Miracle-dz/UniFAR-FTUs huggingface dataset:
Selenium-Containing Polysaccharide-Protein Complex in Se-Enriched Ulva fasciata Induces Mitochondria-Mediated Apoptosis in A549 Human Lung Cancer Cells

The role of selenium (Se) and Ulva fasciata as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical, and clinical studies. In this study, Se-containing polysaccharide-protein complex (Se-PPC), a novel organoselenium compound, a Se-containing polysaccharide-protein complex in Se-enriched Ulva fasciata, is a potent anti-proliferative agent against human lung cancer A549 cells. Se-PPC markedly inhibited the growth of cancer cells via induction of apoptosis which was accompanied by the formation of apoptotic bodies, an increase in the population of apoptotic sub-G1 phase cells, upregulation of p53, and activation of caspase-3 in A549 cells. Further investigation on intracellular mechanisms indicated that cytochrome C was released from mitochondria into cytosol in A549 cells after Se-PPC treatment. Se-PPC induced depletion of mitochondrial membrane potential (ΔΨm) in A549 cells through regulating the expression of anti-apoptotic (Bcl-2, Bcl-XL) and pro-apoptotic (Bax, Bid) proteins, resulting in disruption of the activation of caspase-9. This is the first report to demonstrate the cytotoxic effect of Se-PPC on human cancer cells and to provide a possible mechanism for this activity. Thus, Se-PPC is a promising novel organoselenium compound with potential to treat human cancers.
MiR‐127‐3p inhibits cell growth and invasiveness by targeting ITGA6 in human osteosarcoma

Osteosarcoma (OS) is one of the most universal malignant bone tumors that occur mostly in children and adolescents. This study aimed to investigate the roles of miR‐127‐3p and integrin subunit‐α 6 (ITGA6) in OS proliferation, apoptosis, invasion and migration, and to explore the possible molecular mechanism and target relationship. By conducting quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot, the microRNA (miRNA) and protein expressions of miR‐127‐3p and ITGA6 in both tissues and cells were determined. The expression of apoptosis and migration related were also detected by western blot. The target relationship between miR‐127‐3p and ITGA6 was predicted by TargetScan and verified by dual‐luciferase reporter assay. The biological functions of miR‐127‐3p and ITGA6 in OS were investigated by following experiments: cell counting kit 8 (CCK‐8) and colony formation assays to inspect cell proliferation, flow cytometry, and caspase 3 activity assay to examine apoptosis, and transwell and wound healing assays to analyze invasion and migration. Significant down‐regulation of miR‐127‐3p and up‐regulation of ITGA6 was found out in OS tissues and cells. ITGA6 was proved to be the downstream target gene of miR‐127‐3p and functioned as a tumor promotor in OS, while miR‐127‐3p restrained deterioration of OS by suppressing cell viability, reducing migration and invasion, and promoting apoptosis. MiR‐127‐3p suppressed proliferation, invasion, and migration while stimulated apoptosis of OS cells through knocking down ITGA6. © 2018 IUBMB Life, 70(5):411–419, 2018
Wing 1 of protein HOP2 is as important as helix 3 in DNA binding by MD simulation

The repair of programmed DNA double-strand breaks through recombination is required for proper association and disjunction of the meiotic homologous chromosomes. Meiosis-specific protein HOP2 plays essential roles in recombination by promoting recombinase activities. The N-terminal domain of HOP2 interacts with DNA through helix 3 (H3) and wing 1 (W1). Mutations in wing 1 (Y65A/K67A/Q68A) slightly weakened the binding but mutations in helices 2 and 3 (Q30A/K44A/K49A) nearly abolished the binding. To better understand such differential effects at atomic level, molecular dynamics simulations were employed. Despite losing some hydrogen bonds, the W1-mutant DNA complex was rescued by stronger hydrophobic interactions. For the wild type and W1-mutant, the protein was found to slide along the DNA grooves as the DNA rolls along its double-helix axis. This motion could be functionally important to facilitate the precise positioning of the single-stranded DNA with the homologous double-stranded DNA. The sliding motion was reduced in the W1-mutant. The H-mutant nearly lost all intermolecular interactions. Moreover, an additional mutation in wing 1 (Y65A/K67A/Q68A/K69A) also caused complete complex dissociation. Therefore, both wing 1 and helix 3 make important contribution to the DNA binding, which could be important to the strand invasion function of HOP2 homodimer and HOP2-MND1 heterodimer. Similar to cocking a medieval crossbow with the archer’s foot placed in the stirrup, wing 1 may push the minor groove to cause distortion while helix 3 grabs the major groove.
Time for Self-Care: Downtime Recovery as a Buffer of Work and Home/Family Time Pressures

