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We investigated the Michelangelo effect, i.e. the facilitatory effect of a virtual art therapy in motor rehabilitation (Iosa et al. 2021), with a novel virtual reality paradigm in which users are engaged in motor exercises with 3D sculptures. In particular, thirty young adults were immersed in a virtual environment where they could sculpt, by using the real hands, some famous sculptures in the history of art, such as the David of Michelangelo, the Venus of Milo and the statue of Laocoon and His Sons, and their control stimuli, i.e. statues in very low resolution or cubes. We recorded the kinematics (length, the time to complete each trial, mean normalized jerk) and questionnaire answers (objective and subjective beauty, User Satisfaction Evaluation Questionnaire and Nasa Task Load Index). In general, we found that the perception of subjective and objective beauty was higher when sculpting the statues than control stimuli, the judgment of usability of the system was high. The perceived fatigue was not higher when sculpting the statues despite the longer time spent in completing the task that with respect to the control stimuli. Moreover, we found that the interaction with the experimental statues affected the fluidity and symmetry of hands movements. Finally, we discuss this evidence regarding the art therapy and neuroaesthetics principles for motor rehabilitation in the Metaverse with VR, including the possible role of virtual embodiment (illusory feeling to have a virtual body) for boosting the efficacy of the clinical applications., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Radiomics shows promising results in supporting the clinical decision process, and much effort has been put into its standardization, thus leading to the Imaging Biomarker Standardization Initiative (IBSI), that established how radiomics features should be computed. However, radiomics still lacks standardization and many factors, such as segmentation methods, limit study reproducibility and robustness., Aim: We investigated the impact that three different segmentation methods (manual, thresholding and region growing) have on radiomics features extracted from 18 F-PSMA-1007 Positron Emission Tomography (PET) images of 78 patients (43 Low Risk, 35 High Risk). Segmentation was repeated for each patient, thus leading to three datasets of segmentations. Then, feature extraction was performed for each dataset, and 1781 features (107 original, 930 Laplacian of Gaussian (LoG) features, 744 wavelet features) were extracted. Feature robustness and reproducibility were assessed through the intra class correlation coefficient (ICC) to measure agreement between the three segmentation methods. To assess the impact that the three methods had on machine learning models, feature selection was performed through a hybrid descriptive-inferential method, and selected features were given as input to three classifiers, K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), Random Forest (RF), AdaBoost and Neural Networks (NN), whose performance in discriminating between low-risk and high-risk patients have been validated through 30 times repeated five-fold cross validation., Conclusions: Our study showed that segmentation methods influence radiomics features and that Shape features were the least reproducible (average ICC: 0.27), while GLCM features the most reproducible. Moreover, feature reproducibility changed depending on segmentation type, resulting in 51.18% of LoG features exhibiting excellent reproducibility (range average ICC: 0.68-0.87) and 47.85% of wavelet features exhibiting poor reproducibility that varied between wavelet sub-bands (range average ICC: 0.34-0.80) and resulted in the LLL band showing the highest average ICC (0.80). Finally, model performance showed that region growing led to the highest accuracy (74.49%), improved sensitivity (84.38%) and AUC (79.20%) in contrast with manual segmentation.

The mucosal immune response is recognized to be important in the early control of infection sustained by viruses with mucosal tissues as the primary site of entry and replication, such as SARS-CoV-2. Mucosal IgA has been consistently reported in the mouth and eye of SARS-CoV-2 infected subjects, where it correlated inversely with COVID-19 symptom severity. Yet, there is still scarce information on the comparative ability of the diverse SARS-CoV-2 vaccines to induce local IgA responses at the virus entry site. Thus, the aim of this study was to assess the presence of anti-SARS-CoV-2 IgA in the saliva of 95 subjects vaccinated with a booster dose and different combinations of vaccines, including mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Vaxzevria (AstraZeneca). The results showed the presence of a mucosal response in 93.7% of vaccinated subjects, with a mean IgA titer of 351.5 ± 31.77 U/mL, strongly correlating with the serum anti-SARS-CoV-2 IgG titer ( p < 0.0001). No statistically significant differences emerged between the vaccine types, although the salivary IgA titer appeared slightly higher after receiving a booster dose of the mRNA-1273 vaccine (Moderna) following two doses of BNT162b2 (Pfizer-BioNTech), compared to the other vaccine combinations. These data confirm what was previously reported at the eye level and suggest that monitoring salivary IgA may be a useful tool for driving forward vaccine design and surveillance strategies, potentially leading to novel routes of vaccine administration and boosting.

The purpose of this work is to advance in the computational study of connectome graphs from a topological point of view. Specifically, starting from a sequence of hypergraphs associated to a brain graph (obtained using the Boundary Scale model, BS2), we analyze the resulting scale-space representation using classical topological features, such as Betti numbers and average node and edge degrees. In this way, the topological information that can be extracted from the original graph is substantially enriched, thus providing an insightful description of the graph from a clinical perspective. To assess the qualitative and quantitative topological information gain of the BS2 model, we carried out an empirical analysis of neuroimaging data using a dataset that contains the connectomes of 96 healthy subjects, 52 women and 44 men, generated from MRI scans in the Human Connectome Project. The results obtained shed light on the differences between these two classes of subjects in terms of neural connectivity.

Radiofrequency (RF) ablation represents an efficient strategy to reduce the volume of thyroid nodules. In this study, a finite element model was developed with the aim of optimizing RF parameters, e.g., input power and treatment duration, in order to achieve the target volume reduction rate (VRR) for a thyroid nodule. RF ablation is modelled as a coupled electro-thermal problem wherein the electric field is applied to induce tissue heating. The electric problem is solved with the Laplace equation, the temperature distribution is estimated with the Pennes bioheat equation, and the thermal damage is evaluated using the Arrhenius equation. The optimization model is applied to RF electrode with different active tip lengths in the interval from 5 mm to 40 mm at the 5 mm step. For each case, we also explored the influence of tumour blood perfusion rate on RF ablation outcomes. The model highlights that longer active tips are more efficient as they require lesser power and shorter treatment time to reach the target VRR. Moreover, this condition is characterized by a reduced transversal ablation zone. In addition, a higher blood perfusion increases the heat dispersion, requiring a different combination of RF power and time treatment to achieve the target VRR. The model may contribute to an improvement in patient-specific RF ablation treatment.

