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Abstract The i-DREAMS project focuses on establishing a framework known as the ‘Safety Tolerance Zone (STZ)’ to ensure drivers operate within safe boundaries. This study compares Long-Short-Term-Memory Networks and shallow Neural Networks to assess participants’ safety levels during i-DREAMS on-road trials. Thirty German drivers’ trips and Forty-Three Belgian drivers were analyzed using these methods, revealing factors contributing to risky behavior. Results indicate i-DREAMS interventions significantly enhance driving behavior, with Neural Networks displaying superior performance among the algorithms considered.

Causative verbs in the Albanian variety of Arbëresh take a finite complement clause, with the causee realized as a nominative or as an oblique (like the dative/instrumental causee in Italian). We argue that causatives are biclausal and that their complement is non-phasal, of different sizes (e.g., vP in Italian and IP/CP in Arbëresh). Being non-phasal, it is transparent to φ-Agree with the matrix v*. The non-phasal vP-complement in Italian triggers an ergative alignment, with the causee realized as an oblique in transitives (or accusative with intransitives/unaccusatives). This option is also available in Arbëresh under contact with Italian, although with a finite complement. The option of a nominative causee in Arbëresh is directly accounted for as φ-Agree with the embedded I. Standard Albanian (and Greek) have an accusative causee, as in English. Given that the embedded I is finite in Albanian, φ-Agree with matrix v* is an instance of hyper-raising. We argue that this option is linked to the null-subject property of Albanian. Finite I is ‘strong enough’ to label by itself (Chomsky 2015), freeing the DP to enter Agree with a higher φ-probe.

Mitochondrial genomes (mtDNA) encode essential subunits of the mitochondrial respiratory chain. Mutations in mtDNA can cause a shortage in cellular energy supply, which can lead to numerous mitochondrial diseases. How cells secure mtDNA integrity over generations has remained unanswered. Here, we show that the single-celled yeast Saccharomyces cerevisiae can intracellularly distinguish between functional and defective mtDNA and promote generation of daughter cells with increasingly healthy mtDNA content. Purifying selection for functional mtDNA occurs in a continuous mitochondrial network and does not require mitochondrial fission but necessitates stable mitochondrial subdomains that depend on intact cristae morphology. Our findings support a model in which cristae-dependent proximity between mtDNA and the proteins it encodes creates a spatial “sphere of influence,” which links a lack of functional fitness to clearance of defective mtDNA.

From the socio-economic and political crisis in southern Europe during the last few decades, to the more recent global healthcare crisis created by the COVID-19 pandemic, contemporary societies have faced and are still under the impact of considerable sociocultural change [...]

This paper revisits c- and s-selection in the context of wh-clausal complements. The standard treatment of predicate-complement selection can be traced back to generative approaches of 70’s and says that the selection of a complement by a predicate is evaluated both in syntax and semantics. As regards syntax, the grammatical category of the complement must belong to the subcategorization frame of the predicate, and vis-à-vis semantics, the semantic type of the complement must fall in the set of types selected by the predicate. The present paper examines several licit instances of wh-clausal selection that should have been ungrammatical under the standard treatment, but they are not. The analysis offered here says that c-selection reduces to argument selection and is computed derivationally (at the point of External Merge), while s-selection reduces to an interpretation function that spans a larger grammatical domain and is evaluated representationally (at the syntax-semantics interface).

Shipping is a pivotal industry not only for transportation, but for the global economy. In today's globalized world, most goods are being transported by ships. However, the high utilization of maritime transport entails a negative environmental footprint. This challenge has brought greening and decarbonization at the forefront of research in the maritime literature. Despite the efforts of policy makers and relevant stakeholders, the most effective pathway to sustainability remains unclear. The pandemic has created additional complexities, making the achievement of sustainability goals even more challenging. Through a structured literature review, the aim of this study is to present the main avenues of sustainable shipping within a typology of clean fuel and clean propulsion systems. The analysis provides an assessment of the drawbacks and benefits of new solutions that may be implemented toward a greener post COVID-19 maritime industry.

