Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-18 Is Critical for Mucosa-Associated Invariant T Cell Gamma Interferon Responses to Francisella Species In Vitro but Not In Vivo

ABSTRACT Mucosa-associated invariant T (MAIT) cells are a subset of innate T cells that express a semi-invariant Vα chain paired with limited Vβ chains. MAIT cells are activated by riboflavin metabolite derivatives presented by the nonpolymorphic major histocompatibility complex class I (MHC-I)-like molecule MR1. The precise mechanisms required to activate MAIT cells are an area of intense interest. Here we used two closely related intracellular pathogens with distinct inflammasome activation phenotypes to probe the role of innate cytokines in MAIT cell activation. Using an in vitro assay containing transgenic murine MAIT cells, we show that macrophages infected with Francisella novicida, a strong inflammasome activator, released high levels of interleukin-18 (IL-18) and stimulated high levels of MAIT cell gamma interferon (IFN-γ) through a partially MR1-independent pathway. In contrast, macrophages infected with Francisella tularensis live vaccine strain (LVS), a weak inflammasome activator, generated little IL-18 and stimulated low MAIT cell IFN-γ through an MR1-dependent pathway. By manipulating the quantities of IL-18 in these cultures, we show that the IL-18 concentration is sufficient to influence the magnitude of MAIT cell IFN-γ production. Correspondingly, infected IL-18-deficient macrophages failed to induce substantial MAIT cell IFN-γ. In contrast, we found that MAIT cell IFN-γ production in the lungs of IL-18-deficient mice was not significantly different from that in WT mice during F. tularensis LVS pulmonary infection. Overall, we demonstrate that while IL-18 is essential for the MAIT cell IFN-γ response in vitro, it is not essential for MAIT cell IFN-γ production during in vivo LVS pulmonary infection, suggesting that additional signals can drive MAIT cell IFN-γ production in vivo.
How Emotions Shape Moral Behavior: Some Answers (and Questions) for the Field of Moral Psychology

Within the past decade, the field of moral psychology has begun to disentangle the mechanics behind moral judgments, revealing the vital role that emotions play in driving these processes. However, given the well-documented dissociationbetweenattitudesand behaviors,we propose thatanequally important issue is how emotions inform actual moral behavior – a question that has been relatively ignored up until recently. By providing a review of recent studies that have begun to explore how emotions drive actual moral behavior, we propose that emotions are instrumental in fueling real-life moral actions. Because research examining the role of emotional processes on moral behavior is currently limited, we push for the use of behavioral measures in the field in the hopes of building a more complete theory of real-life moral behavior.
Comparative Analysis of Epidermal Differentiation Genes of Crocodilians Suggests New Models for the Evolutionary Origin of Avian Feather Proteins

Abstract The epidermis of amniotes forms a protective barrier against the environment and the differentiation program of keratinocytes, the main cell type in the epidermis, has undergone specific alterations in the course of adaptation of amniotes to a broad variety of environments and lifestyles. The epidermal differentiation complex (EDC) is a cluster of genes expressed at late stages of keratinocyte differentiation in both sauropsids and mammals. In the present study, we identified and analyzed the crocodilian equivalent of the EDC. The gene complement of the EDC of both the American alligator and the saltwater crocodile were determined by comparative genomics, de novo gene prediction and identification of EDC transcripts in published transcriptome data. We found that crocodilians have an organization of the EDC similar to that of their closest living relatives, the birds, with which they form the clade Archosauria. Notable differences include the specific expansion of a subfamily of EDC genes in crocodilians and the loss of distinct ancestral EDC genes in birds. Identification and comparative analysis of crocodilian orthologs of avian feather proteins suggest that the latter evolved by cooption and sequence modification of ancestral EDC genes, and that the amplification of an internal highly cysteine-enriched amino acid sequence motif gave rise to the feather component epidermal differentiation cysteine-rich protein in the avian lineage. Thus, sequence diversification of EDC genes contributed to the evolutionary divergence of the crocodilian and avian integuments.
Obstetrics at Decisive Crossroads Regarding Pattern-Recognition of Fetal Heart Rate Decelerations: Scientific Principles and Lessons From Memetics