Beach sand may act as a reservoir for potential human pathogens, posing a public health risk. Despite this, the microbiological monitoring of sand microbiome is rarely performed to determine beach quality. In this study, the sand microbial population of a Northern Adriatic Sea beach sand was profiled by microbiological (CFU counts) and molecular methods (WGS, microarray), showing significant presence of potential human pathogens including drug-resistant strains. Consistent with these results, the potential of quicklime as a restoring method was tested in vitro and on-field. Collected data showed that adding 1-3% quicklime ( w / w ) to sand provided an up to -99% of bacteria, fungi, and viruses, in a dose- and time-dependent manner, till 45 days post-treatment. In conclusion, data suggest that accurate monitoring of sand microbiome may be essential, besides water, to assess beach quality and safety. Moreover, first evidences of quicklime potential for sand decontamination are provided, suggesting its usage as a possible way to restore the microbiological quality of sand in highly contaminated areas.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multifactorial disease that causes increasing morbidity worldwide, and many individuals with ME/CFS symptoms remain undiagnosed due to the lack of diagnostic biomarkers. Its etiology is still unknown, but increasing evidence supports a role of herpesviruses (including HHV-6A and HHV-6B) as potential triggers. Interestingly, the infection by these viruses has been reported to impact the expression of microRNAs (miRNAs), short non-coding RNA sequences which have been suggested to be epigenetic factors modulating ME/CFS pathogenic mechanisms. Notably, the presence of circulating miRNAs in plasma has raised the possibility to use them as valuable biomarkers for distinguishing ME/CFS patients from healthy controls. Thus, this study aimed at determining the role of eight miRNAs, which were selected for their previous association with ME/CFS, as potential circulating biomarkers of the disease. Their presence was quantitatively evaluated in plasma from 40 ME/CFS patients and 20 healthy controls by specific Taqman assays, and the results showed that six out of the eight of the selected miRNAs were differently expressed in patients compared to controls; more specifically, five miRNAs were significantly upregulated (miR-127-3p, miR-142-5p, miR-143-3p, miR-150-5p, and miR-448), and one was downmodulated (miR-140-5p). MiRNA levels directly correlated with disease severity, whereas no significant correlations were observed with the plasma levels of seven pro-inflammatory cytokines or with the presence/load of HHV-6A/6B genome, as judged by specific PCR amplification. The results may open the way for further validation of miRNAs as new potential biomarkers in ME/CFS and increase the knowledge of the complex pathways involved in the ME/CFS development.

Osteochondral tissue (OC) is a complex and multiphasic system comprising cartilage and subchondral bone. The discrete OC architecture is layered with specific zones characterized by different compositions, morphology, collagen orientation, and chondrocyte phenotypes. To date, the treatment of osteochondral defects (OCD) remains a major clinical challenge due to the low self-regenerative capacity of damaged skeletal tissue, as well as the critical lack of functional tissue substitutes. Current clinical approaches fail to fully regenerate damaged OC recapitulating the zonal structure while granting long-term stability. Thus, the development of new biomimetic treatment strategies for the functional repair of OCDs is urgently needed. Here, we review recent developments in the preclinical investigation of novel functional approaches for the resurfacing of skeletal defects. The most recent studies on preclinical augmentation of OCDs and highlights on novel studies for the in vivo replacement of diseased cartilage are presented.

Bone tissue is mainly composed at the nanoscale of apatite minerals, collagen molecules and water that form the mineralized collagen fibril (MCF). In this work, we developed a 3D random walk model to investigate the influence of bone nanostructure on water diffusion. We computed 1000 random walk trajectories of water molecules within the MCF geometric model. An important parameter to analyse transport behaviour in porous media is tortuosity, computed as the ratio between the effective path length and the straight-line distance between initial and final points. The diffusion coefficient is determined from the linear fit of the mean squared displacement of water molecules as a function of time. To achieve more insight into the diffusion phenomenon within MCF, we estimated the tortuosity and diffusivity at different quotes in the longitudinal direction of the model. Tortuosity is characterized by increasing values in the longitudinal direction. As expected, the diffusion coefficient decreases as tortuosity increases. Diffusivity outcomes confirm the findings achieved by experimental investigations. The computational model provides insights into the relation between the MCF structure and mass transport behaviour that may contribute to the improvement of bone-mimicking scaffolds.

Microbial contamination in the hospital environment is a major concern for public health, since it significantly contributes to the onset of healthcare-associated infections (HAIs), which are further complicated by the alarming level of antimicrobial resistance (AMR) of HAI-associated pathogens. Chemical disinfection to control bioburden has a temporary effect and can favor the selection of resistant pathogens, as observed during the COVID-19 pandemic. Instead, probiotic-based sanitation (probiotic cleaning hygiene system, PCHS) was reported to stably abate pathogens, AMR, and HAIs. PCHS action is not rapid nor specific, being based on competitive exclusion, but the addition of lytic bacteriophages that quickly and specifically kill selected bacteria was shown to improve PCHS effectiveness. This study aimed to investigate the effect of such combined probiotic-phage sanitation (PCHSφ) in two Italian hospitals, targeting staphylococcal contamination. The results showed that PCHSφ could provide a significantly higher removal of staphylococci, including resistant strains, compared with disinfectants (-76%, p < 0.05) and PCHS alone (-50%, p < 0.05). Extraordinary sporadic chlorine disinfection appeared compatible with PCHSφ, while frequent routine chlorine usage inactivated the probiotic/phage components, preventing PCHSφ action. The collected data highlight the potential of a biological sanitation for better control of the infectious risk in healthcare facilities, without worsening pollution and AMR concerns.

