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Research has identified that children differ in the extent to which they spontaneously focus on numerical aspects of the environment (Spontaneous Focusing on Numerosity, SFON) and that this correlates with their mathematics achievement. It is assumed that the mechanism underpinning this relationship is that children who spontaneously focus on numerical features of their environment will experience more self-initiated practice with number concepts. We explored this mechanism by investigating whether 4- to 5-year-old children's verbal SFON scores on a picture description task related to their spontaneous focusing on number while engaged in play activities with their parent. We found that the scores derived from a picture description task were strongly correlated with the scores derived from the play sessions, r[subscript s] = 0.638, 95% CI [0.433, 0.781], providing evidence for this mechanism. We further investigated the role that verbal abilities may play in children's performance on the picture description task, finding that general verbal abilities were not associated with verbal SFON scores. These results contribute to our understanding of the role played by verbal SFON tendencies in explaining differences in numerical development, and demonstrate the ecological validity of SFON picture tasks.

Mesenchymal stem cells (MSCs) are highly plastic, with the capacity to differentiate into a spectrum of tissue-specific stromal cells. In the field of bone regeneration, MSCs have largely been considered for their osteogenic differentiation capacity. MSCs are increasingly being appreciated for their immunomodulatory potential following exposure to pro-inflammatory stimuli (licensing). Pro-inflammatory environments arise following bone injury via activation of resident immune cells like macrophages. We describe the use of a mineralized collagen scaffold as a bone-mimetic in vitro model to study the influence of paracrine versus direct cell-to-cell contact of THP-1 macrophages on MSC osteogenic and immunomodulatory potential. Paracrine stimuli from macrophages enhance MSC osteogenic and immunomodulatory potential via upregulation of key transcriptomic markers as well as via soluble biomolecule production. Direct co-culture of MSCs and macrophages decreased immunomodulatory potential in MSCs, especially for licensed MSCs, but enhanced matrix remodeling and expression of genes related to macrophage chemotaxis. These data demonstrate the significant effect macrophage-derived paracrine factors and direct contact have on MSC activity in a biomaterial model of bone regeneration. This work illuminates a critical need to further understand these processes in more clinically relevant cell models to inform biomaterial design.

ABSTRACT: Computer-assisted sperm analysis (CASA) has become the predominant tool for assessing bull semen in AI programs. Despite such popularity CASA's ability to predict fertility has been limited, especially when emphasis is based on single motion characteristics. Our hypothesis is that numerical sets of CASA measures provide a more effective method to differentiate the potential fertilization capacity of bulls and that bulls can be clustered based on sets of CASA measures. Therefore, we used CASA to evaluate frozen-thawed semen samples from 307 Holstein and 152 Jersey bulls sourced from USDA Agricultural Research Service's National Animal Germplasm Program gene bank. Sperm was evaluated immediately after thawing and 30 min later. We evaluated sperm kinetic and morphometric means and variances to capture the structure of CASA data in relation to various sources of variation. These data were subjected to univariate and multivariate statistical methods to investigate animal and management factors affecting sperm characteristics measured by CASA. Clustering with K-means identified 4 clusters of bulls based upon each cluster's set of CASA parameters after thawing. There was little overlap among clusters for sets of CASA measures. At the extremes, bull cluster 1 (BC1, n = 180) and BC3 (n = 101) had different sire conception rates (SCR) −0.07 versus −1.29, respectively, and sets of CASA measures. Interestingly, bull cluster 2 (BC2) had CASA measures that could be perceived as negative, for example, cell size at 8.18 mm2 versus 6.37 mm2 for bull cluster 4 (BC4) and total motility of 29.7% versus 48.7% for BC3, but SCR for BC2 were higher (−0.79) than those for BC3 (−1.29). Despite such discrepancies for some BC2 CASA values it appears the potentially negative effects were offset by the levels of other CASA values. Our findings suggest improved approaches for using CASA could lie in evaluating multiple CASA measures as sets within specific numerical ranges rather than as independent measures.

The interaction between the surgical instrument and tissue is a yet little-exploited source of information. Vibroacoustic signals resulting from an interaction can be analyzed to extract relevant information related to the tissue. This work presents a summary of feasibility studies with synthetic-, animal-, and ex-vivo tissue specimen. A standard palpation probe is equipped with a vibration measurement system. A manual and robot-assisted setup is used for data acquisition. Simple features derived from the signals are used in a subsequent classification step using kNN and SVM. The obtained results show the capability to differentiate various tissues, such as subchondral bone with an accuracy of 98.44%. This demonstrates the potential of the approach to provide tissue related information based on instrument interactions.