The i-DREAMS project established a ‘Safety Tolerance Zone (STZ)’ to maintain operators within safe boundaries through real-time and post-trip interventions, based on the crucial role of the human element in driving behavior. This paper aims to model the inter-relationship among driving task complexity, operator and vehicle coping capacity, and crash risk. Towards that aim, data from 80 drivers, who participated in a naturalistic driving experiment carried out in three countries (i.e., Belgium, Germany, and Portugal), resulting in a dataset of approximately 19,000 trips were collected and analyzed. The exploratory analysis included the development of Generalized Linear Models (GLMs) and the choice of the most appropriate variables associated with the latent variables “task complexity” and “coping capacity” that are to be estimated from the various indicators. In addition, Structural Equation Models (SEMs) were used to explore how the model variables were interrelated, allowing for both direct and indirect relationships to be modeled. Comparisons on the performance of such models, as well as a discussion on behaviors and driving patterns across different countries and transport modes, were also provided. The findings revealed a positive relationship between task complexity and coping capacity, indicating that as the difficulty of the driving task increased, the driver’s coping capacity increased accordingly, (i.e., higher ability to manage and adapt to the challenges posed by more complex tasks). The integrated treatment of task complexity, coping capacity, and risk can improve the behavior and safety of all travelers, through the unobtrusive and seamless monitoring of behavior. Thus, authorities should utilize a data system oriented towards collecting key driving insights on population level to plan mobility and safety interventions, develop incentives for road users, optimize enforcement, and enhance community building for safe traveling.

Background: tixagevimab/cilgavimab, distributed under the name “Evusheld”, was the first available pre-exposure prophylaxis for COVID-19 other than vaccination. It received an EUA from the FDA after sufficient trial data showed efficacy in preventing SARS-CoV-2 infections and subsequent severe disease. Its potential benefits for high-risk immunocompromised patients generated a lot of interest. Individuals with multiple myeloma fall into this category, as they are characterized by attenuated immune responses and, in some cases, vaccines have limited efficacy. Methods: this single-center, prospective study included consecutive patients with multiple myeloma. All individuals were considered high-risk for COVID-19 due to their underlying disease. Baseline demographic and clinical characteristics, as well as data regarding COVID-19 infection and antibodies, were collected. Patients were administered two intramuscular 150 mg doses of Evusheld and were monitored during the follow-up period. Results: one hundred and eleven multiple myeloma patients were included in this analysis, with a median age of 64 years (range 58–69) and fifty-three were females (47.7%). Fourteen patients (12.6%) had a prior history of COVID-19 and all patients were vaccinated with either three or four doses of mRNA-based vaccines. An increase was observed in the median neutralizing-antibody levels before and after tixagevimab/cilgavimab administration, from 92.6% to 97.3%. The high levels were sustainable, with a median neutralizing-antibody level of 95.4% at 3 months post Evusheld administration. Overall, nine patients (8.1%) were diagnosed with COVID-19 during the follow-up period, at a median of 31 days. There were no SARS-CoV-2- infection-related hospitalizations or deaths. The monoclonal antibody combination was well tolerated, with no infusion-related reactions or major adverse events, and pain at the injection site only was reported by 33 patients (30%). Conclusions: tixagevimab/cilgavimab (Evusheld) seemed beneficial for patients with multiple myeloma, who presented high neutralizing-antibody levels and a low incidence of COVID-19 during the initial Omicron wave. No new safety concerns emerged. However, novel combinations of monoclonal antibodies against the new circulating variants of SARS-CoV-2 are deemed necessary in view of the emergence of immune tolerance.

