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Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51-69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO 2  < 95% at admission. All-cause mortality occurred in 105 (21.5%) cases. It was higher in nonvaccinated versus vaccinated SOTR (23.4% vs 13.8%, P = 0.04). Patients in the entire cohort were classified into phenotypes A (n = 149, 30.5%), B (n = 187, 38.3%), and C (n = 152, 31.1%), with mortality rates of 8.7%, 16.6%, and 40.1%, respectively, which were similar to those of nonvaccinated SOTR (9.5%, 16.7%, and 52.0%) and lower in vaccinated SOTR (4.4%, 15.8%, and 17.3%, respectively), with difference between nonvaccinated and vaccinated in the phenotype C (P < 0.001). In conclusion, COVID-19 clinical phenotypes are useful in SOTR, and all-cause mortality decreases in vaccinated patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Statement: The views expressed in this publication are the sole responsibility of the authors and the Commission is not responsible for any use that may be made of the information it contains., (© 2024. The Author(s).)

Somatic mutations of hematopoietic cells in the peripheral blood of normal individuals refer to clonal hematopoiesis of indeterminate potential (CHIP), which is associated with a 0.5-1% risk of progression to hematological malignancies and cardiovascular diseases. CHIP has also been reported in Multiple Myeloma (MM) patients, but its biological relevance remains to be elucidated. In this study, high-depth targeted sequencing of peripheral blood from 76 NDMM patients revealed CHIP in 46% of them, with a variant allele frequency (VAF) ranging from ~ 1 to 34%. The most frequently mutated gene was DNMT3A, followed by TET2. More aggressive disease features were observed among CHIP carriers, who also exhibited higher proportion of high-risk stages (ISS and R-ISS 3) compared to controls. Longitudinal analyses at diagnosis and during follow-up showed a slight increase of VAFs (p = 0.058) for epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (TP53; p = 0.0123). A more stable frequency was observed among other genes, suggesting different temporal dynamics of CH clones. Adverse clinical outcomes, in term of overall and progression-free survivals, were observed in CHIP carriers. These patients also exhibited weakened immune T-cells and enhanced frailty, predicting greater toxicity and consequently shorter event-free survival. Finally, correlation analysis identified platelets count as biomarker for higher VAF among CHIP carriers, regardless of the specific variant. Overall, our study highlights specific biological and clinical features, paving the way for the development of tailored strategies for MM patients carrying CHIP., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Freezing of gait (FOG) in Parkinson's disease (PD) can be triggered by sensomotor, cognitive or limbic factors. The limbic system's impact on FOG is attributed to elevated limbic load, characterized by aversive stimuli, potentially depleting cognitive resources for movement control, resulting in FOG episodes. However, to date, PD patients with and without FOG have not shown alterations of anticipatory postural adjustments during gait initiation after exposure to emotional images, possibly because visual stimuli are less immediately disruptive than auditory stimuli, which can more directly affect attention and the limbic system. This study aims to determine if step initiation is influenced by ecological auditory stimuli with emotional content in patients with FOG compared to those without. Forty-five participants, divided into 3 groups (15 PD with FOG, 15 PD without FOG in ON state, and 15 healthy subjects), stood on a force platform and were asked to step forward in response to neutral, pleasant, or unpleasant ecological auditory stimuli. Anticipatory postural adjustments were investigated in imbalance and unloading phases, while spatio-temporal parameters, including center of pressure (CoP) displacements, were computed for step initiation. PD with FOG showed a reduction of CoP displacements after listening to unpleasant stimuli. Conversely, pleasant stimuli facilitated CoP displacements in these subjects. No influence of affective stimuli on CoP displacements was found in the other two groups. Multiple regression analysis revealed that the behavioral pattern in PD with FOG, modulated by stimuli with affective valence, was mainly associated with the limbic area (i.e., depression). The findings showed that the emotional network plays a crucial role in the pathophysiology of freezing, generating probably interference with attentional reserves that trigger FOG., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Obesity is associated with fatty liver disease. Available therapies show modest efficacy, and nutraceuticals with good effectiveness and safety are largely investigated. We focused on five natural compounds, three plant phenolic compounds (carvacrol, rosmarinic acid, silybin), and two thyroid hormones (T2: 3,5-diiodo-l-thyronine; T3: 3,5,3'-triiodo-L-thyronine) as comparison, to assess their beneficial effects on two cellular models of hepatosteatosis and adipogenesis. All compounds ameliorated the lipid accumulation and oxidative stress in both models, but with different potencies. The peroxisome proliferator-activated receptors (PPARs) are pivotal controllers of adipogenesis and lipid metabolism. For the main isoforms, PPARγ and PPARa, we assessed their possible binding to the compounds by molecular docking calculations, and their expression pattern by real-time PCR. All compounds bind both PPARs with different affinity, while not all compounds affect their expression. The results may clarify the distinctive molecular mechanisms underlying the action of the five compounds in the different cell models with possible applications to treat obesity., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Secondary metabolites play important physiological roles being bioactive as defences against other organisms, or attractive signals used for various purposes, including reproduction. Their production and the emission in the environment may be viewed as an adaptive feature subjected to evolutionary selection. They were demonstrated to be useful for applications in various biotechnological fields, such as pharmaceutical, nutraceutical and cosmeceutical. Sponges and microalgae, including diatoms, are the most promising sources of bioactive compounds from the sea. We aimed at detecting the ecotoxicological effects of crude extracts and fractions obtained from three marine sponges, Geodia cydonium, Haliclona (Halichoclona) vansoesti and Agelas oroides and two benthic diatoms, Nanofrustulum shiloi and Cylindrotheca closterium on model marine organisms. We tested their effects on the Mediterranean purple sea urchin, Paracentrotus lividus, and on two diatoms, Phaeodactylum tricornutum and Cylindrotheca closterium, chosen because they are considered standard indicators for assessment of ecological impacts. Our results showed that extracts and fractions from both sponges and diatoms may be harmful for model invertebrates. However, eggs appeared "protected" from sponge allelochemicals when still unfertilized. The majority of sponge fractions exhibited noticeable impacts during the post-fertilization treatments. In contrast, fractions from diatoms notably increased the rate of malformations compared to the control, both in pre- and post-fertilization treatments., (© 2024. The Author(s).)

