Miracle-dz/UniFAR-FTUs huggingface dataset:
Fetal Cell‐Free Nucleic Acids in the Maternal Circulation: New Clinical Applications

Abstract: Six years after the demonstration of the presence of cell‐free fetal nucleic acids in maternal plasma, perinatal clinical applications continue to expand. The focus of this article is on advances that have occurred since the CNAPS II conference held in Hong Kong in 2001. Circulating fetal DNA levels (fDNA) are elevated in pregnancies complicated by fetal trisomies 13 and 21 but not 18. Measurement of fDNA levels improves the performance of the current standard maternal serum screen, by increasing the detection of Down syndrome cases by 5% with no increase in the false‐positive rate. fDNA levels are elevated in women who have developed clinical symptoms of preeclampsia, but they are also elevated by the early second trimester in women who will eventually develop preeclampsia. fDNA and mRNA gamma globin measurement may have clinical utility as markers for fetomaternal hemorrhage in the late first trimester. Cell‐free fetal DNA levels are quite high in the amniotic fluid, permitting fetal genomic isolation and analysis using comparative genomic hybridization techniques. Fetal DNA crosses the blood‐brain barrier and is detectable in maternal cerebrospinal fluid in a subset of pregnant women. The biological implications of this are currently unknown. Review of the literature suggests that the placenta is the predominant source of the circulating fetal nucleic acids. However, detection of gamma globin mRNA sequences in the plasma of pregnant women suggests that fetal blood cells also contribute to the pool of nucleic acids. Widespread incorporation of fetal nucleic acid measurement into routine prenatal care depends on the identification of a readily accessible gender‐independent fetal marker.
Mapping community innovation: Using social network analysis to map the interactional field, identify facilitators, and foster community development

Abstract Can community networks be mapped to facilitate innovation? This study focuses on social structure and network interactions that can be used to identify key individuals and relationships with the potential to facilitate community innovation and development. Viewed through the lenses of social network analysis (SNA), interactional community theory, and social capital (trust), this study examines the dynamics of network interactions and the community field in a developing research park. Operated by two US Department of Energy national laboratories in California, the interactional environment of this research park is similar to the social structures and processes of small, place-based communities. SNA is used to identify critical community actors and map the core of a community field shared by two national laboratories. Findings suggest that SNA can be productively applied to community field mapping with the potential to strengthen collaboration, overcome innovation barriers, and identify facilitating actors who can foster community development.
Myelofibrosis: an update on current pharmacotherapy and future directions

Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by symptoms mainly derived from anemia and splenomegaly and constitutional symptoms and associated with a median survival around 6 years. Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapy of MF but is applicable to a minority of patients. Discovery of the JAK2 mutation has provided the basis for the introduction of a new class of drugs, the JAK inhibitors, in the treatment of MF. Areas covered: A literature review on the therapy of MF has been performed through a PubMed search, with special attention being paid to the available data on transplantation, the JAK inhibitors, and other new drugs. Expert opinion: Conventional therapy of MF is usually adjusted to the predominant clinical symptoms in each patient, and its impact on survival is limited. Reduced-intensity conditioning regimens have increased the number of patients eligible for allo-SCT, but this procedure is still associated with substantial morbidity and mortality. The JAK inhibitors, such as ruxolitinib, can achieve profound symptomatic relief of the splenomegaly and the constitutional symptoms. However, they often accentuate the anemia and do not reduce the JAK2 allele burden, therefore lacking the potential to modify the natural history of MF.
Mining Process Model Variants: Challenges, Techniques, Examples

During the last years a new generation of process-aware information systems has emerged, which enables process model configurations at buildtime as well as process instance changes during runtime. Respective model adaptations result in large collections of process model variants that are derived from same process model, but slightly differ in structure. Generally, such model variants are expensive to maintain and configure. Starting with a collection of related process model variants, the major goal of this thesis is to discover a reference process model out of which these variants can be easily configured; i.e., a reference process model with minimal average change distance to the variants. To achieve this goal we present two advanced algorithms which are applicable in different scenarios. Our clustering algorithm does not presume any knowledge about the original reference process model out of which the process model variants were configured. By only looking at the process model variants, this algorithm can quickly discover a reference process model in polynomial time, which allows us to scale up when solving real-world problems. Our heuristic algorithm, in turn, can take the original reference model into account as well. In particular, the user can control to what degree the discovered model differs from the original one. This way we can avoid spaghetti-like process models and additionally control how many changes we want to perform on the original reference model. We systematically evaluate and compare the two algorithms based on simulations that comprise more than 7000 process models. Simulation results indicate good performance and make the differences between the two algorithms explicit. For example, the simulation results indicate that our clustering algorithm runs significantly faster than our heuristic algorithm. However, our heuristic algorithm can identify important changes at the beginning of the search and can discover better results than the clustering algorithm. We successfully applied the two algorithms to cases from the automotive and the healthcare domain. During these case studies, the practical relevance and benefit of our work has become evident once more.
A twin study of rheumatoid arthritis in the Japanese population

