Miracle-dz/UniFAR-FTUs huggingface dataset:
Human pain genetics database: a resource dedicated to human pain genetics research

Abstract The Human Pain Genetics Database (HPGDB) is a comprehensive variant-focused inventory of genetic contributors to human pain. After curation, the HPGDB currently includes 294 studies reporting associations between 434 distinct genetic variants and various pain phenotypes. Variants were then submitted to a comprehensive analysis. First, they were validated in an independent high-powered replication cohort by testing the association of each variant with 10 different pain phenotypes (n = 1320-26,973). One hundred fifty-five variants replicated successfully (false discovery rate 20%) in at least one pain phenotype, and the association P values of the HPGDB variants were significantly lower compared with those of random controls. Among the 155 replicated variants, 21 had been included in the HPGDB because of their association with analgesia-related and 13 with nociception-related phenotypes, confirming analgesia and nociception as pathways of vulnerability for pain phenotypes. Furthermore, many genetic variants were associated with multiple pain phenotypes, and the strength of their association correlated between many pairs of phenotypes. These genetic variants explained a considerable amount of the variance between different pairs of pain phenotypes, indicating a shared genetic basis among pain phenotypes. In addition, we found that HPGDB variants show many pleiotropic associations, indicating that genetic pathophysiological mechanisms are also shared among painful and nonpainful conditions. Finally, we demonstrated that the HPGDB data set is significantly enriched for functional variants that modify gene expression, are deleterious, and colocalize with open chromatin regions. As such, the HPGDB provides a validated data set that represents a valuable resource for researchers in the human pain field.
Cardiac sympathetic innervation, from a different point of (re)view

The audience of basic and clinical scientists is familiar with the notion that the sympathetic nervous system controls heart function during stresses. However, evidence indicates that the neurogenic control of the heart spans from the maintenance of housekeeping functions in resting conditions to the recruitment of maximal performance, in the fight‐or‐flight responses, across a whole range of intermediate states. To perform such sophisticated functions, sympathetic ganglia integrate both peripheral and central inputs, and transmit information to the heart via ‘motor’ neurons, directly interacting with target cardiomyocytes. To date, the dynamics and mode of communication between these two cell types, which determine how neuronal information is adequately translated into the wide spectrum of cardiac responses, are still blurry. By combining the anatomical and structural information brought to light by recent imaging technologies and the functional evidence in cellular systems, we focus on the interface between neurons and cardiomyocytes, and advocate the existence of a specific ‘neuro‐cardiac junction’, where sympathetic neurotransmission occurs in a ‘quasi‐synaptic’ way. The properties of such junctional‐type communication fit well with those of the physiological responses elicited by the cardiac sympathetic nervous system, and explain its ability to tune heart function with precision, specificity and elevated temporal resolution.
A comparative study of characteristics of polytetrafluoroethylene fibers manufactured by various processes

A series of polytetrafluoroethylene (PTFE) fibers were manufactured by three processing methods including extrusion process, split-sheet process and split-film process. The influence of processing methods on fiber properties were systematically studied using four PTFE powders with various molecular weights (3.86 × 107, 4.71 × 107, 4.92 × 107 and 5.11 × 107, respectively). Morphology, crystallinity, tensile behavior and friction properties of PTFE fibers were compared by scanning electron micrograph, X-ray diffraction pattern, strength-elongation curves and friction coefficients, respectively. The results showed that the in terms of flat filaments, mechanical properties became weak with the increase of molecular weight of PTFE powders at first, but were improved dramatically with further enhancement of molecular weight. In the case of both round filaments and split-film fibers, fiber properties were improved with growth of molecular weight. Based on characteristics and friction coefficients, potential applications of three types of PTFE samples were analyzed. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43553.
Evidence That the Microbiota Counteracts Male Outbreeding Strategy by Inhibiting Sexual Signaling in Females

