The Effect of Sampling Context on Preschoolers' Finite Verb Morphology Composite Scores.

PURPOSE: The finite verb morphology composite (FVMC) is a valid measure for charting children's tense development and for differentiating children with and without language impairment during preschool and early elementary years. However, it is unclear whether FVMC scores vary as a function of language sample elicitation contexts. The current study evaluated the performance on FVMC in preschool-aged children across different language sampling contexts. METHOD: Participants were 38 English-speaking children who were between the ages of 3 and 4 years and below the mastery level of tense usage in three language sampling contexts, including conversation (free-play), picture description, and narratives (story retell). FVMC from each sampling context was computed by calculating the overall accuracy of copula be, auxiliary be, third-person singular present -s, and past tense -ed combined. A linear mixed-effects model comparison was carried out to determine the effect of sampling context on FVMC scores. RESULTS: After controlling for child age, mean length of utterance, and the number of obligatory contexts for FVMC scoring, FVMC scores were significantly higher in conversation than in picture description and narratives. In addition, FVMC scores across the three sampling contexts were significantly correlated (rs ≥ .62, p < .001). CONCLUSIONS: Although children's performance on FVMC relative to each other was quite stable across sampling contexts, FVMC scores may vary with sampling contexts. As compared to picture description and narratives, conversation may not adequately capture the limitation in preschoolers' tense development that is important for therapeutic planning.

CCL5 promotes the epithelial-mesenchymal transition of circulating tumor cells in renal cancer.

BACKGROUND: Circulating tumor cells (CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear. METHODS: This study investigated C-C motif chemokine ligand 5 (CCL5)'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients' CTCs prognostic value through Lasso regression and Kaplan-Meier survival curves. RESULTS: Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various CTCs, correlating with poor prognosis in renal cancer. In 786-O-CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed CTCs, with mesenchymal CTCs having the highest value. CONCLUSIONS: In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.

Regulating the Pore Structure and Heteroatom Doping of Soybean Straw Carbon Based on a Bifunctional Template Method for the High-Performance Carbon Supercapacitor.

The previous research addressed the waste problem of agriculture and forestry residues by exploring the efficient utilization of liquefied soybean straw in supercapacitor. The structures of the liquefied soybean straw were controlled by coupling microwave hydrothermal treatment with carbonization under the influence of a C3N4 bifunctional template. What's more, C3N4 could effectively regulate the pore structures and provide an effective N active site of carbon materials C3N4. The obtained N-SLR Carbon-700 possess a specific surface area of up to 1593.7 m2 g -1, and the pore size is mainly concentrated in the range of 1.8-2.5 nm, providing efficient ions transmission channels and storage space. Its specific capacitance is up to 261.5 F g-1 (current density of 0.5 A g-1), and the capacity retention is 74.04 % when the current density is expanded by 20 times. In the two-electrode system, the energy density of N-SLR Carbon-700 could reach to 31.3 W h kg-1 at a power density of 360 W kg-1, as well as the energy surface density is maintained at 69 % when the power density is increased by a factor of 20. This work enhances effectively the charging and discharging stability and capacitance value of carbon-based supercapacitor.

The Contribution of Noun and Verb Lexicon Sizes to Later Grammatical Outcomes in Mandarin-Speaking Children With Cochlear Implants.

PURPOSE: The present study evaluated the applicability of the sentence-focused framework to Mandarin-speaking children with cochlear implants (CIs) by examining the relative contribution of receptive/expressive noun and verb lexicon sizes to later grammatical complexity. METHOD: Participants were 51 Mandarin-speaking children who received cochlear implantation before 30 months of age. At 12 months after CI activation, parents were asked to endorse words that their child could understand only or understand and say using the infant version of the Early Vocabulary Inventory. At 24 months after CI activation, parents were asked to endorse the grammatical structures that their children were able to say using the Grammatical Complexity subtest in the Mandarin Communicative Development Inventory-Taiwan. Children's receptive/expressive noun and verb lexicon sizes and grammatical complexity scores were computed from these parent checklists. RESULTS: Correlational analyses showed that children's receptive/expressive noun and verb lexicon sizes at 12 months after CI activation were all highly correlated with their grammatical complexity scores at 24 months after CI activation (ρs = .52-.63, ps < .001). Regression analyses further revealed that verb lexicon sizes at 12 months after CI activation outweighed noun lexicon sizes in accounting for grammatical complexity at 24 months after CI activation. CONCLUSIONS: Our findings supported the prediction of the sentence-focused framework. Emphasizing the role of verbs in early intervention has the potential to enhance grammatical outcomes in Mandarin-speaking children with CIs. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26129044.

