Miracle-dz/UniFAR-FTUs huggingface dataset:
RNA-guided gene editing of the murine gammaherpesvirus 68 genome reduces infectious virus production

Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) are cancer-causing viruses that establish lifelong infections in humans. Gene editing using the Cas9-guideRNA (gRNA) CRISPR system has been applied to decrease the latent load of EBV in human Burkitt lymphoma cells. Validating the efficacy of Cas9-gRNA system in eradicating infection in vivo without off-target effects to the host genome will require animal model systems. To this end, we evaluated a series of gRNAs against individual genes and functional genomic elements of murine gammaherpesvirus 68 (MHV68) that are both conserved with KSHV and important for the establishment of latency or reactivation from latency in the host. gRNA sequences against ORF50, ORF72 and ORF73 led to insertion, deletion and substitution mutations in these target regions of the genome in cell culture. Murine NIH3T3 fibroblast cells that stably express Cas9 and gRNAs to ORF50 were most resistant to replication upon de novo infection. Latent murine A20 B cell lines that stably express Cas9 and gRNAs against MHV68 were reduced in their reactivation by approximately 50%, regardless of the viral gene target. Lastly, co-transfection of HEK293T cells with the vector expressing the Cas9-MHV68 gRNA components along with the viral genome provided a rapid read-out of gene editing and biological impact. Combinatorial, multiplex MHV68 gRNA transfections in HEK293T cells led to near complete ablation of infectious particle production. Our findings indicate that Cas9-gRNA editing of the murine gammaherpesvirus genome has a deleterious impact on productive replication in three independent infection systems.
DUNEuro—A software toolbox for forward modeling in bioelectromagnetism

Accurate and efficient source analysis in electro- and magnetoencephalography using sophisticated realistic head geometries requires advanced numerical approaches. This paper presents DUNEuro, a free and open-source C++ software toolbox for the numerical computation of forward solutions in bioelectromagnetism. Building upon the DUNE framework, it provides implementations of modern fitted and unfitted finite element methods to efficiently solve the forward problems of electro- and magnetoencephalography. The user can choose between a variety of different source models that are implemented. The software’s aim is to provide interfaces that are extendable and easy-to-use. In order to enable a closer integration into existing analysis pipelines, interfaces to Python and MATLAB are provided. The practical use is demonstrated by a source analysis example of somatosensory evoked potentials using a realistic six-compartment head model. Detailed installation instructions and example scripts using spherical and realistic head models are appended.
Consensusability of First-Order Multiagent Systems Under Distributed PID Controller With Time Delay

This article analyzes the consensus of first-order multiagent systems under the network topology with a directed spanning tree. A distributed PID controller with time delay is designed. D-parameterization approach is used and the crossing set consisting of frequencies such that at least one characteristic root is on the imaginary axis is identified. It is proven that the rightward crossings of the characteristic roots are always guaranteed. The exact delay margin is then determined. Numerical simulation is proposed to demonstrate the theoretical analysis.
Metformin mediates MicroRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy: an in-silico and clinical study

Abstract Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN. Highlights MMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population. The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9. In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p. Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.
Studies on heavy metal resistance of bacterial isolates from a former uranium mining area

