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Objective: Segmentation of brain sulci in pre-term infants is crucial for monitoring their development. While magnetic resonance imaging has been used for this purpose, cranial ultrasound (cUS) is the primary imaging technique used in clinical practice. Here, we present the first study aiming to automate brain sulci segmentation in pre-term infants using ultrasound images., Methods: Our study focused on segmentation of the Sylvian fissure in a single cUS plane (C3), although this approach could be extended to other sulci and planes. We evaluated the performance of deep learning models, specifically U-Net and ResU-Net, in automating the segmentation process in two scenarios. First, we conducted cross-validation on images acquired from the same ultrasound machine. Second, we applied fine-tuning techniques to adapt the models to images acquired from different vendors., Results: The ResU-Net approach achieved Dice and Sensitivity scores of 0.777 and 0.784, respectively, in the cross-validation experiment. When applied to external datasets, results varied based on similarity to the training images. Similar images yielded comparable results, while different images showed a drop in performance. Additionally, this study highlighted the advantages of ResU-Net over U-Net, suggesting that residual connections enhance the model's ability to learn and represent complex anatomical structures., Conclusion: This study demonstrated the feasibility of using deep learning models to automatically segment the Sylvian fissure in cUS images. Accurate sonographic characterisation of cerebral sulci can improve the understanding of brain development and aid in identifying infants with different developmental trajectories, potentially impacting later functional outcomes., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Plastic pollution is widely recognized as one of the major threats to marine ecosystems. However, our knowledge on the ecological interactions between plastic and marine fauna is still limited. Here, we analyzed the substrate preferences for oviposition in the small-spotted catshark (Scyliorhinus canicula) and explored the influence of pollution, environmental conditions, and fishing pressure as potential drivers. For the first time, we report this catshark species using marine debris for oviposition, unraveling a behavioral shift in the oviposition substrate preferences towards plastics, particularly ghost fishing gear, when biological substrates are unavailable. Our results indicate that this behavioral change may be driven by the combined effects of plastic pollution and habitat degradation. Preferences also change with depth, with a larger preference for the hydrozoan Lytocarpia myriophyllum on the continental shelf, followed by sponges, as in this region mesophotic and deep benthic communities are still more abundant although impacted by human pressures. In contrast, on the continental slope, the preference shifts to tube-dwelling polychaetes and plastics, primarily ghost fishing gear, due to the limited availability of biological substrates in this region. We highlight that plastic-fish interactions may become increasingly recurrent as plastic substrates increase and habitat forming invertebrates decline due to trawl fishing and other anthropogenic activities, especially in the Mediterranean Sea. The implications of this behavior for catshark fitness are still largely unknown, which prompts further research concerning the potential impact on its survival and/or dispersal in the plastic age and highlights the urgency of preserving biogenic habitats., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this work, strategies for the detection of pyrimidine-rich DNA target sequences based on the formation of duplex and antiparallel triplex structures are studied. The presence of the target is detected from the changes in fluorescence of silver nanoclusters stabilized by the corresponding complementary DNA probes. In all cases, the formation of intermolecular structures has been assessed by means of melting experiments and multivariate analysis. In the case studied, it has been observed that the formation of antiparallel triplex structures produces changes in fluorescence properties that could be more useful for analytical purposes than those observed when only duplex structures are formed. In particular, the use of silver nanoclusters confined within a loop rich in cytosine-type bases in the antiparallel triplex structure resulting from the interaction of probe and analyte has been shown to produce an increase in red fluorescence. This latter probe has been shown to be selective against target sequences that have mismatches that could affect the formation of stable duplex structures, while it has been shown to tolerate a small number of purine mismatches that could affect the stability of the resulting antiparallel triplex structure. As a final remark, it should be noted that this methodology could also be used in the development of analytical procedures that allow the detection of antiparallel triplex structures, which are difficult to observe with other spectroscopic methods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raimundo Gargallo reports financial support was provided by Spain Ministry of Science and Innovation. Ramon Eritja reports financial support was provided by Marathon Foundation of Tv3. If there are other authors, they 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Inhaled therapy is essential in cystic fibrosis; however, inhalers have a significant environmental impact due to the greenhouse gases (GHGs) emitted. The environmental impact of a product is estimated by its carbon footprint (CF). Pressurized metered-dose inhalers (pMDIs) have a higher CF than dry powder inhalers (DPIs) and soft mist inhalers (SMIs) due to the incorporation of GHGs. The objectives are to analyze the consumption of inhalers (β2-adrenergic agonist bronchodilators, anticholinergics, and/or corticosteroids) in a cystic fibrosis unit and estimate the generated CF., Method: Retrospective determination (January 2018-December 2023) of consumption and CF (tCO2eq) by type of inhaler was conducted. Consumption and CF trends were evaluated using lineal regression., Results: Annually, 1,529 (1,279-1,613) pMDIs, 1,055 (855-1,333) DPIs, and 28 (20-42) SMIs were dispensed, representing 55.97%, 42.33%, and 1.70%, respectively. A statistically significant positive trend in the consumption of SMIs was observed. The median annual CF was: pMDI 38.3 (31.2-40.3) tCO2eq, DPIs 0.8 (0.6-0.9) tCO2eq, and SMIs 0.02 (0.02-0.03) tCO2eq, representing 97.86, 2.04, and 0.10%, respectively., Conclusions: pMDIs were the inhalers with the highest consumption and CF, although their consumption appears to be decreasing, with an increase in the consumption of SMIs., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Processing of edible insects typically involves fractionating into high-value food ingredients, which results in by-products containing chitin and insoluble proteins. This study examined the effectiveness of lactic acid bacteria (LAB) in removing proteins from chitin in insect processing residues. Lesser mealworm processing residues were biologically treated for 48 and 120 h using LAB strains without added carbon sources. Results showed partial deproteinization, up to 29 % with Levilactobacillus brevis after 120 h. Most LAB grew up to 2 log 10 colony-forming units/mL in the first 48 h. Confocal microscopy and Fourier-transform infrared spectra indicated that some protein remained attached to chitin. The molecular weight of solubilized proteins was affected by strain and time of incubation, with antioxidant activity increasing significantly after 120 h with Lacticaseibacillus paracasei. The biological treatment of insect processing streams can be a sustainable approach to producing high amounts of LAB biomass with subsequent protein solubilization and chitin release., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associated with performance on a task aimed at assessing facial emotion recognition. In this study, we explored the association between hypomimia, recognition of facial expressions of basic emotions using the Ekman 60 Faces Test (EF), and brain correlates of both hypomimia and performance on the EF. A total of 94 subjects underwent clinical assessments (neurological and neuropsychological examinations), and 56 of them participated in the neuroimaging study. We found significant correlation between hypomimia, EF Disgust (r = -0.242, p = 0.022) and EF Happiness (r = -0.264, p = 0.012); an independent reduction in Cortical Thickness (Cth) in the postcentral gyrus, insula, middle and superior temporal gyri, supramarginal gyrus, banks of the superior temporal sulcus, bilateral fusiform gyri, entorhinal cortex, parahippocampal gyrus, inferior and superior parietal cortex, and right cuneus and precuneus; and multiple correlations between negative emotions such as EF Disgust or EF Anger and a reduced Cth in fronto-temporo-parietal regions. In conclusion, these results suggest that the association between hypomimia and emotion recognition deficits in individuals with PD might be mediated by shared circuits, supporting the concept that hypomimia is not only the result of the dysfunction of motor circuits, but also of higher cognitive functions., Competing Interests: Declarations. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Consent to participate: Informed consent was obtained from all participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: This paper describes a novel circuit for intraoperative analysis with ICBCT in maxillofacial surgery. The aim is to establish guidelines, define indications, and conduct an analysis of the implementation of the circuit for intraoperative comparison of surgical outcomes in relation to 3D virtual planning in maxillofacial surgery., Methods: The study included 150 maxillofacial surgical procedures. Intraoperative actions involved fluoroscopy localization, intraoperative CBCT acquisition, segmentation, and superimposition, among other steps. Surgical times due to intraoperative superposition were measured, including time required for ICBCT positioning and acquisition, image segmentation, and comparison of 3D surfaces from the surgical planning., Results: Successful intraoperative comparison was achieved in all 150 cases, enabling surgeons to detect and address modifications before concluding the surgery. Out of the total, 26 patients (17.33%) required intraoperative revisions, with 11 cases (7.33%) needing major surgical revisions. On average, the additional surgical time with this circuit implementation was 10.66 ± 3.03 min (n = 22)., Conclusion: The results of our research demonstrate the potential for performing intraoperative surgical revision, allowing for immediate evaluation, enhancing surgical outcomes, and reducing the need for re-interventions., Competing Interests: Declarations. Conflict of interest: Authors declare no conflict of interest. Ethical approval: This study was approved by the Ethics Committee and conducted in compliance with the Helsinki Declaration (Fortaleza, Brazil, October 2013). The informed consent was requested when necessary., (© 2024. CARS.)

