Plasma miRNAs as biomarkers for endometriosis

STUDY QUESTION: Can plasma miRNAs be used for the non-invasive diagnosis of endometriosis in infertile women? SUMMARY ANSWER: miRNA-based diagnostic models for endometriosis failed the test of independent validation. WHAT IS KNOWN ALREADY: Circulating miRNAs have been described to be differentially expressed in patients with endometriosis compared with women without endometriosis, suggesting that they could be used for the non-invasive diagnosis of endometriosis. However, these studies have shown limited consistency or conflicting results, and no miRNA-based diagnostic test has been validated in an independent patient cohort. STUDY DESIGN, SIZE, DURATION: We performed genome-wide miRNA expression profiling by small RNA sequencing to identify a set of plasma miRNAs with discriminative potential between patients with and without endometriosis. Expression of this set of miRNAs was confirmed by RT-qPCR. Diagnostic models were built using multivariate logistic regression with stepwise feature selection. In a final step, the models were tested for validation in an independent patient cohort. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Plasma of all patients was available in the biobank of the Leuven Endometriosis Centre of Excellence. Biomarker discovery and model development were performed in a discovery cohort of 120 patients (controls= 38, endometriosis= 82), and models were tested for validation in an independent cohort of 90 patients (controls= 30, endometriosis= 60). RNA was extracted with the miRNeasy Plasma Kit. Genome-wide miRNA expression analysis was done by small RNA sequencing using the NEBNext small RNA library prep kit and the NextSeq 500 System. cDNA synthesis and qPCR were performed using the Qiagen miScript technology. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a set of 42 miRNAs with discriminative power between patients with and without endometriosis based on genome-wide miRNA expression profiling. Expression of 41 miRNAs was confirmed by RT-qPCR, and 3 diagnostic models were built. Only the model for minimal-mild endometriosis (Model 2: hsa-miR-125b-5p, hsa-miR-28-5p and hsa-miR-29a-3p) had diagnostic power above chance performance in the independent validation (AUC= 60%) with an acceptable sensitivity (78%) but poor specificity (37%). LIMITATIONS, REASONS FOR CAUTION: The diagnostic models were built and tested for validation in two patient cohorts from a single tertiary endometriosis centre. Further validation tests in large cohorts with patients from multiple endometriosis centres are needed. WIDER IMPLICATION OF THE FINDINGS: Our study supports a possible biological link between certain miRNAs and endometriosis, but the potential of these miRNAs as clinically useful biomarkers is questionable in women with infertility. Large studies in well-described patient cohorts, with rigorous methodology for miRNA expression analysis, sufficient statistical power and an independent validation step, are necessary to answer the question of whether miRNAs can be used as diagnostics markers for endometriosis

Bristlebots in swarm robotics - new approaches in modeling and agent development

Bristlebots are vibration-driven mobile robots. They are characterized by small size, high speed, simple design and low costs of production and application, which are ad- vantageous qualities for agents of swarm robotic systems. In this paper, new ap- proaches in modeling and development of swarm agents are given. It is shown that a simple mass point model can be used to simulate the motion behavior of a bristlebot as complex as necessary for swarm studies. A robot prototype is presented, which has on-board everything needed as a robotic agent. The results of simulations and exper-iments are presented and compared

Seroprevalence of Lyme borreliosis in Finland 50 years ago

ObjectivesLyme borreliosis (LB) is a tick-borne infection common in Europe. In Finland, the LB seroprevalence in the healthy population was 3.9% in 2011. While the present-day seroprevalence of LB is well characterized in several European areas, there are no studies on the seroprevalence of LB before the description of the infection in the late 1970s.MethodsWe used a subset of historical serum samples (n = 994) collected during the Finnish Mobile Clinic Health Survey, a nationwide cross-sectional health survey of the 1960s and 1970s. All samples were screened with Borrelia burgdorferi whole-cell sonicate IgG ELISA. The seropositivity of the samples was further confirmed by the C6 peptide ELISA and recomBead IgG 2.0 bead immunoassay. The association of LB seropositivity with risk factors and with self-reported diseases and symptoms relating to disseminated LB were analysed by logistic regression.ResultsB. burgdorferi IgGs were detected in 199 of 994 analysed samples; hence, the overall seroprevalence was 20.0% (95% confidence interval: 17.6–22.6). The highest seroprevalence was observed in persons aged ≥50 years (165/696), in those currently not working (92/383), and in the regions of South and Central Finland (91/226 and 27/88, respectively). Further, perception of feeling unhealthy (129/197 versus 412/794) was higher among LB-seropositive individuals compared to LB-seronegative participants.ConclusionLB seroprevalence was considerably higher in Finland in the late 1960s and early 1970s than in 2011. This result questions the perception of an unprecedentedly high LB seroprevalence in present-day Europe