Angiopoietin-like protein 2 inhibits thrombus formation.

Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and thrombus formation in vitro through binding with immunoglobulin-like receptor B, an immunoglobulin superfamily receptor. However, the mechanism by which it regulates platelet function in vivo remains unclear. In this study, we investigated the role of ANGPTL2 during thrombosis in relationship with ST-segment elevation myocardial infarction (STEMI) with spontaneous recanalization (SR). In a cohort of 276 male and female patients, we measured plasma ANGPTL2 protein levels. Using male Angptl2-knockout and wild-type mice, we examined the inhibitory effect of Angptl2 on thrombosis and platelet activation both in vivo and ex vivo. We found that plasma and platelet ANGPTL2 levels were elevated in patients with STEMI with SR compared to those in non-SR (NSR) patients, and was an independent predictor of SR. Angptl2 deficiency accelerated mesenteric artery thrombosis induced by FeCl3 in Angptl2-/- compared to WT animals, promoted platelet granule secretion and aggregation induced by thrombin and collogen while purified ANGPTL2 protein supplementation reversed collagen-induced platelet aggregation. Angptl2 deficiency also increased platelet spreading on immobilized fibrinogen and clot contraction. In collagen-stimulated Angptl2-/- platelets, Src homology region 2 domain-containing phosphatase (Shp)1-Y564 and Shp2-Y580 phosphorylation were attenuated while Src, Syk, and Phospholipase Cγ2 (PLCγ2) phosphorylation increased. Our results demonstrate that ANGPTL2 negatively regulated thrombus formation by activating ITIM which can suppress ITAM signaling pathway. This new knowledge provides a new perspective for designing future antiplatelet aggregation therapies.

Validating the Use of Percent Grammatical Utterances for Assessing Mandarin-Speaking Children's Grammatical Skill: Evidence From 3-Year-Olds.

PURPOSE: The study examined the use of percent grammatical utterances (PGUs) for assessing grammatical skills in Mandarin-speaking 3-year-old children. METHOD: Participants were 30 Mandarin-speaking 3-year-olds with typical development. Language samples were collected in two visits for each child using a picture description task. Children were asked to talk about 16 pictures in response to questions and prompts at each visit. Pictures for the language sample collection were identical across the visits. PGUs were computed, and the grammatical errors that children produced in the task were coded and tallied for error types at each visit. Test-retest reliability, split-half reliability, and concurrent criterion validity of PGUs were evaluated. RESULTS: The mean PGU level was approximately 78% at Visit 1 and 81% at Visit 2, both of which were significantly below the mastery level (i.e., 90%). The correlation coefficient for test-retest reliability of PGU was large (r = .70, p < .01); the correlation coefficient for split-half reliability was medium at Visit 1 (r = .47, p < .01) and large (r = .65, p < .01) at Visit 2. In addition, the correlation coefficient for concurrent criterion validity of PGU was medium for both visits (rs ≥ .35, ps ≤ .03). The ranking and proportion of each error type were similar between the visits. CONCLUSION: The initial evidence from psychometric properties suggests that PGU computed from the picture description task is a reliable and valid measure for evaluating grammatical skills in Mandarin-speaking 3-year-old children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25395499.

A network meta-analysis evaluating the efficacy and safety of adjuvant therapy after nephrectomy in renal cell carcinoma.