Abstract Objectives: Rheumatoid arthritis (RA) is the most common immune-related inflammatory arthritis affecting 0.5–1.0% of the population. Both genetic and environmental factors are associated with RA onset. Twin studies reported from European countries estimated heritability of RA as 53–65%. However, no twin studies have been reported from Asian countries. Methods: We collected a total of 43 monozygotic and 43 dizygotic twins from 7550 patients with RA and obtained information of RA status in the twin pairs. We characterized RA patients whose twin siblings had RA. Variance components analysis was performed to estimate heritability in RA in the Japanese population. Results: Four and one patients with RA over 43 monozygotic (9.3%) and 43 dizygotic twins (2.3%), respectively, had twin siblings with RA. All the patients whose information of sero-positivity was available and whose twin siblings had RA were sero-positive. Heritability of RA was estimated as 62.2% and 56.1% in the AE and ACE models, respectively. The estimated heritability was comparable with those reported in the Europeans, compatible with previous overlap of RA susceptibility genes between Japanese and European populations. Conclusions: Heritability of RA onset in the Japanese population is estimated to be comparable with that in European populations.
Adaptation and evaluation of generic model matching strategies. (Une approche pour l'adaptation et l'évaluation de stratégies génériques d'alignement de modèles)

Model matching is gaining importance in Model-Driven Engineering (MDE). The goal of model matching is to identify correspondences between the elements of two metamodels or two models. One of the main application scenarios is the derivation of model transformations from metamodel correspondences. Model correspondences, in turn, offer a potential to address other MDE needs. Manually finding of correspondences is labor intensive and error-prone when (meta)models are large. To automate the process, research community proposes matching strategies combining multiple heuristics. A problem is that the heuristics are limited to certain representation formalisms instead of being reusable. Another problem is the difficulty to systematically evaluate the quality of matching strategies. This work contributes an approach to deal with the mentioned issues. To promote reusability, the approach consists of strategies whose heuristics are loosely coupled to a given formalism. To systematize model matching evaluation, the approach automatically extracts a large set of modeling test cases from model repositories, and uses megamodels to guide strategy execution. We have validated the approach by developing the AML domain specific language on top of the AmmA platform. By using AML, we have implemented a library of strategies and heuristics. To demonstrate that our approach goes beyond the modeling context, we have tested our strategies on ontology test cases as well. At last, we have contributed three use cases that show the applicability of (meta)model matching to interesting MDE topics: model co-evolution, pivot metamodel evaluation, and model synchronization
The Association of Health Risks With Workers’ Compensation Costs

Thepurpose of this study was to investigate the association between health risksand workers’ compensation (WC) costs. The 4-year study used Health RiskAppraisal data and focused on 1996-to-1999 WC costs among XeroxCorporation’s long-term employees. High WC costs were related toindividual health risks, especially Health Age Index (a measure ofcontrollable risks), smoking, poor physical health, physical inactivity, andlife dissatisfaction. WC costs increased with increasing health risk status(low-risk to medium-risk to high-risk). Low-risk employees had the lowestcosts. In this population, 85% of WC costs could be attributed to excess risks(medium- or high-risk) or non-participation. Among those with claims, asavings of $1238 per person per year was associated with Health Risk Appraisalparticipation. Addressing WC costs by focusing on employee health statusprovides an important additional strategy for health promotionprograms.
Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines.

SETTING A hospital-based study at the Makati Medical Center, Makati City, Philippines, a hyperendemic area for tuberculosis (TB). OBJECTIVE To determine the susceptibility of Mycobacterium tuberculosis to ciprofloxacin and ofloxacin. DESIGN Retrospective analysis of drug susceptibility tests (DST) of M. tuberculosis isolated from 1995-2000. RESULTS Resistance to ciprofloxacin was 26.8%, ofloxacin 35.3%, and multidrug resistance (MDR) was 17.2%. Of the MDR strains, 51.4% were resistant to ciprofloxacin and ofloxacin. Acquired resistance was significantly higher for all first-line drugs and for ciprofloxacin, but not for ofloxacin. A significant increase in resistance to ciprofloxacin and ofloxacin was noted compared to 1989-1994, while resistance to the firstline drugs was not significantly different. CONCLUSION Ciprofloxacin and ofloxacin are now a significantly less effective alternative therapy in tuberculosis, particularly MDR-TB, due to a selection pressure from their widespread use in the treatment of TB and possibly other infections in the community, which is hyperendemic for tuberculosis.
Invadopodia, Regulation, and Assembly in Cancer Cell Invasion

