Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of potential prognostic TF‐associated lncRNAs for predicting survival in ovarian cancer

The pathophysiology of ovarian cancer (OV) is complex and depends on multiple biological processes and pathways. Therefore, there is an urgent need to identify reliable prognostic biomarkers for predicting clinical outcomes and helping personalize treatment of OV. A long non‐coding RNA (lncRNA)‐based risk score model was constructed to infer the prognostic efficacy of transcription factors (TFs) based on the OV dataset from The Cancer Genome Atlas. The risk score model was further validated in other independent cohorts from Gene Expression Omnibus. Time‐dependent receiver operating characteristic curves were used to evaluate the survival prediction performance in comparison with other clinical and molecular variables. Our results revealed that the top‐ranked TF‐associating lncRNAs were significantly associated with overall survival, progression‐free survival and disease‐free survival. Stratification analysis according to clinical variables indicated the prognostic independence of POLR2A‐associating lncRNAs. In comparison, the signature of POLR2A‐associating lncRNAs was more sensitive and specific than existing clinical and molecular signatures. Functional and experimental analysis suggested that POLR2A‐associating lncRNAs may be involved in known biological processes and pathways of OV. Our findings revealed that the lncRNA‐based risk score model can provide helpful information on OV prognosis stratification and discovery of therapeutic biomarkers.
High-throughput elucidation of thrombus formation reveals sources of platelet function variability

In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based on assessment of the inter- and intra-subject variability in parameters of microspot-based thrombus formation, we aimed to determine the platelet factors contributing to this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional platelet phenotyping: i.e. hematologic parameters, platelet glycoprotein (GP) expression levels and activation markers (24 parameters). Furthermore, platelets were activated by ADP, CRP-XL or TRAP. Parallel samples were investigated for whole-blood thrombus formation (6 microspots, providing 48 parameters of adhesion, aggregation and activation). Microspots triggered platelet activation through GP Ib-V-IX, GPVI, CLEC-2 and integrins. For most thrombus parameters, inter-subject variation was 2-4 times higher than the intra-subject variation. Principal component analyses indicated coherence between the majority of parameters for the GPVI-dependent microspots, partly linked to hematologic parameters, and glycoprotein expression levels. Prediction models identified parameters per microspot that were linked to variation in agonist-induced αIIbβ3 activation and secretion. Common sequence variation of GP6 and FCER1G, associated with GPVI-induced αIIbβ3 activation and secretion, affected parameters of GPVI-and CLEC-2-dependent thrombus formation. Subsequent analysis of blood samples from patients with Glanzmann thrombasthenia or storage pool disease revealed thrombus signatures of aggregation-dependent parameters that were subject-dependent, but not linked to GPVI activity. Taken together, this high-throughput elucidation of thrombus formation revealed patterns of inter-subject differences in platelet function, which were partly related to GPVI-induced activation and common genetic variance linked to GPVI, but also included a distinct platelet aggregation component.
Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases

Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution strategies. Deeper insights into the pathophysiology of AI has led to the development of new therapeutics targeting inflammatory cytokines and the introduction of new iron formulations. Moreover, the discovery that the hormone, hepcidin, plays a key regulatory role in AI has stimulated the development of several therapeutic approaches targeting the function of this peptide. Hence, inflammation-driven hepcidin elevation causes iron retention in cells and tissues. Besides pathophysiological concepts and diagnostic approaches for AI, this review discusses current guidelines for iron replacement therapies with special emphasis on benefits, limitations, and unresolved questions concerning oral versus parenteral iron supplementation in chronic inflammatory diseases. Furthermore, the review explores how therapies aiming at curing the disease underlying AI can also affect anemia and discusses emerging hepcidin antagonizing drugs, which are currently under preclinical or clinical investigation.
Intelligent Hearing Assistance Using Self-Organizing Feature Maps

A novel hearing assistance system is proposed which classifies sounds and selectively tunes them according to the needs of the hearing impaired. This differs from the usual hearing aids available today in that it uses computational intelligence to filter and tune sounds based on real life categorical classifications. The system can significantly improve audibility for the hearing impaired, including bringing completely inaudible tones into audibility. For classification a self-organizing feature map is used with a vector of sound features from the joint time-frequency domain. The map is trained with input sounds until a map of neurons is clustered according to its these. The resulting map is used to classify new sounds. Based on this classification, a sound can be tuned to improve audibility for the hearing impaired. Techniques proposed for audio output include gammatone frequency filtering, Fourier compression, low pass filtering, spectral subtraction, and an original algorithm to choose how to best boost the amplitude of deaf frequencies.
A systematic review protocol

