Miracle-dz/UniFAR-FTUs huggingface dataset:
Trichloroethylene exposure alters dimethylated histone three lysine four in protein kinase A signaling pathway chromatin of rat sperm †

Histone three lysine four dimethylation (H3k4me2) in sperm is conserved across species and is linked to transgenerational epigenetic inheritance. To test whether H3K4me2 is a target for transgenerational inheritance of toxicity, a daily gavage bolus exposure of trichloroethylene (TCE) (1000 mg/kg/day) was given to rats for 14 weeks, then epididymal sperm were isolated and native chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) of H3K4me2 was performed. Differential region analysis determined there were 2608 significantly differential H3K4me2 regions after TCE exposure, 477 were significantly increased and 2131 were significantly decreased. Z-score enrichment of differential regions determined there were significantly decreased H3k4me2 in the coding and regulatory regions of genes in the PKA signaling pathway. These changes account for TCE induced spermatozoal toxicity and show H3K4me2 is a target for paternal inheritance of toxicity.
Impact of Naturally Contaminated Substrates on Alphitobius diaperinus and Hermetia illucens: Uptake and Excretion of Mycotoxins

Insects are considered a suitable alternative feed for livestock production and their use is nowadays regulated in the European Union by the European Commission Regulation No. 893/2017. Insects have the ability to grow on a different spectrum of substrates, which could be naturally contaminated by mycotoxins. In the present work, the mycotoxin uptake and/or excretion in two different insect species, Alphitobius diaperinus (Lesser Mealworm, LM) and Hermetia illucens (Black Soldier Fly, BSF), grown on naturally contaminated substrates, was evaluated. Among all the substrates of growth tested, the Fusarium toxins deoxynivalenol (DON), fumonisin 1 and 2 (FB1 and FB2) and zearalenone (ZEN) were found in those based on wheat and/or corn. No mycotoxins were detected in BSF larvae, while quantifiable amount of DON and FB1 were found in LM larvae, although in lower concentration than those detected in the growing substrates and in the residual fractions. Mass balance calculations indicated that BSF and LM metabolized mycotoxins in forms not yet known, accumulating them in their body or excreting in the faeces. Further studies are required in this direction due to the future employment of insects as feedstuff.
R-Map: A Map Metaphor for Visualizing Information Reposting Process in Social Media

We propose R-Map (Reposting Map), a visual analytical approach with a map metaphor to support interactive exploration and analysis of the information reposting process in social media. A single original social media post can cause large cascades of repostings (i.e., retweets) on online networks, involving thousands, even millions of people with different opinions. Such reposting behaviors form the reposting tree, in which a node represents a message and a link represents the reposting relation. In R-Map, the reposting tree structure can be spatialized with highlighted key players and tiled nodes. The important reposting behaviors, the following relations and the semantics relations are represented as rivers, routes and bridges, respectively, in a virtual geographical space. R-Map supports a scalable overview of a large number of information repostings with semantics. Additional interactions on the map are provided to support the investigation of temporal patterns and user behaviors in the information diffusion process. We evaluate the usability and effectiveness of our system with two use cases and a formal user study.
Systematic review of the psychometric properties of the Victorian Institute of Sports Assessment – Achilles tendinopathy questionnaire