B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM). The aim of this study was to assess the effectiveness and tolerability of monotherapy with the conjugated anti-BCMA monoclonal antibody belantamab mafodotin in triple-class refractory patients with MM in real-world practice. Patients refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 monoclonal antibody received belantamab mafodotin at 2.5 mg/kg intravenously every 3 weeks. Overall, 27 patients with a median age of 65 years (range 41–81) were included. Of these, 52% were male and the median number of prior lines of treatment was 5 (4–10). The overall response rate (partial response or better) was 52%, whereas the disease control rate (stable disease or better) was 70%. The median progression-free survival (PFS) was 2 months (95%CI: 0–7), whereas the median PFS among the responders was 12 months (95%CI: 6–18). Regarding the toxicity profile, the most common toxicity was eye toxicity, in 44% of the patients. Keratopathy grade 2–3 was reported in 33.3% of the patients. In conclusion, belantamab mafodotin showed a safety and efficacy profile consistent with the results of the registrational study. Importantly, heavily pretreated patients who responded to treatment derived a substantial survival benefit.

Abstract Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM (n = 213), SMM (n = 38), and MGUS (n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (p

BackgroundOver the past few years, technological innovations have been increasingly employed to augment the rehabilitation of stroke patients. Virtual reality (VR) has gained attention through its ability to deliver a customized training session and to increase patients’ engagement. Virtual reality rehabilitation programs allow the patient to perform a therapeutic program tailored to his/her needs while interacting with a computer-simulated environment.PurposeThis study aims to investigate the effectiveness of a fully immersive rehabilitation program using a commercially available head-mounted display in stroke patients.MethodsA systematic search was conducted in three databases, namely, PubMed, Google Scholar, and PEDro. Four hundred thirty-two references were identified. The keywords used for the literature search were in English, which are given as follows: immersive, virtual reality, neurorehabilitation, stroke, and head-mounted display. Additionally, applicable articles were identified through screening reference lists of relevant articles.ResultsOnly 12 studies used head-mounted display for immersing the patient into the virtual world. Apart from the feasibility of this new technology, a range of benefits were identified, especially in terms of functional ability as measured by FIM or Barthel, the Action Research arm Test, Box and Block Test, Fugl-Meyer assessment of physical performance, strength, and balance outcomes.ConclusionThe results from this review support the potential beneficial effect of fully immersive virtual reality in the rehabilitation of stroke patients, maximizing recovery through increased motivation and adherence.

The annotation of animated motion-captured segments is a challenging, interdisciplinary task, especially when it comes to characterizing movement qualitatively. The lack of intuitive, easy-to-learn-and-use frameworks is considered to be one of the biggest challenges in this process; another is the lack of approaches able to motivate a wide audience of users, from the broader public to dance experts, researchers and performers, to contribute with annotations. In this paper we present Motion Hollow, a story-driven playful experience that uses metaphors based on Laban Movement Analysis, an established framework for movement analysis and annotation, to familiarize novice users with the process of qualitative characterization of dance moves. This work proposes a first step into introducing movement annotation to non-expert users, and as such, its main goal is to explore the implications and potential of such an approach. The evaluation of the experience confirms its potential to transform the annotation of dance movement segments into an engaging and enjoyable experience as well as to foster a deeper understanding of movement annotation both as a concept and process.

Background: Thrombocytopenia is a common feature of myelofibrosis (MF), a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded MF patients with low platelet counts (

Social interaction has been recognized as positively affecting learning, with dialogue–as a common form of social interaction–comprising an integral part of collaborative learning. Interactive storytelling is defined as a branching narrative in which users can experience different story lines with alternative endings, depending on the choices they make at various decision points of the story plot. In this research, we aim to harness the power of dialogic practices by incorporating dialogic activities in the decision points of interactive digital storytelling experiences set in a history education context. Our objective is to explore interactive storytelling as a collaborative learning experience for remote learners, as well as its effect on promoting historical empathy. As a preliminary validation of this concept, we recorded the perspective of 14 educators, who supported the value of the specific conceptual design. Then, we recruited 15 adolescents who participated in our main study in 6 groups. They were called to experience collaboratively an interactive storytelling experience set in the Athens Ancient Agora (Market) wherein we used the story decision/branching points as incentives for dialogue. Our results suggest that this experience design can indeed support small groups of remote users, in-line with special circumstances like those of the COVID-19 pandemic, and confirm the efficacy of the approach to establish engagement and promote affect and reflection on historical content. Our contribution thus lies in proposing and validating the application of interactive digital storytelling as a dialogue-based collaborative learning experience for the education of history.

