Miracle-dz/UniFAR-FTUs huggingface dataset:
Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis

Initial clinical research comparing the diagnostic performance of PET/MRI and PET/CT has largely shown equivalent diagnostic capabilities for these modalities in oncology. These uncertainties about the magnitude of diagnostic benefit are compounded by the considerable health economic challenges associated with clinical implementation. Therefore, there is a need to identify ways to extend the use of this technology beyond simple diagnosis so that PET/MRI can add sufficient clinical value beyond PET/CT or MRI alone and become a cost-effective imaging modality in clinical practice. A major advantage of PET/MRI over other imaging modalities is the ability to generate multiple quantitative images from a single examination. This article describes how a multiparametric PET/MRI approach not only can add clinical value through contributing to precision medicine but also can establish PET/MRI as a potentially cost-effective imaging modality in oncology.
Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion

Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects.
A Loop-Based Methodology for Reducing Computational Redundancy in Workload Sets

The design of general purpose processors relies heavily on a workload gathering step in which representative programs are collected from various application domains. Processor performance, when running the workload set, is profiled using simulators that model the targeted processor architecture. However, simulating the entire workload set is prohibitively time-consuming, which precludes considering a large number of programs. To reduce simulation time, several techniques in the literature have exploited the internal program repetitiveness to extract and execute only representative code segments. Existing solutions are based on reducing cross-program computational redundancy or on eliminating internal-program redundancy to decrease execution time. In this paper, we propose an orthogonal and complementary loop-centric methodology that targets loop-dominant programs by exploiting internal-program characteristics to reduce cross-program computational redundancy. The approach employs a newly developed framework that extracts and analyzes core loops within workloads. The collected characteristics model memory behavior, computational complexity, and data structures of a program, and are used to construct a signature vector for each program. From these vectors, cross-workload similarity metrics are extracted, which are processed by a novel heuristic to exclude similar programs and reduce redundancy within the set. Finally, a reverse engineering approach that synthesizes executable micro-benchmarks having the same instruction mix as the loops in the original workload is introduced. A tool that automates the flow steps of the proposed methodology is developed. Simulation results demonstrate that applying the proposed methodology to a set of workloads reduces the set size by half, while preserving the main characterizations of the initial workloads.
Amphiphysin IIm Is Required for Survival of Chlamydia pneumoniae in Macrophages

Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae–induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.
Prediction of driving behavior based on sequence to sequence model with parametric bias

Prediction of driving behavior is important in safer advanced driving assistance systems to prevent potential risk of traffic accidents. To predict the driving behavior, driving style, i.e., the difference of tendency of driving behavior for each driver, is also important. We propose a prediction method for time-series driving behavior based on the driving style. The proposed method consists of a sequence-to-sequence (S2S) model and embeds driver information considering with the driving style into S2S model in order to improve prediction performance. We evaluated efficiency of the proposed method by two experiments using actual driving behavior data on a test track. We found that the proposed method could predict driving behavior better than comparative methods. We also found that the proposed method could change the driving style from one driver to another driver by changing driver information input to the proposed model.
Comparison of the effects of human recombinant epidermal growth factor and platelet-rich plasma on healing of rabbit patellar tendon.

OBJECTIVES This study aims to compare the histological healing process and gene expression profile in tendon after the administration of human recombinant epidermal growth factor (hrEGF) and platelet-rich plasma (PRP). MATERIALS AND METHODS A total of 24 mature New Zealand white rabbits (6-month-old; weight 2.5-3.0 kg) were used in the study. Patellar tendons of rabbits were tenotomized and then repaired. Rabbits were separated into three groups and repair areas were injected with 1 mL hrEGF in group 1 (n=9) and 1 mL PRP in group 2 (n=9). No injection was performed in group 3 (controls, n=6). Tissue samples were obtained from the repaired patellar tendons of three rabbits each from groups 1 and 2 and of two rabbits from group 3 at the end of the first, second, and fourth weeks, and these tissues were histologically and genetically assessed. Expression levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, and chemokine receptors (CXCR1, CXCR2) were examined. RESULTS The frequency of neovascularization was detected to be higher in group 1 compared to group 3 at the end of the second and fourth weeks (p=0.018 and p=0.009, respectively). Group 1 was detected to show more increase in terms of the prevalence of tenocytes (p=0.014 and p=0.009, respectively) at the end of the second week, and in terms of collagen intensity at the end of the fourth week (p=0.0018 and p=0.034, respectively) compared to groups 2 and 3. Highest levels of TNF-α, IL-6, and IL-8 were detected in group 1, followed by groups 2 and 3 at all time points. Highest CXCR2 gene expression was detected in group 1. CONCLUSION Compared to PRP, hrEGF caused more increase in healing tissue at neovascularization, tenocyte, fibroblast, collagen, and tissue macrophage levels; and higher levels of TNF-α, IL-6, IL8, and CXCR2. Intralesional hrEGF administration can effectively accelerate tendon healing.
Reattachment rate of human retinal pigment epithelium to layers of human Bruch's membrane.