The reversible modulation of acidity using molecular photoswitches enables the remote control of a variety of (bio)chemical processes with light. Herein we investigated the structural features that allow amplifying photoinduced p K a variation in phenol-diarylethene conjugates, which toggle between low- and high-acidity states by switching the conjugation between the ionizable moiety and electron-withdrawing groups upon photoisomerization. By tuning the structure of these conjugates, high p K a modulation amplitudes were accomplished that surpass those previously reported.

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as "proof of concept" regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Understanding the origin of eukaryotic cells is one of the most difficult problems in all of biology. A key challenge relevant to the question of eukaryogenesis is reconstructing the gene repertoire of the last eukaryotic common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture of early eukaryotic cellular complexity requires provision of analytical resources and a commitment to data sharing. Here, we summarise progress towards understanding the biology of LECA and outline a community approach to inferring its wider gene repertoire. Once assembled, a robust LECA gene set will be a useful tool for evaluating alternative hypotheses about the origin of eukaryotes and understanding the evolution of traits in all descendant lineages, with relevance in diverse fields such as cell biology, microbial ecology, biotechnology, agriculture, and medicine. In this Consensus View, we put forth the status quo and an agreed path forward to reconstruct LECA's gene content., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Richards et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Malaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023-2030) for malaria control and elimination., Methods and Analyses: This prospective genomic surveillance study aims to generate Plasmodium falciparum genetic data to monitor diagnostic failures due to pfhrp2/3 deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination). The study, to be conducted between 2024 and 2026, will use three sampling schemes: a multicluster probabilistic health facility survey in the 10 provinces of the country to detect pfhrp2/3 deletions and markers of antimalarial drug resistance; dense sampling of all clinical cases in representative districts in the south targeted for elimination to characterise malaria importation and identify sources of transmission; and testing of pregnant women for malaria at their first antenatal care visit to assess malaria burden and molecular trends. Using a multiplex amplicon-based sequencing approach, the study will target microhaplotypes informative of genomic diversity and relatedness, as well as key drug resistance-associated genes, pfhrp2/3 deletion and malaria vaccine targets. Key genomic information will be visualised in a dashboard integrated into the District Health Information System V.2-based Malaria Information Storage System for programmatic use., Ethics and Dissemination: The protocol was reviewed and approved by the national ethics committee of Mozambique (Comité Nacional de Bioética para Saúde, Ref: 680/CNBS/23). Project results will be presented to all stakeholders using study-specific brochures and published in open-access journals., Trial Registration Number: NCT06529237., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Sex differences in the composition and functionality of gut microbiota are an emerging field of interest in neurodevelopmental disorders, as they may help in understanding the phenotypic disparities between males and females. This study aimed to characterize sex-related specific alterations in gut microbiota composition in a mouse model of Down syndrome (Ts65Dn mice, TS mice) through the sequencing of the PCR-amplified 16S ribosomal DNA fraction. Moreover, it intended to examine whether the modulation of gut microbiota by the administration of a synbiotic (SYN) treatment would be beneficial for the behavioral alterations observed in male and female TS mice. Our results show that male, but not female, TS mice exhibit alterations in beta diversity compared to their wild-type (WT) littermates. Sex-dependent differences are also observed in the relative abundance of the classes Bacilli and Clostridia. Administering the SYN effectively counteracts hypersociability in females, and normalizes the overall abundance of Bacilli, specifically by increasing Lactobacillaceae. On the contrary, it rescues emotional recognition deficits in male TS mice and increases the relative abundance of the families Lactobacillaceae, Streptococcaceae and Atopobiaceae. In addition, a metagenome KEGG analysis of differentially enriched pathways shows relevant changes in the cofactor biosynthesis and the amino acid synthesis categories. Finally, following SYN treatment, both male and female TS mice exhibit a robust increase in propionic acid levels compared to WT littermates. These findings suggest sex-specific mechanisms that could link gut microbiota composition with behavior in TS mice, and underscore the potential of targeted gut microbiota interventions to modulate social abnormalities in neurodevelopmental disorders., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Electron paramagnetic resonance (EPR) pulsed dipolar spectroscopy (PDS) using triplet states of organic molecules is a growing area of research due to the favourable properties that these transient states may afford over stable spin centers, such as switchability, increased signal intensity when the triplet is formed in a non-Boltzmann distribution and the triplet signal is used for detection, and high orientation selection, when the triplet signal is probed by microwave pulses. This arises due to the large spectral width at low fields, a result of the large zero field splitting, and limited bandwidth of microwave pulses used. Here we propose the triplet state of a substituted BODIPY moiety as a spin label in light induced PDS, coupled to a nitroxide, in a model peptide with a rigid structure. Orientation selection allows information on the relative position of the centres of the two labels to be obtained with respect to the nitroxide reference frame. Additionally, magnetophotoselection effects are employed to introduce optical selection and additional constraints for the determination of the relative orientation of the spin labels considering the reference frame of the triplet state.

