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Abstract Background Tracking gait and balance impairment in time is paramount in the care of older neurological patients. The Minimal Detectable Change (MDC), built upon the Standard Error of the Measurement (SEM), is the smallest modification of a measure exceeding the measurement error. Here, a novel method based on linear mixed-effects models (LMMs) is applied to estimate the standard error of the measurement from data collected before and after rehabilitation and calculate the MDC of gait and balance measures. Methods One hundred nine older adults with a gait impairment due to neurological disease (66 stroke patients) completed two assessment sessions before and after inpatient rehabilitation. In each session, two trials of the 10-meter walking test and the Timed Up and Go (TUG) test, instrumented with inertial sensors, have been collected. The 95% MDC was calculated for the gait speed, TUG test duration (TTD) and other measures from the TUG test, including the angular velocity peak (ωpeak) in the TUG test’s turning phase. Random intercepts and slopes LMMs with sessions as fixed effects were used to estimate SEM. LMMs assumptions (residuals normality and homoscedasticity) were checked, and the predictor variable ln-transformed if needed. Results The MDC of gait speed was 0.13 m/s. The TTD MDC, ln-transformed and then expressed as a percentage of the baseline value to meet LMMs’ assumptions, was 15%, i.e. TTD should be

Abstract People are able to perceive emotions in the eyes of others and can therefore see emotions when individuals wear face masks. Research has been hampered by the lack of a good test to measure basic emotions in the eyes. In two studies respectively with 358 and 200 participants, we developed a test to see anger, disgust, fear, happiness, sadness and surprise in images of eyes. Each emotion is measured with 8 stimuli (4 male actors and 4 female actors), matched in terms of difficulty and item discrimination. Participants reliably differed in their performance on the Seeing Emotions in the Eyes test (SEE-48). The test correlated well not only with Reading the Mind in the Eyes Test (RMET) but also with the Situational Test of Emotion Understanding (STEU), indicating that the SEE-48 not only measures low-level perceptual skills but also broader skills of emotion perception and emotional intelligence. The test is freely available for research and clinical purposes.

Abstract Long-read sequencing allows analyses of single nucleic-acid molecules and produces sequences in the order of tens to hundreds kilobases. Its application to whole-genome analyses allows identification of complex genomic structural-variants (SVs) with unprecedented resolution. SV identification, however, requires complex computational methods, based on either read-depth or intra- and inter-alignment signatures approaches, which are limited by size or type of SVs. Moreover, most currently available tools only detect germline variants, thus requiring separate computation of sample pairs for comparative analyses. To overcome these limits, we developed a novel tool (Germline And SOmatic structuraL varIants detectioN and gEnotyping; GASOLINE) that groups SV signatures using a sophisticated clustering procedure based on a modified reciprocal overlap criterion, and is designed to identify germline SVs, from single samples, and somatic SVs from paired test and control samples. GASOLINE is a collection of Perl, R and Fortran codes, it analyzes aligned data in BAM format and produces VCF files with statistically significant somatic SVs. Germline or somatic analysis of 30 $$\times $$ × sequencing coverage experiments requires 4–5 h with 20 threads. GASOLINE outperformed currently available methods in the detection of both germline and somatic SVs in synthetic and real long-reads datasets. Notably, when applied on a pair of metastatic melanoma and matched-normal sample, GASOLINE identified five genuine somatic SVs that were missed using five different sequencing technologies and state-of-the art SV calling approaches. Thus, GASOLINE identifies germline and somatic SVs with unprecedented accuracy and resolution, outperforming currently available state-of-the-art WGS long-reads computational methods.

People are able to perceive emotions in the eyes of others and can therefore see emotions when individuals wear face masks. Research has been hampered by the lack of a good test to measure basic emotions in the eyes. In two studies respectively with 358 and 200 participants, we developed a test to see anger, disgust, fear, happiness, sadness and surprise in images of eyes. Each emotion is measured with 8 stimuli (4 male actors and 4 female actors), matched in terms of difficulty and item discrimination. Participants reliably differed in their performance on the Seeing Emotions in the Eyes test (SEE-48). The test correlated well not only with Reading the Mind in the Eyes Test (RMET) but also with the Situational Test of Emotion Understanding (STEU), indicating that the SEE-48 not only measures low-level perceptual skills but also broader skills of emotion perception and emotional intelligence. The test is freely available for research and clinical purposes.

ObjectiveThis study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression.MethodsAn international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability.ResultsThe panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed.ConclusionsThis research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.