Es gibt nur wenige Untersuchungen, die sich mit der Metallresistenz von Gram-positiven Bakterien und insbesondere mit der okologisch sehr wichtigen Gruppe der Actinobakterien befassen. Haufig zielen Studien, die sich mit Resistenzmechanismen beschaftigen, auf Einzelprozesse wie bspw. Kationenefflux-Transport ab. Haufig losen Stressoren aber eine Vielzahl von Reaktionen aus. Die vorgestellten Untersuchungen zur Metallresistenz von Aktinobakterien verbinden aus diesem Grunde drei verschiedene Mechanismen der Detoxifizierung: Intrazellulare Sequestrierung von Metallen, Immobilisierung von Metallen an der Zellwand und Exkretion von Chelatbildnern in das Millieu. Bergbaugebiete, in denen jahrzehntelang Erzgewinnung erfolgt ist, stellen ideale Untersuchungsflachen fur Forschungsprojekte uber Metall-Mikroorganismus-Interaktionen dar. Die Gewinnung von 124 Mio t Uranerz innerhalb einer Flache von 74 km2 der Ronneburger Lagerstatte in Ostthuringen fuhrte zur grosflachigen Entstehung von metallhaltigen Habitaten. Nickel ist ein haufiges Begleitmetall von Uranerzen; es kommt in Konzentrationen bis zu 2000 ppm im Haldenmaterial dieses Bergbaugebietes vor. Die grose Anzahl von Abraumhalden mit einem Gesamtvolumen von 140 Mio t verursachte die Bildung saurer Bergbauabwasser, die uber den Wasserpfad in Verbindung mit den Mikrobenpopulationen der Habitate stehen.
G protein-coupled receptors as candidates for modulation and activation of the chemical senses in decapod crustaceans

Many studies have characterized class A GPCRs in crustaceans; however, their expression in crustacean chemosensory organs has yet to be detailed. Class A GPCRs comprise several subclasses mediating diverse functions. In this study, using sequence homology, we classified all putative class A GPCRs in two chemosensory organs (antennular lateral flagellum [LF] and walking leg dactyls) and brain of four species of decapod crustaceans (Caribbean spiny lobster Panulirus argus, American lobster Homarus americanus, red-swamp crayfish Procambarus clarkii, and blue crab Callinectes sapidus). We identified 333 putative class A GPCRs– 83 from P. argus, 81 from H. americanus, 102 from P. clarkii, and 67 from C. sapidus–which belong to five distinct subclasses. The numbers of sequences for each subclass in the four decapod species are (in parentheses): opsins (19), small-molecule receptors including biogenic amine receptors (83), neuropeptide receptors (90), leucine-rich repeat-containing GPCRs (LGRs) (24), orphan receptors (117). Most class A GPCRs are predominately expressed in the brain; however, we identified multiple transcripts enriched in the LF and several in the dactyl. In total, we found 55 sequences with higher expression in the chemosensory organs relative to the brain across three decapod species. We also identified novel transcripts enriched in the LF including a metabotropic histamine receptor and numerous orphan receptors. Our work establishes expression patterns for class A GPCRs in the chemosensory organs of crustaceans, providing insight into molecular mechanisms mediating neurotransmission, neuromodulation, and possibly chemoreception.
PCR-RFLP molecular confirmation of color dilution alopecia in dogs in Brazil

Color dilution alopecia (CDA) is a dermatopathy observed exclusively in animals having a diluted coat color. In dogs, color dilution occurs as a result of a single-nucleotide variation (SNV) c. -22G > A in the melanophilin gene. We standardized a PCR–restriction-fragment length polymorphism (PCR-RFLP) technique to identify this mutation and determine its frequency in dogs in Brazil. The standardized PCR-RFLP technique could efficiently identify the SNV c. -22G > A in the melanophilin gene, with mutated allele frequencies of 0.1, 0.1, and 0.0875 in Dachshund, Miniature Pinscher, and Yorkshire Terrier breeds, respectively, with no statistical difference among the breeds (p = 0.252). The mutation was identified in 2 homozygous Dachshund dogs with alopecia, confirming the clinical characteristic of CDA. The standardization of a simpler and more accessible molecular technique for recognition of the SNV c. -22G > A in the melanophilin gene allows identification of heterozygous (phenotypically normal) dogs that can be excluded from reproduction, to avoid the birth of dogs with diluted coat color and consequently CDA.
Psychometric properties of the Cambridge‐Mindreading Face‐Voice Battery for Children in children with ASD