COVID-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (MM) compared with healthy individuals, whereas the SARS-CoV-2-specific immunity fades over time. The purpose of this study was to explore the kinetics of SARS-CoV-2 neutralizing antibodies (NAbs) in patients with MM after vaccination with the BNT162b2 mRNA vaccine, focusing on their response before (B4D) and at 1 month after the fourth vaccination (M1P4D). Overall, 201 patients with a median age of 67 years were included, whereas 114 (56.7%) were men. The median NAbs levels B4D were 80.0% (±3.5%) and at M1P4D they increased to a median value of 96.1% (±3.7%). The NAb values at M1P4D were similar to those at 1 month post the third dose and superior to all previous timepoints. At M1P4D, the NAbs levels of all the treatment groups increased, apart from the anti-BCMA group. A significant increase in median NAbs values was observed for those receiving CD38-based treatment (n = 43, from 71.0% B4D to 96.0% at M1P4D) and those who did not receive CD38- or BCMA-targeted therapy (n = 137, from 89.6% B4D to 96.3% at M1P4D). Regarding the patients under BCMA-based therapy (n = 21), there was no remarkable increase in NAbs values following the second booster shot (from 3.0% B4D to 4.0% at M1P4D). In conclusion, booster vaccination with the BNT162b2 results in a substantially improved humoral response against SARS-CoV-2 in patients with MM. Anti-BCMA treatment remains an adverse predictive factor for NAbs response; thus, tailored prevention measures should be considered for this patient subgroup.

Motorways are typically the safest road environment in terms of injury crashes per million vehicle kilometres; however, given the high severity of crashes occurring therein, there is still space for road safety improvements. The objective of this study is to compare the classification performance of five machine learning techniques for predictions of crash risk levels of motorway segments. To that end, data on crash risk levels, driving behaviour metrics, and road geometry characteristics of 668 motorway segments were exploited. The utilized dataset was divided into training and test subsets, with a proportion of 75% and 25%, respectively. The training subset was used to train the models, whereas the test subset was used for the evaluation of their performance. The response variable of the models was the crash risk level of the considered motorway segments, while the predictors were various road design characteristics and naturalistic driving behaviour metrics. The techniques considered were Logistic Regression, Decision Tree, Random Forest, Support Vector Machine, and K-Nearest Neighbours. Among the five techniques, the Random Forest model achieved the best classification performance (overall accuracy: 89.3%, macro-averaged precision: 89.0%, macro-averaged recall: 88.4%, macro-averaged F1 score: 88.6%). Moreover, the Shapley additive explanations were calculated in order to assist with the interpretation of the model’s outcomes. The findings of this study are particularly useful as the Random Forest model could be used as a highly promising proactive road safety tool for identifying potentially hazardous motorway segments.

Over the past decades, 360-degree virtual tours have been used to provide the public access to accurate representations of cultural heritage sites and museums. The COVID-19 pandemic has contributed to a rise in the popularity of virtual tours as a means of engaging with locations remotely and has raised an interesting question: How could we use such experiences to bring the public closer to locations that are otherwise unreachable in real life or not considered to be tourist destinations? In this study, we examine the effectiveness of promoting engagement with a city through the virtual presentation of unknown and possibly also inaccessible points of interest through a 360-degree panoramic virtual tour. The evaluation of the experience with 31 users through an online questionnaire confirms its potential to spark curiosity, promote engagement, foster reflection, and motivate users to explore the location and its attractions at their leisure, thus enabling them to experience it from their personal point of view. The outcomes highlight the need for further research to explore this potential and identify best practices for virtual experience design.