Background: The COVID-19 pandemic has highlighted the extent to which the public transportation environment, such as in subways, may be important for the transmission of potential pathogenic microbes among humans, with the possibility of rapidly impacting large numbers of people. For these reasons, sanitation procedures, including massive use of chemical disinfection, were mandatorily introduced during the emergency and remain in place. However, most chemical disinfectants have temporary action and a high environmental impact, potentially enhancing antimicrobial resistance (AMR) of the treated microbes. By contrast, a biological and eco-sustainable probiotic-based sanitation (PBS) procedure was recently shown to stably shape the microbiome of treated environments, providing effective and long-term control of pathogens and AMR spread in addition to activity against SARS-CoV-2, the causative agent of COVID-19. Our study aims to assess the applicability and impact of PBS compared with chemical disinfectants based on their effects on the surface microbiome of a subway environment., Results: The train microbiome was characterized by both culture-based and culture-independent molecular methods, including 16S rRNA NGS and real-time qPCR microarray, for profiling the train bacteriome and its resistome and to identify and quantify specific human pathogens. SARS-CoV-2 presence was also assessed in parallel using digital droplet PCR. The results showed a clear and significant decrease in bacterial and fungal pathogens (p < 0.001) as well as of SARS-CoV-2 presence (p < 0.01), in the PBS-treated train compared with the chemically disinfected control train. In addition, NGS profiling evidenced diverse clusters in the population of air vs. surface while demonstrating the specific action of PBS against pathogens rather than the entire train bacteriome., Conclusions: The data presented here provide the first direct assessment of the impact of different sanitation procedures on the subway microbiome, allowing a better understanding of its composition and dynamics and showing that a biological sanitation approach may be highly effective in counteracting pathogens and AMR spread in our increasingly urbanized and interconnected environment. Video Abstract., (© 2023. The Author(s).)

Objectives: Fatigue in multiple sclerosis (MS) is a frequent and invalidating symptom, which can be relieved by non-invasive neuromodulation, which presents only negligible side effects. A 5-day transcranial direct-current stimulation, 15 min per day, anodically targeting the somatosensory representation of the whole body against a larger occipital cathode was efficacious against MS fatigue (fatigue relief in multiple sclerosis, Faremus treatment). The present proof-of-concept study tested the working hypothesis that Faremus S1 neuromodulation modifies the homology of the dominant and non-dominant corticospinal (CST) circuit recruitment., Methods: CST homology was assessed via the Fréchet distance between the morphologies of motor potentials (MEPs) evoked by transcranial magnetic stimulation in the homologous left- and right-hand muscles of 10 fatigued MS patients before and after Faremus., Results: In the absence of any change in MEP features either as differences between the two body sides or as an effect of the treatment, Faremus changed in physiological direction the CST's homology. Faremus effects on homology were more evident than recruitment changes within the dominant and non-dominant sides., Conclusions: The Faremus-related CST changes extend the relevance of the balance between hemispheric homologs to the homology between body sides. With this work, we contribute to the development of new network-sensitive measures that can provide new insights into the mechanisms of neuronal functional patterning underlying relevant symptoms.

The aim of this study was to investigate the usefulness of radiomics in the absence of well-defined standard guidelines. Specifically, we extracted radiomics features from multicenter computed tomography (CT) images to differentiate between the four histopathological subtypes of non-small-cell lung carcinoma (NSCLC). In addition, the results that varied with the radiomics model were compared. We investigated the presence of the batch effects and the impact of feature harmonization on the models' performance. Moreover, the question on how the training dataset composition influenced the selected feature subsets and, consequently, the model's performance was also investigated. Therefore, through combining data from the two publicly available datasets, this study involves a total of 152 squamous cell carcinoma (SCC), 106 large cell carcinoma (LCC), 150 adenocarcinoma (ADC), and 58 no other specified (NOS). Through the matRadiomics tool, which is an example of Image Biomarker Standardization Initiative (IBSI) compliant software, 1781 radiomics features were extracted from each of the malignant lesions that were identified in CT images. After batch analysis and feature harmonization, which were based on the ComBat tool and were integrated in matRadiomics, the datasets (the harmonized and the non-harmonized) were given as an input to a machine learning modeling pipeline. The following steps were articulated: (i) training-set/test-set splitting (80/20); (ii) a Kruskal-Wallis analysis and LASSO linear regression for the feature selection; (iii) model training; (iv) a model validation and hyperparameter optimization; and (v) model testing. Model optimization consisted of a 5-fold cross-validated Bayesian optimization, repeated ten times (inner loop). The whole pipeline was repeated 10 times (outer loop) with six different machine learning classification algorithms. Moreover, the stability of the feature selection was evaluated. Results showed that the batch effects were present even if the voxels were resampled to an isotropic form and whether feature harmonization correctly removed them, even though the models' performances decreased. Moreover, the results showed that a low accuracy (61.41%) was reached when differentiating between the four subtypes, even though a high average area under curve (AUC) was reached (0.831). Further, a NOS subtype was classified as almost completely correct (true positive rate ~90%). The accuracy increased (77.25%) when only the SCC and ADC subtypes were considered, as well as when a high AUC (0.821) was obtained-although harmonization decreased the accuracy to 58%. Moreover, the features that contributed the most to models' performance were those extracted from wavelet decomposed and Laplacian of Gaussian (LoG) filtered images and they belonged to the texture feature class.. In conclusion, we showed that our multicenter data were affected by batch effects, that they could significantly alter the models' performance, and that feature harmonization correctly removed them. Although wavelet features seemed to be the most informative features, an absolute subset could not be identified since it changed depending on the training/testing splitting. Moreover, performance was influenced by the chosen dataset and by the machine learning methods, which could reach a high accuracy in binary classification tasks, but could underperform in multiclass problems. It is, therefore, essential that the scientific community propose a more systematic radiomics approach, focusing on multicenter studies, with clear and solid guidelines to facilitate the translation of radiomics to clinical practice.

Tissue fibrosis can affect every type of tissue or organ, often leading to organ malfunction; however, the mechanisms involved in this process are not yet clarified. A role has been hypothesized for Human Cytomegalovirus (HCMV) and Human Herpesvirus 6 (HHV-6) infections as triggers of systemic sclerosis (SSc), a severe autoimmune disease causing progressive tissue fibrosis, since both viruses and antiviral immune responses toward them have been detected in patients. Moreover, HCMV or HHV-6A infection was reported to increase the expression of fibrosis-associated transcriptional factors and miRNAs in human dermal fibroblasts. However, it is unlikely that they have separate effects in the infected host, as both viruses are highly prevalent in the human population. Thus, our study aimed to investigate, by quantitative real-time PCR microarray, the impact of HCMV/HHV-6A coinfection on the expression of pro-fibrotic miRNAs in coinfected cells, compared to the effect of single viruses. The results showed a possible synergistic effect of the two viruses on pro-fibrotic miRNA expression, thus suggesting that HCMV and HHV-6 may enhance each other and cooperate at inducing enhanced miRNA-driven fibrosis. These data may also suggest a possible use of virus-induced miRNAs as novel diagnostic or prognostic biomarkers for SSc and its clinical treatment., Competing Interests: The authors declare no conflicts of interest.