The microbiota is increasingly being recognized as having important impacts on many host biological processes. However, evidence of its effects on animal communication and breeding strategy is lacking. In this three-factorial study, we show that females were more willing to mate with related males, with relatedness likely being assessed through the microbiota. By contrast, male mating investment is concurrently determined by both the relatedness and microbiota status of the female. When the microbiota in female Drosophila melanogaster is altered by an antibiotic, male investment in sperm number increased when mating with unrelated females compared to related ones. Contrastingly, the presence of an intact microbiota in females cancelled this male outbreeding strategy. As a consequence, the microbiota, when intact, decreased the fitness of the mating couple. Furthermore, we showed that female sexual signaling (cuticular hydrocarbons), with regards to kin recognition, significantly interacts with microbiota. Interestingly, the interaction is significant for hydrocarbons expressed by both sexes, but not for female-specific compounds. Taken together, our results suggest that microbiota can influence kin recognition by disfavoring male outbreeding strategies, likely by inhibiting key olfactory sexual signaling. This represents the first evidence of a host outbreeding strategy counteracted by their microbiota.
Support vector machine applied to predict the zoonotic potential of E. coli O157 cattle isolates

Significance Zoonotic infections with enterohemorrhagic Escherchia coli O157 have emerged as a serious threat to human health. Conventional sequence-based analyses indicate that most human infections originate from particular pathogenic lineages. In this study, we apply a machine-learning approach to complex pangenome information and predict the human infection potential of cattle E. coli O157 isolates. We demonstrate that only a small subset of bovine strains is likely to cause human disease, even within previously defined pathogenic lineages. The approach was tested across isolates from the United Kingdom and United States and verified with food and cattle isolates from outbreak investigations. This finding has important implications for targeting of control strategies in herds. Sequence analyses of pathogen genomes facilitate the tracking of disease outbreaks and allow relationships between strains to be reconstructed and virulence factors to be identified. However, these methods are generally used after an outbreak has happened. Here, we show that support vector machine analysis of bovine E. coli O157 isolate sequences can be applied to predict their zoonotic potential, identifying cattle strains more likely to be a serious threat to human health. Notably, only a minor subset (less than 10%) of bovine E. coli O157 isolates analyzed in our datasets were predicted to have the potential to cause human disease; this is despite the fact that the majority are within previously defined pathogenic lineages I or I/II and encode key virulence factors. The predictive capacity was retained when tested across datasets. The major differences between human and bovine E. coli O157 isolates were due to the relative abundances of hundreds of predicted prophage proteins. This finding has profound implications for public health management of disease because interventions in cattle, such a vaccination, can be targeted at herds carrying strains of high zoonotic potential. Machine-learning approaches should be applied broadly to further our understanding of pathogen biology.
Remote Sensing and Cropping Practices: A Review

For agronomic, environmental, and economic reasons, the need for spatialized information about agricultural practices is expected to rapidly increase. In this context, we reviewed the literature on remote sensing for mapping cropping practices. The reviewed studies were grouped into three categories of practices: crop succession (crop rotation and fallowing), cropping pattern (single tree crop planting pattern, sequential cropping, and intercropping/agroforestry), and cropping techniques (irrigation, soil tillage, harvest and post-harvest practices, crop varieties, and agro-ecological infrastructures). We observed that the majority of the studies were exploratory investigations, tested on a local scale with a high dependence on ground data, and used only one type of remote sensing sensor. Furthermore, to be correctly implemented, most of the methods relied heavily on local knowledge on the management practices, the environment, and the biological material. These limitations point to future research directions, such as the use of land stratification, multi-sensor data combination, and expert knowledge-driven methods. Finally, the new spatial technologies, and particularly the Sentinel constellation, are expected to improve the monitoring of cropping practices in the challenging context of food security and better management of agro-environmental issues.
Impact of urbanization on user expectations related to public transport accessibility

An analysis of experience and expectations of urban residents towards accessibility to public transport systems from a number of cities at varying levels of urbanization is presented. A framework suitable to investigate differences of walking time to public transport facilities was initially established. It is then demonstrated that there is a relationship between the level of service of accessibility to public transport systems in a given urban area and expectations of its residents. Access to bus stops as well as railway stations has been considered. The paper provides a framework for planners to identify the perceived value of improvements to accessibility by accounting for the difference between the improvement of a physical measure of accessibility and the increased level of expectation of the subject community. The analysis has shown that it is important to keep the walking time for access to public transport systems below a specific value to ensure that the level of service associated with accessibility is within community expectations.
Zinc oxide and silver nanoparticles toxicity in the baker's yeast, Saccharomyces cerevisiae