Biological soil covers (BSCs) play a pivotal role in ecosystem functioning by enhancing soil stability, mediating nutrient cycling, and influencing soil hydrology. Recognized as ecosystem engineers, they can physically modify, maintain, or create habitats, facilitating plant community development. Through these intricate interactions, BSCs contribute significantly to ecological processes, highlighting their importance in the overall health and functionality of the ecosystems of the Iberian Peninsula. Here we present the results obtained from the contributions of the citizen scientists uploaded from November 2019 to January 2021 with eBryoSoil, an app that allows citizens to participate in mapping the BSC communities across the Iberian Peninsula. Here, we emphasize the importance of habitats and consequently, their interaction with climatic variables for the persistence of BSCs (lichens and bryophytes). Conservation efforts targeted at preserving diverse habitats are essential to ensure the continued presence of lichen and bryophyte communities. Despite challenges posed by the SARS-CoV-2 outbreak, this citizen science project demonstrated success in utilizing a specifically tailored app to gather valuable information on BSC communities, providing insights into their vulnerability to climate change. This program serves as an illustrative example of how citizen science can effectively identify and study vulnerable habitats, offering a blueprint for future studies focused on understudied organisms., (© 2024. The Author(s).)

Vitality Forms (VFs) constitute the dynamic essence of human actions, providing insights into how individuals engage in activities. The ability to perceive and express VFs during interpersonal interactions is pivotal for understanding others' intentions, behaviors, and fostering effective social communication. Despite their ubiquity in all actions, research exploring the role of VFs in neurodivergent conditions related to social and communicative skills, particularly in autism, remains limited. This study aims to investigate the expression of different VFs during the execution of both social and non-social actions in children with an Autism Spectrum Condition (ASC) in comparison to neurotypical children (NT). ASC children and NT children were asked to move a small bottle either towards a target point (non-social context) or moving it towards a receiver (social context) with different VFs specifically neutral, gentle, or rude. Videotaped tasks were subsequently analyzed to study kinematic parameters characterizing VFs. Our results highlighted three main findings: (1) overall, ASC children are able to tune the motor profile of their actions, effectively conveying both gentle and rude VFs; (2) distinct kinematic parameters in the execution of VFs are able to distinguish autistic children from NT children; (3) the social context significantly influences the child's ability to express positive and negative VFs in autism. Taken together, these findings provide new insights to understand how VFs contribute to the complex dynamics of social communication in neurodivergent autistic children, providing a valuable contribution for future interventions and support strategies., (© 2024. The Author(s).)

This study aimed to compare the effects of photobiomodulation therapy (PBMT) with 660 and 980 nm diode lasers on differentiation of periodontal ligament mesenchymal stem cells (PDLMSCs). In this in vitro, experimental study, PDLMSCs were obtained from the Iranian Genetic Bank and cultured in osteogenic medium. They were then subjected to irradiation of 660 and 980 nm diode lasers, and their viability was assessed after one, two, and three irradiation cycles using the methyl thiazolyl tetrazolium (MTT) assay. The cells also underwent DAPI staining, cell apoptosis assay by using the Annexin V/PI, Alizarin Red staining, and real-time polymerase chain reaction (PCR) for assessment of the expression of osteogenic genes. Data were analyzed by two-way ANOVA. The two laser groups had no significant difference in cell apoptosis according to the results of DAPI staining. Both laser groups showed higher cell viability in the MTT assay at 4 and 6 days compared with the control group. Annexin V/PI results showed higher cell viability in both laser groups at 4 days compared with the control group. Rate of early and late apoptosis was lower in both laser groups than the control group at 4 days. Necrosis had a lower frequency in 980 nm laser group than the control group on day 6. Alizarin Red staining showed higher cell differentiation in both laser groups after 3 irradiation cycles than the control group. The highest expression of osteopontin (OPN), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2) was noted in 660 nm laser group with 3 irradiation cycles at 14 days, compared with the control group. PBMT with 660 and 980 nm diode lasers decreased apoptosis and significantly increased PDLMSC differentiation after 3 irradiation cycles., (© 2024. The Author(s).)