Abstract Objective To review the different versions of The Victorian Institute of Sports Assessment – Achilles questionnaire for Achilles tendinopathy to evaluate its psychometric properties and the methodological quality of these studies. Methods This study is a systematic review. Setting A search was conducted in the PubMed, SCOPUS, CINAHL, Physiotherapy Evidence Database and Google Scholar databases, based on the following inclusion criteria: population with Achilles tendinopathy >18 years; validation studies of the Victorian Institute of Sports Assessment-Achilles questionnaire, in different languages, with no time limit. Two of the present authors independently assessed the quality of the studies located and extracted the relevant data. Terwee’s criteria and the COSMIN checklist were employed to ensure adequate methodological quality. Results Eleven instruments met the inclusion criteria for this review. Significant methodological flaws were detected, mostly regarding construct validity and responsiveness. Conclusions The cultural adaptation of the Spanish-language and Brazilian-Portuguese-language VISA-A presents adequate methodological quality. However, further studies are required, with greater methodological rigor, of the cultural adaptations of measurement instruments. IMPLICATIONS FOR REHABILITATION On available evidence, the Spanish-language and Brazilian-Portuguese language versions of the Victorian Institute of Sports Assessment – Achilles questionnaire are the most appropriate for patients with Achilles tendinopathy. Robust methods should be designed and implemented to obtain higher quality instruments for patients with Achilles tendinopathy to be used systematically in daily clinical practice. Most previous transcultural versions of the Victorian Institute of Sports Assessment – Achilles tendinopathy questionnaire have presented inadequate evidence of their psychometric properties and should be used with caution for patients with Achilles tendinopathy.
Identification and Application of Epitopes in EtMIC1 of Eimeria tenella Recognized by the Monoclonal Antibodies 1-A1 and 1-H2

Eimeria tenella microneme-1 protein (EtMIC1) has been proposed to be a transmembrane protein, but this characteristic has not yet been confirmed experimentally. Furthermore, despite EtMIC1 being an important candidate antigen, its key epitope has not been reported. ABSTRACT Eimeria tenella microneme-1 protein (EtMIC1) has been proposed to be a transmembrane protein, but this characteristic has not yet been confirmed experimentally. Furthermore, despite EtMIC1 being an important candidate antigen, its key epitope has not been reported. Here, two linear B-cell epitopes of EtMIC1, 91LITFATRSK99 and 698ESLISAGE705, were identified by Western blotting using specific monoclonal antibodies (MAbs) and were named epitope I (located in the I-domain) and epitope CTR (located in the CTR domain), respectively. Sequence comparative analyses of these epitopes among Eimeria species that infect chickens showed that epitope I differs greatly across species, whereas epitope CTR is relatively conserved. Point mutation assay results indicate that all the amino acid residues of the epitopes recognized by MAb 1-A1 or 1-H2 are key amino acids involved in recognition. Comparative analyses of indirect immunofluorescence assay (IFA) results for MAbs 1-A1 and 1-H2 under both nonpermeabilization and permeabilization conditions indicate that epitope I is located on the outer side of the sporozoite surface membrane whereas epitope CTR is located on the inner side, together providing experimental evidence that EtMIC1 is a transmembrane protein. IFA also labeled the EtMIC1 protein on the parasitophorous vacuole membrane and on the surface of schizonts, which suggests that the EtMIC1 protein may play an important role in parasitophorous vacuole formation and E. tenella development. Immunoprotective efficacy experiments revealed that epitope I has good immunogenicity, as evidenced by its induction of high serum antibody levels, blood lymphocyte proliferation, and CD4+ blood lymphocyte percentage.
Effects of a 12-Week Resistance Training Program on Arterial Stiffness: A Randomized Controlled Trial

Abstract Werner, TJ, Pellinger, TK, Rosette, VD, and Ortlip, AT. Effects of a 12-week resistance training program on arterial stiffness: a randomized controlled trial. J Strength Cond Res 35(12): 3281–3287, 2021—Arterial stiffness is an indicator of disease and is an independent predictor of cardiovascular events. Some reports indicate that resistance training increases indices of arterial stiffness, whereas others report no association. This study sought to determine the association between 2 common resistance training models and indices of arterial stiffness. We recruited 30 male, untrained subjects (18–30 years) and randomized them into 1 of 3 groups: control (CON, n = 10), high-intensity resistance exercise (HI, n = 10), and high-volume resistance exercise (HV, n = 10). Subjects randomized to the resistance training groups were required to perform whole-body strength training exercises 3–5 days a week for 12 weeks. The exercise regimen consisted of 2–3 sets of 3–8 repetitions (80–90% of 1 repetition maximum [1RM]) for the HI group and 3–4 sets of 10–15 repetitions (50–70% of 1RM) for the HV group. Anthropometry, carotid artery diameters, peripheral and central blood pressure, and maximal dynamic strength were measured before and after the 12-week study period. Subjects were instructed to maintain their normal diet and avoid aerobic exercise during the study. After the intervention, both the HI and HV groups increased their maximal strength on the back squat, bench press, and seated row (all p < 0.05). However, there were no changes in arterial stiffness indices between the groups. Using a randomized controlled trial with validated measurements of arterial stiffness, chronic resistance training does not appear to influence central arterial stiffness, regardless of training volume and load.
Survey of activity pacing across healthcare professionals informs a new activity pacing framework for chronic pain/fatigue

