Isolation of salivary cell-free DNA for cancer detection.

Saliva is an emerging source of disease biomarkers, particularly for cancers of the head and neck. Although analysis of cell-free DNA (cfDNA) in saliva holds promise as a liquid biopsy for cancer detection, currently there are no standardized methodologies for the collection and isolation of saliva for the purposes of studying DNA. Here, we evaluated various saliva collection receptacles and DNA purification techniques, comparing DNA quantity, fragment size, source, and stability. Then, using our optimized techniques, we tested the ability to detect human papillomavirus (HPV) DNA- a bona fide cancer biomarker in a subset of head and neck cancers- from patient saliva samples. For saliva collection, we found that the Oragene OG-600 receptacle yielded the highest concentration of total salivary DNA as well as short fragments <300 bp corresponding to mononucleosomal cell-free DNA. Moreover, these short fragments were stabilized beyond 48 hours after collection in contrast to other saliva collection receptacles. For DNA purification from saliva, the QIAamp Circulating Nucleic Acid kit yielded the highest concentration of mononucleosome-sized DNA fragments. Freeze-thaw of saliva samples did not affect DNA yield or fragment size distribution. Salivary DNA isolated from the OG-600 receptacle was found to be composed of both single and double-stranded DNA, including mitochondrial and microbial sources. While levels of nuclear DNA were consistent over time, levels of mitochondrial and microbial DNA were more variable and increased 48 hours after collection. Finally, we found that HPV DNA was stable in OG-600 receptacles, was reliably detected within the saliva of patients with HPV-positive head and neck cancer, and was abundant among mononucleosome-sized cell-free DNA fragments. Our studies have defined optimal techniques for isolating DNA from saliva that will contribute to future applications in liquid biopsy-based cancer detection.

Developmental Language Disorder Is Associated With Slower Processing Across Domains: A Meta-Analysis of Time-Based Tasks.

PURPOSE: Individuals with developmental language disorder (DLD) often exhibit slower processing on time-based tasks in comparison with age-matched peers. Processing speed has been linked to various linguistic skills and might serve as a global indicator of individual differences in language abilities. Despite an extensive literature on processing speed in DLD, it remains unclear whether slower processing is domain general or restricted to linguistic and/or auditory tasks. METHOD: This meta-analysis used robust variance estimation to compare response/reaction times (RTs) of DLD and age-matched groups (N = 812 DLD, 870 neurotypical; M age [DLD] = 8.9 years, range: 4.3-22.7 years). Moderators included task (simple RT, choice RT, naming, congruent/baseline conditions of interference control tasks), stimulus type (linguistic/nonlinguistic), stimulus modality (auditory/nonauditory), and response modality (verbal/nonverbal). Age and publication year were covariates. RESULTS: The overall effect based on 46 studies and 144 estimates indicated longer mean RTs in DLD groups (g = .47, p < .001, 95% CI [.38, .55]). Moderator analyses indicated larger effects when tasks required verbal as opposed to nonverbal responses. No other moderators approached significance. All subgroup analyses were significant, indicating longer mean RTs in DLD groups across tasks, stimulus types, stimulus modalities, and response modalities. CONCLUSIONS: Individuals with DLD exhibit longer RTs across verbal and nonverbal tasks, which may contribute to observed difficulties in language, motor skills, and executive functioning. Simple processing speed measures should be included in screening for language delays but may not be suitable for differential diagnosis, given that slower processing may occur across multiple disorders. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21809355.

Slower Processing Speed in Autism Spectrum Disorder: A Meta-analytic Investigation of Time-Based Tasks.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting information processing across domains. The current meta-analysis investigated whether slower processing speed is associated with the ASD neurocognitive profile and whether findings hold across different time-based tasks and stimuli (social vs. nonsocial; linguistic vs. nonlinguistic). Mean RTs of ASD and age-matched neurotypical comparison groups (N = 893 ASD, 1063 neurotypical; mean age ASD group = 17 years) were compared across simple RT, choice RT, and interference control tasks (44 studies, 106 effects) using robust variance estimation meta-analysis. Simple RT tasks required participants to respond to individual stimuli, whereas choice RT tasks required forced-choice responses to two or more stimuli. Interference control tasks required a decision in the context of a distractor or priming stimulus; in an effort to minimize inhibitory demands, we extracted RTs only from baseline and congruent conditions of such tasks. All tasks required nonverbal (motor) responses. The overall effect-size estimate indicated significantly longer mean RTs in ASD groups (g = .35, 95% CI = .16; .54) than comparison groups. Task type moderated effects, with larger estimates drawn from simple RT tasks than interference control tasks. However, across all three task types, ASD groups exhibited significantly longer mean RTs than comparison groups. Stimulus type and age did not moderate effects. Generalized slowing may be a domain-general characteristic of ASD with potential consequences for social, language, and motor development. Assessing processing speed may inform development of interventions to support autistic individuals and their diverse cognitive profiles.

