Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2–91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1–76.2), 2B2t (65.5%, 95% CI: 58.5–72.0), GST-Ag5t (64.5%, 95% CI: 57.5–71.1) and GST-DIPOL (63.1%, 95% CI: 56.0–69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3–99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6–50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.
The impact of diet during adolescence on the neonatal health of offspring: evidence on the importance of preconception diet. The HUNT study

Abstract Emerging evidence suggests that parents’ nutritional status before and at the time of conception influences the lifelong physical and mental health of their child. Yet little is known about the relationship between diet in adolescence and the health of the next generation at birth. This study examined data from Norwegian cohorts to assess the relationship between dietary patterns in adolescence and neonatal outcomes. Data from adolescents who participated in the Nord-Trøndelag Health Study (Young-HUNT) were merged with birth data for their offspring through the Medical Birth Registry of Norway. Young-HUNT1 collected data from 8980 adolescents between 1995 and 1997. Linear regression was used to assess associations between adolescents’ diet and later neonatal outcomes of their offspring adjusting for sociodemographic factors. Analyses were replicated with data from the Young-HUNT3 cohort (dietary data collected from 2006 to 2008) and combined with Young-HUNT1 for pooled analyses. In Young-HUNT1, there was evidence of associations between dietary choices, meal patterns, and neonatal outcomes, these were similar in the pooled analyses but were attenuated to the point of nonsignificance in the smaller Young-HUNT3 cohort. Overall, energy-dense food products were associated with a small detrimental impact on some neonatal outcomes, whereas healthier food choices appeared protective. Our study suggests that there are causal links between consumption of healthy and unhealthy food and meal patterns in adolescence with neonatal outcomes for offspring some years later. The effects seen are small and will require even larger studies with more state-of-the-art dietary assessment to estimate these robustly.
Noninvasive Measurement of [11C]PiB Distribution Volume Using Integrated PET/MRI

A noninvasive image-derived input function (IDIF) method using PET/MRI was applied to quantitative measurements of [11C] Pittsburgh compound-B (PiB) distribution volume (DV) and compared with other metrics. Fifty-three patients suspected of early dementia (71 ± 11 y) underwent 70 min [11C]PiB PET/MRI. Nineteen of them (68 ± 11 y) without head motion during the scan were enrolled in this study and compared with 16 age-matched healthy controls (CTL: 68 ± 11 y). The dynamic frames reconstructed from listmode PET data were used for DV calculation. IDIF with metabolite correction was applied to the Logan plot method, and DV was normalized into DV ratio (DVR) images using the cerebellar reference (DVRL). DVR and standardized uptake value ratio (SUVR) images were also calculated using the reference tissue graphical method (DVRr) and the 50–70 min static data with cerebellar reference, respectively. Cortical values were compared using the 3D-T1WI MRI segmentation. All patients were assigned to the early Alzheimer’s disease (eAD) group because of positive [11C]PiB accumulation. The correlations of regional values were better for DVRL vs. DVRr (r2 = 0.97) than for SUVR vs. DVRr (r2 = 0.88). However, all metrics clearly differentiated eAD from CTL with appropriate thresholds. Noninvasive quantitative [11C]PiB PET/MRI measurement provided equivalent DVRs with the two methods. SUVR images showed acceptable results despite inferior variability and image quality to DVR images.
The Weight of IgA Anti-β2glycoprotein I in the Antiphospholipid Syndrome Pathogenesis: Closing the Gap of Seronegative Antiphospholipid Syndrome

The specific value of IgA Anti-β2glycoprotein I antibodies (aB2GP1) in the diagnosis and management of antiphospholipid syndrome (APS) is still controversial and a matter of active debate. The relevance of the IgA aB2GP1 isotype in the pathophysiology of APS has been increasingly studied in the last years. There is well know that subjects with multiple positive APS tests are at increased risk of thrombosis and/or miscarriage. However, these antibodies are not included in the 2006 APS classification criteria. Since 2010 the task force of the Galveston International Congress on APS recommends testing IgA aB2GP1 isotype in patients with APS clinical criteria in the absence of criteria antibodies. In this review, we summarize the molecular and clinical “state of the art” of the IgA aB2GP in the context of APS. We also discuss some of the characteristics that may help to evaluate the real value of the IgA aB2GP1 determination in basic research and clinical practice. The scientific community should be aware of the importance of clarifying the role of IgA aB2GP1 in the APS diagnosis.
The Use of Delphi Method and Analytical Hierarchy Process in the Establishment of Assessment Tools in Premature Ejaculation: The Scoring System for Premature Ejaculation Treatment Outcomes