Objective: Opportunities for people to recover from stress are insufficient, because demanding and excessive life activities leave little time for recovery. Downtime is a self-care behavior that can occur in any life domain (ie, work, home/family, leisure). Methods: Using survey data from a cross-section of 422 U.S. workers, we tested hypotheses regarding downtime as a buffer of the effects of time pressure and whether downtime's benefits were related to the domain in which it was taken, or influenced by perceived time control. Results: In situations of high time pressure, work and home/family downtime were beneficial when time control was high, while relaxing leisure was beneficial when time control was low. Conclusions: Downtime is available whenever people recognize their need for recovery and respond by entering a state of physical relaxation and psychological detachment from stressors.
Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” (fem) Mutants by Induction of the Stringent Stress Response

ABSTRACT Studies with methicillin-resistant Staphylococcus aureus (MRSA) strain COL have shown that the optimal resistance phenotype requires not only mecA but also a large number of “auxiliary genes” identified by Tn551 mutagenesis. The majority of auxiliary mutants showed greatly increased levels of oxacillin resistance when grown in the presence of sub-MICs of mupirocin, suggesting that the mechanism of reduced resistance in the auxiliary mutants involved the interruption of a stringent stress response, causing reduced production of penicillin-binding protein 2A (PBP 2A).
Social circle analysis on ego-network based on context frequent pattern mining

Effective organization and management of a user's ego-network is one of the effective means to deal with information overload. Manual organization methods are often time-consuming and difficult to promote. In this paper, an automatic identification of social circles model is proposed, which takes three factors into account: user's profile, relationship information, and interactive context information. Using closed frequent itemsets mining on users' interactive context, a user in ego-network can belong to more than one social circles or even no one. The experiments show that our model can effectively detect social circles on ego-network.
Did Androgen-Binding Protein Paralogs Undergo Neo- and/or Subfunctionalization as the Abp Gene Region Expanded in the Mouse Genome?

The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution.
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.

BACKGROUND Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity. METHODS In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group. CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).
Influence of Cryopreservation Solution on the In Vitro Culture of Skin Tissues Derived from Collared Peccary (Pecari tajacu Linnaeus, 1758).

Skin vitrification is a promising and alternative tool for the conservation of biodiversity, especially for wild mammals, such as collared peccaries. Several factors can affect the success of this procedure, such as the cryoprotectant solution used. Therefore, this study was carried out to compare the efficiency of various vitrification solutions for recovery of viable cells after in vitro culture of cryopreserved skin tissues derived from the collared peccary, aiming to study the application in biobanking, where cellular use is not immediately required. Then, Dulbecco's modified Eagle's medium (DMEM) composed of 2.2 g/L sodium bicarbonate and 10% fetal bovine serum (FBS) was supplemented with 3.0 M ethylene glycol (EG) or 3.0 M dimethyl sulfoxide (DMSO) or 1.5 M EG plus 1.5 M DMSO with or without sucrose (SUC; 0.25 M) to produce six solutions for solid-surface vitrification. After warming, skin tissues were cultured in vitro and recovered cells were analyzed for morphology, adhesion, subconfluence, and proliferative activity for developing the growth curve and determining the population doubling time (PDT), and viability by Trypan Blue. The vitrification did not alter the ability of the tissues to adhere to the culture dish, as well as the day of all explants with cell growth, subconfluence samples, subconfluence total time, and PDT (p > 0.05). Moreover, independent of the cryoprotectant solution used, the vitrification altered the day of all attached explants (p < 0.05). Nevertheless, for viability after the first passage, only the EG-SUC (86.9%) and DMSO-SUC (91.4%) groups maintained viable cell recovery similar to the nonvitrified group (96.3%, p > 0.05). Additionally, for viability after the third passage, only the EG-SUC group maintained the cell quality (88.3%), when compared with the nonvitrified (97.8%, p > 0.05). In conclusion, DMEM with 10% FBS, 3.0 M EG, and 0.25 M sucrose was the most efficient solution for vitrifying collared peccary skin tissues, leading to the in vitro culture of viable cells.
Early detection of Crossfire attacks using deep learning