Prevention of oral and maxillofacial trauma secondary to orofacial dyskinesias associated with anti-N-methyl-D-aspartate receptor encephalitis: a case series.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a multi-stage autoimmune-mediated disease associated with a multitude of neuropsychiatric and dysautonomic features. Orofacial dyskinesias are frequently associated with this condition and manifest as abnormal movements of the orofacial musculature. These involuntary movements may result in significant trauma to the oral and maxillofacial complex including the avulsion of the dentition and orofacial lacerations. CASE PRESENTATION: We describe the course of two female patients with anti-NMDARE in whom significant involuntary self-inflicted maxillofacial trauma was suffered despite the use of complex parenteral sedation regimens. The application of traditional maxillomandibular wiring techniques and pharmacologic strategies, including botulinum toxin, to immobilize the mandible were initially unsuccessful. These difficulties led to the fabrication and wire-based fixation of a patient-specific acrylic oral appliance that maintained the mandible in a depressed position and mitigated all lateral and protrusive movements. DISCUSSION AND CONCLUSIONS: These cases illustrate the first known successful use of an appliance-based therapy for managing orofacial dyskinesias in the anti-NMDARE patient population through an adaptation of traditional maxillomandibular fixation techniques. This approach eliminated further orofacial trauma and afforded physicians with safer means to manage and assess patients afflicted with this condition during their protracted intensive care unit admissions.

Improving college students' fact-checking strategies through lateral reading instruction in a general education civics course.

College students lack fact-checking skills, which may lead them to accept information at face value. We report findings from an institution participating in the Digital Polarization Initiative (DPI), a national effort to teach students lateral reading strategies used by expert fact-checkers to verify online information. Lateral reading requires users to leave the information (website) to find out whether someone has already fact-checked the claim, identify the original source, or learn more about the individuals or organizations making the claim. Instructor-matched sections of a general education civics course implemented the DPI curriculum (N = 136 students) or provided business-as-usual civics instruction (N = 94 students). At posttest, students in DPI sections were more likely to use lateral reading to fact-check and correctly evaluate the trustworthiness of information than controls. Aligning with the DPI's emphasis on using Wikipedia to investigate sources, students in DPI sections reported greater use of Wikipedia at posttest than controls, but did not differ significantly in their trust of Wikipedia. In DPI sections, students who failed to read laterally at posttest reported higher trust of Wikipedia at pretest than students who read at least one problem laterally. Responsiveness to the curriculum was also linked to numbers of online assignments attempted, but unrelated to pretest media literacy knowledge, use of lateral reading, or self-reported use of lateral reading. Further research is needed to determine whether improvements in lateral reading are maintained over time and to explore other factors that might distinguish students whose skills improved after instruction from non-responders.

Engaging Adolescent and Young Adults in Microbiome Sample Self-Collection: Strategies for Success.

Human microbiome research provides rich opportunities to elucidate factors influencing health, uncover novel biomarkers, and expand disease treatment options. A well-conducted microbiome study depends not only on a rigorous design but also on successfully engaging participants in collecting quality samples. In this paper, we aim to describe (1) strategies our team used to engage adolescents and young adults in vaginal and gut microbiome sample self-collection and (2) their effectiveness. In our prospective, longitudinal, feasibility study of 20 female adolescents and young adults, research participants self-collected vaginal and gut microbiome samples at home. Using a participatory and iterative process, we developed strategies to engage participants in sample self-collection, including (1) providing clear instructions to ensure comprehension and buy-in, (2) providing a user-friendly take-home package, (3) minimizing disgust/embarrassment associated with sample collection, and (4) follow-up communications to facilitate sample collections and return. With these strategies, we achieved 100% participant retention and 100% sample return rates. All samples (n = 80, 100%) were usable for downstream 16s rRNA gene sequencing and analysis. All participants rated the study procedures as acceptable, and qualitative data showed that strategies were well received by participants. This study suggests that carefully planning and implementing strategies to engage participants in sample self-collection can result in high degrees of participant compliance, sample quality, and participant satisfaction in microbiome research.

CD301 mediates fusion in IL-4-driven multinucleated giant cell formation.

Multinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301+ MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold (P<0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.This article has an associated First Person interview with the first author of the paper.

