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PurposeThe aim of this study is to prospectively evaluate whether women with copper-containing intrauterine devices (Cu-IUD), currently listed as MR conditional, can safely undergo 3.0 Tesla (3 T) magnetic resonance imaging (MRI).Methods73 women, age 18-54 years old, with a Cu-IUD who were undergoing MRI for any reason were included consecutively. Pre- and post-MRI standard pelvic ultrasound examinations were completed to determine the appropriate pre- and post-MRI positioning of the Cu-IUD. Displaced IUDs were defined by IUD crossbars not in the fundal portion of the endometrial cavity, a visualized tip in the mid or lower uterus, any part of the device located in the cervical canal or outside of the endometrial canal, a fractured device, or a non-visualized IUD. Additionally, a questionnaire was completed by participants to determine the level of pre- and post-MRI pelvic pain.ResultsThere were zero observed displaced Cu-IUDs on post-MRI pelvic ultrasounds (p = 0/70, 95% CI 0, .043). Three participants were dropped from the study due to malpositioned IUDs on pre-MRI pelvic ultrasound. Six patients reported new or worsening pelvic pain/discomfort during or after their MRI examination.ConclusionOur results suggest that performing 3 T MRI using a low SAR setting does not cause displacement of Cu-IUDs, with zero out of 70 patients demonstrating IUD displacement.

The process of adaptation to the partner in the course of an interaction is still not well understood. In the case of explanatory dialogues, to provide satisfying explanations, explainers have to consider the needs of the explainees. This requires mental representations of the explainees, i.e., “partner models”. Little is known about whether and how modifications of partner models during an explanation take place. We assumed that they get informed by the interactive behaviour of the explainee and investigated partner models in relation to explainees' verbal moves. A total of 59 dyadic explanations were investigated in an observation study. The comparison of the partner models before and after the explanation showed changes regarding, e.g., knowledge, interest in the explanation, cooperation, and mood. Moves such as questions as well as summarising and paraphrasing information given by the explainees were associated with the partner model dimensions interest in the explanation and co-construction.

In novel situations, the productive communicative behavior of shy children can require more time than that of their less shy peers. Investigating 14 preschoolers, we asked which situational demands and changes contribute to the individual processing. Whereas children's shyness was measured by a standardized questionnaire given to caregivers, their processing of situational demands was measured by their nonverbal turn-timing over two sessions with a social robot. We focused on how children respond to their partner when the situation changes in comparison to a familiar one. Our results, based on grouping children by shyness level, indicate that while differences in turn-timing were not significant, shy children's turn-timing was consistently characterized by higher latencies compared to the less shy children across sessions and tasks, particularly when introduced to a new task. Correlational analysis, accounting for the full shyness spectrum, confirmed this trend. Findings clarify how children perceive a situation and situational changes.

Abstract The equilibrium of sex ratios in sexually reproducing species is often disrupted by various environmental and genetic factors, including endosymbionts like Wolbachia. In this study, we explore the highly female‐biased sex ratio observed in the flea beetle, Altica lythri, and its underlying mechanisms. Ancient hybridization events between Altica species have led to mitochondrial DNA introgression, resulting in distinct mitochondrial haplotypes that go along with different Wolbachia infections (HT1‐wLytA1, HT1*‐ uninfected, HT2‐wLytA2, and HT3‐wLytB). Notably, beetles with some haplotypes exclusively produce female offspring, suggesting potential Wolbachia‐induced phenomena such as feminization of genetic males. However, the observed female bias could also be a consequence of the ancient hybridization resulting in nuclear–cytoplasmic conflicts between introgressed mtDNA and nuclear genes. Through transcriptomic analysis and the program SEX‐DETector, we established markers for genotypic sex differentiation for A. lythri, enabling genetic sexing via qPCR. Our findings suggest that feminization of genetic males is contributing to the skewed sex ratios, highlighting the intricate dynamics of sex determination and reproductive strategies in this flea beetle. This study provides valuable insights into the dynamics of genetic conflicts, endosymbionts, and sex ratios, revealing the novel phenomenon of genetic male feminization in the flea beetle A. lythri.

Highlights A stable Zn anode was obtained by patterning Zn foil surfaces and endowing a zincphilic interface in microchannels. The accumulation of electrons in the microchannel and the zincphilic interface promoted preferential heteroepitaxial Zn deposition in the microchannel region and subsequent homoepitaxial Zn deposition on the array surface. The Zn symmetrical cells could undergo repeated plating/stripping for more than 25,000 cycles at the current densities of 10 and 20 mA cm−2.