Glioblastoma (GBM), one of the deadliest brain tumors, accounts for approximately 50% of all primary malignant CNS tumors, therefore novel, highly effective remedies are urgently needed. Boron neutron capture therapy, which has recently repositioned as a promising strategy to treat high-grade gliomas, requires a conspicuous accumulation of boron atoms in the cancer cells. With the aim of selectively deliver sodium borocaptate (BSH, a 12 B atoms-including molecule already employed in the clinics) to GBM cells, we developed novel cell membrane-derived vesicles (CMVs), overcoming the limits of natural extracellular vesicles as drug carriers, while maintaining their inherent homing abilities that make them preferable to fully synthetic nanocarriers. Purified cell membrane fragments, isolated from patient-derived GBM stem-like cell cultures, were used to prepare nanosized CMVs, which retained some membrane proteins specific of the GBM parent cells and were devoid of potentially detrimental genetic material. In vitro tests evidenced the targeting ability of this novel nanosystem and ruled out any cytotoxicity. The CMVs were successfully loaded with BSH, by following two different procedures, i.e. sonication and electroporation, demonstrating their potential applicability in GBM therapy., (© 2024. The Author(s).)

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO 2 /FiO 2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH 2 O versus 11.4 [10.3-14.6] cmH 2 O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS., (© 2024. The Author(s).)

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson's disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing., (© 2024. The Author(s).)

In this paper the photobiomodulation on isolated mitochondria of bovine liver is studied as a thermodynamic process of conversion of energy. This analysis is conducted by considering a particular set-up for the photobiomodulation experiments of interest. It allows, in particular, the computation of the electromagnetic field and the related energetic quantities in the stimulated organelles. The measurements of the excess of biochemical power density produced by the illuminated mitochondria are performed at regular time intervals after the experiments. The calculations and the measurements finally allow us to obtain the first results on the efficiency of the process of conversion of electromagnetic energy into excess of biochemical energy released by the isolated organelles., (© 2024. The Author(s).)

Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms., (© 2024. The Author(s).)

Transient absorption, or pump-probe microscopy is an absorption-based technique that can explore samples ultrafast dynamic properties and provide fluorescence-free contrast mechanisms. When applied to graphene and its derivatives, this technique exploits the graphene transient response caused by the ultrafast interband transition as the imaging contrast mechanism. The saturation of this transition is fundamental to allow for super-resolution optical far-field imaging, following the reversible saturable optical fluorescence transitions (RESOLFT) concept, although not involving fluorescence. With this aim, we propose a model to numerically compute the temporal evolution under saturation conditions of the single-layer graphene molecular states, which are involved in the transient absorption. Exploiting an algorithm based on the fourth order Runge-Kutta (RK4) method, and the density matrix approach, we numerically demonstrate that the transient absorption signal of single-layer graphene varies linearly as a function of excitation intensity until it reaches saturation. We experimentally verify this model using a custom pump-probe super-resolution microscope. The results define the intensities necessary to achieve super-resolution in a pump-probe nanoscope while studying graphene-based materials and open the possibility of predicting such a saturation process in other light-matter interactions that undergo the same transition., (© 2024. The Author(s).)

Extreme atmospheric-marine events, known as medicanes (short for "Mediterranean hurricanes"), have affected the Mediterranean basin in recent years, resulting in extensive coastal flooding and storm surges, and have occasionally been responsible for several casualties. Considering that the development mechanism of these events is similar to tropical cyclones, it is plausible that these phenomena are strongly affected by sea surface temperatures (SSTs) during their development period (winter and autumn seasons). In this study, we compared satellite data and the numerical reanalysis of SSTs from 1969 to 2023 with in situ data from dataloggers installed at different depths off the coast of southeastern Sicily as well as from data available on Argo floats on the Mediterranean basin. A spectral analysis was performed using a continuous wavelet transform (CWT) for each SST time series to highlight the changes in SSTs prior to the occurrence of Mediterranean Hurricanes as well as the energy content of the various frequencies of the SST signal. The results revealed that decreases in SST occurred prior to the formation of each Mediterranean hurricane, and that this thermal drop phenomenon was not observed in intense extra-tropical systems. The spectral analyses revealed that high CWT coefficients representing high SST energy contents were observed before the occurrence of a Mediterranean hurricane. This information may provide a useful fingerprint for distinguishing Mediterranean hurricanes from common seasonal storms at the onset of these events., (© 2024. The Author(s).)

Motor imagery (MI) is the mental execution of actions without overt movements that depends on the ability to imagine. We explored whether this ability could be related to the cortical activity of the brain areas involved in the MI network. To this goal, brain activity was recorded using high-density electroencephalography in nineteen healthy adults while visually imagining walking on a straight path. We extracted Event-Related Desynchronizations (ERDs) in the θ, α, and β band, and we measured MI ability via (i) the Kinesthetic and Visual Imagery Questionnaire (KVIQ), (ii) the Vividness of Movement Imagery Questionnaire-2 (VMIQ), and (iii) the Imagery Ability (IA) score. We then used Pearson's and Spearman's coefficients to correlate MI ability scores and average ERD power (avgERD). Positive correlations were identified between VMIQ and avgERD of the middle cingulum in the β band and with avgERD of the left insula, right precentral area, and right middle occipital region in the θ band. Stronger activation of the MI network was related to better scores of MI ability evaluations, supporting the importance of testing MI ability during MI protocols. This result will help to understand MI mechanisms and develop personalized MI treatments for patients with neurological dysfunctions., (© 2024. The Author(s).)

