Miracle-dz/UniFAR-FTUs huggingface dataset:
Reference Values for Kaolin-Activated Thromboelastography in Healthy Children

BACKGROUND:The hemostatic system of children changes with age and differs significantly from the hemostatic system of adults. Age-specific reference values are therefore required for most hemostatic variables. Thromboelastography (TEG®) is a point-of-care coagulation test that may provide superior evaluation and management of coagulopathies after cardiac surgery, when large-dose unfractionated heparin is administered for cardiopulmonary bypass. In this study, we established reference values for kaolin-activated TEG in healthy children, to facilitate accurate interpretation of pediatric TEG results. METHODS:Kaolin-activated TEG was performed on 100 healthy children undergoing elective day surgery and 25 healthy adult volunteers. The following TEG variables were recorded: reaction time, coagulation time, &agr; angle, maximum amplitude, percentage lysis 30 min after maximum amplitude was reached, and the coagulation index. Differences between age-groups were evaluated using analysis of variance. RESULTS:Age-specific reference values for kaolin-activated TEG in healthy children between 1 mo and 16 yr of age are presented. No significant differences between children and adults were observed. CONCLUSIONS:TEG results, from a particular clinical setting, must be compared to age-specific, as well as analyzer- and activator-specific, reference values to allow for correct interpretation of the results. Reference values provided here will be of use in acute clinical situations where a practical monitor of hemostasis is required.
A Dynamic Lumped Parameter Model of the Left Ventricular Assisted Circulation

A lumped parameter model of the cardiovascular system (CVS) and its interaction with an implantable rotary blood pump (iRBP) is presented. The CVS model consists of the heart, the systemic and the pulmonary circulations. The pump model is made up of three differential equations, i.e. the motor equation, the torque equation and the hydraulic equation. Qualitative comparison with data from ex vivo porcine experiments suggests that the model is able to simulate different physiologically significant pumping states with varying pump speed set points. The combined CVS- iRBP model is suitable for use as a tool for investigating changes in the circulatory system parameters in the presence of the pump, and for testing control algorithms.
The effect of mGlu8 deficiency in animal models of psychiatric diseases

The metabotropic glutamate receptor subtype 8 (mGlu8) is presynaptically located and regulates the release of the transmitter. Dysfunctions of this mechanism are involved in the pathophysiology of different psychiatric disorders. mGlu8 deficient mice have been previously investigated in a range of studies, but the results are contradictory and there are still many open questions. Therefore, we tested mGlu8‐deficient animals in different behavioral tasks that are commonly used in neuropsychiatric research. Our results show a robust contextual fear deficit in mGlu8‐deficient mice. Furthermore, novel object recognition, chlordiazepoxide‐facilitated extinction of operant conditioning and the acoustic startle response were attenuated by mGlu8 deficiency. We found no changes in sensory processing, locomotor activity, prepulse inhibition, phencyclidine‐induced changes in locomotion or prepulse inhibition, operant conditioning, conditioned fear to a discrete cue or in animal models of innate fear and post‐traumatic stress disorder. We conclude that mGlu8 might be a potential target for disorders with pathophysiological changes in brain areas where mGlu8 modulates glutamate and gamma‐amino butyric acid (GABA) transmission. Our data especially point to anxiety disorders involving exaggerated contextual fear, such as generalized anxiety disorders, and to conditions with disturbed declarative memory.
Pharmacokinetics and dosimetry studies for optimization of anti-carcinoembryonic antigen x anti-hapten bispecific antibody-mediated pretargeting of Iodine-131-labeled hapten in a phase I radioimmunotherapy trial.