The study investigates two different ways of guiding the addressee of an explanation - an explainee, through action demonstration: contrastive and non-contrastive. Their effect was tested on attention to specific action elements (goal) as well as on event memory. In an eye-tracking experiment, participants were shown different motion videos that were either contrastive or non-contrastive with respect to the segments of movement presentation. Given that everyday action demonstration is often multimodal, the stimuli were created with respect to their visual and verbal presentation. For visual presentation, a video combined two movements in a contrastive (e.g., Up-motion following a Down-motion) or non-contrastive way (e.g., two Up-motions following each other). For verbal presentation, each video was combined with a sequence of instruction descriptions in the form of negative (i.e., contrastive) or assertive (i.e., non-contrastive) guidance. It was found that a) attention to the event goal increased for this condition in the later time window, and b) participants’ recall of the event was facilitated when a visually contrastive motion was combined with a verbal contrast.

This work focuses on a very narrow region in the quaternary system Na2O-P2O5-SiO2-ZrO2 to explore the occasionally proposed deficiency in zirconium and oxygen content of Na+ super-ionic conductor (NaSICON) materials. In addition, this region is known for the formation of glass-ceramics, but a systematic study of such materials has not been carried out yet. For this purpose, 2 series of compositions were defined and synthesized: Na3.4Zr2-3x/4Si2.4-x/4P0.6+x/4O12-11x/8 and Na3.4Zr2-3x/4Si2.4+x/4P0.6+1.5x/4O12-x/16. They only differ in the silicate and phosphate content. In the first series the molar content is constant, nSi + nP = 3. The latter series allows an excess of the 2 cations to meet the composition Na3.1Zr1.55Si2.3P0.7O11 or alternatively re-written as Na3.4Zr1.7Si2.52P0.77Ol2, which was formerly regarded as a superior material to the frequently reported composition Na3Zr2Si2POl2.Several characterization techniques were applied to better understand the relationships between phase formation, processing, and properties of the obtained glass ceramics in the context of the quasi-quaternary phase diagram. The investigations gave clear evidence that a glass phase is progressively formed with increasing x. Therefore, compounds with x > 0.2 have to be regarded as glass-ceramic composites. The resulting NaSICON materials revealed a very limited Zr deficiency with charge compensation by Na ions and a non-detectable amount of oxygen vacancies verified by neutron scattering and atomistic simulations.Hence, this work is the first systematic investigation of pretended Zr-deficient NaSICON materials, which clearly show the chemistry of a 2-phase region. The 2 investigated series are directed toward a region that is orthogonal to the series Na3Zr3-ySi2PyO11.5+y/2 reported in the first part of this series of publications.

Abstract Background Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort. Methods NMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons. Results Here, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients. Conclusions We present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.

Abstract Spatial transcriptomics of histological sections have revolutionized research in life sciences and enabled unprecedented insights into genetic processes involved in tissue reorganization. However, in contrast to genomic analysis, the actual biomolecular composition of the sample has fallen behind, leaving a gap of potentially highly valuable information. Raman microspectroscopy provides untargeted spatiomolecular information at high resolution, capable of filling this gap. In this study we demonstrate spatially resolved Raman “spectromics” to reveal homogeneity, heterogeneity and dynamics of cell matrix on molecular levels by repurposing state-of-the-art bioinformatic analysis tools commonly used for transcriptomic analyses. By exploring sections of murine myocardial infarction and cardiac hypertrophy, we identify myocardial subclusters when spatially approaching the pathology, and define the surrounding metabolic and cellular (immune-) landscape. Our innovative, label-free, non-invasive “spectromics” approach could therefore open perspectives for a profound characterization of histological samples, while additionally allowing the combination with consecutive downstream analyses of the very same specimen.

Research about explanation processes is gaining relevance because of the increased popularity of artificial systems required to explain their function or outcome. Following an interactive approach, not only explainers but also explainees contribute to successful interactions. However, little is known about how explainees actively guide explanation processes and how their involvement relates to learning. We explored the occurrence and type of explainees’ questions in 20 adult–adult explanation dialogues about unknown present and absent objects. Crucially, we related the question types to the explainees’ subsequent recall of the unknown object labels. We found that explainees asked different types of questions, especially about the object’s label and facts. Questions about the object’s function were asked more when objects were present. In addition, requests for labeling were linked to better recall. The results contribute to designing explainable AI that aim to provide relevant explanations and to further experimental approaches to study explanations.