Engineered nanomaterials (ENMs) are increasingly incorporated into a variety of commercial applications and consumer products; however, ENMs may possess cytotoxic properties due to their small size. This study assessed the effects of two commonly used ENMs, zinc oxide nanoparticles (ZnONPs) and silver nanoparticles (AgNPs), in the model eukaryote Saccharomyces cerevisiae. A collection of ≈4600 S. cerevisiae deletion mutant strains was used to deduce the genes, whose absence makes S. cerevisiae more prone to the cytotoxic effects of ZnONPs or AgNPs. We demonstrate that S. cerevisiae strains that lack genes involved in transmembrane and membrane transport, cellular ion homeostasis, and cell wall organization or biogenesis exhibited the highest sensitivity to ZnONPs. In contrast, strains that lack genes involved in transcription and RNA processing, cellular respiration, and endocytosis and vesicular transport exhibited the highest sensitivity to AgNPs. Secondary assays confirmed that ZnONPs affected cell wall function and integrity, whereas AgNPs exposure decreased transcription, reduced endocytosis, and led to a dysfunctional electron transport system. This study supports the use of S. cerevisiae Gene Deletion Array as an effective high-throughput technique to determine cellular targets of ENM toxicity.
Abnormal Somatosensory Synchronization in Patients With Paroxysmal Kinesigenic Dyskinesia: A Magnetoencephalographic Study

Paroxysmal kinesigenic dyskinesia (PKD) is a rare group of hyperkinetic movement disorders characterized by brief attacks of choreoathetosis or dystonia. To clarify the alterations of the functional connectivity within the somatosensory network in PKD patients, magnetoencephalographic (MEG) responses to paired median-nerve electrical stimulation were recorded in 10 PKD patients treated by carbamazepine or oxcarbamazepine and 22 age-matched controls. In patients, MEG recordings were obtained during drug-on and -off periods. Source-based functional connectivity analysis was performed between contralateral primary (cSI) and secondary (cSII), and ipsilateral secondary (iSII) somatosensory areas. During drug-off periods, patients with PKD demonstrated decreased cSI-iSII and increased cSII-iSII somatosensory connectivity at theta band. Drug-on periods lowered the functional connectivity in cSI-cSII at alpha and beta bands and in cSII-iSII at theta band compared with the drug-off periods. We suggest that altered theta functional connectivity in cSI-iSII and cSII-iSII could be the neurophysiological signatures in PKD.
Melinjo (Gnetum gnemon) Seed Extract Consumption during Lactation Improved Vasodilation and Attenuated the Development of Hypertension in Female Offspring of Fructose-Fed Pregnant Rats.

BACKGROUND Fructose intake has been correlated with increased prevalence of metabolic disorders including hypertension. In pregnant rats, fructose intake has been reported to have adverse effects on the health of its offspring. This study investigated the effects of gestational maternal fructose consumption and if supplementation with melinjo seed extracts to the maternal diet during lactation could benefit the offspring in later life. METHODS Pregnant rats were randomly divided into three groups: untreated (CC), fructose-treated (FC), and fructose and melinjo-treated (FM). FC and FM groups received 100 g/L of D(-)-fructose solution by means of the drinking water during gestation while CC received normal drinking water. During lactation, CC and FC groups were given standard commercial laboratory diet, while the FM group was given commercial laboratory diet with 0.1% melinjo seed extracts. After weaning, the offspring were given normal drinking water and standard commercial diet until week 17. The blood pressure of the offspring was monitored until the 16th week. During week 17, the offspring were killed, and the kidneys were collected and analyzed. RESULTS The level of renal phosphorylated AMP-activated protein kinase (pAMPK) in FM of 17-week female offspring was significantly higher compared with FC and CC groups. Maternal fructose intake down-regulated the renal endothelial isoform of nitric oxide synthetase expression in FC and maternal melinjo seed extract consumption maintained renal endothelial isoform of nitric oxide synthetase expression in FM of 17-week female offspring. In addition, maternal melinjo seed extract intake during lactation lowered the systolic blood pressure in FM of 17-week female offspring. CONCLUSION Female offspring were more vulnerable to the effects of placental fructose and melinjo seed extracts, suggesting sex-specific sensitivities. In summary, our data show that melinjo seed extract consumption during lactation improved vasodilation and attenuated the development of hypertension in the 17-week female offspring of fructose-fed pregnant rats. Birth Defects Research 110:27-34, 2018. © 2017 Wiley Periodicals, Inc.
Inelastic parametric analysis of two-way asymmetrical multi-storey buildings

