Miracle-dz/UniFAR-FTUs huggingface dataset:
Gamma regression improves Haseman‐Elston and variance components linkage analysis for sib‐pairs

Existing standard methods of linkage analysis for quantitative phenotypes rest on the assumptions of either ordinary least squares (Haseman and Elston [1972] Behav. Genet. 2:3–19; Sham and Purcell [2001] Am. J. Hum. Genet. 68:1527–1532) or phenotypic normality (Almasy and Blangero [1998] Am. J. Hum. Genet. 68:1198–1199; Kruglyak and Lander [1995] Am. J. Hum. Genet. 57:439–454). The limitations of both these methods lie in the specification of the error distribution in the respective regression analyses. In ordinary least squares regression, the residual distribution is misspecified as being independent of the mean level. Using variance components and assuming phenotypic normality, the dependency on the mean level is correctly specified, but the remaining residual coefficient of variation is constrained a priori. Here it is shown that these limitations can be addressed (for a sample of unselected sib‐pairs) using a generalized linear model based on the gamma distribution, which can be readily implemented in any standard statistical software package. The generalized linear model approach can emulate variance components when phenotypic multivariate normality is assumed (Almasy and Blangero [1998] Am. J. Hum Genet. 68: 1198–1211) and is therefore more powerful than ordinary least squares, but has the added advantage of being robust to deviations from multivariate normality and provides (often overlooked) model‐fit diagnostics for linkage analysis. Genet Epidemiol 26:97–107, 2004. © 2004 Wiley‐Liss, Inc.
An age-related decline of CD62L and vaccine response

Aging process can affect T cell and antibody response to vaccination and an age-related decline in the expression of CD62L on CD8+ T-lymphocyte is one of the important factors that contribute. A recent report demonstrated that percentage of CD3+CD8+CD62L+ cells and CD8+ T-lymphocyte microRNA-92a levels significantly decline with the age and were positively correlated. These results suggested that the age-related attrition of human naïve T cells could be connected to a reduced microRNA-92a in T-lymphocytes and downregulation of the microRNA-92a level might indicate exhaustion of naïve T-cells due to alteration of the immunologic condition with aging. Further studies are necessary to evaluate whether targeting microRNA-92a as microRNA mimics could be one of the therapeutic strategies in improving vaccine response in elderly.
CEOP-21 Versus CEOP-14 Chemotherapy With or Without Rituximab for the First-Line Treatment of Patients With Aggressive Lymphomas: Results of the HE22A99 Trial of the Hellenic Cooperative Oncology Group

Background:In this study we investigated whether administering CEOP (cyclophosphamide, epirubicin, vincristine [Oncovin], and prednisone) every 2 weeks (CEOP-14) instead of every 3 weeks (the standard CEOP-21 regimen) improves outcomes in patients with previously untreated aggressive lymphomas. In a secondary analysis we evaluated the impact of adding rituximab to CEOP-14/CEOP-21 chemotherapy. Study Design:The trial opened in March 1999, and patients were randomly assigned to either CEOP-14 or CEOP-21. All patients enrolled from May 2002 onward received rituximab with each chemotherapy cycle, and those attaining a complete response received rituximab consolidation. Results:Complete and overall response rates in the CEOP-21 ± rituximab (N = 114) and CEOP-14 ± rituximab (N = 103) arms were similar, as were the overall survival (P = 0.769) and time to progression distributions (P = 0.969). Rituximab was shown to have a beneficial effect both on the overall survival and on the time to progression. Conclusions:Thus far, no significant improvement in outcome has been demonstrated with CEOP-14 ± rituximab versus CEOP-21 ± rituximab. However, with addition of rituximab to CEOP-21/CEOP-14, significant improvements in time to progression and overall survival were achieved.
Contrasting CD25hiCD4+T Cells/FOXP3 Patterns in Chronic Rejection and Operational Drug-Free Tolerance