Closing the symbolic reference gap to support flexible reasoning about the passage of time.

This commentary relates Hoerl & McCormack's dual systems perspective to models of cognitive development emphasizing representational redescription and the role of culturally constructed tools, including language, in providing flexible formats for thinking. We describe developmental processes that enable children to construct a mental time line, situate themselves in time, and overcome the primacy of the here and now.

Factors underlying cross-cultural differences in stigma toward autism among college students in Lebanon and the United States.

Although stigma negatively impacts autistic people globally, the degree of stigma varies across cultures. Prior research suggests that stigma may be higher in cultures with more collectivistic orientations. This study aimed to identify cultural values and other individual differences that contribute to cross-cultural differences in autism stigma (assessed with a social distance scale) between college students in Lebanon (n = 556) and those in the United States (n = 520). Replicating prior work, stigma was lower in women than men and in the United States relative to Lebanon. Heightened autism knowledge, quality of contact with autistic people, openness to experience, and reduced acceptance of inequality predicted lower stigma. Collectivism was not associated with heightened stigma. Findings highlight the need to address structural inequalities, combat harmful misconceptions, and foster positive contact to combat stigma.

An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathologic Processes.

Monocyte lineage cells play important roles in health and disease. Their differentiation into macrophages is crucial for a broad array of immunologic processes that regulate inflammation, neoplasia, and infection. In certain pathologic conditions, such as foreign body reactions and peripheral inflammatory lesions, monocytes fuse to form large, multinucleated giant cells (MGCs). Currently, our knowledge of the fusion mechanisms of monocytes and the regulation of MGC formation and function in discrete pathologies is limited. Herein, we consider the types and function of MGCs in disease and assess the mechanisms by which monocyte fusion contributes to the formation of MGCs. An improved understanding of the cellular origins and metabolic functions of MGCs will facilitate their identification and ultimately the treatment of diseases and disorders that involve MGCs.

Is there a bilingual advantage on interference-control tasks? A multiverse meta-analysis of global reaction time and interference cost.

A contentious issue in contemporary psycholinguistics is whether bilingualism enhances executive functions. Here, we report a meta-analysis of 80 studies (253 effect sizes) comparing performance of monolinguals and bilinguals on non-verbal interference-control tasks, while examining potential moderators of effects on two dependent variables (DVs): global reaction time (RT) and interference cost. We used a multiverse approach to determine how robust conclusions were to several dataset construction and analysis decisions. In our "preferred" analysis, using a broad definition of bilinguals and standard versions of interference-control tasks, there was a very small but significant bilingual advantage for global RT (g =.13), which became non-significant once corrected for publication bias. For interference cost, there was a very small but significant bilingual advantage (g =.11). Effects were not significantly moderated by task or participant age, but were moderated by an interaction between age of second language acquisition (AoA) and the DV. Unexpectedly, larger effect sizes for interference cost were observed for studies involving bilinguals with late as opposed to early AoA. The multiverse analysis produced results largely consistent with the preferred analysis, confirming our conclusion that evidence for a bilingual advantage on interference-control tasks is weak.

Primary aneurysmal bone cyst of the mandibular condyle with USP6-CDH11 fusion.

Primary aneurysmal bone cyst (ABC) is a cystic bone neoplasm characterized by disease-defining gene fusions involving the USP6/Tre2 gene. The literature describing gnathic ABC is limited. This case report describes a 27-year-old man presenting with a long-standing left-sided facial asymmetry. Multi-detector computed tomography imaging demonstrated a large expansile lesion positioned within the left condylar head. The lesion was biopsied and resected. The specimen showed a giant cell-rich cystic neoplasm, with fibrous tissue lined by multinucleated giant cells. Next-generation sequencing confirmed the presence of a USP6-CDH11 fusion gene, consistent with classification as a primary ABC, the first reported to be translocation-positive in the head of the mandibular condyle.

Associations Between Manual Dexterity and Language Ability in School-Age Children.

