CDK4/6 and autophagy inhibitors synergize to suppress the growth of human head and neck squamous cell carcinomas.

Head and neck squamous cell carcinoma (HNSCC) accounts for over 10,000 deaths in the United States annually. Approximately 80% of HNSCC are human papillomavirus (HPV)-negative which have an overall poorer prognosis compared to the HPV-positive disease. Treatment options are mainly nontargeted chemotherapy, radiation, and surgery. The cyclin-d-CDK4/6-RB pathway, which regulates cell cycle progression, is often deregulated in HNSCC, making it an attractive therapeutic target. In the current study, we investigated the therapeutic effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in preclinical models of HNSCCs. Our results show that the specific CDK4/6 inhibitor, abemaciclib, inhibited cell growth, and induced apoptosis in HNSCC cell lines. We also demonstrated that both the pro-survival autophagy pathway and the ERK pathway in HNSCC cells were activated with abemaciclib treatment through the generation of reactive oxygen species (ROS). Coinhibition of CDK4/6 and autophagy synergistically decreased cell viability, induced apoptosis, and inhibited tumor growth in both in vitro and in vivo preclinical HNSCC models. These results reveal a potential therapeutic strategy that supports the rationale for further clinical development of a combination of CDK4/6 and autophagy inhibitors in HNSCC.

Remote First-Language Assessment: Feasibility Study With Vietnamese Bilingual Children and Their Caregivers.

PURPOSE: There is a shortage of bilingual speech-language pathologists (SLPs) in the United States. For Vietnamese, less than 1% of SLPs speak the language compared with a Vietnamese American population of > 2.1 million. This study examines the feasibility and social validity of remote child language assessment with the help of a caregiver to address the need for first language assessments among Vietnamese-speaking children. METHOD: Twenty-one dyads of caregivers and typically developing children (aged 3-6 years) completed two assessment sessions in their first language, Vietnamese, using Zoom videoconferencing. Sessions were counterbalanced between two conditions in which either the clinician or the caregiver was the task administrator. Children's language samples were elicited using narrative tasks. Social validity was also assessed through caregiver and child questionnaires at the end of each session. RESULTS: There were no significant differences between conditions on language sample measures nor the measures of social validity. Both caregivers and their children felt positively about the sessions. The caregivers' feelings were related to their perception of children's feelings about the sessions. Children's feelings were related to their Vietnamese language proficiency, caregiver-reported language ability, and whether they were born outside of the United States. CONCLUSIONS: Findings build the evidence base for telepractice as an effective and socially valid service delivery model for bilingual children in the United States. This study supports the potential for caregivers as task administrators in a telepractice setting, making assessment in a child's first language more feasible and accessible. Future investigation is needed to extend results to bilingual populations with disorders.

Reading Attitudes in Vietnam: Initial Study of the Early School Years.

Whereas cognitive and linguistic factors for learning to read have been extensively studied, less is known about affective factors including children's attitudes toward reading. Studies primarily from English-speaking and Western countries show gradual declines in reading attitudes in elementary school (McKenna et al., 1995) and a positive association between reading attitudes and achievement (Petscher, 2010). Children from Asian and African countries are underrepresented in this literature; whether these patterns can be generalized across cultures needs further investigation. This longitudinal study examined the reading attitudes of 84 children in Vietnam from grades 1 to 2 and their relations to reading performance, as measured by translated and adapted versions of the Elementary Reading Attitude Survey and Early Grade Reading Assessment, respectively. This sample from Vietnam showed a small decline in reading attitudes over time, particularly in attitudes toward academic reading. However, children on average reported feeling happy about reading in both grades. Correlations revealed different patterns of association between reading attitudes and performance based on the reading measure employed, grade level, and type of reading in question (academic versus recreational). In grade 2, reading attitudes explained unique variance in reading comprehension even after text fluency and mother's education were considered. We present a margins plot to visualize the role of reading attitudes on reading comprehension. We discuss educational implications and future directions.

Grammatical Characteristics of Vietnamese and English in Developing Bilingual Children.

Purpose Defining parameters for typical development in bilingual children's first and second languages can serve as the basis for accurate language assessment. This is the first study to characterize Vietnamese and English grammatical development in a sample of bilingual children. Method Participants were 89 Vietnamese-English bilingual children, aged 3-8 years. Children completed story retell tasks in Vietnamese and English. Stories were transcribed and analyzed for grammaticality, error patterns, subordination index, and types of subordinating clauses. Of key interest were associations with age and identifying developmental patterns that were shared across languages or unique to a given language. Results Age correlated with more measures in English than in Vietnamese, suggesting that older children had higher grammaticality and greater syntactic complexity in English than younger children. Children also produced greater syntactic complexity with age in Vietnamese, but not higher grammaticality. There were a set of error patterns shared across languages (e.g., object omission) and patterns specific to each language (e.g., classifier errors in Vietnamese, tense errors in English). While children produced nominal, adverbial, and relative clauses in Vietnamese and English, the proportion of each clause type differed by language. Conclusions Results from this typically developing sample provide a reference point to improve clinical practice. Characterizing developmental patterns in sentence structure in Vietnamese and English lays the groundwork for investigations of language disorders in this bilingual population.

