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When speaking to infants, adults often produce speech that differs systematically from that directed to other adults. To quantify the acoustic properties of this speech style across a wide variety of languages and cultures, we extracted results from empirical studies on the acoustic features of infant-directed speech. We analysed data from 88 unique studies (734 effect sizes) on the following five acoustic parameters that have been systematically examined in the literature: fundamental frequency (f0), f0 variability, vowel space area, articulation rate and vowel duration. Moderator analyses were conducted in hierarchical Bayesian robust regression models to examine how these features change with infant age and differ across languages, experimental tasks and recording environments. The moderator analyses indicated that f0, articulation rate and vowel duration became more similar to adult-directed speech over time, whereas f0 variability and vowel space area exhibited stability throughout development. These results point the way for future research to disentangle different accounts of the functions and learnability of infant-directed speech by conducting theory-driven comparisons among different languages and using computational models to formulate testable predictions.

Transforming growth factor [beta] (TGF-[beta]) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-[beta] remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-[beta] in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-[beta]. The activation of latent TGF-[beta] requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin [[alpha].sub.V] (ITGAV). Conditional ablation of WNT5A or its downstream targets prevented activation of latent TGF-[beta], rebalanced TGF-[beta] signaling, and ameliorated experimental fibrosis. We thus uncovered what we believe to be a novel mechanism for the aberrant activation of latent TGF-[beta] in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach., Introduction Fibrosis is defined as the excessive deposition of extracellular matrix in the affected tissues. Activated myofibroblasts are the principal source of extracellular matrix production in physiologic tissue repair as [...]

From the earliest months of life, infants prefer listening to and learn better from infant-directed speech (IDS) than adult-directed speech (ADS). Yet, IDS differs within communities, across languages, and across cultures, both in form and in prevalence. This large-scale, multi-site study used the diversity of bilingual infant experiences to explore the impact of different types of linguistic experience on infants' IDS preference. As part of the multi-lab ManyBabies 1 project, we compared lab-matched samples of 333 bilingual and 385 monolingual infants' preference for North-American English IDS (cf. ManyBabies Consortium, 2020: ManyBabies 1), tested in 17 labs in 7 countries. Those infants were tested in two age groups: 6-9 months (the younger sample) and 12-15 months (the older sample). We found that bilingual and monolingual infants both preferred IDS to ADS, and did not differ in terms of the overall magnitude of this preference. However, amongst bilingual infants who were acquiring North-American English (NAE) as a native language, greater exposure to NAE was associated with a stronger IDS preference, extending the previous finding from ManyBabies 1 that monolinguals learning NAE as a native language showed a stronger preference than infants unexposed to NAE. Together, our findings indicate that IDS preference likely makes a similar contribution to monolingual and bilingual development, and that infants are exquisitely sensitive to the nature and frequency of different types of language input in their early environments.

Children vary widely in their lexical development. These differences have been shown to carry through later ages and can even be found in adults. One parameter often found as a predictor of varying vocabulary size is speed of processing, measuring the reaction time in familiar word recognition tasks. However, the underlying nature of speed of processing is still unclear: Is it a purely linguistic phenomenon or is it tied to the general cognitive abilities of the child. Our study aims to shed light on the nature of speed of processing, by testing 17-month-olds in a word learning experiment and assessing their reaction time during word recognition for both newly acquired and familiar words as well as visual reaction times. Our results can thus disentangle how broad or narrow lexical speed of processing is and help us better understand the origin of its link with language skills across the lifespan.

Infant research is often underpowered, undermining the robustness and replicability of our findings. Improving the reliability of infant studies offers a solution for increasing statistical power independent of sample size. Here, we discuss two senses of the term reliability in the context of infant research: reliable (large) effects and reliable measures. We examine the circumstances under which effects are strongest and measures are most reliable and use synthetic datasets to illustrate the relationship between effect size, measurement reliability, and statistical power. We then present six concrete solutions for more reliable infant research: (a) routinely estimating and reporting the effect size and measurement reliability of infant tasks, (b) selecting the best measurement tool, (c) developing better infant paradigms, (d) collecting more data points per infant, (e) excluding unreliable data from the analysis, and (f) conducting more sophisticated data analyses. Deeper consideration of measurement in infant research will improve our ability to study infant development.

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure.

As they develop into mature speakers of their native language, infants must not only learn words but also the sounds that make up those words. To do so, they must strike a balance between accepting speaker-dependent variation (e.g., mood, voice, accent) but appropriately rejecting variation when it (potentially) changes a word's meaning (e.g., cat vs. hat). This meta-analysis focuses on studies investigating infants' ability to detect mispronunciations in familiar words, or mispronunciation sensitivity. Our goal was to evaluate the development of infants' phonological representations for familiar words as well as explore the role of experimental manipulations related to theoretical questions and of analysis choices. The results show that although infants are sensitive to mispronunciations, they still accept these altered forms as labels for target objects. Interestingly, this ability is not modulated by age or vocabulary size, suggesting that a mature understanding of native language phonology may be present in infants from an early age, possibly before the vocabulary explosion. These results support several theoretical assumptions made in the literature, such as sensitivity to mispronunciation size and position of the mispronunciation. We also shed light on the impact of data analysis choices that may lead to different conclusions regarding the development of infants' mispronunciation sensitivity. Our article concludes with recommendations for improved practice in testing infants' word and sentence processing online.

