Miracle-dz/UniFAR-FTUs huggingface dataset:
Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells

Background Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3). Methods ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. Results Exposure of cells to ZnO NPs resulted in a dose-dependent loss of cell viability, and the characteristic apoptotic features such as rounding and loss of adherence, enhanced reactive oxygen species generation, and loss of mitochondrial membrane potential were observed in the ZnO NP-treated cells. Furthermore, the cells treated with ZnO NPs showed significant double-strand DNA breaks, which are gained evidences from significant number of γ-H2AX and Rad51 expressed cells. ZnO NP-treated cells showed upregulation of p53 and LC3, indicating that ZnO NPs are able to upregulate apoptosis and autophagy. Finally, the Western blot analysis revealed upregulation of Bax, caspase-9, Rad51, γ-H2AX, p53, and LC3 and downregulation of Bcl-2. Conclusion The study findings demonstrated that the ZnO NPs are able to induce significant cytotoxicity, apoptosis, and autophagy in human ovarian cells through reactive oxygen species generation and oxidative stress. Therefore, this study suggests that ZnO NPs are suitable and inherent anticancer agents due to their several favorable characteristic features including favorable band gap, electrostatic charge, surface chemistry, and potentiation of redox cycling cascades.
Frozen embryo transfer: a review on the optimal endometrial preparation and timing

STUDY QUESTION What is the optimal endometrial preparation protocol for a frozen embryo transfer (FET)? SUMMARY ANSWER Although the optimal endometrial preparation protocol for FET needs further research and is yet to be determined, we propose a standardized timing strategy based on the current available evidence which could assist in the harmonization and comparability of clinic practice and future trials. WHAT IS KNOWN ALREADY Amid a continuous increase in the number of FET cycles, determining the optimal endometrial preparation protocol has become paramount to maximize ART success. In current daily practice, different FET preparation methods and timing strategies are used. STUDY DESIGN, SIZE, DURATION This is a review of the current literature on FET preparation methods, with special attention to the timing of the embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS Literature on the topic was retrieved in PubMed and references from relevant articles were investigated until June 2017. MAIN RESULTS AND THE ROLE OF CHANCE The number of high quality randomized controlled trials (RCTs) is scarce and, hence, the evidence for the best protocol for FET is poor. Future research should compare both the pregnancy and neonatal outcomes between HRT and true natural cycle (NC) FET. In terms of embryo transfer timing, we propose to start progesterone intake on the theoretical day of oocyte retrieval in HRT and to perform blastocyst transfer at hCG + 7 or LH + 6 in modified or true NC, respectively. LIMITATIONS REASONS FOR CAUTION As only a few high quality RCTs on the optimal preparation for FET are available in the existing literature, no definitive conclusion for benefit of one protocol over the other can be drawn so far. WIDER IMPLICATIONS OF THE FINDINGS Caution when using HRT for FET is warranted since the rate of early pregnancy loss is alarmingly high in some reports. STUDY FUNDING/COMPETING INTEREST(S) S.M. is funded by the Research Fund of Flanders (FWO). H.T. and C.B. report grants from Merck, Goodlife, Besins and Abbott during the conduct of the study. TRIAL REGISTRATION NUMBER Not applicable.
Hierarchical Heuristic Learning towards Effcient Norm Emergence

Social norms serve as an important mechanism to regulate the behaviors of agents and to facilitate coordination among them in multiagent systems. One important research question is how a norm can rapidly emerge through repeated local interaction within an agent society under different environments when their coordination space becomes large. To address this problem, we propose a Hierarchically Heuristic Learning Strategy (HHLS) under the hierarchical social learning framework, in which subordinate agents report their information to their supervisors, while supervisors can generate instructions (rules and suggestions) based on the information collected from their subordinates. Subordinate agents heuristically update their strategies based on both their own experience and the instructions from their supervisors. Extensive experiment evaluations show that HHLS can support the emergence of desirable social norms more efficiently and is applicable in a much wider range of multiagent interaction scenarios compared with previous work. We also investigate the effectiveness of HHLS by separating out the different components of the HHLS and evaluating the relative importance of those components. The influence of key related factors (e.g., hierarchical factors, non-hierarchical factors, fixed-strategy agents) are investigated as well.
Humanizing Human-Robot Interaction: On the Importance of Mutual Understanding

In conjunction with what is often called the industry 4.0, the new machine age, or the rise of the robots, the authors of this paper have each experienced the following phenomenon. At public events and roundtable discussions, among our circles of friends, or during interviews with the media, we are asked on a surprisingly regular basis: "How must humankind adapt to the imminent process of technological change? What do we have to learn in order to keep pace with the smart new machines? What new skills do we need to understand the robots? "
Childhood Trauma Is Associated With Severity of Hallucinations and Delusions in Psychotic Disorders: A Systematic Review and Meta-Analysis

