Lexical Morphology as a Source of Risk and Resilience for Learning to Read With Dyslexia: An fNIRS Investigation.

PURPOSE: We examined the neurocognitive bases of lexical morphology in children of varied reading abilities to understand the role of meaning-based skills in learning to read with dyslexia. METHOD: Children completed auditory morphological and phonological awareness tasks during functional near-infrared spectroscopy neuroimaging. We first examined the relation between lexical morphology and phonological processes in typically developing readers (Study 1, N = 66, Mage = 8.39), followed by a more focal inquiry into lexical morphology processes in dyslexia (Study 2, N = 50, Mage = 8.62). RESULTS: Typical readers exhibited stronger engagement of language neurocircuitry during the morphology task relative to the phonology task, suggesting that morphological analyses involve synthesizing multiple components of sublexical processing. This effect was stronger for more analytically complex derivational affixes (like + ly) than more semantically transparent free base morphemes (snow + man). In contrast, children with dyslexia exhibited stronger activation during the free base condition relative to derivational affix condition. Taken together, the findings suggest that although children with dyslexia may struggle with derivational morphology, they may also use free base morphemes' semantic information to boost word recognition. CONCLUSION: This study informs literacy theories by identifying an interaction between reading ability, word structure, and how the developing brain learns to recognize words in speech and print. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25944949.

Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

HDAC6/aggresome processing pathway importance for inflammasome formation is context-dependent.

The inflammasome is a large multiprotein complex that assembles in the cell cytoplasm in response to stress or pathogenic infection. Its primary function is to defend the cell and promote the secretion of pro-inflammatory cytokines, including IL-1ß and IL-18. Previous research has shown that in immortalized bone marrow-derived macrophages (iBMDMs) inflammasome assembly is dependent on the deacetylase HDAC6 and the aggresome processing pathway (APP), a cellular pathway involved in the disposal of misfolded proteins. Here we used primary BMDMs from mice in which HDAC6 is ablated or impaired and found that inflammasome activation was largely normal. We also used human peripheral blood mononuclear cells and monocyte cell lines expressing a synthetic protein blocking the HDAC6-ubiquitin interaction and impairing the APP and found that inflammasome activation was moderately affected. Finally, we used a novel HDAC6 degrader and showed that inflammasome activation was partially impaired in human macrophage cell lines with depleted HDAC6. Our results therefore show that HDAC6 importance in inflammasome activation is context-dependent.

Examining the Association Between Trauma Characteristics and Adult Depression and Anxiety: Analysis of Types, Variety, Repetition, and Timing of Past Trauma.

Past research has emphasized the impact of prior trauma on adult depression and anxiety rates. However, few studies have examined the simultaneous connection between various trauma characteristics (e.g., type, variety, repetition, timing) and symptoms of depression and anxiety in adults. Understanding how these different trauma characteristics relate to mental health issues can offer valuable insight into predicting the onset of such problems. We conducted a cross-sectional analysis with 356 adult participants to explore the associations between lifetime trauma history and depression/anxiety scores. Participants retrospectively reported on five different traumatic experiences from birth to the present, including childhood physical abuse, witnessing parental violence, lifetime experiences of rape, witnessing trauma to loved ones, and the unexpected death of loved ones. For each trauma type, participants indicated the timing of their first exposure and the frequency of subsequent occurrences. Depression and anxiety symptoms in the past 2 weeks were also self-reported. Multiple regression analyses with covariates were employed. On average, participants experienced two out of the five trauma types. Regardless of the type, having at least one traumatic experience was linked to higher depression and anxiety scores. Those who experienced all five trauma types reported the highest levels of depression and anxiety. Repeated instances of rape, witnessing trauma to loved ones, and the death of loved ones were significantly associated with elevated depression and anxiety scores. The timing of exposure to the unexpected death of loved ones predicted higher depression scores in childhood compared to adulthood, while no relationship between timing and anxiety scores was observed. Other trauma types did not show significant associations. Our study enhances knowledge of the link between trauma and depression/anxiety by elucidating how various trauma characteristics, such as type, variety, repetition, and timing of trauma, have differential influences on depression and anxiety scores.

Studying Cell Migration (Random and Wound Healing) Parameters with Imaging and MATLAB Analysis.