This study examined the psychometric characteristics of the Cambridge‐Mindreading Face‐Voice Battery for Children (CAM‐C) for a sample of 333 children, ages 6–12 years with ASD (with no intellectual disability). Internal consistency was very good for the Total score (0.81 for both Faces and Voices) and respectable for the Complex emotions score (0.72 for Faces and 0.74 for Voices); however, internal consistency was lower for Simple emotions (0.65 for Faces and 0.61 for Voices). Test–retest reliability at 18 and 36 weeks was very good for the faces and voices total (0.76–0.81) and good for simple and complex faces and voices (0.53–0.75). Significant correlations were found between CAM‐C Faces and scores on another measure of face‐emotion recognition (Diagnostic Analysis of Nonverbal Accuracy‐Second Edition), and between Faces and Voices scores and child age, IQ (except perceptual IQ and Simple Voice emotions), and language ability. Parent‐reported ASD symptom severity and the Emotion Recognition scale on the SRS‐2 were not related to CAM‐C scores. Suggestions for future studies and further development of the CAM‐C are provided.
Novel EDGE encoding method enhances ability to identify genetic interactions

Assumptions are made about the genetic model of single nucleotide polymorphisms (SNPs) when choosing a traditional genetic encoding: additive, dominant, and recessive. Furthermore, SNPs across the genome are unlikely to demonstrate identical genetic models. However, running SNP-SNP interaction analyses with every combination of encodings raises the multiple testing burden. Here, we present a novel and flexible encoding for genetic interactions, the elastic data-driven genetic encoding (EDGE), in which SNPs are assigned a heterozygous value based on the genetic model they demonstrate in a dataset prior to interaction testing. We assessed the power of EDGE to detect genetic interactions using 29 combinations of simulated genetic models and found it outperformed the traditional encoding methods across 10%, 30%, and 50% minor allele frequencies (MAFs). Further, EDGE maintained a low false-positive rate, while additive and dominant encodings demonstrated inflation. We evaluated EDGE and the traditional encodings with genetic data from the Electronic Medical Records and Genomics (eMERGE) Network for five phenotypes: age-related macular degeneration (AMD), age-related cataract, glaucoma, type 2 diabetes (T2D), and resistant hypertension. A multi-encoding genome-wide association study (GWAS) for each phenotype was performed using the traditional encodings, and the top results of the multi-encoding GWAS were considered for SNP-SNP interaction using the traditional encodings and EDGE. EDGE identified a novel SNP-SNP interaction for age-related cataract that no other method identified: rs7787286 (MAF: 0.041; intergenic region of chromosome 7)–rs4695885 (MAF: 0.34; intergenic region of chromosome 4) with a Bonferroni LRT p of 0.018. A SNP-SNP interaction was found in data from the UK Biobank within 25 kb of these SNPs using the recessive encoding: rs60374751 (MAF: 0.030) and rs6843594 (MAF: 0.34) (Bonferroni LRT p: 0.026). We recommend using EDGE to flexibly detect interactions between SNPs exhibiting diverse action.
Predictors of Palliative Care Knowledge: Findings from the Health Information National Trends Survey

