julilili42/papers huggingface dataset:
Abstract 98: Point-of-care Testing of Coagulation in Patients Treated With the Non-vitamin K Antagonist Oral Anticoagulant Edoxaban
2018-01-22

Introduction: Edoxaban, alongside other non-vitamin K antagonist oral anticoagulants (NOAC), is increasingly used for stroke prevention in patients with atrial fibrillation. Despite treatment, stroke rate in these patients remains one to two percent per year. In this growing population of edoxaban/NOAC-treated stroke patients, rapid assessment of coagulation would be useful to guide the decision for thrombolysis or reversal therapy in case of a neurovascular emergency. However, no data exists on the effect of edoxaban on available point-of-care test (POCT) systems. Hypothesis: Test assays of the commercially available CoaguChek® (CC) and Hemochron® are able to detect clinically relevant concentrations of edoxaban in a blood sample. Methods: We studied patients receiving their first dose of edoxaban. Subjects receiving other anticoagulants were excluded. Six blood samples were collected from each patient: before drug intake, 30 minutes, one, two, and eight hours after intake, as well as before the next dose. Coagulation-POCT and mass spectrometry for gold standard-determination of edoxaban plasma concentration were performed at each time point. Results: 120 blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban concentrations ranged from 0 to 302ng/mL. CC-INR ranged from 0.9 to 2.3. Pearson’s correlation coefficient showed a strong correlation between CC-INR and edoxaban concentrations (r=0.73). Edoxaban concentrations &gt; 30ng/mL (threshold for thrombolysis according to the European Stroke Organisation) were detected by CC-INR ≥ 1.1 with 96% sensitivity and 44% specificity (89% sensitivity and 88% specificity for CC-INR ≥ 1.2; AUC=0.92). Conclusions: Our study represents the first systematic evaluation of coagulation POCT in edoxaban-treated patients. Available coagulation POCT devices may be able to reliably detect clinically relevant edoxaban concentrations in blood samples of stroke patients in the emergency setting. In addition to edoxaban-POCT analyses, we will present further data on NOAC-specific POCT from our SPOCT-NOAC study.
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018
2018-01-23

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.
Viscous Dissipation and Heat Conduction in Binary Neutron-Star Mergers
2018-01-23

Inferring the properties of dense matter is one of the most exciting prospects from the measurement of gravitational waves from neutron star mergers. However, it requires reliable numerical simulations that incorporate viscous dissipation and energy transport as these can play a significant role in the survival time of the post-merger object. We calculate time scales for typical forms of dissipation and find that thermal transport and shear viscosity will not be important unless neutrino trapping occurs, which requires temperatures above 10 MeV and gradients over length scales of 0.1 km or less. On the other hand, if direct-Urca processes remain suppressed, leaving modified-Urca processes to establish flavor equilibrium, then bulk viscous dissipation could provide significant damping to density oscillations right after merger. When comparing with data from state-of-the-art merger simulations, we find that the bulk viscosity takes values close to its resonant maximum in a typical merger, motivating a more careful assessment of the role of bulk viscous dissipation in the gravitational-wave signal from merging neutron stars.
The role of the clinician in the multi‐omics era: are you ready?
2018-01-23

Abstract Since Garrod's first description of alkaptonuria in 1902, and newborn screening for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive, personalized, and participatory) has been a reality for the clinician serving patients with inherited metabolic diseases. The era of high‐throughput technologies promises to accelerate its scale dramatically. Genomics, transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics offer an amazing opportunity for holistic investigation and contextual pathophysiologic understanding of inherited metabolic diseases for precise diagnosis and tailored treatment. While each of the ‐omics technologies is important to systems biology, some are more mature than others. Exome sequencing is emerging as a reimbursed test in clinics around the world, and untargeted metabolomics has the potential to serve as a single biochemical testing platform. The challenge lies in the integration and cautious interpretation of these big data, with translation into clinically meaningful information and/or action for our patients. A daunting but exciting task for the clinician; we provide clinical cases to illustrate the importance of his/her role as the connector between physicians, laboratory experts and researchers in the basic, computer, and clinical sciences. Open collaborations, data sharing, functional assays, and model organisms play a key role in the validation of ‐omics discoveries. Having all the right expertise at the table when discussing the diagnostic approach and individualized management plan according to the information yielded by ‐omics investigations (e.g., actionable mutations, novel therapeutic interventions), is the stepping stone of P4 medicine. Patient participation and the adjustment of the medical team's plan to his/her and the family's wishes most certainly is the capstone. Are you ready?
Determination of pitch rotation in a spherical birefringent microparticle
2018-01-23