There is a lack of objective tools to comprehensively evaluate premature ejaculation (PE) treatment results clinically. We aimed to describe the development of a novel scoring system for PE treatment results as an example of using the Delphi method and an analytical hierarchy process for complex decision-making in the field of sexual medicine. A Delphi question survey was adopted to collect expert opinions from 47 Chinese specialists in andrology/urology on the assessment of PE treatment outcomes based on four primary properties, that is, the improvement in intravaginal ejaculation latency time, a couple’s mental status, the ability to control ejaculation, and sexual intercourse satisfaction. Different weights on those primary properties were assigned to create a mathematical hierarchy matrix and then perform an analysis. The scores were assigned according to the calculated weights. The ratio among the combined weights of the four primary properties was 1:3:2:3. The total numerical score was 36. Scores above 27, between 26 and 18, and below 17 indicated significant improvement, moderate improvement, and no improvement in PE, respectively, with selected treatments. The scoring system with 36 points can be used by physicians, patients, and their sexual partners to comprehensively and objectively assess quantitative PE treatment results.
AphaMax®, an Aphanizomenon Flos-Aquae Aqueous Extract, Exerts Intestinal Protective Effects in Experimental Colitis in Rats

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a “superfood” for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax®, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax® (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-κB, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax® treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax® reduced the histological colonic damage and decreased MPO activity, NF-κB activation, as well as iNOS and COX-2 expression. AphaMax® treatment improved the altered immune response associated with colonic inflammation reducing IL-1β, IL-6 expression. Lastly, AphaMax® reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax® attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax® could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.
Mobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis in Pseudomonas aeruginosa

Iron homeostasis offers a significant bacterial vulnerability because pathogens obtain essential iron from their mammalian hosts, but host-defenses maintain vanishingly low levels of free iron. Although pathogens have evolved mechanisms to procure host-iron, these depend on well-regulated iron homeostasis. To disrupt iron homeostasis, our work has targeted iron mobilization from the iron storage protein bacterioferritin (BfrB) by blocking a required interaction with its cognate ferredoxin partner (Bfd). The blockade of the BfrB–Bfd complex by deletion of the bfd gene (Δbfd) causes iron to irreversibly accumulate in BfrB. In this study we used mass spectrometry and NMR spectroscopy to compare the proteomic response and the levels of key intracellular metabolites between wild type (wt) and isogenic Δbfd P. aeruginosa strains. We find that the irreversible accumulation of unusable iron in BfrB leads to acute intracellular iron limitation, even if the culture media is iron-sufficient. Importantly, the iron limitation and concomitant iron metabolism dysregulation trigger a cascade of events that lead to broader metabolic homeostasis disruption, which includes sulfur limitation, phenazine-mediated oxidative stress, suboptimal amino acid synthesis and altered carbon metabolism.
A Critical Review of the Social and Behavioral Contributions to the Overdose Epidemic

More than 750,000 people in the United States died from an overdose between 1999 and 2018; two-thirds of those deaths involved an opioid. In this review, we present trends in opioid overdose rates during this period and discuss how the proliferation of opioid prescribing to treat chronic pain, changes in the heroin and illegally manufactured opioid synthetics markets, and social factors, including deindustrialization and concentrated poverty, contributed to the rise of the overdose epidemic. We also examine how current policies implemented to address the overdose epidemic may have contributed to reducing prescription opioid overdoses but increased overdoses involving illegal opioids. Finally, we identify new directions for research to understand the causes and solutions to this critical public health problem, including research on heterogeneous policy effects across social groups, effective approaches to reduce overdoses of illegal opioids, and the role of social contexts in shaping policy implementation and impact.
Rewired phenolic metabolism and improved saccharification efficiency of a Zea mays cinnamyl alcohol dehydrogenase 2 (zmcad2) mutant.