Epilepsy surgery is an option for people with focal onset drug-resistant (DR) seizures but a delayed or incorrect diagnosis of epileptogenic zone (EZ) location limits its efficacy. Seizure semiological manifestations and their chronological appearance contain valuable information on the putative EZ location but their interpretation relies on extensive experience. The aim of our work is to support the localization of EZ in DR patients automatically analyzing the semiological description of seizures contained in video-EEG reports. Our sample is composed of 536 descriptions of seizures extracted from Electronic Medical Records of 122 patients. We devised numerical representations of anamnestic records and seizures descriptions, exploiting Natural Language Processing (NLP) techniques, and used them to feed Machine Learning (ML) models. We performed three binary classification tasks: localizing the EZ in the right or left hemisphere, temporal or extra-temporal, and frontal or posterior regions. Our computational pipeline reached performances above 70% in all tasks. These results show that NLP-based numerical representation combined with ML-based classification models may help in localizing the origin of the seizures relying only on seizures-related semiological text data alone. Accurate early recognition of EZ could enable a more appropriate patient management and a faster access to epilepsy surgery to potential candidates., (© 2024. The Author(s).)

The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3-6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life.Clinical trial registration: Clinicaltrial.gov (NCT01899352)., (© 2024. The Author(s).)

Besides action vitality forms, facial expressions represent another fundamental social cue which enables to infer the affective state of others. In the present study, we proposed the iCub robot as an interactive and controllable agent to investigate whether and how different facial expressions, associated to different action vitality forms, could modulate the motor behaviour of participants. To this purpose, we carried out a kinematic experiment in which 18 healthy participants observed video-clips of the iCub robot performing a rude or gentle request with a happy or angry facial expression. After this request, they were asked to grasp an object and pass it towards the iCub robot. Results showed that the iCub facial expressions significantly modulated participants motor response. Particularly, the observation of a happy facial expression, associated to a rude action, decreased specific kinematic parameters such as velocity, acceleration and maximum height of movement. In contrast, the observation of an angry facial expression, associated to a gentle action, increased the same kinematic parameters. Moreover, a behavioural study corroborated these findings, showing that the perception of the same action vitality form was modified when associated to a positive or negative facial expression., (© 2024. The Author(s).)

The dynamics of the brain results from the complex interplay of several neural populations and is affected by both the individual dynamics of these areas and their connection structure. Hence, a fundamental challenge is to derive models of the brain that reproduce both structural and functional features measured experimentally. Our work combines neuroimaging data, such as dMRI, which provides information on the structure of the anatomical connectomes, and fMRI, which detects patterns of approximate synchronous activity between brain areas. We employ cluster synchronization as a tool to integrate the imaging data of a subject into a coherent model, which reconciles structural and dynamic information. By using data-driven and model-based approaches, we refine the structural connectivity matrix in agreement with experimentally observed clusters of brain areas that display coherent activity. The proposed approach leverages the assumption of homogeneous brain areas; we show the robustness of this approach when heterogeneity between the brain areas is introduced in the form of noise, parameter mismatches, and connection delays. As a proof of concept, we apply this approach to MRI data of a healthy adult at resting state., (© 2023. The Author(s).)

The objectives of this study were (1) to analyse the relationship between the colour of the protectors and the outcome of 895 matches in the six Olympic Games in which taekwondo has been included, and (2) to analyse the effect of confounding factors through the different degrees of asymmetry between contestants. Data were recorded on the colour of each athlete's protectors, the scoring system, the sex of the athlete, the weight category, the round of competition, the winner of the match, the method of victory and the points scored by each athlete. Among the main results, a relationship emerged between male athletes wearing red and winning the match (p = 0.034) under the manual scoring system. There were relationships between female athletes wearing blue and winning the match in the quarterfinal (p = 0.014) and last 16 rounds (p = 0.021) using the manual and electronic scoring systems respectively. In female athletes, relationships emerged between wearing blue and winning the match with small (p = 0.008) and medium (p = 0.047) asymmetry under the manual system and with large (p = 0.036) asymmetry under the electronic system. The electronic system had a positive impact on the fairness of Olympic competition. Red tends to gain in importance as the asymmetry between the two athletes decreases, but not enough to give a competitive advantage. The results for Olympic competition held in the now concluded era of the manual system confirmed the presence of the colour effect as a result of psychological factors attributable to referees and judges., (© 2023. The Author(s).)

Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO 2 /FiO 2 ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO 2 /FiO 2 ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype., (© 2023. Springer Nature Limited.)

To verify the existence of a preparatory process for the 6 February 2023, Mw 7.8 Kahramanmaraş earthquake, southern Türkiye, we analyze the temporal evolution of seismic catalog information for ~ 7500 earthquakes with magnitudes M L  ≥ 1.5, which occurred along the main segments of the East Anatolian Fault (EAF) since 2014. We find the EAF fault segments showing different temporal patterns in the proportion of nonclustered seismicity, which we interpret as temporal variation of coupling. We also study the evolution of the b-value, fractal dimension and energy rate. These seismic features show for the Amanos and Pazarcık fault segments a long-term trend during the period 2020-2022 that might correspond to a quiescence phase. The latter is followed by a change in earthquakes clustering and characteristics that starts about eight months before the Mw 7.8 Kahramanmaraş event. Our observations confirm the existence of a long-lasting preparatory phase for the 2023, Mw 7.8 Kahramanmaraş earthquake and can stimulate new investigations on the East Anatolian Fault mechanic. Intercepting when a fault starts deviating from its steady behavior, might be the key for identifying the preparatory phase of large earthquakes and mitigate seismic risk., (© 2023. Springer Nature Limited.)

Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51-8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field., (© 2023. Springer Nature Limited.)