OBJECTIVES To determine the reattachment rate of human retinal pigment epithelium (RPE) to different layers of human Bruch's membrane (BM). METHODS Explants of BM were prepared from 10 human cadaver eyes by removing native RPE. The RPE basal lamina, inner collagenous layer, elastin layer, and outer collagenous layer were exposed by sequentially removing each apical layer by mechanical or enzymatic means. First-passage human RPE was plated onto the surface and the RPE reattachment rate to each layer of BM was determined. RESULTS Retinal pigment epithelial cell reattachment was highest to the inner aspects of BM and decreased as deeper layers of BM were exposed (ie, reattachment rate to basal lamina was higher than to the inner collagenous layer, which was higher than to the elastin layer, which was higher than to the outer collagenous layer). The reattachment rate to the inner collagenous layer, elastin layer, and outer collagenous layer harvested from elderly donors (age >60 years) was less than the reattachment rate to corresponding layers harvested from younger (age <50 years) donors. CONCLUSIONS Retinal pigment epithelial cell reattachment depends on the anatomical layer of BM present in the host tissue. Age-related changes in BM may interfere with RPE reattachment. Our observations may have implications for understanding the pathogenesis of age-related macular degeneration and its potential treatment with RPE transplantation techniques.
Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos

How divergent genetic systems regulate a common pathway during the development of two serial structures, forelimbs and hindlimbs, is not well understood. Specifically, HAND2 has been shown to regulate Shh directly to initiate its expression in the posterior margin of the limb mesenchyme. Although the Hand2-Shh morphoregulatory system operates in both the forelimb and hindlimb bud, a recent analysis suggested that its upstream regulation is different in the forelimb and hindlimb bud. A combination of all four Hox9 genes is required for Hand2 expression in the forelimb-forming region; however, it remains elusive what genetic system regulates the Hand2-Shh pathway in the hindlimb-forming region. By conditional inactivation of Islet1 in the hindlimb-forming region using the Hoxb6Cre transgene, we show that Islet1 is required for establishing the posterior hindlimb field, but not the forelimb field, upstream of the Hand2-Shh pathway. Inactivation of Islet1 caused the loss of posterior structures in the distal and proximal regions, specifically in the hindlimb. We found that Hand2 expression was downregulated in the hindlimb field and that Shh expression was severely impaired in the hindlimb bud. In the Hoxb6Cre; Islet1 mutant pelvis, the proximal element that is formed in a Shh-independent manner, displayed complementary defects in comparison with Pitx1–/– hindlimbs. This suggests that Islet1 and Pitx1 function in parallel during girdle development in hindlimbs, which is in contrast with the known requirement for Tbx5 in girdle development in forelimbs. Our studies have identified a role for Islet1 in hindlimb-specific development and have revealed Islet1 functions in two distinct processes: regulation upstream of the Hand2-Shh pathway and contributions to girdle development.
Mitochondrial Stress Evokes Reduced Activity of the Ubiquitin / Proteasome-System Modulating Pathogenesis of Human Metabolic Diseases

Segref, A. , Kevei, É. , Pokrzywa, W. , Schmeisser, K. , Mansfeld, J., Livnat­Levanon, N. , Ensenauer, R. , Glickman, M. H. , Ristow, M. and Hoppe, T. (2014) Pathogenesis of human mitochondrial diseases is modulated by reduced activity of the ubiquitin/proteasome system. Cell Metabolism, 19 (4). pp. 642­ 652. ISSN 1550­4131 doi: https://doi.org/10.1016/j.cmet. 2014.01. 016 Available at http://centaur.reading. ac.uk/65857/
Methodology and Indications of H2‐Breath Testing in Gastrointestinal Diseases: the Rome Consensus Conference

BACKGROUND Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.
Insecticide Resistance in the Dengue Vector Aedes aegypti from Martinique: Distribution, Mechanisms and Relations with Environmental Factors

Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies). The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the “knock-down resistance” V1016I Kdr mutation at high frequency (>87%). Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA) performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed.
Yield Stress Materials in Soft Condensed Matter