BACKGROUND: In the past few years, there has been a continuous rise in the occurrence of renal cell carcinoma (RCC), with RCC recurrence becoming the primary factor behind fatalities. Despite numerous clinical trials, the impact of different medications on the long-term survival of patients with RCC after surgery remains uncertain. This network meta-analysis aimed to evaluate the impact of various medications on the survival and safety of drugs in individuals with RCC following nephrectomy. METHODS: We conducted a thorough search in various databases, including CNKI, WAN FANG DATA, VIP, Web of Science, Cochrane Library (CENTRAL), PubMed, Scopus, and Embase, for articles published prior to June 2, 2023. This meta-analysis incorporated randomized controlled trials (RCTs). RESULTS: The analysis included 17 studies with 14,298 participants. The findings from the disease-free survival (DFS) analysis indicated that pembrolizumab demonstrated efficacy in enhancing DFS among patients with RCC following nephrectomy when compared to the placebo group (HR = 0.83, 95%CI 0.70 to 0.99). None of the drugs included in the study significantly improved overall survival (OS) and recurrence-free survival (RFS) after nephrectomy. For adverse events (AEs), sorafenib, pazopanib, sunitinib, and nivolumab plus ipilimumab interventions showed a higher incidence of adverse events compared with placebo. CONCLUSION: The network meta-analysis yielded strong evidence indicating that pembrolizumab could potentially enhance DFS in patients with RCC following nephrectomy, surpassing the effectiveness of a placebo.

Downregulation of peripheral luteinizing hormone rescues ovariectomy-associated cognitive deficits in APP/PS1 mice.

Alzheimer's disease (AD) is more prevalent in women than men, supposing due to the decline of estrogens in menopause, accompanied by increased gonadotropins such as luteinizing hormone (LH). We and others found that the transcription factor early growth response-1 (EGR1) regulates cholinergic function including the expression of acetylcholinesterase (AChE) and plays a significant role in cognitive decline of AD. Here we investigated in APP/PS1 mice by ovariectomy (OVX) and estradiol (E2) supplementation or inhibition of LH the effect on hippocampus-related cognition and related molecular changes. We found that OVX-associated cognitive impairment was accompanied by increased dorsal hippocampal EGR1 expression, which was rescued by downregulating peripheral LH rather than by supplementing E2. We also found in postmortem AD brains a higher expression of pituitary LH-mRNA and higher EGR1 expression in the posterior hippocampus. Both, in human and mice, there was a significant positive correlation between respectively posterior/dorsal hippocampal EGR1 and peripheral LH expression. We conclude that peripheral increased LH and increased posterior hippocampal EGR1 plays a significant role in AD pathology.

Nanoscale Oxygenous Heterogeneity in FePC Glass for Highly Efficient and Reusable Catalytic Performance.

Metallic glass, with its unique disordered atomic structure and high density of low-coordination sites, is regarded as the most competitive new catalyst for environmental catalysis. However, the efficiency and stability of metallic glass catalysts are often affected by their atomic configuration. Thus, the design and regulation of the nanoscale structure of metallic glasses to improve their catalytic efficiency and stability remains a challenge. Herein, a non-noble component, Fe75 P15 C10 amorphous ribbon, is used as a precursor to fabricate a hierarchical gradient catalyst with nanoscale heterogeneous and oxygenous amorphous structure by simple annealing and acid-immersing. The resulting catalyst offers an ultrahigh catalytic ability of kSA• C0 = 3101 mg m-2  min-1 and excellent reusability of 39 times without efficiency decay in dye wastewater degradation. Theoretical calculations indicate that the excellent catalytic performance of the catalyst can be attributed to its unique heterogeneous nanoglass structure, which induces oxygen atoms. Compared to the FePC structure, the FeP/FePCO structure exhibits strong charge transferability, and the energy barrier of the rate-determining steps of the conversion of S2 O8 2- to SO4 -• is reduced from 2.52 to 0.97 eV. This study reveals that a heterogeneous nanoglass structure is a new strategy for obtaining high catalytic performance.