PURPOSE Pharmacokinetics and dosimetry of hMN-14 x m734 bispecific monoclonal antibody (BsMAb) and (131)I-labeled di-diethylenetriaminepentaacetic acid-indium ((131)I-hapten) were studied to optimize pretargeted radioimmunotherapy. EXPERIMENTAL DESIGN Thirty-five patients with carcinoembryonic antigen-expressing tumors were included. In a first group of 12 patients, (131)I-trace-labeled BsMAb doses were escalated from 10 to 100 mg/m(2), and 3.7 GBq of (131)I-hapten were administered 7 days later. In a second group, 12 patients received 75 mg/m(2) BsMAb and 2.6-4.2 GBq of (131)I-hapten 5 days later. The BsMAb dose was then reduced to 40 mg/m(2), and 10 patients received 1.9-5.5 GBq of (131)I-hapten. Blood samples were collected. Biodistribution was monitored by quantitative scintigraphy. RESULTS Directly labeled BsMAb pharmacokinetics was described by two exponentials: half-lives were 8.1 h (2.0-18.1 h) and 48.2 h (22.8-79.4 h); blood clearance was 123 ml/h (64-195 ml/h). With a 7-day interval, 10 or 30 mg/m(2) BsMAb resulted in fast elimination and very low tumor uptake of hapten, whereas 50 or 100 mg/m(2) resulted in favorable tumor accretion. With 75 mg/m(2) BsMAb and a 5-day interval, hapten clearance was 152 ml/h (81-298 ml/h). Calculated radiation dose to tumor was 3.9 Gy/GBq (0.4-22.4 Gy/GBq) for the hapten, compared with 2.0 Gy/GBq (0.3-3.8 Gy/GBq) for the BsMAb, but hematological toxicity prevented dose escalation. Reduction of the BsMAb dose to 40 mg/m(2) accelerated hapten clearance to 492 ml/h (113-2544 ml/h) and reduced hematological toxicity without compromising tumor uptake [5.2 Gy/GBq (0.5-12.6 Gy/GBq)]. CONCLUSIONS Optimized BsMAb doses and time interval will allow for the administration of higher, tumoricidal, activity doses.
Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea‐pig

Intestinal secretion is regulated by submucosal neurones of the enteric nervous system. Inflammation of the intestines leads to aberrant secretory activity; therefore we hypothesized that the synaptic and electrical behaviours of submucosal neurones are altered during colitis. To test this hypothesis, we used intracellular microelectrode recording to compare the excitability and synaptic properties of submucosal neurones from normal and trinitrobenzene sulphonic acid (TNBS)‐inflamed guinea‐pig colons. Inflammation differentially affected the electrophysiological characteristics of the two functional classes of submucosal neurones. AH neurones from inflamed colons were more excitable, had shorter action potential durations and reduced afterhyperpolarizations. Stimulus‐evoked fast and slow excitatory postsynaptic potentials (EPSPs) in S neurones were larger during colitis, and the incidence of spontaneous fast EPSPs was increased. In control preparations, fast EPSPs were almost completely blocked by the nicotinic receptor antagonist hexamethonium, whereas fast EPSPs in inflamed S neurones were only partially inhibited by hexamethonium. In inflamed tissues, components of the fast EPSP in S neurones were sensitive to blockade of P2X and 5‐HT3 receptors while these antagonists had little effect in control preparations. Control and inflamed S neurones were equally sensitive to brief application of acetylcholine, ATP and 5‐HT, suggesting that synaptic facilitation was due to a presynaptic mechanism. Immunoreactivity for 5‐HT in the submucosal plexus was unchanged by inflammation; this indicates that altered synaptic transmission was not due to anatomical remodelling of submucosal nerve terminals. This is the first demonstration of alterations in synaptic pharmacology in the enteric nervous system during inflammation.
Performance analysis of OFDM systems for broadband power line communications under impulsive noise and multipath effects