Background: Despite advances made in treatments for atopic dermatitis (AD), information on its impact and interaction with atopic comorbidities, such as asthma, rhinoconjunctivitis, and ocular disease is limited. This study aims to assess the clinical-epidemiological characteristics of patients with AD-treatment response included-while taking into consideration atopic comorbidities like these., Materials and Methods: Data were analyzed from the multicenter BIOBADATOP registry (a prospective cohort of AD patients initiating systemic treatment). We conducted a descriptive analysis of the main characteristics collected in the registry in relation to atopic comorbidity., Results: We included a total of 509 patients, mostly adults (81.9%) with severe AD (73.7%). Patients with personal atopic comorbidity (64%) more frequently exhibited flexural dermatitis (89.7% vs 81.5%), a higher mean of previous systemic treatments (1.6 vs. 1.3), and higher baseline values on the POEM scale (19.6 vs. 17.9). Patients with familial atopic comorbidity (40.7%) had a higher incidence of pediatric/adolescent patients (24.2% vs. 13.9%) and a history of allergic rhinoconjunctivitis (61.1% vs. 47.1%). No differences regarding treatment response were observed at the 6- and 12-month follow-ups based on the presence or absence of atopic comorbidities., Conclusions: Results suggest that a history of atopic comorbidity is associated with an early onset and persistent course of AD. Although no differences were reported in the short-term treatment response, further follow-up is required to better understand the impact of comorbidities on AD., Competing Interests: Conflicto de intereses M. Munera-Campos ha participado como investigadora en ensayos clínicos patrocinados por Sanofi, Abbvie, Lilly, Leo-Pharma, Pfizer, Almirall, Galderma y Novartis, y ha recibido honorarios como ponente y consultora de Sanofi, Lilly, Leo Pharma, Abbvie y Galderma. P. Chicharro ha participado en consultorías, coloquios y ensayos clínicos organizados por las siguientes compañías: Janssen Pharmaceuticals, Almirall, Sanofi Genzyme, Lilly, Abbvie, Novartis, Leo-Pharma y Pfizer-Wyeth. A. González Quesada ha participado como consultora, como ponente y ha participado en ensayos clínicos de Abbvie, Pfizer, Novartis, Sanofi, Boehringer, Bristol-Meyer, Leo-Pharma, Janssen. Á. Flórez Menéndez ha actuado como conferenciante y/o consultora y/o realizado ensayos clínicos y proyectos de investigación para Abbvie, ACELYRIN Inc, Alcedis GmbH, Almirall, Amgen, BMS, Celgene, Galderma, Incyte Corporation, Janssen-Cilag, Kyowa Kirin, Leo Pharma, Lilly, MSD, Novartis, Pfizer, Roche Farma, Sanofi-Aventis, Sun Pharma, Takeda y UCB Biosciences GmbH. P. de la Cueva Dobao ha actuado como asesor y/o investigador y/o ponente de: Abbvie, Almirall, BMS, Boehringer, Celgene, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Roche, Sanofi y UCB. AM. Giménez Arnau es o fue recientemente ponente y/o asesora y/o ha recibido financiamiento para la investigación de Almirall, Amgen, AstraZeneca, Avene, Celldex, Escient Pharmaceutials, Genentech, GSK, Instituto Carlos III-FEDER, Leo Pharma, Menarini, Mitsubishi Tanabe Pharma, Novartis, Sanofi–Regeneron, Servier, Thermo Fisher Scientific, Uriach Pharma y Noucor. Y. Gilaberte-Calzada ha participado como asesora de Isdin y Roche Posay, Galderma, en conferencias para Almirall, Sanofi, Avene, Rilastil, Lylly, Uriage, Novartis, Cantabria Labs, y ha participado en proyectos de investigación de Almirall, Sanofi, Pfizer, AbbVie y LEO Pharma. M. Rodríguez Serna ha participado en asesorías para Sanofi, Pfizer, Leo, Novartis y Abbie. M. Elosua-González ha participado como investigadora y/o ponente para AbbVie, Lilly, Galderma, LEO Pharma, Pfizer, UCB Pharma y Sanofi Genzyme. J.F. Silvestre Salvador ha colaborado como ponente, asesor y/o investigador para: AbbVie, Almirall, Amgen, Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte, Leo Pharma, Novartis, Pfizer, Regeneron y Sanofi Genzyme. M. Elosua-González ha recibido honorarios/colaboración para actividades de formación, ponencias y/o como asesora de Abbvie, Lilly, Galderma, Novartis, GSK, LEO Pharma, Pfizer, Pierre Fabre Ibérica, UCB Pharma y Sanofi Genzyme. E. del Alcázar-Viladomiu ha participado como ponente y/o investigadora principal y/o subinvestigadora en ensayos clínicos para Amgen, Almirall, Janssen, Lilly, LEO Pharma, Novartis, UCB y AbbVie. A. Batalla ha recibido honorarios/colaborado para actividades de formación, consultoría o participación en ensayos clínicos de Abbvie, Celgene, Faes pharma, Isdin, Janssen, Leopharma, Lethipharma, Lilly, Mylan, Novartis, Pfizer, Pierre Fabre y Sanofi. H. J. Suh Oh ha colaborado como ponente, asesora y/o investigadora para: Abbvie, Almirall, Amgen, Celgene, Janssen, Kyowa Kirin, Leo-Pharma, Lilly, Novartis, Pfizer, Roche Farma, Sanofi, Sun Pharma, Takeda, UCB Pharma. C. Couselo-Rodríguez ha participado como subinvestigadora o ponente en proyectos patrocinados por: Abbvie, Sanofi, Leo-Pharma, Lilly, UCB, Novartis, Pierre Fabre y Janssen. L. Curto-Barredo ha recibido honorarios por la realización de ponencias y/o como asesora por parte de Sanofi, Abbvie, Leo Pharma, Lilly y Novartis. M. Bertolín-Colilla ha recibido honorarios por la realización de ponencias y/o como asesora por parte de Sanofi y Leo Pharma. R. Botella Estrada es o ha sido miembro del consejo asesor y/o ponente y/o participante en ensayos clínicos para Pfizer, AbbVie, Almirall, Novartis, Janssen, Leo Pharma, Lilly, Celgene, Roche, SunPharma. I. Betlloch-Mas ha participado como asesora en proyectos de Sanofi y Abbvie. G. Roustan Gullón ha recibido honorarios por la realización de ponencias y/o como asesora por parte de Sanofi, Abbvie, Leo Pharma, Lilly y Novartis. A. Rosell-Díaz ha recibido honorarios por la realización de ponencias y/o como asesora por parte de Sanofi, Abbvie, Leo Pharma. M. Loro-Pérez ha recibido honorarios/colaboración para actividades de formación, ponencias y/o como asesora de Abbvie, Johnson & Johnson, Galderma, Novartis, UCB Pharma y Sanofi Genzyme. J.M. Carrascosa ha participado como investigador principal/subinvestigador y/o recibido honorarios como ponente y/o miembro de comité de expertos o steering comitee para AbbVie, Novartis, Janssen, Lilly, Sandoz, Amgen, Almirall, BMS, Boehringer Ingelheim, Biogen, UCB. El resto de los autores declara no tener ningún conflicto de intereses., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Importance: Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant problem following cardiopulmonary bypass (CPB). Various strategies are proposed to attenuate CSA-AKI, including extracorporeal blood purification (EBP), but little is known about the effect of EBP through an acrylonitrile-sodium methallylsulfonate/polyethyleneimine membrane during CPB., Objective: To determine whether the use of an EBP device in a nonemergent cardiac surgery population reduces CSA-AKI after CPB., Design, Setting, and Participants: This double-blind, randomized clinical trial was conducted in 2 tertiary hospitals in Spain. Patients 18 years or older undergoing nonemergent cardiac surgery who were at high risk for CSA-AKI were enrolled from June 15, 2016, through November 5, 2021, with follow-up data through February 5, 2022. Of 1156 patients assessed, 343 patients were randomized (1:1) to either receive EBP or standard care., Intervention: Nonselective EBP device connected to the CPB circuit., Main Outcomes and Measures: The primary outcome was the rate of CSA-AKI in the 7 days after randomization., Results: Among 343 patients randomized (169 to receive EBP and 174 to receive usual care), the mean (SD) age was 69 (9) years and 119 were females. The rate of CSA-AKI was 28.4% (95% CI, 21.7%-35.8%) in the EBP group vs 39.7% (95% CI, 32.3%-47.3%) in the standard care group (P = .03), with an adjusted difference of 10.4% (95% CI, 2.3%-18.5%) using a log-binomial model (P = .01). No significant differences (P > .05) were observed in most of the predefined clinical secondary end points or post hoc exploratory end points. In a sensitivity analysis, EBP was found to be more effective in terms of CSA-AKI reduction in patients with chronic kidney disease, diabetes, hypertension, low left ventricular ejection fraction (<40%), and lower body mass index (<30). No differences were observed between the groups in adverse events tracking., Conclusions and Relevance: The use of a nonselective EBP device connected to the CPB circuit in a nonemergent population of patients undergoing cardiac surgery was associated with a significant reduction of CSA-AKI in the first 7 days after surgery., Trial Registration: ClinicalTrials.gov Identifier: NCT02518087.

Introduction: Bacteremia is a life-threatening condition that can progress to sepsis and septic shock, leading to significant mortality in the emergency department (ED). The standard diagnostic method, blood culture, is time-consuming and prone to false positives and false negatives. Although not widely accepted, several clinical and artificial intelligence-based algorithms have been recently developed to predict bacteremia. However, these strategies require further identification of new variables to improve their diagnostic accuracy. This study proposes a novel strategy to predict positive blood cultures by assessing sepsis-induced immunosuppression status through endotoxin tolerance assessment., Methods: Optimal assay conditions have been explored and tested in sepsis-suspected patients meeting the Sepsis-3 criteria. Blood samples were collected at ED admission, and endotoxin (lipopolysaccharide, LPS) challenge was performed to evaluate the innate immune response through cytokine profiling., Results: Clinical variables, immune cell population biomarkers, and cytokine levels (tumor necrosis factor [TNFα], IL-1β, IL-6, IL-8, and IL-10) were measured. Patients with positive blood cultures exhibited significantly lower TNFα production after LPS challenge than did those with negative blood cultures. The study also included a validation cohort to confirm that the response was consistent., Discussion: The results of this study highlight the innate immune system immunosuppression state as a critical parameter for sepsis diagnosis. Notably, the present study identified a reduction in monocyte populations and specific cytokine profiles as potential predictive markers. This study showed that the LPS challenge can be used to effectively distinguish between patients with bloodstream infection leading to sepsis and those whose blood cultures are negative, providinga rapid and reliable diagnostic tool to predict positive blood cultures. The potential applicability of these findings could enhance clinical practice in terms of the accuracy and promptness of sepsis diagnosis in the ED, improving patient outcomes through timely and appropriate treatment., Competing Interests: EH-J, AU, XP, and JS are employees/advisors of the spin-off company Loop Diagnostics related to this biomarker. EH-J, EP-M, XP and JS are shareholders of a spin-off company Loop Diagnostics related to this biomarker. AL and EM have received honoraria from Loop Diagnostics. JS and EH-J are the authors of a PCT patent application to protect against the use of the method and kit for the early detection of sepsis WO2021245025A1. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hernández-Jiménez, Plata-Menchaca, Berbel, López de Egea, Dastis-Arias, García-Tejada, Sbraga, Malchair, García Muñoz, Larrad Blasco, Molina Ramírez, Pérez Fernández, Sabater Riera and Ulsamer.)

