Computational rehabilitation of neglect:Using state-space models to understand the recovery mechanisms

Unilateral spatial neglect is a neuropsychological syndrome often observed in right hemisphere stroke patients. The symptoms differ from subject to subject. A few rehabilitation approaches, e.g. prism adaptation, have demonstrated some effect in reducing the symptoms, but the underlying mechanisms are still largely unclear. Recently, neural models have been proposed to qualitatively describe cortical lesions, the resulting neglect symptoms and the effects of treatment. However, these predictions are qualitative and cannot be used to compare different hypotheses or to interpret symptoms at individual subjects level. Here we propose a computational model of the trial-by-trial dynamics of training-induced recovery from neglect. Neglect is modelled in terms of an impaired internal representation of visual stimuli in the left hemispace. The model assumes that recovery is driven by the mismatch between defective representations of visual stimuli and the corresponding hand positions. The model reproduces the main observations of prism adaptation experiments. Using standard system identification techniques, we fitted the model to data from a rehabilitation trial based on a novel rehabilitation approach based on virtual reality, involving reaching movements within an adaptive environment. Our results suggest that the model can be used to interpret data from individual subjects and to formulate testable hypotheses on the mechanisms of recovery and directions for treatment

Learning bio-inspired head-centric representations of 3D shapes in an active fixation setting

When exploring the surrounding environment with the eyes, humans and primates need to interpret three-dimensional (3D) shapes in a fast and invariant way, exploiting a highly variant and gaze-dependent visual information. Since they have front-facing eyes, binocular disparity is a prominent cue for depth perception. Specifically, it serves as computational substrate for two ground mechanisms of binocular active vision: stereopsis and binocular coordination. To this aim, disparity information, which is expressed in a retinotopic reference frame, is combined along the visual cortical pathways with gaze information and transformed in a head-centric reference frame. Despite the importance of this mechanism, the underlying neural substrates still remain widely unknown. In this work, we investigate the capabilities of the human visual system to interpret the 3D scene exploiting disparity and gaze information. In a psychophysical experiment, human subjects were asked to judge the depth orientation of a planar surface either while fixating a target point or while freely exploring the surface. Moreover, we used the same stimuli to train a recurrent neural network to exploit the responses of a modelled population of cortical (V1) cells to interpret the 3D scene layout. The results for both human performance and from the model network show that integrating disparity information across gaze directions is crucial for a reliable and invariant interpretation of the 3D geometry of the scene

Lung cancer stage distribution from before COVID-19 through 18 months of the pandemic: the experience of a large-volume oncological referral centre

We observed a significant decrease in early-stage cases at our national oncological referral centre for thoracic surgery and lung cancer screening. This cannot plausibly be ascribed to a lower lung cancer incidence. On the other end, the impact of lockdown measures on the reduction of early-stage lung cancer and other malignancies diagnoses should be investigated and addressed. People's fear of hospitals resulted in a diagnostic delay, whose most severe effects occurred in the first months of 2022. The COVID-19 pandemic has accelerated the need for a digital revolution in health car

A Modular BLE-Based Body Area Network Embedded into a Smart Garment for Rescuers Real-Time Monitoring in Emergency Scenarios

In this work, we present a prototype of a smart technical underwear for first responders involved in searchand-rescue operations, to be worn under the rescuer’s professional uniform. Polymer-based electrodes able to detect ECG and EMG signals, and organic transistor for joint angles estimation are embedded into the smart garment. The technical underwear implements a body sensor network of BLE nodes able to acquire, process in real-time and transmit electrophysiological and biomechanical data from the sensors to a custom Android app on the rescuer’s smartphone. The app geolocates the data by using the information of the GPS integrated into the smartphone and sends them to the control center for remote monitoring. The system features high modularity, as the rescuer can adopt a subset of sensors depending on the specific operative context, without any app configuration