Background: Guidelines for degenerative cerebellar ataxia neurorehabilitation suggest intensive coordinative training based on physiotherapeutic exercises. Scientific studies demonstrate virtual exergaming therapeutic value. However, patient-based personalization, post processing analyses and specific audio-visual feedbacks are not provided. This paper presents a wearable motion tracking system with recording and playback features. This system has been specifically designed for ataxic patients, for upper limbs coordination studies with the aim to retrain movement in a neurorehabilitation setting. Suggestions from neurologists and ataxia patients were considered to overcome the shortcomings of virtual systems and implement exergaming., Methods: The system consists of the mixed-reality headset Hololens2 and a proprietary exergaming implemented in Unity. Hololens2 can track and save upper limb parameters, head position and gaze direction in runtime., Results: Data collected from a healthy subject are reported to demonstrate features and outputs of the system., Conclusions: Although further improvements and validations are needed, the system meets the needs of a dynamic patient-based exergaming for patients with cerebellar ataxia. Compared with existing solutions, the mixed-reality system is designed to provide an effective and safe therapeutic exergaming that supports both primary and secondary goals of an exergaming: what a patient should do and how patient actions should be performed.

To assess long-term clinical, radiological, and functional follow-up of patients hospitalized for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia of different grades of severity. Two-hundred-thirty and three patients (Group 1, patients needed invasive mechanical ventilation, n = 69; Group 2, patients needed noninvasive mechanical ventilation, n = 78; Group 3, patients needed <12 L/min of O 2 supply, n = 96) with a postdischarge follow-up >12 months were studied. Follow-up visits, chest computed tomography (CT) scan and pulmonary function tests (diffusing capacity of the lung for carbon monoxide [DLCO], 6-min walking tests [6MWT], spirometry) were done at 3, 6, and 12 months after discharge. Male sex was more frequent in Group 1 (n = 50, 72.5%) compared with Group 2 (n = 49, 62.5%) and Group 3 (n = 44, 51.2%), p = 0.024. Group 2 patients had more comorbidities and higher BMI compared with others. At Month 12, the main reported symptoms were fatigue (mainly in Group 3) and dyspnea; most symptoms resolved during follow-up, except brain fog, memory loss, and anosmia/dysgeusia that, when present at Month 3, usually persisted at Month 12. DLCO and 6MWT normalized at Month 12 in almost all patients. Only nine patients (13%) in Group 1 had a normal chest CT at Month 12, while 20 (29%) had >3 abnormalities, compared with 14 (17.9%) in Group 2 and 11 (11.4%) in Group 3, respectively (p = 0.04). Different clinical symptoms persist up to 12 months in patients hospitalized for SARS-CoV-2 pneumonia. Despite the persistence of abnormalities at chest CT scan after 12 months, an impairment of pulmonary function persists only in a minority of subjects. A longer follow-up is needed to assess the evolution of radiological abnormalities in COVID-19 population., (© 2023 Wiley Periodicals LLC.)

Secretory IgA (sIgA), which may play an important role in the early defense against SARS-CoV-2 infection, were detected in the eye of COVID-19 patients. However, an evaluation of the sIgA response in the tears of vaccinated or non-vaccinated COVID-19 subjects is still lacking. Aimed at characterizing sIgA mucosal immunity in the eye, this study analyzed tear samples from 77 COVID-19 patients, including 63 vaccinated and 14 non-vaccinated subjects. The groups showed similar epidemiological features, but as expected, differences were observed in the percentage of asymptomatic/pauci-symptomatic subjects in the vaccinated vs. non-vaccinated cohort (46% and 29% of the total, respectively). Consistent with this, ocular sIgA values, evaluated by a specific quantitative ELISA assay, were remarkably different in vaccinated vs. non-vaccinated group for both frequency (69.8% vs. 57.1%, respectively) and titer (1372.3 U/mL vs. 143.7 U/mL, respectively; p = 0.01), which was significantly differently elevated depending on the type of administered vaccine. The data show for the first time significant differences of available vaccines to elicit sIgA response in the eye and suggest that quantitative tear-based sIgA tests may potentially serve as a rapid and easily accessible biomarker for the assessment of the development of a protective mucosal immunity toward SARS-CoV-2.

Introduction: Dizziness is a common complaint affecting up to 23% of the world population. Diagnosis is of utmost importance and routinely involves several tests to be performed in specialized centers. The advent of a new generation of technical devices would make envision their use for a valid objective vestibular assessment. Microsoft HoloLens 2 (HL2) mixed reality headset has the potential to be a valuable wearable technology that provides interactive digital stimuli and inertial measurement units (IMUs) to objectively quantify the movements of the user in response to various exercises. The aim of this study was to validate the integration of HoloLens with traditional methods used to analyze the vestibular function in order to obtain precise diagnostic values., Methods: Twenty-six healthy adults completed the Dynamic Gait Index tests both with a traditional evaluation and while wearing HL2 headset, thus allowing to collect kinematic data of the patients' head and eyes. The subjects had to perform 8 different tasks, and the scores were independently assigned by two otolaryngology specialists., Results: The maximum of the mean position of the walking axis of the subjects was found in the second task (-0.14 ± 0.23 m), while the maximum value of the standard deviation of the walking axis was found in the fifth task (-0.12 ± 0.27 m). Overall, positive results were obtained in regard to the validity of the HL2 use to analyze kinematic features., Conclusion: The accurate quantification of gait, movement along the walking axis, and deviation from the normality using HL2 provide an initial evidence for its useful adoption as a valuable tool in gait and mobility assessment., (© 2023 S. Karger AG, Basel.)

This study aimed to validate a sensorized version of a perceptive surface that may be used for the early assessment of misperception of body midline representation in subjects with right stroke, even when they are not yet able to stand in an upright posture. This device, called SuPerSense, allows testing of the load distribution of the body weight on the back in a supine position. The device was tested in 15 patients with stroke, 15 age-matched healthy subjects, and 15 young healthy adults, assessing three parameters analogous to those conventionally extracted by a baropodometric platform in a standing posture. Subjects were hence tested on SuPerSense in a supine position and on a baropodometric platform in an upright posture in two different conditions: with open eyes and with closed eyes. Significant correlations were found between the lengths of the center of pressure path with the two devices in the open-eyes condition (R = 0.44, p = 0.002). The parameters extracted by SuPerSense were significantly different among groups only when patients were divided into those with right versus left brain damage. This last result is conceivably related to the role of the right hemisphere of the brain in the analysis of spatial information.

