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BackgroundSubjective reports can reveal relevant information regarding the nature of the impairment of brain tumor patients, unveiling potential gaps in current assessment practices. The co-occurrence of language and memory impairments has been previously reported, albeit scarcely. The aim of this study is therefore to understand the co-occurrence of subjective language and memory complaints in the preoperative state of brain tumor patients and its impact on Quality of Life (QoL).Methods31 brain tumor patients (12 LGG, 19 HGG) underwent a semi-structured interview to assess subjective complaints of language deficits, co-occurrences between language and memory dysfunction, and changes in QoL. Group and subgroup analyses were conducted to provide general and tumor grade specific data.Results48.4% of patients mentioned co-occurrence of language and memory impairments in reading, writing, and conversation. The HGG group reported co-occurrences in all three of these (reading: 31.6%; writing: 21.1%; conversation: 26.3%), while the LGG only described co-occurrences in reading (25%) and conversation (8.3%), although these were not statistically significant. All patients with co-occurring language and memory deficits reported these to be linked to reduced QoL (48.4%). In patients with an HGG, this number was slightly higher (52.6%) than in patients with an LGG (41.7%).ConclusionLanguage impairments co-occur with memory dysfunction as perceived in patients’ daily life. Patients see these impairments as affecting their quality of life. Further attention to dedicated language and memory tasks seems necessary.

Abstract Background The immune system has a central role in preventing carcinogenesis. Alteration of systemic immune cell levels may increase cancer risk. However, the extent to which common genetic variation influences blood traits and cancer risk remains largely undetermined. Here, we identify pleiotropic variants and predict their underlying molecular and cellular alterations. Methods Multivariate Cox regression was used to evaluate associations between blood traits and cancer diagnosis in cases in the UK Biobank. Shared genetic variants were identified from the summary statistics of the genome-wide association studies of 27 blood traits and 27 cancer types and subtypes, applying the conditional/conjunctional false-discovery rate approach. Analysis of genomic positions, expression quantitative trait loci, enhancers, regulatory marks, functionally defined gene sets, and bulk- and single-cell expression profiles predicted the biological impact of pleiotropic variants. Plasma small RNAs were sequenced to assess association with cancer diagnosis. Results The study identified 4093 common genetic variants, involving 1248 gene loci, that contributed to blood–cancer pleiotropism. Genomic hotspots of pleiotropism include chromosomal regions 5p15-TERT and 6p21-HLA. Genes whose products are involved in regulating telomere length are found to be enriched in pleiotropic variants. Pleiotropic gene candidates are frequently linked to transcriptional programs that regulate hematopoiesis and define progenitor cell states of immune system development. Perturbation of the myeloid lineage is indicated by pleiotropic associations with defined master regulators and cell alterations. Eosinophil count is inversely associated with cancer risk. A high frequency of pleiotropic associations is also centered on the regulation of small noncoding Y-RNAs. Predicted pleiotropic Y-RNAs show specific regulatory marks and are overabundant in the normal tissue and blood of cancer patients. Analysis of plasma small RNAs in women who developed breast cancer indicates there is an overabundance of Y-RNA preceding neoplasm diagnosis. Conclusions This study reveals extensive pleiotropism between blood traits and cancer risk. Pleiotropism is linked to factors and processes involved in hematopoietic development and immune system function, including components of the major histocompatibility complexes, and regulators of telomere length and myeloid lineage. Deregulation of Y-RNAs is also associated with pleiotropism. Overexpression of these elements might indicate increased cancer risk.

Purpose: In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties). Method: Seven hundred thirty-one Dutch-speaking individuals without dementia from the Second Manifestations of ARTerial disease-Magnetic Resonance study responded to an animal fluency task (120 s). We obtained cluster size and number of switches for the task, and eight different word properties for each correct word produced. We detected variables that determine total word count with random forests, and used conditional inference trees to assess points along the scales of such variables, at which total word count changes significantly. Results: Number of switches, average cluster size, lexical decision response times, word frequency, and concreteness determined total correct word count in animal fluency. People who produced more correct words produced more switches and bigger clusters. People who produced fewer words produced fewer switches and more frequent words. Conclusions: Concurrent with existing literature, individuals without dementia rely on language and executive functioning to produce words in animal fluency. The novelty of our work is that such results were shown based on a data-driven approach using sequence information and item-level metrics.