Noun and Verb Lexicons Differentially Predict Later Grammatical Development in Mandarin-Speaking Children With and Without Late Language Emergence.

PURPOSE: The current investigation evaluated the extent to which early noun, verb, and adjective lexicon sizes predicted later grammatical outcomes in Mandarin-speaking children with and without late language emergence (LLE) using a parent report. METHOD: In Study 1, the parents of 24 Mandarin-speaking children with typical language filled out the toddler version of Mandarin-Chinese Communicative Development Inventory-Taiwan (MCDI-T) when these children were 24 and 36 months old. In Study 2, the parents of 23 children with LLE completed the same form when these children were 24, 36, and 48 months old. Noun, verb, and adjective lexicon sizes and grammatical complexity scores were computed from the MCDI-T form for each child. RESULTS: Study 1 showed that verb lexicon size, but not noun or adjective lexicon size, at 24 months predicted grammatical complexity scores at 36 months for children with typical language. Study 2 revealed that noun lexicon size, but not verb or adjective lexicon size, at 24 months predicted grammatical complexity scores at 36 months for children with LLE. Noun lexicon size at 36 months was also the only significant predictor for grammatical complexity scores at 48 months in children with LLE. CONCLUSIONS: Noun and verb lexicon size differentially predicted later grammatical outcomes in young Mandarin-speaking children with and without LLE. The finding suggested that children with LLE may have approached grammatical learning differently from their typical peers due to the small verb lexicon size in the early phase of language development.

MMP9 and TYROBP affect the survival of circulating tumor cells in clear cell renal cell carcinoma by adapting to tumor immune microenvironment.

Circulating tumor cells (CTCs) play a key role in tumor metastasis. CTCs have altered gene expression and can survive in the bloodstream. Finding the key genes whose expression are altered in CTCs could help explain the mechanism of tumor metastasis. We searched for genes differentially expressed in CTCs by analyzing four CTCs and primary tumor gene expression datasets in the GEO database. Key genes of clear cell renal cell carcinoma (ccRCC) CTCs were identified. The correlation between key genes and the immune microenvironment of ccRCC was explored. Finally, the CTCs cell model of ccRCC was constructed by in vivo screening method, and the expression of key genes was detected at the cell and tissue levels. A total of 771 DEGs were obtained. Gene enrichment analysis showed that DEGs of CTCs were mainly involved in the regulation of the tumor immune process and tumor cell apoptosis. Finally, we found 2 key genes, MMP9 and TYROBP in ccRCC CTCs. The high expression of these 2 genes predicted a poor prognosis of ccRCC, and the expression levels of these 2 genes were significantly increased in CTCs and ccRCC tissues. Our study suggested that genetic alterations in CTCs contribute to the ability of CTCs to survive in the blood by adapting to the tumor microenvironment. MMP9 and TYROBP are potential therapeutic and prognostic targets for ccRCC.

Effect of Predicate Types on the Production of Copula "Is" in 2-Year-Old Children Who Speak General American English.

PURPOSE: Prior work has shown that subject types affected the production of copula BE in young children who spoke General American English (GAE). However, the role of predicate types on the production of copula BE remains unclear. This study examined how predicate types affected the production of copula "is" in young GAE-speaking children. METHOD: Seventeen 2-year-old children with typical language development who spoke GAE were included in this study. Children's production rate of copula "is" in sentences with nominal (e.g., The dog is a king ), permanent-adjectival (e.g., The dog is white ), temporary-adjectival (e.g., The dog is very hot ), or locative (e.g., The dog is outside ) predicates was examined using an elicited repetition task. RESULTS: Two-year-old children who spoke GAE were more likely to repeat copula "is" correctly with nominal, permanent-adjectival, and temporary-adjectival predicates than with locative predicates after sentence length was controlled. There were no other significant differences between predicate types. CONCLUSIONS: Overall, locative predicates are the least facilitative for the production of copula "is" as compared to other predicate types. Predicate types, especially locative predicates, should be considered when the clinician creates sentences to evaluate the production of copula BE and to provide intervention for GAE-speaking children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22630726.