Color Doppler (CD) imaging is widely used in diagnostics since it allows real-time detection and display of blood flow superimposed on the B-mode image. Nevertheless, to date, a shared worldwide standard on Doppler equipment testing is still lacking. In this context, the study herein proposed would give a contribution focusing on the combination of five test parameters to be included in a novel Quality Assessment (QA) protocol for CD systems testing. A first approach involving the use of the Kiviat diagram was investigated, assuming the diagram area, normalized with respect to one of the gold standards, as an index of the overall Doppler system performance. The QA parameters were obtained from the post-processing of CD data through the implementation of custom-written image analysis methods and procedures, here applied to three brand-new high-technology-level ultrasound systems. Experimental data were collected through phased and convex array probes, in two configuration settings, by means of a Doppler flow phantom set at different flow rate regimes. The outcomes confirmed that the Kiviat diagram might be a promising tool applied to quality controls of Doppler equipment, although further investigations should be performed to assess the sensitivity and specificity of the proposed approach.

Summary: It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Purpose: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography ( 18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL)., Methods: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS)., Results: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUV mean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM&#95;Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM&#95;Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both., Conclusions: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival., (© 2022 Wiley Periodicals LLC.)

It has recently been discovered that during a virtual reality task of painting, if the subjects have the illusion of recreating an artistic masterpiece, they improve their performances and perceive less fatigue compared to simply coloring a virtual canvas. This phenomenon has been called the Michelangelo effect. However, it was unclear if this effect was related to the aesthetic experience of beauty or if it was specific to artistic stimuli. To clarify this point, 26 healthy subjects performed the virtual task of erasing a blank sheet on the canvas, revealing an image that could be a painting or a photo, classified as beautiful or not. Beautiful paintings were famous artistic portraits, non-beautiful paintings were rough reproductions of them. Photos of popular people were matched with paintings according to their similarity for somatic traits, posture, and clothes. Beautiful and non-beautiful photos were classified according to whether the pictured person was famous or not for their beauty. For each stimulus the objective beauty, subjective beauty, and effort to complete the task perceived by the subject were self-assessed on a numerical rating scale, recorded and analyzed. Furthermore, the hand kinematic trajectory was instrumentally recorded and its spatiotemporal parameters were computed. Less fatigue was perceived for the paintings than for the photos (p = .020), but not for beautiful versus non-beautiful stimuli (p = .325). Only in the artistic stimuli, subjective beauty was found to be negatively correlated with perceived fatigue (p = .030) and performed errors (p = .005). The kinematic parameters were found to be affected by the interactions between the gender of the participant and that of the person in the photo. These results supported the idea that the Michelangelo effect was stronger when subjects interacted with artefacts, modulated by the perceived beauty of the artistic stimulus., (© 2022 The Authors. PsyCh Journal published by Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Radiomics aims to support clinical decisions through its workflow, which is divided into: (i) target identification and segmentation, (ii) feature extraction, (iii) feature selection, and (iv) model fitting. Many radiomics tools were developed to fulfill the steps mentioned above. However, to date, users must switch different software to complete the radiomics workflow. To address this issue, we developed a new free and user-friendly radiomics framework, namely matRadiomics, which allows the user: (i) to import and inspect biomedical images, (ii) to identify and segment the target, (iii) to extract the features, (iv) to reduce and select them, and (v) to build a predictive model using machine learning algorithms. As a result, biomedical images can be visualized and segmented and, through the integration of Pyradiomics into matRadiomics, radiomic features can be extracted. These features can be selected using a hybrid descriptive-inferential method, and, consequently, used to train three different classifiers: linear discriminant analysis, k-nearest neighbors, and support vector machines. Model validation is performed using k-fold cross-Validation and k-fold stratified cross-validation. Finally, the performance metrics of each model are shown in the graphical interface of matRadiomics. In this study, we discuss the workflow, architecture, application, future development of matRadiomics, and demonstrate its working principles in a real case study with the aim of establishing a reference standard for the whole radiomics analysis, starting from the image visualization up to the predictive model implementation.

Systemic sclerosis (SSc) is a severe autoimmune disease likely triggered by genetic and environmental factors, including viral infections. Human cytomegalovirus (HCMV) and human herpesvirus 6A species (HHV-6A) have been associated with SSc, based on in vivo and in vitro evidence, but the data are still inconclusive. Furthermore, despite both viruses being highly prevalent in humans and able to exacerbate each other's effects, no data are available on their joint effects. Hence, we aimed to study their simultaneous impact on the expression of cell factors correlated with fibrosis and apoptosis in in vitro coinfected fibroblasts, representing the main target cell type in SSc. The results, obtained by a microarray detecting 84 fibrosis/apoptosis-associated factors, indicated that coinfected cells underwent higher and more sustained expression of fibrosis-associated parameters compared with single-infected cells. Thus, the data, for the first time, suggest that HCMV and HHV-6A may cooperate in inducing alterations potentially leading to cell fibrosis, thus further supporting their joint role in SSc. However, further work is required to definitively answer whether β-herpesviruses are causally linked to the disease and to enable the possible use of targeted antiviral treatments to improve clinical outcomes.

