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Introduction: Physical exercise (PE) improves symptoms and quality of life in people with multiple sclerosis (pwMS). However, incorporating PE into daily lives of pwMS pose difficulties. As an alternative to in-person PE, e-based PE has been proposed because of its advantages in terms of accessibility and convenience., Objective: To synthesize existing evidence on e-based PE at home in adults MS and discuss study designs, rehabilitation programs, intervention effects and possible knowledge gaps., Methods: In this scoping review, a systematic search in electronic databases including Embase, Medline, CINAHL and Cochrane Library was conducted following the PRISMA guidelines. Peer-reviewed articles in English on e-based PE interventional studies at home involving adult pwMS, published from 2008 until April 2023, were identified and exported to Covidence. Data from the included studies were extracted and synthesized. This scoping review identified different types of e-based PE interventions used in pwMS across different study designs, but when evaluating intervention effects, this review focused solely on randomized controlled trials (RCTs)., Results: A total of 3,006 studies were retrieved and 179 studies were screened in full text, resulting in the inclusion of 54 studies with a total of 2,359 pwMS. Of those, 33 were RCTs and three were qualitative studies. The studies reported on various e-based interventions including video-based programs, telerehabilitation, and web-based programs. The interventions evaluated muscle strength, cardiorespiratory fitness, walking speed, endurance, balance, and fatigue, as well as symptoms of depression and cognitive dysfunction. E-based PE interventions at home in RCTs demonstrated improvement of depressive symptoms and anxiety, while inconsistent results were reported for fatigue, walking speed and balance. No significant benefits were observed regarding dexterity. Results were generally heterogeneous and were limited by small sample sizes. Several limitations were identified, such as lack of physical activity assessment prior to the intervention and poor reporting of duration, intensity, frequency and adherence to e-based PE interventions., Conclusion: E-based PE interventions in pwMS may improve MS-related symptoms, but the study quality is generally low, and findings are often inconsistent. Several important limitations of the existing literature have been identified in the present review, which can guide future research., Competing Interests: BW receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for neuromyelitis optica spectrum disorders, served on adjudication committee for clinical trials conducted by MedImmune/VielaBio, Alexion, and UCB Biosciences and consulted for Chugai/Roche/Genentech, Horizon Therapeutics and Mitsubishi-Tanabe regarding neuromyelitis optica spectrum disorders. He has received honoraria for speaking at internal meetings of Genentech, Novartis, and Horizon and at external meetings for Roche. FP served on the scientific advisory boards of Novartis and MedImmune; received travel funding and/or speaker honoraria from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an associate editor of Neurology: Neuroimmunology & Neuroinflammation; is an academic editor of PLoS ONE; consulted for Sanofi Genzyme, Biogen, MedImmune, Shire, and Alexion; received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Geynzme, Alexion, and Merck Serono; and received research support from the German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy-Jackson Charitable Foundation, and NMSS. SSk received personal fees from Munksgaard, TrustMe-Ed, and Nestlé Health Science, outside the submitted work, and co-founder of GLA:D®, a not-for profit initiative hosted at University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice. SSk was funded by a program grant from Region Zealand (Exercise First) and two grants from the European Union's Horizon 2020 research and innovation program, one from the European Research Council (MOBILIZE, grant agreement No. 801790) and the other under grant agreement No. 945377 (ESCAPE). UD has received research support, travel grants and/or teaching honorary from Biogen, Merck Serono, Novartis, Bayer Schering and Sanofi Aventis as well as honoraria from serving on scientific meetings of Biogen and Sanofi Genzyme. 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 author(s) 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 Adnan, Roikjaer, Samadzadeh, Richter, Weinshenker, Paul, Skou, Dalgas and Asgari.)

Literary reading is an interactive process between a reader and a text that depends on a balance between cognitive effort and emotional rewards. By studying both the crucial features of the text and of the subjective reader reception, a better understanding of this interactive process can be reached. In the present study, subjects ( N =31) read and rated a work of narrative fiction that was written in a poetic style, thereby offering the readers two pathways to cognitive rewards: Aesthetic appreciation and narrative immersion. Using purely text-based quantitative descriptors, we were able to independently and accurately predict the subjective ratings in the dimensions comprehensibility, valence, arousal, and liking across roughly 140 pages of naturalistic text. The specific text features that were most important in predicting each rating dimension are discussed in detail. In addition, the implications of the findings are discussed more generally in the context of existing models of literary processing and future research avenues for empirical literary studies., Competing Interests: 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., (Copyright © 2024 Tilmatine, Lüdtke and Jacobs.)

Background: Recent years have seen a rapid growth in the number of online health communities targeted at patients with long-term conditions. Myasthenia Gravis (MG) is a rare neurological disease for which such communities have not been analysed before. The aim of this study was to better understand the needs of the MG population through the collation and categorisation of questions that users of MG social media were asking fellow users on these platforms., Methodology: Systematic observation of four MG Facebook groups was conducted over a 2-month period. Groups were selected for analysis based on the following systematic criteria: Language (English), Membership (≥ 5,000 members), group activity (≥ 2 posts per week), target audience (general MG population) and researcher engagement with group administrators. The study protocol was reviewed by the institutional review board of the Charité-Universitätsmedizin Berlin (EA2/106/22). During the observation period, data were extracted from individual posts featuring questions made across each group using a systematic and objective coding scheme. All data points were coded directly from the source and collated into an SPSS database (IBM SPSS V.27, SPSS). Absolute and relative frequencies were calculated for categorical variables and proportions were compared across groups to validate the credibility and relevance of different requests., Results: Of the 2,062 posts observed ( N  = 2,062), 1,392 featured questions ( n  = 1,392). Questions were asked by 787 unique users: 531 were identified as one-time users (67%) and 256 were identified as repeat users (33%). Six hundred and fifty six users were classified as presumed diagnosed (83%), 61 as seeking diagnosis (8%), 69 as family and/or friends (9%) and as other (<0%). Eight unique categories of questions were observed including MG treatment (31%), Symptoms (19%), Living with MG (12%), Diagnosis (10%), non-MG medication (11%), Tests (8%), Location (4%) and Other (4%)., Conclusion: Members of the MG population make active use of online health communities to seek and discuss practical information concerning various aspects of the disease, its diagnosis and care. The openness and willingness of the sample population to share sensitive medical information shows a high need for information not entirely catered to by the medical profession., Competing Interests: SL has received speakers’ honoraria from Alexion, Argenx, Hormosan and UCB and honoraria for attendance at advisory boards from Alexion, Argenx, Biogen, UCB and Roche. MS has received speaker’s honoraria and honoraria for attendance at advisory boards from Argenx and Alexion. AM has received speaker or consultancy honoraria or financial research support (paid to his institution) from Alexion Pharmaceuticals, Argenx, Axunio, Destin, Grifols, Hormosan Pharma, Janssen, Merck, Octapharma, UCB, and Xcenda. AM serves as medical advisory board Chairman of the German Myasthenia Gravis Society. 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 Legg, Meisel, Stein, Gerischer, Herdick, Krüger, Mergenthaler, Masanneck and Lehnerer.)

Introduction: Prenatal mental health problems are associated with morbidity for the pregnant person, and their infants are at long-term risk for poor health outcomes. We aim to explore how the SARS-CoV-2 pandemic affected the mental health of pregnant people in the United Kingdom (UK), and to further identify resilience factors which may have contributed to varying mental health outcomes. We also aim to examine the quality of antenatal care provided during the pandemic in the UK and to identify potential inadequacies to enhance preparedness for future events., Methods: During June-November 2020, we recruited 3666 individuals in the UK for the EPPOCH pregnancy cohort (Maternal mental health during the COVID-19 pandemic: Effect of the Pandemic on Pregnancy Outcomes and Childhood Health). Participants were assessed for depression, anxiety, anger and pregnancy-related anxiety using validated scales. Additionally, physical activity, social support, individualized support and personal coping ability of the respondents were assessed as potential resilience factors., Results: Participants reported high levels of depression (57.05%), anxiety (58.04%) and anger (58.05%). Higher levels of social and individualized support and personal coping ability were associated with lower mental health challenges. Additionally, pregnant individuals in the UK experienced higher depression during the pandemic than that reported in Canada. Finally, qualitative analysis revealed that restrictions for partners and support persons during medical appointments as well as poor public health communication led to increased mental health adversities and hindered ability to make medical decisions., Discussion: This study revealed increased mental health challenges among pregnant individuals in the UK during the SARS-CoV-2 pandemic. These results highlight the need for reassessing the mental health support measures available to pregnant people in the UK, both during times of crisis and in general., Competing Interests: 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. The author(s) 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 Datye, Smiljanic, Shetti, MacRae-Miller, van Teijlingen, Vinayakarao, Peters, Lebel, Tomfohr-Madsen, Giesbrecht, Khashu and Conrad.)

Fast and effective anesthesia is the key for refining many invasive procedures in fish and gaining reliable data. For fish as for all vertebrates, it is also required by European law to reduce pain, suffering, and distress to the unavoidable minimum in husbandry and experiments. The most often used substance to induce anesthesia in zebrafish is tricaine (MS-222). When properly prepared and dosed, tricaine causes rapid loss of mobility, balance and reaction to touch. These signs are interpreted as a stage of deep anesthesia although its effects on the central nervous system have not convincingly been shown. Therefore, it might be possible that tricaine first acts only on the periphery, resulting in a paralyzed instead of an anesthetized fish. This has severe implications for animals undergoing procedures. To investigate the effects of tricaine on the central nervous system, we used zebrafish larvae [Tg( elavl3 :H2B-GCaMP6s)] at 4 days post fertilization (dpf), expressing a calcium indicator (GCaMP6s) in all neurons, that allows monitoring and quantifying the neuronal activity. After treating larvae with 168 mg/L tricaine, a rapid loss of neuronal activity in the forebrain was observed in confocal microscopy. In contrast, only mild effects were seen in the midbrain and hindbrain. In conclusion, the different larval brain areas showed differences in the sensitivity to tricaine treatment. The effects on the central nervous system are indicative of tricaine's anesthetic function and are consistent with behavioral observations of inactivity and unresponsiveness to touch., Competing Interests: 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., (Copyright © 2024 Ohnesorge, Wilzopolski, Steinfath, Lewejohann, Banneke and Heinl.)