Background. Although immunosuppression withdrawal in kidney recipients usually leads to rejection, in some patients it does not, leading to a state of clinical operational tolerance. Methods. We compared these highly contrasted situations by analyzing blood cell phenotype and transcriptional patterns in drug-free spontaneously tolerant kidney recipients, recipients with chronic rejection, recipients with stable graft function under standard or minimal immunosuppression and healthy individuals Results. The blood cell phenotype of clinically tolerant patients did not differ from that of healthy individuals. In contrast, recipients with chronic rejection had significantly less CD25hiCD4+T cells and lower levels of FOXP3 transcripts compared with clinically tolerant recipients. Patients with chronic rejection also displayed CD25−CD4+T cells expressing NKG2D+CD94+ and CD57+CD27−CD28− cytotoxic-associated markers (P<0.05). Conclusion. These data show that whereas clinically tolerant recipients displayed normal levels of CD25hiCD4+T cells and FOXP3 transcripts, chronic rejection is associated with a decrease in CD25hiCD4+T cells and FOXP3 transcripts, suggesting that clinically “operational tolerance” may be due to a maintained phenomenon of natural tolerance that is lacking in patients with chronic rejection.
Replacement of fish meal by soybean ( Glycine max ) in the formulation of fish feed ingredients essential for Immunostimulation and growth performance of carps

Fishmeal is the preferred protein ingredient in aquaculture feed and contributes significantly to the variable production cost in the aquaculture industry. However, decreasing fishmeal supply relative to demand and increasing costs threaten the sustainability and growth of the aquaculture industry. The way to sustain the industry is to remove or reduce the use of fishmeal. Past studies have demonstrated that complete or partial substitution of fishmeal with alternative proteins does not adversely affect fish performance. Soybean is probably the most promising alternative protein source for fish meal. It is widely used as the cost effective alternative for high quality fish meal in feeds for many aquaculture fish species due to its high protein content, excellent amino acid profile, low cost, availability and steady supply as compared to the other plant protein sources. Hence taking into account this consideration the present feed formulation has been undertaken, are introduce while formulating the feed. Hence for the present work soybean (Glycine max) has been selected as the raw material for formulation of fish feed along with ingredients essential for growth, disease resistance and the binding agent to hold the feed for Nile tilapia (Oreochromis niloticus).
Distributed convergence to nash equilibrium of antagonistic optimization networks

In this paper, we propose a distributed subgradient-based algorithm for a network consisting of two subnetworks to solve the antagonistic optimization problem. The two subnetworks have the same sum objective function, where one wants to minimize it and the other one wants to maximize it. Then the network is engaged in a zero-sum game scenario. We show that the network can achieve a Nash equilibrium by the proposed algorithm for weight-balanced digraphs under mild connectivity and stepsize conditions.
Ultra compact band pass filters implemented through complementary spiral resonators (CSRs)

In this work, it is shown that complementary spiral resonators (CSRs) etched in the ground plane of a microstrip line are useful for the implementation of band pass filters with very small dimensions and wide stop bands. By combining the CSRs with two series capacitive gaps and inductive vias, two transmission zeros arise. By properly allocating such transmission zeros at both sides of the pass band of interest, the out-of band rejection and frequency selectivity of the filters can be controlled. A prototype device example is reported to illustrate the performance and size of these CSR-based filters. This is an order-three Chebyshev band pass filter centered at ƒo=1.1GHz with 10% fractional bandwidth. Measured in-band losses (optimum value) are IL=−4.42dB, in-band return losses are better than 9dB, and stop band rejection is better than 55dB up to 2.57GHz. Filter area is as small as 23.2 mm × 8.9 mm, that is 0.22 λ × 0.08 λ, where λ is the wavelength (at the central filter frequency) of a 50Ω microstrip line in the considered substrate. The key novel and advantageous aspect of the reported filters is their small size, which is related to the small electrical size of CSRs. Another advantage is frequency selectivity, which is due to the presence of a transmission zero at both edges of the pass band. The limitative aspect is their relatively small unloaded quality factor (Qu), this being attributed to the small dimensions of the considered resonators. These CSR-based devices can be of interest in those applications where size and frequency selectivity are the most severe requirements.
Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy.