Within the world of natural food supplements, organic extracts deriving from young plant meristematic tissue (bud-derivatives) are becoming attractive, thanks to their richness in bioactive molecules. This natural source is scarce, but every year, tons of plant material, including buds, come from city pruning. If this sustainable source is rather promising from a circular economy point of view, the safety of the obtained supplements must be assessed. In fact, anthropic microcontaminants, such as polycyclic aromatic hydrocarbons (PAHs), could adsorb onto the urban buds, leading to a possible contamination of the bud-derivatives. In this study, we developed a magnetic dispersive solid phase extraction (m-dSPE) based on molecularly imprinted microparticles, combined with GC-MS, to quantify the 16 priority PAHs in such extracts. The D-optimal experimental design was implemented to maximize analytes' recovery with the smallest set of experiments. The optimized method was characterized by great selectivity thanks to the molecular imprinted polymer and ease of use provided by m-dSPE. Moreover, it complies with green principles, thanks to the minimum consumption of organic solvent (1.5 mL of acetone per sample). The recoveries ranged from 76 to 100% and procedural precision was below 10% for most PAHs. Despite the matrix complexity, low quantification limits (0.7-12.6 μg kg -1 ) were reached. This guaranteed the PAHs' quantitation at levels below those indicated as safe by a European Community regulation on food supplements. None of the analyzed samples, coming from different anthropically impacted areas, showed concerning PAHs levels., (© 2023. Springer Nature Limited.)

In this paper, we examine the impact of the circular economy on global resource extraction. To this end, we make an input-output analysis dynamic by combining it with an agent-based model of the capital sector. This approach allows us to study the evolution of the circular economy due to the endogenous decisions of firms on whether to invest in the capital expansion of primary or secondary sectors. Previous studies have examined the macroeconomic effects of the circular economy using scenarios that exogenously impose higher recycling rates, improved resource efficiency, or lowered demand on the economy. Such studies typically assume static consumer budgets, no price adjustments, capital investments in recycling infrastructure, or technological innovation. We relax these assumptions in a novel agent-based input-output model (ABM-IO). We show that the circular economy can significantly reduce the extraction of iron, aluminum, and nonferrous metals if implemented globally. However, the leakage effect may also cause some metal-intensive industries to relocate outside the EU, offsetting the circular economy efforts. The risk of the leakage effect is especially high for copper., (© 2023. Springer Nature Limited.)

When we perform an action, self-elicited movement induces suppression of somatosensory information to the cortex, requiring a correct motor-sensory and inter-sensory (i.e. cutaneous senses, kinesthesia, and proprioception) integration processes to be successful. However, recent works show that blindness might impact some of these elements. The current study investigates the effect of movement on tactile perception and the role of vision in this process. We measured the velocity discrimination threshold in 18 sighted and 18 blind individuals by having them perceive a sequence of two movements and discriminate the faster one in passive and active touch conditions. Participants' Just Noticeable Difference (JND) was measured to quantify their precision. Results showed a generally worse performance during the active touch condition compared to the passive. In particular, this difference was significant in the blind group, regardless of the blindness duration, but not in the sighted one. These findings suggest that the absence of visual calibration impacts motor-sensory and inter-sensory integration required during movement, diminishing the reliability of tactile signals in blind individuals. Our work spotlights the need for intervention in this population and should be considered in the sensory substitution/reinforcement device design., (© 2023. Springer Nature Limited.)

Microcapsules of ciriguela peel extracts obtained by ultrasound-assisted extraction were prepared by spray drying, whose results were compared with those of freeze-drying as a control. The effects of spray-drying air temperature, feed flow rate and ratio of encapsulating agents (maltodextrin and arabic gum) were studied. Encapsulation efficiency, moisture content, total phenolic compounds (TPC), water activity, hygroscopicity, solubility, colorimetric parameters, phenolic profile by HPLC/DAD, simulated gastrointestinal digestion and morphology of spray-dried and freeze-dried microcapsules were evaluated, as well as their stability of TPC during 90 days storage at 7 and 25 °C. Spray-dried extract showed higher encapsulation efficiency (98.83%) and TPC (476.82 mg GAE g -1 ) than freeze-dried extract. The most abundant compounds in the liquid extract of ciriguela peel flour were rutin, epicatechin gallate, chlorogenic acid and quercetin. Rutin and myricetin were the major flavonoids in the spray-dried extract, while quercetin and kaempferol were in the freeze-dried one. The simulated gastrointestinal digestion test of microencapsulated extracts revealed the highest TPC contents after the gastric phase and the lowest one after the intestinal one. Rutin was the most abundant compound after the digestion of both spray-dried (68.74 µg g -1 ) and freeze-dried (93.98 µg g -1 ) extracts. Spray-dried microcapsules were of spherical shape, freeze-dried products of irregular structures. Spray-dried microcapsules had higher phenolic compounds contents after 90 days of storage at 7 °C compared to those stored at 25 °C, while the lyophilized ones showed no significant difference between the two storage temperatures. The ciriguela agro-industrial residue can be considered an interesting alternative source of phenolic compounds that could be used, in the form of bioactive compounds-rich powders, as an ingredient in pharmaceutical, cosmetic and food industries., (© 2023. Springer Nature Limited.)