Test‐retest reliability—establishing that measurements remain consistent across multiple testing sessions—is critical to measuring, understanding, and predicting individual differences in infant language development. However, previous attempts to establish measurement reliability in infant speech perception tasks are limited, and reliability of frequently used infant measures is largely unknown. The current study investigated the test‐retest reliability of infants' preference for infant‐directed speech over adult‐directed speech in a large sample (N = 158) in the context of the ManyBabies1 collaborative research project. Labs were asked to bring in participating infants for a second appointment retesting infants on their preference for infant‐directed speech. This approach allowed us to estimate test‐retest reliability across three different methods used to investigate preferential listening in infancy: the head‐turn preference procedure, central fixation, and eye‐tracking. Overall, we found no consistent evidence of test‐retest reliability in measures of infants' speech preference (overall r = 0.09, 95% CI [−0.06,0.25]). While increasing the number of trials that infants needed to contribute for inclusion in the analysis revealed a numeric growth in test‐retest reliability, it also considerably reduced the study's effective sample size. Therefore, future research on infant development should take into account that not all experimental measures may be appropriate for assessing individual differences between infants. Research Highlights: We assessed test‐retest reliability of infants' preference for infant‐directed over adult‐directed speech in a large pre‐registered sample (N = 158).There was no consistent evidence of test‐retest reliability in measures of infants' speech preference.Applying stricter criteria for the inclusion of participants may lead to higher test‐retest reliability, but at the cost of substantial decreases in sample size.Developmental research relying on stable individual differences should consider the underlying reliability of its measures. [ABSTRACT FROM AUTHOR]

Before infants become mature speakers of their nativelanguage, they must acquire a robust word-recognition systemwhich allows them to strike the balance between allowingsome variation (mood, voice, accent) and recognizingvariability that potentially changes meaning (e.g. cat vs hat).The current meta-analysis quantifies how the latter, termedmispronunciation sensitivity, changes over infants’ first threeyears, testing competing predictions of mainstream languageacquisition theories. Our results show that infants weresensitive to mispronunciations, but accepted them as labelsfor target objects. Interestingly, and in contrast to predictionsof mainstream theories, mispronunciation sensitivity was notmodulated by infant age, suggesting that a sufficientlyflexible understanding of native language phonology is inplace at a young age.

Theories of language acquisition and perceptual learningincreasingly rely on statistical learning mechanisms. Thecurrent meta-analysis aims to clarify the robustness of thiscapacity in infancy within the word segmentation literature.Our analysis reveals a significant, small effect size forconceptual replications of Saffran, Aslin, & Newport (1996),and a nonsignificant effect across all studies that incorporatetransitional probabilities to segment words. In bothconceptual replications and the broader literature, however,statistical learning is moderated by whether stimuli arenaturally produced or synthesized. These findings invitedeeper questions about the complex factors that influencestatistical learning, and the role of statistical learning inlanguage acquisition.

Objective Methods Results Conclusion Deregulation of the cJUN/AP‐1 and hedgehog/GLI2 signaling pathways has been implicated in fibroblast activation in systemic sclerosis (SSc). However, the consequences of their concomitant up‐regulation are unknown. Here, we tested the hypothesis that mutual amplification of both pathways might drive persistent fibroblast activation.Cultured fibroblasts and skin sections of patients with diffuse SSc and healthy volunteers were analyzed. cJUN/AP‐1 signaling and hedgehog/GLI2 signaling were inhibited using knockdown and pharmacologic approaches. Hedgehog signaling was activated in mice by fibroblast‐specific overexpression of constitutively active Smoothened.cJUN and GLI2 are concomitantly up‐regulated and colocalize in fibroblasts of patients with SSc compared to healthy controls. Activation of hedgehog/GLI2 signaling induces the expression of cJUN in vitro and in vivo, whereas inactivation of GLI2 inhibits cJUN expression. Likewise, inactivation of cJUN impairs the expression of GLI2. This mutual regulation occurs at the level of transcription with binding of cJUN and GLI2 to specific binding motifs. Interference with this mutual amplification of cJUN signaling and GLI2 signaling inhibits fibroblast activation and collagen release: Inhibition of cJUN/AP‐1 signaling ameliorates hedgehog‐induced fibroblast activation and skin fibrosis in SmoACT mice with a reduction of skin thickness of 103% (P = 0.0043) in the treatment group compared to the fibrotic control group. Moreover, combined pharmacologic inhibition of cJUN/AP‐1 and hedgehog/GLI2 exerts additive antifibrotic effects in a model of TGFβ‐driven experimental fibrosis (TBRACT mice).The transcription factors cJUN and GLI2 reinforce each other's activity to promote fibroblast activation in SSc. Interruption of this crosstalk by combined inhibition of both pathways exerts additive antifibrotic effects at well‐tolerated doses. [ABSTRACT FROM AUTHOR]

Meta-analysis is a powerful yet underused tool in cognitive sci-ence. It allows researchers to leverage entire bodies of litera-ture to get a broad and quantitative overview of a particularphenomenon, thereby promoting theory development, and tomake more precise estimates of effect sizes, which enablesrobust planning of prospective studies (e.g. through power-analyses). In this tutorial, we will introduce meta-analysis as atool with which to inform everyday research, and provide par-ticipants with hands-on experience conducting their own meta-analysis. We will also present an online platform we have de-veloped for conducting meta-analyses in the field of languagedevelopment: MetaLab (http://metalab.stanford.edu).