Cell migration is an essential biological process for organisms, in processes including embryonic development, immune response, and cancer metastasis. To elucidate the regulatory machinery of this vital process, methods that mimic in vivo migration, including in vitro wound healing assay and random migration assay, are widely used for cell behavior investigation. However, several concerns are raised with traditional cell migration experiment analysis. First, a manually scratched wound often presents irregular edges, causing the speed analysis difficult. Second, only the migration speed of leading cells is considered in the wound healing assay. Here, we provide a reliable analysis method to trace each cell in the time-lapse images, eliminating the concern about wound shape and creating a more comprehensive understanding of cell migration-not only of collective migration speed but also single-cell directionality and coordination between cells.

Studying Cellular Focal Adhesion Parameters with Imaging and MATLAB Analysis.

Cell signaling is highly integrated for the process of various cell activities. Although previous studies have shown how individual genes contribute to cell migration, it remains unclear how the integration of these signaling pathways is involved in the modulation of cell migration. In our two-hit migration screen, we revealed that serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) worked synergistically, and the suppression of both genes could further lead to suppression in cell migration. Furthermore, based on our analysis of cellular focal adhesion (FA) parameters using MATLAB analysis, we are able to find out the synergistic reduction of STK40 and MAPK that further abolished the increased FA by shSTK40. While FA identification in previous studies includes image analysis using manual selection, our protocol provides a semi-automatic manual selection of FAs using MATLAB. Here, we provide a method that can shorten the amount of time required for manual identification of FAs and increase the precision for discerning individual FAs for various analyses, such as FA numbers, area, and mean signals.

Impact of asymmetric electrodes on ferroelectricity of sub-10 nm HZO thin films.

In this study, platinum (Pt) and tungsten (W), two materials with dissimilar coefficients of thermal expansion (CTE) and work functions (WF), are used as the top electrode (TE) and the bottom electrode (BE) in metal/ferroelectric/metal (MFM) structures to explore the ferroelectricity of hafnium zirconium oxide (HZO) with a thickness less than 10 nm. The electrical measurements indicate that a higher CTE mismatch between HZO and TE/BE is beneficial for enhancing the ferroelectric properties of nanoscale HZO thin films. The different WFs of TE and BE generate a built-in electric field in the HZO layer, leading to shifts in the hysteresis loops and the capacitance-voltage characteristics. The structural characterizations reveal that the preferred formation of the orthorhombic phase in HZO is dominated by the W BE. The device in which W is used as the TE and BE (the W/HZO/W MFM structure) presents the optimal ferroelectric performance of a high remanent polarization (2Pr= 55.2µC cm-2). The presence of tungsten oxide (WOx) at the W/HZO interfaces, as revealed by high-resolution transmission microscopy, is also responsible for the enhancement of ferroelectric properties. This study demonstrates the significant effects of different CTEs and WFs of TE and BE on the properties of ferroelectric HZO thin films.

Newly Generated Ca-Feldspar during Sintering Processes Enhances the Mechanical Strength of Coal Gangue-Based Insulation Bricks.

Coal gangue is a solid waste with low carbon content discharged during the course of the coal mining process. The resource utilization of coal gangue could solve environmental problems caused by its excessive production, such as soil contamination and land occupation. This study proposed to produce high-strength thermal insulation bricks using coal gangue as the primary material and three other mineral powders as auxiliary materials, including K-feldspar, CaCO3 and fly ash. A systematic analysis was conducted to explore the optimum raw material addition ratio and optimum sintering temperature; then, the intrinsic structure of thermal insulation bricks and their sintering formation mechanisms were revealed. The results showed that the optimal ratios of coal gangue, K-feldspar, CaCO3 and fly ash were 65 wt%, 15 wt%, 10 wt% and 10 wt%, respectively; the compressive strength of the thermal insulation brick produced under this ratio was 22.5 MPa; thermal conductivity was 0.39 W m-1 k-1. During sintering processes, mineral powders sufficiently fused to form a skeleton, and the CO2 derived from CaCO3 formed pores. The optimum sintering temperature was 1150 °C, because at this temperature, K-feldspar had the best effect in promoting the conversion of CaCO3 to Ca-feldspar. The high level of the relative crystallinity of Ca-feldspar (about 76.0%) helped raise the Si-O network's polymerization degree (NBO/T = 1.24), finally raising the compressive strength of thermal insulation bricks. The innovative method of using coal gangue to make thermal insulation bricks not only solved the environmental pollution caused by coal gangue but also provided excellent construction materials with high practical application value.