Capitalizing on cross-language similarities in intervention with bilingual children.

PURPOSE: This study examined the effects of a vocabulary intervention for bilingual children that was conducted in children's first language, Spanish, and included explicit instruction on cognates. We measured effects in terms of change from pre- to post-intervention in Spanish as well as associations with the non-target language, English. METHOD: Participants were 12 Spanish-English bilingual children, aged 6-8 years, with and without Developmental Language Disorder. Children completed the intervention in pairs (one child with DLD and a typically developing peer) for 70-minute sessions, 3 days a week, for four weeks. Intervention targeted 32 words (16 cognates, 16 non-cognates) using four storybooks (8 words/book) and interactive activities that highlighted similarities across languages. Pre- and post-intervention measures in Spanish and English included tasks of word definition and cognate facilitation. RESULTS: As a group, children showed improvement in definition quality and cognate naming in Spanish. There was a positive correlation between definition quality and cognate naming for the typically developing children, but not for the children with DLD. All children showed positive cross-language correlations on post-intervention measures. CONCLUSIONS: Bilingual children, with and without DLD, have the capacity to improve in their awareness and use of cognates. Explicit teaching of cognates can be an effective tool for building vocabulary skills. Children with DLD may need additional time and support to apply their knowledge of cognates to vocabulary learning.

Identifying Developmental Language Disorder in Vietnamese Children.

Purpose Developmental language disorder (DLD), defined by low language performance despite otherwise normal development, can negatively impact children's social and academic outcomes. This study is the 1st to examine DLD in Vietnamese. To lay the foundation, we identified cases of DLD in Vietnam and explored language-specific characteristics of the disorder. Method Teacher ratings of 1,250 kindergarteners living in Hanoi, Vietnam, were used to recruit children with and without risk for DLD. One hundred four children completed direct measures of vocabulary and language sampling, and their parents completed in-depth surveys. We examined convergence and divergence across tasks to identify measures that could serve as reliable indicators of risk. Then, we compared performance on direct language measures across ability levels. Results There were positive associations between teacher and parent report and between report and direct language measures. Three groups were identified based on convergence across measures: DLD, some risk for DLD, and no risk. The DLD group performed lowest on measures of receptive and expressive vocabulary, mean length of utterance, and grammaticality. Although children with DLD exhibited a greater number of errors, the types of errors found were similar across DLD and No Risk groups. Conclusions Similar to rates found globally, 7% of the kindergarten population in Vietnam exhibited risk for DLD. Results highlight the importance of parent and teacher report and the value of multiple measures to identify DLD. We discuss potential clinical markers for DLD in the Vietnamese language and outline future directions.

Learning Words and Definitions in Two Languages: What Promotes Cross-Language Transfer?

This study used a brief vocabulary training paradigm to examine two factors for cross-language transfer: how similar the first language (L1) is to the second language (L2) and L1-L2 proficiency levels. Fifty-four sequential bilingual children (aged 6-8) with similar L2 English proficiency levels were assigned to three equal groups: a Vietnamese-English group with low L1 proficiency, a Spanish-English group with low L1 proficiency, and a Spanish-English group with high L1 proficiency. Individual training consisted of two mediated learning experiences conducted in the L1 targeting eight vocabulary items using narrative-based activities. Four of eight target words were cognates between Spanish and English. Pre- and posttesting measured definition quality in the L1 and L2. All groups showed improvement in the L1 following training, but only the Spanish-English group with high L1 proficiency improved in L2 English, revealing a degree of spontaneous cross-language transfer among children with high L1-L2 proficiency.

Nonword repetition stimuli for Vietnamese-speaking children.

Nonword repetition (NWR) has been a widely used measure of language-learning ability in children with and without language disorders. Although NWR tasks have been created for a variety of languages, minimal attention has been given to Asian tonal languages. This study introduces a new set of NWR stimuli for Vietnamese. The stimuli include 20 items ranging in length from one to four syllables. The items consist of dialect-neutral phonemes in consonant-vowel (CV) and CVC sequences that follow the phonotactic constraints of the language. They were rated high on wordlikeness and have comparable position segments and biphone probabilities across stimulus lengths. We validated the stimuli with a sample of 59 typically developing Vietnamese-English bilingual children, ages 5 to 8. The stimuli exhibited the expected age and length effects commonly found in NWR tasks: Older children performed better on the task than younger children, and longer items were more difficult to repeat than shorter items. We also compared different scoring systems in order to examine the individual phoneme types (consonants, vowels, and tones) and composite scores (proportions of phonemes correct, with and without tone). The study demonstrates careful construction and validation of the stimuli, and future directions are discussed.