Lignocellulosic biomass is an abundant byproduct from cereal crops that can potentially be valorized as a feedstock to produce biomaterials. Zea mays CINNAMYL ALCOHOL DEHYDROGENASE 2 (ZmCAD2) is involved in lignification and is a promising target to improve the cellulose-to-glucose conversion of maize stover. Here, we analyzed a field-grown zmcad2 Mutator transposon insertional mutant. Zmcad2 mutant plants had an 18% lower Klason lignin content whereas their cellulose content was similar to that of control lines. The lignin in zmcad2 mutants contained increased levels of hydroxycinnamaldehydes, i.e., the substrates of ZmCAD2, ferulic acid, and tricin. Ferulates decorating hemicelluloses were not altered. Phenolic profiling further revealed that hydroxycinnamaldehydes are partly converted into (dihydro)ferulic acid and sinapic acid and their derivatives in zmcad2 mutants. Syringyl lactic acid hexoside, a metabolic sink in CAD-deficient dicot trees, appeared not to be a sink in zmcad2 maize. The enzymatic cellulose-to-glucose conversion efficiency was determined after ten different thermochemical pretreatments. Zmcad2 yielded significantly higher conversions compared to controls for almost every pretreatment. However, the relative increase in glucose yields after alkaline pretreatment was not higher than the relative increase when no pretreatment was applied, suggesting that the positive effect of the incorporation of hydroxycinnamaldehydes was leveled off by the negative effect of reduced p-coumarate levels in the cell wall. Taken together, our results reveal how phenolic metabolism is affected in CAD-deficient maize and further support mutating CAD genes in cereal crops as a promising strategy to improve lignocellulosic biomass for sugar-platform biorefineries.
Comprehensive analysis of lncRNA expression profiles in cytopathic biotype BVDV-infected MDBK cells provides an insight into biological contexts of host–BVDV interactions

ABSTRACT Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea-mucosal disease, which significantly affects the production performance of cattle, causing serious economic losses to the cattle industries worldwide. Up to now, some mechanisms involved in host–BVDV interaction are still not fully understood. The discovery of long non-coding RNAs (lncRNAs) has provided a new perspective on gene regulation in diverse biological contexts, particularly in viral infection and host immune responses. However, little is known about the profiles and functions of lncRNAs in host cells in response to BVDV infection. Here, we utilized Illumina sequencing to explore lncRNAs profiles in cytopathic (CP) biotype BVDV-infected MDBK cells to further reveal the potential roles of lncRNAs in BVDV infection and host–BVDV interaction with integrated analysis of lncRNAs and mRNA expression profiles. A total of 1747 significantly differentially expressed genes, DEGs (156 lncRNAs and 1591 mRNAs) were obtained via RNA-seq in BVDV-infected MDBK cells compared to mock-infected cells. Next, these DE lncRNAs and mRNAs were subjected to construct lncRNAs-mRNAs co-expression network followed by the prediction of potential functions of the DE lncRNAs. Co-expression network analysis elucidated that DE lncRNAs were significant enrichment in NOD-like receptor, TNF, NF-ĸB, ErbB, Ras, apoptosis, and fatty acid biosynthesis pathways, indicating that DE lncRNAs play important roles in host–BVDV interactions. Our data give an overview of changes in transcriptome and potential roles of lncRNAs, providing molecular biology basis for further exploring the mechanisms of host–BVDV interaction.
Speed-accuracy trade-offs in sample-based decisions.