The development of a broad-spectrum retaining ß-exo-galactosidase activity-based probe.

Acid ß-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-ß-galactosidases involved in lysosomal glycoconjugate metabolism. Deficiency of GLB1 may result in the lysosomal storage disorders GM1 gangliosidosis, Morquio B syndrome, and galactosialidosis, and deficiency of GALC may result in Krabbe disease. Activity-based protein profiling (ABPP) is a powerful technique to assess the activity of retaining glycosidases in relation to health and disease. This work describes the use of fluorescent and biotin-carrying activity-based probes (ABPs) to assess the activity of both GLB1 and GALC in cell lysates, culture media, and tissue extracts. The reported ABPs, which complement the growing list of retaining glycosidase ABPs based on configurational isomers of cyclophellitol, should assist in fundamental and clinical research on various ß-galactosidases, whose inherited deficiencies cause debilitating lysosomal storage disorders.

Phonological and morphological literacy skills in English and Chinese: A cross-linguistic neuroimaging comparison of Chinese-English bilingual and monolingual English children.

Over the course of literacy development, children learn to recognize word sounds and meanings in print. Yet, they do so differently across alphabetic and character-based orthographies such as English and Chinese. To uncover cross-linguistic influences on children's literacy, we asked young Chinese-English simultaneous bilinguals and English monolinguals (N = 119, ages 5-10) to complete phonological and morphological awareness (MA) literacy tasks. Children completed the tasks in the auditory modality in each of their languages during functional near-infrared spectroscopy neuroimaging. Cross-linguistically, comparisons between bilinguals' two languages revealed that the task that was more central to reading in a given orthography, such as phonological awareness (PA) in English and MA in Chinese, elicited less activation in the left inferior frontal and parietal regions. Group comparisons between bilinguals and monolinguals in English, their shared language of academic instruction, revealed that the left inferior frontal was less active during phonology but more active during morphology in bilinguals relative to monolinguals. MA skills are generally considered to have greater language specificity than PA skills. Bilingual literacy training in a skill that is maximally similar across languages, such as PA, may therefore yield greater automaticity for this skill, as reflected in the lower activation in bilinguals relative to monolinguals. This interpretation is supported by negative correlations between proficiency and brain activation. Together, these findings suggest that both the structural characteristics and literacy experiences with a given language can exert specific influences on bilingual and monolingual children's emerging brain networks for learning to read.

Real-world effectiveness of national pit and fissure sealants program in Taiwan.

OBJECTIVES: This study investigated the effectiveness of a national population-based pit and fissure sealants (PFS) program in Taiwan. METHODS: Part 1 (effectiveness of national PFS program) involved children who had participated in the PFS program from 2015 to 2019. After propensity score matching, 670,840 children were selected for analysis until the end of 2019. During follow-up, the permanent first molars of the participants were assessed for caries-related treatments by employing multilevel Cox proportional hazards models. In Part 2 (effectiveness of retained sealants), which involved 1,561 children, sealant retention was evaluated 3 years after placement. A structured questionnaire was employed to collect information on family and individual factors. The endpoints were the same as in Part 1. RESULTS: In Part 1, the adjusted hazard ratios (HRs) for caries-related treatments among participants in the PFS program were 0.90 (95% confidence interval [CI] = 0.89, 0.91) for dental restoration, 0.42 (95% CI = 0.38, 0.46) for initiation of endodontic treatment, 0.46 (95% CI = 0.41, 0.52) for completion of endodontic treatment, and 0.25 (95% CI = 0.18, 0.34, all Ps < 0.0001) for extraction. In Part 2, the adjusted HR for dental restoration of teeth with retained sealants was 0.70 (95% CI = 0.58, 0.85), significantly lower than that for teeth without retained sealants (P = 0.0002). CONCLUSIONS: Participation in the national PFS program was associated with a significant reduction of at least 10% in the risk of caries-related treatments, and an additional 30% risk reduction may have been attributed to sealant retention. CLINICAL SIGNIFICANCE: In a real-world setting, schoolchildren in the national PFS program were associated with a significant reduction of at least 10% in the likelihood of caries-related treatments. The program provided moderate protection against caries for the study population and could be improved by increasing the sealant retention rate.