Background: Characterized by diffuse hepatic fibrosis and nodule formation, hepatitis B cirrhosis (HBC), an important result of chronic hepatitis B development, mainly contains compensated and decompensated stage. Compensated cirrhosis can further develop into decompensated stage and hepatocellular carcinoma with serious complications and high mortality. Antiviral therapy using interferon (IFN) or nucleos(t)ide analogs (NUCs) is essential for improving the prognosis of the disease but IFN has large side effects while NUCs often develop drug resistance. Antifibrosis is also an important strategy, but currently there is no effective antifibrosis drug. Pharmacologic studies have demonstrated that oxymatrine (OM) exhibits anti-hepatitis B virus (HBV) and antifibrosis effects. An increasing number of clinical controlled studies also have found that OM combined with conventional therapy could improve the curative effect and reduce adverse events incidence in treating HBC but there is no systematic review of it. Based on the extensive collection of literature, we will use meta-analysis to assess the efficacy and safety of OM for HBC. Methods: PubMed, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database will be searched to obtain the eligible studies published up to July 15, 2018. The primary outcome will be liver function indexes, liver fibrosis indexes, and Child–Pugh score. The secondary outcome will be hepatitis B virus DNA quantification, HBV DNA seroconversion rate, hepatitis B e antigen (HBeAg) seroconversion rate, and adverse events incidence. Data analysis will be conducted using RevMan 5.3 and Stata V.9. 0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. Results: This systematic review will provide a high quality synthesis of OM for HBC from various evaluation aspects including liver function indexes, liver fibrosis indexes and Child-Pugh score, HBV DNA quantification, HBV DNA seroconversion rate, HBeAg seroconversion rate and adverse events incidence. Conclusion: The systematic review will provide evidence to assess the efficacy and safety of OM in the treatment of HBC. PROSPERO registration number: PROSPERO CRD42018095275. Abbreviations: ADV = adefovir, CHB = chronic hepatitis B, CIs = confidence intervals, CNKI = China National Knowledge Infrastructure, EASL= European Association for the study of liver, ETV= entecavir, HA= hyaluronic acid, HBC= hepatitis B cirrhosis, HBeAg= hepatitis B e antigen, HBsAg= hepatitis B surface antigen, HBV= hepatitis B virus, HCC= hepatocellular carcinoma, IFN= interferon, IV-C = type IV collagen, LAM = lamivudine, LDT = telbivudine, LN = laminin, NUCs = nucleos(t)ide analogs, OM = oxymatrine, PC-III = procollagen type III, PROSPERO = Prospective Register of Systematic Reviews, RCTs = randomized controlled trials, TLV = tenofovir, TSA = trial sequential analysis, VIP = Chinese Scientific Journals Database.
Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review

Chagas’ disease and Human African Trypanosomiasis are parasitic diseases that remain major health problems, mainly among the poorest and the most marginalized communities from Latin America and Africa. The scarcity of effective chemotherapy, due to the low investment in the research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasize the urgent need for new prophylactic and therapeutic agents. Over the ages, humans have employed natural products to treat a wide spectrum of diseases. Recently, the pharmaceutical industry has focused on plant research and a large body of evidence has been collected to demonstrate the immense potential of medicinal plants as a source of bioactive compounds and lead molecules. In the field of parasitic diseases, drug development from plants has been successful for the sesquiterpene lactone (STL) artemisinin, which is employed as an antimalarial agent. STLs are a large group of naturally occurring terpenoids derived from plants that mostly belong to the Asteraceae family which exhibit a variety of skeletal arrangements and are the largest and most diverse category of natural products with an α-methylene-λ-lactone motif. STLs display a broad spectrum of biological activities such as antitumor, cytotoxic, antibacterial, anthelmintic, uterus contracting, antimalarial, neurotoxic, antiprotozoal and allergic (contact dermatitis) activities. In this context, the purpose of the present review is to provide an overview of the trypanocidal activity reported for STLs against Trypanosoma cruzi and T. brucei rhodesiense over the period 1993–2015.
Iconography : Prise en charge de l'infection par le virus de l'hépatite C dans une population de toxicomanes suivis dans un centre spécialisé ambulatoire

Malades et méthodes — La réalisation d’une sérologie C était proposée systématiquement aux malades suivis dans un Centre de Soins Spécialisés pour Toxicomanes. Des explorations complémentaires et un traitement anti-viral si nécessaire étaient ensuite proposés en cas de sérologie VHC positive. Lorsqu’il existait une indication thérapeutique (score Métavir ≥ F2), le suivi était pratiqué conjointement par un médecin du centre et un hépatologue hospitalier.
Contribution à la commande non linéaire robuste des systèmes d'alimentation en air des piles à combustible de type PEM