In multicellular organisms, the indole melatonin synthesized by aralkylamine N-acetyltransferase (AANATI) serves as an antioxidant. To test this, sex-mixed 3-day-old mated fly adults bw 1 and AANAT1 homozygous recessive loss-of-function mutant (bw AANAT1 lo ) of Drosophila melanogaster were fed by a standard diet or by one containing paraquat (PQ, 1,1'-dimethyl-4,4'-bipyridilium dichloride hydrate) at a final concentration of 15.5 mM. Experiment lasted 8 h and began at 11 a.m. In bw 1 flies the paraquat treatment resulted in a significant (evaluated by Student's t-tests) decrease of the superoxide dismutase (SOD) activity and an increase the catalase (CAT) and glutathione S-transferase (GST) activities. Meanwhile, in these flies, total Antioxidative capacity (TAC) was significantly curbed by the paraquat presence. Importantly, these changes were not observed in the AANAT1-mutants. Thus, melatonin seems to play an important defence role against the oxidative stress elicited by paraquat., (© 2024 Wiley Periodicals LLC.)

Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined., Objectives: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups., Methods: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them., Results: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals., Conclusions: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Emerging research implicates tau protein dysregulation in the pathophysiology of Huntington's disease., Objective: This study investigated skin tau quantification as a potential biomarker for Huntington's disease and its correlation with disease burden outcomes., Methods: In this cross-sectional study, we measured skin tau levels using enzyme-linked immunosorbent assay in 23 Huntington's disease mutations carriers and eight control subjects, examining group discrimination, correlations with genetic markers, clinical assessments, and neuroimaging data. Brain atrophy was quantified by both volumetric measurements from brain segmentation and a voxel-based morphometry approach., Results: Our findings showed elevated skin tau levels in manifest Huntington's disease compared with premanifest and healthy controls. These levels correlated with CAG repeat length, CAG-Age-Product score, composite Unified Huntington's Disease Rating Scale Total Motor Score, cognitive assessments, and disease-related cortical and subcortical volumes, all independent of age and gender. Using skin tau levels in cluster analysis along with genetic and clinical measures led to improved subject stratification, providing enhanced distinction and validity of clusters., Conclusions: This study not only confirms the feasibility of skin tau quantification in Huntington's disease but also establishes its potential as a biomarker for enhancing group classification and assessing disease severity across the Huntington's disease spectrum, opening new directions in biomarker research. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Objective: Cognitive impairment in Parkinson's disease (PD) can show a very heterogeneous trajectory among patients. Here, we explored the mechanisms involved in the expression and prediction of different cognitive phenotypes over 4 years., Methods: In 2 independent cohorts (total n = 475), we performed a cluster analysis to identify trajectories of cognitive progression. Baseline and longitudinal level II neuropsychological assessments were conducted, and baseline structural magnetic resonance imaging, resting electroencephalogram and neurofilament light chain plasma quantification were carried out. Linear mixed-effects models were used to study longitudinal changes. Risk of mild cognitive impairment and dementia were estimated using multivariable hazard regression. Spectral power density from the electroencephalogram at baseline and source localization were computed., Results: Two cognitive trajectories were identified. Cluster 1 presented stability (PD-Stable) over time, whereas cluster 2 showed progressive cognitive decline (PD-Progressors). The PD-Progressors group showed an increased risk for evolving to PD mild cognitive impairment (HR 2.09; 95% CI 1.11-3.95) and a marked risk for dementia (HR 4.87; 95% CI 1.34-17.76), associated with progressive worsening in posterior-cortical-dependent cognitive processes. Both clusters showed equivalent clinical and sociodemographic characteristics, structural magnetic resonance imaging, and neurofilament light chain levels at baseline. Conversely, the PD-Progressors group showed a fronto-temporo-occipital and parietal slow-wave power density increase, that was in turn related to worsening at 2 and 4 years of follow-up in different cognitive measures., Interpretation: In the absence of differences in baseline cognitive function and typical markers of neurodegeneration, the further development of an aggressive cognitive decline in PD is associated with increased slow-wave power density and with a different profile of worsening in several posterior-cortical-dependent tasks. ANN NEUROL 2024;96:981-993., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

After injury, severed axons separated from their somas activate programmed axon degeneration, a conserved pathway to initiate their degeneration within a day. Conversely, severed projections deficient in programmed axon degeneration remain morphologically preserved with functional synapses for weeks to months after axotomy. How this synaptic function is sustained remains currently unknown. Here, we show that dNmnat overexpression attenuates programmed axon degeneration in distinct neuronal populations. Severed projections remain morphologically preserved for weeks. When evoked, they elicit a postsynaptic behavior, a readout for preserved synaptic function. We used ribosomal pulldown to isolate the translatome from these projections 1 week after axotomy. Translatome candidates of enriched biological classes identified by transcriptional profiling are validated in a screen using a novel automated system to detect evoked antennal grooming as a proxy for preserved synaptic function. RNAi-mediated knockdown reveals that transcripts of the mTORC1 pathway, a mediator of protein synthesis, and of candidate genes involved in protein ubiquitination and Ca 2+ homeostasis are required for preserved synaptic function. Our translatome dataset also uncovers several uncharacterized Drosophila genes associated with human disease. It may offer insights into novel avenues for therapeutic treatments., (© 2024. The Author(s).)

Objective: To determine the cost-effectiveness of different imaging modalities for initial detection of multiple myeloma (MM)-defining bone lesions., Methods: A Markov model from the health care system perspective for patients with MGUS was used to evaluate the incremental cost-effectiveness of five imaging techniques: skeletal survey (SS), low-dose computed tomography (LDCT), positron emission computed tomography (PETCT), and whole-body magnetic resonance imaging (WBMRI) with and without diffusion (DIFF). Model inputs, including probabilities, utilities, and costs were obtained from comprehensive literature review. Costs were estimated in 2024 U.S. dollars, effectiveness was measured in quality adjusted life years (QALYs), willingness-to-pay (WTP) threshold was set to $100,000/QALY, and timeframe of the simulation was 20 years. Model analyses included Monte Carlo microsimulation and probabilistic sensitivity analysis (PSA)., Results: The most cost-effective imaging strategy was dependent on the number of patient risk factors for progression from MGUS to myeloma. At a WTP threshold of $100,000, for patients with no risk factors for progression, LDCT amassed the greatest net monetary benefit (NMB) ($1,030,913.57) while incurring the second lowest costs ($44,870.73). For patients with 1 or 2 risk factors for progression, WBMRI + DIFF amassed the greatest NMB (1 risk factor: $802,637.30, 2 risk factors: $664,430.36). WBMRI and PETCT were absolutely dominated in all cases. PSA also found that the most cost-effective strategy was dependent on the WTP threshold., Conclusion: Our model suggests that LDCT and WBMRI + DIFF can be the most cost-effective imaging strategies for the initial diagnosis of MM in patients, depending on the number of risk factors for progression., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

The brain is a complex non-equilibrium system capable of expressing many different dynamics as well as the transitions between them. We hypothesized that the level of non-equilibrium can serve as a signature of a given brain state, which was quantified using the arrow of time (the level of irreversibility). Using this thermodynamic framework, the irreversibility of emergent cortical activity was quantified from local field potential recordings in male Lister-hooded rats at different anesthesia levels and during the sleep-wake cycle. This measure was carried out on five distinct brain states: slow-wave sleep, awake, deep anesthesia-slow waves, light anesthesia-slow waves, and microarousals. Low levels of irreversibility were associated with synchronous activity found both in deep anesthesia and slow-wave sleep states, suggesting that slow waves were the state closest to the thermodynamic equilibrium (maximum symmetry), thus requiring minimum energy. Higher levels of irreversibility were found when brain dynamics became more asynchronous, for example, in wakefulness. These changes were also reflected in the hierarchy of cortical dynamics across different cortical areas. The neural dynamics associated with different brain states were characterized by different degrees of irreversibility and hierarchy, also acting as markers of brain state transitions. This could open new routes to monitoring, controlling, and even changing brain states in health and disease., (© 2024. The Author(s).)