This article presents a parametric study on the lateral-torsional coupling behaviour of the simplified bidirectional asymmetric multi-storey dual lateral load-resisting model. The implementation process for establishing the simplification model is shown in an illustrative example on a three-storey reinforced concrete building system. Combined with the force–displacement relationships of the lateral load-resisting members and the inter-story restoring force models, the dynamic stiffness matrix and the equations of motion under different loading conditions can also be determined. On this basis, parametric analyses for the systems are carried out through the whole loading process from the elastic stage to the inelastic stage. Effects of uncoupled torsion to lateral frequency ratios (Ω) and the stiffness eccentricities on the frequencies are investigated. The analysis shows that the asymmetrical system with a smaller Ω value has a smaller torsional stiffness and a stronger lateral-torsional coupling effect. The effects of the eccentricities in both directions on the frequencies are remarkably different. Smaller Ω values and greater eccentricities lead to greater reductions in the effects of Ω and eccentricities on the frequencies in the inelastic stage.
Treatment Patterns Among Patients with Psoriatic Arthritis Treated with a Biologic in the United States: Descriptive Analyses from an Administrative Claims Database

BACKGROUND: In patients with psoriatic arthritis (PsA), limited data exist regarding patterns of biologic therapy use. OBJECTIVE: To examine treatment patterns and therapy modifications in U.S. patients with PsA receiving a tumor necrosis factor inhibitor (TNFi) or an anti-interleukin (IL)-12/23 inhibitor. METHODS: Adults with PsA who newly initiated a biologic therapy (index biologic) between January 1, 2013, and January 31, 2015, were included from the Optum Research Database. Biologic therapies comprised those that were approved by the FDA for the treatment of PsA at the time of the study initiation (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or ustekinumab). Outcomes included adherence, persistence, and discontinuation of the index biologic; initiation of adjunctive medications (nonbiologics, including those commonly used for pain and/or inflammation); and dose escalation of the index biologic during the 12-month follow-up period. RESULTS: Of the 1,235 patients included, 52.5% were female, and mean (SD) age was 50.3 (12.1) years. The mean (SD) duration of persistence with a newly initiated index biologic (etanercept [48.1%], adalimumab [24.0%], infliximab [10.4%], golimumab [8.3%], ustekinumab [7.2%], or certolizumab pegol [2.0%]) was 246 (128) days; 44.5% of patients persisted with the index biologic for ≥ 12 months. During the 12-month follow-up period, 22.9% of patients switched to a different biologic, 26.8% discontinued without switching or restarting, and 5.8% discontinued and restarted the index biologic. Of the 1,010 patients who persisted with the index biologic for > 90 days, 45.6% received ≥ 1 adjunctive medication during the period from 90 days after the index date to the end of persistence or 12 months. The most commonly initiated adjunctive medications were corticosteroids (22.0%), opioids (17.1%), and nonsteroidal anti-inflammatory drugs (12.9%). Overall, 9.6% of patients had a dose escalation of the index biologic in the immediate 12-month post-index period. CONCLUSIONS: This real-world study of treatment patterns for PsA, which used a large U.S. claims database, demonstrated that the majority of patients with PsA discontinued their index biologic (TNFi or anti-IL-12/23 inhibitor) before 12 months. Nearly half of patients initiated an adjunctive medication, many of which were pain and conventional anti-inflammatory medications.
A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy

Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (PCHISQ = 3.425e−14, n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet–Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and <5% are motile. This suggests that BBS4 contributes to flagella motility but not formation in the dog. Our results suggest a promising opportunity for studying Bardet–Biedl syndrome in a large animal model.
Exploratory assessment of left ventricular strain–volume loops in severe aortic valve diseases

Severe aortic valve diseases are common cardiac abnormalities that are associated with poor long‐term survival. Before any reduction in left ventricular (LV) function, the left ventricle undergoes structural remodelling under the influence of changing haemodynamic conditions. In this study, we combined temporal changes in LV structure (volume) with alterations in LV functional characteristics (strain, ԑ) into a ԑ–volume loop, in order to provide novel insight into the haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV ejection fraction. We showed that our novel ԑ–volume loop and the specific loop characteristics provide additional insight into the functional and mechanical haemodynamic consequences of severe aortic valve diseases (with preserved LV ejection fraction). Finally, we showed that the ԑ–volume loop characteristics provide discriminative capacity compared with conventional measures of LV function.