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs

Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis

BackgroundJCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer.MethodsWe reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size <20 mm; wedge resections or lobectomies with or without lymph node dissection; NSCLC as the only primary tumor during the follow-up period. We excluded: multiple invasive lung cancer; positive resection margin; preoperative evidence of nodal disease; distant metastasis at presentation; follow-up time <5 years. The reverse Kaplan – Meier method estimated the median OS and PFS and compared them by the log-rank test. The stratified backward stepwise Cox regression model was employed for multivariable survival analyses.Results539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 – 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23).ConclusionsLobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection

Trafficking and intracellular processing of exogenous and endogenous proteins: VacA toxin from Helicobacter pylori as a tool

INTRODUCTION Eukaryotic cells are complex systems, which require a continuous flow of communication and material exchange between the intracellular and extracellular environments. The importance of a precise and fine-tuned cellular organization is demonstrated by the development of intracellular aggregates, such Particle-rich Cytoplasmic Structure (PaCS), as a result of altered trafficking or the failure of the degradation quality system to manage misfolded proteins. PaCSs were firstly identified in Helicobacter pylori (Hp) infected human superficial gastric epithelium and are present in a variety of cultured cell lines and ex vivo tissue. Inside PaCSs, it was found out the presence of Vacuolation toxin A (VacA), which has been recognized to be the key of the bacterium's ability to adapt in a hostile environment. VacA is a multifunctional toxin, with a similar structure and cleavage to the AB family of bacterial toxins. Intracellularly VacA can promote the formation of large vacuoles, arising from late endosome, but can alter also mitochondria functioning and intracellular calcium signaling, suggesting that the toxin could achieved the Endoplasmic Reticulum (ER). AIM The aims of this work are: to deeply characterize aggregates such as PaCSs, Lafora Bodies (LBs), Justanuclear Quality Control (JUNQ) and Insoluble Protein Deposit (IPOD) in order to investigate their nature and development; to elucidate the effect of trafficking inhibitor on VacA-induced vacuolization; to investigate VacA trafficking at different time. RESULTS Our results demonstrated that these aggregates are different inclusions, even if they share some similarities either structural or cytochemical. We observed that PaCSs and LBs are glycogen and laforin positive. A comprehensive analysis of JUNQ and IPOD showed that these aggregates have different ultrastructure from PaCSs and that they are mutually exclusive. Considering that inside PaCSs, VacA is accumulated together with polyubiquitin proteins and proteasome components, we evaluate if the toxin is ubiquitinated inside cells. Using histidine-tagged ubiquitin and metal affinity purification, we found out two bands, which might represent ubiquitinated VacA. We next analyzed the effect of eight different trafficking inhibitors, among which, EGA virtually abolish VacA-induced vacuolization. EGA effects was achieved also when vacuolization was already promoted, but it did not prevent toxin binding or internalization process. Binding-on-ice results support the idea that VacA can exploit the retrograde movement to reach ER. A preincubation time with EGA showed that the inhibitor can relocated the toxin to other organelles. CONCLUSION We demonstrated that PaCSs are unique aggregates and that VacA could be ubiquitinated inside cytoplasm. Our VacA ubiquitination and trafficking results supports the idea that the toxin could escape ER, reach the cytoplasm, ubiquitinated and later accumulated inside PaCSs. This approach could be a cell’s tool to prevent VacA cytotoxic effect and promote degradation, making vacuoles only an intermediate step of toxin trafficking. Moreover, we found out that EGA, a newly inhibitor with a powerful effect on several toxins, virtually abolished the toxin activity in all experiments. Its effects, associated to a low toxicity in mouse model, make it look like a potent inhibitor and interesting tool to develop therapeutic strategy against bacterial toxins

The Electronic Nose’s Emerging Role in Respiratory Medicine

New interest has grown in the respiratory disorder diagnosis and monitoring, throughout electronic nose technologies. This technology has several advantages compared to classic approach. In this short letter, we aim to emphasize electronic nose role in respiratory medicine

Biomarkers in Early Diagnosis and Early Stage Lung Cancer: The Clinician’s Point of View

Starting from the work of Ulivi and colleagues, we aim to summarize the research area of biomarkers for early diagnosis and early stage lung cancer