Abstract The occurrence of invadopodia has been, since its characterization, a hallmark of cancerous cell invasion and metastasis. These structures are now the subject of a controversy concerning their cellular function, molecular regulation, and assembly. The terms invadopodia and podosomes have been used interchangeably since their discovery back in 1980. Since then, these phenotypes are now more established and accepted by the scientific community as vital structures for 3D cancer cell motility. Many characteristics relating to invadopodia and podosomes have been elucidated, which might prove these structures as good targets for metastasis treatment. In this review, we briefly review the actin reorganization process needed in most types of cancer cell motility. We also review the important characteristics of invadopodia, including molecular components, assembly, markers, and the signaling pathways, providing a comprehensive model for invadopodia regulation.
REINNERVATION OF SYNGENEIC PANCREATICO-DUODENAL GRAFTS IN RATS1

Background. Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngeneic pancreas grafts were reinnervated in rats. Methods. Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duodenum were removed 4 or 40 weeks after implantation, and processed for indirect immunofluorescence using antibodies directed against vasoactive intestinal peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5. Results. Four weeks after transplantation a moderate to rich number of protein gene product 9.5-positive nerve fibers were found homogeneously distributed through the pancreas, probably representing the intrapancreatic nervous system, because the grafted pancreas lacked both a sympathetic (TH/NPY) and sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of the animals there was a marked increase in SP-immunoreactive nerves (lacking CGRP), most conspicuous in the duodenal portion, both 4 and 40 weeks after transplantation probably secondary to a chronic pancreatitis. The fibers seemed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive intestinal peptide-containing nerve fibers probably also emanating from local ganglia could be seen throughout the grafted pancreas both 4 and 40 weeks after transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerve fibers were still virtually lacking in the pancreas. To trace the origin of the ingrowing nerve fibers, the tracer True Blue was injected into the grafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the celiac ganglion (presumably sympathetic nerves) and few in dorsal root ganglia (sensory nerves). Conclusions. The data suggest that the transplanted rat pancreas becomes reinnervated by mainly sympathetic nerve fibers.
Perianal Condyloma Acuminata: Factors that Contribute to the Recurrence

Introduction . Condyloma Acuminata (CA) is the most common sexually transmitted disease caused by HPV with high recurrence rate up to 70%. Factors contribute to the recurrence such as age, site of predilection, previous treatment, HIV infection and sexual behavior were noted in perianal CA. To date the correlation of these factors to the recurrence remains unknown. Method . A cross sectional study was conducted. Patients with history of CA managed in clinic of surgery during period of January 2010 to June 2015 were reviewed. Subject characteristics, i.e. age, infected site, previous treatment, HIV infection and sexual behavior and recurrence were the variables of the study. Data collected from medical record were statistically analyzed. Significant correlation found if p value <0.05. Results. There were 48 subjects with the history of CA. On the analysis, age variable has a significant correlation with the recurrence p = 0.008 (OR = 5.83; 95% CI 1.66–20.56;). The recurrence was higher in productive age compared to non–productive age. Previous anal CA and high risk negative sexual behavior showed a higher recurrence risk than previous non–anal CA and positive sexual behavior (OR = 1.89 and 2.14, respectively). Conclusion. There was significant correlation between age and CA recurrence, anal CA and negative sexual behavior showing 1.89 and 2.14 times, respectively more likely to have recurrence
Allosteric interactions across native adenosine-A3 receptor homodimers: quantification using single-cell ligand-binding kinetics

A growing awareness indicates that many G‐protein‐coupled receptors (GPCRs) exist as homodimers, but the extent of the cooperativity across the dimer interface has been largely unexplored. Here, measurement of the dissociation kinetics of a fluorescent agonist (ABA‐X‐BY630) from the human A1 or A3 adenosine receptors expressed in CHO‐K1 cells has provided evidence for highly cooperative interactions between protomers of the A3‐receptor dimer in single living cells. In the absence of competitive ligands, the dissociation rate constants of ABA‐X‐BY630 from A1 and A3 receptors were 1.45 ± 0.05 and 0.57 ± 0.07 min−1, respectively. At the A3 receptor, this could be markedly increased by both orthosteric agonists and antagonists [15‐, 9‐, and 19‐fold for xanthine amine congener (XAC), 5'‐(N‐ethyl carboxamido)adenosine (NECA), and adenosine, respectively] and reduced by coexpression of a nonbinding (N250A) A3‐receptor mutant. The changes in ABA‐X‐BY630 dissociation were much lower at the A1 receptor (1.5‐, 1.4‐, and 1.5‐fold). Analysis of the pEC50 values of XAC, NECA, and adenosine for the ABA‐X‐BY630‐occupied A3‐receptor dimer yielded values of 6.0 ± 0.1, 5.9 ± 0.1, and 5.2 ± 0.1, respectively. This study provides new insight into the spatial and temporal specificity of drug action that can be provided by allosteric modulation across a GPCR homodimeric interface. —May, L. T. , Bridge, L. J., Stoddart, L. A. , Briddon, S. J., Hill, S. J. Allosteric interactions across native adenosine‐A3 receptor homodimers: quantification using single‐cell ligand‐binding kinetics. FASEB J. 25, 3465–3476 (2011). www.fasebj. org
Possible therapeutic effect of direct haemoperfusion with a polymyxin B immobilized fibre column (PMX‐DHP) on pulmonary oxygenation in acute exacerbations of interstitial pneumonia