Success on many tasks depends on a trade-off between speed and accuracy. In a novel variant, a speed-accuracy trade-off with sample-based decisions in which both speed and accuracy jointly depend on (self-truncated) sample size, we found strong accuracy biases. On every trial of a sequential investment game, participants chose between 2 investment funds based on binary samples of the funds' past outcomes. Participants could stop sampling and decide whenever they felt sufficiently informed. Total payoff was the product of choice accuracy and number of choices completed within the available time (speed). Participants' failure to understand the dominance of speed over accuracy-that speed decreases more than accuracy improves with increasing sample size-led to dramatic oversampling. Our research aimed to examine to what extent metacognitive functions of monitoring and control could correct for the accuracy bias. Experiments 1a through 1c demonstrated similarly strong accuracy biases and payoff losses in psychology and economics students, depressed, and control patients. In Experiments 2 through 4, the accuracy bias persisted despite several manipulations (feedback, sample limit, choice difficulty, payoff, sampling truncation as default) that underlined the speed advantage, reflecting a conspicuous metacognitive deficit. Even when participants faced no risk of losing on incorrect trials but could still win on correct trials (Experiment 3) and when sampling was contingent on the active solicitation of every new element (Experiment 4), participants continued to sample too much and failed to overcome the accuracy bias. The final discussion focuses on psychological reasons and possible remedies for the metacognitive deficit in trade-off regulation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
How the concavity of reproduction/survival trade-offs impacts the evolution of life history strategies

ABSTRACT Previous works using different mathematical techniques, however, show that the concavity of the trade-off relationship can alter the expected life history strategies. Thus we developed a model and found that the concavity of the reproduction–survival curve can still have a large impact on life history strategies in an ecological model with Darwinian evolution.
Characteristics, Properties and Analytical/Bioanalytical Methods of 5-Aminosalicylic Acid: A Review

Abstract Five-aminosalicylic acid (5-ASA) is an anti-inflammatory drug indicated in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Among the analytical methods of quantification of 5-ASA described in the literature, the High Efficiency Liquid Chromatography stands out, a sensitive technique but with a high cost. In recent years, alternative methods have been developed, presenting efficiency and reduced cost, such as UV/visible spectrophotometric, spectrofluorescent, and electrochemical methods, techniques recommended for the application in quality control and quantification of 5-ASA in pharmaceutical forms and biological fluids. This article aims to review the physicochemical characteristics, pharmacokinetics, mechanisms of action, controlled release systems, and the different analytical and bioanalytical methods for the quantification of 5-ASA.
IMIX: a multivariate mixture model approach to association analysis through multi-omics data integration

MOTIVATION Integrative genomic analysis is a powerful tool used to study the biological mechanisms underlying a complex disease or trait across multiplatform high-dimensional data, such as DNA methylation, copy number variation, and gene expression. It is common to perform large-scale genome-wide association analysis of an outcome for each data type separately and combine the results ad hoc, leading to loss of statistical power and uncontrolled overall false discovery rate (FDR). RESULTS We propose a multivariate mixture model (IMIX) framework that integrates multiple types of genomic data and allows modeling of inter-data-type correlations. We investigated the across-data-type FDR control in IMIX and demonstrated lower misclassification rates at controlled overall FDR than established individual data type analysis strategies, such as the Benjamini-Hochberg FDR control, the q-value, and the local FDR control by extensive simulations. IMIX features statistically principled model selection, FDR control, and computational efficiency. Applications to The Cancer Genome Atlas (TCGA) data provided novel multi-omics insights into the genes and mechanisms associated with the luminal and basal subtypes of bladder cancer and the prognosis of pancreatic cancer. AVAILABILITY We have implemented our method in R package "IMIX" available at https://github.com/ziqiaow/IMIX, as well as CRAN soon. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Synthesis and Conformational Analysis of Fluorinated Uridine Analogues Provide Insight into a Neighbouring-Group Participation Mechanism

Fluorinated nucleoside analogues have attracted much attention as anticancer and antiviral agents and as probes for enzymatic function. However, the lack of direct synthetic methods, especially for 2′,3′-dideoxy-2′,3′-difluoro nucleosides, hamper their practical utility. In order to design more efficient synthetic methods, a better understanding of the conformation and mechanism of formation of these molecules is important. Herein, we report the synthesis and conformational analysis of a 2′,3′-dideoxy-2′,3′-difluoro and a 2′-deoxy-2′-fluoro uridine derivative and provide an insight into the reaction mechanism. We suggest that the transformation most likely diverges from the SN1 or SN2 pathway, but instead operates via a neighbouring-group participation mechanism.