Abstract Background In recent years, advances in high-throughput sequencing technologies have enabled the use of genomic information in many fields, such as precision medicine, oncology, and food quality control. The amount of genomic data being generated is growing rapidly and is expected to soon surpass the amount of video data. The majority of sequencing experiments, such as genome-wide association studies, have the goal of identifying variations in the gene sequence to better understand phenotypic variations. We present a novel approach for compressing gene sequence variations with random access capability: the Genomic Variant Codec (GVC). We use techniques such as binarization, joint row- and column-wise sorting of blocks of variations, as well as the image compression standard JBIG for efficient entropy coding. Results Our results show that GVC provides the best trade-off between compression and random access compared to the state of the art: it reduces the genotype information size from 758 GiB down to 890 MiB on the publicly available 1000 Genomes Project (phase 3) data, which is 21% less than the state of the art in random-access capable methods. Conclusions By providing the best results in terms of combined random access and compression, GVC facilitates the efficient storage of large collections of gene sequence variations. In particular, the random access capability of GVC enables seamless remote data access and application integration. The software is open source and available at https://github.com/sXperfect/gvc/ .

Explanation has been identified as an important capability for AI-based systems, but research on systematic strategies for achieving understanding in interaction with such systems is still sparse. Negation is a linguistic strategy that is often used in explanations. It creates a contrast space between the affirmed and the negated item that enriches explaining processes with additional contextual information. While negation in human speech has been shown to lead to higher processing costs and worse task performance in terms of recall or action execution when used in isolation, it can decrease processing costs when used in context. So far, it has not been considered as a guiding strategy for explanations in human-robot interaction. We conducted an empirical study to investigate the use of negation as a guiding strategy in explanatory human-robot dialogue, in which a virtual robot explains tasks and possible actions to a human explainee to solve them in terms of gestures on a touchscreen. Our results show that negation vs. affirmation 1) increases processing costs measured as reaction time and 2) increases several aspects of task performance. While there was no significant effect of negation on the number of initially correctly executed gestures, we found a significantly lower number of attempts—measured as breaks in the finger movement data before the correct gesture was carried out—when being instructed through a negation. We further found that the gestures significantly resembled the presented prototype gesture more following an instruction with a negation as opposed to an affirmation. Also, the participants rated the benefit of contrastive vs. affirmative explanations significantly higher. Repeating the instructions decreased the effects of negation, yielding similar processing costs and task performance measures for negation and affirmation after several iterations. We discuss our results with respect to possible effects of negation on linguistic processing of explanations and limitations of our study.

ABSTRACT Clostridioides difficile infections begin when its metabolically dormant spores germinate in response to sensing bile acid germinants alongside amino acid and divalent cation co-germinants in the small intestine. While bile acid germinants are essential for C. difficile spore germination, it is currently unclear whether both co-germinant signals are required. One model proposes that divalent cations, particularly Ca2+, are essential for inducing germination, while another proposes that either co-germinant class can induce germination. The former model is based on the finding that spores defective in releasing large stores of internal Ca2+ in the form of calcium dipicolinic acid (CaDPA) cannot germinate when germination is induced with bile acid germinant and amino acid co-germinant alone. However, since the reduced optical density of CaDPA-less spores makes it difficult to accurately measure their germination, we developed a novel automated, time-lapse microscopy-based germination assay to analyze CaDPA mutant germination at the single-spore level. Using this assay, we found that CaDPA mutant spores germinate in the presence of amino acid co-germinant and bile acid germinant. Higher levels of amino acid co-germinants are nevertheless required to induce CaDPA mutant spores to germinate relative to WT spores because CaDPA released by WT spores during germination can function in a feedforward loop to potentiate the germination of other spores within the population. Collectively, these data indicate that Ca2+ is not essential for inducing C. difficile spore germination because amino acid and Ca2+ co-germinant signals are sensed by parallel signaling pathways. IMPORTANCE Clostridioides difficile spore germination is essential for this major nosocomial pathogen to initiate infection. C. difficile spores germinate in response to sensing bile acid germinant signals alongside co-germinant signals. There are two classes of co-germinant signals: Ca2+ and amino acids. Prior work suggested that Ca2+ is essential for C. difficile spore germination based on bulk population analyses of germinating CaDPA mutant spores. Since these assays rely on optical density to measure spore germination and the optical density of CaDPA mutant spores is reduced relative to WT spores, this bulk assay is limited in its capacity to analyze germination. To overcome this limitation, we developed an automated image analysis pipeline to monitor C. difficile spore germination using time-lapse microscopy. With this analysis pipeline, we demonstrate that, although Ca2+ is dispensable for inducing C. difficile spore germination, CaDPA can function in a feedforward loop to potentiate the germination of neighboring spores.

