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Despite their high prevalence, somatoform pain disorders are often not recognized early enough, not diagnosed reliably enough and not treated appropriately. Patients often experience a high level of suffering and the feeling of not being understood. For the medical care system, the symptoms represent a diagnostic and therapeutic challenge. Having the aim to get a better understanding of the disease, this study investigated the patients' emotion processing. In addition, the influence of surgical masks on facial affect processing was investigated, which has become more important since the onset of the Covid-19. The study involved an electroencephalogram (EEG) experimental paradigm extracting visual event-related potentials (vERP) evoked by emotional faces with and without surgical masks. Overall, the results of the face-related vERP indicate that the healthy control participants process the different emotional faces in a differentiated way. This can be seen from the fact that in this group the amplitudes of the vERP differ according to the different affects. In contrast, the patient group does not show any affect-specific potential differences in the vERP components. Besides, in healthy control participants, masks appear to limit the brain's ability to process emotions by hiding important facial information. Patients do not show any differences in the way they process images with and without masks, which suggests that patients generally process this content more rudimentary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Understanding the evolution of virulence, that is, the harm pathogens cause their hosts, has major and wide-spread repercussions. A central concept of virulence evolution is the so-called 'trade-off hypothesis', a seemingly straightforward relationship between virulence and transmission. However, substantial ambiguity in terminology related to this hypothesis threatens progress in the field. To address this, we apply a Hierarchy-of-Hypotheses approach to provide structured, visual representations of ideas linked to this hypothesis. We illustrate that the trade-off hypothesis is a complex set of many different hypotheses and trade-offs, and we clarify ambiguities and biases in commonly used terminology in the literature. Thereby, we hope to facilitate a more precise understanding of what the trade-off hypothesis means, enabling more targeted and precise hypothesis testing., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025. Published by Elsevier Ltd.)

Dissociative symptoms are a frequent complication in posttraumatic stress disorders affecting about a third of all PTSD patients. While theoretical models predict a physiological hypoarousal during posttraumatic dissociations, empirical evidence is lacking. We addressed this by studying spontaneously occurring dissociative symptoms and related heart rate changes in an ecological momentary assessment. Therefore, we continuously measured heart rate for five to ten days with mobile ECG in 47 female inpatients diagnosed with posttraumatic stress disorder and dissociative symptoms. During this observation period, patients tracked each dissociative event on a smartphone app and reported on symptom characteristics. Patients reported a total of 164 dissociative events. Those typically lasted <30 min and involved co-occuring depersonalization and derealization of moderate to severe intensity. Tracked symptoms correlated positively with some conventional self-reports for depersonalization and derealization. Heart rate during dissociative symptoms varied greatly between and within individuals and was on average not different from baseline assessment. There was also no significant relation between dissociation intensity and heart rate change. These results challenge the theory of reactive hypoarousal during chronic dissociation and support the view that physiological adaptation modifies in the course of posttraumatic chronification. They also highlight the individual variability of dissociative symptoms and underscore the necessity of detailed assessment for targeted therapeutic approaches., Competing Interests: Declaration of competing interest None of the authors reports a conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Stroke results in long-term impacts on a person's life requiring ongoing management after formal rehabilitation ends. Coaching can support people to build competencies and skills for managing health-related challenges and has the potential to support stroke survivors to continue achieving goals on their own following rehabilitation. This review sought to describe the research on coaching interventions for adults living with stroke., Materials and Methods: A scoping review to explore how coaching is defined and used in stroke rehabilitation intervention research. PubMed, CINAHL, Medline, and PsycINFO databases were searched using terms to represent coaching, rehabilitation practitioners, and stroke, the results were extracted into COVIDENCE. Data were described and synthesized to identify similarities and differences among coaching interventions., Results: Twenty-eight articles describing 15 interventions were included and categorized based on their focus as Health Coaching, Coaching for Exercise and Physical Activity, Coaching for Engagement in Activity or Participation, and Transition Coaching. Common elements of coaching interventions were goal setting, problem solving and education with emotional support being infrequent. Notably, coaching definitions and techniques were frequently not described., Conclusions: Coaching in stroke rehabilitation is diverse but has common foci and elements. More research using clear descriptions of coaching is required.