Purpose of the Report: PET with 18F-DOPA can be used to evaluate grading and aggressiveness of pediatric cerebral gliomas. However, standard uptake parameters may underperform in circumscribed lesions and in diffuse pontine gliomas. In this study, we tested whether dynamic 18F-DOPA PET could overcome these limitations., Patients and Methods: Patients with available dynamic 18F-DOPA PET were included retrospectively. Static parameters (tumor/striatum ratio [T/S] and tumor/cortex ratio [T/N]) and dynamic ones, calculated on the tumor time activity curve (TAC), including time-to-peak (TTP), slope steepness, the ratio between tumor and striatum TAC steepness (dynamic slope ratio [DSR]), and TAC shape (accumulation vs plateau), were evaluated as predictors of high/low grading (HG and LG) and of progression-free survival and overall survival., Results: Fifteen patients were included; T/S, T/N, TTP, TAC slope steepness, and DSR were not significantly different between HG and LG. The accumulation TAC shape was more prevalent in the LG than in the HG group (75% vs 27%). On progression-free survival univariate analysis, TAC accumulation shape predicted longer survival (P < 0.001), whereas T/N and DSR showed borderline significance; on multivariate analyses, only TAC shape was retained (P < 0.01, Harrell C index, 0.93-0.95). On overall survival univariate analysis, T/N (P < 0.05), DSR (P < 0.05), and TAC "accumulating" shape predicted survival (P < 0.001); once more, only this last parameter was retained in the multivariate models (P < 0.05, Harrell C index, 0.86-0.89)., Conclusions: Dynamic 18F-DOPA PET analysis outperforms the static parameter evaluation in grading assessment and survival prediction. Evaluation of the curve shape is a simple-to-use parameter with strong predictive power., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aimed at investigating outcome of systemic treatments in advanced breast PT., Methods: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed., Results: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months., Conclusion: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Antimicrobial resistance (AMR) represents a major threat to public health, especially in the hospital environment, and the massive use of disinfectants to prevent COVID-19 transmission might intensify this risk, possibly leading to future AMR pandemics. However, the control of microbial contamination is crucial in hospitals, since hospital microbiomes can cause healthcare-associated infections (HAIs), which are particularly frequent and severe in pediatric wards due to children having high susceptibility., Aim: We have previously reported that probiotic-based sanitation (PCHS) could stably decrease pathogens and their AMR in the hospital environment, reduce associated HAIs in adult hospitals, and inactivate enveloped viruses. Here, we aimed to test the effect of PCHS in the emergency room (ER) of a children's hospital during the COVID-19 pandemic., Methods: Conventional chemical disinfection was replaced by PCHS for 2 months during routine ER sanitation; the level of environmental bioburden was characterized before and at 2, 4, and 9 weeks after the introduction of PCHS. Microbial contamination was monitored simultaneously by conventional culture-based CFU count and molecular assays, including 16S rRNA NGS for bacteriome characterization and microarrays for the assessment of the resistome of the contaminating population. The presence of SARS-CoV-2 was also monitored by PCR., Results and Conclusions: PCHS usage was associated with a stable 80% decrease in surface pathogens compared to levels detected for chemical disinfection ( P < 0.01), accompanied by an up to 2 log decrease in resistance genes ( Pc < 0.01). The effects were reversed when reintroducing chemical disinfection, which counteracted the action of the PCHS. SARS-CoV-2 was not detectable in both the pre-PCHS and PCHS periods. As the control of microbial contamination is a major issue, especially during pandemic emergencies, collected data suggest that PCHS may be successfully used to control virus spread without simultaneous worsening of the AMR concern., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Soffritti et al.)

Background: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge., Methods: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected., Results: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up., Conclusion: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed., (© 2022. The Author(s).)

Background: Nutritional status impacts quality of life and prognosis of patients with respiratory diseases, including idiopathic pulmonary fibrosis (IPF). However, there is a lack of studies performing an extensive nutritional assessment of IPF patients. This study aimed to investigate the nutritional status and to identify nutritional phenotypes in a cohort of IPF patients at diagnosis., Methods: Patients underwent a thorough pulmonary and nutritional evaluation including questionnaires on nutritional status, and physical activity, anthropometry, body impedance, dynamometry, 4-m gait speed and blood tests., Results: 90 IPF patients (78.9% males, mean age 72.7 years) were enrolled. The majority of patients were classified as Gender-Age-Physiology Index stage 2 (47, 52.2%) with an inactive lifestyle according to International Physical Activity Questionnaire score (39, 43.3%), and had mean forced vital capacity and diffusing capacity for carbon monoxide 86.5% and 54.2%, respectively. In regards to nutritional phenotypes, the majority of patients were normally nourished (67.8%, 95% CI 58.6-77.7%), followed by non-sarcopenic obese (25.3%, 95% CI 16.1-35.2%), sarcopenic (4.6%, 95% CI 0.0-14.5%) and sarcopenic obese (2.3%, 95% CI 0.0-12.2%). Among the normally nourished, 49.2% showed early signs of nutritional and physical performance alterations, including body mass index ≥30 kg·m -2 in 4.3%, history of weight loss ≥5% in 11.9%, and reduction of gait speed and hand grip strength in 11.9% and 35.6%, respectively. Low vitamin D values were observed in 56.3% of cases., Conclusions: IPF patients at diagnosis are mainly normally nourished and obese, but early signs of nutritional and physical performance impairment can already be identified at this stage., Competing Interests: Conflict of interest: P. Faverio reports personal fees from Boehringer Ingelheim and grants from Roche, outside the submitted work. Conflict of interest: A. Fumagalli has nothing to disclose. Conflict of interest: S. Conti has nothing to disclose. Conflict of interest: F. Madotto has nothing to disclose. Conflict of interest: F. Bini has nothing to disclose. Conflict of interest: S. Harari reports personal fees from Actelion, Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Mondoni has nothing to disclose. Conflict of interest: T. Oggionni has nothing to disclose. Conflict of interest: E. Barisione reports personal fees from Chiesi Farmaceutici, Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. Conflict of interest: P. Ceruti has nothing to disclose. Conflict of interest: M.C. Papetti has nothing to disclose. Conflict of interest: B.D. Bodini has nothing to disclose. Conflict of interest: A. Caminati reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Valentino has nothing to disclose. Conflict of interest: S. Centanni has nothing to disclose. Conflict of interest: D. Noè has nothing to disclose. Conflict of interest: M. Della Zoppa has nothing to disclose. Conflict of interest: S. Crotti has nothing to disclose. Conflict of interest: M. Grosso reports personal fees from Chiesi Farmaceutici and Johnson & Johnson, outside the submitted work. Conflict of interest: S.G. Sukkar has nothing to disclose. Conflict of interest: D. Modina has nothing to disclose. Conflict of interest: M. Andreoli has nothing to disclose. Conflict of interest: R. Nicali has nothing to disclose. Conflict of interest: G. Suigo has nothing to disclose. Conflict of interest: F. De Giacomi has nothing to disclose. Conflict of interest: S. Busnelli has nothing to disclose. Conflict of interest: E. Cattaneo has nothing to disclose. Conflict of interest: L.G. Mantovani has nothing to disclose. Conflict of interest: G. Cesana has nothing to disclose. Conflict of interest: A. Pesci has nothing to disclose. Conflict of interest: F. Luppi reports lectures fee from Roche and from Boehringer Ingelheim., (Copyright ©The authors 2022.)