SERPINE1 and its co-expressed genes are associated with the progression of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma(ccRCC) is a frequently occurring malignant tumor of the urinary system. Despite extensive research, the regulatory mechanisms underlying the pathogenesis and progression of ccRCC remain largely unknown. METHODS: We downloaded 5 ccRCC expression profiles from the Gene Expression Omnibus (GEO) database and obtained the list of differentially expressed genes (DEGs). Using String and Cytoscape tools, we determined the hub genes of ccRCC, and then analyzed their relationship with ccRCC patient survival. Ultimately, we identified SERPINE1 as a prognostic factor in ccRCC. Meanwhile, we confirmed the role of SERPINE1 in 786-O cells by cell transfection and in vitro experiments. RESULTS: Our analysis yielded a total of 258 differentially expressed genes, comprising 105 down-regulated genes and 153 up-regulated genes. Survival analysis of SERPINE1 expression in The Cancer Genome Atlas (TCGA) confirmed its association with the increase of tumor grade, lymph node metastasis, and tumor stage, as well as with shorter survival. Furthermore, we found that SERPINE1 expression levels were associated with CD8 + T cells, CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells. Cell experiments showed that knockdown SERPINE1 expression could inhibit the proliferation, migration and invasion of ccRCC cells. Among the co-expressed genes with the highest correlation, ITGA5, SLC2A3, SLC2A14, SHC1, CEBPB, and ADA were overexpressed and associated with shorter overall survival (OS) in ccRCC. CONCLUSIONS: In this study, we identified hub genes that are strongly related to ccRCC, and highlights the potential utility of overexpressed SERPINE1 and its co-expressed genes could be used as prognostic and diagnostic biomarkers in ccRCC.

Evaluating Different Scoring Systems for a Picture Description Task Among Preschool Children Who Speak African American English.

PURPOSE: Measures of grammatical accuracy are effective measures of children's language skills. However, many measures, such as percent grammatical utterances, were developed for children who speak General American English (GAE) and, therefore, may not be appropriate for students who speak other dialects. This study examines different scoring systems for a picture description task to explore the impact of different systems for children who speak African American English (AAE). METHOD: Eighteen preschool-age children who speak AAE completed a play-based language sample and a picture description task. The Index of Productive Syntax (IPSyn) was calculated for the play-based language samples and used as the reference measure. The picture description task was scored using four scoring systems: an expansive AAE scoring system, a GAE scoring system, and two strategic scoring systems. Scores were compared for each scoring system, and correlations between IPSyn scores and picture description scores were conducted. RESULTS: Scores on the picture description task were highest in the expansive AAE scoring system, followed by scores in the strategic scoring systems, all of which were higher than scores in the GAE scoring system. There was a significant correlation between IPSyn scores and picture description scores when using the GAE scoring system and the strategic scoring systems, but not when using the expansive AAE scoring system. CONCLUSIONS: Different scoring systems affect AAE-speaking preschoolers' scores on measures of grammatical accuracy, and the use of an expansive AAE scoring system, based on lists of nonmainstream features, may diminish the ability to differentiate between children with different ability levels. Future research is needed to refine scoring systems and to explore the validity of different scoring systems for detecting differences between preschoolers who speak AAE, with and without developmental language disorder. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21498618.

ECT2 promotes malignant phenotypes through the activation of the AKT/mTOR pathway and cisplatin resistance in cervical cancer.