Crossfire attack is a recently proposed threat designed to disconnect whole geographical areas, such as cities or states, from the Internet. Orchestrated in multiple phases, the attack uses a massively distributed botnet to generate low-rate benign traffic aiming to congest selected network links, so-called target links. The adoption of benign traffic, while simultaneously targeting multiple network links, makes the detection of the Crossfire attack a serious challenge. In this paper, we propose a framework for early detection of Crossfire attack, i.e., detection in the warm-up period of the attack. We propose to monitor traffic at the potential decoy servers and discuss the advantages comparing with other monitoring approaches. Since the low-rate attack traffic is very difficult to distinguish from the background traffic, we investigate several deep learning methods to mine the spatiotemporal features for attack detection. We investigate Autoencoder, Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) Network to detect the Crossfire attack during its warm-up period. We report encouraging experiment results.
Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic-Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model

ABSTRACT Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD), and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were examined in neutropenic infected mice, and the data were analyzed by a population PK model. Dose fractionation study was performed for total daily doses between 2.06 and 24.8 mg base/kg of weight against Pseudomonas aeruginosa ATCC 27853, PAO1, and FADDI-PA022 (MIC of 1 mg/liter for all three strains). Histopathological examination of the lung was undertaken at 24 h posttreatment in both healthy and neutropenic infected mice. A two-compartment PK model was required for both epithelial lining fluid (ELF) and plasma drug exposure. The model consisted of central and peripheral compartments and was described by bidirectional first-order distribution clearance. The ratio of the area under the curve to the MIC (AUC/MIC) was the most predictive PK/PD index to describe the antimicrobial efficacy of aerosolized polymyxin B in treating lung infections in mice (R2 of 0.70 to 0.88 for ELF and 0.70 to 0.87 for plasma). The AUC/MIC targets associated with bacteriostasis against the three P. aeruginosa strains were 1,326 to 1,506 in ELF and 3.14 to 4.03 in plasma. Histopathological results showed that polymyxin B aerosols significantly reduced lung inflammation and preserved lung epithelial integrity. This study highlights the advantageous PK/PD characteristics of pulmonary delivery of polymyxin B over intravenous administration in achieving high drug exposure in ELF.
Umbilical cord blood and maternal visfatin (PBEF/NAMPT) concentrations in preterm birth with and without preterm premature rupture of membranes

Abstract Objectives: The aim of the study is to investigate differences in visfatin concentrations between mothers with term and preterm birth (PTB) and between mothers who delivered within seven days and after more than seven days following admission for PTB/preterm premature rupture of membranes (PPROMs). Methods: Maternal peripheral blood and cord blood were collected from 56 mothers with PTB (31 with PPROM) and 71 mothers with term delivery (three with PPROM). Results: Maternal visfatin concentration was significantly higher for given gestational age in PTBs compared to term deliveries (p = .021) and also in mothers who delivered within seven days after admission for PTB or PPROM, compared to those who delivered after more than seven days (p = .027; p = .039). Cord blood visfatin concentration was found to be decreased in preterm compared to term infants (p = .007). Conclusions: Visfatin in both maternal and fetal circulation may play an important role in the pathogenesis of PTB/PPROM and could be used to distinguish between women who will deliver in a short period of time after clinical presentation of PTB/PPROM and those who deliver later. Nevertheless, additional research is necessary in order to identify its direct involvement in PTB/PPROM.
PIM-Check: development of an international prescription-screening checklist designed by a Delphi method for internal medicine patients

