Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.

Epigenetic aging clocks have been widely used to validate rejuvenation effects during cellular reprogramming. However, these predictions are unverifiable because the true biological age of reprogrammed cells remains unknown. We present an analytical framework to consider rejuvenation predictions from the uncertainty perspective. Our analysis reveals that the DNA methylation profiles across reprogramming are poorly represented in the aging data used to train clock models, thus introducing high epistemic uncertainty in age estimations. Moreover, predictions of different published clocks are inconsistent, with some even suggesting zero or negative rejuvenation. While not questioning the possibility of age reversal, we show that the high clock uncertainty challenges the reliability of rejuvenation effects observed during in vitro reprogramming before pluripotency and throughout embryogenesis. Conversely, our method reveals a significant age increase after in vivo reprogramming. We recommend including uncertainty estimation in future aging clock models to avoid the risk of misinterpreting the results of biological age prediction.

Influence of Mechanical Loading on the Process of Tribochemical Action on Physicochemical and Biopharmaceutical Properties of Substances, Using Lacosamide as an Example: From Micronisation to Mechanical Activation.

Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal structure. The aim of this work is to study in situ dynamic, dispersion, chemical, biological and surface properties of lacosamide powder after a complete cycle of mechanical loading by laser scattering, electron microscopy, FR-IR and biopharmaceutical approaches. The SLS method demonstrated the spontaneous tendency toward surface-energy reduction due to aggregation during micronisation. DLS analysis showed conformational changes of colloidal particles as supramolecular complexes depending on the loading time on the solid. SEM analysis demonstrated the conglomeration of needle-like lacosamide particles after 60 min of milling time and the transition to a glassy state with isotropy of properties by the end of the tribochemistry cycle. The following dynamic properties of lacosamide were established: elastic and plastic deformation boundaries, region of inhomogeneous deformation and fracture point. The ratio of dissolution-rate constants in water of samples before and after a full cycle of loading was 2.4. The lacosamide sample, which underwent a full cycle of mechanical loading, showed improved kinetics of API release via analysis of dissolution profiles in 0.1 M HCl medium. The observed activation-energy values of the cell-death biosensor process in aqueous solutions of the lacosamide samples before and after the complete tribochemical cycle were 207 kJmol-1 and 145 kJmol-1, respectively. The equilibrium time of dissolution and activation of cell-biosensor death corresponding to 20 min of mechanical loading on a solid was determined. The current study may have important practical significance for the transformation and management of the properties of drug substances in solid form and in solutions and for increasing the strength of drug matrices by pre-strain hardening via structural rearrangements during mechanical loading.

Neuronal travelling waves explain rotational dynamics in experimental datasets and modelling.

Spatiotemporal properties of neuronal population activity in cortical motor areas have been subjects of experimental and theoretical investigations, generating numerous interpretations regarding mechanisms for preparing and executing limb movements. Two competing models, representational and dynamical, strive to explain the relationship between movement parameters and neuronal activity. A dynamical model uses the jPCA method that holistically characterizes oscillatory activity in neuron populations by maximizing the data rotational dynamics. Different rotational dynamics interpretations revealed by the jPCA approach have been proposed. Yet, the nature of such dynamics remains poorly understood. We comprehensively analyzed several neuronal-population datasets and found rotational dynamics consistently accounted for by a traveling wave pattern. For quantifying rotation strength, we developed a complex-valued measure, the gyration number. Additionally, we identified parameters influencing rotation extent in the data. Our findings suggest that rotational dynamics and traveling waves are typically the same phenomena, so reevaluation of the previous interpretations where they were considered separate entities is needed.

Verb-Mediated Prediction in Bilingual Toddlers.