Low power consumption mini rotary actuator with SMA wires

Shape memory alloys (SMAs) are smart materials widely used as actuators for their high power to weight ratio despite their well-known low energy efficiency and limited mechanical bandwidth. For robotic applications, SMAs exhibit limitations due to high power consumption and limited stroke, varying from 4% to 7% of the total length. Hysteresis, during the contraction and extension cycle, requires a complex control algorithm. On the positive side, the small size and low weight are eminently suited for the design of mini actuators for robotic platforms. This paper describes the design and construction of a light weight and low power consuming mini rotary actuator with on-board contact-less position and force sensors. The design is specifically intended to reduce (i) energy consumption, (ii) dimensions of the sensory system, and (iii) provide a simple control without any need for SMA characterisation. The torque produced is controlled by on-board force sensors. Experiments were performed to investigate the energy consumption and performance (step and sinusoidal angle profiles with a frequency varying from 0.5 to 10 Hz and maximal amplitude of 15?). We describe a transient capacitor effect related to the SMA wires during the sinusoidal profile when the active SMA wire is powered and the antagonist one switched-off, resulting in a transient current time varying from 300 to 400 ms

Commentary on Guyll et al. (2023): Misuse of Statistical Method Results in Highly Biased Interpretation of Forensic Evidence

Since the National Academy of Sciences released their report outlining paths for improving reliability, standards, and policies in the forensic sciences NAS (2009), there has been heightened interest in evaluating and improving the scientific validity within forensic science disciplines. Guyll et al. (2023) seek to evaluate the validity of forensic cartridge-case comparisons. However, they make a serious statistical error that leads to highly inflated claims about the probability that a cartridge case from a crime scene was fired from a reference gun, typically a gun found in the possession of a defendant. It is urgent to address this error since these claims, which are generally biased against defendants, are being presented by the prosecution in an ongoing homicide case where the defendant faces the possibility of a lengthy prison sentence (DC Superior Court, 2023)

Caregiver Use of the Core Components of Technology-Enhanced Helping the Noncompliant Child: A Case Series Analysis of Low-Income Families

Children from low-income families are more likely to develop early-onset disruptive behavior disorders (DBDs) compared to their higher income counterparts. Low-income families of children with early-onset DBDs, however, are less likely to engage in the standard-of-care treatment, behavioral parent training (BPT), than families from other sociodemographic groups. Preliminary between-group findings suggested technology-enhanced BPT was associated with increased engagement and boosted treatment outcomes for low-income families relative to standard BPT. The current study used a case series design to take this research a step further by examining whether there was variability in use of, and reactions to, the smartphone enhancements within technology-enhanced BPT and the extent to which this variability paralleled treatment outcome. Findings provide a window into the uptake and use of technology-enhanced service delivery methods among low-income families, with implications for the broader field of children’s mental health

Annotations for Rule-Based Models

The chapter reviews the syntax to store machine-readable annotations and describes the mapping between rule-based modelling entities (e.g., agents and rules) and these annotations. In particular, we review an annotation framework and the associated guidelines for annotating rule-based models of molecular interactions, encoded in the commonly used Kappa and BioNetGen languages, and present prototypes that can be used to extract and query the annotations. An ontology is used to annotate models and facilitate their description

POMK regulates dystroglycan function via LARGE-mediated elongation of matriglycan

Matriglycan [-GlcA-β1,3-Xyl-α1,3-]n serves as a scaffold in many tissues for extracellular matrix proteins containing laminin-G domains including laminin, agrin, and perlecan. Like-acetylglucosaminyltransferase-1 (LARGE1) synthesizes and extends matriglycan on α-dystroglycan (α-DG) during skeletal muscle differentiation and regeneration; however, the mechanisms which regulate matriglycan elongation are unknown. Here, we show that Protein O-Mannose Kinase (POMK), which phosphorylates mannose of core M3 (GalNac-β1,3-GlcNac-β1,4-Man) preceding matriglycan synthesis, is required for LARGE1-mediated generation of full-length matriglycan on α-DG (~150 kDa). In the absence of Pomk in mouse skeletal muscle, LARGE1 synthesizes a very short matriglycan resulting in a ~90 kDa α-DG which binds laminin but cannot prevent eccentric contraction-induced force loss or muscle pathology. Solution NMR spectroscopy studies demonstrate that LARGE1 directly interacts with core M3 and binds preferentially to the phosphorylated form. Collectively, our study demonstrates that phosphorylation of core M3 by POMK enables LARGE1 to elongate matriglycan on α-DG, thereby preventing muscular dystrophy