Introduction: Holistic phenotyping of rodent models is increasing, with a growing awareness of the 3Rs and the fact that specialized experimental setups can also impose artificial restrictions. Activity is an important parameter for almost all basic and applied research areas involving laboratory animals. Locomotor activity, the main form of energy expenditure, influences metabolic rate, muscle mass, and body weight and is frequently investigated in metabolic disease research. Additionally, it serves as an indicator of animal welfare in therapeutic, pharmacological, and toxicological studies. Thus, accurate and effective measurement of activity is crucial. However, conventional monitoring systems often alter the housing environment and require handling, which can introduce artificial interference and lead to measurement inaccuracies., Methods: Our study focused on evaluating circadian activity profiles derived from the DVC and comparing them with conventional activity measurements to validate them statistically and assess their reproducibility. We utilized data from metabolic studies, an Alzheimer's disease model known for increased activity, and included DVC monitoring in a project investigating treatment effects on activity in a type-1-like diabetes model., Results: The DVC data yielded robust, scientifically accurate, and consistent circadian profiles from group-housed mice, which is particularly advantageous for longitudinal experiments. The activity profiles from both systems were fully comparable, providing matching profiles. Using DVC monitoring, we confirmed the hyperactivity phenotype in an AD model and reproduced a decline in activity in type-1-like diabetes model., Discussion: In our work, we derived robust circadian activity profiles from the DVC data of group-housed mice, which were scientifically accurate, reproducible and comparable to another activity measurement. This approach can not only improve animal welfare according to the 3R principles but can also be implement in high-throughput longitudinal studies. Furthermore, we discuss the advantages and limitations of DVC activity measurements to highlight its potential and avoid confounders., Competing Interests: 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., (Copyright © 2024 Sun, Gaerz, Oeing, Mai and Brachs.)

Aggression is an adaptive social behavior crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual wellbeing. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in regulating impulsive and aggressive behaviors. Mice lacking in brain serotonin, due to the ablation of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in serotonin synthesis, could serve as a potential model for studying pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviors in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on the everyday expression of social and non-social behaviors and their correlations in undisturbed, group-living Tph2 -deficient and wildtype mice. By training a machine learning algorithm on behavioral time series, "allogrooming", "struggling at feeder", and "eating" emerged as key behaviors dissociating one genotype from the other. Although Tph2 -deficient mice exhibited characteristics of pathological aggression and reduced communication compared to wildtype animals, they still demonstrated affiliative huddle behaviors to normal levels. Altogether, such a distinct and dynamic phenotype of Tph2 -deficient mice influenced the group's structure and the subsequent development of its hierarchical organization. These aspects were analyzed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on various aspects of life, both at the individual and group levels. Home cage monitoring allows the observation of the natural behaviors of mice in a semi-natural habitat, providing an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and its potential role in complex brain disorders., Competing Interests: YW owns equity in PhenoSys. 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 author(s) 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 Rivalan, Alonso, Mosienko, Bey, Hyde, Bader, Winter and Alenina.)

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain's physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain's nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain's dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou's ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain's response to injury and pathology, embracing Malabou's concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice., Competing Interests: 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., (Copyright © 2024 Fekonja, Schenk, Schröder, Tomasello, Tomšič and Picht.)

Background: Insomnia is a prevalent disorder that impacts quality of life and leads to significant economic costs. Treatment includes both non-medication and pharmacological interventions, with international guidelines recommending cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment., Objective: To describe current insomnia treatment practices in South Korea, focusing on pharmacological and non-medication treatments, and to identify gaps in guideline implementation., Methods: This cohort study used data from the Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2002 to 2019 and identified 18,003 patients newly diagnosed with insomnia between 2015 and 2019. This study analyzed treatment patterns and utilization rates., Results: Of the 18,003 patients, 16,181 (89.9%) received pharmacological treatment, resulting in 35,638 prescriptions. Zolpidem (60%) and benzodiazepines (30-40%) were the most prescribed medications. Most patients were treated in clinics, with consistent dosages and increasing treatment lengths. Psychotherapy claims rose from 3.20% in 2015 to 9.14% in 2019, particularly in general hospitals (22.06% to 48.37%), but remained low in clinics (1.26% to 2.08%)., Conclusion: Pharmacological treatments dominate insomnia management in South Korea, with CBT-I being underutilized. Future efforts should focus on integrating non-pharmacological treatment into routine practice and exploring treatment risks and effectiveness based on patient demographics., Competing Interests: Authors DM and DL were employed by the company WELT Corp. Ltd.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 Moon, Piao, Lee and Han.)

Introduction: Some cyanobacteria can use far-red light (FRL) to drive oxygenic photosynthesis, a phenomenon known as Far-Red Light Photoacclimation (FaRLiP). It can expand photosynthetically active radiation beyond the visible light (VL) range. Therefore, it holds promise for biotechnological applications and may prove useful for the future human exploration of outer space. Typically, FaRLiP relies on a cluster of ~20 genes, encoding paralogs of the standard photosynthetic machinery. One of them, a highly divergent D1 gene known as chlF (or psbA4 ), is the synthase responsible for the formation of the FRL-absorbing chlorophyll f (Chl f ) that is essential for FaRLiP. The minimum gene set required for this phenotype is unclear. The desert cyanobacterium Chroococcidiopsis sp. CCMEE 010 is unusual in being capable of FaRLiP with a reduced gene cluster (15 genes), and it lacks most of the genes encoding FR-Photosystem I., Methods: Here we investigated whether the reduced gene cluster of Chroococcidiopsis sp. CCMEE 010 is transcriptionally regulated by FRL and characterized the spectral changes that occur during the FaRLiP response of Chroococcidiopsis sp. CCMEE 010. In addition, the heterologous expression of the Chl f synthase from CCMEE 010 was attempted in three closely related desert strains of Chroococcidiopsis ., Results: All 15 genes of the FaRLiP cluster were preferentially expressed under FRL, accompanied by a progressive red-shift of the photosynthetic absorption spectrum. The Chl f synthase from CCMEE 010 was successfully expressed in two desert strains of Chroococcidiopsis and transformants could be selected in both VL and FRL., Discussion: In Chroococcidiopsis sp. CCME 010, all the far-red genes of the unusually reduced FaRLiP cluster, are transcriptionally regulated by FRL and two closely related desert strains heterologously expressing the chlF010 gene could grow in FRL. Since the transformation hosts had been reported to survive outer space conditions, such an achievement lays the foundation toward novel cyanobacteria-based technologies to support human space exploration., Competing Interests: 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. The author(s) 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 di Stefano, Battistuzzi, La Rocca, Selinger, Nürnberg and Billi.)

Background: Guided Internet-based interventions (IBIs) are typically found to be more effective than unguided ones, but the reasons behind this are not well understood. The therapist-client working alliance, crucial in face-to-face psychotherapy, is also increasingly recognized as an important factor in IBIs. This study examines trajectories of the working alliance and its relationship to therapeutic guidance through a secondary analysis of a randomized controlled trial (RCT) on Selfapy, a 12-week IBI based on cognitive behavioral therapy for depressive disorders. The trial compared a therapist-guided version (with weekly calls) to an unguided version (n = 301, mean age 37 years, 83% female, mean BDI-II = 30.09)., Methods: Based on an intention-to-treat approach, this study investigates within- and between-group differences in the quality of the working alliance, assessed with the WAI-SR questionnaire at mid- and post-treatment via repeated measures ANOVA. Furthermore, correlations and mediation analyses were conducted to explore the relationship between the working alliance and outcomes, as well as adherence parameters., Results: Findings indicate that the IBI was successful in fostering a robust working alliance in both intervention groups, with similar ratings at mid-treatment but significantly higher ratings in the guided group at post-treatment (Cohen's d = -0.38). Post-treatment working alliance scores were positively linked to symptom reduction at post-treatment (guided: r = .25, unguided r = .15) and follow-up (guided: r = .25, unguided: r = .17). In the unguided group, the association was primarily driven by the subscale task. Serial mediation analysis indicated that the relationship between guidance and outcomes at follow-up was mediated by working alliance (b = 0.59; 95% CI: 0.14, 1.22) and a link between working alliance and adherence (b = 0.15; 95% CI: 0.04, 0.34)., Conclusions: Considering limitations like using a questionnaire developed for face-to-face therapy, findings support the importance of the working alliance in guided IBIs, while also providing new insights into its role and formation in unguided IBIs. The potential benefits of a strong working alliance, notably by improving adherence, may prove crucial for integrating guided as well as unguided IBIs into routine use, indicating the need for additional research in this context., Clinical Trial Registration: https://tinyurl.com/2p9h5hnx, German Clinical Trials Register DRKS00017191., Competing Interests: Author RK was employed by the company Selfapy as a student from November 2016 to September 2017. Author SK received consultancy fees for the DiGA Selfapy, he was consultant/advisor/speaker for Janssen, Otsuka, ROVI and received lecturer’s royalties for psychotherapy workshops, e.g. CBASP. Author JK received funding for clinical studies from the German Federal Ministry of Health and Servier. He received payment for lectures on internet interventions from Oberberg, Servier, and Stillachhaus. He also received consulting fees from companies involved in the development and distribution of internet interventions (all about me, Ethypharm, sympatient). Additionally, he received royalties for books from Beltz, Elsevier, Hogrefe, and Springer, and honoraria for workshops, including psychotherapy workshops (e.g., CBASP). 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 Haaf, Schefft, Krämer, Klein and Köhler.)

Antimicrobial resistance mediated by extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated cephalosporinase (AmpC)-producing Enterobacterales, as well as carbapenemase-producing Enterobacterales have globally increased among companion animals, posing a potential health risk to humans in contact with them. This prospective longitudinal study investigates the transfer of ESBL/AmpC- and carbapenemase-producing Enterobacterales between companion animals and their cohabitant humans in Portugal (PT) and the United Kingdom (UK) during animal infection. Fecal samples and nasal swabs collected from dogs and cats with urinary tract infection (UTI) or skin and soft tissue infection (SSTI), and their cohabitant humans were screened for resistant strains. Relatedness between animal and human strains was established by whole-genome sequencing (WGS). ESBL/AmpC-producing Enterobacterales were detected in companion animals (PT = 55.8%; UK = 36.4%) and humans (PT = 35.9%; UK = 12.5%). Carbapenemase-producing Enterobacterales carriage was observed in one dog from Portugal (2.6%) and another dog from the UK (4.5%). Transmission of index clinical ESBL-producing Escherichia coli and Klebsiella pneumoniae strains to cohabitant humans was observed in three Portuguese households (6.9%, n = 43), with repeated isolation of the index strains on fecal samples from the animals and their cohabiting humans. In addition, longitudinal sharing of E. coli strains carried by companion animals and their owners was observed in other two Portuguese households and two households from the UK. Furthermore, a multidrug-resistant ACT-24-producing Enterobacter hormaechei subsp. hoffmannii strains were also shared within another Portuguese household. These results highlight the importance of the household as an epidemiological unit in the efforts to mitigate the spread of antimicrobial resistance, further emphasizing the need for antimicrobial surveillance in this context, capable of producing data that can inform and evaluate public health actions., Competing Interests: 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., (Copyright © 2024 Menezes, Frosini, Weese, Perreten, Schwarz, Amaral, Loeffler and Pomba.)