IntroductionHomonymous visual field defects (HVFDs) following acquired brain lesions affect independent living by hampering several activities of everyday life. Available treatments are intensive and week- or month-long. Transcranial Direct current stimulation (tDCS), a plasticity-modulating non-invasive brain stimulation technique, could be combined with behavioral trainings to boost their efficacy or reduce treatment duration. Some promising attempts have been made pairing occipital tDCS with visual restitution training, however less is knows about which area/network should be best stimulated in association with compensatory approaches, aimed at improving exploratory abilities, such as multisensory trainings.MethodsIn a proof-of-principle, sham-controlled, single-blind study, 15 participants with chronic HVFDs underwent four one-shot sessions of active or sham anodal tDCS applied over the ipsilesional occipital cortex, the ipsilesional or contralesional posterior parietal cortex. tDCS was delivered during a compensatory multisensory (audiovisual) training. Before and immediately after each tDCS session, participants carried out a visual detection task, and two visual search tasks (EF and Triangles search tests). Accuracy (ACC) and response times (RTs) were analyzed with generalized mixed models. We investigated differences in baseline performance, clinical-demographic and lesion factors between tDCS responders and non-responders, based on post-tDCS behavioral improvements. Lastly, we conducted exploratory analyses to compare left and right brain-damaged participants.ResultsRTs improved after active ipsilesional occipital and parietal tDCS in the visual search tasks, while no changes in ACC were detected. Responders to ipsilesional occipital tDCS (Triangle task) had shorter disease duration and smaller lesions of the parietal cortex and the superior longitudinal fasciculus. On the other end, on the EF test, those participants with larger damage of the temporo-parietal cortex or the fronto-occipital white matter tracts showed a larger benefit from contralesional parietal tDCS. Overall, the visual search RTs improvements were larger in participants with right-sided hemispheric lesions.ConclusionThe present result shows the facilitatory effects of occipital and parietal tDCS combined with compensatory multisensory training on visual field exploration in HVFDs, suggesting a potential for the development of new neuromodulation treatments to improve visual scanning behavior in brain-injured patients.

Abstract In humans, motor resonance effects can be tracked by measuring the enhancement of corticospinal excitability by action observation. Uncovering factors driving motor resonance is crucial for optimizing action observation paradigms in experimental and clinical settings. In the present study, we deepen motor resonance properties for grasping movements. Thirty-five healthy subjects underwent an action observation task presenting right-hand grasping movements differing from their action goal. Single-pulse transcranial magnetic stimulation was applied over the left primary motor cortex at 100, 200, or 300 ms from the onset of the visual stimulus depicting the action. Motor-evoked potentials were recorded from four muscles of the right hand and forearm. Results show a muscle-specific motor resonance effect at 200 ms after movement but selectively for observing a socially relevant grasp towards another human being. This effect correlates with observers’ emotional empathy scores, and it was followed by inhibition of motor resonance at 300 ms post-stimulus onset. No motor resonance facilitation emerged while observing intransitive hand movement or object grasping. This evidence highlights the social side of motor resonance and its dependency on temporal factors.

Summary: The becoming of the human being is a multisensory process that starts in the womb. By integrating spontaneous neuronal activity with inputs from the external world, the developing brain learns to make sense of itself through multiple sensory experiences. Over the past ten years, advances in neuroimaging and electrophysiological techniques have allowed the exploration of the neural correlates of multisensory processing in the newborn and infant brain, thus adding an important piece of information to behavioral evidence of early sensitivity to multisensory events. Here, we review recent behavioral and neuroimaging findings to document the origins and early development of multisensory processing, particularly showing that the human brain appears naturally tuned to multisensory events at birth, which requires multisensory experience to fully mature. We conclude the review by highlighting the potential uses and benefits of multisensory interventions in promoting healthy development by discussing emerging studies in preterm infants.

Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer296/pSer297 or pThr306/pThr310 provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ. In white adipose tissue, phosphorylation of residues Ser296/Ser297 was enhanced upon agonist activation whilst Thr306/Thr310 did not become phosphorylated. By contrast, in immune cells from Peyer’s patches Thr306/Thr310 become phosphorylated in a strictly agonist-dependent fashion whilst in enteroendocrine cells of the colon both Ser296/Ser297 and Thr306/Thr310 were poorly phosphorylated. The concept of phosphorylation bar-coding has centred to date on the potential for different agonists to promote distinct receptor phosphorylation patterns. Here, we demonstrate that this occurs for the same agonist-receptor pairing in different patho-physiologically relevant target tissues. This may underpin why a single G protein-coupled receptor can generate different functional outcomes in a tissue-specific manner.