Abstract Introduction Activity pacing is considered a key component of rehabilitation programmes for chronic pain/fatigue. However, there are no widely used guidelines to standardize how pacing is delivered. This study aimed to undertake the first stage in developing a comprehensive evidence‐based activity pacing framework. Methods An online survey across pain/fatigue services in English National Health Service trusts explored healthcare professionals' opinions on the types/uses of pacing, aims, facets and perceived effects. Data were analysed using descriptive statistics for closed‐ended questions and thematic analysis for open‐ended questions. Purposeful recruitment with a snowball effect engaged 92 healthcare professionals (physiotherapists, occupational therapists, nurses, doctors and psychologists) to the study. Results Pacing was highly utilized, with perceived long‐term benefits for patients (n = 83, 90.2% healthcare professionals instructed pacing). The most endorsed aim of pacing was “achievement of meaningful activities” (24.5% of ranked votes). The least endorsed aim was “to conserve energy” (0.1% of ranked votes). The most frequently supported facet of pacing was “breaking down tasks” (n = 91, 98.9%). The least supported facet was “stopping activities when symptoms increase” (n = 6, 6.5%). Thematic analysis showed recurring themes that pacing involved flexibility and sense of choice. Conclusions Pacing is a multidimensional coping strategy and complex behaviour. The message is clear that pacing should enable increases in meaningful activities, as opposed to attempting to avoid symptoms. The survey findings have informed the development of an activity pacing framework to guide healthcare professionals on the multiple components of pacing. This will help to standardize and optimize treatments for chronic pain/fatigue and enable future investigations.
Stat3-mTOR signaling mediates the stimulation of GLP-1 production induced by IL-27.

GLP-1 is a potent glucose-dependent insulinotropic hormone derived from intestinal L cells. Inflammatory Interleukin-27 (IL-27), a pleiotropic two-chain cytokine, is composed of EBI3 and IL-27 p28 subunits. IL-27 has a protective effect on pancreatic β-cell function. The relationship between IL-27 and GLP-1 is still unexplored. Here we showed Interleukin-27 stimulated GLP-1 production via the Stat3-mTOR dependent mechanism. Interleukin 27 receptor subunit alpha (IL-27 Rα) was detected in ileum and STC-1 cells. Co-localization of EBI3 and GLP-1 was observed not only in mouse ileums but also in human ileums and colons. Third-ventricular infusion of IL-27 increased ileal and plasma GLP-1 in both lean C57BL/6J mice and diet-induced obese and diabetic mice. These changes were associated with a significant increase in Stat3-mTOR activity. Treatment of STC-1 cells with IL-27 contributed to the increments of Stat3-mTOR signaling and GLP-1. Interference of mTOR activity by mTOR siRNA or rapamycin abolished the stimulation of GLP-1 production induced by IL-27 in STC-1 cells. Stat3 siRNA also blocked the stimulus effect of IL-27 on GLP-1. IL-27 increased the interaction of mTOR and Stat3 in STC-1 cells. Our results identify Stat3-mTOR as a critical signaling pathway for the stimulation of GLP-1 induced by IL-27.
Mass Spectrometry Fingerprints of Small-Molecule Metabolites in Biofluids - Building a Spectral Library of Recurrent Spectra for Urine Analysis.