PURPOSE To compare the diagnostic performance of ultrasonography (US), computed tomography (CT), T1-weighted dual-echo magnetic resonance (MR) imaging, and point-resolved proton (hydrogen 1[(1)H]) MR spectroscopy in the assessment of hepatic steatosis in patients undergoing liver resection. MATERIALS AND METHODS This prospective study was approved by the institutional review board, and patients gave written informed consent. US, CT, T1-weighted MR imaging, and (1)H MR spectroscopy were performed preoperatively in 46 patients. Imaging results were correlated (Spearman correlation coefficient) with histopathologic analysis of results of intraoperative liver biopsies. To assess differences between groups, one-way analysis of variance was used. Sensitivity and specificity were calculated for each imaging modality by using receiver operating characteristic curve analysis, with a histopathologic cut-off value of 5% macrovesicular steatosis. Differences in sensitivity and specificity were assessed by means of McNemar analysis. RESULTS At histopathologic examination, 23 patients had no (0%-5%) macrovesicular steatosis, 11 had mild (5%-33%), nine had moderate (33%-66%), and three had severe (>66%). MR imaging and (1)H MR spectroscopic measurements of hepatic fat had stronger correlation with histopathologic steatosis assessment (r = 0.85, P < .001 and r = 0.86, P < .001, respectively) than did US (r = 0.66, P < .001) and CT (r = -0.55, P < .001). Only T1-weighted MR imaging and (1)H MR spectroscopy showed differences across steatosis grades: none versus mild (P = .001 for both), mild versus moderate (P < .001 for both), and moderate versus severe (P = .04 and .01, respectively). Sensitivity of US, CT, T1-weighted MR imaging, and (1)H MR spectroscopy was 65% (13 of 20), 74% (17 of 23), 90% (19 of 21), and 91% (21 of 23), respectively, and specificity was 77% (17 of 23), 70% (14 of 20), 91% (20 of 22), and 87% (20 of 23), respectively. CONCLUSION In contrast to US and CT, T1-weighted MR imaging and (1)H MR spectroscopy strongly correlate with histopathologic steatosis assessment and are able to demonstrate differences across steatosis grades. T1-weighted dual-echo MR imaging and (1)H MR spectroscopy had the best diagnostic accuracy in depicting hepatic steatosis.
Primary sensory afferent innervation of the developing superficial dorsal horn in the South American opossum Monodelphis domestica

The development of the primary sensory innervation of the superficial dorsal horn (SDH) was studied in postnatal opossums Monodelphis domestica by using DiI labelling of primary afferents and with GSA‐IB4 lectin binding and calcitonin gene‐related peptide (CGRP) immunoreactivity to label primary afferent subpopulations. We also compared the timing of SDH innervation in the cervical and lumbar regions of the spinal cord. The first primary afferent projections to SDH emerge from the most lateral part of the dorsal root entry zone at postnatal day 5 and project around the lateral edge of the SDH toward lamina V. Innervation of the SDH occurs slowly over the second and third postnatal weeks, with the most dorsal aspect becoming populated by mediolaterally oriented varicose fibers before the rest of the dorsoventral thickness of the SDH becomes innervated by fine branching varicose fibers. Labelling with GSA‐IB4 lectin also labelled fibers at the lateral edge of the dorsal horn and SDH at P5, indicating that the GSA‐IB4 is expressed on SDH/lamina V primary afferents at the time when they are making their projections into the spinal cord. In contrast, CGRP‐immunoreactive afferents were not evident until postnatal day 7, when a few short projections into the lateral dorsal horn were observed. These afferents then followed a pattern similar to the development of GSA‐IB4 projects but with a latency of several days. The adult pattern of labelling by GSA‐IB4 is achieved by about postnatal day 20, whereas the adult pattern of CGRP labelling was not seen until postnatal day 30. Electron microscopy revealed a few immature synapses in the region of the developing SDH at postnatal day 10, and processes considered to be precursors of glomerular synapses (and thus of primary afferent origin) were first seen at postnatal day 16 and adopted their definitive appearance between postnatal days 28 and 55. Although structural and functional development of forelimbs of neonatal Monodelphis is more advanced than the hindlimbs, we found little evidence of a significant delay in the invasion of the spinal cord by primary afferents in cervical and lumbar regions. These observations, together with the broadly similar maturational appearance of histological sections of rostral and caudal spinal cord, suggest that, unlike the limbs they innervate, the spinal regions do not exhibit a large rostrocaudal gradient in their maturation. J. Comp. Neurol. 495:37–52, 2006. © 2006 Wiley‐Liss, Inc.
Opportunistic Adversaries: On Imminent Threats to Learning-Based Business Automation