Background: Transcranial temporal interference stimulation (tTIS) is a new, emerging neurostimulation technology that utilizes two or more electric fields at specific frequencies to modulate the oscillations of neurons at a desired spatial location in the brain. The physics of tTIS offers the advantage of modulating deep brain structures in a non-invasive fashion and with minimal stimulation of the overlying cortex outside of a selected target. As such, tTIS can be effectively employed in the context of therapeutics for the psychiatric disease of disrupted brain connectivity, such as major depressive disorder (MDD). The subgenual anterior cingulate cortex (sgACC), a key brain center that regulates human emotions and influences negative emotional states, is a plausible target for tTIS in MDD based on reports of its successful neuromodulation with invasive deep brain stimulation., Methods: This pilot, single-site, double-blind, randomized, sham-controlled interventional clinical trial will be conducted at St. Michael's Hospital - Unity Health Toronto in Toronto, ON, Canada. The primary objective is to demonstrate target engagement of the sgACC with 130 Hz tTIS using resting-state magnetic resonance imaging (MRI) techniques. The secondary objective is to estimate the therapeutic potential of tTIS for MDD by evaluating the change in clinical characteristics of participants and electrophysiological outcomes and providing feasibility and tolerability estimates for a large-scale efficacy trial. Thirty participants (18-65 years) with unipolar, non-psychotic MDD will be recruited and randomized to receive 10 sessions of 130 Hz tTIS or sham stimulation ( n = 15 per arm). The trial includes a pre- vs. post-treatment 3T MRI scan of the brain, clinical evaluation, and electroencephalography (EEG) acquisition at rest and during the auditory mismatch negativity (MMN) paradigm., Discussion: This study is one of the first-ever clinical trials among patients with psychiatric disorders examining the therapeutic potential of repetitive tTIS and its neurobiological mechanisms. Data obtained from this trial will be used to optimize the tTIS approach and design a large-scale efficacy trial. Research in this area has the potential to provide a novel treatment option for individuals with MDD and circuitry-related disorders and may contribute to the process of obtaining regulatory approval for therapeutic applications of tTIS., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05295888., Competing Interests: AD is an employee of Soterix Medical, Inc. AH was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, 424778381 – TRR 295), Deutsches Zentrum für Luft- und Raumfahrt (DynaSti grant within the EU Joint Programme Neurodegenerative Disease Research, JPND), the National Institutes of Health (R01 13478451, 1R01NS127892-01, 2R01 MH113929, and UM1NS132358) as well as the New Venture Fund (FFOR Seed Grant), and reports lecture fees for Boston Scientific and is a consultant for Functional Neuromodulation Ltd. and Abbott. SHK has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, Canadian Institutes of Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, Sun Pharmaceuticals, and holds stock in Field Trip Health. ESB is an inventor on the Temporal Interference (TI) Stimulation patent and a co-founder of TI Solutions, a for-profit company. VB is supported by the Academic Scholar Award from the University of Toronto Department of Psychiatry and has received research support from the Canadian Institutes of Health Research, Brain & Behavior Foundation, Ontario Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of National Defence (Government of Canada), New Frontiers in Research Fund, Associated Medical Services Inc. Healthcare, American Foundation for Suicide Prevention, Roche Canada, Novartis, and Eisai. 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 Demchenko, Rampersad, Datta, Horn, Churchill, Kennedy, Krishnan, Rueda, Schweizer, Griffiths, Boyden, Santarnecchi and Bhat.)

Background: Adverse effects of chronically high levels of stress on physical and mental health are well established. In physicians, the effects of elevated stress levels exceed the individual level and include treatment errors and reduced quality of patient-doctor relationships. Breathing and mindfulness-based exercises have been shown to reduce stress and could serve as an immediate and easy-to-implement anti-stress intervention among physicians. Due to the heterogeneity of their effect on stress, we aim to evaluate the intervention effect of performing a short daily breathwork-based or mindfulness-based intervention on the everyday level of perceived stress in physicians in residence in Germany in a series of N-of-1 trials., Methods: Study participants will choose between two short interventions, box breathing, and one guided more complex mindfulness-based breathing exercise. Each participant subsequently will be randomly allocated to a sequence of 1-week intervention (A) and control (B, everyday life) phases. Each N-of-1 trial consists of two two-week cycles (AB or BA), resulting in a total trial duration of 4 weeks (ABAB or BABA). Perceived levels of stress will be assessed daily via the StudyU App on the participant's smartphone. Additionally, participants will be asked to complete a questionnaire at baseline and three months after completion of the study that contains questions about basic participant characteristics, lifestyle factors, individual living situations, and validated psychological questionnaires. Intervention effects will be estimated by Bayesian multi-level random effects models on the individual and population level., Discussion: This study contributes to the development of short-term solutions to reduce work-related stress for physicians in residence. This is expected to benefit the individual and increase the quality of overall healthcare due to a reduction in treatment errors and an increase in the quality of doctor-patient relationships., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05745545., Competing Interests: TK reports outside of the submitted work receiving research grants from the Gemeinsamer Bundesausschuss G-BA Federal Joint Committee, Germany and the Bundesministerium für Gesundheit BMG - Federal Ministry of Health, Germany. He has also received personal compensation from Eli Lilly and Company, the BMJ, and Frontiers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Vetter, Kurth and Konigorski.)

Mammalian cells produce and metabolize almost exclusively L-lactate, bacterial species have the capacity to produce both D-lactate and L-lactate. The aim of this study was to evaluate the intrinsic production of D- and L-lactate in the most common pathogenic microorganisms causing septic arthritis (SA) and periprosthetic joint infection (PJI) as a potential biomarker for the diagnosis of infection. Following microorganisms were grown according to ATCC culture guides and tested for production of D- and L-lactate: Staphylococcus aureus (ATCC 43300), Staphylococcus epidermidis (ATCC 35984), Enterococcus faecalis (ATCC 19433), Streptococcus pyogenes (ATCC 19615), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Cutibacterium acnes (ATCC 11827), and Candida albicans (ATCC 90028). Pathogens were inoculated in 8 ml of appropriate liquid media and incubated as planktonic or biofilm form in either aerobic, anaerobic or CO 2 atmosphere up to 312 h. D- and L-lactate measurements were performed at different time points: 0, 6, 9, 12 and 24 h, then once per day for slow-growing pathogens. Samples were serially diluted and plated for colony counting. Liquid culture media without microorganisms served as a negative control. Production of D-lactate was observed in all tested microorganisms, whereas no L-lactate was detected in E. coli , P. aeruginosa, and C. albicans . Maximal concentration of D-lactate was produced by S. aureus (10.99 mmol/L), followed by E. coli (1.22 mmol/L), and S. epidermidis (0.48 mmol/L). Maximal L-lactate concentration was observed in S. pyogenes (10.12 mmol/L), followed by S. aureus (9.71 mmol/L), E. faecalis (2.64 mmol/L), and S. epidermidis (2.50 mmol/L). S. epidermidis bacterial biofilm produced significantly higher amount of D- and L-lactate compared to planktonic form ( p  = 0.015 and p  = 0.002, respectively). Our study has demonstrated that the most common pathogenic microorganisms causing SA and PJI have the capability to generate measurable amounts of D-lactate in both planktonic and biofilm form, highlighting the practical value of this biomarker as an indicator for bacterial and fungal infections. In contrast to D-lactate, the absence of L-lactate production in certain tested bacteria, as well as in fungi, suggests that L-lactate is not eligible as a biomarker for diagnosing microbial infections., Competing Interests: 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., (Copyright © 2024 Morovic, Gonzalez Moreno, Trampuz and Karbysheva.)

N-methyl-D-aspartate (NMDA) receptor antagonists are widely used to pharmacologically model schizophrenia and have been recently established in the treatment of treatment-resistant major depression demonstrating that the pharmacology of this substance class is complex. Cortical gamma oscillations, a rhythmic neuronal activity associated with cognitive processes, are increased in schizophrenia and deteriorated in depressive disorders and are increasingly used as biomarker in these neuropsychiatric diseases. The opposite use of NMDA receptor antagonists in schizophrenia and depression raises the question how their effects are in accordance with the observed disease pathophysiology and if these effects show a consequent sex-specificity. In this study in rats, we investigated the effects of subchronic (14 days) intraperitoneal injections of the NMDA receptor antagonist MK-801 at a subanesthetic daily dose of 0.2 mg/kg on the behavioral phenotype of adult female and male rats and on pharmacologically induced gamma oscillations measured ex vivo from the hippocampus. We found that MK-801 treatment leads to impaired recognition memory in the novel object recognition test, increased stereotypic behavior and reduced grooming, predominantly in female rats. MK-801 also increased the peak power of hippocampal gamma oscillations induced by kainate or acetylcholine only in female rats, without affecting the peak frequency of the oscillations. The findings indicate that blockade of NMDA receptors enhances gamma oscillations predominantly in female rats and this effect is associated with behavioral changes in females. The results are in accordance with clinical electrophysiological findings and highlight the importance of hippocampal gamma oscillations as a biomarker in schizophrenia and depression., Competing Interests: 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., (Copyright © 2024 Neuhäusel and Gerevich.)

Background: Over the last three decades, the number of randomized controlled trials (RCTs) using stimulation of auricular vagal sensory nerves by means of electrical stimulation, auricular acupuncture, or acupressure to support weight loss has increased markedly. This systematic review focuses on the effects of auricular stimulation (AS) on anthropometric parameters and obesity-related blood chemistry., Methods and Analysis: The following databases were searched until November 2021: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, and Scopus Database. Data collection and analysis were conducted by two reviewers independently. Quality and risk assessment of included studies was performed using the risk of bias tool of the Cochrane Handbook, and the meta-analysis of the effect of the most frequently assessed biomarkers was conducted using the statistical software RevMan., Results: The full texts of 1,274 studies were screened; 22 contained data on obesity-related outcomes, and 15 trials with 1,333 patients were included in the meta-analysis. The overall quality of the included trials was moderate. AS significantly reduced body mass index (BMI) (mean difference (MD) = -0.38 BMI points, 95% CI (-0.55 to -0.22), p  < 0.0001), weight (MD = -0.66 kg, 95% CI (-1.12 to -0.20), p  = 0.005), waist circumference (MD = -1.44 cm, 95% CI (-2.69 to -0.20), p  = 0.02), leptin, insulin, and HOMA insulin resistance compared to controls. No significant reduction was found in body fat, hip circumference, ratio of waist/hip circumference, cholesterol, LDL, triglycerides, adiponectin, ghrelin, and glucose levels. The AS was safe throughout the trials, with only minor adverse reactions., Conclusion: The study results suggest that a reduction of weight and BMI can be achieved by AS in obese patients; however, the size of the effect does not appear to be of clinical relevance. The effects might be underestimated due to active sham trials., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021231885., Competing Interests: 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., (Copyright © 2024 Hua, Usichenko, Cummings, Bernatik, Willich, Brinkhaus and Dietzel.)

Objectives: Increasing psychological flexibility is considered an important mechanism of change in psychotherapy across diagnoses. In particular, Acceptance and Commitment Therapy (ACT) primarily aims at increasing psychological flexibility in order to live a more fulfilling and meaningful life. The purpose of this study is to examine 1) how psychological flexibility changes during an ACT-based treatment in a transdiagnostic day hospital and 2) how this change is related to changes in symptomatology, quality of life, and general level of functioning., Methods: 90 patients of a psychiatric day hospital participated in the study. Psychological flexibility, symptomatology, and quality of life were assessed at three measurement time points (admission, discharge, and 3-month follow-up). The level of functioning was assessed at admission and discharge. Differences in psychological flexibility were tested via two-sided paired samples t -tests. Correlations of residualized change scores were calculated to detect associations between changes in psychological flexibility and other outcomes., Results: Psychological flexibility increased significantly from pre-treatment to post-treatment ( d = .43, p <.001) and from pre-treatment to follow-up ( d = .54, p <.001). This change was significantly correlated to a decrease in symptomatology ( r = .60 -.83, p <.001) and an increase in most dimensions of quality of life ( r = -.43 - -.75, p <.001) and general level of functioning ( r =-.34, p = .003)., Discussion: This study adds further evidence for psychological flexibility as a transdiagnostic process variable of successful psychotherapy. Limitations are discussed., Competing Interests: RR was employed by Vivantes and worked as an employee for the evaluation during data collection and analysis. Previously, RR had worked as a psychologist in the day clinic during the implementation of the therapy program. CR is the head physician and behavioural therapist at Vivantes. 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 Rutschmann, Romanczuk-Seiferth, Gloster and Richter.)

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies., Competing Interests: 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., (Copyright © 2024 Staabs, Foverskov Rasmussen, Buthut, Höltje, Li, Stöcker, Teegen and Prüss.)

Staphylococcus aureus ´ biofilm-forming ability and rapid resistance development pose a significant challenge to successful treatment, particularly in postoperative complications, emphasizing the need for enhanced therapeutic strategies. Bacteriophage (phage) therapy has reemerged as a promising and safe option to combat multidrug-resistant bacteria. However, questions regarding the efficacy of phages against biofilms and the development of phage resistance require further evaluation. Expanding on the adaptable and evolutionary characteristics of phages, we introduce an evolutionary approach to enhance the activity of S. aureus phages against biofilms. Unlike other in vitro directed evolution methods performed in planktonic cultures, we employed pre-stablished biofilms to do a serial-passage assay to evolve phages monitored by real-time isothermal microcalorimetry (IMC). The evolved phages demonstrated an expanded host range, with the CUB&#95;MRSA-COL&#95;R9 phage infecting 83% of strains in the collection ( n  = 72), surpassing the ISP phage, which represented the widest host range (44%) among the ancestral phages. In terms of antimicrobial efficacy, IMC data revealed superior suppression of bacterial growth by the evolved phages compared to the ancestral CUB-M and/or ISP phages against the respective bacterial strain. The phage cocktail exhibited higher efficacy, achieving over 90% suppression relative to the growth control even after 72 h of monitoring. Biofilm cell-counts, determined by RT-qPCR, confirmed the enhanced antibiofilm performance of evolved phages with no biofilm regrowth up to 48 h in treated MRSA15 and MRSA-COL strains. Overall, our results underscore the potential of biofilm-adapted phage cocktails to improve clinical outcomes in biofilm-associated infections, minimizing the emergence of resistance and lowering the risk of infection relapse. However, further investigation is necessary to evaluate the translatability of our results from in vitro to in vivo models, especially in the context of combination therapy with the current standard of care treatment., Competing Interests: 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. The author(s) 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 Ponce Benavente, Wagemans, Hinkel, Aguerri Lajusticia, Lavigne, Trampuz and Gonzalez Moreno.)

Significant advancements have been achieved in delineating the progress of the Global PROMS (PROMS) Initiative. The PROMS Initiative, a collaborative endeavor by the European Charcot Foundation and the Multiple Sclerosis International Federation, strives to amplify the influence of patient input on MS care and establish a cohesive perspective on Patient-Reported Outcomes (PROs) for diverse stakeholders. This initiative has established an expansive, participatory governance framework launching four dedicated working groups that have made substantive contributions to research, clinical management, eHealth, and healthcare system reform. The initiative prioritizes the global integration of patient (For the purposes of the Global PROMS Initiative, the term "patient" refers to the people with the disease (aka People with Multiple Sclerosis - pwMS): any individual with lived experience of the disease. People affected by the disease/Multiple Sclerosis: any individual or group that is affected by the disease: E.g., family members, caregivers will be also engaged as the other stakeholders in the initiative). insights into the management of MS care. It merges subjective PROs with objective clinical metrics, thereby addressing the complex variability of disease presentation and progression. Following the completion of its second phase, the initiative aims to help increasing the uptake of eHealth tools and passive PROs within research and clinical settings, affirming its unwavering dedication to the progressive refinement of MS care. Looking forward, the initiative is poised to continue enhancing global surveys, rethinking to the relevant statistical approaches in clinical trials, and cultivating a unified stance among 'industry', regulatory bodies and health policy making regarding the application of PROs in MS healthcare strategies., Competing Interests: LuC was employed by Hoffmann-La Roche. LoC was employed by Ad Scientiam. PK was employed by Merck KGaA. ACV has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Colombia, Genzyme Colombia, Merck Colombia, Roche Colombia, Novartis Colombia. CB has received travel support and/or research grants and/or lecture fees and/or advisory services by Novartis, Merck, Genesis, Sanofi, Teva, Roche, Biogen, Mylan, Tikun Europe ECC has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Argentina and LATAM, Genzyme Argentina, Merck Argentina and LATAM, Roche Argentina and LATAM, Raffo, Novartis Argentina, AstraZeneca Argentina, Horizon therapeutics, LACTRIMS, Harvard Medical School MP has received reimbursement for developing educational presentations from Biogen and Merck. SG has received reimbursement for developing educational presentations, research grants, consultation fees, and/or travel stipends from Roche, Merck and the Sumaira Foundation. VC received a grant from the European Charcot Foundation, received support for scientific meetings from Biogen, Janssen, Novartis, BMS, Roche and speaking honoraria from Novartis and Alexion. VR reports fees for traveling from Novartis, Merck, Biogen and Roche, speaker’s honoraria from Novartis, Sandoz, Merck, Biogen, consulting fees from Biogen, Merck, Novartis, Janssen, M3 Global Research and Atheneum Partners, all outside of the submitted work. 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. H-PH declared that he was 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 Zaratin, Samadzadeh, Seferoğlu, Ricigliano, dos Santos Silva, Tunc, Brichetto, Coetzee, Helme, Khan, McBurney, Peryer, Weiland, Baneke, Battaglia, Block, Capezzuto, Carment, Cortesi, Cutter, Leocani, Hartung, Hillert, Hobart, Immonen, Kamudoni, Middleton, Moghames, Montalban, Peeters, Sormani, van Tonder, White, Comi and Vermersch.)

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future., Competing Interests: MAN is in the scientific advisory board of Neuroelectrics and Précis’s. 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 reviewer BL declared a past co-authorship with the authors AF and MAN to the handling editor., (Copyright © 2024 Meinzer, Shahbabaie, Antonenko, Blankenburg, Fischer, Hartwigsen, Nitsche, Li, Thielscher, Timmann, Waltemath, Abdelmotaleb, Kocataş, Caisachana Guevara, Batsikadze, Grundei, Cunha, Hayek, Turker, Schlitt, Shi, Khan, Burke, Riemann, Niemann and Flöel.)

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI., Methods: Synovial fluids of 99 patients ( n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute ( n = 33) and low-grade ( n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant., Results: Active MPO was higher in PJI than AF ( P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78-0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11-83.81%, positive likelihood ratio 5.88, 95% CI: 2.31-14.98 and negative likelihood ratio 0.35, 95%CI: 0.24-0.51). No difference in MPO levels was found between acute and chronic low-grade PJI., Conclusion: The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice., Competing Interests: 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. The author(s) 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 Maritati, De Rito, Rosta, Cervellati, Cristina Manfrinato, Alberto Zanoli, De Giorgio, Guarino, Costanzini, Contini, Ning, Trampuz and Trentini.)