The survival of cardiotocography (CTG) as a tool for intrapartum fetal monitoring seems threatened somewhat unjustifiably and unwittingly despite the absence of better alternatives. Fetal heart rate (FHR) decelerations are center-stage (most important) in the interpretation of CTG with maximum impact on three-tier classification. The pattern-discrimination of FHR decelerations is inexorably linked to their nomenclature. Unscientific or flawed nomenclature of decelerations can explain the dysfunctional CTG interpretation leading to errors in detection of acidemic fetuses. There are three contrasting concepts about categorization of FHR decelerations: 1) all rapid decelerations (the vast majority) should be grouped as “variable” because they are predominantly due to cord-compression, 2) all decelerations are due to chemoreflex from fetal hypoxemia hence their timing is not important, and 3) FHR decelerations should be categorized into “early/late/variable” based primarily on their time relationship to contractions. These theoretical concepts are like memes (ideas/beliefs). Lessons from “memetics” are that the most popular, attractive or established beliefs may not necessarily be true, scientific, beneficial or even without harm. Decelerations coincident with contractions with trough corresponding to the peak of contractions cannot be explained by cord-compression or increasing hypoxia (from compromised uteroplacental perfusion, cord-compression or even cerebral hypoperfusion/anoxia purportedly conceivable from head-compression). Decelerations due to hypoxemia would be associated with delayed recovery of decelerations (lag phase). It is a scientific imperative to cast away disproven/falsified theories. Practices based on unscientific theories lead to patient harm. Clinicians should urgently adopt the categorization of FHR decelerations based primarily of the time relationship to contractions as originally proposed by Hon and Caldeyro-Barcia. This analytical review shows it to be underpinned by most robust physiological and scientific hypotheses unlike the other categorizations associated with untruthful hypotheses, irreconcilable fallacies and contradictions. Without truthful framework and meaningful pattern-recognition of FHR decelerations, the CTG will not fulfil its true potential.
Comparison of Single Course High-Dose Dexamethasone and Prednisone for Initial Treatment of Primary Immune Thrombocytopenia in Children : A Prospective Randomized Trial

Introduction: Prednisone (PDN) is the most commonly used first-line treatment for primary immune thrombocytopenia (ITP) in children. Recently, a short-course high-dose dexamethasone (HD-DXM) therapy has been reported to be efficacious in childhood primary ITP. However, the choice of best corticosteroid as an initial therapy in primary ITP in children is still a matter of debate. Methods: This single-blind prospective randomized clinical trial was conducted at Pediatrics Department, NRS Medical College and Hospital, Kolkata, a tertiary care teaching institute in the state of West Bengal from the month of July 2014 to June 2017 to compare the efficacy and safety of HD-DXM and conventional PDN as firstline strategies for newly diagnosed primary ITP in children. Patients enrolled were randomized to receive DXM 20 mg/m 2 /day for 4 days (n=49) or PDN 2.0 mg/kg/day for 10 day and then tapered over 2-3 weeks (n=47). Results: Single courses of HD-DXM resulted in a higher incidence of overall initial response (95.92% vs 82.98%, P = 0.049) and complete response (69.39% vs 34.04%, P = 0.001) compared with prednisone. Median time to response was shorter in the HD-DXM group [4 days (1-6) vs 6 days (2-9), P = < 0.0001). Bleeding was more effectively controlled on day 3 (P = 0.009) in children who had received HD-DXM compared with prednisone. Sustained response was achieved in 71.43% of patients in the HD-DXM arm and 42.55% in the PDN arm (P = 0.007). Initial complete response was associated with a decreased likelihood of loss of response. Both the corticosteroids were tolerated better with no statistically significant difference regarding treatment related overall toxicities (P = 0.0604). Conclusion: We concluded that HD-DXM could be a preferred corticosteroid strategy for first-line management of primary ITP in children.
Early parenting and the reduction of educational inequality in childhood and adolescence

ABSTRACT Socioeconomic status (SES) differences in parenting are often implicated in widening the SES-achievement gap. Using nationally representative data (N = 12,887), the author tested for variation across SES in the types and intensity of parenting behaviors utilized and then examined SES differences in the relationship between parenting and student achievement growth from kindergarten to Grade 8. Exploratory factor analysis identifies three dimensions of early parenting: Educational engagement, stimulating parent–child interaction, and discursive discipline. Regression results indicate that all three are used most heavily by high-SES families. However, only educational engagement consistently predicts achievement growth. Surprisingly, it is positively associated with achievement for lower-, but not higher-SES students in Grades 1–8. Further, educational engagement is beneficial for low-SES children because it is particularly beneficial for low-achieving students, consistent with a compensatory hypothesis.
Production and Characterization of Fungal α-Amylase from Marine Alternaria alternata Utilizing Lignocellulosic Wastes and Its Application.