Background: Injury to the internal carotid artery (ICA) during functional endoscopic sinus surgery is a rare but potentially fatal complication. Although treatment algorithms have been developed, guidelines for effectively managing iatrogenic ICA injury have not been established. A case of ICA perforation during functional endoscopic sinus surgery treated with cerebral bypass utilizing a cephalic vein graft is presented., Observations: A woman in her late 50s presented with a left cavernous ICA injury that had occurred during endoscopic nasal polypectomy at an outside hospital. Hemostasis was achieved with intranasal Foley catheter placement. Left common carotid artery angiography revealed a high-flow carotid-cavernous fistula. Cerebral revascularization was chosen as the optimal procedure. The initial intent was to use a radial artery graft, but the radial artery was found to be occluded intraoperatively. Postoperatively, the patient experienced decreased vision and left eye movement but was otherwise neurologically intact. Postoperative angiography showed complete resolution of the fistula., Lessons: In cases involving ICA injury and carotid-cavernous fistula formation, microsurgical trapping with high-flow bypass is a favorable treatment option. The cephalic vein is a viable graft option when unexpected challenges arise with a radial artery graft. https://thejns.org/doi/10.3171/CASE24222.

Experimental and clinical studies of consciousness identify brain states (i.e. quasi-stable functional cerebral organization) in a non-systematic manner and largely independent of the research into brain state modulation. In this narrative review, we synthesize advances in the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anaesthesia) and pathological (disorders of consciousness) states of altered consciousness in humans. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication is sparser, less efficient, and less complex. The results also highlight damaged resting-state networks, in particular the default mode network, decreased connectivity in long-range connections and especially in the thalamocortical loops. Next, we show that therapeutic approaches to treat disorders of consciousness, through pharmacology (e.g. amantadine, zolpidem), and (non-) invasive brain stimulation (e.g. transcranial direct current stimulation, deep brain stimulation) have shown partial effectiveness in promoting consciousness recovery. Although some features of conscious brain states may improve in response to neuromodulation, targeting often remains non-specific and does not always lead to (behavioural) improvements. The fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when integrated, might propel the development of new and better-targeted techniques for disorders of consciousness. We here propose a therapeutic framework for the identification and modulation of brain states to facilitate the interaction between the two fields. We propose that brain states should be identified in a predictive setting, followed by theoretical and empirical testing (i.e. in animal models, under anaesthesia and in patients with a disorder of consciousness) of neuromodulation techniques to promote consciousness in line with such predictions. This framework further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. It will become apparent that one angle of opportunity is provided through the addition of computational modelling. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multimodal and multi-species approaches outlined throughout the review., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking., Objective: To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort., Methods: A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed., Results: Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason., Conclusion: Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, we describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. We discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research., Competing Interests: Competing interests: RKW acted as consultant for Takeda Pharmaceuticals, received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico and Ferring and received speaker’s fees from MSD, Abbvie and Janssen Pharmaceuticals. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inflammatory bowel diseases (IBDs) pose a significant challenge due to their diverse, often debilitating, and unpredictable clinical manifestations. The absence of prognostic tools to anticipate the future complications that require therapy intensification presents a substantial burden to patient private life and health. We aimed to explore whether the gut microbiome is a potential biomarker for future therapy intensification in a cohort of 90 IBD patients., Methods: We conducted whole-genome metagenomics sequencing on fecal samples from these patients, allowing us to profile the taxonomic and functional composition of their gut microbiomes. Additionally, we conducted a retrospective analysis of patients' electronic records over a period of 10 years following the sample collection and classified patients into (1) those requiring and (2) not requiring therapy intensification. Therapy intensification included medication escalation, intestinal resections, or a loss of response to a biological treatment. We applied gut microbiome diversity analysis, dissimilarity assessment, differential abundance analysis, and random forest modeling to establish associations between baseline microbiome profiles and future therapy intensification., Results: We identified 12 microbial species (eg, Roseburia hominis and Dialister invisus) and 16 functional pathways (eg, biosynthesis of L-citrulline and L-threonine) with significant correlations to future therapy intensifications. Random forest models using microbial species and pathways achieved areas under the curve of 0.75 and 0.72 for predicting therapy intensification., Conclusions: The gut microbiome is a potential biomarker for therapy intensification in IBD patients and personalized management strategies. Further research should validate our findings in other cohorts to enhance the generalizability of these results., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

The experimental approach developed in this research demonstrated how the cloud, the Internet of Things (IoT), edge computing, and Artificial Intelligence (AI), considered key technologies in Industry 4.0, provide the expected horizon for adaptive vision in Continued Process Verification (CPV), the final stage of Process Validation (PV). Pichia pastoris producing Candida rugosa lipase 1 under the regulation of the constitutive GAP promoter was selected as an experimental bioprocess. The bioprocess worked under hypoxic conditions in carbon-limited fed-batch cultures through a physiological control based on the respiratory quotient ( RQ ). In this novel bioprocess, a digital twin (DT) was built and successfully tested. The implementation of online sensors worked as a bridge between the microorganism and AI models, to provide predictions from the edge and the cloud. AI models emulated the metabolism of Pichia based on critical process parameters and actionable factors to achieve the expected quality attributes. This innovative AI-aided Adaptive-Proportional Control strategy (AI-APC) improved the reproducibility comparing to a Manual-Heuristic Control strategy (MHC), showing better performance than the Boolean-Logic-Controller (BLC) tested. The accuracy, indicated by the Mean Relative Error (MRE), was for the AI-APC lower than 4%, better than the obtained for MHC (10%) and BLC (5%). Moreover, in terms of precision, the same trend was observed when comparing the Root Mean Square Deviation (RMSD) values, becoming lower as the complexity of the controller increases. The successful automatic real time control of the bioprocess orchestrated by AI models proved the 4.0 capabilities brought by the adaptive concept and its validity in biopharmaceutical upstream operations., Competing Interests: Authors JW, FM and TM were employed by Aizon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors FV and XG-O declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gasset, Van Wijngaarden, Mirabent, Sales-Vallverdú, Garcia-Ortega, Montesinos-Seguí, Manzano and Valero.)