False positives and negatives are inevitable in real-world classification problems. In general, machine-learning-based business process automation is still viable with reduced classification accuracy due to such false decisions, thanks to business models that replace human decision processes with automated decision processes covering the costs of introducing automation and the losses from rare mistakes by the automation with the profits from relatively large savings in human-factor costs. However, under certain conditions, it is possible for attackers to outsmart a classifier at a reasonable cost and thus destroy the business model that the learner system depends on. Attackers may eventually detect the misclassification cases they can benefit from and try to create similar inputs that will be misclassified by the unaware learner system. We call adversaries of this type "opportunistic adversaries". This paper specifies the environmental patterns that can expose vulnerabilities to opportunistic adversaries and presents some likely business scenarios for these threats. Then we propose a countermeasure algorithm to detect such attacks based on change detection in the post-classification data distributions. Experimental results show that our algorithm has higher detection accuracy than other approaches based on outlier detection or change-point detection.
AZD-3043: A Novel, Metabolically Labile Sedative–Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis

Background: Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the &ggr;-aminobutyric acid type A (GABAA) receptor containing a metabolically labile ester moiety. The authors postulated that its metabolic pathway would result in a short-acting clinical profile. Methods: The effects of AZD-3043, propofol, and propanidid were studied on GABAA receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results: AZD-3043 potentiated GABAA receptor-mediated chloride currents and inhibited [35S]tert-butylbicyclophosphorothionate binding to GABAA receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared with propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions: AZD-3043 is a positive allosteric modulator of the GABAA receptor in vitro and a sedative–hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative–hypnotic agent with rapid and predictable recovery.
Discriminative Bayesian Nonparametric Clustering

We propose a general framework for discriminative Bayesian nonparametric clustering to promote the inter-discrimination among the learned clusters in a fully Bayesian nonparametric (BNP) manner. Our method combines existing BNP clustering and discriminative models by enforcing latent cluster indices to be consistent with the predicted labels resulted from probabilistic discriminative model. This formulation results in a well-defined generative process wherein we can use either logistic regression or SVM for discrimination. Using the proposed framework, we develop two novel discriminative BNP variants: the discriminative Dirichlet process mixtures, and the discriminative-state infinite HMMs for sequential data. We develop efficient data-augmentation Gibbs samplers for posterior inference. Extensive experiments in image clustering and dynamic location clustering demonstrate that by encouraging discrimination between induced clusters, our model enhances the quality of clustering in comparison with the traditional generative BNP models.
Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment

Tris(2‐butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP) and tris(1‐chloro‐2‐propyl) phosphate (TCIPP) are current high‐volume organophosphate flame retardants/plasticizers (PFRs) and are abundant in the indoor environment. While recent in vitro research has indicated potential toxic effects in the endocrine system, biotransformation of these compounds is still underexplored. In this study, we aimed to characterize the metabolite formation for three PFRs in primary human hepatocytes, an in vitro system that mimics in vivo liver metabolism more closely than hepatic subcellular fractions or cell lines. Cryopreserved human hepatocytes were thawed and suspended in media with 50 μm TBOEP or TCIPP, or 20 μm TPHP up to 2 h. Extracts were analyzed by liquid chromatography–quadrupole‐time‐of‐flight‐mass spectrometry. Quantification of biotransformation products in hepatocytes exposed for 2 h revealed that bis(1‐chloro‐2‐propyl) phosphate and diphenyl phosphate corresponded to less than half of the depletion of TCIPP and TPHP, respectively, while bis(2‐butoxyethyl) 2‐hydroxyethyl phosphate compared to 40–66% of the depletion of TBOEP. Other metabolite structures of these PFRs were produced at 4‐ to 10‐fold lower rates. These findings help interpret biological levels of the major metabolites and relate it to levels of their parent PFR. Percentage of substrate depletion was largest for TBOEP followed by comparable values for TPHP and TCIPP, indicating that hepatic clearance of TPHP and TCIPP would be slower than that of TBOEP. The resulting higher levels and longer presence of TPHP in the circulation after exposure, would allow TPHP a larger time window to exert its suspected adverse effects compared to TBOEP. Copyright © 2016 John Wiley & Sons, Ltd.
Electroencephalograms of epileptics following sleep deprivation.

