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Oral mucositis (OM) is a common debilitating dose-limiting toxicity of cancer treatment, including hematopoietic stem cell transplantation (HSCT). We hypothesized that the oral microbiome is disturbed during allogeneic HSCT, partially accounting for the variability in OM severity. Using 16S ribosomal RNA gene sequence analysis, metabolomic profiling, and computational methods, we characterized the behavior of the salivary microbiome and metabolome of 184 patients pre- and post-HSCT. Transplantation was associated with a decrease in oral α diversity in all patients. In contrast to the gut microbiome, an association with overall survival was not detected. Among 135 patients given methotrexate for graft-versus-host disease prophylaxis pre-HSCT, Kingella and Atopobium abundance correlated with future development of severe OM. Posttransplant, Methylobacterium species were significantly enriched in patients with severe OM. Moreover, the oral microbiome and metabolome of severe OM patients underwent distinct changes post-HSCT, compared with patients with no or mild OM. Changes in specific metabolites were well explained by microbial composition, and the common metabolic pathway was the polyamines pathway, which is essential for epithelial homeostasis. Together, our findings suggest that salivary microbial composition and metabolites are associated with the development of OM, offering new insights on pathophysiology and potential avenues of intervention.

The sentence repetition (SR) test is considered as a promising diagnostic tool for detecting language proficiency in monolingual learners, but less is known about its potential to identify dual language learners' (DLLs) linguistic proficiency. Considering that challenges with language learning, such as developmental language disorders (DLDs), is evident in both first and second language (L1 and L2), it is important to use tools that can assess language functions in both languages whenever feasible. We found that students' L1 and L2 SR performance levels draw upon their phonological short-term memory capacity, vocabulary and grammar skills in the language being assessed. We also found a positive relationship between students' L1 phonological memory and L2 SR scores, suggesting that DLLs' phonological short-term memory capacity assessed in their L1 indicates individual differences in short-term verbal memory that support SR performance, as assessed in L2. The results highlight a challenge in both research and clinical settings which often use monolingual assessment tools and associated norms to identify DLLs who might be at risk of developing DLDs or other learning difficulties.

This cross-sectional study investigated first (L1) and second (L2) language receptive and expressive vocabulary in a sample of 542 typically developing bilingual children of immigrants (age range 6-13), coming from six different L1 backgrounds in Norway. Results demonstrated that children's L1 and L2 vocabulary skills increased with age. From a deficit perspective, the study confirms that in each age group, there is a vocabulary gap between the ranges of Norwegian vocabulary known by Norwegian monolinguals and by Norwegian L2 children. At the same time, when an additive, conceptual scoring approach (taking into account bilingual children's known L1 and/or L2 vocabulary) was used, the persistent gap in vocabulary knowledge diminished or disappeared altogether. This finding is most evident in older age groups. Conceptual scoring provides a more sensitive and positive picture of bilingual children's overall range of vocabulary. The findings demonstrate a need for more nuanced assessment procedures of semantic knowledge across children's' L1 and L2.

This study examined (a) the identification of various reading groups across languages in Chinese (L1) adolescents learning English as a second language (ESL), in terms of their word-reading and reading comprehension skills, (b) overlap in reading group membership across languages, and (c) the performance of the various reading groups on reading-related language comprehension measures in English. The participants were 246 eighth-grade students from an English-immersion program in a middle school in China. Latent profile analysis identified three reading groups in each language: (a) a typically developing reader group with average or above-average word-reading and reading comprehension, (b) a group with poor decoding/word-reading skills and weak reading comprehension, and (c) a group with poor reading comprehension in the absence of poor decoding/word reading. The overlap in profile characteristics across languages for typically developing readers and poor decoders was high (about 68% for typically developing readers and 54% for poor decoders), whereas the overlap for being poor comprehenders in each language was moderate (about 37%). Furthermore, poor decoders in either language performed more poorly than the typically developing and poor comprehender groups on word reading in the other language, while poor comprehenders in either language performed more poorly than the typically developing and poor decoder groups on reading comprehension in the other language. The comparison of the reading groups' performance on English reading-related language comprehension measures showed that poor comprehenders and poor decoders performed worse than typically developing readers. Implications for identification and instruction of ESL children with reading difficulties are discussed.

Conjunctions facilitate text cohesion and comprehension by making explicit the logical relationships between ideas in written language. Conjunctions may be challenging for English language learners (ELLs) because of their novel, abstract, and text-connecting role. In this longitudinal study we aimed to clarify the connections among comprehension of logical relationships, general vocabulary knowledge, and reading comprehension in elementary school-aged ELLs. We assessed these skills--along with decoding, working memory, and nonverbal reasoning--in 74 ELLs in Grades 3 and 4. Path analysis revealed that comprehension of logical relationships was a direct predictor of concurrent reading skills in Grades 3 and 4, and an indirect predictor of reading comprehension in Grade 4, where vocabulary and prior comprehension performance acted as partial mediators. Results point to the confluence of general vocabulary with conjunctions in contributing to individual differences in ELLs' reading comprehension. Conjunctions represent a specialized form of vocabulary knowledge that should not be subsumed developmentally or instructionally under general vocabulary knowledge.

PurposeKEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC).MethodsThis phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti-vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability.ResultsA total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2.1 to 18.9 months). Median overall survival was 31.4 months (95% CI, 21.4 months to not reached) and not reached (95% CI, 19.2 months to not reached). Treatment-related grade 3-4 adverse events occurred in 10 patients (16%) in cohort A and 8 (13%) in cohort B, with the most common occurring in ≥ 2 patients being pancreatitis, fatigue, increased alanine aminotransferase, and increased lipase (2 patients each; 3%) in cohort A.ConclusionPembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.

This study examined the sources of reading comprehension difficulties in English language learners (ELLs). The characteristics of ELL poor comprehenders were compared to their English as a first language (EL1) peers. Participants included 124 ELLs who spoke Chinese as an L1 and 79 EL1 students. Using a regression technique based on age, non-verbal reasoning, word reading accuracy, and word reading fluency, three types of comprehenders (poor, average, and good) were identified within each language group. The groups were then compared on measures of oral language skills (vocabulary breadth, vocabulary depth, and listening comprehension), metalinguistic skills (morphological awareness and syntactic awareness), working memory, and higher-level processing skills (inference, conjunction use, and comprehension monitoring). ELL poor comprehenders had significantly lower scores than ELL average and good comprehenders on vocabulary breadth, listening comprehension, and morphological awareness, whereas there were no significant differences between the average and good comprehender groups on these skills. Additionally, both ELL poor and average comprehenders had lower scores than ELL good comprehenders on all three higher-level skills. Finally, results showed that ELL poor comprehenders scored lower than EL1 poor comprehenders on vocabulary breadth, listening comprehension, and morphological awareness, but the two groups did not differ on higher-level skills. Theoretical and educational implications for the identification and instruction of ELL poor comprehenders are discussed.

BACKGROUND:The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. METHODS:Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m2 on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). RESULTS:In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy). CONCLUSIONS:Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. CLINICAL TRIAL:ClinicalTrials.gov NCT02335411.

Multimodal constructions which intertwine language and music are characteristic of the discourse of creative encounters among musicians. This interactional linguistic study reports on one such construction: the 'music-taking-predicate' (MTP) construction. MTP constructions consist of a projective verbal predicate, and a stretch of sung or played musical expression following it. Based on naturalistic video data of Hebrew-speaking musicians in rehearsals and production sessions, I show that instances of this construction emerge as formulae for the achievement of several interactional tasks integral to the process of joint music making. [ABSTRACT FROM AUTHOR]

This study aims to provide an update on the clinical presentation, diagnostic workup, operative strategies, and midterm outcomes in children undergoing ventricular fibroma resection. Single-center, retrospective cohort study of patients undergoing ventricular fibroma resection between 2000 and 2023. Among 52 patients, median age at surgery was 2.0 years (interquartile range, 0.8-4.6) and median tumor volume index was 69 mL/m2 (interquartile range, 49-169). Tumor distorted the atrioventricular valve/subvalvar apparatus in 30 patients (58%) and abutted major epicardial coronary arteries in 41 patients (79%). Surgery was indicated for arrhythmia (n = 45, 86%), symptoms (n = 14, 27%), or hemodynamic compromise (n = 11, 21%). Tumor was debulked in 34 patients (65%), including the last 21 patients. Concomitant atrioventricular valvuloplasty was performed in 18 patients and ventricular cavity closure in 15 patients (29%). During a median follow-up of 2.4 years (interquartile range, 0.8-6.2), there was no mortality, cardiac arrests, heart transplants, or single ventricle palliation. The 15-year risk of reoperation and clinical ventricular tachycardia/fibrillation was 6.7% (95% CI, 0-14.3) and 2.4% (95% CI, 0-7.2), respectively. On latest imaging, pre- and postdebulking left ventricular ejection fraction did not significantly differ (P =.069), whereas no patients had signs of outflow tract obstruction, inflow tract obstruction, or moderate or greater atrioventricular valve regurgitation. Large ventricular fibromas can be resected safely with appropriate surgical planning and an emphasis on debulking. Most children maintain left ventricular function and remain free of recurrent ventricular arrhythmias at follow-up. Extended follow-up is warranted to understand whether patients remain at risk for scar-based ventricular arrhythmias in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Models of reading development point to a role for knowledge about the orthography quite late in children's reading development; here we explore the contributions of early orthographic knowledge -- of the features of print -- to word reading development between kindergarten and Grade 1. We did so in a longitudinal study of 93 emergent bilingual children whose formal instruction was in French, a different language than they spoke at home, followed from senior kindergarten to Grade 1. Linear regression analyses showed that early print knowledge in both English and French significantly predicted French word reading in Grade 1; no such relations emerged to English word reading. Analyses included control measures of parental education and English vocabulary, phonological awareness, rapid automatized naming, and autoregressive controls of earlier word reading. These results suggest that print knowledge can be used to predict progress in second language word reading in emergent bilingual children.