Purpose: We aimed to determine whether individual differences in manual dexterity are associated with specific language skills (nonword repetition, receptive vocabulary, and receptive grammar) after controlling for nonverbal abilities (visual-spatial working memory and intelligence). Method: We assessed manual dexterity using the pegboard task and examined relationships with verbal and nonverbal abilities in a diverse community sample of children (N = 63, mean age = 8;2 [year;months], range: 6;0-10;8) varying in language ability (Comprehensive Evaluation of Language Fundamentals-Fourth Edition core language score M = 105, range: 62-126; Semel, Wiig, & Secord, 2003). Results: Correlational analyses indicated significant relationships between manual dexterity and performance on tests of nonword repetition, receptive vocabulary, receptive grammar, and nonverbal intelligence, after controlling for multiple comparisons. In regression analyses, manual dexterity remained a significant predictor of nonword repetition after controlling for nonverbal abilities and age. In contrast, manual dexterity was no longer significant in predicting receptive vocabulary or grammar when nonverbal intelligence was included as a factor in the model. Conclusions: These findings build on prior work implicating poor fine motor control in child language disorders by identifying a robust relationship between manual dexterity and nonword repetition. Relationships between manual dexterity and receptive language abilities appear to be indirect and mediated by nonword repetition. For clinicians, the results underscore the importance of screening children with poor fine motor control for concomitant language impairments.

Generalization of content and emotional prosody across speakers varying in gender in youth with Autism Spectrum Disorder.

AIMS: We employed a discrimination-choice procedure, embedded in a custom-made videogame, to evaluate whether youth with Autism Spectrum Disorder (ASD), including nonverbal individuals, distinguish sentences on the basis of emotional tone-of-voice and generalize linguistic information across speaker gender. METHODS AND PROCEDURES: Thirteen youth with ASD (7-21 years) and 13 age-matched typical controls heard pairs of pre-recorded sentences varying in lexical content and prosody (e.g., enthusiastic "Dave rode a bike'' vs. grouchy "Mark held a key''). After training to select a target sentence, participants heard test probes comprising re-combinations of the content and prosodic features of the sentences. Interspersed generalization trials used a voice opposite in gender to the voice used in training. OUTCOMES AND RESULTS: Youth with ASD were less accurate than controls in discriminating sentences based on emotional tone-of-voice. Nonverbal and verbal youth did not differ in this regard. The ASD group showed only slight decrements in generalizing to the opposite-gender voice. CONCLUSIONS AND IMPLICATIONS: The finding of intact generalization of linguistic information across male/female speakers contrasts with the widely held view that autism is characterized by deficits in generalization. This suggests the need to test generalization under varying task demands to identify limits on performance.

Stigma associated with autism among college students in Japan and the United States: An online training study.

Misconceptions and stigma associated with autism vary across cultures and may be influenced by various factors. Undergraduates in Japan (N = 212) and the United States (US) (N = 365) completed an online autism training, with pre- and posttest surveys assessing autism-related stigma (i.e., social distance) and knowledge. Aims were to examine differences in autism stigma and knowledge in Japan and the US, while extending prior research demonstrating benefits of an online autism training in the US and Lebanon to Japan. The results revealed that Japanese students indicated greater autism-related stigma than US students, which was not attributable to differences in autism knowledge, prior experience with autism, or college major. In both countries, students majoring in "helping professions" exhibited greater willingness to engage with people with autism. Japanese and US students varied in their misconceptions about autism, with significant differences on about half of the knowledge items. Japanese students showed decreased stigma after completing the autism training, yet continued to exhibit greater social distance towards people with autism relative to US students. Future research should focus on identifying specific cultural factors (e.g., conformity to social norms and homogeneity within communities) that contribute to fear and exclusion of people with autism in different societies.

Assessing the impact of conversational overlap in content on child language growth.

When engaged in conversation, both parents and children tend to re-use words that their partner has just said. This study explored whether proportions of maternal and/or child utterances that overlapped in content with what their partner had just said contributed to growth in mean length of utterance (MLU), developmental sentence score, and vocabulary diversity over time. We analyzed the New England longitudinal corpus from the CHILDES database, comprising transcripts of mother-child conversations at 14, 20, and 32 months, using the CHIP command to compute proportions of utterances with overlapping content. Rates of maternal overlap, but not child overlap, at earlier time-points predicted child language outcomes at later time-points, after controlling for earlier child MLU. We suggest that maternal overlap plays a formative role in child language development by providing content that is immediately relevant to what the child has in mind.

Bullying and Identity Development: Insights from Autistic and Non-autistic College Students.

Reduced cognitive empathy may put autistic people at risk for bullying. We compared interpretations of bullying provided by 22 autistic and 15 non-autistic college students. Autistic (and non-autistic) students reported less severe bullying in college relative to earlier in development. Chronic bullying was associated with improvements in self-descriptions and self-acceptance. Autistic students who were chronically bullied were more likely to self-identify as autistic when asked to explain their disability. Autistic and non-autistic students demonstrated similar levels of cognitive empathy, providing no evidence that a "double empathy problem" contributes to bullying for all autistic individuals. Findings suggest that recovery from bullying can contribute to resilience and that autistic people gain insights about bullying and how to overcome it with development.