A marine Alternaria alternata was tested for its ability to produce amylase by solid state fermentation (SSF) and submerged fermentation (SMF). Various lignocellulosic wastes such as corn cobs, wheat bran, potato shells, wheat straw and rice straw were used as solid substrates. The highest titer of amylase activity was obtained on potato shells by SSF (46.47 U/g solid substrate) compared to 41.19 U/g solid substrate by SMF after 14 day of fermentation. The highest extraction yield of α-amylase (183.57 U/g solid substrate) was obtained with acetate buffer (0.05 M, pH 5) as a leaching agent, 75% sea water concentration and pre-treatment of the waste by boiling in water for 60 min. Repeated washes under the optimum conditions showed that most of the enzyme (about 90.31%) was recovered in four repeated extractions. The calculated values of the half life for the crude amylase at 50, 55 and 60:C were 189.86, 99.82 and 93.77 min, respectively. Optimum α-amylase enzyme activity was observed at 40:C and active at wide range of pH. The calculated Km and Vmax for α-amylase were 1.90 mg/ml and 0.33 U/mg protein, respectively. Presence of Na + enhanced amylase activity by 2-fold. Moreover, the enzyme was able to hydrolyze corn starch under optimized conditions with efficiency 85%.
Raft-partitioning of the ubiquitin ligases Cbl and Nedd4 upon IgE-triggered cell signaling

The high affinity receptor for IgE, FcɛRI on mast cells and basophils plays an essential role in immunological defense. Upon multivalent antigen binding, FcɛRI becomes phoshorylated by the protein-tyrosine kinase Lyn, as a result of receptor clustering in lipid rafts. FcɛRI has been shown to be ubiquitinated. Ubiquitination can lead to degradation by proteasomes, but it can also act as a sorting signal to internalize proteins destined to the endosomal/lysosomal pathway. We have analyzed whether FcɛRI ubiquitination takes place within rafts. We report biochemical and imaging evidence in rat basoleukemia cells for the presence of ubiquitinated FcɛRI in clustered rafts upon receptor activation. Moreover, we demonstrated that the ubiquitin ligases Cbl and Nedd4 colocalize with FcɛRI patches and showed that both ligases become associated with lipid rafts after activation of IgE signaling. Because Cbl is known to interact with the FcɛRI signaling complex, ubiquitination is likely to be an important parameter regulating IgE-triggered signaling occurring in rafts.
Timing of First Respiratory Virus Detections in Infants: A Community-Based Birth Cohort Study

Abstract Background Determining timing of first virus detection episodes (fVDEs) for different respiratory viruses in infants identifies risk periods and informs preventive interventions, including vaccination. We describe the ages and nature of fVDEs in an infant birth cohort and explore factors associated with increased odds of symptomatic fVDEs. Methods The Observational Research in Childhood Infectious Diseases (ORChID) study is a community-based birth cohort describing acute respiratory infections in infants until their second birthday. Parents recorded daily symptoms and collected nose swabs weekly, which were batch-tested using polymerase chain reaction assays for 17 respiratory viruses. Results One hundred fifty-eight infants participated in ORChID. The median age for fVDEs was 2.9 months for human rhinovirus (HRV) but was ≥13.9 months for other respiratory viruses. Overall, 52% of HRV fVDEs were symptomatic, compared with 57%–83% of other fVDEs. Respiratory syncytial virus and human metapneumovirus fVDEs were more severe than HRV fVDEs. Older age and the winter season were associated with symptomatic episodes. Conclusions Infants do not always experience respiratory symptoms with their fVDE. Predominance of early HRV detections highlights the need for timing any intervention early in life. fVDEs from other respiratory viruses most commonly occur when maternal vaccines may no longer provide protection.
Primary and Secondary Syphilis — United States, 2005–2013