Spontaneous intracerebral hemorrhage (ICH) is a type of stroke less prevalent than ischemic stroke but associated with high mortality rates. Hematoma expansion (HE) is an increase in the bleeding that affects 30%-38% of hemorrhagic stroke patients. It is observed within 24 h of onset and associated with patient worsening. Clinically it is relevant to detect the patients that will develop HE from their initial computed tomography (CT) scans which could improve patient management and treatment decisions. However, this is a significant challenge due to the predictive nature of the task and its low prevalence, which hinders the availability of large datasets with the required longitudinal information. In this work, we present an end-to-end deep learning framework capable of predicting which cases will exhibit HE using only the initial basal image. We introduce a deep learning framework based on the 2D EfficientNet B0 model to predict the occurrence of HE using initial non-contrasted CT scans and their corresponding lesion annotation as priors. We used an in-house acquired dataset of 122 ICH patients, including 35 HE cases, containing longitudinal CT scans with manual lesion annotations in both basal and follow-up (obtained within 24 h after the basal scan). Experiments were conducted using a 5-fold cross-validation strategy. We addressed the limited data problem by incorporating synthetic images into the training process. To the best of our knowledge, our approach is novel in the field of HE prediction, being the first to use image synthesis to enhance results. We studied different scenarios such as training only with the original scans, using standard image augmentation techniques, and using synthetic image generation. The best performance was achieved by adding five generated versions of each image, along with standard data augmentation, during the training process. This significantly improved (p=0.0003) the performance obtained with our baseline model using directly the original CT scans from an Accuracy of 0.56 to 0.84, F1-Score of 0.53 to 0.82, Sensitivity of 0.51 to 0.77, and Specificity of 0.60 to 0.91, respectively. The proposed approach shows promising results in predicting HE, especially with the inclusion of synthetically generated images. The obtained results highlight the significance of this research direction, which has the potential to improve the clinical management of patients with hemorrhagic stroke. The code is available at: https://github.com/NIC-VICOROB/HE-prediction-SynthCT., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To retrospectively evaluate the correlation between intradiscal gas and infection in patients percutaneously biopsied for suspected discitis-osteomyelitis., Materials and Methods: We retrospectively reviewed all CT-guided discitis-osteomyelitis biopsies performed between 2002 and 2022. Two independent trained musculoskeletal radiologists evaluated for presence of gas on CT and/or MRI within 1 week of the biopsy. Disagreements were resolved by a third musculoskeletal radiologist. CT was considered the gold standard for the detection of intradiscal gas. Pathology, microbiology, and imaging and clinical follow-up were used as the gold standard for presence of infection. Interrater agreement on CT and MRI, sensitivity, and positive predictive value were calculated, using the presence of gas as an indicator (test positive) for "no infection.", Results: There were 284 biopsies in 275 subjects (mean age 58 ± 1.0 (range 4-99) years; 101 (37%) females and 174 (63%) males). Of the biopsies, 12 (4%) were cervical, 80 (28%) were thoracic, 192 (68%) were lumbar, and 200 (70%) were considered true discitis-osteomyelitis based on pathology, imaging, and clinical follow-up. Interrater agreement was excellent for CT (kappa = 0.83) and poor for MRI (kappa =  - 0.021). The presence of gas had a 94% specificity and 76% negative predictive value for the absence of infection., Conclusion: CT is the preferred method for detecting intradiscal gas. The presence of gas means that discitis-osteomyelitis is unlikely. If intradiscal gas is present in the setting of discitis-osteomyelitis, the gas bubbles tend to be smaller and fewer in number., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Pleural effusions are challenging to diagnose, with approximately 20-50% of malignant effusions not diagnosed by cytology. Human epididymal protein 4 (HE4) may be useful in the differential diagnosis of pleural effusions. In serum, this biomarker shows false-positive results in some benign diseases. The aim of this study was to evaluate the diagnostic utility of HE4 in this setting and to identify false positives., Methods: Concentrations of HE4, adenosine deaminase, % polynuclear cells, and C-reactive protein, were determined in 238 pleural fluid samples and the estimated glomerular filtration rate (eGFr) in serum., Results: HE4 values ​​differed significantly (p < 0.01) between malignant [median (IQR)] [1065 (2085)] pmol/L and benign effusions [699 (589)] pmol/L. HE4 concentrations in gynecological and pulmonary tumors were significantly higher than in other tumors. For a cut-off point of 3050 pmol/L, 22 % sensitivity and 100 % specificity were obtained. In patients with benign disease, significant increases in HE4 were identified only in those with eGFr < 30 mL/min/1.73 m 2 [1050(596)] pmol/L, and not in those with eGFr > 30 mL/min/1.73 m 2 [597(532)] pmol/L). Two cut-offs were established for maximum specificity, depending on the eGFr: 3050 pmol/L for eGFr < 30 mL/min/1.73 m 2 and 1992 pmol/L for eGFr > 30 mL/min/1.73 m 2 . A sensitivity of 28.5 % was obtained for patients with eGFr > 30 mL/min/1.73 m 2 and 36.3 % for patients with eGFr < 30 mL/min/1.73 m 2 . The sensitivity using a specific cut-off point was 29.7 %., Conclusions: The determination of HE4 in pleural fluids demonstrates high specificity and low sensitivity. The use of specific cutoff points that are clinically adjusted improves sensitivity while maintaining maximum specificity., 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 © 2024 Elsevier B.V. All rights reserved.)

Enzymatic browning caused by polyphenol oxidases, tyrosinase and laccase, continues to be one of the main problems in winemaking. Therefore, wineries are very interested in studying the mechanisms of browning and procedures for decreasing the use sulphur dioxide. This research proposes a model to study tyrosinase activity from grape must using different substrates: one monophenol (p-hydroxybenzoic acid), two diphenols (caftaric acid and (-)-epicatechin) and one triphenol (gallic acid). The kinetic constants of tyrosinase, Vmax and K M , indicate that caftaric acid is the best substrate for tyrosinase, followed in decreasing order by (-)-epicatechin, gallic acid and p-hydroxybenzoic acid. This last acid does not appear to be susceptible to browning by the action of grape must tyrosinase. The influence of pH, temperature and ethanol on grape must tyrosinase were also determined and the results indicate that tyrosinase Vmax increases when pH and temperature are higher and that the presence of ethanol reduces it., 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 © 2024. Published by Elsevier Ltd.)

This study investigated the upcycling of distilled spent grain (DSG), a melanoidin-rich by-product of the Chinese liquor industry, via fungal solid-state fermentation (SSF). Two fungi, Aspergillus oryzae and Aspergillus awamori, were tested, with A. awamori growing better on DSG than A. oryzae. SSF with A. awamori increased the concentration of water-soluble protein and phenolic compounds in DSG extracts by 46.5 % and 52.5 %, respectively, and reduced melanoidin level by 73.5 % w/w of DSG, suggesting A. awamori could metabolize melanoidins. Submerged fermentation (SmF) using isolated DSG melanoidins as sole carbon and nitrogen sources confirmed this observation. After 3 days of fermentation, A. awamori and A. oryzae biomass reached 2.5 g/L and 1.5 g/L, quenching melanoidin color by 24.4 % and 12.4 %, respectively. SmF by A. awamori also released free arabinose, glucose, and xylose. Data highlighted the possibility of converting melanoidins into edible mycelia resources, potentially applicable to various melanoidin-rich food by-products., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective : Brain-computer interface (BCI) control systems monitor neural activity to detect the user's intentions, enabling device control through mental imagery. Despite their potential, decoding neural activity in real-world conditions poses significant challenges, making BCIs currently impractical compared to traditional interaction methods. This study introduces a novel motor imagery (MI) BCI control strategy for operating a physically assistive robotic arm, addressing the difficulties of MI decoding from electroencephalogram (EEG) signals, which are inherently non-stationary and vary across individuals.&#xD; Approach : A proof-of-concept BCI control system was developed using commercially available hardware, integrating MI with eye tracking in an augmented reality (AR) user interface to facilitate a shared control approach. This system proposes actions based on the user's gaze, enabling selection through imagined movements. A user study was conducted to evaluate the system's usability, focusing on its effectiveness and efficiency.&#xD; Main results: Participants performed tasks that simulated everyday activities with the robotic arm, demonstrating the shared control system's feasibility and practicality in real-world scenarios. Despite low online decoding performance (mean accuracy: 0.52 9, F1: 0.29, Cohen's Kappa: 0.12), participants achieved a mean success rate of 0.83 in the final phase of the user study when given 15 minutes to complete the evaluation tasks. The success rate dropped below 0.5 when a 5-minute cutoff time was selected.&#xD; Significance : These results indicate that integrating AR and eye tracking can significantly enhance the usability of BCI systems, despite the complexities of MI-EEG decoding. While efficiency is still low, the effectiveness of our approach was verified. This suggests that BCI systems have the potential to become a viable interaction modality for everyday applications&#xD;in the future., (Creative Commons Attribution license.)

Purpose: The aim of this study is to propose a classification for patients with recurrent head and neck squamous cell carcinoma (HNSCC) treated with salvage surgery based on the location of the primary tumor and data commonly found in the pathological report of the resection., Methods: Retrospective study of 665 patients with HNSCC treated with a salvage surgery after a local and/or regional recurrence of the tumor., Results: We propose a new postoperative classification for patients with recurrent HNSCC treated with salvage surgery. PATH classification stratifies patients into 4 stages based on the glottic or non-glottic location of the primary tumor, the local and regional pathologic extension of the tumor, the status of the surgical margins, and the presence of lymph node metastases with extracapsular spread. The PATH classification was more homogeneous in the prognosis of patients included in each of its stages, and it had a better prognostic discrimination capacity between stages than the rpTNM classification. According to the PATH classification, the 5-year disease-specific survival was: PATH I (n = 306) 82.8%; PATH II (n = 119) 47.1%; PATH III (n = 202) 24.4%; PATH IV (n = 38) 3.7%. For the rpTNM classification, the 5-year disease-specific survival was: stage I (n = 119) 85.1%; stage II (n = 134) 68.4%; stage III (n = 111) 59.5%; stage IV (n = 301) 33.3%., Conclusion: The PATH classification for HNSCC patients with local and/or regional recurrence treated with salvage surgery had a better prognostic capacity than the rpTNM classification., Level of Evidence: Level IV., (© 2024. The Author(s).)