Abstract Background Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch‐like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS‐associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. Methods Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). Results and Discussion More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.

Abstract Atxurra cave has a decorated assemblage composed of more than a hundred engraved animal depictions. All of them are located in deep parts of the cave and most of them are hidden in raised areas, away from the main path. The main sector is the “Ledge of the Horses”, located at 330 m from the entrance of the cave. It is a space of 12 m long and 1.5 m wide, elevated 4 m above the cave floor. This area includes almost fifty engraved and painted animals accompanied by a dozen flint tools, three fireplaces, and around one hundred charcoal fragments from torches. This extraordinary archaeological record allows us to value the complexity of the artistic production inside the caves during the Upper Palaeolithic. Our study has confirmed that there is planning prior to artistic production, both in terms of the iconographic aspects (themes, techniques, formats), its location (visibility, capacity), and the lighting systems. Furthermore, the data indicates the panel was decorated to be seen by third parties from different positions and was expressly illuminated for this purpose. This evidence supports the role of rock art as a visual communication system in Upper Palaeolithic societies.

Objective: Patients with left perisylvian gliomas might undergo language mapping with nTMS in preparation for awake brain surgery. Action naming is an important addition to the presurgical language mapping protocol. However, it has not yet been determined whether specific action stimuli can influence mapping outcomes in terms of number and/or localisation of induced errors. Methods: We investigated this question by employing tractography-based nTMS language mapping of the left arcuate fasciculus (AF) with two types of verbs: transitive and intransitive. Data were collected from 22 patients with a left perisylvian glioma. Results: Our results demonstrated that nTMS induced a higher error rate with transitive rather than intransitive verbs, specifically during stimulation of the posterior temporal terminations of the left AF (transitive error rate: 8.3%; intransitive error rate: 4.8%). The effect was absent when gliomas displaced the temporal terminations of the AF. Also, nTMS triggered a higher number of semantic errors with transitive (vs intransitive) actions during stimulation of the posterior temporal terminations of the AF (semantic error rate – transitives: 3.3%; semantic error rate – intransitives: 0%). Conclusion: Our work highlights that clinical outcomes of language mapping with nTMS are affected by the choice of linguistic stimuli. Transitive verbs may be suited to achieve optimal nTMS mapping outcomes in posterior temporal areas of the left AF in this population. Displacement of white matter terminations due to the tumor can affect these results, and semantic errors may indicate core language processes that can be mapped when administering transitive verbs.

Background: Subjective reports can reveal relevant information regarding the nature of the impairment of brain tumor patients, unveiling potential gaps in current assessment practices. The co-occurrence of language and memory impairments has been previously reported, albeit scarcely. The aim of this study is therefore to understand the co-occurrence of subjective language and memory complaints in the preoperative state of brain tumor patients and its impact on Quality of Life (QoL). Methods: 31 brain tumor patients (12 LGG, 19 HGG) underwent a semi-structured interview to assess subjective complaints of language deficits, co-occurrences between language and memory dysfunction, and changes in QoL. Group and subgroup analyses were conducted to provide general and tumor grade specific data. Results: 48.4% of patients mentioned co-occurrence of language and memory impairments in reading, writing, and conversation. The HGG group reported co-occurrences in all three of these (reading: 31.6%; writing: 21.1%; conversation: 26.3%), while the LGG only described co-occurrences in reading (25%) and conversation (8.3%), although these were not statistically significant. All patients with co-occurring language and memory deficits reported these to be linked to reduced QoL (48.4%). In patients with an HGG, this number was slightly higher (52.6%) than in patients with an LGG (41.7%). Conclusion: Language impairments co-occur with memory dysfunction as perceived in patients' daily life. Patients see these impairments as affecting their quality of life. Further attention to dedicated language and memory tasks seems necessary. [ABSTRACT FROM AUTHOR]