In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates due to the concomitant disease- and treatment-related immunosuppression. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and the ritonavir-boosted nirmatrelvir. This prospective study investigated the effect of these two agents on SARS-CoV-2 infection severity and mortality in patients with MM. Patients received either ritonavir-nirmatrelvir or molnupiravir. Baseline demographic and clinical characteristics, as well as levels of neutralizing antibodies (NAbs), were compared. A total of 139 patients was treated with ritonavir-nirmatrelvir while the remaining 30 patients were treated with molnupiravir. In total, 149 patients (88.2%) had a mild infection, 15 (8.9%) had a moderate infection, and five (3%) had severe COVID-19. No differences in the severity of COVID-19-related outcomes were observed between the two antivirals. Patients with severe disease had lower neutralizing antibody levels before the COVID-19 infection compared to patients with mild disease (p = 0.04). Regarding treatment, it was observed that patients receiving belantamab mafodotin had a higher risk of severe COVID-19 (p < 0.001) in the univariate analysis. In conclusion, ritonavir-nirmatrelvir and molnupiravirmay prevent severe disease in MM patients with SARS-CoV-2 infection. This prospective study indicated the comparable effects of the two treatment options, providing an insight for further research in preventing severe COVID-19 in patients with hematologic malignancies.

Poly(lactic acid) (PLA) is considered the most promising biobased substitute for fossil-derived polymers due to its compostability, biocompatibility, renewability, and good thermomechanical properties. However, PLA suffers from several shortcomings, such as low heat distortion temperature, thermal resistance, and rate of crystallization, whereas some other specific properties, i.e., flame retardancy, anti-UV, antibacterial or barrier properties, antistatic to conductive electrical characteristics, etc., are required by different end-use sectors. The addition of different nanofillers represents an attractive way to develop and enhance the properties of neat PLA. Numerous nanofillers with different architectures and properties have been investigated, with satisfactory achievements, in the design of PLA nanocomposites. This review paper overviews the current advances in the synthetic routes of PLA nanocomposites, the imparted properties of each nano-additive, as well as the numerous applications of PLA nanocomposites in various industrial fields.

In this work we explore the effect of personality traits on user interaction in virtual reality (VR), on the less widely studied aspect of task performance during object manipulation. We conducted an experiment measuring the performance of 39 users interacting with a virtual environment using the virtual hand metaphor to execute a simple selection and positioning task, with or without virtual obstacles. Our findings suggest concrete correlations between user personality traits and behavior data. Perspective-taking, in particular, seems to be strongly affecting task performance, highlighting the need for further research. Besides the wider implications of our results in relation to the effect of personality on how users experience VR, our main contribution lies in identifying specific traits that should be taken into account when designing experiments involving users performing such tasks. The study of these traits may also significantly advance our understanding of personality traits as part of the user model in a wider range of VR applications, including those offering personalization and recommendation functionality.

Background: Recent findings associate asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) with the prognosis of acute myocardial infarction (AMI). The purpose of the current study was to associate patients' lifestyle, sociodemographic, and somatometric characteristics with the time course of ADMA and SDMA concentrations in the serum of AMI patients. Patients and Methods: In the serum of 66 AMI patients, ADMA, SDMA, troponin T, and C-reactive protein (CRP) were measured upon hospital admission (