ObjectiveTo determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth.DesignCase control.SettingCalifornia hospitals.Participants868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010.MethodsLogistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes.Primary outcomePreterm delivery status.ResultsAdjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686.ConclusionTraditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women.

This is a joint work of two labs that offers a perspective ondevelopment and learning, which complements theconference’s focus on “changes in representation andprocessing abilities in development”. Strong background inecological psychology allowed us to recognize the richnessand multilayered structuring of infants’ environment, whichactively engages them and to which infants tune their action-perception. We conceptualize this environment as reliable“social physics”, constituted of predictable, enacted socialevents, in which infants learn to participate. Using bothtraditional (qualitative and quantitative) and dynamicalsystems methods, we show the structuring of such events onmultiple timescales and levels and how participating in themsculpts the child’s agency in the social world. We show howthis background allows a fresh look on language acquisitionand how it informs computational modelling of languageemergence and models of human-robot interaction.

When young children learn to use language, they start to use their hands in co-verbal gesturing. There are, however, considerable differences between children, and it is not completely understood what these individual differences are due to. We studied how children at 4 years of age employ speech and iconic gestures to convey meaning in different kinds of spatial event descriptions, and how this relates to their cognitive abilities. Focusing on spontaneous illustrations of actions, we applied a semantic feature (SF) analysis to characterize combinations of speech and gesture meaning and related them to the child's visual-spatial abilities or abstract/concrete reasoning abilities (measured using the standardized SON-R 2 1/2-7 test). Results show that children with higher cognitive abilities convey significantly more meaning via gesture and less solely via speech. These findings suggest that young children's use of cospeech representational gesturing is positively related to their mental representation and reasoning abilities.

In empirical research, scholars can choose between an exploratory causes-of-effects analysis, a confirmatory effects-of-causes approach, or a mechanism-of-effects analysis that can be either exploratory or confirmatory. Understanding the choice between the approaches is important for two reasons. First, the added value of each approach depends on how much is known about the phenomenon of interest at the time of the analysis. Second, because of the specializations of methods, there are benefits to a division of labor between researchers who have expertise in the application of a given method. In this preregistered study, we test two hypotheses that follow from these arguments. We theorize that exploratory research is chosen when little is known about a phenomenon and a confirmatory approach is taken when more knowledge is available. A complementary hypothesis is that quantitative researchers opt for confirmatory designs and qualitative researchers for exploration because of their academic socialization. We test the hypotheses with a survey experiment of more than 900 political scientists from the United States and Europe. The results indicate that the state of knowledge has a significant and sizeable effect on the choice of the approach. In contrast, the evidence about the effect of methods expertise is more ambivalent.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A2-2 (CA2-2) using an in vitro CRPC model. CA2-2 induced a G2/M-phase cell cycle arrest in human prostate cancer PC-3 cells and caspase-dependent apoptosis executed via an intrinsic pathway. Additionally, the drug inhibited the formation and growth of CRPC cell colonies at low micromolar concentrations. A global proteome analysis performed using the 2D-PAGE technique, followed by MALDI-MS and bioinformatical evaluation, revealed alterations in the proteins involved in cellular processes such as metastatic potential, invasion, and apoptosis. Among others, the regulation of keratin 81, CrkII, IL-1β, and cathepsin B could be identified by our proteomics approach. The effects were validated on the protein level by a 2D Western blotting analysis. Our results demonstrate the promising anticancer activity of CA2-2 in a prostate cancer model and provide insights on the underlying mode of action.

People use speech and gesture together when describing an event or action, where both modalities have different expressiveopportunities (Kendon, 2004). One question is how the two modalities are semantically coordinated, i.e. how meaning isdistributed across speech and accompanying gestures. While this has been studied only for adult speakers so far, here, wepresent a study on how young children (4 years of age) semantically coordinate speech and gesture, and how this relatesto their cognitive and (indirectly) their verbal skills. Results indicate significant positive correlations between cognitiveskills of the children and gesture-speech coordination. In addition, high cognitive skills correlate with the number ofsemantically relevant child descriptions revealing a link between verbal and cognitive skills.

ACKR3 is a critical regulator of platelet-mediated thrombosis and organ injury following ischemia/reperfusion. Platelet ACKR3 surface expression is independently associated with all-cause mortality in patients with cardiovascular diseases.