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Disorders of Consciousness (DoC) are clinical conditions following a severe acquired brain injury (ABI) characterized by absent or reduced awareness, known as coma, Vegetative State (VS)/Unresponsive Wakefulness Syndrome (VS/UWS), and Minimally Conscious State (MCS). Misdiagnosis rate between VS/UWS and MCS is attested around 40% due to the clinical and behavioral fluctuations of the patients during bedside consciousness assessments. Given the large body of evidence that some patients with DoC possess “covert” awareness, revealed by neuroimaging and neurophysiological techniques, they are candidates for intervention with brain-computer interfaces (BCIs). The aim of the present work is to describe the characteristics of BCI systems based on electroencephalography (EEG) evaluated in DoC patients, in terms of control signals adopted to control the system, characteristics of the paradigm implemented, classification algorithms and applications and to evaluate the performance of DoC patients with BCI. Among the 527 papers identified with the first run of the search, 27 papers were included in the systematic review. Data extracted from the studies were related to the characteristics of the sample of participants and behavioral assessment, the control signals employed to control the BCI and the classification algorithms, the characteristics of the paradigm, the applications and performance of BCI. The control signals used to control the BCI were: P300 (N=19), P300 and Steady-State Visual Evoked Potentials (SSVEP; hybrid system, N=4), sensorimotor rhythms (SMRs; N=5) and brain rhythms elicited by an emotional task (N=1). The possible applications of BCI with DoC patients were: assessment, communication, prognosis, and rehabilitation. The P300 is the most widespread control signal used to control a BCI and the assessment is the most frequent application. Despite the BCI is a promising tool in the management of DoC patients, supporting diagnosis and prognosis evaluation, results are still preliminary, and no definitive conclusions may be drawn; even though neurophysiological methods, such as BCI, are more sensitive to covert cognition, it is mandatory to adopt a multimodal approach and a repeated assessment strategy.

Our objective was to investigate the capacity to control a P3-based brain-computer interface (BCI) device for communication and its related (temporal) attention processing in a sample of amyotrophic lateral sclerosis (ALS) patients with respect to healthy subjects. The ultimate goal was to corroborate the role of cognitive mechanisms in event-related potential (ERP)-based BCI control in ALS patients. Furthermore, the possible differences in such attentional mechanisms between the two groups were investigated in order to unveil possible alterations associated with the ALS condition. Thirteen ALS patients and 13 healthy volunteers matched for age and years of education underwent a P3-speller BCI task and a rapid serial visual presentation (RSVP) task. The RSVP task was performed by participants in order to screen their temporal pattern of attentional resource allocation, namely: (i) the temporal attentional filtering capacity (scored as T1%); and (ii) the capability to adequately update the attentive filter in the temporal dynamics of the attentional selection (scored as T2%). For the P3-speller BCI task, the online accuracy and information transfer rate (ITR) were obtained. Centroid Latency and Mean Amplitude of N200 and P300 were also obtained. No significant differences emerged between ALS patients and Controls with regards to online accuracy ( = 0.13). Differently, the performance in controlling the P3-speller expressed as ITR values (calculated offline) were compromised in ALS patients ( < 0.05), with a delay in the latency of P3 when processing BCI stimuli as compared with Control group ( < 0.01). Furthermore, the temporal aspect of attentional filtering which was related to BCI control ( = 0.51; < 0.05) and to the P3 wave amplitude ( = 0.63; < 0.05) was also altered in ALS patients ( = 0.01). These findings ground the knowledge required to develop sensible classes of BCI specifically designed by taking into account the influence of the cognitive characteristics of the possible candidates in need of a BCI system for communication.

The purpose of this study was to investigate the support of attentional and memory processes in controlling a P300-based brain-computer interface (BCI) in people with amyotrophic lateral sclerosis (ALS). Eight people with ALS performed two behavioral tasks: (i) a rapid serial visual presentation (RSVP) task, screening the temporal filtering capacity and the speed of the update of the attentive filter, and (ii) a change detection task, screening the memory capacity and the spatial filtering capacity. The participants were also asked to perform a P300-based BCI spelling task. By using correlation and regression analyses, we found that only the temporal filtering capacity in the RSVP task was a predictor of both the P300-based BCI accuracy and of the amplitude of the P300 elicited performing the BCI task. We concluded that the ability to keep the attentional filter active during the selection of a target influences performance in BCI control.