A large fraction of ions observed in electrospray liquid chromatography-mass spectrometry (LC-ESI-MS) experiments of biological samples remain unidentified. One of the main reasons for this is that spectral libraries of pure compounds fail to account for the complexity of the metabolite profiling of complex materials. Recently, the NIST Mass Spectrometry Data Center has been developing a novel type of searchable mass spectral library that includes all recurrent unidentified spectra found in the sample profile. These libraries, in conjunction with the NIST tandem mass spectral library, allow analysts to explore most of the chemical space accessible to LC-MS analysis. In this work, we demonstrate how these libraries can provide a reliable fingerprint of the material by applying them to a variety of urine samples, including an extremely altered urine from cancer patients undergoing total body irradiation. The same workflow is applicable to any other biological fluid. The selected class of acylcarnitines is examined in detail and derived libraries and related software are freely available. They are intended to serve as online resources for continuing community review and improvement.
An Adversarial Robustness Perspective on the Topology of Neural Networks

In this paper, we investigate the impact of neural networks (NNs) topology on adversarial robustness. Specifically, we study the graph produced when an input traverses all the layers of a NN, and show that such graphs are different for clean and adversarial inputs. We find that graphs from clean inputs are more centralized around highway edges, whereas those from adversaries are more diffuse, leveraging under-optimized edges. Through experiments on a variety of datasets and architectures, we show that these under-optimized edges are a source of adversarial vulnerability and that they can be used to detect adversarial inputs.
Generation and validation of a limited sampling strategy to monitor mycophenolic acid exposure in children with nephrotic syndrome.

BACKGROUND Mycophenolate mofetil (MMF) plays an increasingly important role in the treatment of children with nephrotic syndrome, especially in steroid sparing protocols. Recent publications show the relationship of exposure to its active moiety mycophenolic acid (MPA) and clinical efficacy. Performance of full time pharmacokinetic (PK) profiles, however, is inconvenient and laborious. Established limited sampling strategies (LSS) to estimate the area under the concentration versus time curve of MPA (MPA-AUC) in pediatric renal transplant recipients cannot be easily transferred to children suffering from nephrotic syndrome, mainly because of the lack of concomitant immunosuppressive therapy. We therefore aimed for the generation and validation of a LSS to estimate MPA exposure to facilitate therapeutic drug monitoring in children with nephrotic syndrome. METHODS We performed 27 complete PK profiles in 23 children in remission [mean age (±SD):12.3±4.26 years] in order to generate and validate an LSS. Sampling time points were before administration (C0) and 0.5, 1, 1.5, 2, 4, 6, 8 and 12 hours after the administration of MMF. MPA was measured by enzyme multiplied immunoassay technique (Emit). There was no concomitant treatment with calcineurin inhibitors. RESULTS Mean daily dose of mycophenolate mofetil (MMF) was 927±209 mg/m BSA resulting in a mean MPA-AUC0-12 value of 59.2±29.3 mg*h/L and a pre-dose level of 3.03±2.24 mg/L. Between-patient variability of dose-normalized MPA-AUC0-12 was high (coefficient of variation: 45.5%). Correlation of pre-dose levels with the corresponding MPA-AUC0-12 was moderate (r=0.59) in a subgroup of 18 patients (20 PK profiles, generation group). An algorithm based on three PK sampling time points during the first 2 hours after MMF dosing (estimated AUC0-12= 8.7+4.63*C0+1.90*C1+1.52* C2) was able to predict MPA-AUC with a low percentage prediction error (3.88%) and a good correlation of determination (r=0.90). Validation of this algorithm in a randomized separate group of 6 patients (7 PK profiles, validation group) resulted in comparably good correlation (r=0.95) and low percentage prediction error (5.57%). CONCLUSIONS An abbreviated profile within the first 2 hours after MMF dosing gives a good estimate of MPA exposure in children with nephrotic syndrome and hence has the potential to optimize MMF therapy.
Large-scale identification of pathogen essential genes during coinfection with sympatric and allopatric microbes