Background and objective: Acute exacerbations of interstitial pneumonias (IP) can occasionally occur, and have an extremely poor prognosis. Recently, direct haemoperfusion with a polymyxin B immobilized fibre column (PMX‐DHP) was shown to have a beneficial effect in acute exacerbations of IPF. However, little is known about the efficacy of PMX‐DHP in acute exacerbations of other IP. This study investigated the effectiveness and safety of PMX‐DHP in acute exacerbations of IP.
Identification of four candidate cGMP targets in Dictyostelium

In Dictyostelium, a transient increase in intracellular cGMP is important for cytoskeletal rearrangements during chemotaxis. There must be cGMP-binding proteins in Dictyostelium that regulate key cytoskeletal components after treatment with chemoattractants, but to date, no such proteins have been identified. Using a bioinformatics approach, we have found four candidate cGMP-binding proteins (GbpA–D). GbpA and -B have two tandem cGMP-binding sites downstream of a metallo β-lactamase domain, a superfamily that includes cAMP phosphodiesterases. GbpC contains the following nine domains (in order): leucine-rich repeats, Ras, MEK kinase, Ras guanine nucleotide exchange factor N-terminal (RasGEF-N), DEP, RasGEF, cGMP-binding, GRAM, and a second cGMP-binding domain. GbpD is related to GbpC, but is much shorter; it begins with the RasGEF-N domain, and lacks the DEP domain. Disruption of the gbpC gene results in loss of all high-affinity cGMP-binding activity present in the soluble cellular fraction. GbpC mRNA levels increase dramatically 8 h after starvation is initiated. GbpA, -B, and -D mRNA levels show less dramatic changes, with gbpA mRNA levels highest 4 h into starvation, gbpB mRNA levels highest in vegetative cells, and gbpD levels highest at 8 h. The identification of these genes is the first step in a molecular approach to studying downstream effects of cGMP signaling in Dictyostelium.
A Comparative Analysis of Novel Fluorescent Proteins as Reporters for Gene Transfer Studies

We evaluated novel fluorescent proteins (FPs) as reporters for gene transfer in animals and cells with the aim to develop more-sensitive assays for vector development and the optimization of gene transfer strategies in gene therapy. Adeno-associated virus serotype 5 vectors carrying an expression cassette with a chicken β-actin promoter encoding the green FPs ZsGreen1, AcGFP1, hMGFP (with and without intron), and EGFP and the red FPs DsRed2 and TurboRFP were administered to mice at identical doses for each organ to target liver, lung, and muscle. Despite the fact that all FPs were expressed from an identical vector backbone, the observed number of fluorescent cells and fluorescence intensities varied between, but was consistent within, each combination of a specific protein and organ. The highest number of fluorescent cells was observed in liver with EGFP and in lung with ZsGreen1 and EGFP. In muscle, AcGFP1 and ZsGreen1 produced the most-intense fluorescence in fibers. In contrast, in culture cells, ZsGreen1 showed substantially stronger fluorescence than all other proteins. Our data demonstrate that each FP has tissue-specific expression profiles that need to be taken into consideration when comparing the performance of vectors in different organs.
Balancing in the U.S. States, 1978–2009

Since the Civil War, the president’s party has lost seats in the U.S. House of Representatives in all but three midterm election cycles. Many attribute this pattern to “balancing” by moderate voters who prefer a Democratic Congress when Republicans control the White House, and vice versa. Although a number of scholars have tested the balancing hypothesis, the debate remains unsettled. We argue that the U.S. states provide an excellent way to analyze the issue further. Similar to the national government, states feature an executive and (in most cases) a bicameral legislature whose members come up for election in both gubernatorial and state midterm years. If voters balance, one should observe such behavior in state elections when an executive’s partisanship is known and a legislative choice is necessary. We examine state legislative elections from 1978 to 2009 and find evidence consistent with the balancing hypothesis.
Insights into mitotic checkpoint by integrating CRISPR and RNAi

ABSTRACT Our recent study of the mitotic checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) revealed several apparent BUB1 knock-out cell lines expressing low levels of BUB1 protein sufficient to support spindle assembly checkpoint activity. This rings alarm bells on the application of CRISPR technology.