Sources of Heterogeneity in Functional Connectivity During English Word Processing in Bilingual and Monolingual Children.

Diversity and variation in language experiences, such as bilingualism, contribute to heterogeneity in children's neural organization for language and brain development. To uncover sources of such heterogeneity in children's neural language networks, the present study examined the effects of bilingual proficiency on children's neural organization for language function. To do so, we took an innovative person-specific analytical approach to investigate young Chinese-English and Spanish-English bilingual learners of structurally distinct languages. Bilingual and English monolingual children (N = 152, M(SD)age = 7.71(1.32)) completed an English word recognition task during functional near-infrared spectroscopy neuroimaging, along with language and literacy tasks in each of their languages. Two key findings emerged. First, bilinguals' heritage language proficiency (Chinese or Spanish) made a unique contribution to children's language network density. Second, the findings reveal common and unique patterns in children's patterns of task-related functional connectivity. Common across all participants were short-distance neural connections within left hemisphere regions associated with semantic processes (within middle temporal and frontal regions). Unique to more proficient language users were additional long-distance connections between frontal, temporal, and bilateral regions within the broader language network. The study informs neurodevelopmental theories of language by revealing the effects of heterogeneity in language proficiency and experiences on the structure and quality of emerging language neural networks in linguistically diverse learners.

Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases.

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH's global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities making them mutually exclusive between NER and transcription initiation. By sequentially coordinating the XPB and XPD DNA-unwinding activities, the switch ensures precise DNA incision in NER. Mapping TFIIH disease mutations onto network models reveals clustering into distinct mechanistic classes, affecting translocase functions, protein interactions and interface dynamics.

Morphological awareness and its role in early word reading in English monolinguals, Spanish-English, and Chinese-English simultaneous bilinguals.

Words' morphemic structure and their orthographic representations vary across languages. How do bilingual experiences with structurally distinct languages influence children's morphological processes for word reading? Focusing on English literacy in monolinguals and bilinguals (N = 350, ages 5-9), we first revealed unique contributions of derivational ( friend-li-est) and compound (girl-friend) morphology to early word reading. We then examined mechanisms of bilingual transfer in matched samples of Spanish-English and Chinese-English dual first language learners. Results revealed a principled cross-linguistic interaction between language group (Spanish vs. Chinese bilinguals) and type of morphological awareness. Specifically, bilinguals' proficiency with the type of morphology that was less characteristic of their home language explained greater variance in their English literacy. These findings showcase the powerful effects of bilingualism on word reading processes in children who have similar reading proficiency but different language experiences, thereby advancing theoretical perspectives on literacy across diverse learners.

Quality of dental treatments under intravenous sedation among patients with disability: A self-matching study.

Background/purpose: Patients with disabilities usually have difficulties in communication and mobility, and the quality of the dental treatments are often inferior. This study uses the Taiwan National Health Insurance Database to analyze the quality of dental treatment for patients with disabilities who receive intravenous sedation (IVS). Materials and methods: This study selected patients with disabilities who received dental treatment under IVS. Their oral cavity was divided into three major sections: anterior teeth, upper posterior teeth, and lower posterior teeth. Self-matching of the same section was conducted to observe whether operative dental treatment (OD) with or without IVS affected the occurrence of dental retreatment. This study observed the occurrence of refilling and the duration from the end of treatment until retreatment to compare treatment differences with or without IVS. Results: After self-matching, this study found 158 patients who received dental treatment within the same section with and without IVS. During a follow-up period of 17 years, 75.18% of the patients who received OD treatment required refilling, 10.87% required endodontic treatment, and 5.67% required tooth extraction. After OD treatment with IVS, the risks of refilling, endodontic treatment, and tooth extraction were 0.71 (95% CI: 0.58-0.87, P < 0.001), 0.77 (95% CI: 0.48-1.23, P = 0.28), and 0.64 (95% CI: 0.32-1.27, P = 0.20), respectively. Conclusion: For patients with disabilities, OD treatment with IVS significantly reduces the risk of refilling compared with OD treatment without IVS. IVS can be ideal for people with disabilities who receive dental treatment.