According to the Componential Model of Reading (CMR; Aaron, Joshi, Gooden, & Bentum, 2008), reading comprehension can be explained by 3 domains--cognitive, psychological, and ecological domains. We examined the direct and indirect contributions of these 3 domains to reading comprehension in bilingual learners. Participants included 124 bilingual children in Grades 4 through 6 who spoke Chinese as their first language. They were administered a battery of language and literacy measures, and motivation and acculturation questionnaires. Additionally, the participants' parents completed a home literacy environment questionnaire in Chinese. Using structural equation modeling, we found direct effects of the cognitive and psychological domains on reading comprehension. The ecological domain only had an indirect influence on reading comprehension via the cognitive and psychological domains. The findings support and extend the CMR model and advance our understanding of the nature of the relationships among the different components of the model among bilingual learners.

This article analyzes the contents of Arabic grammar curricula authorized for the upper years of primary school by the ministries of education of Israel, Palestine, Jordan, Lebanon, and Saudi Arabia. The article aims to determine the attitudes and rationales behind these curricula, as well as their objectives, the grammatical materials they cover, the amount of time they allocate to the study of grammar, and their educational and pedagogical approach. Drawing on the results of a comparative analysis, the authors propose developmental alternatives to the current curricula. Arabic language instruction in Hebrew language schools in Israel is not addressed. The results of the study suggest that the examined curricula fail to achieve the functional standards for grammar instruction they set for themselves and to integrate the various domains of linguistic study, and that they suffer from other weaknesses that must be addressed.

The purpose of the present study was to examine the predictive value of a dynamic test of English and French lexical specificity on at-risk reading classification in 13 at-risk and 44 not at-risk emerging English (L1)-French (L2) bilingual Grade 1 children (M = 75.87 months, SD = 3.18) enrolled in an early French immersion program in Canada. Lexical specificity was assessed with a computerized word learning game in which children were taught new English (e.g., "foal" and "sole") and French (e.g., "bac" "bin" and "bague" "ring") word pairs contrasted by minimal phonological differences. The results indicated that the dynamic test of lexical specificity in English contributed significantly to the prediction of children's French at-risk reading status at the end of Grade 1 after controlling for French phonological awareness and nonverbal reasoning skills. However, French lexical specificity did not predict children's reading risk classification in French after controlling for French phonological awareness. Thus, it may be feasible to identify at-risk status in emerging bilinguals using dynamic measures in their stronger language.

Pancreatic cancer has a poor prognosis and limited treatment options. Approximately 9% of pancreatic cancers harbor a germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation. Because poly (ADP-ribose) polymerase inhibitors have significant activity in BRCA1/2-mutant ovarian and breast cancers, RUCAPANC investigated the efficacy and safety of rucaparib in BRCA1/2-mutant pancreatic cancer. RUCAPANC enrolled patients with measurable locally advanced/metastatic pancreatic cancer who had received one to two prior chemotherapy regimens. Patients received oral rucaparib (600 mg twice daily) until disease progression. The primary end point was objective response rate. Nineteen patients were enrolled. Sixteen of 19 BRCA1/2 mutations were germ-line; three were somatic. Patients had received a median of two prior chemotherapy regimens. Four patients achieved a response; two partial responses and one complete response (CR) were confirmed (objective response rate, 15.8%; 3 of 19), with an additional CR unconfirmed. The disease control rate (CR, partial response, or stable disease for ≥ 12 weeks) was 31.6% (6 of 19) in all patients and 44.4% (4 of 9) in those who had received one prior chemotherapy regimen. As prespecified in the protocol, enrollment was stopped because of an insufficient response rate among the first 15 patients. Treatment-emergent adverse events included nausea (63.2%) and anemia (47.4%). Grade ≥ 3 adverse events included anemia (31.6%), fatigue (15.8%), and ascites (15.8%). Secondary resistance mutations were detected in circulating free tumor DNA in two patients with a germline BRCA2 mutation. These mutations are predicted to lead to the reversion of a somatic-not germline-mutation. Rucaparib provided clinical benefit to patients with advanced pancreatic cancer and a BRCA1/2 mutation, and demonstrated an acceptable safety profile. Additional trials of rucaparib in this population are warranted.