The impulsive noise and multipath effects are the main reasons to cause bit errors in power line communications. In this paper, the bit error rate (BER) performance of the orthogonal frequency division multiplexing (OFDM) system under the impulsive noise and multipath effects are theoretically analyzed in terms of closed form formulas. Through the analysis, it is shown that OFDM can mitigate the adverse effect of the impulsive noise and only the heavily disturbed impulsive noise will interfere the BER performance of the OFDM system. It is also shown that the adverse effect of multipath is more serious than that of impulsive noise. In this paper, the guard interval is used to improve the BER performance of the OFDM system. As the longer guard interval is inefficient in using the signal power, the optimum guard interval that can achieve the best BER performance is studied.
Biochemical and ultrastructural study of Blastocystis hominis

This study was prompted by the paradox of strong presence of mitochondria in an anaerobic protozoan, recently reclassified from the yeasts. Stemming from publication in 1911 to 1912, Blastocystis hominis has been generally accepted as a harmless intestinal yeast of humans, with short standardized textbook (parasitology) descriptions, even to the present day. Reports since 1967 have changed the classification of B. hominis from yeast to protozoan (Sarcodina), and this has been followed by interest in B. hominis-caused disease, resulting in documentation of disease in humans and other primates. In this study of B. hominis, the basic ultrastructure of the mitochondria was shown by thin-section electron microscopy to be identical to that of an archetypical mitochondrion. There were hundreds of them in large B. hominis cells (100 to 200 microns in diameter). Mitochondria were confined to a peripheral ring of cytoplasm bounded by the outer cell membrane (there is no cell wall) and the membrane of the large, spherical, organelle-free central body that constitutes 75% of the cell's volume. Mitochondria tended to surround the cell's usual two to four nuclei. Rhodamine 123 stained the mitochondria selectively, visualized by fluorescence microscopy. The cell was devoid of cytochromes. Addition of 0.1% cytochrome c to the growth medium increased utilization of glucose by 34% and that of lactate by 17%. Furthermore, it markedly increased the number of mitochondrion-filled cells. At higher concentrations, cytochrome c inhibited the growth of the cells. Despite the presence of large numbers of mitochondria, activities of the mitochondrial enzymes pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, isocitrate dehydrogenase, glutamate dehydrogenase, and cytochrome c oxidase were absent. Thus, the function of the mitochondria in B. hominis remains unknown. Considerable activities of aspartate aminotransferase and alanine aminotransferase were found. Aldolase activity was prominent. Pyruvate decarboxylase was present. Diaphorase and lactate dehydrogenase were detectable but in suspect quantities. Other missing enzymes were gamma glutamyl transpeptidase, alkaline phosphatase (a lysosomal marker), and creatine kinase isoenzymes.
This item is the archived peer-reviewed author-version of: Lipophilicity of PCBs and fatty acids determines their mobilisation from blubber of weaned northern elephant seal pups

Polychlorinated biphenyls (PCBs) exhibit lipophilic properties that lead to their bioaccumulation in adipose tissue. Being characterised by large adipose tissue stores, northern elephant seals ( Mirounga angustirostris ) are contaminated by PCBs. During lipolytic periods such as the post-weaning fast, fatty acids (FAs) from triglycerides and PCBs are mobilised from their blubber. Our results showed that the degree of lipophilicity of FAs and PCBs was a determinant factor affecting their release: the more lipophilic FAs and PCBs tended to be more conserved in blubber over the fast than the less lipophilic ones. This led to an enrichment of more lipophilic compounds within adipocytes with the progression of the fast.
Pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients.

