1. In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway.
Periendoscopic management of direct oral anticoagulants: a prospective cohort study

Objective To assess the frequency of adverse events associated with periendoscopic management of direct oral anticoagulants (DOACs) in patients undergoing elective GI endoscopy and the efficacy and safety of the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) recommendations (NCT 02734316). Design Consecutive patients on DOACs scheduled for elective GI endoscopy were prospectively included. The timing of DOAC interruption and resumption before and after the procedures were recorded, along with clinical and procedural data. Procedures were stratified into low-risk and high-risk for GI-related bleeding, and patients into low-risk and high-risk for thromboembolic events. Patients were followed-up for 30 days for major and clinically relevant non-major bleeding events (CRNMB), arterial and venous thromboembolism and death. Results Of 529 patients, 38% and 62% underwent high-risk and low-risk procedures, respectively. There were 45 (8.5%; 95% CI 6.3% to 11.2%) major or CRNMB events and 2 (0.4%; 95% CI 0% to 1.4%) thromboembolic events (transient ischaemic attacks). Overall, the incidence of bleeding events was 1.8% (95% CI 0.7% to 4%) and 19.3% (95% CI 14.1% to 25.4%) in low-risk and high-risk procedures, respectively. For high-risk procedures, the incidence of intraprocedural bleeding was similar in patients who interrupted anticoagulation according to BSG/ESGE guidelines or earlier (10.3%vs10.8%, p=0.99), with a trend for a lower risk as compared with those who stopped anticoagulation later (10.3%vs25%, p=0.07). The incidence of delayed bleeding appeared similar in patients who resumed anticoagulation according to BSG/ESGE guidelines or later (6.6%vs7.7%, p=0.76), but it tended to increase when DOAC was resumed earlier (14.4%vs6.6%, p=0.27). The risk of delayed major bleeding was significantly higher in patients receiving heparin bridging than in non-bridged ones (26.6%vs5.9%, p=0.017). Conclusion High-risk procedures in patients on DOACs are associated with a substantial risk of bleeding, further increased by heparin bridging. Adoption of the BSG/ESGE guidelines in periendoscopic management of DOACs seems to result in a favourable benefit/risk ratio. Trial registration number NCT 02734316; Pre-results.
Effective Parallel Corpus Mining using Bilingual Sentence Embeddings

This paper presents an effective approach for parallel corpus mining using bilingual sentence embeddings. Our embedding models are trained to produce similar representations exclusively for bilingual sentence pairs that are translations of each other. This is achieved using a novel training method that introduces hard negatives consisting of sentences that are not translations but have some degree of semantic similarity. The quality of the resulting embeddings are evaluated on parallel corpus reconstruction and by assessing machine translation systems trained on gold vs. mined sentence pairs. We find that the sentence embeddings can be used to reconstruct the United Nations Parallel Corpus (Ziemski et al., 2016) at the sentence-level with a precision of 48.9% for en-fr and 54.9% for en-es. When adapted to document-level matching, we achieve a parallel document matching accuracy that is comparable to the significantly more computationally intensive approach of Uszkoreit et al. (2010). Using reconstructed parallel data, we are able to train NMT models that perform nearly as well as models trained on the original data (within 1-2 BLEU).
TRIUMPH Trial: One Small Step Could Become One Giant Leap for Precision Oncology in Head and Neck Cancer

413 Copyright c 2019 by the Korean Cancer Association This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Cancer Res Treat. 2019;51(1):413-414 pISSN 1598-2998, eISSN 2005-9256
Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated with LPS

The incidence of inflammatory bowel disease is increasing all over the world, especially in industrialized countries. The aim of the present work was to verify the anti-inflammatory activity of metabolites. In particular, cell-free supernatants of Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Lactobacillus reuteri, and Saccharomyces boulardii have been investigated. Metabolites produced by these probiotics were able to downregulate the expression of PGE-2 and IL-8 in human colon epithelial HT-29 cells. Moreover, probiotic supernatants can differently modulate IL-1β, IL-6, TNF-α, and IL-10 production by human macrophages, suggesting a peculiar anti-inflammatory activity. Furthermore, supernatants showed a significant dose-dependent radical scavenging activity. This study suggests one of the mechanisms by which probiotics exert their anti-inflammatory activity affecting directly the intestinal epithelial cells and the underlying macrophages. This study provides a further evidence to support the possible use of probiotic metabolites in preventing and downregulating intestinal inflammation as adjuvant in anti-inflammatory therapy.
Type of cardioplegic solution as a factor influencing the clinical outcome of open-heart congenital procedures

Introduction Cardioplegia is one of the most important modalities of myocardial protection during heart surgery. Aim To assess the impact of blood cardioplegia on postoperative variables, in comparison with two types of crystalloid cardioplegic solutions during pediatric heart surgery. Material and methods One thousand one hundred and twenty-nine patients underwent surgical correction of congenital heart disease with cardioplegia administration between 2006 and 2012. Nonlinear regression models of postoperative low cardiac output syndrome (LCOS) incidence, catecholamine index and total complication count were developed using a genetic algorithm. The Akaike information criterion was applied for selection of the best model. The following explanatory variables were evaluated: cardioplegia type (ST – Saint Thomas, n = 440; FR – Fresenius, n = 432; BL – Calafiore, n = 257), congenital heart diseases (CHD) type, age, sex, genetic disorder presence, body surface area (BSA), cardiopulmonary bypass (CBP) time, aortic cross-clamp time, operation urgency, redo surgery, surgeon. Results Low cardiac output syndrome presence and higher than average catecholamine indexes were negatively influenced by use of crystalloid cardioplegia (ST or FR), presence of specific CHDs, redo surgery and prolonged CBP time. Increased complication count was related to: crystalloid cardioplegia, presence of specific CHDs, redo surgery, urgency of operation, operation time and CBP time. Higher BSA had a protective effect against higher catecholamine index and increased complication count. Older age was protective against LCOS. Conclusions Cardioplegic solutions type influences postoperative variables in children after heart surgery by the negative impact of crystalloid cardioplegia. Blood cardioplegia presents potential advantages for patients – its application may reduce the incidence of low cardiac output syndrome and related complications.
Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study

Febrile seizures (FS) are the most common neurological disorder in childhood and are a great stress for parents due to their dramatic clinical appearance. Using test for determination of homozygously recessive characteristics in humans (HRC test) we analyzed presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits among FS patients (N=121) and control (N=121) to determine a possible deviation in the homozygosity level and genetic loads in the group of affected children and whether there is a predisposition to the occurrence of FS. The results of our study show a statistically significant difference in the mean values of the HRC tested (x¯HRC/20 CN = 3.2 ± 0.2; x¯HRC/20 FS = 4.6 ± 0.2, t= 5.74 , p< 0.0001), as well as in the distribution and variability of two studied samples (VC=55,3%, VFS= 39,6%), which indicates a complex polygenic difference among the tested groups of subjects. The differences in the degree of genetic homozygosity and variability are also present between the genders (t Cf/FSf = 4.12; t Cm/FSm = 3.98; p <0.0001) (VCf=56.9%, VFSf= 39.3%; VCm=54.1%, VFSm=40.1%). Obtained results indicate the enlargement of recessively homozygous genetic loads in the group of children with FS which may represent some kind of predisposition for expressivity of this type of seizures.