In 2013, based on data reported as of April 28, 2014, the rate of reported primary and secondary syphilis in the United States was 5.3 cases per 100,000 population, more than double the lowest-ever rate of 2.1 in 2000. To characterize the recent epidemiology of syphilis in the United States, CDC analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) for cases of primary and secondary syphilis diagnosed during 2005-2013 with a focus on states that reported the sex of sex partners during 2009-2012 to describe reported syphilis among gay, bisexual, and other men who have sex with men (collectively referred to as MSM). During 2005-2013, primary and secondary syphilis rates increased among men of all ages and races/ethnicities across all regions of the United States. Recent years have shown an accelerated increase in the number of cases, with the largest increases occurring among MSM. Among women, rates increased during 2005-2008 and decreased during 2009-2013, with different trends among different racial/ethnic groups. Racial/ethnic disparities in reported syphilis persisted during 2005-2013, likely reflecting social determinants of health, such as socioeconomic status, that might contribute to the burden of syphilis in a community. These findings underscore the need for continued syphilis prevention measures among MSM.
Has the Basel II Accord Encouraged Risk Management During the 2008-09 Financial Crisis?

The Basel II Accord requires that banks and other Authorized Deposit-taking Institutions (ADIs) communicate their daily risk forecasts to the appropriate monetary authorities at the beginning of each trading day, using one or more risk models to measure Value-at-Risk (VaR). The risk estimates of these models are used to determine capital requirements and associated capital costs of ADIs, depending in part on the number of previous violations, whereby realised losses exceed the estimated VaR. In this paper we define risk management in terms of choosing sensibly from a variety of risk models, discuss the selection of optimal risk models, consider combining alternative risk models, discuss the choice between a conservative and aggressive risk management strategy, and evaluate the effects of the Basel II Accord on risk management. We also examine how risk management strategies performed during the 2008-09 financial crisis, evaluate how the financial crisis affected risk management practices, forecasting VaR and daily capital charges, and discuss alternative policy recommendations, especially in light of the financial crisis. These issues are illustrated using Standard and Poor's 500 Index, with an emphasis on how risk management practices were monitored and encouraged by the Basel II Accord regulations during the financial crisis.
Exploring the variability in Behçet’s disease prevalence: a meta-analytical approach

Background Surveys of Behçet's disease (BD) have shown substantial geographic variations in prevalence, but some of these differences may result from methodological inconsistencies. This meta-analysis explored the effect of geographic location and study methodology on the prevalence of BD. Methods We systematically searched the literature in electronic databases and by handsearching to identify population-based prevalence surveys of BD. Studies were eligible if they provided an original population-based prevalence estimate for BD with the number of prevalent cases identified in the study area. Pooled prevalence proportions across all studies were computed by using random effects models based on a Poisson normal distribution. Pre-defined subgroup analyses and meta-regression were used to investigate the effect of covariates on the prevalence proportions. Results We included 45 reports published from 1974 to 2015 and covering worldwide areas. The pooled estimates of prevalence proportions (expressed as cases/100 000 inhabitants) were 10.3 (95% CI 6.1, 17.7) for all studies and 119.8 (59.8, 239.9) for Turkey, 31.8 (12.9, 78.4) for the Middle East, 4.5 (2.2, 9.4) for Asia and 3.3 (2.1, 5.2) for Europe. Subgroup analyses showed a strikingly greater prevalence for studies with a sample survey design than a census design [82.5 (95% CI 47.3, 143.9) vs 3.6 (2.6, 5.1)]. Metaregression identified study design as an independent covariate significantly affecting BD prevalence proportions. Conclusions Differences in BD prevalence proportions likely reflect a combination of true geographic variation and methodological artefacts. In particular, use of a sample or census study design may strongly affect the estimated prevalence.
Model test panel for processing and characterization studies of Honeycomb composite structures