IN A PREVIOUS study we called attention to the activating effects of sleep deprivation on the electroencephalograms (EEGs) of epileptics with normal interictal records. 1 The precipitation of seizures in susceptible subjects by fatigue and pro--longed wakefulness has also been described by other investigators. 2-6 Although the diagnosis of a seizure disorder must be based ultimately on clinical data, the demonstration of electrographic abnormalities may not only provide valuable information about the type of seizure and its cause but also serve as a guide to therapy. In order to increase the occurrence of abnormal cerebral discharges, many techniques are used currently, such as hyperventilation, photic stimulation, and recording during sleep. Even when these techniques are used, many patients with unquestioned seizures have normal EEGs. The need exists for additional techniques that increase the incidence of abnormal discharges in epileptics without giving misleadingn activation in normal subjects and are both simple
13C‐urea breath test for Helicobacter pylori in young children: cut‐off point determination by finite mixture model

The 13C‐urea breath test (UBT) is currently regarded as one of the most important noninvasive diagnostic methods for detecting Helicobacter pylori (H. pylori) infection in adults and children. However, for infants and young children, the standard for UBT interpretation has not been validated, and its reliability has not been established for diagnosing H. pylori infection in this group. The primary outcome data from UBT consist of mixture data, which come from subjects whose H. pylori infection classifications are unconfirmed. In this paper, we propose the finite mixture distribution method to identify a reliable UBT cut‐off value in a large baseline sample in which gastric biopsy is not available to confirm the H. pylori infection in younger children. Maximum likelihood estimators of the parameters in the mixture model were obtained using an expectation maximization (EM) algorithm. The standard deviation of the cut‐off point was estimated by bootstrap methods. We applied the same analytical methods to the UBT results yielded from the follow up, as well as the overall UBT results in the longitudinal cohort data. The cut‐off points from those UBT data sets are similar. The advantage of the finite mixture model is that it may be used to calculate sensitivity and specificity in the absence of other diagnostic tests. Copyright © 2004 John Wiley & Sons, Ltd.
Personal Health Record: uma revisão sobre os modelos e experimentos atuais

Objetivo: Realizar uma revisao integrativa da literatura para verificar que modelos de personal health record (PHR) eletronico estao sendo desenvolvidos e que aspectos influenciam na sua adocao por meio da analise dos experimentos realizados. Metodos: Uma busca nas bases de dados PubMed e LILACS foi realizada inicialmente para selecionar artigos publicados entre 2010 e 2012. Resultados: Foram recuperados 319 artigos originais publicados entre abril de 2010 e maio de 2012. A aplicacao dos criterios de exclusao resultou em 36 artigos para leitura completa e foram validados 29 artigos. Foram identificados 14 modelos de PHR e tres aplicativos. Os estudos foram categorizados em relacao ao objetivo em termos de desenvolvimento e usabilidade, compartilhamento, impacto, atitudes dos consumidores e barreiras. Um conjunto basico de funcionalidades, conteudo e interacao com o usuario que influenciam positivamente na sua adocao foi identificado. Conclusao: O PHR ainda esta em fase de desenvolvimento e outras questoes devem ser propostas e avaliadas.