How, when and where large earthquakes are generated remain fundamental unsolved scientific questions. Intercepting when a fault system starts deviating from its steady behavior by monitoring the spatio-temporal evolution and dynamic source properties of micro-to-small earthquakes can have high potential as tool for identifying the preparatory phase of large earthquakes. We analyze the seismic activity that preceded the Mw 6.3 earthquake that hit L'Aquila on 6 April 2009 in central Italy, and we show that the seismic catalog information can be transformed into features allowing us to track in a statistical framework the spatio-temporal evolution of seismicity. Features associated to foreshocks show different patterns from the background seismicity that occurred in the previous years. We show that features ensemble allows to clearly capture the activation phase of the main event. Nonetheless, foreshocks share similar clustering properties of previous seismic sequences not culminating in large earthquakes, and thus generating questions on their use as potential precursor for earthquake sequences prone to evolve into catastrophic sequences., (© 2023. Springer Nature Limited.)

Epigenetic dysregulation of chromatin is one of the hallmarks of cancer development and progression, and it is continuously investigated as a potential general bio-marker of this complex disease. One of the nuclear factors involved in gene regulation is the unique DEK protein-a histone chaperon modulating chromatin topology. DEK expression levels increase significantly from normal to cancer cells, hence raising the possibility of using DEK as a tumor marker. Although DEK is known to be implicated in epigenetic and transcriptional regulation, the details of these interactions and their relevance in cancer development remain largely elusive. In this work, we investigated the spatial correlation between the nuclear distribution of DEK and chromatin patterns-alongside breast cancer progression-leveraging image cross-correlation spectroscopy (ICCS) coupled with Proximity Ligation Assay (PLA) analysis. We performed our study on the model based on three well-established human breast cell lines to consider this tumor's heterogeneity (MCF10A, MCF7, and MDA-MB-231 cells). Our results show that overexpression of DEK correlates with the overall higher level of spatial proximity between DEK and histone marks corresponding to gene promoters regions (H3K9ac, H3K4me3), although it does not correlate with spatial proximity between DEK and gene enhancers (H3K27ac). Additionally, we observed that colocalizing fractions of DEK and histone marks are lower for the non-invasive cell subtype than for the highly invasive cell line (MDA-MB-231). Thus, this study suggests that the role of DEK on transcriptionally active chromatin regions varies depending on the subtype of the breast cancer cell line., (© 2023. Springer Nature Limited.)

Contrary to a photographer, who puts a great effort in keeping the lens still, eyes insistently move even during fixation. This benefits signal decorrelation, which underlies an efficient encoding of visual information. Yet, camera motion is not sufficient alone; it must be coupled with a sensor specifically selective to temporal changes. Indeed, motion induced on standard imagers only results in burring effects. Neuromorphic sensors represent a valuable solution. Here we characterize the response of an event-based camera equipped with fixational eye movements (FEMs) on both synthetic and natural images. Our analyses prove that the system starts an early stage of redundancy suppression, as a precursor of subsequent whitening processes on the amplitude spectrum. This does not come at the price of corrupting structural information contained in local spatial phase across oriented axes. Isotropy of FEMs ensures proper representations of image features without introducing biases towards specific contrast orientations., (© 2023. The Author(s).)

Nowadays, catheter-based ablation in patients with post-ischemic ventricular tachycardia (VT) is performed in arrhythmogenic sites identified by electrophysiologists by visual inspection during electroanatomic mapping. This work aims to present the development of machine learning tools aiming at supporting clinicians in the identification of arrhythmogenic sites by exploiting innovative features that belong to different domains. This study included 1584 bipolar electrograms from nine patients affected by post-ischemic VT. Different features were extracted in the time, time scale, frequency, and spatial domains and used to train different supervised classifiers. Classification results showed high performance, revealing robustness across the different classifiers in terms of accuracy, true positive, and false positive rates. The combination of multi-domain features with the ensemble tree is the most effective solution, exhibiting accuracies above 93% in the 10-time 10-fold cross-validation and 84% in the leave-one-subject-out validation. Results confirmed the effectiveness of the proposed features and their potential use in a computer-aided system for the detection of arrhythmogenic sites. This work demonstrates for the first time the usefulness of supervised machine learning for the detection of arrhythmogenic sites in post-ischemic VT patients, thus enabling the development of computer-aided systems to reduce operator dependence and errors, thereby possibly improving clinical outcomes., (© 2023. The Author(s).)

Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35-37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device. Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine samples were collected at T0 (urine produced in the first 15 min after the beginning of normothermic reperfusion), T30, T60 and T120. Multiple algorithms, support vector machine learning and partial least squares discriminant analysis were used to select the most discriminative proteins during NMP. Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 during NMP. Machine learning algorithms identified the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1 and F9) in the kidney and urine after NMP. Latexin (LXN), an endogenous carboxypeptidase inhibitor, resulted the most-upregulated protein at T120, and this result was confirmed by ELISA. In addition, functional analysis revealed that the most strongly upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins represented the complement system and coagulation cascade. Our proteomic analysis demonstrated that even brief periods of NMP induce remarkable metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic., (© 2023. The Author(s).)

In point-scanning microscopy, optical sectioning is achieved using a small aperture placed in front of the detector, i.e. the detection pinhole, which rejects the out-of-focus background. The maximum level of optical sectioning is theoretically obtained for the minimum size of the pinhole aperture, but this is normally prevented by the dramatic reduction of the detected signal when the pinhole is closed, leading to a compromise between axial resolution and signal-to-noise ratio. We have recently demonstrated that, instead of closing the pinhole, one can reach a similar level of optical sectioning by tuning the pinhole size in a confocal microscope and by analyzing the resulting image series. The method, consisting in the application of the separation of photons by lifetime tuning (SPLIT) algorithm to series of images acquired with tunable pinhole size, is called SPLIT-pinhole (SPLIT-PIN). Here, we share and describe a SPLIT-PIN software for the processing of series of images acquired at tunable pinhole size, which generates images with reduced out-of-focus background. The software can be used on series of at least two images acquired on available commercial microscopes equipped with a tunable pinhole, including confocal and stimulated emission depletion (STED) microscopes. We demonstrate applicability on different types of imaging modalities: (1) confocal imaging of DNA in a non-adherent cell line; (2) removal of out-of-focus background in super-resolved STED microscopy; (3) imaging of live intestinal organoids stained with a membrane dye., (© 2023. The Author(s).)

Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H 2 O 2 exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2-a fragment that has eluded identification so far-could readily be detected after H 2 O 2 treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H 2 O 2 challenge, as well as mitigated H 2 O 2 -mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H 2 O 2 , favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and γ-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10., (© 2023. The Author(s).)

Brainstem dysfunctions are very common in Multiple Sclerosis (MS) and are a critical predictive factor for future disability. Brainstem functionality can be explored with blink reflexes, subcortical responses consisting in a blink following a peripheral stimulation. Some reflexes are already employed in clinical practice, such as Trigeminal Blink Reflex (TBR). Here we propose for the first time in MS the exploration of Hand Blink Reflex (HBR), which size is modulated by the proximity of the stimulated hand to the face, reflecting the extension of the peripersonal space. The aim of this work is to test whether Machine Learning (ML) techniques could be used in combination with neurophysiological measurements such as TBR and HBR to improve their clinical information and potentially favour the early detection of brainstem dysfunctionality. HBR and TBR were recorded from a group of People with MS (PwMS) with Relapsing-Remitting form and from a healthy control group. Two AdaBoost classifiers were trained with TBR and HBR features each, for a binary classification task between PwMS and Controls. Both classifiers were able to identify PwMS with an accuracy comparable and even higher than clinicians. Our results indicate that ML techniques could represent a tool for clinicians for investigating brainstem functionality in MS. Also, HBR could be promising when applied in clinical practice, providing additional information about the integrity of brainstem circuits potentially favouring early diagnosis., (© 2022. The Author(s).)

In a murine model of acute ischemic stroke, SIRT6 knockdown resulted in larger cerebral infarct size, worse neurological outcome, and higher mortality, indicating a possible neuro-protective role of SIRT6. In this study, we aimed at evaluating the prognostic value of serum SIRT6 levels in patients with acute ischemic stroke (AIS). Serum levels of SIRT6, collected within 72 h from symptom-onset, were measured in 317 consecutively enrolled AIS patients from the COSMOS cohort. The primary endpoint of this analysis was 90-day mortality. The independent prognostic value of SIRT6 was assessed with multivariate logistic and Cox proportional regression models. 35 patients (11%) deceased within 90-day follow-up. After adjustment for established risk factors (age, NIHSS, heart failure, atrial fibrillation, and C reactive protein), SIRT6 levels were negatively associated with mortality. The optimal cut-off for survival was 634 pg/mL. Patients with SIRT6 levels below this threshold had a higher risk of death in multivariable Cox regression. In this pilot study, SIRT6 levels were significantly associated with 90-day mortality after AIS; these results build on previous molecular and causal observations made in animal models. Should this association be confirmed, SIRT6 could be a potential prognostic predictor and therapeutic target in AIS., (© 2022. The Author(s).)

This paper formalizes smooth curve coloring (i.e., curve identification) in the presence of curve intersections as an optimization problem, and investigates theoretically properties of its optimal solution. Moreover, it presents a novel automatic technique for solving such a problem. Formally, the proposed algorithm aims at minimizing the summation of the total variations over a given interval of the first derivatives of all the labeled curves, written as functions of a scalar parameter. The algorithm is based on a first-order finite difference approximation of the curves and a sequence of prediction/correction steps. At each step, the predicted points are attributed to the subsequently observed points of the curves by solving an Euclidean bipartite matching subproblem. A comparison with a more computationally expensive dynamic programming technique is presented. The proposed algorithm is applied with success to elastic periodic metamaterials for the realization of high-performance mechanical metafilters. Its output is shown to be in excellent agreement with desirable smoothness and periodicity properties of the metafilter dispersion curves. Possible developments, including those based on machine-learning techniques, are pointed out., (© 2022. The Author(s).)

Anthropogenic microparticles (AMs) were found for the first time in specimens of Trematomus bernacchii collected in 1998 in the Ross Sea (Antarctica) and stored in the Antarctic Environmental Specimen Bank. Most of the identified AMs were fibers of natural and synthetic origin. The natural AMs were cellulosic, the synthetic ones were polyester, polypropylene, polypropylene/polyester, and cellulose acetate. The presence of dyes in the natural AMs indicates their anthropogenic origin. Five industrial dyes were identified by Raman spectroscopy with Indigo occurring in most of them (55%). Our research not only adds further data to the ongoing knowledge of pollution levels in the Antarctic ecosystem, it provides an interesting snapshot of the past, highlighting that microplastics and anthropogenic fiber pollution had already entered the Antarctic marine food web at the end of the '90 s. These findings therefore establish the foundations for understand the changes in marine litter pollution over time., (© 2022. The Author(s).)

Studying biomolecules in their native environment represents the ideal sample condition for structural biology investigations. Here we present a novel protocol which allows to delivery proteins into eukaryotic cells through a mild thermal stimulation. The data presented herein show the efficacy of this approach for delivering proteins in the intracellular environment of mammalian cells reaching a concentration range suitable for successfully applying biophysical methods, such as double electron electron resonance (DEER) measurements for characterising protein conformations., (© 2022. The Author(s).)

