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Giroud, N.

Publications and source records attributed to Giroud, N..

6 recordsLinked to original sources

Comparison of Fixed Single Cell RNA-seq Methods to Enable Transcriptome Profiling of Neutrophils in Clinical Samples

Monitoring neutrophil gene expression is a powerful tool for understanding disease mechanisms, developing new diagnostics, therapies and optimizing clinical trials. Neutrophils are sensitive to the processing, storage and transportation steps that are involved in clinical sample analysis. This study is the first to evaluate the capabilities of technologies from 10X Genomics, PARSE Biosciences, and HIVE (Honeycomb Biotechnologies) to generate high-quality RNA data from human blood-derived neutrophils. Our comparative analysis shows that all methods produced high quality data, importantly capturing the transcriptomes of neutrophils. 10X FLEX cell populations in particular showed a close concordance with the flow cytometry data. Here, we establish a reliable single-cell RNA sequencing workflow for neutrophils in clinical trials: we offer guidelines on sample collection to preserve RNA quality and demonstrate how each method performs in capturing sensitive cell populations in clinical practice.

genomics↗

Hearing and cognitive decline in aging differentially impact neural tracking of context-supported versus random speech across linguistic timescales

Cognitive decline and hearing loss are common in older adults and often co-occur while investigated separately, affecting the neural processing of speech. This study investigated the interaction between cognitive decline, hearing loss, and contextual cues in speech processing. Participants aged 60 years and older were assessed for cognitive decline using the Montreal Cognitive Assessment and for hearing ability using a four-frequency pure tone average. They listened to in-house-designed matrix-style sentences that either provided supportive context or were random, while we recorded their electroencephalography. Neurophysiological responses were analyzed through auditory evoked potentials and speech tracking at different linguistic timescales (i.e., phrase, word, syllable and phoneme rate) using phase-locking values. The results showed that cognitive decline was associated with a lower chance of correct responses in a speech recognition task. Cognitive decline significantly impacted the P2 component of auditory evoked potentials, while hearing loss influenced speech tracking at the word and phoneme rates, but not at the phrase or syllable rates. Contextual cues enhanced speech tracking at the syllable rate. These findings suggest that cognitive decline and hearing loss differentially affect the neural mechanisms underlying speech processing, with contextual cues playing a significant role in enhancing syllable rate tracking. This study emphasises the importance of considering both cognitive and auditory factors when studying speech processing in older people and highlights the need for further research to investigate the interplay between cognitive decline, hearing loss and contextual cues in speech processing.

neuroscience↗

Charting the Heterogeneity of Colorectal Cancer Consensus Molecular Subtypes using Spatial Transcriptomics

The heterogeneity of colorectal cancer (CRC) contributes to substantial differences in patient response to standard therapies. The consensus molecular subtypes (CMS) of CRC is the most widely-used gene expression-based classification and has contributed to a better understanding of disease heterogeneity and prognosis. Nevertheless, CMS intratumoral heterogeneity restricts its clinical application, stressing the necessity of further characterizing the composition and architecture of CRC. Here, we used Spatial Transcriptomics (ST) in combination with single-cell RNA sequencing (scRNA-seq) to decipher the spatially resolved cellular and molecular composition of CRC. In addition to mapping the intratumoral heterogeneity of CMS and their microenvironment, we identified cell communication events in the tumor-stroma interface of CMS2 carcinomas. This includes tumor growth-inhibiting as well as -activating signatures, such as the potential regulation of the ETV4 transcriptional activity by DCN or the PLAU-PLAUR ligand-receptor interaction. Our data show the power of ST to bring the CMS-based classification of CRC to another level and thereby gain useful molecular insights for personalized therapy.

cancer biology↗

Selective Attention Modulates Neural Envelope Tracking of Informationally Masked Speech in Healthy Older Adults