Introduction Childhood trauma is a risk factor for the development of psychosis. Furthermore, a number of theories propose specific mechanisms by which childhood trauma may contribute to more severe positive and negative psychotic symptoms, some of which are supported empirically. The robustness of this empirical evidence is unclear due to mixed results and methodological limitations of individual studies. A systematic review and meta-analysis of the evidence for associations between childhood trauma and severity of hallucinations, delusions, and negative psychotic symptoms in clinical populations with a diagnosed psychotic disorder is needed. Method A systematic search was conducted. Reference lists of relevant review articles were hand-searched, and authors contacted for data and additional unpublished studies. Study reporting bias and quality was assessed. Results In total, 6667 studies were identified and of these 41 studies met inclusion criteria. Of these, 29 studies (4680 participants) were meta-analyzed. Among individuals with psychosis, childhood trauma was significantly correlated with severity of hallucinations (r = .199, P < .001) and delusions (r = .172, P < .001) but contrary to our hypothesis, not correlated with severity of negative symptoms (r = .049, P = .095). Severity of childhood neglect was correlated with negative symptoms (r = .142, P = .005). Conclusion The results lend support for cognitive and biological theories that traumas in childhood may lead to hallucinations and delusions within psychotic disorders and have important implications for clinical practice.
Multi-stakeholder perspectives in defining health-services quality in cataract care

Objective To develop a method to define a multi-stakeholder perspective on health-service quality that enables the expression of differences in systematically identified stakeholders' perspectives, and to pilot the approach for cataract care. Design Mixed-method study between 2014 and 2015. Setting Cataract care in the Netherlands. Participants Stakeholder representatives. Intervention(s) We first identified and classified stakeholders using stakeholder theory. Participants established a multi-stakeholder perspective on quality of cataract care using concept mapping, this yielded a cluster map based on multivariate statistical analyses. Consensus-based quality dimensions were subsequently defined in a plenary stakeholder session. Main outcome measure(s) Stakeholders and multi-stakeholder perspective on health-service quality. Results Our analysis identified seven definitive stakeholders, as follows: the Dutch Ophthalmology Society, ophthalmologists, general practitioners, optometrists, health insurers, hospitals and private clinics. Patients, as dependent stakeholders, were considered to lack power by other stakeholders; hence, they were not classified as definitive stakeholders. Overall, 18 stakeholders representing ophthalmologists, general practitioners, optometrists, health insurers, hospitals, private clinics, patients, patient federations and the Dutch Healthcare Institute sorted 125 systematically collected indicators into the seven following clusters: patient centeredness and accessibility, interpersonal conduct and expectations, experienced outcome, clinical outcome, process and structure, medical technical acting and safety. Importance scores from stakeholders directly involved in the cataract service delivery process correlated strongly, as did scores from stakeholders not directly involved in this process. Conclusions Using a case study on cataract care, the proposed methods enable different views among stakeholders concerning quality dimensions to be systematically revealed, and the stakeholders jointly agreed on these dimensions. The methods helped to unify different quality definitions and facilitated operationalisation of quality measurement in a way that was accepted by relevant stakeholders.
Development of an adverse outcome pathway for chemically induced hepatocellular carcinoma: case study of AFB1, a human carcinogen with a mutagenic mode of action

Abstract Adverse outcome pathways (AOPs) are frameworks starting with a molecular initiating event (MIE), followed by key events (KEs) linked by KE relationships (KERs), ultimately resulting in a specific adverse outcome. Relevant data for the pathway and each KE/KER are evaluated to assess biological plausibility, weight-of-evidence, and confidence. We aimed to describe an AOP relevant to chemicals directly inducing mutation in cancer critical gene(s), via the formation of chemical-specific pro-mutagenic DNA adduct(s), as an early critical step in tumor etiology. Such chemicals have mutagenic modes-of-action (MOA) for tumor induction. To assist with developing this AOP, Aflatoxin B1 (AFB1) was selected as a case study because it has a rich database and is considered to have a mutagenic MOA. AFB1 information was used to define specific KEs, KERs, and to inform development of a generic AOP for mutagen-induced hepatocellular carcinoma (HCC). In assessing the AFB1 information, it became clear that existing data are, in fact, not optimal and for some KEs/KERs, the definitive data are not available. In particular, while there is substantial information that AFB1 can induce mutations (based on a number of mutation assays), the definitive evidence – the ability to induce mutation in the cancer critical gene(s) in the tumor target tissue – is not available. Thus, it is necessary to consider the patterns of results in the weight-of-evidence for KEs and KERs. It was important to determine whether there was sufficient evidence that AFB1 can induce the necessary critical mutations early in the carcinogenic process, which was the case.
Consistency of effects of tropical‐forest disturbance on species composition and richness relative to use of indicator taxa