Epithelial cell transforming sequence 2 (ECT2) is expressed at high levels in various malignancies and contributes to malignant phenotypes in cancers. However, ECT2 is still not fully understood regarding its function and carcinogenic mechanism in cervical cancer. This research indicated that ECT2 expression was elevated in cervical cancer based on bioinformatics analysis and clinical specimens. Experiments in vitro and in vivo confirmed that ECT2 knockdown could suppress the proliferation and metastasis of cervical carcinoma cells. In addition, we found that silencing ECT2 could enhance the sensitivity to cisplatin and promote cell apoptosis. Mechanistically, we observed that ECT2 knockdown could inhibit the AKT/mTOR pathway and activate apoptosis, while ECT2 overexpression induced the opposite effect. The relationship between ECT2 and AKT was further confirmed by immunoprecipitation and rescue experiments. We found that the ECT2 and AKT could interact to form a complex, and knockdown AKT could offset all of the effects induced by ECT2. Our study emphasized the key point of ECT2 in the reversal of cisplatin resistance, and ECT2 could become a potential therapeutic target in cervical cancer.

The Plasma DIA-Based Quantitative Proteomics Reveals the Pathogenic Pathways and New Biomarkers in Cervical Cancer and High Grade Squamous Intraepithelial Lesion.

OBJECTIVE: The process of normal cervix changing into high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer is long and the mechanisms are still not completely clear. This study aimed to reveal the protein profiles related to HSIL and cervical cancer and find the diagnostic and prognostic molecular changes. METHODS: Data-independent acquisition (DIA) analysis was performed to identify 20 healthy female volunteers, 20 HSIL and 20 cervical patients in a cohort to screen differentially expressed proteins (DEPs) for the HSIL and cervical cancer. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for functional annotation of DEPs; the protein-protein interaction (PPI) and weighted gene co-expression network analysis (WGCNA) were performed for detection of key molecular modules and hub proteins. They were validated using the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: A total of 243 DEPs were identified in the study groups. GO and KEGG analysis showed that DEPs were mainly enriched in the complement and coagulation pathway, cholesterol metabolism pathway, the IL-17 signaling pathway as well as the viral protein interaction with cytokine and cytokine receptor pathway. Subsequently, the WGCNA analysis showed that the green module was highly correlated with the cervical cancer stage. Additionally, six interesting core DEPs were verified by ELISA, APOF and ORM1, showing nearly the same expression pattern with DIA. The area under the curve (AUC) of 0.978 was obtained by using ORM1 combined with APOF to predict CK and HSIL+CC, and in the diagnosis of HSIL and CC, the AUC can reach to 0.982. The high expression of ORM1 is related to lymph node metastasis and the clinical stage of cervical cancer patients as well as the poor prognosis. CONCLUSION: DIA-ELSIA combined analysis screened and validated two previously unexplored but potentially useful biomarkers for early diagnosis of HSIL and cervical cancer, as well as possible new pathogenic pathways and therapeutic targets.

Characteristics of Early Expressive Vocabulary in Mandarin-Speaking Children With Cochlear Implants.

PURPOSE: The aim of this study is to evaluate whether Mandarin-speaking children with cochlear implants (CIs) demonstrated early lexical composition similar to their hearing peers who were at the same vocabulary level and the extent to which children with CIs were sensitive to linguistic and conceptual properties when developing early lexicon. METHOD: Participants were 77 Mandarin-speaking children with CIs who received CIs before 30 months of age. Their expressive vocabulary was documented using the Infant Checklist of the Early Vocabulary Inventory for Mandarin Chinese 9 or 12 months after CI activation. Percent social words, common nouns, predicates (verbs, adjectives), and closed-class words in total vocabulary were computed for children at different vocabulary levels. Common nouns and verbs were further coded for their word class (noun, verb), word frequency, word length, and imageability to predict how likely a given noun or verb would be produced by children with CIs. RESULTS: Like children with typical hearing, social words were the most dominant category when vocabulary size in children with CIs was smaller than 20 words; common nouns became the most dominant category when the vocabulary size reached 21 words. The difference in percent common nouns and percent predicates (i.e., noun bias) was similar in children with CIs and their hearing peers. In addition, verbs, common words, monosyllabic words, and more imageable words were more likely to be produced by children with CIs than their counterparts. CONCLUSIONS: Mandarin children with CIs showed language-specific patterns in early lexical composition like their hearing peers. They were able to use multiple linguistic and conceptual cues when approaching early expressive vocabulary despite perceptual and processing constraints. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21357723.