How does a naive language learner deal with speaker variationirrelevant to distinguishing word meanings? Experimental datais contradictory, and incompatible models have been proposed.Here, we examine basic assumptions regarding the acousticsignal the learner deals with: Is speaker variability a hurdle indiscriminating sounds or can it easily be ignored? To this end,we summarize existing infant data. We then present machine-based discriminability scores of sound pairs obtained withoutany language knowledge. Our results show that speaker vari-ability decreases sound contrast discriminability, and that somecontrasts are affected more than others. However, chance per-formance is rare; most contrasts remain discriminable in theface of speaker variation. We take our results to mean thatspeaker variation is not a uniform hurdle to discriminatingsound contrasts, and careful examination is necessary whenplanning and interpreting studies testing whether and to whatextent infants (and adults) are sensitive to speaker differences.

Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an 'autonomous,' self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-[beta] induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-[beta]-dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases., Introduction Fibrotic tissue remodeling imposes a major burden on modern societies and has been estimated to contribute to up to 45% of deaths in the developed world and to cause [...]

Previous work suggests that key factors for replicability, a necessary feature for theory building, include statistical power and appropriate research planning. These factors are examined by analyzing a collection of 12 standardized meta-analyses on language development between birth and 5 years. With a median effect size of Cohen's d = 0.45 and typical sample size of 18 participants, most research is underpowered (range = 6%-99%; median = 44%); and calculating power based on seminal publications is not a suitable strategy. Method choice can be improved, as shown in analyses on exclusion rates and effect size as a function of method. The article ends with a discussion on how to increase replicability in both language acquisition studies specifically and developmental research more generally.

Objective Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Novel biomarkers are crucial to improve outcomes in SSc-ILD. We aimed to compare the performance of potential serum biomarkers of SSc-ILD that reflect different pathogenic processes: KL-6 and SP-D (epithelial injury), CCL18 (type 2 immune response), YKL-40 (endothelial injury and matrix remodelling) and MMP-7 (ECM remodelling). Methods Baseline and follow-up serum samples from 225 SSc patients were analysed by ELISA. Progressive ILD was defined according to the 2022-ATS/ERS/JRS/ALAT guidelines. Linear mixed models and random forest models were used for statistical analyses. Results Serum levels of KL-6 [MD 35.67 (95% CI 22.44–48.89, P  < 0.01)], SP-D [81.13 (28.46–133.79, P  < 0.01)], CCL18 [17.07 (6.36–27.77, P  < 0.01)], YKL-40 [22.81 (7.19–38.44, P  < 0.01)] and MMP-7 [2.84 (0.88–4.80, P  < 0.01)] were independently associated with the presence of SSc-ILD. A machine-learning model including all candidates classified patients with or without ILD with an accuracy of 85%. The combination of KL-6 and SP-D was associated with the presence [0.77 (0.53–1.00, P'  <0.01)] and previous progression of SSc-ILD [OR 1.28 (1.01–1.61, P'  =0.047)]. Higher baseline levels of KL-6 [OR 3.70 (1.52–9.03, P  < 0.01)] or SP-D [OR 2.00 (1.06–3.78, P  = 0.03)] increased the odds of future SSc-ILD progression, independent of other conventional risk factors, and the combination of KL-6 and SP-D [1.109 (0.665–1.554, P  < 0.01)] showed improved performance compared with KL-6 and SP-D alone. Conclusion All candidates performed well as diagnostic biomarkers for SSc-ILD. The combination of KL-6 and SP-D might serve as biomarker for the identification of SSc patients at risk of ILD progression. [ABSTRACT FROM AUTHOR]

Infants start learning words, the building blocks of language, at least by 6 months. To do so, they must be able to extract the phonological form of words from running speech. A rich literature has investigated this process, termed word segmentation. We addressed the fundamental question of how infants of different ages segment words from their native language using a meta-analytic approach. Based on previous popular theoretical and experimental work, we expected infants to display familiarity preferences early on, with a switch to novelty preferences as infants become more proficient at processing and segmenting native speech. We also considered the possibility that this switch may occur at different points in time as a function of infants' native language and took into account the impact of various task- and stimulus-related factors that might affect difficulty. The combined results from 168 experiments reporting on data gathered from 3,774 infants revealed a persistent familiarity preference across all ages. There was no significant effect of additional factors, including native language and experiment design. Further analyses revealed no sign of selective data collection or reporting. We conclude that models of infant information processing that are frequently cited in this domain may not, in fact, apply in the case of segmenting words from native speech.