La pile a combustible (PaC) est un dispositif qui produit de l'electricite a partir d'une reaction chimique entre l'hydrogene et l'oxygene. Le systeme a PaC necessite un certain nombre d'auxiliaires pour fonctionner. Pour cela, un systeme de commande est indispensable pour optimiser la performance de la PaC.Dans ce travail de these, nous nous sommes interesses a trois types de problematiques de commande de la PaC. La premiere est celle de l'optimisation de la puissance delivree par la PaC en controlant le rapport d'exces d'oxygene via le debit d'air du compresseur ; en prenant en compte les variations parametriques, les incertitudes et les perturbations externes. Ce probleme est resolu en utilisant la commande non-lineaire par mode glissant d'ordre 2. Deux types d'algorithme sont synthetises, l'algorithme du mode glissant d'ordre 2 sous-optimal et l'algorithme du Super Twisting adaptatif. Les performances de ces lois de commande ont ete validees grâce a un simulateur Hardware In Loop. La deuxieme concerne la maximisation de la puissance nette fournie par la pile, tout en maintenant le fonctionnement du compresseur centrifuge dans sa zone nominale et tout en evitant le manque d'oxygene a la cathode, lors des variations rapides de charge. La solution proposee pour resoudre ce probleme est un gestionnaire de charge qui consiste en un filtre a coefficient de filtrage ajustable. Deux approches d'ajustement de ce coefficient basees sur la technique de l'Extremum Seeking sont appliquees, comparees et validees experimentalement. La troisieme problematique abordee dans cette these est celle de la regulation de la difference de pression entre l'anode et la cathode, lors de variations de charge en presence de variations parametriques et d'incertitudes. Une solution basee sur un controleur multi-variable par mode glissant d'ordre 2 associe a une etude de robustesse est proposee.
Eimeria challenge adversely affected long bone attributes linked to increased resorption in 14-day-old broiler chickens

ABSTRACT There is limited information on the effects of enteric pathogen on bone quality in rapidly growing broiler chicks. We examined tibia and femur attributes (length, diameter, relative weight of ash content [AC] to the BW, ash concentration [AP]) and serum bone‐turnover markers including receptor activator of nuclear factor kappa‐B ligand (RANKL) for resorption, alkaline phosphatase (ALP) for mineralization, and selected serum metabolites in 14‐day‐old broilers challenged with Eimeria. A total of 160 (80 males and 80 females) 1‐day‐old Ross × Ross 708 chicks were used. Based on BW, birds were placed within sex in cages (5 birds per cage) and fed chick starter diets to day 9 of age. On day 9, half of the cages were orally gavaged with 1 mL of Eimeria culture (100,000 oocysts of E. acervulina and 25,000 oocysts of E. maxima) and the other half (unchallenged control) received 1 mL 0.9% saline in distilled water. On day 14, 2 birds were randomly selected and necropsied for intestinal lesion score, blood, tibia, and femur samples. Data were analyzed in a 2 (challenged vs. unchallenged) × 2 (males vs. females) factorial arrangement. There was no interaction (P > 0.05) between Eimeria and sex on any measurement. Whereas there were no intestinal lesions in unchallenged birds, Eimeria resulted in lesion score (0 to 4) of 3.35, 2.59 and 0.11 in duodenum, jejunum and ileum, respectively. Eimeria challenge decreased (P < 0.05) tibia AC and AP by 10 and 8.2%, respectively but had no (P > 0.10) effect on femur attributes. Generally, males showed (P < 0.05) longer and wider bones with more AC compared with the female. Circulating serum RANKL concentration increased (P = 0.017) in response to Eimeria challenge and was negatively correlated with tibia AC (‐0.731; P = 0.021). Our findings showed that Eimeria damage to the intestinal physiology had adverse effects on long bone attributes linked to increased resorption.
Chiral events in developing gametophores of Physcomitrella patens and other moss species are driven by an unknown, universal direction-sensing mechanism.

PREMISE OF THE STUDY We used the model species Physcomitrella patens to examine chirality in moss gametophores. Chirality is manifested in the direction of consecutive apical cell divisions, cell plate configurations, and deviations of leaf connecting lines from the vertical course. However, the frequencies of chiral configurations of all these processes as well as their mutual dependence-especially in the case of gametophore branching-are not known. Other moss species were checked to determine the universality of our findings. METHODS The gametophore structure of Physcomitrella patens grown in the laboratory under controlled conditions was investigated using light microscopy and compared with that of other moss species collected from their natural stands. KEY RESULTS In all investigated moss species, the tetrahedral apical cell exhibits either clockwise or counterclockwise consecutive divisions, and selection of this directionality in the primary axis is random. It is, however, related to cell plate configuration. If the plate is skewed, leaf-producing segments arising from the apical cell cleavage exhibit circumferential rotation. Three parallel lines connecting the leaves deviate from a vertical course, but always in the same direction as that of leaf initiation; thus, the angular distance between consecutive leaves increases to >120°. Lateral branches are exclusively antidromous. CONCLUSIONS Gametophore chiral configuration appears to be useful in resolving problems of moss modular growth and branching. Morphological and anatomical evidence strongly suggests that an unknown direction-sensing mechanism controls the development of moss axial organs. We propose that leaves are responsible for a horizontal gradient of sugar signals that develops along the gametophore circumference, thus influencing branching-unit chirality.
Du sens aux sens : les représentations mentales dans l’acte de lecture