Significance Studies of the microbial communities living in association with animals, with plants, and in the environment have revolutionized our understanding of microbial diversity, but the interactions between these microbes remain largely elusive. Here, we characterize pairwise interactions during infection between a human pathogen and 25 diverse microbes from both sympatric (same) and allopatric (different) environments. We demonstrate that allopatric microbes increase survival of the pathogen. Furthermore, we identify the large set of genes (33% of the genome) that are essential for pathogen survival during coinfection, including a core set that are also required in monoinfection and diverse accessory essential genes. This work advances our understanding of how coinfecting microbes modulate the genes required for survival in vivo. Recent evidence suggests that the genes an organism needs to survive in an environment drastically differ when alone or in a community. However, it is not known if there are universal functions that enable microbes to persist in a community and if there are functions specific to interactions between microbes native to the same (sympatric) or different (allopatric) environments. Here, we ask how the essential functions of the oral pathogen Aggregatibacter actinomycetemcomitans change during pairwise coinfection in a murine abscess with each of 15 microbes commonly found in the oral cavity and 10 microbes that are not. A. actinomycetemcomitans was more abundant when coinfected with allopatric than with sympatric microbes, and this increased fitness correlated with expanded metabolic capacity of the coinfecting microbes. Using transposon sequencing, we discovered that 33% of the A. actinomycetemcomitans genome is required for coinfection fitness. Fifty-nine “core” genes were required across all coinfections and included genes necessary for aerobic respiration. The core genes were also all required in monoinfection, indicating the essentiality of these genes cannot be alleviated by a coinfecting microbe. Furthermore, coinfection with some microbes, predominately sympatric species, induced the requirement for over 100 new community-dependent essential genes. In contrast, in other coinfections, predominately with nonoral species, A. actinomycetemcomitans required 50 fewer genes than in monoinfection, demonstrating that some allopatric microbes can drastically alleviate gene essentialities. These results expand our understanding of how diverse microbes alter growth and gene essentiality within polymicrobial infections.
Cloning and Functional Assessments of Floral-Expressed SWEET Transporter Genes from Jasminum sambac

Sugar transporters of the SWEET family mediate cross membrane movement of mono- and disaccharides and play vital roles in diverse physiological and pathophysiological processes, including sink–source relationship, pathogen responses, reproductive growth, and development. However, it remains to be determined how these transporters function in non-module plants of agricultural significance, given the evolutionarily diverse traits. In this study, we combined transcriptome analysis, rapid amplification of cDNA ends-cloning (RACE-cloning), expression profiling, and heterologous functional assay to identify SWEET genes that may have potential roles during flower opening and sexual reproduction in Jasminum sambac . During the anthesis, the floral organs of J. sambac express seven SWEET homologous genes from all four clades of the family. JsSWEET9 and 2 are significantly upregulated when flowers are fully opened, up to 6- and 3-fold compared to unopened buds, respectively. The other transporters, JsSWEET1, 5, 10, and 17 are also accumulated slightly at stage associated with fragrance release, whereas only the vacuole transporter JsSWEET16 showed small decrease in transcript level after anthesis. The JsSWEET5, a clade II member, is capable to complement yeast cell uptake on most tested sugar substrates with a preference for hexoses, while the clade I transporter JsSWEET1 mediates merely galactose import when expressed in yeast. Our results provide first evidence for further investigation on sugar transport and allocation during flowering and reproductive processes in J. sambac.
Quasi-Synchronization of Discrete-Time Lur’e-Type Switched Systems With Parameter Mismatches and Relaxed PDT Constraints

This paper investigates the problem of quasi-synchronization for a class of discrete-time Lur’e-type switched systems with parameter mismatches and transmission channel noises. Different from the previous studies referring to the persistent dwell-time (PDT) switching signals, the average dwell-time (ADT) constraints combined with the PDT are considered simultaneously in this paper to relax the limitation of dwell-time requirements and to improve the flexibility of the PDT switching signal design. By virtue of the semi-time-varying (STV) Lyapunov function, the synchronization criteria for transmitter–receiver systems in a switched version are obtained to satisfy a prescribed synchronization error bound. An estimate of the synchronization error bound is provided via the reachable set approach and, further, an explicit description of the error bounds is given. Then, sufficient conditions on the existence of STV observers are derived with a predetermined error bound, and the corresponding observer gains are calculated via solving a group of linear matrix inequalities. Finally, the effectiveness and validness of the developed theoretical results are demonstrated via a numerical example.