Druggable pockets are protein regions that have the ability to bind organic small molecules, and their characterization is essential in target-based drug discovery. However, deriving pocket descriptors is challenging and existing strategies are often limited in applicability. We introduce PocketVec, an approach to generate pocket descriptors via inverse virtual screening of lead-like molecules. PocketVec performs comparably to leading methodologies while addressing key limitations. Additionally, we systematically search for druggable pockets in the human proteome, using experimentally determined structures and AlphaFold2 models, identifying over 32,000 binding sites across 20,000 protein domains. We then generate PocketVec descriptors for each site and conduct an extensive similarity search, exploring over 1.2 billion pairwise comparisons. Our results reveal druggable pocket similarities not detected by structure- or sequence-based methods, uncovering clusters of similar pockets in proteins lacking crystallized inhibitors and opening the door to strategies for prioritizing chemical probe development to explore the druggable space., (© 2024. The Author(s).)

A computational study on the interplay between ligand functionalization and guest effects on the transition temperature ( T 1/2 ) in the [Fe 2 (L 1 R ) 3 ]@X (L 1 = 1,3-bis-(3-(pyridin-2-yl)-1 H -pyrazol-5-yl)benzene, X = H - , F - , Cl - , Br - , I - and [BF 4 ] - , R = H, F, or CH 3 has a linear correlation with the increasing guest size. More importantly, small guests can move away from the center of the cavity, thus enhancing the two-step characteristic of the transition. All the data can be understood by analyzing the underlying electronic structure of the studied systems in terms of the relevant d-based molecular orbitals. These results can help in the rational design of new MOCs that can operate as sensors at specific temperatures, thus accelerating the discovery of new SCO devices with tailored properties.T 1/2 as expected, while the guest effect in lowering the T 1/2 has a linear correlation with the increasing guest size. More importantly, small guests can move away from the center of the cavity, thus enhancing the two-step characteristic of the transition. All the data can be understood by analyzing the underlying electronic structure of the studied systems in terms of the relevant d-based molecular orbitals. These results can help in the rational design of new MOCs that can operate as sensors at specific temperatures, thus accelerating the discovery of new SCO devices with tailored properties.

This study delves into the intriguing properties of the 1H/1T-TaS 2 van der Waals heterostructure, focusing on the transparency of the 1H layer to the charge density wave of the underlying 1T layer. Despite the sizable interlayer separation and metallic nature of the 1H layer, positive bias voltages result in a pronounced superposition of the 1T charge density wave structure on the 1H layer. The conventional explanation relying on tunneling effects proves insufficient. Through a comprehensive investigation combining low-temperature scanning tunneling microscopy, scanning tunneling spectroscopy, non-contact atomic force microscopy, and first-principles calculations, we propose an alternative interpretation. The transparency effect arises from a weak yet substantial electronic coupling between the 1H and 1T layers, challenging prior understanding of the system. Our results highlight the critical role played by interlayer electronic interactions in van der Waals heterostructures to determine the final ground states of the systems.

Increasing seawater influence in coastal areas is an ongoing environmental issue. Gardening is a widespread activity mainly in touristic areas such as the Mediterranean coasts. However, the use of exotic species well adapted to salinity encompasses the risk of invasive species introduction. This study aimed to evaluate salinity tolerance of native geophytes, Pancratium maritimum L. and Eryngium maritimum L., to assess their use as ornamental species in salt affected coastal areas. Experiments were conducted using cultivated plants for flowering response and physiological and enzymatic antioxidant response. Six treatments were applied for two months, exposing plants to seawater (SW) dilutions (Tap-Water, 6.25%SW, 12.5%SW, 25%SW, 50%SW and 100%SW). Taxa decreased inflorescence production being this effect more architectonical in E. maritimum and affecting all inflorescence integrity in P. maritimum . Flowering time was strongly delayed and reduced in P. maritimum , while E. maritimum showed smaller effects among treatments. Physiological and biochemical response showed at moderate salinity levels (1/4SW) variation concomitant with late stress response and senescence in P. maritimum, with decreased water use efficiency, NPQ values, and enzymatic activity, and increased malondialdehyde (MDA) levels. In contrast, E. maritimum showed early stress response with steady gas exchange response, increasing NPQ values and catalase (CAT) and superoxide dimutase (SOD) activity, and decreasing MDA levels with salinity. Glutathione enzymes showed limited participation in both species. The results of this study suggest that neither species can be classified as halophytes, but they exhibit tolerance to low and moderate salinity levels, making them suitable for ornamental use., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01502-0., Competing Interests: Conflict of interestThe 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. On behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2024.)

Subtype 5 metabotropic glutamate receptors (mGlu 5 ) are known to play an important role in regulating cognitive, social and valence systems. However, it remains largely unknown at which circuits and neuronal types mGlu 5 act to influence these behavioral domains. Altered tissue- or cell-specific expression or function of mGlu 5 has been proposed to contribute to the exacerbation of neuropsychiatric disorders. Here, we examined how these receptors regulate the activity of somatostatin-expressing (SST+) neurons, as well as their influence on behavior and brain rhythmic activity. Loss of mGlu 5 in SST+ neurons elicited excitatory synaptic dysfunction in a region and sex-specific manner together with a range of emotional imbalances including diminished social novelty preference, reduced anxiety-like behavior and decreased freezing during retrieval of fear memories. In addition, the absence of mGlu 5 in SST+ neurons during fear processing impaired theta frequency oscillatory activity in the medial prefrontal cortex and ventral hippocampus. These findings reveal a critical role of mGlu 5 in controlling SST+ neurons excitability necessary for regulating negative emotional states., (© 2024. The Author(s).)

Psychotic disorders entail intricate conditions marked by disruptions in cognition, perception, emotions, and social behavior. Notably, psychotic patients who use cannabis tend to show less severe deficits in social behaviors, such as the misinterpretation of social cues and the inability to interact with others. However, the biological underpinnings of this epidemiological interaction remain unclear. Here, we used the NMDA receptor blocker phencyclidine (PCP) to induce psychotic-like states and to study the impact of adolescent cannabinoid exposure on social behavior deficits and synaptic transmission changes in hippocampal area CA2, a region known to be active during social interactions. In particular, adolescent mice underwent 7 days of subchronic treatment with the synthetic cannabinoid, WIN 55, 212-2 (WIN) followed by one injection of PCP. Using behavioral, biochemical, and electrophysiological approaches, we showed that PCP persistently reduced sociability, decreased GAD67 expression in the hippocampus, and induced GABAergic deficits in proximal inputs from CA3 and distal inputs from the entorhinal cortex (EC) to CA2. Notably, WIN exposure during adolescence specifically restores adult sociability deficits, the expression changes in GAD67, and the GABAergic impairments in the EC-CA2 circuit, but not in the CA3-CA2 circuit. Using a chemogenetic approach to target EC-CA2 projections, we demonstrated the involvement of this specific circuit on sociability deficits. Indeed, enhancing EC-CA2 transmission was sufficient to induce sociability deficits in vehicle-treated mice, but not in animals treated with WIN during adolescence, suggesting a mechanism by which adolescent cannabinoid exposure rescues sociability deficits caused by enhanced EC-CA2 activity in adult mice., 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 © 2024 Elsevier Ltd. All rights reserved.)

Brain atrophy measurements derived from magnetic resonance imaging (MRI) are a promising marker for the diagnosis and prognosis of neurodegenerative pathologies such as Alzheimer's disease or multiple sclerosis. However, its use in individualized assessments is currently discouraged due to a series of technical and biological issues. In this work, we present a deep learning pipeline for segmentation-based brain atrophy quantification that improves upon the automated labels of the reference method from which it learns. This goal is achieved through tissue similarity regularization that exploits the a priori knowledge that scans from the same subject made within a short interval must have similar tissue volumes. To train the presented pipeline, we use unlabeled pairs of T1-weighted MRI scans having a tissue similarity prior, and generate the target brain tissue segmentations in a fully automated manner using the fsl&#95;anat pipeline implemented in the FMRIB Software Library (FSL). Tissue similarity regularization is enforced during training through a weighted loss term that penalizes tissue volume differences between short-interval scan pairs from the same subject. In inference, the pipeline performs end-to-end skull stripping and brain tissue segmentation from a single T1-weighted MRI scan in its native space, i.e., without performing image interpolation. For longitudinal evaluation, each image is independently segmented first, and then measures of change are computed. We evaluate the presented pipeline in two different MRI datasets, MIRIAD and ADNI1, which have longitudinal and short-interval imaging from healthy controls (HC) and Alzheimer's disease (AD) subjects. In short-interval scan pairs, tissue similarity regularization reduces the quantification error and improves the consistency of measured tissue volumes. In the longitudinal case, the proposed pipeline shows reduced variability of atrophy measures and higher effect sizes of differences in annualized rates between HC and AD subjects. Our pipeline obtains a Cohen's d effect size of d=2.07 on the MIRIAD dataset, an increase from the reference pipeline used to train it (d=1.01), and higher than that of SIENA (d=1.73), a well-known state-of-the-art approach. In the ADNI1 dataset, the proposed pipeline improves its effect size (d=1.37) with respect to the reference pipeline (d=0.80) and surpasses SIENA (d=1.33). The proposed data-driven deep learning regularization reduces the biases and systematic errors learned from the reference segmentation method, which is used to generate the training targets. Improving the accuracy and reliability of atrophy quantification methods is essential to unlock brain atrophy as a diagnostic and prognostic marker in neurodegenerative pathologies., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Liver transplantation remains the only definitive treatment for end-stage liver diseases. However, the increasing prevalence of fatty liver disease among potential donors exacerbates the shortage of suitable organs. This study evaluates the efficacy of the preservation solution Institut Georges Lopez-2 (IGL-2) compared to Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions in mitigating ischemia-reperfusion injury (IRI) in steatotic livers. Using Zucker Obese rat livers, we assessed the impact of 24-h static cold storage (SCS) with each solution on transaminase release, glutathione redox balance, antioxidant enzyme activity, lipoperoxidation, and inflammation markers. IGL-2 and UW solutions demonstrated reduced transaminase and lactate levels compared to HTK, indicating better preservation of liver integrity. IGL-2 maintained a higher reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, suggesting more effective management of oxidative stress. Antioxidant enzyme activities catalase, superoxide dismutase, and glutathione peroxidase (CAT, SOD, GPX) were higher in IGL-2 preserved livers, contributing to decreased oxidative damage. Lipid peroxidation markers and inflammatory markers were lower in IGL-2 than in HTK, indicating reduced oxidative stress and inflammation. Additionally, improved mitochondrial function was observed in the IGL-2 group, correlating with reduced reactive oxygen species (ROS) production and lipid peroxidation. These findings suggest that IGL-2 offers superior preservation of liver viability, reduces oxidative stress, and minimizes inflammation compared to HTK and UW solutions. By maintaining a higher ratio of reduced glutathione and antioxidant enzyme activity, IGL-2 effectively mitigates the harmful effects of ischemia-reperfusion injury. The reduced lipid peroxidation and inflammation in the IGL-2 group further underscore its potential in improving liver transplant outcomes. These results highlight the importance of optimizing preservation solutions to enhance the viability and functionality of donor organs, potentially expanding the donor pool and improving the success rates of liver transplantation. Future research should focus on refining preservation techniques and exploring additional protective agents to further improve organ preservation and transplant outcomes.

Background: Performing rhinoplasty in patients with craniofacial malformations remains a challenge, even for experienced surgeons. Advances in 3D technology and its application in surgical planning and printing of cutting guides and splints have become important tools to improve aesthetic and functional results., Objectives: To describe an in-house workflow for surgical planning and printing of cutting guides and splints for complex rhinoplasty cases., Methods: This article describes an in-house workflow for complex rhinoplasty, as used in the maxillofacial department of a children's hospital specialized in the treatment of cleft and craniofacial malformations., Results: Customized surgical guides help the surgeon to harvest and mold potential septal and costochondral grafts more accurately, to reduce surgical time and to verify the dimensions of the sculpted nasal shape following surgical planning templates. Patient satisfaction degree according to Rhinoplasty Outcome Evaluation questionnaire was 18/24., Conclusions: The presented workflow represents a potential asset in obtaining more accurate and satisfactory results in complex rhinoplasties., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Emotions and behavior can be affected by social chemosignals from conspecifics. For instance, olfactory signals from stressed individuals induce stress-like physiological and synaptic changes in naïve partners. Direct stress also alters cognition, but the impact of socially transmitted stress on memory processes is currently unknown. Here we show that exposure to chemosignals produced by stressed individuals is sufficient to impair memory retrieval in unstressed male mice. This requires astrocyte control of information in the olfactory bulb mediated by mitochondria-associated CB1 receptors (mtCB1). Targeted genetic manipulations, in vivo Ca 2+ imaging and behavioral analyses reveal that mtCB1-dependent control of mitochondrial Ca 2+ dynamics is necessary to process olfactory information from stressed partners and to define their cognitive consequences. Thus, olfactory bulb astrocytes provide a link between social odors and their behavioral meaning., (© 2024. The Author(s).)

This study evaluates an innovative control approach to assistive robotics by integrating brain-computer interface (BCI) technology and eye tracking into a shared control system for a mobile augmented reality user interface. Aimed at enhancing the autonomy of individuals with physical disabilities, particularly those with impaired motor function due to conditions such as stroke, the system utilizes BCI to interpret user intentions from electroencephalography signals and eye tracking to identify the object of focus, thus refining control commands. This integration seeks to create a more intuitive and responsive assistive robot control strategy. The real-world usability was evaluated, demonstrating significant potential to improve autonomy for individuals with severe motor impairments. The control system was compared with an eye-tracking-based alternative to identify areas needing improvement. Although BCI achieved an acceptable success rate of 0.83 in the final phase, eye tracking was more effective with a perfect success rate and consistently lower completion times (p<0.001). The user experience responses favored eye tracking in 11 out of 26 questions, with no significant differences in the remaining questions, and subjective fatigue was higher with BCI use (p=0.04). While BCI performance lagged behind eye tracking, the user evaluation supports the validity of our control strategy, showing that it could be deployed in real-world conditions and suggesting a pathway for further advancements.

Brain-computer interfaces (BCI) enable users to control devices through their brain activity. Motor imagery (MI), the neural activity resulting from an individual imagining performing a movement, is a common control paradigm. This study introduces a user-centric evaluation protocol for assessing the performance and user experience of an MI-based BCI control system utilizing augmented reality. Augmented reality is employed to enhance user interaction by displaying environment-aware actions, and guiding users on the necessary imagined movements for specific device commands. One of the major gaps in existing research is the lack of comprehensive evaluation methodologies, particularly in real-world conditions. To address this gap, our protocol combines quantitative and qualitative assessments across three phases. In the initial phase, the BCI prototype's technical robustness is validated. Subsequently, the second phase involves a performance assessment of the control system. The third phase introduces a comparative analysis between the prototype and an alternative approach, incorporating detailed user experience evaluations through questionnaires and comparisons with non-BCI control methods. Participants engage in various tasks, such as object sorting, picking and placing, and playing a board game using the BCI control system. The evaluation procedure is designed for versatility, intending applicability beyond the specific use case presented. Its adaptability enables easy customization to meet the specific user requirements of the investigated BCI control application. This user-centric evaluation protocol offers a comprehensive framework for iterative improvements to the BCI prototype, ensuring technical validation, performance assessment, and user experience evaluation in a systematic and user-focused manner., Competing Interests: MO and BV were employed by imec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dillen, Omidi, Díaz, Ghaffari, Roelands, Vanderborght, Romain and De Pauw.)