Le statut des representations mentales dans la lecture n’a fait l’objet que de peu d’etudes approfondies. Les travaux fondateurs menes en theorie litteraire insistent surtout sur la dimension conceptuelle de ces representations. Les sciences cognitives, de leur cote, s’interessent egalement aux modalites de la comprehension des textes, mais ne prennent en compte ni la dimension esthetique de ces derniers ni la singularite de l’acte de lecture. Nous proposons d’instaurer un dialogue interdisciplinaire afin de montrer que les representations mentales contiennent des composantes aussi bien sensorielles qu’emotionnelles et conceptuelles.
Ibrutinib significantly inhibited Bruton’s tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model

ABSTRACT Pediatric and adult patients with recurrent/refractory Burkitt lymphoma (BL) continue to have poor outcomes, emphasizing the need for newer therapeutic agents. Bruton’s tyrosine kinase (BTK) is activated following B-cell receptor stimulation and in part regulates normal B-cell development. Ibrutinib, a selective and irreversible BTK inhibitor, has been efficacious in chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström’s macroglobulinemia, and marginal zone lymphoma. In this study, we investigated the efficacy of ibrutinib alone and in selective adjuvant combinations against BL in-vitro and in a human BL xenografted immune-deficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mouse model. Our data demonstrated that phospho-BTK level was significantly reduced in BL cells treated with ibrutinib (p < 0.001). Moreover, we observed a significant decrease in cell proliferation as well as significant decrease in IC50 of ibrutinib in combination with dexamethasone, rituximab, obinutuzumab, carfilzomib, and doxorubicin (p < 0.001). In-vivo studies demonstrated ibrutinib treated mice had a significantly prolonged survival with median survival of mice following ibrutinib treatment (32 days) (24 days) (p < 0.02). In conclusion, our findings demonstrate the significant in-vitro and preclinical in-vivo effects of ibrutinib in BL. Based on our preclinical results in this investigation, there is an on-going clinical trial comparing overall survival in children and adolescents with relapsed/refractory BL treated with chemoimmunotherapy with or without ibrutinib (NCT02703272).
Systematic analysis of business processes

In the business literature, analysis of business processes aims at certain specific characteristics, such as performance measures, the role of information technology or human resource planning. Business analysts, however, perform the analysis of their processes in the light of a basic problem: they wish to improve customer service or efficiency. It is often unclear how these basic questions relate to the existing analysis theory and techniques. In this paper we present a systematic approach for the analysis of business processes, starting from basic objectives leading to bottlenecks and solutions. Copyright © 2000 John Wiley & Sons, Ltd.
Speciation in a biodiversity hotspot: Phylogenetic relationships, species delimitation, and divergence times of Patagonian ground frogs from the Eupsophus roseus group (Alsodidae)

The alsodid ground frogs of the Eupsophus genus are divided into two groups, the roseus (2n = 30) and vertebralis (2n = 28), which are distributed throughout the temperate Nothofagus forests of South America. Currently, the roseus group is composed by four species, while the vertebralis group consists of two. Phylogenetic relationships and species delimitation within each group are controversial. In fact, previous analyses considered that the roseus group was composed of between four to nine species. In this work, we evaluated phylogenetic relationships, diversification times, and species delimitation within the roseus group using a multi-locus dataset. For this purpose, mitochondrial (D-loop, Cyt b, and COI) and nuclear (POMC and CRYBA1) partial sequences from 164 individuals were amplified, representing all species. Maximum Likelihood (ML) and Bayesian approaches were used to reconstruct phylogenetic relationships. Species tree was estimated using BEAST and singular value decomposition scores for species quartets (SVDquartets). Species limits were evaluated with six coalescent approaches. Diversification times were estimated using mitochondrial and nuclear rates with LogNormal relaxed clock in BEAST. Nine well-supported monophyletic lineages were recovered in Bayesian, ML, and SVDquartets, including eight named species and a lineage composed by specimens from the Villarrica population (Bootstrap:>70, PP:> 0.99). Single-locus species delimitation analyses overestimated the species number in E. migueli, E. calcaratus, and E. roseus lineages, while multi-locus analyses recovered as species the nine lineages observed in phylogenetic analyses (Ctax = 0.69). It is hypothesized that Eupsophus diversification occurred during Mid-Pleistocene (0.42–0.14 Mya), with most species having originated after the Last Southern Patagonian Glaciation (0.18 Mya). Our results revitalize the hypothesis that the E. roseus group is composed of eight species and support the Villarrica lineage as a new putative species.