Lawton et al. (1998) found, in a highly cited study, that the species richness of 8 taxa each responds differently to anthropogenic disturbance in Cameroon forests. Recent developments in conservation science suggest that net number of species is an insensitive measure of change and that understanding which species are affected by disturbance is more important. It is also recognized that all disturbance types are not equal in their effect on species and that grouping species according to function rather than taxonomy is more informative of responses of biodiversity to change. In a reanalysis of most of the original Cameroon data set (canopy and ground ants, termites, canopy beetles, nematodes, and butterflies), we focused on changes in species and functional composition rather than richness and used a more inclusive measure of forest disturbance based on 4 component drivers of change: years since disturbance, tree cover, soil compaction, and degree of tree removal. Effects of disturbance on compositional change were largely concordant between taxa. Contrary to Lawton et al.’s findings, species richness for most groups did not decline with disturbance level, providing support for the view that trends in species richness at local scales do not reflect the resilience of ecosystems to disturbance. Disturbance affected species composition more strongly than species richness for butterflies, canopy beetles, and litter ants. For these groups, disturbance caused species replacements rather than just species loss. Only termites showed effects of disturbance on species richness but not composition, indicating species loss without replacement. Although disturbance generally caused changes in composition, the strength of this relationship depended on the disturbance driver. Butterflies, litter ants, and nematodes were correlated with amount of tree cover, canopy beetles were most strongly correlated with time since disturbance, and termites were most strongly correlated with degree of soil disturbance. There were moderately divergent responses to disturbance between functional feeding groups. Disturbance was most strongly correlated with compositional differences of herbivores within beetles and nematodes and humus feeders within termites. Our results suggest that consideration of the impact of different forms of disturbance on species and functional composition, rather than on net numbers of species, is important when assessing the impacts of disturbance on biodiversity.
Log-Bilinear Document Language Model for Ad-hoc Information Retrieval

Incorporating semantic information into document representation is effective and potentially significant to improve retrieval performance. Recently, log-bilinear language model (LBL), as a form of neural language model, has been proved to be an effective way to learn semantic word representations, but its feasibility and effectiveness in information retrieval is mostly unknown. In this paper, we study how to efficiently use LBL to improve as-hoc retrieval. We propose a log-bilinear document language model (LB-DM) within the language modeling framework. The key idea is to learn semantically oriented representations for words, and estimate document language models based on these representations. Noise-constrictive estimation is employed to perform fast training on large document collections. Experiment results on standard TREC collections show that LB-DM performs better than translation language model and LDA-based retrieval model.
Caries detection and quantification around stained pits and fissures in occlusal tooth surfaces with fluorescence

Abstract. Occlusal discoloration due to staining frequently occurs on the pits and fissures of teeth. Noncariogenic discoloration (non-CD) refers to the attachment of staining chromogens to sound surfaces, whereas cariogenic discoloration (CD) represents the discoloration of porous structures due to bacterial metabolites and mineral loss from the enamel surface. This study evaluated whether it is possible to distinguish between non-CD and CD on stained occlusal surfaces with fluorescence assessed by the quantitative light-induced fluorescence (QLF) technology. Sixty-two extracted human permanent teeth with suspected discolorations on the pit and fissure were examined. The maximum values of fluorescence loss (ΔFmax) and red fluorescence gain (ΔRmax) were calculated using QLF images. Using histology as the gold standard, it was found that 12 teeth were sound (non-CD), while 50 teeth had enamel and dentine caries (CD). The validity tests at the enamel histological caries level, ΔRmax (ρ = 0.80) were strongly correlated with the histology (P < 0.001). At the optimum threshold (105.0) of ΔRmax, it showed high levels of sensitivity and specificity (0.96 and 0.83, respectively). Therefore, QLF can be used to distinguish non-CD from CD on occlusal surfaces using red fluorescence values with high validity.
Attachment Style and Internet Addiction: An Online Survey