Objectives Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection. Design Five-step study involving selection of medical domains, literature review and 17 semistructured interviews, a two-round Delphi survey, a forward/back-translation process and an electronic tool development. Setting 22 University and general hospitals from Canada, Belgium, France and Switzerland. Participants 40 physicians and 25 clinical pharmacists were involved in the study. Agreement with the checklist statements and their usefulness for healthcare professional training were evaluated using two 6-point Likert scales (ranging from 0 to 5). Primary and secondary outcome measures Agreement and usefulness ratings were defined as: >65% of the experts giving the statement a rating of 4 or 5, during the first Delphi-round and >75% during the second. Results 166 statements were generated during the first two steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36) and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5 (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final checklist includes 160 statements in 17 medical domains and 56 pathologies. An algorithm of approximately 31 000 lines was developed including comorbidities and medications variables to create the electronic tool. Conclusion PIM-Check is the first electronic prescription-screening checklist designed to detect PIM in internal medicine. It is intended to help young healthcare professionals in their clinical practice to detect PIM, to reduce medication errors and to improve patient safety.
Health Geomatics: An Enabling Suite of Technologies in Health and Healthcare

This Methodolical Review describes how health geomatics can improve our understanding of the important relationship between location and health, and thus assist us in Public Health tasks like disease prevention, and also in better healthcare service planning. The reader is first introduced to health geography and its two main divisions, disease ecology and healthcare delivery, followed by an overview of the basic concepts and principles of health geomatics. Topics covered include geographical information systems (GIS), GIS modeling, and GIS-related technologies (remote sensing and the global positioning system). We also present a number of real-life health geomatics applications and projects, with pointers to further studies and resources. Finally, we discuss the barriers facing the adoption of GIS technology in the health sector, including data availability/quality issues. The authors believe that we still need to combat many cultural and organizational barriers, including "spatial illiteracy" among healthcare workers, while making the tools cheaper and easier to learn and use, before health geomatics can become a mainstream technology in the health sector like today's spreadsheets and databases.
A deep learning approach for fetal QRS complex detection

Objective: Non-invasive foetal electrocardiography (NI-FECG) has the potential to provide more additional clinical information for detecting and diagnosing fetal diseases. We propose and demonstrate a deep learning approach for fetal QRS complex detection from raw NI-FECG signals by using a convolutional neural network (CNN) model. The main objective is to investigate whether reliable fetal QRS complex detection performance can still be obtained from features of single-channel NI-FECG signals, without canceling maternal ECG (MECG) signals. Approach: A deep learning method is proposed for recognizing fetal QRS complexes. Firstly, we collect data from set-a of the PhysioNet/computing in Cardiology Challenge database. The sample entropy method is used for signal quality assessment. Part of the bad quality signals is excluded in the further analysis. Secondly, in the proposed method, the features of raw NI-FECG signals are normalized before they are fed to a CNN classifier to perform fetal QRS complex detection. We use precision, recall, F-measure and accuracy as the evaluation metrics to assess the performance of fetal QRS complex detection. Main results: The proposed deep learning method can achieve relatively high precision (75.33%), recall (80.54%), and F-measure scores (77.85%) compared with three other well-known pattern classification methods, namely KNN, naive Bayes and SVM. Significance: the proposed deep learning method can attain reliable fetal QRS complex detection performance from the raw NI-FECG signals without canceling MECG signals. In addition, the influence of different activation functions and signal quality assessment on classification performance are evaluated, and results show that Relu outperforms the Sigmoid and Tanh on this particular task, and better classification performance is obtained with the signal quality assessment step in this study.