Prediction is an important mechanism for efficient language processing. It has been shown that as a part of sentence processing, both children and adults predict nouns based on semantically constraining verbs. Language proficiency is said to modulate prediction: the higher proficiency, the better the predictive skill. Children growing up acquiring two languages are often more proficient in one of them, and as such, investigation of the predictive ability in young bilingual children can shed light on the role of language proficiency. Furthermore, according to production-based models, the language production system drives the predictive ability. The present study investigates whether bilingual toddlers predict upcoming nouns based on verb meanings in both their languages, and whether this ability is associated with expressive vocabulary. Seventeen Norwegian-English bilingual toddlers (aged 2;5-3;3), dominant in Norwegian, participated in the study. Verb-mediated predictive ability was measured via a visual world paradigm (VWP) experiment, including sentences with semantically constraining and neutral verbs. Expressive vocabulary was measured by MacArthur-Bates CDI II. The results suggested that the toddler group predicted upcoming noun arguments in both their dominant and non-dominant languages, but were faster in their dominant language. This finding highlights the importance of language dominance for predictive processing. There was no significant relationship between predictive ability and expressive vocabulary in either language.

What Influences Language Impairment in Bilingual Aphasia? A Meta-Analytic Review.

Patterns of language impairment in multilingual speakers with post-stroke aphasia are diverse: in some cases the language deficits are parallel, that is, all languages are impaired relatively equally, whereas in other cases deficits are differential, that is, one language is more impaired than the other(s). This diversity stems from the intricate structure of the multilingual language system, which is shaped by a complex interplay of influencing factors, such as age of language acquisition, frequency of language use, premorbid proficiency, and linguistic similarity between one's languages. Previous theoretical reviews and empirical studies shed some light on these factors, however no clear answers have been provided. The goals of this review were to provide a timely update on the increasing number of reported cases in the last decade and to offer a systematic analysis of the potentially influencing variables. One hundred and thirty cases from 65 studies were included in the present systematic review and effect sizes from 119 cases were used in the meta-analysis. Our analysis revealed better performance in L1 compared to L2 in the whole sample of bilingual speakers with post-stroke aphasia. However, the magnitude of this difference was influenced by whether L2 was learned early in childhood or later: those who learned L2 before 7 years of age showed comparable performance in both of their languages contrary to the bilinguals who learned L2 after 7 years of age and showed better performance in L1 compared to L2. These robust findings were moderated mildly by premorbid proficiency and frequency of use. Finally, linguistic similarity did not appear to influence the magnitude of the difference in performance between L1 and L2. Our findings from the early bilingual subgroup were in line with the previous reviews which included mostly balanced early bilinguals performing comparably in both languages. Our findings from the late bilingual subgroup stressed the primacy of L1 and the importance of age of L2 learning. In addition, the evidence from the present review provides support for theories emphasizing the role of premorbid proficiency and language use in language impairment patterns in bilingual aphasia.

The Russian version of the Oxford Cognitive Screen: Validation study on stroke survivors.

OBJECTIVE: The Oxford Cognitive Screen (OCS) is a screening tool for the assessment of poststroke deficits in attention, memory, praxis, language, and number processing. The goal of the present study was to develop a Russian version of the OCS (Rus-OCS) via translation of the original battery, its cultural and linguistic adaptations, and reporting preliminary findings on its psychometric properties. METHOD: All parts of OCS were translated by native Russian-speaking neuropsychologists. Russian-speaking stroke patients (N = 205) were assessed with the Rus-OCS. Their performance was compared with performance of 60 healthy Russian-speaking adults aged between the ages of 18 and 91 years. The performance of 15 stroke patients and 42 healthy adults were assessed with a parallel version within 7 days of first testing. Convergent validity of the Rus-OCS was established via correlations with comparable tasks. Performance of three stroke groups with different lesion lateralization (right, left, and bilateral) was compared on language and visual attention subtasks. Preliminary normative data based on 5th to 95th percentile were also reported. RESULTS: Measures of internal consistency and test-retest reliability ranged from acceptable to very good and estimates of convergent validity ranged from moderate to high. Sensitivity and specificity was found to range from .56 to 1 and from .73 to 1, respectively. Significant differences in performance between stroke and healthy groups on all subtasks confirmed the discriminative power of the Rus-OCS was good. CONCLUSIONS: Rus-OCS is a promising cognitive screening instrument for Russian-speaking patients. However, further validation is needed. Constraints of socioeconomic differences between Russian speakers in the wider population should be considered. (PsycINFO Database Record (c) 2019 APA, all rights reserved).