Referential Choice in the Narratives of Italian Speakers with Klinefelter Syndrome

Klinefelter Syndrome (KS) is a genetic disorder characterized by an uneven neuro-linguistic profile. Whereas cognitive abilities appear to be within the normal range, KS patients often show poor linguistic abilities and language-based learning disorders. Although it has been proposed that KS can be considered a genetic model of language impairment, it is not yet well established whether speakers with KS are impaired in specific psycholinguistics aspects, such as reference production. The choice of an adequate referential expression (whether a full noun phrase, a null or overt pronoun, etc.) involves the use of memory mechanisms to represent the characters and actions involved, but also the ability to judge the attention and the knowledge of the hearer.The present work focuses on KS speakers’ ability to report a story based on a Sylvester and Tweety cartoon (Arnold et al., 2009). We examine the ability to choose an appropriate referent (overt pronouns vs. null pronoun vs. full noun phrase) made during a narrative by Italian adolescents and young adults with KS (n = 8) and age-matched typically developing controls. In addition, we administered to each participant a full battery of cognitive and linguistic tests.Overall our results indicate that the correct use of referential expressions did not appear to be significantly predicted by the cognitive level of the speakers. Therefore the ability to choose an appropriate referential expression is preserved in KS whereas receptive vocabulary and comprehension skills are significantly lower as compared to controls

Dissection of partial 21q monosomy in different phenotypes: Clinical and molecular characterization of five cases and review of the literature

BACKGROUND: Partial deletion of chromosome 21q is a very rare chromosomal abnormality associated with highly variable phenotypes, such as facial dysmorphic features, heart defects, seizures, psychomotor delay, and severe to mild intellectual disability, depending on the location and size of deletions. So far, three broad deletion regions of 21q have been correlated with the clinical phenotype. RESULTS: We described the clinical and genetic features of three family members (father and two siblings) and other two unrelated patients with very wide range in age of diagnosis. All of them showed intellectual disability with very variable symptoms, from mild to severe, and carried 21q interstitial deletions with different sizes and position, as detected by conventional karyotype and array-CGH. CONCLUSIONS: Our study provided additional cases of partial 21q deletions, allowing to better delineate the genotype-phenotype correlations. In contrast to previous observations, we showed that deletions of the 21q proximal region are not necessarily associated with severe phenotypes and, therefore, that mild phenotypes are not exclusively related to distal deletions. To the best of our knowledge, this is the first report showing 21q deletions in adult patients associated with mild phenotypes, mainly consisting of neurobehavioral abnormalities, such as obsessive-compulsive disorders, poor social interactions and vulnerability to psychosis

Significance of PD-L1 in Metastatic Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors

Importance Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial. Objectives To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs. Data Sources PubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023. Study Selection Two authors independently screened the studies. Included studies were randomized and nonrandomized clinical trials enrolling patients with mUC receiving ICIs with available overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) data, separated between patients with PD-L1-positive and -negative tumors. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Two reviewers independently extracted data. Fixed- or random-effects models were used depending on the heterogeneity among the studies. Main Outcomes and Measures Primary outcomes were odds ratios (ORs) for ORR and hazard ratios (HRs) for OS, comparing patients with PD-L1-positive tumors and patients with PD-L1-negative tumors. Secondary outcomes were the PFS HR between patients with PD-L1-positive and -negative tumors and OS HR between ICI arms and non-ICI arms of only randomized clinical trials. Results A total of 14 studies were selected, comprising 5271 patients treated with ICIs (2625 patients had PD-L1-positive tumors). The ORR was 13.8% to 78.6% in patients with PD-L1-positive tumors and 5.1% to 63.2% in patients with PD-L1-negative tumors, with an association between PD-L1 status and ORR favoring patients with PD-L1-positive tumors (OR, 1.94; 95% CI, 1.47-2.56; P < .001). Median OS ranged from 8.4 to 24.1 months in patients with PD-L1-positive tumors and from 6.0 to 19.1 months in patients with PD-L1-negative tumors. The pooled HR showed a significant reduction for patients with PD-L1-positive tumors compared with those with PD-L1-negative tumors in the risk of death (HR, 0.71; 95% CI, 0.57-0.89; P = .003) and risk of progression (HR, 0.55; 95% CI, 0.44-0.69; P < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response. Conclusions and Relevance This systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents