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Stiller, C.

Publications and source records attributed to Stiller, C..

2 recordsLinked to original sources

CORSICA: Reproducible Suppression of Cochlear Implant Artifacts in EEG evoked by Continuous Speech

ObjectiveElectroencephalography (EEG) is a key tool for studying auditory processing in cochlear implant (CI) users. In particular, EEG recordings obtained during continuous speech are becoming increasingly important for assessing speech and language processing in CI users, and may be utilized for neurofeedback. However, CIs also induce strong stimulation artifacts that are time-locked to the stimulus and mask the neural responses that have smaller magnitudes. Existing artifact reduction methods are typically based on event-related potentials (ERPs) or require manual component selection, making them unsuitable for naturalistic listening conditions or large datasets. ApproachWe develop CORSICA (CORrelation-baSed ICA artifact rejection), a reproducible, parameter-efficient method for CI artifact reduction in EEG responses to continuous speech. CORSICA operates on independent components (ICs) obtained through Infomax ICA and requires no manual component labelling, with performance governed by a single tunable threshold. It exploits the observation that CI artifacts temporally follow the audio signal without delay, whereas neural responses have an inherent lag due to auditory pathway latencies. For each IC, CORSICA computes the cross-correlation with the speech stimulus. Artifacts are identified by a high signal-to-noise ratio (SNR) of the correlation peak near zero lag, and the component is rejected if this SNR exceeds a threshold. To benchmark CORSICA, we evaluate two alternatives: a TRF-based SNR method, in which temporal response functions are fitted to each IC and artifact-driven peaks near zero lag are used for rejection, and a variant replacing ICA with second-order blind identification (SOBI) as the source separation step. Main resultsCORSICA effectively suppressed CI artifacts while preserving neural activity, enabling recovery of physiologically plausible TRFs with only 2% of ICs rejected. Both benchmark methods confirmed the validity of the SNR-based rejection framework, but CORSICA outperformed the TRF-based alternative in artifact suppression quality. Replacing ICA with SOBI as the source separation step required more ICs to be rejected, further supporting ICA as the preferred backbone for CORSICA. SignificanceCORSICA provides a fully objective, label-free approach to identifying CI artifacts in speech-evoked EEG data, with no manual intervention required. By centering artifact rejection on a single interpretable threshold, it offers a reproducible preprocessing standard for future EEG studies on speech processing in CI users. ConclusionOur findings demonstrate that objective CI artifact suppression in speech-evoked EEG data is feasible on the basis of the ICs temporal response patterns.

neuroscience↗

Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

Molnupiravir is an orally available antiviral drug candidate that is in phase III trials for the treatment of COVID-19 patients1,2. Molnupiravir increases the frequency of viral RNA mutations3,4 and impairs SARS-CoV-2 replication in animal models4-6 and in patients2. Here we establish the molecular mechanisms that underlie molnupiravir-induced RNA mutagenesis by the RNA-dependent RNA polymerase (RdRp) of the coronavirus SARS-CoV-2. Biochemical assays show that the RdRp readily uses the active form of molnupiravir, {beta}-D-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of CTP or UTP. Incorporation of NHC monophosphate into nascent RNA does not impair further RdRp progression. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp-RNA complexes containing mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism likely applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.

biochemistry↗