A comprehensive review is presented of the physical behavior of yield stress materials in soft condensed matter, which encompasses a broad range of materials from colloidal assemblies and gels to emulsions and non-Brownian suspensions. All these disordered materials display a nonlinear flow behavior in response to external mechanical forces due to the existence of a finite force threshold for flow to occur: the yield stress. Both the physical origin and rheological consequences associated with this nonlinear behavior are discussed and an overview is given of experimental techniques available to measure the yield stress. Recent progress is discussed concerning a microscopic theoretical description of the flow dynamics of yield stress materials, emphasizing, in particular, the role played by relaxation time scales, the interplay between shear flow and aging behavior, the existence of inhomogeneous shear flows and shear bands, wall slip, and nonlocal effects in confined geometries.
Gender bias in careseeking practices in 57 low– and middle–income countries

Background Preventive and curative medical interventions can reduce child mortality. It is important to assess whether there is gender bias in access to these interventions, which can lead to preferential treatment of children of a given sex. Methods Data from Demographic and Health Surveys carried out in 57 low– and middle–income countries were used. The outcome variable was a composite careseeking indicator, which represents the proportion of children with common childhood symptoms or illnesses (diarrhea, fever, or suspected pneumonia) who were taken to an appropriate provider. Results were stratified by sex at the national level and within each wealth quintile. Ecological analyses were carried out to assess if sex ratios varied by world region, religion, national income and its distribution, and gender inequality indices. Linear multilevel regression models were used to estimate time trends in careseeking by sex between 1994 and 2014. Findings Eight out of 57 countries showed significant differences in careseeking; in six countries, girls were less likely to receive care (Colombia, Egypt, India, Liberia, Senegal and Yemen). Seven countries had significant interactions between sex and wealth quintile, but the patterns varied from country to country. In the ecological analyses, lower careseeking for girls tended to be more common in countries with higher income concentration (P = 0.039) and higher Muslim population (P = 0.006). Coverage increased for both sexes; 0.95 percent points (pp) a year among girls (32.9% to 51.9%), and 0.91 pp (34.8% to 52.9%) among boys. Conclusion The overall frequency of careseeking is similar for girls and boys, but not in all countries, where there is evidence of gender bias. A gender perspective should be an integral part of monitoring, accountability and programming. Countries where bias is present need renewed attention by national and international initiatives, in order to ensure that girls receive adequate care and protection.
Characterization of Interface Strength as Function of Temperature and Moisture Conditions

Since Moisture Sensitivity Level (MSL) tests are part of the international reliability qualification standards, all the microelectronics components/products have to pass these specifications. Therefore, it is important to be able to efficiently and accurately characterize and predict the moisture related material and interface behavior in the real manufacturing, processing, testing and application conditions. The success of interfacial fracture mechanics approach to analyze moisture-induced failures in IC packaging strongly depend on accurate characterization of the critical adhesion strength, Gc. However, its measurement is complicated by the fact that adhesion depends not only on moisture concentration, C, but also temperature, T, and mode mixity, ψ. This paper described our research to develop a reliable methodology for interface toughness evaluation as function of temperature, humidity and mode mixity. Our methodology includes using the four-point bending test and shaft-loaded-blister method. Dedicated specimens consisting of various types of moulding compounds bonded onto leadframe are manufactured. Besides temperature, moisture content and mode mixity effects, also the influences of surface treatment (leadframe oxidation and contamination) and production process on the interface fracture toughness are evaluated. Multi-physics-based numerical methods are used to transfer the experimental critical loads to an interface strength parameter. These analysis covers mechanical, moisture diffusion, vapor pressure, hygro-swelling and CTE-mismatch modeling. To test and improve the methodology, various effects are evaluated, such as crack-length dependency, material properties, specimen- width, displacement-rate of the upper support/shaft, etc. The results of the proposed methodology indicate, as expected, a change in interface toughness by mode mixity, moisture content and temperature. It is found that Gc decreases with increasing moisture content and temperature. The presence of moisture at the given interface is observed as the important factor in the reduction of interfacial strength (20 %～45%). Furthermore, Gc increases by a factor 3～4 when the mode mixity shifts towards mode II.
Early growth response‐1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp 1b transcription

Postprandial insulin desensitization plays a critical role in maintaining whole‐body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene‐1 (Egr‐1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr‐1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr‐1 decreased insulin sensitivity. Furthermore, deletion of Egr‐1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR‐1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase‐1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR‐1 overexpression. Our results indicate that EGR‐1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption. —Wu, J., Tao, W. ‐W. , Chong, D. ‐Y. , Lai, S. ‐S. , Wang, C. , Liu, Q. , Zhang, T. ‐Y. , Xue, B. , Li, C. ‐J. Early growth response‐1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription. FASEB J. 32, 4370–4379 (2018). www.fasebj. org