Abstract Case–control studies have shown an association of BARD1 with hereditary breast and/or ovarian cancer (HBOC) predisposition. BARD1 alternatively spliced isoforms are abundant and some are highly expressed in different cancer types. In addition, a number of BARD1 germline pathogenic variants have been reported among HBOC patients. In previous reports, BARD1 c.1977A>G variant has been classified as pathogenic since it produces a frameshift transcript lacking exons 2 to 9. In the present study, we sought to validate the mRNA splicing results previously published and to contribute with new evidence to refine the classification of this substitution according to ACMG/AMP guidelines. The presence of the variant was screened in patients and controls. RT-PCR was performed in order to compare the transcriptional profiles of two variant carriers and ten non-carrier controls. In addition, allele-specific expression was assessed. No differences in variant frequency were detected between patients and controls. The RNA assay confirmed the presence of the shorter transcript lacking exons 2–9, but it was detected both in carriers and non-carriers. Furthermore, allelic imbalance was discarded and no significant differences in the proportion of full-length and shorter transcript were detected between carriers and controls. The shorter transcript detected corresponds to BARD1 isoform η, constituted by exons 1, 10 and 11. Our results support that this transcript is a constitutive splicing product rather than an aberrant transcript caused by BARD1 c.1977A>G variant, and for this reason this variant should be considered as likely benign following ACMG/AMP guidelines.

Abstract Healthy ageing leads to changes in the brain that impact upon sensory and cognitive processing. It is not fully clear how these changes affect the processing of everyday spoken language. Prediction is thought to play an important role in language comprehension, where information about upcoming words is pre-activated across multiple representational levels. However, evidence from electrophysiology suggests differences in how older and younger adults use context-based predictions, particularly at the level of semantic representation. We investigate these differences during natural speech comprehension by presenting older and younger subjects with continuous, narrative speech while recording their electroencephalogram. We use time-lagged linear regression to test how distinct computational measures of (1) semantic dissimilarity and (2) lexical surprisal are processed in the brains of both groups. Our results reveal dissociable neural correlates of these two measures that suggest differences in how younger and older adults successfully comprehend speech. Specifically, our results suggest that, while younger and older subjects both employ context-based lexical predictions, older subjects are significantly less likely to pre-activate the semantic features relating to upcoming words. Furthermore, across our group of older adults, we show that the weaker the neural signature of this semantic pre-activation mechanism, the lower a subject’s semantic verbal fluency score. We interpret these findings as prediction playing a generally reduced role at a semantic level in the brains of older listeners during speech comprehension and that these changes may be part of an overall strategy to successfully comprehend speech with reduced cognitive resources.

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Los estudios focalizados en la Prehistoria Reciente peninsular han sido escasos en el cauce bajo del valle del Ebro (Tarragona). La investigación en esta área se caracteriza sobre todo por el estudio de los materiales recuperados en intervenciones arqueológicas de urgencia o bien en su inventario. Esto deriva en la emergencia de una problemática definida por una continua ausencia de interpretaciones válidas respecto a las dinámicas ocupacionales del territorio. Para poder analizar las dinámicas ocupacionales y cronoculturales, en este trabajo se presenta el análisis y estudio de varios conjuntos líticos procedentes de prospecciones no sistemáticas de cuatro áreas −Vall del Llop, La Conca, Vall de Mantons y Vall de Carrinya− desde una perspectiva morfo-tecno-tipológica. Se pretende poder establecer estimaciones cronológicas de los conjuntos y combinarlas con la observación off-site. Para ello el enfoque se basa en la aplicación de técnicas de modelización bayesiana que puedan aproximarnos al contexto espaciotemporal de los artefactos analizados.

Since the founding work of Efremov in 1940 [...]

Introduction: Fluency tasks require language (i.e., semantics, phonological output lexicon, and phonological assembly) and executive functions (i.e., inhibition; mental set shifting; updating, and monitoring). Little is known about whether people with human immunodeficiency virus (HIV) are more impaired on a specific type of fluency task and what aspects of language and executive functions drive such performance.Aims: To understand (1) whether people with HIV are more impaired in animal, letter, or unconstrained fluency relative to a normative sample; (2) whether there exist differences between tasks relative to the total number of words; and (3) which aspects of executive function and language are involved in their performance.Methods: Data from animal, letter, and unconstrained fluency of 50 Spanish-speaking people with HIV were analyzed. The number of switches and mean cluster size for each task and 10 word properties (e.g., frequency, age of acquisition, length in graphemes) for each of the correct words were measured. A chi-square test was used to address Aim 1, linear mixed effects models for Aim 2, and random forests and conditional inference trees for Aim 3. The results were cross-validated with a normative sample.Results: People with HIV were not more impaired in animal, letter, or unconstrained fluency relative to a normative sample. People with HIV produced fewer words in letter fluency compared to animal and unconstrained fluency. In addition, they produced fewer words in animal fluency compared to unconstrained fluency. Number of switches emerged as the most important variable to predict the total number of correct words when considering the three tasks together and for each task separately. Word frequency was relevant to predict animal fluency, age of acquisition to predict letter fluency, and cluster size to predict unconstrained fluency. These results were cross-validated with the exception cluster size.Conclusion: People with HIV rely on language (phonological output lexicon, not necessarily semantics) and executive functioning (updating and monitoring) to produce words in fluency tasks. These results concur with the current literature. Future work may correlate fluency scores with other tests measuring language and executive functions or study other types of fluency tasks (e.g., action, cities, supermarket, and professions).