Background: Palliative care plays an important role in improving the quality of life for patients with cancer and their caregivers and has been associated with increased patient satisfaction. However, palliative care knowledge in the general population is limited, and often physician referral occurs late in prognosis. The objective of this analysis was to examine factors associated with palliative care knowledge. Method: Using data from the 2018 NCI's Health Information National Trends Survey (HINTS) 5 Cycle 2, descriptive statistics, bivariate analyses, and multivariable logistic regressions were used to assess factors associated with respondents' palliative care knowledge using ORs and 95% confidence intervals as measures of association. The outcome of interest was measured with the item “How would you describe your level of knowledge about palliative care? ” Possible response selections were “I've never heard of it,” “I know a little bit about palliative care,” and “I know what palliative care is and could explain it to someone else. ” To reduce the risk of type 1 error, jackknife variance estimations with repeated replications were used. All analyses were conducted with the SURVEYLOGISTIC command using SAS 9.4 (SAS Institute Inc.), and the statistical significance level was set at P < 0.05. Results: A total of 3,450 respondents (weighted sample size: 249,489,772) met the inclusion criteria. About 89% (n = 3,000) of all respondents had inadequate knowledge of palliative care. Multivariable analyses indicated that frequent health care utilization as defined as ≥ 2 times per year [OR, 3.01; 95% confidence interval (CI), 2.65–3.58], female gender (OR, 2.15; 95% CI, 1.31–3.59), being married (OR, 2.02; 95% CI, 1.14–3.59), having a college degree or higher (OR, 13.83; 95% CI, 1.71–12.04), and having a regular source of care (OR, 2.67; 95% CI, 1.37–1.90) had greater odds of adequate palliative care knowledge. Those without a cancer diagnosis were less likely to have adequate knowledge of palliative care (OR, 0.49; 95% CI, 0.41–0.89). Conclusions: Knowledge of palliative care in the United States is low, particularly for those not already actively using their available healthcare system. Public health education efforts are needed to target subgroups of the U.S. population identified by this analysis to increase palliative care knowledge. Impact: Healthcare providers have a major role to play in improving palliative care knowledge.
Mental Health, Behavior Change Skills, and Eating Behaviors in Postpartum Women

Excessive postpartum weight retention conveys risks for future metabolic diseases. Eating behaviors influence postpartum weight retention; however, the modifiable predictors of eating behaviors remain unclear. Using data from a three-arm, randomized controlled trial, the purpose of this study was to examine the longitudinal associations of mental health (e.g., depressive symptoms) and behavior change skills (e.g., self-efficacy) with eating behaviors (i.e., compensatory restraint, routine restraint, emotional eating, and external eating) among women (N = 424) over 18-months postpartum. Results revealed that depressive symptoms, perceived stress, healthy eating self-efficacy, overeating self-efficacy, self-weighing, and problem-solving confidence were associated with one or more of the examined eating behaviors. Furthermore, depressive symptoms moderated the association between healthy eating self-efficacy and routine restraint. Perceived stress moderated the associations between healthy eating/overeating self-efficacy and emotional eating. The findings suggest that mental health and behavior change skills may serve as targets for interventions designed to improve postpartum women’s eating behaviors. Clinical trials registry:ClinicalTrials.gov #NCT01331564
Project Echo and Primary Care Buprenorphine Treatment for Opioid Use Disorder: Implementation and Clinical Outcomes

Background: Our rural health system sought to (1) increase the number of primary care clinicians waivered to prescribe buprenorphine for treatment of opioid use disorder (OUD) and (2) consequently increase the number of our patients receiving this treatment. Methods: We used the Project for Extension for Community Health Outcomes (ECHO) tele-education model as an implementation strategy. We examined the number of clinicians newly waivered, the number of patients treated with buprenorphine, the relationship between clinician engagement with ECHO training and rates of buprenorphine prescribing, and treatment retention at 180 days. Results: The number of clinicians with a waiver and number of patients treated increased during and after ECHO training. There was a moderate correlation between the number of ECHO sessions attended by a clinician and number of their buprenorphine prescriptions (r = 0.50, p = 0.01). The 180-day retention rate was 80.7%. Conclusions: Project ECHO was highly effective for increasing access to this evidence-based treatment. The high retention rate in this rural context indicates that most patients are increasing their likelihood of favorable outcomes.
Utilizing literature-based rodent toxicology data to derive potency estimates for quantitative risk assessment

Abstract Evaluating the potential occupational health risk of engineered nanomaterials is an ongoing need. The objective of this meta-analysis, which consisted of 36 studies containing 86 materials, was to assess the availability of published in vivo rodent pulmonary toxicity data for a variety of nanoscale and microscale materials and to derive potency estimates via benchmark dose modeling. Additionally, the potency estimates based on particle mass lung dose associated with acute pulmonary inflammation were used to group materials based on toxicity. The commonalities among the physicochemical properties of the materials in each group were also explored. This exploration found that a material’s potency tended to be associated primarily with the material class based on chemical composition and form (e.g. carbon nanotubes, TiO2, ZnO) rather than with particular physicochemical properties. Limitations in the data available precluded a more extensive analysis of these associations. Issues such as data reporting and appropriate experimental design for use in quantitative risk assessment are the main reasons publications were excluded from these analyses and are discussed.
Cardiac index predicts long-term outcomes in patients with heart failure

Background The role of cardiac index (CI) and right atrial pressure (RAP) for predicting long-term outcomes of heart failure has not been well established. The aim of this study was to investigate long-term cardiac outcomes in patients with heart failure having various combinations of CI and RAP. Methods A total of 787 heart failure patients who underwent right-heart catheterization were retrospectively categorized into the following four groups: Preserved CI (≥2.5 L/min/m2) and Low RAP (<8 mmHg) (PRE-CI/L-RAP; n = 285); Preserved CI (≥2.5 L/min/m2) and High RAP (≥8 mmHg) (PRE-CI/H-RAP; n = 242); Reduced CI (<2.5 L/min/m2) and Low RAP (<8 mmHg) (RED-CI/L-RAP; n = 123); and Reduced CI (<2.5 L/min/m2) and High RAP (≥8 mmHg) (RED-CI/H-RAP; n = 137). Survival analysis was applied to investigate which groups were associated with major adverse cardiovascular events (MACE). Results The RED-CI/L-RAP and RED-CI/H-RAP groups were significantly associated with MACE as compared with the PRE-CI/L-RAP and PRE-CI/H-RAP groups after adjustment for confounding factors (RED-CI/L-RAP vs. PRE-CI/L-RAP: HR 2.11 [95% CI 1.33–3.37], p = 0.002; RED-CI/H-RAP vs. PRE-CI/L-RAP: HR 2.18 [95% CI 1.37–3.49], p = 0.001; RED-CI/L-RAP vs. PRE-CI/H-RAP: HR 1.86 [95% CI 1.16–3.00], p = 0.01; RED-CI/H-RAP vs. PRE-CI/H-RAP: HR 1.92 [95% CI 1.26–2.92], p = 0.002), whereas the difference between the RED-CI/H-RAP and RED-CI/L-RAP groups was not significant (HR 1.03 [95% CI 0.64–1.66], p = 0.89). Conclusions The hemodynamic severity categorized by CI and RAP levels provided clear risk stratification in patients with symptomatic heart failure. Low CI was an independent predictor of long-term cardiac outcomes.
Long-term medical and productivity costs of severe trauma: Results from a prospective cohort study

Background Through improvements in trauma care there has been a decline in injury mortality, as more people survive severe trauma. Patients who survive severe trauma are at risk of long-term disabilities which may place a high economic burden on society. The purpose of this study was to estimate the health care and productivity costs of severe trauma patients up to 24 months after sustaining the injury. Furthermore, we investigated the impact of injury severity level on health care utilization and costs and determined predictors for health care and productivity costs. Methods This prospective cohort study included adult trauma patients with severe injury (ISS≥16). Data on in-hospital health care use, 24-month post-hospital health care use and productivity loss were obtained from hospital registry data and collected with the iMTA Medical Consumption and Productivity Cost Questionnaire. The questionnaires were completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to investigate the drivers of health care and productivity costs. Results In total, 174 severe injury patients were included in this study. The median age of participants was 55 years and the majority were male (66.1%). The mean hospital stay was 14.2 (SD = 13.5) days. Patients with paid employment returned to work 21 weeks after injury. In total, the mean costs per patient were €24,760 with in-hospital costs of €11,930, post-hospital costs of €7,770 and productivity costs of €8,800. Having an ISS ≥25 and lower health status were predictors of high health care costs and male sex was associated with higher productivity costs. Conclusions Both health care and productivity costs increased with injury severity, although large differences were observed between patients. It is important for decision-makers to consider not only in-hospital health care utilization but also the long-term consequences and associated costs related to rehabilitation and productivity loss.