Rotational motion of a three dimensional spherical microscopic object can happen either in pitch, yaw or roll fashion. Among these, the yaw motion has been conventionally studied using the intensity of scattered light from birefringent microspheres through crossed polarizers. Up until now, however, there is no way to study the pitch motion in spherical microspheres. Here, we suggest a new method to study the pitch motion of birefringent microspheres under crossed polarizers by measuring the 2-fold asymmetry in the scattered signal either using video microscopy or with optical tweezers. We show a couple of simple examples of pitch rotation determination using video microscopy for a microsphere attached with a kinesin molecule while moving along a microtubule and of a particle diffusing freely in water.
Implicit and Explicit Motivational Tendencies to Faces Varying in Trustworthiness and Dominance in Men
2018-01-23

Motivational tendencies to happy and angry faces are well-established, e.g., in the form of aggression. Approach-avoidance reactions are not only elicited by emotional expressions, but also linked to the evaluation of stable, social characteristics of faces. Grounded in the two fundamental dimensions of face-based evaluations proposed by Oosterhof and Todorov (2008), the current study tested whether emotionally neutral faces varying in trustworthiness and dominance potentiate approach-avoidance in 50 healthy male participants. Given that evaluations of social traits are influenced by testosterone, we further tested for associations of approach-avoidance tendencies with endogenous and prenatal indicators of testosterone. Computer-generated faces signaling high and low trustworthiness and dominance were used to elicit motivational reactions in three approach-avoidance tasks, i.e., one implicit and one explicit joystick-based paradigm, and an additional rating task. When participants rated their behavioral tendencies, highly trustworthy faces evoked approach, and highly dominant faces evoked avoidance. This pattern, however, did not translate to faster initiation times of corresponding approach-avoidance movements. Instead, the joystick tasks revealed general effects, such as faster reactions to faces signaling high trustworthiness or high dominance. These findings partially support the framework of Oosterhof and Todorov (2008) in guiding approach-avoidance decisions, but not behavioral tendencies. Contrary to our expectations, neither endogenous nor prenatal indicators of testosterone were associated with motivational tendencies. Future studies should investigate the contexts in which testosterone influences social motivation.
Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in Adipocytes Is Associated With Dual Signaling Defects Mediated by PKC-ζ
2018-01-23

A hyperglycemic and hyperinsulinemic environment characteristic of type 2 diabetes causes insulin resistance. In adipocytes, defects in both insulin sensitivity and maximum response of glucose transport have been demonstrated. To investigate the molecular mechanisms, freshly isolated rat adipocytes were incubated in control (5.6 mM glucose, no insulin) and high glucose (20 mM)/high insulin (100 nM) (HG/HI) for 18 hours to induce insulin resistance. Insulin-resistant adipocytes manifested decreased sensitivity of glucose uptake associated with defects in insulin receptor substrate (IRS)-1 Tyr phosphorylation, association of p85 subunit of phosphatidylinositol-3-kinase, Akt Ser473 and Thr308 phosphorylation, accompanied by impaired glucose transporter 4 translocation. In contrast, protein kinase C (PKC)-ζ activity was augmented by chronic HG/HI. Inhibition of PKC-ζ with a specific cell-permeable peptide reversed the signaling defects and insulin sensitivity of glucose uptake. Transfection of dominant-negative, kinase-inactive PKC-ζ blocked insulin resistance, whereas constitutively active PKC-ζ recapitulated the defects. The HG/HI incubation was associated with stimulation of IRS-1 Ser318 and Akt Thr34 phosphorylation, targets of PKC-ζ. Transfection of IRS-1 S318A and Akt T34A each partially corrected insulin signaling, whereas combined transfection of both completely normalized insulin signaling. In vivo hyperglycemia/hyperinsulinemia in rats for 48 hours similarly resulted in activation of PKC-ζ and increased phosphorylation of IRS-1 Ser318 and Akt Thr34. These data indicate that impairment of insulin signaling by chronic HG/HI is mediated by dual defects at IRS-1 and Akt mediated by PKC-ζ.
Fear of Being Laughed at in Borderline Personality Disorder
2018-01-23