PURPOSE While most patients with ovarian cancer respond to first-line treatment, 50-75% of these patients will eventually relapse. Pegylated liposomal doxorubicin (PLD) is an active agent indicated for the treatment of patients with disease that is refractory to both paclitaxel- and platinum-based regimens, but skin toxicity remains the dose-limiting toxicity of the drug. The primary objective of this retrospective study was to evaluate the activity and safety of this agent in patients with heavily pretreated ovarian cancer. PATIENTS AND METHODS Patients with platinum-refractory/ resistant, paclitaxel-pretreated epithelial ovarian carcinoma were treated with PLD 50 mg/m2 in 4-week courses until disease progression or unacceptable toxicity. All patients had progressive disease (PD) before starting PLD. Primary endpoints were response rate, progression free survival (PFS) and toxicity and secondary endpoints duration of response (DOS) and overall survival (OS). RESULTS Seventeen heavily pretreated patients (median number of previous chemotherapy regimens 3, range 1-5) with taxane- and platinum-refractory disease were analysed. No complete response (CR) was achieved, while 3 (17%) partial responses (PR) and 2 (11%) cases with stable disease (SD) were observed. The median PFS was 15 weeks (range 10-21) and median OS 32 weeks (range 16-47). Palmar plantar erythrodysesthesia (PPE) occurred in 4 (23%) patients and was of grade 4 in 1 (6%) patient. Stomatitis occurred in 3 (17%) patients and was grade 3 in 1 (6%) patient. Grade 3-4 neutropenia occurred in only 2 (12%) patients. No febrile neutropenia was encountered. CONCLUSION Pegylated liposomal doxorubicin is an active and tolerable agent in heavily pretreated epithelial ovarian cancer patients.
A Deficiency in the Flavoprotein of Arabidopsis Mitochondrial Complex II Results in Elevated Photosynthesis and Better Growth in Nitrogen-Limiting Conditions1[W][OA]

Mitochondrial complex II (succinate dehydrogenase [SDH]) plays roles both in the tricarboxylic acid cycle and the respiratory electron transport chain. In Arabidopsis (Arabidopsis thaliana), its flavoprotein subunit is encoded by two nuclear genes, SDH1-1 and SDH1-2. Here, we characterize heterozygous SDH1-1/sdh1-1 mutant plants displaying a 30% reduction in SDH activity as well as partially silenced plants obtained by RNA interference. We found that these plants displayed significantly higher CO2 assimilation rates and enhanced growth than wild-type plants. There was a strong correlation between CO2 assimilation and stomatal conductance, and both mutant and silenced plants displayed increased stomatal aperture and density. By contrast, no significant differences were found for dark respiration, chloroplastic electron transport rate, CO2 uptake at saturating concentrations of CO2, or biochemical parameters such as the maximum rates of carboxylation by Rubisco and of photosynthetic electron transport. Thus, photosynthesis is enhanced in SDH-deficient plants by a mechanism involving a specific effect on stomatal function that results in improved CO2 uptake. Metabolic and transcript profiling revealed that mild deficiency in SDH results in limited effects on metabolism and gene expression, and data suggest that decreases observed in the levels of some amino acids were due to a higher flux to proteins and other nitrogen-containing compounds to support increased growth. Strikingly, SDH1-1/sdh1-1 seedlings grew considerably better in nitrogen-limiting conditions. Thus, a subtle metabolic alteration may lead to changes in important functions such as stomatal function and nitrogen assimilation.
The Non-homologous End-Joining (NHEJ) Mathematical Model for the Repair of Double-Strand Breaks: II. Application to Damage Induced by Ultrasoft X Rays and Low-Energy Electrons

We investigated the kinetics of simple and complex types of double-strand breaks (DSB) using our newly proposed mechanistic mathematical model for NHEJ DSB repair. For this purpose the simulated initial spectrum of DNA DSB, induced in an atomistic canonical model of B-DNA by low-energy single electron tracks, 100 eV to 4.55 keV, and the electrons generated by ultrasoft X rays (CK, AlK and TiK), were subjected to NHEJ repair processes. The activity elapsed time of sequentially independent steps of repair performed by proteins involved in NHEJ repair process were calculated for separate DSB. The repair kinetics of DSBs were computed and compared with published data on repair kinetics obtained by pulsed-field gel electrophoresis method. The comparison shows good agreement for V79-4 cells irradiated with ultrasoft X rays. The average times for the repair of simple and complex DSB confirm that double-strand break complexity is a potential explanation for the slow component of DSB repair observed in V79-4 cells irradiated by ultrasoft X rays.
Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat

The pallido‐subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep–wake cycle, single‐unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non‐anaesthetized head‐restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1–2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical ‘direct/indirect’ model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.
Dynamic changes in host–virus interactions associated with colony founding and social environment in fire ant queens (Solenopsis invicta)

Abstract The dynamics of host–parasite interactions can change dramatically over the course of a chronic infection as the internal (physiological) and external (environmental) conditions of the host change. When queens of social insects found a colony, they experience changes in both their physiological state (they develop their ovaries and begin laying eggs) and the social environment (they suddenly stop interacting with the other members of the mother colony), making this an excellent model system for examining how these factors interact with chronic infections. We investigated the dynamics of host–viral interactions in queens of Solenopsis invicta (fire ant) as they transition from mating to colony founding/brood rearing to the emergence of the first workers. We examined these dynamics in naturally infected queens in two different social environments, where queens either founded colonies as individuals or as pairs. We hypothesized that stress associated with colony founding plays an important role in the dynamics of host–parasite interactions. We also hypothesized that different viruses have different modalities of interaction with the host that can be quantified by physiological measures and genomic analysis of gene expression in the host. We found that the two most prevalent viruses, SINV‐1 and SINV‐2, are associated with different fitness costs that are mirrored by different patterns of gene expression in the host. In fact SINV‐2, the virus that imposes the significant reduction of a queen's reproductive output is also associated with larger changes of global gene expression in the host. These results show the complexity of interactions between S. invicta and two viral parasites. Our findings also show that chronic infections by viral parasites in insects are dynamic processes that may pose different challenges in the host, laying the groundwork for interesting ecological and evolutionary considerations.
Different temporal expression of immunodominant Ro60/60 kDa‐SSA and La/SSB apotopes

Opsonization of apoptotic cardiocytes by maternal anti‐Ro/SSA and anti‐La/SSB antibodies contributes to tissue injury in the neonatal lupus syndrome. The objective of the current study was to quantify the surface membrane expression of Ro/La components during different phases of apoptosis and map the Ro/La apotopes (epitopes expressed on apoptotic cells) bound by cognate antibodies. Multi‐parameter flow cytometry was used to define early and late apoptotic populations and their respective binding by monospecific anti‐Ro and anti‐La IgGs. Anti‐Ro60 bound specifically to early apoptotic Jurkat cells and remained accessible on the cell surface throughout early and late apoptosis. In contrast, anti‐La bound exclusively to late apoptotic cells in experiments controlled for non‐specific membrane leakage of IgG. Ro52 was not accessible for antibody binding on either apoptotic population. The immunodominant NH2‐terminal and RNA recognition motif (RRM) epitopes of La were expressed as apotopes on late apoptotic cells, confirming recent in vivo findings. An immunodominant internal epitope of Ro60 that contains the RRM, and is recognized by a majority of sera from mothers of children with congenital heart block (CHB) and patients with primary Sjögren's syndrome, was also accessible as an apotope on early apoptotic cells. The distinct temporal expression of the immunodominant Ro60 and La apotopes indicates that these intracellular autoantigens translocate independently to the cell surface, and supports a model in which maternal antibody populations against both Ro60 and La apotopes act in an additive fashion to increase the risk of tissue damage in CHB.
Maximum Likelihood Analysis for Heteroscedastic One‐Way Random Effects ANOVA in Interlaboratory Studies

Summary. This article presents results for the maximum likelihood analysis of several groups of measurements made on the same quantity. Following Cochran (1937, Journal of the Royal Statistical Society4(Supple), 102–118; 1954, Biometrics10, 101–129; 1980, in Proceedings of the 25th Conference on the Design of Experiments in Army Research, Development and Testing, 21–33) and others, this problem is formulated as a one‐way unbalanced random‐effects ANOVA with unequal within‐group variances. A reparametrization of the likelihood leads to simplified computations, easier identification and interpretation of multimodality of the likelihood, and (through a non‐informative‐prior Bayesian approach) approximate confidence regions for the mean and between‐group variance.