The high and sometimes inappropriate use of disinfectants and antibiotics has led to alarming levels of Antimicrobial Resistance (AMR) and to high water and hearth pollution, which today represent major threats for public health. Furthermore, the current SARS-CoV-2 pandemic has deeply influenced our sanitization habits, imposing the massive use of chemical disinfectants potentially exacerbating both concerns. Moreover, super-sanitation can profoundly influence the environmental microbiome, potentially resulting counterproductive when trying to stably eliminate pathogens. Instead, environmentally friendly procedures based on microbiome balance principles, similar to what applied to living organisms, may be more effective, and probiotic-based eco-friendly sanitation has been consistently reported to provide stable reduction of both pathogens and AMR in treated-environments, compared to chemical disinfectants. Here, we summarize the results of the studies performed in healthcare settings, suggesting that such an approach may be applied successfully also to non-healthcare environments, including the domestic ones, based on its effectiveness, safety, and negligible environmental impact.

Background: Desmoid fibromatosis (DF) is a rare and locally infiltrative monoclonal fibroblastic proliferation arising from connective tissues, with lack of metastatic potential. About 10% of all DF cases are intra-abdominally sited. Complications in this site, due to the locally infiltrative nature of the disease, may be severe and potentially life threatening. However, data on incidence, management, and outcome of these complications are limited., Aim: Data of patients with sporadic or FAP-related intra-abdominal DF treated at Istituto Nazionale dei Tumori (INT) in Milano from 2005 to 2020 who developed a serious complication during the course of their disease were retrospectively collected and analyzed with a descriptive statistics., Methods and Results: Out of 72 intra-abdominal DF, 8 cases were identified (M/F: 5/3, median age: 35 years, FAP-related/sporadic: 2/6): 3 with bowel obstruction, 5 with bowel perforation. In 4 cases the serious complication was the first evidence of disease; in the other 4 cases it occurred at a time interval from diagnosis in the range of 4-44 months (during an active surveillance program in one case and during chemotherapy in the other 3 cases). A surgical treatment was feasible and successful in 5 cases. In 3 surgically unmanageable patients, all progressing and experiencing acute complications while on chemotherapy, a non-surgical approach with intensive supportive treatment and with a prompt change of chemotherapy regimen was implemented, being successful in two, the other patient dying due to a concomitant progressive lymphoma thereafter., Conclusion: In this series of intra-abdominal DF, the incidence of serious complications was 11%. Most patients were successfully treated with surgery. When surgery was deemed to be unfeasible, a conservative management with intensive supportive care and a careful choice of chemotherapy was adopted, ensuring a favorable outcome in most., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Total hip replacement with minimally invasive direct anterior approach using the "Smith Petersen" interval is an alternative technique to conventional surgery aimed at preserving the integrity of the muscles around the hip joint. This study aimed to observe hip biomechanics, gait variables, hip muscle activation and locomotor performance during three locomotor tasks (forward, lateral, and backward walking), in subjects who undergo total hip arthroplasty with direct anterior approach., Methods: Fourteen patients with primary osteoarthritis who underwent direct anterior approach were included in the study. The optoelectronic 3-D motion analysis system integrated with an electromyography surface device was used to acquire the biomechanics of patients before surgery and at 3 and 6 months post-surgery. Spatio-temporal, dynamic, and hip muscle electromyographic parameters were analyzed and compared whit those of healthy controls., Findings: Almost all gait parameters improved after surgery. The majority of gait variables neared to the control group at 6 months, while the hip joint range of motion did not. The abnormally increased activation of the muscles around the hip joint was reduced at 6 months post-surgery during all three locomotor tasks. Conversely, the altered gait phase-related electromyographic pattern did not change after the surgery., Interpretation: Our results indicate that hip and gait function during several locomotor tasks improved after surgery, while simultaneously either preserve or restore the muscle activation around the hip joint. A full biomechanical evaluation of the hip function during locomotion may aid physicians and surgeons in optimizing the management of patients before and after hip replacement surgery., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Patients with Parkinson's disease (PD) suffer from postural disorders. This study aims at investigating the short- and medium-term effects of a shirt with appropriate tie-rods that allows to correct the posture of the trunk., Methods: This is a longitudinal clinical study in which a pressure platform was used to assess the static and dynamic baropodometry and the static stabilometry of 20 patients with PD (70.95 ± 8.39 years old; 13 males, time from the onset of symptoms: 6.95 ± 4.04 years, Unified Parkinson's Disease Rating Scale score: UPDRS = 7.25 ± 6.26) without and with a shirt, specifically designed for improving posture, at baseline and after one month of wearing., Results: The results showed a significant improvement in symmetry of loads (p = 0.015) and an enlargement of the foot contact surface (p = 0.038). A significant correlation was found between the change in forefoot load and time spent daily in wearing the shirt (R = 0.575, p = 0.008), with an optimal value identified at 8 h per day., Conclusion: The use of a postural shirt in patients with PD symmetrized the postural load and enlarged the foot contact surface improving their balance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Artificial intelligence (AI) uses mathematical algorithms to perform tasks that require human cognitive abilities. AI-based methodologies, e.g., machine learning and deep learning, as well as the recently developed research field of radiomics have noticeable potential to transform medical diagnostics. AI-based techniques applied to medical imaging allow to detect biological abnormalities, to diagnostic neoplasms or to predict the response to treatment. Nonetheless, the diagnostic accuracy of these methods is still a matter of debate. In this article, we first illustrate the key concepts and workflow characteristics of machine learning, deep learning and radiomics. We outline considerations regarding data input requirements, differences among these methodologies and their limitations. Subsequently, a concise overview is presented regarding the application of AI methods to the evaluation of thyroid images. We developed a critical discussion concerning limits and open challenges that should be addressed before the translation of AI techniques to the broad clinical use. Clarification of the pitfalls of AI-based techniques results crucial in order to ensure the optimal application for each patient.

Purpose: To propose a new objective, video recording method for the classification of unilateral peripheral facial palsy (UPFP) that relies on mathematical algorithms allowing the software to recognize numerical points on the two sides of the face surface that would be indicative of facial nerve impairment without positioning of markers on the face., Methods: Patients with UPFP of different House-Brackmann (HB) degrees ranging from II to V were evaluated after video recording during two selected facial movements (forehead frowning and smiling) using a software trained to recognize the face points as numbers. Numerical parameters in millimeters were obtained as indicative values of the shifting of the face points, of the shift differences of the two face sides and the shifting ratio between the healthy (denominator) and the affected side (numerator), i.e., the asymmetry index for the two movements., Results: For each HB grade, specific asymmetry index ranges were identified with a positive correlation for shift differences and negative correlation for asymmetry indexes., Conclusions: The use of the present objective system enabled the identification of numerical ranges of asymmetry between the healthy and the affected side that were consistent with the outcome from the subjective methods currently in use., (© 2021. The Author(s).)