Speech understanding in noisy situations is compromised in old age. This study investigated the energetic and informational masking components of multi-talker babble noise and their influence on neural tracking of the speech envelope in a sample of healthy older adults. Twenty-three older adults (age range 65 - 80 years) listened to an audiobook embedded in noise while their electroencephalogram (EEG) was recorded. Energetic masking was manipulated by varying the signal-to-noise ratio (SNR) between target speech and background talkers and informational masking was manipulated by varying the number of background talkers. Neural envelope tracking was measured by calculating temporal response functions (TRFs) between speech envelope and EEG. Number of background talkers, but not SNR modulated the amplitude of an earlier (around 50 ms time lag) and a later (around 300 ms time lag) peak in the TRFs. Selective attention, but not working memory or peripheral hearing additionally modulated the amplitude of the later TRF peak. Finally, amplitude of the later TRF peak was positively related to accuracy in the comprehension task. The results suggest that stronger envelope tracking is beneficial for speech-in-noise understanding and that selective attention is an important ability supporting speech-in-noise understanding in multi-talker scenes.

neuroscience↗

EEG Resting-State and Event-Related Potentials as Markers of Learning Success in Older Adults Following Second Language Training: A Pilot Study

In this pilot study, we evaluated the use of electrophysiological measures at rest as paradigm-independent predictors of L2 development for the first time in older adult learners. We then assessed EEG correlates of the learning outcome in a language-switching paradigm after the training, which to date has only been done in younger adults and at intermediate to advanced L2 proficiency. Ten (Swiss) German-speaking adults between 65-74 years of age participated in an intensive three-weeks English training for beginners. A resting-state EEG was recorded before the training to predict the ensuing L2 development (Experiment 1). A language-switching ERP experiment was conducted after the training to assess the learning outcome (Experiment 2). All participants improved their L2 skills but differed noticeably in their individual development. Experiment 1 showed that beta1 oscillations at rest (13-14.5Hz) predicted these individual differences. We interpret resting-state beta1 oscillations as correlates of attentional capacities and semantic working memory that facilitate the extraction and processing of novel forms and meanings from the L2 input. In Experiment 2, we found that language-switching from the L2 into the native language (L1) elicited an N400 component, which was reduced in the more advanced learners. Thus, for learners beginning the acquisition of an L2 in third age, language switching appears to become less effortful with increasing proficiency, suggesting that the lexicons of the L1 and L2 become more closely linked. In sum, our findings indicate that individual differences in L2 development and proficiency in older adults operate through similar electrophysiological mechanisms as those observed in younger adults.

neuroscience↗

Interacting effects of frontal lobe neuroanatomy and working memory capacity to older listeners' speech recognition in noise

Many older adults are struggling with understanding spoken language, particularly when background noise interferes with comprehension. In the present study, we investigated a potential interaction between two well-known factors associated with greater speech-in-noise (SiN) reception thresholds in older adults, namely a) lower working memory capacity and b) age-related structural decline of frontal lobe regions. In a sample of older adults (N=25) and younger controls (N=13) with normal pure-tone thresholds, SiN reception thresholds and working memory capacity were assessed. Furthermore, T1-weighted structural MR-images were recorded to analyze neuroanatomical traits (i.e., cortical thickness (CT) and cortical surface area (CSA)) of the cortex. As expected, the older group showed greater SiN reception thresholds compared to the younger group. We also found consistent age-related atrophy (i.e., lower CT) in brain regions associated with SiN recognition namely the superior temporal lobe bilaterally, the right inferior frontal and precentral gyrus, as well as the left superior frontal gyrus. Those older participants with greater atrophy in these brain regions also showed greater SiN reception thresholds. Interestingly, the association between CT in the left superior frontal gyrus and SiN reception thresholds was moderated by individual working memory capacity. Older adults with greater working memory capacity benefitted more strongly from thicker frontal lobe regions when it comes to improve SiN recognition. Overall, our results fit well into the literature showing that age-related structural decline in auditory- and cognition-related brain areas is associated with greater SiN reception thresholds in older adults. However, we highlight that this association changes as a function of individual working memory capacity. We therefore believe that future interventions to improve SiN recognition in older adults should take into account the role of the frontal lobe as well as individual working memory capacity. HighlightsO_LISpeech-in-noise (SiN) reception thresholds are significantly increased with higher age, independently of pure-tone hearing loss C_LIO_LIGreater SiN reception thresholds are associated with cortical thinning in several auditory-, linguistic-, and cognitive-related brain areas, irrespective of pure-tone hearing loss C_LIO_LIGreater cortical thinning in the left superior frontal lobe is detrimental for SiN recognition in older, but not younger adults C_LIO_LIOlder adults with greater working memory capacity benefit more strongly from structural integrity of left superior frontal lobe for SiN recognition C_LI

neuroscience↗