Introduction: The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied quantitatively. Therefore, the aim of this study was to explore the structural abilities of people diagnosed with schizophrenia and schizoaffective psychosis using the Levels of Structural Integration Axis of the Operationalized Psychodynamic Diagnosis System (OPD-2-LSIA). The study aimed to determine possible associations between the OPD-2-LSIA and central parameters of illness. Additionally, possible structural differences between people diagnosed with schizophrenia and schizoaffective psychosis were tested., Methods: This cross-sectional study included 129 outpatients with schizophrenia or schizoaffective disorders. Measures of structural integration, symptom load, severity of illness, cognition, and social functioning were obtained. Descriptive statistics were used to analyze the overall structural level and the structural dimensions. Correlation coefficients were computed to measure the associations between OPD-2-LSIA and variables regarding the severity of illness and psychosocial functioning. Regression models were used to measure the influence of illness-related variables on OPD-2-LSIA, and the influence of OPD-2-LSIA on psychosocial functioning. Participants diagnosed with schizophrenia and schizoaffective disorders were examined with regard to possible group differences., Results: The results of the OPD-2-LSIA showed that the overall structural level was between 'moderate to low' and 'low level of structural integration'. Significant correlations were found between OPD-2-LSIA and psychotic symptoms (but not depressive symptoms), as well as between OPD-2-LSIA and psychosocial functioning. It was found that variables related to severity of illness had a significant impact on OPD-2-LSIA, with psychotic, but not depressive symptoms being significant predictors. OPD-2-LSIA was found to predict psychosocial functioning beyond symptoms and cognition. No significant differences were found between participants with schizophrenia and schizoaffective psychosis. There was also no correlation found between OPD-2-LSIA and depressive symptomatology (except for the subdimension Internal communication)., Discussion: Contrary to theoretical assumptions, the results of the study show a heterogenous picture of the psychic structure of people with psychosis. The associations between OPD-2-LSIA and severity of illness, particularly psychotic symptomatology, as well as the influence of OPD-2-LSIA on psychosocial functioning, are discussed., Competing Interests: 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., (Copyright © 2024 Bayer, Bröcker, Stuke, Just, Bertram, Grimm, Maaßen, Büttner, Heinz, Bermpohl, Lempa, von Haebler and Montag.)

Phagocytes maintain homeostasis in a healthy brain. Upon injury, they are essential for repairing damaged tissue, recruiting other immune cells, and releasing cytokines as the first line of defense. However, there seems to be a delicate balance between the beneficial and detrimental effects of their activation in a seizing brain. Blocking the infiltration of peripheral phagocytes (macrophages) or their depletion can partially alleviate epileptic seizures and prevent the death of neurons in experimental models of epilepsy. However, the depletion of resident phagocytes in the brain (microglia) can aggravate disease outcomes. This review describes the role of resident microglia and peripheral infiltrating monocytes in animal models of acutely triggered seizures and epilepsy. Understanding the roles of phagocytes in ictogenesis and the time course of their activation and involvement in epileptogenesis and disease progression can offer us new biomarkers to identify patients at risk of developing epilepsy after a brain insult, as well as provide novel therapeutic targets for treating epilepsy., Competing Interests: 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., (Copyright © 2024 Bröer and Pauletti.)

Our knowledge of alphavirus genetic diversity is mainly based on viruses isolated from anthropophilic mosquito species, humans, and livestock during outbreaks. Studies on alphaviruses from sylvatic amplification cycles in sub-Saharan Africa have been conducted less often than from epizootic environments. To gain insight into alphavirus diversity in enzootic transmission cycles, we collected over 23,000 mosquitoes in lowland rainforest and savannah gallery forest in southwestern Uganda and tested them for alphavirus infections. We detected Sindbis virus (SINV) in a Culex Culex sp. mosquito and Middelburg virus (MIDV) in Eretmapodites intermedius and Mansonia africana . MIDV is a mosquito-borne alphavirus that causes febrile illness in sheep, goats, and horses and was previously not known to occur in Uganda. SINV, also a mosquito-borne alphavirus, causes mild infections in humans. Full genomes of SINV and MIDV were sequenced, showing a nucleotide identity of 99% to related strains. Both isolates replicated to high titres in a wide variety of vertebrate cells. Our data suggest endemic circulation of SINV and MIDV in Uganda., Competing Interests: 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. The author(s) 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 Graff, Eibner, Ochieng, Jones, Nsubuga, Lutwama, Rwego and Junglen.)

The way we establish meaning has been a profound question not only in language research but in developmental science as well. The relation between linguistic form and content has been loosened up in recent pragmatic approaches to communication, showing that code-based models of language comprehension must be augmented by context-sensitive, pragmatic-inferential mechanisms to recover the speaker's intended meaning. Language acquisition has traditionally been thought to involve building a mental lexicon and extracting syntactic rules from noisy linguistic input, while communicative-pragmatic inferences have also been argued to be indispensable. Recent research findings exploring the electrophysiological indicator of semantic processing, the N400, have raised serious questions about the traditional separation between semantic decoding and pragmatic inferential processes. The N400 appears to be sensitive to mentalization-the ability to attribute beliefs to social partners-already from its developmental onset. This finding raises the possibility that mentalization may not simply contribute to pragmatic inferences that enrich linguistic decoding processes but that the semantic system may be functioning in a fundamentally mentalistic manner. The present review first summarizes the key contributions of pragmatic models of communication to language comprehension. Then, it provides an overview of how communicative intentions are interpreted in developmental theories of communication, with a special emphasis on mentalization. Next, it discusses the sensitivity of infants to the information-transmitting potential of language, their ability to pick up its code-like features, and their capacity to track language comprehension of social partners using mentalization. In conclusion, I argue that the recovery of meaning during linguistic communication is not adequately modeled as a process of code-based semantic retrieval complemented by pragmatic inferences. Instead, the semantic system may establish meaning, as intended, during language comprehension and acquisition through mentalistic attribution of content to communicative partners., Competing Interests: The author declares 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 Forgács.)

The spread of antimicrobial resistance (AMR) in animal husbandry is usually attributed to the use of antibiotics and poor hygiene and biosecurity. We therefore conducted experimental trials to improve hygiene management in weaned pig houses and assessed the impact on the spread. For each of the two groups examined, the experimental group (EG) and the control group (CG), three replicate batches of piglets from the same pig breeder, kept in pre-cleaned flat decks, were analyzed. In the flat decks of the experimental groups, the hygiene conditions (cleaning, disinfection, dust removal and fly control) were improved, while regular hygiene measures were carried out in the control groups. The occurrence and spread of AMR were determined in Escherichia coli ( E. coli ; resistance indicator) using cultivation-dependent (CFU) and -independent (qPCR) methods as well as whole genome sequencing of isolates in samples of various origins, including feces, flies, feed, dust and swabs. Surprisingly, there were no significant differences ( p  > 0.05) in the prevalence of resistant E. coli between the flat decks managed with conventional techniques and those managed with improved techniques. Selective cultivation delivered ampicillin- and sulfonamide-resistant E. coli proportions of up to 100% and 1.2%, respectively. While 0.5% E. coli resistant to cefotaxime and no ciprofloxacin resistance were detected. There was a significant difference ( p  < 0.01) in the abundance of the bla TEM-1 gene in fecal samples between EG and CG groups. The colonization of piglets with resistant pathogens before arrival, the movement of flies in the barn and the treatment of bacterial infections with antibiotics obscured the effects of hygiene improvement. Biocide tolerance tests showed no development of resistance to the farm regular disinfectant. Managing hygiene alone was insufficient for reducing antimicrobial resistances in piglet rearing. We conclude that the complex factors contributing to the presence and distribution of AMR in piglet barns underscore the necessity for a comprehensive management strategy., Competing Interests: 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., (Copyright © 2024 Jaleta, Junker, Kolte, Börger, Werner, Dolsdorf, Schwenker, Hölzel, Zentek, Amon, Nübel and Kabelitz.)

When exposed to low temperatures, plants undergo a drastic reprogramming of their transcriptome in order to adapt to their new environmental conditions, which primes them for potential freezing temperatures. While the involvement of transcription factors in this process, termed cold acclimation, has been deeply investigated, the potential contribution of chromatin regulation remains largely unclear. A large proportion of cold-inducible genes carries the repressive mark histone 3 lysine 27 trimethylation (H3K27me3), which has been hypothesized as maintaining them in a silenced state in the absence of stress, but which would need to be removed or counteracted upon stress perception. However, the fate of H3K27me3 during cold exposure has not been studied genome-wide. In this study, we offer an epigenome profiling of H3K27me3 and its antagonistic active mark H3K4me3 during short-term cold exposure. Both chromatin marks undergo rapid redistribution upon cold exposure, however, the gene sets undergoing H3K4me3 or H3K27me3 differential methylation are distinct, refuting the simplistic idea that gene activation relies on a switch from an H3K27me3 repressed chromatin to an active form enriched in H3K4me3. Coupling the ChIP-seq experiments with transcriptome profiling reveals that differential histone methylation only weakly correlates with changes in expression. Interestingly, only a subset of cold-regulated genes lose H3K27me3 during their induction, indicating that H3K27me3 is not an obstacle to transcriptional activation. In the H3K27me3 methyltransferase curly leaf (clf) mutant, many cold regulated genes display reduced H3K27me3 levels but their transcriptional activity is not altered prior or during a cold exposure, suggesting that H3K27me3 may serve a more intricate role in the cold response than simply repressing the cold-inducible genes in naïve conditions., Competing Interests: 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. The author(s) 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 Faivre, Kinscher, Kuhlmann, Xu, Kaufmann and Schubert.)

Introduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA -regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains., Materials and Methods: Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC-MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software., Results: The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins., Conclusion: High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance., Competing Interests: 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., (Copyright © 2024 Recacha, Kuropka, Díaz-Díaz, García-Montaner, González-Tortuero, Docobo-Pérez, Rodríguez-Rojas and Rodríguez-Martínez.)

When comparing themselves with others, people often evaluate their own behaviors more favorably. This egocentric tendency is often categorized as a bias of attribution, with favorable self-evaluation resulting from differing explanations of one's own behavior and that of others. However, studies on information availability in social contexts offer an alternative explanation, ascribing egocentric biases to the inherent informational asymmetries between performing an action and merely observing it. Since biases of attribution and availability often co-exist and interact with each other, it is not known whether they are both necessary for the egocentric biases to emerge. In this study, we used a design that allowed us to directly compare the contribution of these two distinct sources of bias to judgements about the difficulty of an effortful task. Participants exhibited no attribution bias as judgements made for themselves did not differ from those made for others. Importantly, however, participants perceived the tasks they actively performed to be harder than the tasks they observed, and this bias was magnified as the overall task difficulty increased. These findings suggest that information asymmetries inherent to the difference between actively performing a task and observing it can drive egocentric biases in effort evaluations on their own and without a contribution from biases of attribution., Competing Interests: 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., (Copyright © 2024 Stinson, Kagan and Pooresmaeili.)