This work presents a novel approach for detecting underlying pulsatile structures with laparoscopic tools by using proximal vibroacoustic sensing. This new method could detect pulsations at a depth of up to 1.5 cm. The outcome of this work indicates the potential of identifying deep-seated pulsatile structures during robot-assisted laparoscopy, where haptic feedback is highly limited, to help surgeons prevent vascular damage that may lead to injuries.

BackgroundMendelian randomization (MR) is a statistical approach using genetic variants as instrumental variables to estimate causal effects of a single exposure on an outcome. Multivariable MR (MVMR) extends this to estimate the direct effect of multiple exposures simulatiously. MR and MVMR can be biased by the presence of pleiotropic genetic variants in the set used as instrumental variables, violating one of the core IV assumptions. Genetic variants that give outlying estimates are often considered to be potentially pleiotropic variants. Radial plots can be used in MR to help identify these variants. Analogous plots for MVMR have so far been unavailable due to the multidimensional nature of the analysis.MethodsWe propose a radial formulation of MVMR, and an adapted Galbraith radial plot, which allows for the estimated effect of each exposure within an MVMR analysis to be visualised. Radial MVMR additionally includes an option for removal of outlying SNPs which may violate one or more assumptions of MVMR. A RMVMR R package is presented as accompanying software for implementing the methods described.ResultsWe demonstrate the effectiveness of the radial MVMR approach through simulations and applied analyses. We highlight how outliers with respect to all exposures can be visualised and removed through Radial MVMR. We present simulations that illustrate how outlier removal decreases the bias in estimated effects under various forms of pleiotropy. We apply Radial MVMR to estimate the effect of lipid fractions on coronary heart disease (CHD). In combination with simulated examples, we highlight how important features of MVMR analyses can be explored using a range of tools incorporated within the RMVMR R package.ConclusionsRadial MVMR effectively visualises causal effect estimates, and provides valuable diagnostic information with respect to the underlying assumptions of MVMR.

The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP). Cryo-EM and biochemical data revealed that Nanosota-EB1 binds to the glycan cap of GP1, preventing its protease cleavage, while Nanosota-EB2 binds to critical membrane-fusion elements in GP2, stabilizing it in the pre-fusion state. Nanosota-EB2 is a potent neutralizer of EBOV infection in vitro and offers excellent protection in a mouse model of EBOV challenge, while Nanosota-EB1 provides moderate neutralization and protection. Nanosota-EB1 and Nanosota-EB2 are the first nanobodies shown to inhibit authentic EBOV. Combined with our newly developed structure-guided in vitro evolution approach, they lay the foundation for nanobody-based therapies against EBOV and other viruses within the ebolavirus genus.

Objectives The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.Methods Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.Results 121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.Conclusion Serum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.

An editorial is presented by the new editorial team of The Journal of Consumer Research (JCR) outlining their views on the role of the journal and their vision for continuing the stewardship and mission carried forth by their predecessors. They aver that the journal serves as a vital interdisciplinary platform to advance the scientific understanding of consumer behavior by fostering diverse research contributions, improving informativeness, and promoting intellectual humility. The team emphasizes publishing rigorous, innovative, and transparent research that enhances theoretical and practical knowledge across disciplines, while encouraging critical conversations and collaborative learning within the field. With a commitment to efficiency, respect for authors’ goals, and maintaining high standards, the editors aim to position JCR as a leader in consumer behavior research over the next four years.

The idea that changing environmental conditions drive adaptive evolution is a pillar of evolutionary ecology. But, the opposite-that adaptive evolution alters ecological processes-has received far less attention yet is critical for eco-evolutionary dynamics. We assessed the ecological impact of divergent values in a key adaptive trait using 16 populations of the brown anole lizard (Anolis sagrei). Mirroring natural variation, we established islands with short- or long-limbed lizards at both low and high densities. We then monitored changes in lower trophic levels, finding that on islands with a high density of short-limbed lizards, web-spider densities decreased and plants grew more via an indirect positive effect, likely through an herbivore-mediated trophic cascade. Our experiment provides strong support for evolution-to-ecology connections in nature, likely closing an otherwise well-characterized eco-evolutionary feedback loop.