The SARS-CoV-2 pandemic has led significant social repercussions and forced people to wear face masks. Recent research has demonstrated that the human ability to infer emotions from facial configurations is significantly reduced when face masks are worn. Since the mouth region is specifically crucial for deaf people who speak sign language, the current study assessed the impact of face masks on inferring emotional facial expressions in a population of adult deaf signers. A group of 34 congenitally deaf individuals and 34 normal-hearing individuals were asked to identify happiness, sadness, fear, anger, and neutral expression on static human pictures with and without facial masks presented through smartphones. For each emotion, the percentage of correct responses with and without face masks was calculated and compared between groups. Results indicated that face masks, such as those worn due to the SARS-CoV-2 pandemic, limit the ability of people to infer emotions from facial expressions. The negative impact of face masks is significantly pronounced when deaf people have to recognize low-intensity expressions of happiness. These findings are of essential importance because difficulties in recognizing emotions from facial expressions due to mask wearing may contribute to the communication challenges experienced by the deaf community during the SARS-CoV-2 pandemic, generating feelings of frustration and exclusion., (© 2022. The Author(s).)

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8-21.4] and AKI [3.36 (1.44-7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI., (© 2022. The Author(s).)

Elevated circulating levels of nutrient-derived trimethylamine N-oxide (TMAO) have been associated with the onset and progression of cardiovascular disease by promoting athero-thrombosis. However, in conditions like bariatric surgery (Roux-en-Y gastric bypass, RYGB), stable increases of plasma TMAO are associated with improved endothelial function and reduced cardiovascular morbidity and mortality, thus questioning whether a mechanistic relationship between TMAO and endothelial dysfunction exists. Herein, we translationally assessed the effects of acute TMAO exposure on endothelial dysfunction, thrombosis and stroke. After RYGB, fasting circulating levels of TMAO increased in patients and obese rats, in parallel with an improved gluco-lipid profile and higher circulating bile acids. The latter enhanced FXR-dependent signalling in rat livers, which may lead to higher TMAO synthesis post RYGB. In lean rats, acute TMAO injection (7 mg kg -1 ) 1.5-h before sacrifice and ex-vivo 30-min incubation of thoracic aortas with 10 -6  M TMAO did not impair vasodilation in response to acetylcholine (Ach), glucagon-like peptide 1, or insulin. Similarly, in lean WT mice (n = 5-6), TMAO injection prior to subjecting mice to ischemic stroke or arterial thrombosis did not increase its severity compared to vehicle treated mice. Endothelial nitric oxide synthase (eNOS) activity and intracellular stress-activated pathways remained unaltered in aorta of TMAO-injected rats, as assessed by Western Blot. Pre-incubation of human aortic endothelial cells with TMAO (10 -6  M) did not alter NO release in response to Ach. Our results indicate that increased plasmatic TMAO in the near-physiological range seems to be a neutral bystander to vascular function as translationally seen in patients after bariatric surgery or in healthy lean rodent models and in endothelial cells exposed acutely to TMAO., (© 2022. The Author(s).)

Visual processing of emotional stimuli has been shown to engage complex cortical and subcortical networks, but it is still unclear how it affects sensorimotor integration processes. To fill this gap, here, we used a TMS protocol named short-latency afferent inhibition (SAI), capturing sensorimotor interactions, while healthy participants were observing emotional body language (EBL) and International Affective Picture System (IAPS) stimuli. Participants were presented with emotional (fear- and happiness-related) or non-emotional (neutral) EBL and IAPS stimuli while SAI was tested at 120 ms and 300 ms after pictures presentation. At the earlier time point (120 ms), we found that fear-related EBL and IAPS stimuli selectively enhanced SAI as indexed by the greater inhibitory effect of somatosensory afferents on motor excitability. Larger early SAI enhancement was associated with lower scores at the Behavioural Inhibition Scale (BIS). At the later time point (300 ms), we found a generalized SAI decrease for all kind of stimuli (fear, happiness or neutral). Because the SAI index reflects integrative activity of cholinergic sensorimotor circuits, our findings suggest greater sensitivity of such circuits during early (120 ms) processing of threat-related information. Moreover, the correlation with BIS score may suggest increased attention and sensory vigilance in participants with greater anxiety-related dispositions. In conclusion, the results of this study show that sensorimotor inhibition is rapidly enhanced while processing threatening stimuli and that SAI protocol might be a valuable option in evaluating emotional-motor interactions in physiological and pathological conditions., (© 2022. The Author(s).)

Charcot-Marie-Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases., (© 2022. The Author(s).)

Time-of-day influences both physical and mental performances. Its impact on motor learning is, however, not well established yet. Here, using a finger tapping-task, we investigated the time-of-day effect on skill acquisition (i.e., immediately after a physical or mental practice session) and consolidation (i.e., 24 h later). Two groups (one physical and one mental) were trained in the morning (10 a.m.) and two others (one physical and one mental) in the afternoon (3 p.m.). We found an enhancement of motor skill following both types of practice, whatever the time of the day, with a better acquisition for the physical than the mental group. Interestingly, there was a better consolidation for both groups when the training session was scheduled in the afternoon. Overall, our results indicate that the time-of-day positively influences motor skill consolidation and thus must be considered to optimize training protocols in sport and clinical domains to potentiate motor learning., (© 2022. The Author(s).)