Background One of the clinically relevant problems of Internet use is the phenomenon of Internet addiction. Considering the fact that there is ample evidence for the relationship between attachment style and substance abuse, it stands to reason that attachment theory can also make an important contribution to the understanding of the pathogenesis of Internet addiction. Objective The aim of this study was to examine people’s tendency toward pathological Internet usage in relation to their attachment style. Methods An online survey was conducted. Sociodemographic data, attachment style (Bielefeld questionnaire partnership expectations), symptoms of Internet addiction (scale for online addiction for adults), used Web-based services, and online relationship motives (Cyber Relationship Motive Scale, CRMS-D) were assessed. In order to confirm the findings, a study using the Rorschach test was also conducted. Results In total, 245 subjects were recruited. Participants with insecure attachment style showed a higher tendency to pathological Internet usage compared with securely attached participants. An ambivalent attachment style was particularly associated with pathological Internet usage. Escapist and social-compensatory motives played an important role for insecurely attached subjects. However, there were no significant effects with respect to Web-based services and apps used. Results of the analysis of the Rorschach protocol with 16 subjects corroborated these results. Users with pathological Internet use frequently showed signs of infantile relationship structures in the context of social groups. This refers to the results of the Web-based survey, in which interpersonal relationships were the result of an insecure attachment style. Conclusions Pathological Internet use was a function of insecure attachment and limited interpersonal relationships.
Multi-Cultural Interlinking of Web Taxonomies with ACROSS

The Web hosts a huge variety of multi-cultural taxonomies. They encompass product catalogs of e-commerce, general-purpose knowledge bases and numerous domain-specific category systems. The enormous heterogeneity of those sources is a challenging aspect when multiple taxonomies have to be interlinked. In this paper we introduce ACROSS system to support the alignment of independently created Web taxonomies. For mapping categories across different taxonomies, ACROSS harnesses instance-level features as well as distant supervision from an intermediate source like multiple Wikipedia editions. ACROSS includes a reasoning step, which is based on combinatorial optimization. In order to reduce the run time of the reasoning procedure without sacrificing the quality, we study two models of user involvement. Our experiments with heterogeneous taxonomies for different domains demonstrate the viability of our approach and improvement over state-of-the-art baselines.
Aleph1 and the Modal mu-Calculus

For a regular cardinal $\kappa$, a formula of the modal $\mu$-calculus is $\kappa$-continuous in a variable x if, on every model, its interpretation as a unary function of x is monotone and preserves unions of $\kappa$-directed sets. We define the fragment $C_{\aleph_1}(x)$ of the modal $\mu$-calculus and prove that all the formulas in this fragment are $\aleph_1$-continuous. For each formula $\phi(x)$ of the modal $\mu$-calculus, we construct a formula $\psi(x) \in C_{\aleph_1 }(x)$ such that $\phi(x)$ is $\kappa$-continuous, for some $\kappa$, if and only if $\phi(x)$ is equivalent to $\psi(x)$. Consequently, we prove that (i) the problem whether a formula is $\kappa$-continuous for some $\kappa$ is decidable, (ii) up to equivalence, there are only two fragments determined by continuity at some regular cardinal: the fragment $C_{\aleph_0}(x)$ studied by Fontaine and the fragment $C_{\aleph_1}(x)$. We apply our considerations to the problem of characterizing closure ordinals of formulas of the modal $\mu$-calculus. An ordinal $\alpha$ is the closure ordinal of a formula $\phi(x)$ if its interpretation on every model converges to its least fixed-point in at most $\alpha$ steps and if there is a model where the convergence occurs exactly in $\alpha$ steps. We prove that $\omega_1$, the least uncountable ordinal, is such a closure ordinal. Moreover we prove that closure ordinals are closed under ordinal sum. Thus, any formal expression built from 0, 1, $\omega$, $\omega_1$ by using the binary operator symbol + gives rise to a closure ordinal.
Structural and functional analyses reveal the contributions of the C- and N-lobes of Argonaute protein to selectivity of RNA target cleavage

Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ∼23-nucleotide (nt)–long siRNAs are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage. A hallmark of Argonaute proteins is their bilobal structure, but despite the significance of this structure for curtailing slicing activity against mismatched targets, the molecular mechanism remains elusive. Here, our structural and functional studies of a bilobed yeast Argonaute protein and its isolated catalytic C-terminal lobe (C-lobe) revealed that the C-lobe alone retains almost all properties of bilobed Argonaute: siRNA-duplex loading, passenger cleavage/ejection, and siRNA-dependent RNA cleavage. A 2.1 Å–resolution crystal structure revealed that the catalytic C-lobe mirrors the bilobed Argonaute in terms of guide-RNA recognition and that all requirements for transitioning to the catalytically active conformation reside in the C-lobe. Nevertheless, we found that in the absence of the N-terminal lobe (N-lobe), target RNAs are scanned for complementarity only at positions 5–14 on a 23-nt guide RNA before endonucleolytic cleavage, thereby allowing for some off-target cleavage. Of note, acquisition of an N-lobe expanded the range of the guide RNA strand used for inspecting target complementarity to positions 2–23. These findings offer clues to the evolution of the bilobal structure of catalytically active Argonaute proteins.