Inner ear disorders have a variety of causes, and many factors can contribute to the exacerbation of cochlear and vestibular pathology. This systematic review aimed to analyze clinical data on the coexistence and potential causal interaction between allergic diseases and inner ear conditions. A search of PubMed and Web of Science identified 724 articles, of which 21 were selected for full-text analysis based on inclusion and exclusion criteria. The epidemiologic evidence found overwhelmingly supports an association between allergic disease and particular inner ear disorders represented by a high prevalence of allergic reactions in some patients with Ménière's disease (MD), idiopathic sudden sensorineural hearing loss (ISSHL), and acute low-tone hearing loss (ALHL). In addition, patients with MD, ISSHL, and ALHL had higher levels of total serum IgE than healthy subjects. Finally, in some cases, changes in cochlear potential may have been induced by antigen exposure, while desensitization alleviated allergy and inner ear-related symptoms. The exact mechanism of interaction between the auditory/vestibular and immune systems is not fully understood, and further clinical and basic research is needed to understand the relationship between the two systems fully., Competing Interests: 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., (Copyright © 2024 Zeng, Domarecka, Kong, Olze, Scheffel, Moñino-Romero, Siebenhaar and Szczepek.)

Antarctic algae are exposed to prolonged periods of extreme darkness due to polar night, and coverage by ice and snow can extend such dark conditions to up to 10 months. A major group of microalgae in benthic habitats of Antarctica are diatoms, which are key primary producers in these regions. However, the effects of extremely prolonged dark exposure on their photosynthesis, cellular ultrastructure, and cell integrity remain unknown. Here we show that five strains of Antarctic benthic diatoms exhibit an active photosynthetic apparatus despite 10 months of dark-exposure. This was shown by a steady effective quantum yield of photosystem II (Y[II]) upon light exposure for up to 2.5 months, suggesting that Antarctic diatoms do not rely on metabolically inactive resting cells to survive prolonged darkness. While limnic strains performed better than their marine counterparts, Y(II) recovery to values commonly observed in diatoms occurred after 4-5 months of light exposure in all strains, suggesting long recovering times. Dark exposure for 10 months dramatically reduced the chloroplast ultrastructure, thylakoid stacking, and led to a higher proportion of cells with compromised membranes than in light-adapted cells. However, photosynthetic oxygen production was readily measurable after darkness and strong photoinhibition only occurred at high light levels (>800 µmol photons m -2 s -1 ). Our data suggest that Antarctic benthic diatoms are well adapted to long dark periods. However, prolonged darkness for several months followed by only few months of light and another dark period may prevent them to regain their full photosynthetic potential due to long recovery times, which might compromise long-term population survival., Competing Interests: The authors declare 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 Handy, Juchem, Wang, Schimani, Skibbe, Zimmermann, Karsten and Herburger.)

Background: A significant proportion of patients with a depressive disorder show resistance to pharmacological and psychotherapeutic antidepressant treatments. Electroconvulsive therapy (ECT) is still one of the most effective treatment methods, especially in the acute phase. In everyday clinical practice, this usually accompanies pharmacological treatment. It has been shown that pharmacological treatment following acute ECT treatment reduces the rate of relapses. However, the effect of various antidepressants (ADs) and antipsychotics (APs) on the effect during the course of ECT has rarely been investigated., Methods: In this retrospective chart review study, the data of 104 depressive patients treated with ECT were examined. We analyzed the influence of concomitant administration of AD and AP or no psychotropic medication on the effect of ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). We further analyzed the influence of the ADs Bupropion, Venlafaxine, and Sertraline or no AD and the influence of augmentation with Aripiprazole or Quetiapine or Olanzapine., Results/discussion: Psychotropic medication did not have an impact on antidepressant efficacy of ECT as measured with the MADRS scores. In addition, the comparison between the antidepressant or antipsychotic medications themselves did not show any significant difference. However, we found a significantly different seizure duration depending on the antidepressant substance that patients received during ECT ( p = .008). ECT treatment itself led to a highly significant reduction of 13.3 points in the MADRS ( p <.001)., Conclusion: Taken together, our study underlines that concomitant psychotropic medication while doing electroconvulsive therapy does not bare the risk of prolonged seizure duration or does it reduce the effectiveness of ECT. To the best of our knowledge, this study is the first to examine the effect of treatment with antidepressants in combination with antipsychotics while doing ECT. In light of our results, this combination therapy is safe and effective. Bearing in mind the delay in onset of antidepressant action of medication and the importance of antidepressant medication for relapse prevention, this study further supports the recommendation that psychotropic medication should be given in adjunction to ECT., Competing Interests: 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., (Copyright © 2024 Mohamad, Trumm, Treskatsch, Drevs, Bajbouj and Wiedemann.)

Data collected from the German national resistance monitoring program GE RM -Vet showed slowly increasing prevalence of macrolide resistance among bovine respiratory disease (BRD)-associated Pasteurellacae from cattle over the last decade. The focus of this study was to analyze the genetic basis of antimicrobial resistance (AMR) and the prevalence of multidrug-resistance (MDR)-mediating integrative and conjugative elements (ICEs) in 13 German BRD-associated Mannheimia haemolytica isolates collected between 2009 and 2020 via whole-genome sequencing. Antimicrobial susceptibility testing (AST) was performed via broth microdilution according to the recommendations of the Clinical and Laboratory Standards Institute for the macrolides erythromycin, tilmicosin, tulathromycin, gamithromycin, tildipirosin, and tylosin as well as 25 other antimicrobial agents. All isolates either had elevated MICs or were resistant to at least one of the macrolides tested. Analysis of whole-genome sequences obtained by hybrid assembly of Illumina MiSeq and Oxford Nanopore MinION reads revealed the presence of seven novel Tn 7406 -like ICEs, designated Tn 7694 , and Tn 7724 - Tn 7729 . These ICEs harbored the antimicrobial resistance genes erm (T), mef (C), mph (G), floR, catA3, aad(3")(9), aph(3')-Ia, aac(3)-IIa, strA, strB, tet (Y), and sul2 in different combinations. In addition, mutational changes conferring resistance to macrolides, nalidixic acid or streptomycin, respectively, were detected among the M . haemolytica isolates. In addition, four isolates carried a 4,613-bp plasmid with the β-lactamase gene bla ROB - 1 . The detection of the macrolide resistance genes erm (T), mef (C), and mph (G) together with other resistance genes on MDR-mediating ICEs in bovine M. haemolytica may explain the occurrence of therapeutic failure when treating BRD with regularly used antimicrobial agents, such as phenicols, penicillins, tetracyclines, or macrolides. Finally, pathogen identification and subsequent AST is essential to ensure the efficacy of the antimicrobial agents applied to control BRD in cattle., Competing Interests: 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., (Copyright © 2024 Kostova, Hanke, Kaspar, Fiedler, Schwarz and Krüger-Haker.)

Although endangerment towards others is a criterion for an involuntary admission in many countries, research on risk assessment of endangerment among involuntarily admitted individuals is limited. In this retrospective case-control study, we calculated scores for a German-translated version of the Violence Risk Screening-10 (V-RISK-10) and the Brøset Violence Checklist (BVC) in a sample of 111 people undergoing an involuntary admission in Reinickendorf, Berlin. Outcomes were violence, coercive measures, and readmission. In line with our hypotheses, the BVC demonstrated stronger predictive validities for short-term, and V-RISK-10 for long-term events. There was an incremental validity for both instruments for restraint 24 hours after admission and any violence until discharge. These findings support the evidence that structured risk assessment instruments may be useful for individuals undergoing an involuntary admission. Ethical considerations about screening procedures are discussed., Competing Interests: 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., (Copyright © 2024 Kös, Bräunig and Hausam.)

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices., Competing Interests: ND has a financial interest in Turing Medical Inc. and may financially benefit if the company is successful in marketing FIRMM motion monitoring software products, may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc, and is a co-founder of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. AH reports lecture fees for Boston Scientific and is a consultant for FxNeuromodulation and Abbott. RG is an employee of Rune Labs. JO'K is CEO and Founder of Machine Medicine Technologies. W-JN received honoraria for consulting from InBrain – Neuroelectronics that is a neurotechnology company and honoraria for talks from Medtronic that is a manufacturer of deep brain stimulation devices unrelated to this manuscript. SL has received speaking honoraria from Medtronic and is a consultant for Iota Biosciences. SS is a consultant for Zimmer Biomet, Neuropace, Koh Young, Boston Scientfic, Sensoria Therapeutics, Varian Medical; co-founder for Motif Neurotech. LM is an employee of Boston Scientific. AF has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB, Sunovion, and he has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer. AH-B and RR are employees of Medtronic Inc. LM is an employee of Boston Scientific. YP is an employee of Abbott. DG is an employee of NeuroPace, owns NeuroPace stock, and has NeuroPace stock options. SM is a founder and shareholder of Newronika SpA. LK is the CEO of Newronika. MP-N has received speaker honoraria/travel costs from Medtronic, Boston Scientific, Abbott, Bial, and Abbvie and study reimbursements from Zambon, Licher, Boston Scientific, and Abbott. LC has received research support from National Institutes of Health and the National Network of Depression Centers and serves on the Board of Directors for the International Neuroethics Society (unpaid) as well as on the Advisory Council for the Institute of Neuroethics think and do thank (unpaid). CM is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, BrainDynamics, CereGate, Cardionomic, Enspire DBS. NH is a co-founder of Surgical Information Sciences (SIS), Inc. HM received consulting and IP licensing fees from Abbott Laboratories. AK has stock options in Neurawell and Big Health and is a consultant for Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda. NP is a consultant for Abbott and Sensoria Therapeutics. PS receives free research devices from Medtronic and fellowship support funding from Medtronic and BSCI and no personal income from anyone. KF reports receiving research support and fellowship support from Medtronic and Boston Scientific and research support from Functional Neuromodulation. MO serves as Medical Advisor the Parkinson's Foundation, and has received research grants from NIH, Parkinson's Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MO is an associate editor for New England Journal of Medicine Journal, Watch Neurology, and JAMA Neurology. MO has participated in CME and educational activities (past 12-24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not MO receives grants from industry. MO has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. 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 author(s) 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 Johnson, Dosenbach, Gordon, Welle, Wilkins, Bronte-Stewart, Voon, Morishita, Sakai, Merner, Lázaro-Muñoz, Williamson, Horn, Gilron, O'Keeffe, Gittis, Neumann, Little, Provenza, Sheth, Fasano, Holt-Becker, Raike, Moore, Pathak, Greene, Marceglia, Krinke, Tan, Bergman, Pötter-Nerger, Sun, Cabrera, McIntyre, Harel, Mayberg, Krystal, Pouratian, Starr, Foote, Okun and Wong.)