Comprehensive analysis of the collagen family members as prognostic markers in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the common malignant tumors worldwide. There is still a lack of effective diagnostic and therapeutic targets for the recurrence and metastasis of ccRCC. In this study, we sought to identify effective diagnostic and therapeutic targets for ccRCC recurrence and metastasis. Methods: Gene Expression Omnibus (GEO) dataset was used to obtain differentially expressed genes (DEGs) between primary and metastasis ccRCC. We used The Cancer Genome Atlas (TCGA), GeneMANIA, cBioPortal, MethSurv, and TIMER to analyze the expression differences, mutation status, prognostic value, molecular function, and immune infiltration of hub genes in renal cell carcinoma (RCC). Results: We obtained a total of 35 different gene lists. Six collagen family members were identified as hub genes. The expression level of collagen family members was closely related to ccRCC. Moreover, differences in the expression levels of collagen family members were closely related to the stage and prognosis of ccRCC. Members of the collagen family were responsible for more than 15% of the genetic alterations in ccRCC and are involved in multiple signaling pathways. The expression level of collagen family members was closely related to the infiltration of tumor-associated immune cells. Univariate and multivariate Cox regression identified the prognosis-related genes: COL5A1. Conclusions: Our study implied that members of the collagen family may serve as a biomarker for ccRCC metastasis and prognosis.

Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer.

OBJECTIVE: TIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer. METHODS: The expression of CD155 and TIGIT in cervical cancer tissues was detected using flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Changes in the NF-κB and ERK pathways were detected using western blotting (WB) after blocking TIGIT/CD155 signalling. RESULTS: TIGIT expression was elevated in patients with cervical cancer. High TIGIT expression in CD8+ T lymphocytes from patients with cervical cancer promotes the exhaustion of CD8+ T lymphocytes. In addition, CD155 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+ T cells. We found that TIGIT, upon binding to CD155 and being phosphorylated, inhibited NF-κB and ERK activation by recruiting SHIP-1, resulting in the downregulation of cytokine production. Blocking TIGIT in activated CD8+ T cells attenuates the inhibitory effect of SHIP-1 on CD8+ T cells and enhances the activation of NF-κB and ERK. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Injecting the blocking antibody TIGIT in vivo inhibits tumour growth and enhances CD8+ T lymphocyte function. Treatment with a combination of TIGIT and PD-1 inhibitors further increases the efficacy of the TIGIT blocking antibody. CONCLUSIONS: Our research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.

Vocabulary Growth in Mandarin-Speaking Children With Bilateral Cochlear Implants, Bimodal Stimulation, or Unilateral Cochlear Implants During the First Year After Activation.

PURPOSE: The purpose of this study was to evaluate vocabulary development in Mandarin-speaking children with bilateral cochlear implants (CIs), bimodal stimulation (CI plus hearing aids [HAs]), or unilateral CIs during the first year after CI activation. METHOD: Participants included 23 children with simultaneous bilateral CIs, 23 children with bimodal stimulation, and 15 children with unilateral CIs. They all received CIs before 30 months of age. Parents were asked to endorse words that their child could understand only or understand and say using the Early Vocabulary Inventory for Mandarin Chinese at the day of CI activation and 1, 3, 6, 9, and 12 months after CI activation. Receptive and expressive vocabulary sizes were computed. RESULTS: Growth curve analysis revealed that children with simultaneous bilateral CIs demonstrated faster growth of receptive vocabulary than those with bimodal stimulation, followed by those with unilateral CIs. Moreover, children with simultaneous bilateral CIs reached the 100-word mark for receptive vocabulary earlier than children with bimodal stimulation, followed by those with unilateral CIs. There were no significant differences among the three groups in expressive vocabulary. CONCLUSIONS: Bilateral CIs have an advantage over bimodal stimulation in early receptive vocabulary development in Mandarin, a tone language. HA usage is still recommended for those who receive one CI.