Effect of wearable exoskeleton on post-stroke gait: A systematic review and meta-analysis.

BACKGROUND: Wearable exoskeletons are a recently developed technology. OBJECTIVES: The present systematic review aimed to investigate the effect of a wearable exoskeleton on post-stroke walking by considering its use in a gait training system and simply as an orthosis assisting walking. METHODS: We systematically searched for randomised and quasi-randomised controlled trials in PubMed, Scopus, CINAHL and Embase databases from their earliest publication record to July 2021. We chose reports of trials investigating the effects of exoskeleton-assisted training or the effects of wearing an exoskeleton to assist walking. A meta-analysis was conducted to explore the benefits of the wearable exoskeleton on mobility capacity, walking speed, motor function, balance, endurance and activities of daily living. RESULTS: We included 13 studies (492 participants) comparing exoskeleton-assisted training with dose-matched conventional gait training. Studies addressing the effect of wearing a wearable exoskeleton were unavailable. As compared with conventional gait training at the end of the intervention, exoskeleton-assisted training was superior for walking speed (mean difference [MD] 0.13 m/s, 95% CI 0.05; 0.21) and balance (standardized MD [SMD] 0.3, 95% CI 0.07; 0.54). The subgroup with chronic stroke (i.e., > 6 months) presented the outcome favouring exoskeleton-assisted training regarding overall mobility capacity (SMD 0.37, 95% CI 0.04; 0.69). At the end of follow-up, exoskeleton-assisted training was superior to conventional gait training in overall mobility (SMD 0.45, 95% CI 0.07; 0.84) and endurance (MD 46.23 m, 95% CI 9.90; 82.56). CONCLUSIONS: Exoskeleton-assisted training was superior to dose-matched conventional gait training in several gait-related outcomes at the end of the intervention and follow-up in this systematic review and meta-analysis, which may support the use of exoskeleton-assisted training in the rehabilitation setting. Whether wearing versus not wearing a wearable exoskeleton is beneficial during walking remains unknown.

Brain bases of English morphological processing: A comparison between Chinese-English, Spanish-English bilingual, and English monolingual children.

How do early bilingual experiences influence children's neural architecture for word processing? Dual language acquisition can yield common influences that may be shared across different bilingual groups, as well as language-specific influences stemming from a given language pairing. To investigate these effects, we examined bilingual English speakers of Chinese or Spanish, and English monolinguals, all raised in the US (N = 152, ages 5-10). Children completed an English morphological word processing task during fNIRS neuroimaging. The findings revealed both language-specific and shared bilingual effects. The language-specific effects were that Chinese and Spanish bilinguals showed principled differences in their neural organization for English lexical morphology. The common bilingual effects shared by the two groups were that in both bilingual groups, increased home language proficiency was associated with stronger left superior temporal gyrus (STG) activation when processing the English word structures that are most dissimilar from the home language. The findings inform theories of language and brain development during the key periods of neural reorganization for learning to read by illuminating experience-based plasticity in linguistically diverse learners.

Evaluation of the Psychometric Properties of a Newly Developed Chinese Screening Tool for Speech Disorders in Patients With Parkinson's Disease.

The study aimed to analyze the psychometric properties of a newly developed Chinese screening tool, the Chinese Version of the Speech Disorders in Parkinson's Disease Questionnaire (SDPD-C). The SDPD-C contains a 24-item questionnaire with four assessment domains. Overall, 93 patients with idiopathic Parkinson's disease (PD) (age 70.1 ± 8.9 years) and 76 healthy older adults (age 67.2 ± 8.1 years) participated in the psychometric analysis study. The internal consistency of the SDPD-C was .91 (four dimensions: .69-.85), and test-retest reliability was .91 (four dimensions: .85-.88). The SDPD-C was highly correlated with the Voice Handicap Index-10 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale II 2.1 (r = .83 and .78, respectively). The SDPD-C scores also differed significantly between stages 1 and 4 of the Hoehn and Yahr Scale (p < .05). The area under the receiver operating characteristic curve was .955 (95% confidence interval, .927-.983; asymptotic significance p < .001), and the optimal cut-off score of this study was 36, with a sensitivity of .849 and specificity of .947. The results indicate that SDPD-C showed good reliability, validity, accuracy, and discrimination. It can be used as a screening tool for speech disorders in patients with PD.