Motor disability and/or ageing can prevent individuals from fully enjoying home facilities, thus worsening their quality of life. Advance s in the field of accessible user interfaces for domotic appliances can represent a valuable way to improve the independence of these persons. An asynchronous P300-based Brain-Computer Interface (BCI) system was recently validated with the participation of healthy young volunteers for environmental control. In this study, the asynchronous P300-based BCI for the interaction with a virtual home environment was tested with the participation of potential end-users (clients of a Frisian home care organization) with limited autonomy due to ageing and/or motor disabilities. System testing revealed that the minimum number of stimulation sequences needed to achieve correct classification had a higher intra-subject variability in potential end-users with respect to what was previously observed in young controls. Here we show that the asynchronous modality performed significantly better as compared to the synchronous mode in continuously adapting its speed to the users' state. Furthermore, the asynchronous system modality confirmed its reliability in avoiding misclassifications and false positives, as previously shown in young healthy subjects. The asynchronous modality may contribute to filling the usability gap between BCI systems and traditional input devices, representing an important step towards their use in the activities of daily living.

A Brain-Computer Interface (BCI) provides a completely new output pathway that can provide an additional option for a person to express himself/her self if he/she suffers a disorder like amyotrophic lateral sclerosis (ALS), brainstem stroke, brain or spinal cord injury or other diseases which impair the function of the common output pathways which are responsible for the control of muscles. For a P300 based BCI a matrix of randomly flashing characters is presented to the participant. To spell a character the person has to attend to it and to count how many times the character flashes. Although most BCIs are designed to help people with disabilities, they are mainly tested on healthy, young subjects who may achieve better results than people with impairments. In this study we compare measurements, performed on people suffering motor impairments, such as stroke or ALS, to measurements performed on healthy people. The overall accuracy of the persons with motor impairments reached 70.1% in comparison to 91% obtained for the group of healthy subjects. When looking at single subjects, one interesting example shows that under certain circumstances, when it is difficult for a patient to concentrate on one character for a longer period of time, the accuracy is higher when fewer flashes (i.e., stimuli) are presented. Furthermore, the influence of several tuning parameters is discussed as it shows that for some participants adaptations for achieving valuable spelling results are required. Finally, exclusion criteria for people who are not able to use the device are defined.

Abiotic stresses can cause a substantial decline in fruit quality due to negative impacts on plant growth, physiology and reproduction. The objective of this study was to verify if the use of a biostimulant based on plant and yeast extracts, rich in amino acids and that contains microelements (boron, zinc and manganese) can ensure good crop yield and quality in tomato plants grown at elevated temperatures (up to 42 °C). We investigated physiological responses of four different tomato landraces that were cultivated under plastic tunnel and treated with the biostimulant CycoFlow. The application of the biostimulant stimulated growth (plants up to 48.5% taller) and number of fruits (up to 105.3%). In plants treated with the biostimulant, antioxidants contents were higher compared to non-treated plants, both in leaves and in fruits. In particular, the content of ascorbic acid increased after treatments with CycoFlow. For almost all the traits studied, the effect of the biostimulant depended on the genotype it was applied on. Altogether, the use of the biostimulant on tomato plants led to better plant performances at elevated temperatures, that could be attributed also to a stronger antioxidant defence system, and to a better fruit nutritional quality.

Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

In order to foster electric vehicle (EV) adoption rates, the availability of a pervasive and efficient charging network is a crucial requirement. In this paper, we provide a decision support tool for helping policymakers to locate and size EV charging stations. We consider a multi-year planning horizon, taking into account different charging technologies and different time periods (day and night). Accounting for these features, we propose an optimization model that minimizes total investment costs while ensuring a predetermined adequate level of demand coverage. In particular, the setup of charging stations is optimized every year, allowing for an increase in the number of chargers installed at charging stations set up in previous years. We have developed a tailored heuristic algorithm for the resulting problem. We validated our algorithm using case study instances based on the village of Gardone Val Trompia (Italy), the city of Barcelona (Spain), and the country of Luxembourg. Despite the variability in the sizes of the considered instances, our algorithm consistently provided high-quality results in short computational times, when compared to a commercial MILP solver. Produced solutions achieved optimality gaps within 7.5% in less than 90 s, often achieving computational times of less than 5 s.