Bone tissue is composed at the nanoscale of apatite minerals, collagen molecules and water that form the mineralized collagen fibril (MCF). Water has a crucial role in bone biomineralization. We developed a 3D random walk model to investigate the water diffusion process within the MCF for three different scenarios, namely low, intermediate and high mineral volume fraction. The MCF geometric model is obtained after applying 6·10 6 translational and rotational perturbations to an ordered arrangement of mineral. Subsequently, we compute 300 random trajectories of water molecules within the MCF for each mineral volume fraction. Every trajectory is constituted of up to 500 k positions of the water particle. We determined the diffusion coefficient from the linear fit of the mean squared displacement of water molecules as a function of time. We investigate changes in the diffusivity values in relation to variation of bone mineral content. The analysis performed on the random walk data, for all mineralization conditions, leads to diffusion coefficients in good agreement with the diffusivity outcomes achieved from previous experimental studies. Thus, the 3D geometrical configuration adopted in this numerical study appears suitable for modelling the MCF with different volume fractions, from hypo- to hyper-mineralized conditions. We observed that low mineral content is associated with an increase of the water diffusion, while lower values of diffusivity are determined in hypermineralized conditions. In agreement with experimental data, our results highlight the influence of the structural alterations on the mass transport properties., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We aimed to investigate changes in volume and MRI T2-weighted intensity in desmoid-type fibromatosis (DF) receiving methotrexate plus vinca-alkaloids (MTX-VA) at Istituto Nazionale dei Tumori, Milan., Methods: All cases of sporadic DF treated with MTX-VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2-signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables., Results: Thirty-two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2-signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow-up, median T2-signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow-up, a reduction was not observed. High T2-signal intensity at baseline was observed in patients showing RECIST progression during follow-up., Conclusions: In this series, RECIST detected a lower proportion of responses as compared to volumetric and T2-signal changes. T2-signal reduction seemed to better reflect symptomatic improvement. High T2-signal intensity at baseline was related to a higher proportion of further progression., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Bone is a hierarchical biological material, characterized at the nanoscale by a recurring structure mainly composed of apatite mineral and collagen, i.e. the mineralized collagen fibril (MCF). Although the architecture of the MCF was extensively investigated by experimental and computational studies, it still represents a topic of debate. In this work, we developed a 3D continuum model of the mineral phase in the framework of percolation theory, that describes the transition from isolated to spanning cluster of connected platelets. Using Monte Carlo technique, we computed overall 120 × 10 6 iterations and investigated the formation of spanning networks of apatite minerals. We computed the percolation probability for different mineral volume fractions characteristic of human bone tissue. The findings highlight that the percolation threshold occurs at lower volume fractions for spanning clusters in the width direction with respect to the critical mineral volume fractions that characterize the percolation transition in the thickness and length directions. The formation of spanning clusters of minerals represents a condition of instability for the MCF, as it could be the onset of a high susceptibility to fracture. The 3D computational model developed in this study provides new, complementary insights to the experimental investigations concerning human MCF.

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) is an emerging condition with heterogeneous manifestations from both the microbiological and the clinical point of view. Diagnostic and therapeutic guidelines are available but there are still unmet patients' and physicians' needs, including therapy-related adverse events, symptom control, management of comorbidities, risk of re-exposure to the pathogen and unfavourable outcomes. In the present review, we provide currently available evidence for an integrated approach to NTM-PD beyond antibiotic therapy. This includes 1) avoiding exposure to environments where mycobacteria are present and careful evaluation of lifestyle and habits; 2) implementing a personalised pulmonary rehabilitation plan and airway clearance techniques to improve symptoms, exercise capacity, health-related quality of life (QoL) and functional capacity in daily living activities; 3) a nutritional evaluation and intervention to improve health-related QoL and to control gastrointestinal side-effects during antimicrobial therapy, particularly in those with low body mass index and history of weight loss; and 4) managing comorbidities that affect disease outcomes, including structural lung diseases, immune status evaluation and psychological support when appropriate., Competing Interests: Conflict of interest: P. Faverio has nothing to disclose. Conflict of interest: F. De Giacomi has nothing to disclose. Conflict of interest: B.D. Bodini has nothing to disclose. Conflict of interest: A. Stainer has nothing to disclose. Conflict of interest: A. Fumagalli has nothing to disclose. Conflict of interest: F. Bini has nothing to disclose. Conflict of interest: F. Luppi has nothing to disclose. Conflict of interest: S. Aliberti has nothing to disclose., (Copyright ©The authors 2021.)

Purpose: Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution., Methods: A 3D software was used for segmentation of DICOM data of consecutive patients aged 60 years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx's tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses., Results: Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p < 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape., Conclusion: Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum.

Fatigue is a hidden symptom of Multiple Sclerosis (MS) disease that nevertheless impacts severely on patients' everyday life. Evidence indicates the involvement of the sensorimotor network and its inter-nodes communication at the basis of this symptom. Two randomized controlled trials (RCTs) showed that the personalized neuromodulation called Fatigue Relief in Multiple Sclerosis (FaReMuS) efficaciously fights multiple sclerosis (MS) fatigue. By this Proof of Concept study, we tested whether FaReMuS reverts the alteration of the brain-muscular synchronization previously observed occurring with fatigue. The cortico muscular coherence (CMC) was studied in 11 patients before and after FaReMuS, a 5-day tDCS (1.5 mA, 15 min per day) anodal over the whole body's somatosensory representation (S1) via a personalized MRI-based electrode (35 cm 2 ) against the occipital cathode (70 cm 2 ). Before FaReMuS, the CMC was observed at a mean frequency of 31.5 ± 1.6 Hz (gamma-band) and positively correlated with the level of fatigue (p = .027). After FaReMuS, fatigue reduced in average of 28% ± 33% the baseline level, and the CMC frequency reduced to 26.6 ± 1.5 Hz (p = .022), thus forthcoming the physiological beta-band as observed in healthy people. The personalized S1 neuromodulation treatment, ameliorating the central-peripheral communication that subtends simple everyday movements, supports the appropriateness of neuromodulations aiming at increasing the parietal excitability in fighting MS fatigue. The relationship between central-peripheral features and fatigue profile strengthens a central more than peripheral origin of the symptom.