A model test panel was designed to investigate, at a laboratory scale, the core crush problem in honeycomb laminate sandwich processing. The reliability of the results generated from this model test panel was confirmed by comparing them to the data from a large test panel. The results were then explained in terms of core crush mechanisms and information obtained from other analytical methods, such as the permeation test, internal core pressure measurement, DSC and TGA. Additionally, this model test panel was successfully utilized in investigating the effects of autoclave pressure, core thickness, adhesives, and layup methods on core crush
Adaptive Compressive Tracking via Online Vector Boosting Feature Selection

Recently, the compressive tracking (CT) method has attracted much attention due to its high efficiency, but it cannot well deal with the large scale target appearance variations due to its data-independent random projection matrix that results in less discriminative features. To address this issue, in this paper, we propose an adaptive CT approach, which selects the most discriminative features to design an effective appearance model. Our method significantly improves CT in three aspects. First, the most discriminative features are selected via an online vector boosting method. Second, the object representation is updated in an effective online manner, which preserves the stable features while filtering out the noisy ones. Furthermore, a simple and effective trajectory rectification approach is adopted that can make the estimated location more accurate. Finally, a multiple scale adaptation mechanism is explored to estimate object size, which helps to relieve interference from background information. Extensive experiments on the CVPR2013 tracking benchmark and the VOT2014 challenges demonstrate the superior performance of our method.
Antitumor Activity of DLX1008, an Anti-VEGFA Antibody Fragment with Low Picomolar Affinity, in Human Glioma Models

Angiogenesis mediated by vascular endothelial growth factor (VEGF) is a hallmark of glioblastoma. Based on the response rate and improved progression-free survival, although not on overall survival, the 149-kDa anti-VEGF-A IgG antibody bevacizumab (Avastin) has been approved in the United States and Japan for recurrent glioblastoma and in Japan for newly diagnosed glioblastoma; however, it is not approved in the EU. Here we characterize the biologic activity of DLX1008, a 26-kDa anti-VEGF-A single-chain antibody fragment that shows 30-fold stronger affinity to human VEGF-A than bevacizumab. The small molecular size of DLX1008 is predicted to result in improved target coverage over bevacizumab. DLX1008 showed superiority to bevacizumab in the inhibition of VEGF-A binding to VEGF receptor (VEGFR) 1 in enzyme-linked immunosorbent assay by a factor of around 10 and comparable efficacy for the inhibition of VEGF-A–stimulated VEGFR2 dimerization. In a tube-formation assay with human cerebral microvascular endothelial cells, DLX1008 was at least as active as bevacizumab. In vivo, DLX1008 delayed growth in a mouse subcutaneous U87 xenograft model (P = 0.0021) and improved survival in a mouse orthotopic U87 xenograft model (P = 0.00026). Given the exceptionally high affinity and small molecular size of DLX1008, these data warrant further clinical development of DLX1008 as an antiangiogenic agent in glioblastoma.
A 3-Year Study of Predictive Factors for Positive and Negative Appendicectomies

ABSTRACT Background: Early and accurate identification or exclusion of acute appendicitis is the key to avoid the morbidity of delayed treatment for true appendicitis or unnecessary appendicectomy, respectively. We aim (i) to identify potential predictive factors for positive and negative appendicectomies; and (ii) to analyse the use of ultrasound scans (US) and computed tomography (CT) scans for acute appendicitis. Materials and Methods: All appendicectomies that took place at our hospital from the 1st of January 2013 to the 31st of December 2015 were retrospectively recorded. Test results of potential predictive factors of acute appendicitis were recorded. Statistical analysis was performed using Fisher exact test, logistic regression analysis, sensitivity, specificity, and positive and negative predictive values calculation. Results: 208 patients were included in this study. 184 patients had histologically proven acute appendicitis. The other 24 patients had either nonappendicitis pathology or normal appendix. Logistic regression analysis showed statistically significant associations between appendicitis and white cell count, neutrophil count, C-reactive protein, and bilirubin. Neutrophil count was the test with the highest sensitivity and negative predictive values, whereas bilirubin was the test with the highest specificity and positive predictive values (PPV). US and CT scans had high sensitivity and PPV for diagnosing appendicitis. Conclusions: No single test was sufficient to diagnose or exclude acute appendicitis by itself. Combining tests with high sensitivity (abnormal neutrophil count, and US and CT scans) and high specificity (raised bilirubin) may predict acute appendicitis more accurately.