Abstract: To gain insights into the characteristics of clinical resistance to lenalidomide, we evaluated the outcomes of 147 consecutive patients with multiple myeloma (MM) homogeneously treated with immunomodulatory imide drugs (IMiDs) pomalidomide and dexamethasone (Pd) for relapsed and/or refractory MM (median, 3 prior lines of treatment). We focused our analysis on the effect of the lenalidomide dose at which resistance was developed, the duration of lenalidomide exposure, and lenalidomide-free interval. On intent to treat, 33% of patients achieved ≥partial remission (PR) with Pd. When Pd was given immediately after lenalidomide, ≥PR was 32% (vs 37% after bortezomib). The response rates were similar for patients that received 5 to 15 mg vs 25 mg of lenalidomide (38.5% vs 30.5%, P = .329). Response rates were higher for patients that had received at least 12 months of lenalidomide (44% vs 27%) and for those with ≥18 months from last lenalidomide dose to pomalidomide dose (65% vs 23%). Median progression-free survival (PFS) and overall survival (OS) were 5 and 12.1 months, respectively, which was similar for patients who received lenalidomide, bortezomib or other regimens just before Pd and similar for patients who were receiving different doses of lenalidomide. IMiD-free interval ≥18 months was associated with longer PFS (10.3 vs 3.9 months, P = .003) and OS (27.1 vs 9.3, P = .008) as well as duration of last lenalidomide therapy ≥12 months (PFS: 7.8 vs 3.2, P = .023; OS: 16.5 vs 7.9, P = .005) even after adjustment for the number of prior therapies, duration of disease, and last lenalidomide dose.

Abstract: Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data exist on bortezomib with immunomodulatory drug combinations. We report our experience with primary therapy with a bortezomib, lenalidomide, and dexamethasone (VRD) “light” regimen in 34 consecutive patients with AL amyloidosis. The majority (79%) had cardiac involvement, 15% and 23% were Mayo stage 3A and 3B, respectively, and 54% had renal involvement. After the first VRD cycle, 71% of patients achieved a hematologic response (44% at least very good partial response [VGPR]). On intent to treat, 11 (32%) achieved a complete response (of whom 5 of 11 were minimal residual disease [MRD] negative at 10−5), 17 (50%) a VGPR, and 2 (7%) a partial response. The 12-month survival was 73%. Starting lenalidomide dose was 5 mg in 86% of patients. Hematologic toxicity was mild; nonhematologic toxicities included rash (grade 3/4 [16%]), infections (grade ≥3 [12%]), constipation (grade ≥3 [9%]), and peripheral neuropathy (grade 2 [20%]); 37.5% of patients required lenalidomide dose reduction, 27% discontinued lenalidomide, 38% required bortezomib dose reduction, and 12% discontinued bortezomib. We compared VRD to CyBorD in 68 patients matched for Mayo stage and baseline difference between involved minus uninvolved serum free light chain levels, and observed a trend for deeper response at 3 and 6 months with VRD. In conclusion, VRD can be an active regimen for newly diagnosed patients with AL amyloidosis able to induce very deep hematologic responses at the expense of increased toxicity.

Cyanobacteria are one of the most promising microorganisms to produce biofuels and renewable chemicals due to their oxygenic autotrophic growth properties. However, to rely on photosynthesis, which is one of the main reasons for slow growth, low carbon assimlation rate and low production, is a bottleneck. To address this challenge, optimizing the Calvin-Benson-Bassham (CBB) cycle is one of the strategies since it is the main carbon fixation pathway. In a previous study, we showed that overexpression of either aldolase (FBA), transketolase (TK), or fructose-1,6/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), enzymes responsible for RuBP regeneration and vital for controlling the CBB carbon flux, led to higher production rates and titers in ethanol producing strains of Synechocystis PCC 6803. In the present study, we investigated the combined effects of the above enzymes on ethanol production in Synechocystis PCC 6803.The ethanol production of the strains overexpressing two CBB enzymes (FBA ​+ ​TK, FBP/SBPase ​+ ​FBA or FBP/SBPase ​+ ​TK) was higher than the respective control strains, overexpressing either FBA or TK. The co-overexpression of FBA and TK led to more than 9 times higher ethanol production compared to the overexpression of FBA. Compared to TK the respective increase is 4 times more ethanol production. Overexpression of FBP/SBPase in combination with FBA showed 2.5 times higher ethanol production compared to FBA. Finally, co-overexpression of FBP/SBPase and TK reached about twice the production of ethanol compared to overexpression of only TK. This study clearly demonstrates that overexpression of two selected CBB enzymes leads to significantly increased ethanol production compared to overexpression of a single CBB enzyme.