Building on the assumption of a possible link between biases in social information processing frequently associated with borderline personality disorder (BPD) and the occurrence of gelotophobia (i.e., a fear of being laughed at), the present study aimed at evaluating the prevalence rate of gelotophobia among BPD patients. Using the Geloph<15> , a questionnaire that allows a standardized assessment of the presence and severity of gelotophobia symptoms, rates of gelotophobia were assessed in a group of 30 female BPD patients and compared to data gathered in clinical and non-clinical reference groups. Results indicate a high prevalence of gelotophobia among BPD patients with 87% of BPD patients meeting the Geloph<15> criterion for being classified as gelotophobic. Compared to other clinical and non-clinical reference groups, the rate of gelotophobia among BPD patients appears to be remarkably high, far exceeding the numbers reported for other groups in the literature to date, with 30% of BPD patients reaching extreme levels, 37% pronounced levels, and 20% slight levels of gelotophobia.
Fused thia-heterocycles via isothiocyanates. Part II. A convenient synthesis of some new thieno[2,3-b]thiopyran-4-one derivatives
2018-01-23

Abstract A facile synthesis of some methyl 5-(arylamino)-4-oxothieno[2,3- b ]thiopyran-6-carboxylates 6a–g is achieved via direct reaction of deprotonated methyl 3-(2,5-dichlorothien-3-yl)-3-oxopropanoate with aryl isothiocyanates in anhydrous tetrahydrofuran (THF) under reflux. Upon saponification of 6a,b , the ester group is eliminated, most logically via decarboxylation of the presumably-formed carboxyl group. Structures of the new compounds 6a–g and 7a,b are supported by microanalytical and spectral [NMR, MS electron impact (EI) and HRMS] data.
Genetic Diversity of the Plasmodium falciparum Glutamate-Rich Protein R2 Region Before and Twelve Years after Introduction of Artemisinin Combination Therapies among Febrile Children in Nigeria
2018-01-23

The genetic diversity of glutamate-rich protein ( GLURP ) R2 region in Plasmodium falciparum isolates collected before and 12 years after the introduction of artemisinin combination treatment of malaria in Osogbo, Osun State, Nigeria, was compared in this study. Blood samples were collected on filter paper in 2004 and 2015 from febrile children from ages 1–12 years. The R2 region of the GLURP gene was genotyped using nested polymerase chain reaction and by nucleotide sequencing. In all, 12 GLURP alleles were observed in a total of 199 samples collected in the two study years. The multiplicity of infection (MOI) marginally increased over the two study years; however, the differences were statistically insignificant (2004 samples MOI = 1.23 versus 2015 samples MOI = 1.47). Some alleles were stable in their prevalence, whereas two GLURP alleles, VIII and XI, showed considerable variability between both years. This variability was replicated when GLURP sequences from other regions were compared with ours. The expected heterozygosity ( He ) values ( He = 0.87) were identical for the two groups. High variability in the rearrangement of the amino acid repeat units in the R2 region were observed, with the amino acid repeat sequence DKNEKGQHEIVEVEEILPE more prevalent in both years, compared with the two other repeat sequences observed in the study. The parasite population characterized in this study displayed extensive genetic diversity. The detailed genetic profile of the GLURP R2 region has the potential to help guide further epidemiological studies aimed toward the rational design of novel chemotherapies that are antagonistic toward malaria.
Low plasma protein Z levels are associated with an increased risk for perioperative bleedings
2018-01-23