Navigated Transcranial Magnetic Stimulation (nTMS) is used to understand the cortical organization of language in preparation for the surgical removal of a brain tumor. Action naming with finite verbs can be employed for that purpose, providing additional information to object naming. However, little research has focused on the properties of the verbs that are used in action naming tasks, such as their status as transitive (taking an object; e.g., to read) or intransitive (not taking an object; e.g., to wink). Previous neuroimaging data show higher activation for transitive compared to intransitive verbs in posterior perisylvian regions bilaterally. In the present study, we employed nTMS and production of finite verbs to investigate the cortical underpinnings of transitivity. Twenty neurologically healthy native speakers of German participated in the study. They underwent language mapping in both hemispheres with nTMS. The action naming task with finite verbs consisted of transitive (e.g., The man reads the book) and intransitive verbs (e.g., The woman winks) and was controlled for relevant psycholinguistic variables. Errors were classified in four different error categories (i.e., non-linguistic errors, grammatical errors, lexico-semantic errors and, errors at the sound level) and were analyzed quantitatively. We found more nTMS-positive points in the left hemisphere, particularly in the left parietal lobe for the production of transitive compared to intransitive verbs. These positive points most commonly corresponded to lexico-semantic errors. Our findings are in line with previous aphasia and neuroimaging studies, suggesting that a more widespread network is used for the production of verbs with a larger number of arguments (i.e., transitives). The higher number of lexico-semantic errors with transitive compared to intransitive verbs in the left parietal lobe supports previous claims for the role of left posterior areas in the retrieval of argument structure information.

This article from the Journal of Neuropsychology introduces a special issue focused on cognitive neurosurgery. The field of cognitive neurosurgery originated in the 1940s with the work of Brenda Milner and Wilder Penfield, who explored the role of the hippocampus in memory and the human motor cortex. Today, cognitive neurosurgery involves collaboration between neurosurgeons, neuropsychologists, and cognitive science experts to study the brain and cognition. The special issue discusses topics such as postoperative impairments, individualized assessments, and neuropsychological functions beyond language or memory. The articles highlight the importance of standardized testing materials and the use of tasks during surgery to spare damage to cognitive processes. The authors emphasize the need for comprehensive neuropsychological assessments and further research on peri- and intraoperative testing protocols. [Extracted from the article]

Cognitive performance influences the quality of life and survival of people with glioma. Thus, a detailed neuropsychological and language evaluation is essential. In this work, we tested if an analysis of errors in naming can indicate semantic and/or phonological impairments in 87 awake brain surgery patients. Secondly, we explored how language and cognition change after brain tumour resection. Finally, we checked if low‐tumour grade had a protective effect on cognition. Our results indicated that naming errors can be useful to monitor semantic and phonological processing, as their number correlated with scores on tasks developed by our team for testing these domains. Secondly, we showed that – although an analysis at a whole group level indicates a decline in language functions – significantly more individual patients improve or remain stable when compared to the ones who declined. Finally, we observed that having LGG, when compared with HGG, favours patients' outcome after surgery, most probably due to brain plasticity mechanisms. We provide new evidence of the importance of applying a broader neuropsychological assessment and an analysis of naming errors in patients with glioma. Our approach may potentially ensure better detection of cognitive deficits and contribute to better postoperative outcomes. Our study also shows that an individualized approach in post‐surgical follow‐ups can reveal reassuring results showing that significantly more patients remain stable or improve and can be a promising avenue for similar reports. Finally, the study captures that plasticity mechanisms may act as protective in LGG versus HGG after surgery. [ABSTRACT FROM AUTHOR]