Background The optimal treatment approach for hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2-negative MBC) with aggressive characteristics remains controversial, with lack of randomized trials comparing cyclin-dependent kinase (CDK)4/6-inhibitors (CDK4/6i) + endocrine therapy (ET) with chemotherapy + ET. Materials and methods We conducted an open-label randomized phase II trial (NCT03227328) to investigate whether chemotherapy + ET is superior to CDK4/6i + ET for HR+/HER2-negative MBC with aggressive features. PAM50 intrinsic subtypes (IS), immunological features, and gene expression were assessed on baseline samples. Results Among 49 randomized patients (median follow-up: 35.2 months), median progression-free survival (mPFS) with chemotherapy + ET (11.2 months, 95% confidence interval [CI]: 7.7-15.4) was numerically shorter than mPFS (19.9 months, 95% CI: 9.0-30.6) with CDK4/6i + ET (hazard ratio: 1.41, 95% CI: 0.75-2.64). Basal-like tumors under CDK4/6i + ET exhibited worse PFS (mPFS: 11.4 months, 95% CI: 3.00-not reached [NR]) and overall survival (OS; mOS: 18.8 months, 95% CI: 18.8-NR) compared to other subtypes (mPFS: 20.7 months, 95% CI: 9.00-33.4; mOS: NR, 95% CI: 24.4-NR). In the chemotherapy arm, luminal A tumors showed poorer PFS (mPFS: 5.1 months, 95% CI: 2.7-NR) than other IS (mPFS: 13.2 months, 95% CI: 10.6-28.1). Genes/pathways involved in BC cell survival and proliferation were associated with worse outcomes, as opposite to most immune-related genes/signatures, especially in the CDK4/6i arm. CD24 was the only gene significantly associated with worse PFS in both arms. Tertiary lymphoid structures and higher tumor-infiltrating lymphocytes also showed favorable survival trends in the CDK4/6i arm. Conclusions The KENDO trial, although closed prematurely, adds further evidence supporting CDK4/6i + ET use in aggressive HR+/HER2-negative MBC instead of chemotherapy. PAM50 IS, genomic, and immunological features are promising biomarkers to personalize therapeutic choices. Optimal upfront treatment for HR+/HER2− metastatic breast cancer with aggressive characteristics remains controversial. Results of the KENDO randomized trial add to evidence supporting CDK4/6-inhibitors plus endocrine therapy instead of chemotherapy.

Objectives: Low tidal volume ventilation (LTVV) is a ventilatory strategy with the advantages of minimizing diaphragm movements and reducing hypercapnia and barotrauma risks. This preliminary study aims to report on the safety and effectiveness of LTVV applied during percutaneous US-guided liver ablations of focal malignancies. Methods: Patients affected by focal liver malignancies treated with percutaneous microwaves ablation were retrospectively included in this single-center analysis. Arterial gas analysis was performed immediately before and after ablation to evaluate the arterial pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), and plasma lactate levels. The primary endpoint of this study was to evaluate the safety and efficacy of LTVV during percutaneous liver cancer ablation. The secondary endpoint was to assess the procedural technical success in terms of correct needle probe targeting without the need for repositioning. Results: Ten patients affected by a single liver lesion had been analyzed. The ASA score was three in all patients, with three patients also suffering from COPD. The procedural technical success was 100%: ablations were performed with a single liver puncture without the need for changing access or repositioning the needle. No variations in post-ablation arterial gas analysis requiring anesthesiological management remodulation occurred. Lactate levels remained stable and hemodynamic balance was preserved during all procedures. No switch to standard volume ventilation was required. Conclusions: In this preliminary study, LTVV was a safe and effective anesthesiological protocol in patients treated with percutaneous ablations of liver malignancies, offering an ideal balance between patient safety and percutaneous needle probe positioning precision. Larger prospective studies are needed to confirm these findings.