Abstract With the objective of creating an electro‐responsive and antimicrobial device suitable as delivery system for Rose Bengal (RB) to the skin, a hybrid hydrogel combining Chitosan (CS) and Graphene Oxide (GO) are designed, serving as functional polymer support and active filling element, respectively. The hybrid system, synthesized using tripolyphosphate as a crosslinker via ionic gelation, shows a uniform and homogeneous surface, as verified by SEM investigations, high biocompatibility when tested on human fibroblast lung cells MRC‐5 cells, and biodegradability in phosphate buffered medium at physiological pH. Drug loading and release experiments, extensively analyzed using suitable mathematical modeling, shows the enhancement of the binding efficiency conferred by GO (534 and 979 mg g−1 for blank and hybrid hydrogels, respectively) and an electro‐responsive behavior (maximum BR release of 36 and 23% at 0 and 12 V, respectively). Additionally, hybrid hydrogel is found to prevent the adhesion of methicillin‐resistant Staphylococcus aureus and to kill the bacterial cells by taking advantage of the sustained release of the antimicrobial RB.

Abstract Aberrant DNA methylation at CpG dinucleotides is a cancer hallmark that is associated with the emergence of resistance to anti cancer treatment, though molecular mechanisms and biological significance remain elusive. Genome scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG rich regions (CpG islands). We report the first high coverage whole-genome map in cancer using the long read nanopore technology, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, after chemotherapy. Long read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution, and showed that the relapse methylome is characterized by hypermethylation at both CpG islands and sparse CpGs regions. Most differentially methylated genes, however, were not differentially expressed nor enriched for chemoresistance genes. A small fraction of under-expressed and hyper-methylated genes at sparse CpGs, in the gene body, was significantly enriched in transcription factors (TFs). Remarkably, these few TFs supported large gene-regulatory networks including 50% of all differentially expressed genes in the relapsed AMLs and highly-enriched in chemoresistance genes. Notably, hypermethylated regions at sparse CpGs were poorly conserved in the relapsed AMLs, under-represented at their genomic positions and showed higher methylation entropy, as compared to CpG islands. Analyses of available datasets confirmed TF binding to their target genes and conservation of the same gene-regulatory networks in large patient cohorts. Relapsed AMLs carried few patient specific structural variants and DNA mutations, apparently not involved in drug resistance. Thus, drug resistance in AMLs can be mainly ascribed to the selection of random epigenetic alterations at sparse CpGs of a few transcription factors, which then induce reprogramming of the relapsing phenotype, independently of clonal genomic evolution.

Crustacean fisheries are gaining prominence globally amid a decline in finfish stocks. Some decapod crustacean species have experienced increased landings in response to shifting market demands and environmental dynamics. Notably, the caramote prawn (Penaeus kerathurus—Forskål, 1775) in the northern Adriatic Sea, Geographical Sub Area (GSA) 17, has risen in both landings and economic importance in recent years. However, despite its significance, comprehensive information on fishery-dependent data, age, and growth in this region remains lacking. To address this gap, this study employs modal progression analysis and the ELEFAN approach, utilizing the “TropFishR” R package and newly developed functions, including bootstrapping procedures. These advancements aim to overcome issues identified in previous versions and enhance the accuracy and reliability of age and growth estimations. The study leverages one year of monthly length-frequency distributions (LFDs) collected from commercial bottom trawls in the northern Adriatic Sea. The results of the analysis confirm the presence of sexual dimorphism in the caramote prawn species, with females exhibiting faster growth rates compared to males. Additionally, the growth performance index supports this observation, further underscoring the importance of accounting for sexual dimorphism in growth modeling and fisheries management strategies. By contributing to a growing body of knowledge on the growth dynamics of the caramote prawn, this study provides valuable insights for sustainable fisheries management in the northern Adriatic Sea. Understanding the age and growth patterns of key crustacean species is essential for developing effective conservation measures and ensuring the long-term health and productivity of marine ecosystems. The findings of this study serve as a foundation for informed decision-making and proactive management practices aimed at preserving the ecological integrity and economic viability of crustacean fisheries in the region.

How accurately do Sentinel-2 (S2) images describe vine row spatial variability? Can they produce effective management zones (MZs) for precision viticulture? S2 and UAV datasets acquired over two years for different drip-irrigated vineyards in the Colli Morenici region (northern Italy) were used to assess the actual need to use UAV-NDVI maps instead of S2 images to obtain effective MZ maps. First, the correlation between S2 and UAV-NDVI values was investigated. Secondly, contingency matrices and dichotomous tables (considering UAV-MZ maps as a reference) were developed to compare MZ maps produced using S2 and UAV imagery. Moreover, data on grape production and quality were analyzed through linear discrimination analyses (LDA) to evaluate the effectiveness of S2-MZs and UAV-MZs to explain spatial variability in yield and quality data. The outcomes highlight that S2 images can be quite good tools to manage fertilization based on the within-field vigor variability, of which they capture the main features. Nevertheless, as S2-MZs with low and high vigor were over-estimated, S2-MZ maps cannot be used for high-accuracy input management. From the LDA results, the UAV-MZs appeared slightly more performant than the S2-MZs in explaining the variability in grape quality and yield, especially in the case of low-vigor MZs.