Background: Amongst "third-wave" cognitive behavioural therapies, schema therapy demonstrates encouraging efficacy across various mental health conditions. Within this field, clinical interest has begun to converge on the "schema-mode-model" - a conceptualization framework for affective, cognitive and behavioral states that guide individuals' perceptions and behaviours at a given point in time. Schema mode expressions in patients with chronic tinnitus are as-yet unexamined., Methods: The present study reports self-report data from N = 696 patients with chronic tinnitus who completed the Schema Mode- and Tinnitus Handicap Inventories alongside measures of perceived stress, anxiety and depression. The Schema Mode Inventory assesses so-called maladaptive "parent", "child" and "coping" modes. Parent modes can be understood as self-states which are characterized by self-critical and hostile beliefs; child modes are characterized by biographically unmet emotional needs; and coping modes by inflexible attempts to regulate emotion and stabilize one's sense of self. Descriptive, correlational and mediation analyses investigated schema mode expressions (1) in patients with chronic tinnitus, (2) as compared to published reference values from a healthy control sample, (3) in their relation to other psychological constructs, and (4) regarding their potential role in driving tinnitus-related distress., Results: Patients reported mild-to-moderate levels of emotional distress. Compared to healthy controls, patients showed (1) high relative expressions of child-, detachment and compliant coping modes and (2) a conspicuously low relative expression of the 'punitive parent' mode. Correlational patterns suggested strong associations of (1) parent as well as angry child modes with perceived stress and anxiety, (2) the vulnerable child mode with all measured constructs and (3) emotional distress with - intrapersonally - emotional detachment as well as - interpersonally - alleged compliance. Mediation analyses demonstrated that tinnitus-related distress was driven by significant interactions between child and coping modes., Conclusions: The study provides initial clinical evidence for the relevance and applicability of schema-mode based formulation and treatment planning in patients with chronic tinnitus., Competing Interests: 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., (Copyright © 2024 Boecking, Stoettner, Brueggemann and Mazurek.)

Guanosine diphosphate-mannose pyrophosphorylase B (GMPPB) catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, which is required as a mannose donor for the biosynthesis of glycan structures necessary for proper cellular functions. Mutations in GMPPB have been associated with various neuromuscular disorders such as muscular dystrophy and myasthenic syndromes. Here, we report that GMPPB protein abundance increases during brain and skeletal muscle development, which is accompanied by an increase in overall protein mannosylation. To model the human disorder in mice, we generated heterozygous GMPPB KO mice using CIRSPR/Cas9. While we were able to obtain homozygous KO mice from heterozygous matings at the blastocyst stage, homozygous KO embryos were absent beyond embryonic day E8.5, suggesting that the homozygous loss of GMPPB results in early embryonic lethality. Since patients with GMPPB loss-of-function manifest with neuromuscular disorders, we investigated the role of GMPPB in vitro . Thereby, we found that the siRNA-mediated knockdown of Gmppb in either primary myoblasts or the myoblast cell line C2C12 impaired myoblast differentiation and resulted in myotube degeneration. siRNA-mediated knockdown of Gmppb also impaired the neuron-like differentiation of N2A cells. Taken together, our data highlight the essential role of GMPPB during development and differentiation, especially in myogenic and neuronal cell types., Competing Interests: 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., (Copyright © 2024 Schurig, Umeh, Henze, Jung, Gresing, Blanchard, von Maltzahn, Hübner and Franzka.)

Flicker light stimulation (FLS) is a non-pharmacological method of inducing altered states of consciousness (ASCs), producing hallucination-like phenomena as well as effects extending beyond the visual modality, including emotional effects. Research into the psychological and neural mechanisms of FLS is still in its infancy, but can be informed by research into other methods of inducing ASCs. For instance, research on classic psychedelics has reported enhancement of emotional responses to music. Here, we test to what degree FLS might also enhance the emotional response to music, using a study protocol designed to resemble a previous study on the effects of LSD as closely as possible, to allow for comparison of effect sizes across modalities and inform future research into FLS as an ASC-induction method. Twenty participants listened to emotionally evocative music in two conditions - with and without FLS - and reported on their emotional response to the music. FLS showed a significant enhancing effect on reported music-evoked emotion, especially emotions relating to "Joyful Activation"; additionally, we found that the experienced intensity of FLS correlated with reports of higher levels of emotional arousal. These findings motivate further research into FLS as a method for inducing ASCs and into the interactions between visual phenomena and music-evoked emotion., Competing Interests: Within the last 5 years an unrestricted donation from Lumenate Growth Ltd. to Freie Universität Berlin was allocated to TS. This funding was independent of the current study. 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 Montgomery, Amaya and Schmidt.)

Objective: To establish a deep learning model for the detection of hypoxic-ischemic encephalopathy (HIE) features on CT scans and to compare various networks to determine the best input data format., Methods: 168 head CT scans of patients after cardiac arrest were retrospectively identified and classified into two categories: 88 (52.4%) with radiological evidence of severe HIE and 80 (47.6%) without signs of HIE. These images were randomly divided into a training and a test set, and five deep learning models based on based on Densely Connected Convolutional Networks (DenseNet121) were trained and validated using different image input formats (2D and 3D images)., Results: All optimized stacked 2D and 3D networks could detect signs of HIE. The networks based on the data as 2D image data stacks provided the best results ( S100: AUC: 94%, ACC: 79%, S50: AUC: 93%, ACC: 79%). We provide visual explainability data for the decision making of our AI model using Gradient-weighted Class Activation Mapping., Conclusion: Our proof-of-concept deep learning model can accurately identify signs of HIE on CT images. Comparing different 2D- and 3D-based approaches, most promising results were achieved by 2D image stack models. After further clinical validation, a deep learning model of HIE detection based on CT images could be implemented in clinical routine and thus aid clinicians in characterizing imaging data and predicting outcome., Competing Interests: 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., (Copyright © 2024 Molinski, Kenda, Leithner, Nee, Storm, Scheel and Meddeb.)

While there are many studies on psychotherapy and its efficacy - in terms of desired outcomes - there is comparatively little evidence on the possible negative effects of psychotherapy. The aim of this study was to investigate the possible negative effects of a multi-professional psychiatric day hospital treatment for patients with mental health disorders based on Acceptance and Commitment Therapy (ACT), including possible confounding factors. Fifty-one patients with a range of psychiatric diagnoses were assessed three months after an ACT-based psychiatric day hospital treatment. Questionnaires were used to measure negative effects of psychotherapy (INEP), subjective quality of life (WHOQOL-BREF), and symptomatology (BDI-II and SCL-90-R). Correlational analyses and group comparisons were performed to determine the relationship between the sum of reported negative effects on the one hand and symptomology, quality of life, and sociodemographic variables (gender, age, diagnosis, education) on the other hand. At least one negative effect out of a list of 18 possible effects was reported by 45% of participants, and 10% reported more than two. The number of negative effects reported correlates positively with symptomology and negatively with quality of life. The sum of reported negative effects does not correlate with age or gender and does not vary by education level and primary diagnosis. In the light of previous findings, patients included in this study showed lower rates of negative effects, both overall and at item level. Practical implications of these findings are discussed., Competing Interests: CR is the head physician and behavioral therapist. RR worked as a Vivantes employee for the evaluation during data collection and analysis. Previously, she had worked as a psychologist in the day clinic during the implementation of the therapy program. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Richter, Rutschmann and Romanczuk-Seiferth.)

Besides teachers' professional knowledge, their self-efficacy is a crucial aspect in promoting students' scientific reasoning (SR). However, because no measurement instrument has yet been published that specifically refers to self-efficacy beliefs regarding the task of teaching SR, we adapted the Science Teaching Efficacy Belief Instrument (STEBI) accordingly, resulting in the Teaching Scientific Reasoning Efficacy Beliefs Instrument (TSR-EBI). While the conceptual framework of the TSR-EBI is comparable to that of the STEBI in general terms, it goes beyond it in terms of specificity, acknowledging the fact that teaching SR requires very specific knowledge and skills that are not necessarily needed to the same extent for promoting other competencies in science education. To evaluate the TSR-EBI's psychometric quality, we conducted two rounds of validation. Both samples ( N 1 = 114; N 2 = 74) consisted of pre-service teachers enrolled in university master's programs in Germany. The collected data were analyzed by applying Rasch analysis and known-group comparisons. In the course of an analysis of the TSR-EBI's internal structure, we found a 3-category scale to be superior to a 5-category structure. The person and item reliability of the scale proved to be satisfactory. Furthermore, during the second round of validation, it became clear that the results previously found for the 3-category scale were generally replicable across a new (but comparable) sample, which clearly supports the TSR-EBI's psychometric quality. Moreover, in terms of test-criterion relationships, the scale was also able to discriminate between groups that are assumed to have different levels of self-efficacy regarding teaching SR. Nonetheless, some findings also suggest that the scale might benefit from having the selection of individual items reconsidered (despite acceptable item fit statistics). On balance, however, we believe that the TSR-EBI has the potential to provide valuable insights in future studies regarding factors that influence teachers' self-efficacy, such as their professional experiences, prior training, or perceived barriers to effective teaching., Competing Interests: 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., (Copyright © 2024 Welter, Dawborn-Gundlach, Großmann and Krell.)

Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are postoperative neurocognitive disorders (PNDs) that frequently occur in the aftermath of a surgical intervention. Cognitive reserve (CR) is a concept posited to explain why cognitive health varies between individuals. On this qualitative understanding of cognitive health, factors like IQ, education level, and occupational complexity can affect the impact of neuropathological processes on cognitive outcomes., Methods: We investigated the association between CR and POD and CR and POCD on data from 713 patients aged≥65 years with elective surgery. Peak pre-morbid IQ was estimated from vocabulary. Occupational complexity was coded according to the Dictionary of Occupational Titles (DOT). Education level was classed according to the International Standard Classification of Education (ISCED). These three factors were used as proxies of CR. In a series of regression models, age, sex, depression, site of surgery, and several lifestyle and vascular factors were controlled for., Results: Patients with a higher IQ had lower odds of developing POD. We found no significant association between the other two CR markers with POD. None of the CR markers was associated with POCD., Conclusion: The significant association of a higher IQ with lower POD risk allows for the stratification of elderly surgical patients by risk. This knowledge can aid the prevention and/or early detection of POD. Further research should attempt to determine the lack of associations of CR markers with POCD in our study., Competing Interests: GW is coordinator of the BioCog consortium and is chief executive of the company Pharmaimage Biomarker Solutions GmbH (https://www.pi-pharmaimage.com), and employed by PI Health Solutions GmbH. Among other academic and private partners, the company is a partner of the BioCog study. CS and TP are project leaders in BioCog. 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 Borchers, Rumpel, Laubrock, Spies, Kozma, Slooter, van Montfort, Piper, Wiebach, Winterer, Pischon and Feinkohl.)