Abstract Background and objectives Protein Z (PZ) deficiency has been implicated both in bleeding diatheses and in thrombophilia. Considering its ambiguous nature and the conflicting clinical data so far, we set out to evaluate the impact of low PZ on perioperative bleeding in patients who underwent surgical ( ENT ) interventions involving a high risk of bleeding. Patients and methods After exclusion of other coagulation disorders, 154 Patients were stratified into quartiles according to PZ plasma concentrations to evaluate the relation between PZ and bleeding complications. Results Low PZ levels were associated with increased blood loss ( P &lt; .001), increased need for blood transfusions ( P &lt; .001), and a higher rate of surgical revisions ( P = .009) in a concentration‐dependent fashion. Low PZ caused earlier (within 24 hours) and repetitive bleedings ( P = .005). The number of major bleeding episodes was significantly increased when low PZ was combined with bleeding history ( P &lt; .05). Finally, ROC analyses confirmed the predictive value of low PZ for bleeding complications and PZ ‐thresholds for clinical practice were determined. Conclusions Low PZ appears to be an underestimated risk factor for perioperative bleeding. Determination of PZ plasma concentrations might be useful in the preoperative workup in patients with a bleeding history, when detailed clotting analyses remain inconclusive.
Harmonizing semantic annotations for computational models in biology
2018-01-23

Abstract Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition, and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current semantic annotation practices among the COmputational Modeling in BIology NEtwork (COMBINE) community and provide a set of recommendations for building a consensus approach to semantic annotation.
Transsaccadic transfer of distortion adaptation in a natural environment
2018-01-23

Spatially varying distortions in optical elements-for instance prisms and progressive power lenses-modulate the visual world disparately in different visual areas. Saccadic eye movements in such a complexly distorted environment thereby continuously alter the retinal location of the distortions. Yet the visual system achieves perceptual constancy by compensating for distortions irrespective of their retinal relocations at different fixations. Here, we assessed whether the visual system retains its plasticity to distortions across saccades to attain stability. Specifically, we tapped into reference frames of geometric skew-adaptation aftereffects to evaluate the transfer of retinotopic and spatiotopic distortion information across saccades. Adaptation to skew distortion of natural-image content was tested at retinotopic and spatiotopic locations after a saccade was executed between adaptation and test phases. The skew-adaptation information was partially transferred to a new fixation after a saccade. Significant adaptation aftereffects were obtained at both retinotopic and spatiotopic locations. Conceivably, spatiotopic information was used to counterbalance the saccadic retinal shifts of the distortions. Therefore, distortion processing in a natural visual world does not start anew at each fixation; rather, retinotopic and spatiotopic skew information acquired at previous fixations are preserved to mediate stable perception during eye movements.
A Modular Approach of Decision-Making in the Context of Robot Navigation in Domestic Environments
2018-01-23

Decision processes in Artificial Intelligence are often organized hierarchically. One example is robot navigation with a global path planner and a local executor. This paper examines whether a shift from optimizing the two typical modules in navigation towards a dynamic interaction of more, not necessarily hierarchically linked, modules leads to robust navigation behavior. We empirically evaluate different organizations of modules for navigation in a simulated household with a simulated PR2 robot.
A Developer-oriented Hoare Logic
2018-01-23

We present a Hoare logic and verification system designed to be understandable by developers. We discuss both the underlying considerations on the design of the system, and the formal and technical background of the tools. We show that the goals have been achieved by typical examples.
The determinants of food choice
2018-01-24

Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.
BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer
2018-01-24

To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.
The Nonlinear Interaction of Person and Situation (Nips) Model: Theory and Empirical Evidence
2018-01-24

Despite the broad consensus in psychology that human behaviour is influenced by the interaction between characteristics of the person and characteristics of the situation, not much is known about the precise shape of this person–situation (P × S) interaction. To address this issue, we introduce and test the nonlinear interaction of person and situation (NIPS) model. The NIPS model can be applied to explain contradictory research results, offers a more accurate prediction of behaviour, and can be applied to any trait. In three studies and with three different analytical approaches, we test the NIPS model and its implications. In the pre–study, we test whether variability in participants’ behaviour is smaller in extreme aggression–provoking and jealousy–inducing situations than in moderate situations, suggesting the effect of ‘strong’ situations at the extremes of the situation continuum. In Studies 1 and 2, we test the nonlinear relation between person and situation variables in predicting behaviour in within–subject designs and provide support for the predictions of the NIPS model. Future lines of research with the NIPS model are discussed. Copyright © 2018 European Association of Personality Psychology