Introduction: Acute ischemic stroke (AIS) is a time-critical medical emergency. For patients with large-vessel occlusions (LVO), mechanical thrombectomy (MT) is the gold-standard treatment. Mobile Stroke Units (MSUs) provide on-site diagnostic capabilities via computed tomography (CT) and have been shown to improve functional outcomes in stroke patients, but are cost-efficient only in urban areas. Blood biomarkers have recently emerged as possible alternative to cerebral imaging for LVO diagnosis. Prehospital LVO diagnosis offers the potential to transport patients directly to centers that have MT treatment available. In this study, we assess the accuracy of combining two biomarkers, HFABP and NT-proBNP, with clinical indicators to detect LVO using ultra-early prehospital blood samples. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00030399)., Methods and Analysis: We plan a multicenter prospective observational study with 800 patients with suspected stroke enrolled within 24 h of symptom onset. Study participants will be recruited at three sites (MSUs) in Berlin, Germany. Blood-samples will be taken pre-hospitally at the scene and tested for HFABP and NT-proBNP levels. Additional clinical data and information on final diagnosis will be collected and documented in an electronic case report form (eCRF). Sensitivity and specificity of the combination will be calculated through iterative permutation-response calculations., Discussion: This study aims to evaluate the diagnostic capabilities of a combination of the biomarkers HFABP and NT-proBNP in LVO prediction. In contrast to most other biomarker studies to date, by employing MSUs as study centers, ultra-early levels of biomarkers can be analyzed. Point-of-care LVO detection in suspected stroke could lead to faster treatment in both urban and rural settings and thus improve functional outcomes on a broader scale., Clinical Trial Registration: Deutsches Register klinischer Studien https://drks.de/search/de/trial/DRKS00030399, DRKS00030399., Competing Interests: HA reports Presidency in the PREhospital Stroke Organization (PRESTO) and having received consultancy fees from Roche Diagnostics and NovoNordisk. FG owns stocks in JNJ, ABBV, BMY, and PFE. 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 author(s) 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 Kaffes, Bondi, Geisler, Grittner, Haacke, Ihl, Lorenz, Schehadat, Schwabauer, Wendt, Zuber, Kübler-Weller, Lorenz-Meyer, Sanchez, Montaner, Audebert and Weber.)

It has long been debated how humans estimate the numerosity of sets of elements and what role continuous visual properties play in this process. The dot comparison task, in which the more numerous of two dot arrays must be selected, is a dominant method to investigate this phenomenon. It has been shown that the visual properties of the two dot patterns strongly influence the comparison. This influence can be systematically investigated by manipulating visual properties congruently and incongruently with numerosity. However, it remains unclear how learning and prior experience affect the influence of the visual properties. To address this question, we introduced feedback into the classical dot comparison task: during the learning phase, participants in the experimental group received feedback after each trial indicating whether their answer was correct whereas participants in the control group did not. After the learning phase, neither group received feedback. The convex hull of the dot patterns and the average dot diameter were manipulated congruently and incongruently with numerosity. Our results show that feedback had no effect on overall performance. However, when manipulated separately, dot diameter no longer affected performance in the experimental group after the learning phase, but it did in the control group. Moreover, this effect remained visible even when diameter and convex hull were manipulated simultaneously. This pattern of results is consistent with the notion of sensory integration which proposes that weights are assigned to different visual cues and that numerical judgments depend on an additive combination of these weights. We also found a correlation between performance on an arithmetic task and performance on trials in which dot size was manipulated incongruently with numerosity. However, there were no correlations between an inhibition task and performance in the dot comparison task. Taken together, the current results suggest that learning with feedback may affect some visual properties but not others. Future studies should further investigate a wider range of visual properties to examine which of them can be influenced by learning and under what conditions learning occurs., Competing Interests: 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., (Copyright © 2024 Hofmann, Kinder and Pekár.)

Objective: Aquaporin-4-antibody-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) are relapsing neuroinflammatory diseases, frequently leading to chronic pain. In both diseases, the spinal cord (SC) is often affected by myelitis attacks. We hypothesized that regional SC volumes differ between AQP4-IgG + NMOSD and MOGAD and that pain intensity is associated with lower SC volumes. To evaluate changes in the SC white matter (WM), gray matter (GM), and pain intensity in patients with recent relapses (myelitis or optic neuritis), we further profiled phenotypes in a case series with longitudinal imaging and clinical data., Methods: Cross-sectional data from 36 participants were analyzed in this retrospective study, including 20 AQP4-IgG + NMOSD and 16 MOGAD patients. Pain assessment was performed in all patients by the Brief Pain Inventory and painDETECT questionnaires. Segmentation of SC WM, GM, cervical cord volumes (combined volume of WM + GM) was performed at the C2/C3 cervical level. WM% and GM% were calculated using the cervical cord volume as a whole per patient. The presence of pain, pain severity, and clinical disability was evaluated and tested for associations with SC segmentations. Additionally, longitudinal data were deeply profiled in a case series of four patients with attacks between two MRI visits within one year., Results: In AQP4-IgG + NMOSD, cervical cord volume was associated with mean pain severity within 24 h (β = -0.62, p  = 0.009) and with daily life pain interference (β = -0.56, p  = 0.010). Cross-sectional analysis showed no statistically significant SC volume differences between AQP4-IgG + NMOSD and MOGAD. However, in AQP4-IgG + NMOSD, SC WM% tended to be lower with increasing time from the last attack (β = -0.41, p  = 0.096). This tendency was not observed in MOGAD. Our case series including two AQP4-IgG + NMOSD patients revealed SC GM% increased by roughly 2% with either a myelitis or optic neuritis attack between visits. Meanwhile, GM% decreased by 1-2% in two MOGAD patients with a myelitis attack between MRI visits., Conclusion: In AQP4-IgG + NMOSD, lower cervical cord volume was associated with increased pain. Furthermore, cord GM changes were detected between MRI visits in patients with disease-related attacks in both groups. Regional SC MRI measures are pertinent for monitoring disease-related cord pathology in AQP4-IgG + NMOSD and MOGAD., Competing Interests: SA has received speaker honoraria from Alexion, Bayer, and Roche and a research grant from Novartis, unrelated to this publication. TS-H reports research grants form Celgene/bms, speaker honoraria from Bayer. FP reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, and MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. CC has received research support from Novartis and Alexion and writing honoraria from the British Society for Immunology, as well as serves as a member of the Standing Committee on Science for the Canadian Institutes of Health Research (CIHR). 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 Asseyer, Zmira, Busse, Pflantzer, Schindler, Schmitz-Hübsch, Paul and Chien.)

Food-borne Campylobacter jejuni infections constitute serious threats to human health worldwide. Since antibiotic treatment is usually not indicated in infected immune-competent patients, antibiotic-independent treatment approaches are needed to tackle campylobacteriosis. To address this, we orally applied carvacrol, deferoxamine, deoxycholate, and 2-fucosyl-lactose either alone or all in combination to human microbiota-associated IL-10 -/- mice from day 2 until day 6 following oral C. jejuni infection. Neither treatment regimen affected C. jejuni loads in the colon, whereas carvacrol lowered the pathogen numbers in the ileum on day 6 post-infection (p.i.). The carvacrol and combination treatment regimens resulted in alleviated diarrheal symptoms, less distinct histopathological and apoptotic epithelial cell responses in the colon, as well as diminished numbers of colonic neutrophils and T lymphocytes on day 6 p.i., whereas the latter cells were also decreased upon deferoxamine, deoxycholate, or 2-fucosyl-lactose application. Remarkably, the carvacrol, deferoxamine, and combination treatment regimens dampened ex-vivo IFN-γ secretion in the colon, the kidneys, and even in the serum to basal concentrations on day 6 p.i. In conclusion, carvacrol alone and its combination with deferoxamine, deoxycholate, and 2-fucosyl-lactose constitute promising antibiotics-independent treatment options to fight acute campylobacteriosis., Competing Interests: 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. The author(s) 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 Mousavi, Foote, Du, Bandick, Bereswill and Heimesaat.)

Introduction: COVID-19 affected global physical and psychological health. The purpose of this study was to explore the pandemics impact on health-related quality of life (HRQoL), mental health (anxiety, depression, and perceived stress) and eating behavior in people with severe obesity participating in a multimodal conservative behavioral weight loss (BWL) program conducted via videoconferencing. Additionally, the efficacy of the six-month BWL program in a virtual video-based setting during the pandemic was examined., Methods: 297 participants of a face-to-face multimodal behavioral weight loss program prior to the pandemic (PrePAN, May 2014-September 2019) and 146 participants of the in terms of content same intervention in a videoconference-based setting during the pandemic (PAN, July 2020-April 2022) were questioned and compared using standardized questionnaires for HRQoL, symptoms of depressive and anxiety disorders, perceived stress, and eating behavior at baseline and at the end of treatment., Results: Symptoms for anxiety, depression and perceived stress were similar between PrePAN and PAN at baseline. In addition, PAN tended to show lower disinhibition of eating behavior and feelings of hunger than PrePAN. During the pandemic, the BWL intervention resulted in body weight loss (67%) or stabilization (16%) in most of the participants. It also contributed by improving physical HRQoL, lower worries, and improved eating behaviors compared to baseline., Conclusion: During the COVID-19 pandemic, baseline mental health of people with morbid obesity was not worse than before the pandemic. Additionally, the BWL intervention in the virtual video-based setting stabilized and improved physical and mental health during the COVID-19 pandemic., Competing Interests: 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. SZ was 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 Schraml, Bauer, Schild, Klos, Erschens, Stengel, Nieß, Zipfel and Mack.)