Background:  The minimally invasive mitral valve procedure warrants minimal surgical trauma and might influence the postoperative course positively, especially in old patients. In this retrospective study, we reviewed our experience in minimally invasive mitral valve surgery (miMVS) in patients aged ≥ 75 years., Methods:  In this retrospective cohort study, based on propensity score matching, we compared patients aged ≥75 years with patients aged <75 years who underwent miMVS. The primary endpoint was 30-day mortality. Secondary endpoints were myocardial infarction, stroke, and renal failure., Results:  Between January 2011 and February 2021, 761 patients underwent miMVS at our institution. After propensity score matching, a study group (≥75 years, n  = 189) and a control group (<75 years, n  = 189) were formed. Preoperatively patients ≥75 years more often suffered from NYHA III heart failure (60 vs. 46%; p  = 0.013). Their valves were more often frequently replaced (48 vs. 32%; p  < 0.001), and their postoperative ventilation time was longer (13 hours vs. 11 hours; p  < 0.001). There were no statistically significant differences regarding postoperative stroke (3 vs. 0.6%; p  = 0.16), myocardial infarction (0 vs. 1%; p  = 0.32), renal insufficiency with new dialysis (5 vs. 4%; p  = 0.62), and 30-day mortality (4 vs. 2%; p  = 0.56)., Conclusion:  miMVS results in satisfactory early postoperative outcomes in elderly patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Competing Interests: This study was supported by funding from the Foundation “10.13039/501100003042Else Kröner-Fresenius-Stiftung” within the Research Program “Else Kröner-Forschungskolleg AntiAge.” The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: In symptomatic high-risk patients with severe mitral valve regurgitation (MR), who are not eligible for surgery, Transcatheter edge-to-edge repair (TEER) or transcatheter mitral valve replacement (TMVR) may be an option, especially when surgical mitral valve repair by annuloplasty has been performed earlier. After TMVR, the appropriate anticoagulation regimen is still matter of debate., Case Presentation: We here report on a 78-year-old frail lady with heart failure and atrial fibrillation who underwent surgical reconstruction of the mitral valve nine years ago. Due to high surgical risk and after heart team discussion, TMVR using a transcatheter aortic valve prosthesis (valve-in-ring concept) was performed successfully via the transapical access route. Several months later, an excellent result could be confirmed. Since surgical excision of the left atrial appendage was carried out during first surgery, oral anticoagulation was withdrawn. Two months later, the patient presented with a massive LA thrombus mass and severe stenosis of the mitral valve prosthesis requiring re-do surgery., Conclusions: Management of anticoagulation in patients with atrial fibrillation and successfully performed LAA excision is still a matter of debate, in particular after transcatheter heart valve implantation in mitral position. TMVR devices may be very thrombogenic. Thus, caution should be used whenever discontinuing oral anticoagulation in these patients. Despite the lack of evidence, withdrawal of anticoagulation should be avoided here, especially in the absence of bleeding complications. Left atrial appendage closure or excision should not influence this decision., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was given by the patient. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

Cognitive decline is becoming more prevalent as population ages. Technology offers solutions to help people with cognitive decline age in place. A compassionate approach to care can promote engagement in technology use by older adults with cognitive decline and equitable access. This scoping review summarized research literature on approaches to design and selection of technology that could support a compassionate approach to technology use for daily functioning among adults with cognitive decline and their care partners. We used the framework of Arksey and O'Malley. Key words capturing constructs of compassion, technology, and cognitive decline were searched in CINAHL, Medline, and PsycINFO. Peer-reviewed articles about the design for or use of technology by persons with cognitive decline or their care partners were included. Two reviewers screened and extracted data. Data informing compassionate technology use were analysed thematically. Fifty-five included articles represented a variety of technologies and purposes with ethics being the predominant perspective ( n  = 15). Analysis identified four categories: 1) Person- and care partner-centered approach, 2) Tailoring design to abilities, 3) Tailoring selection and application, and 4) Training and support. Using study findings, we developed a framework for compassionate use of technology for people living with cognitive decline and their care partners.

Background: Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI., Methods: Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied., Results: Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23-7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08-1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p < 0.01). There was no significant difference regarding acute kidney injury (OR 1.20, 95%CI 0.50-2.87, p = 0.69)., Conclusions: The analysis suggests that liver dysfunction in patients undergoing PCI is independently associated with higher risk of short-term mortality and increased occurrence of MACCE and bleeding. However, there appears to be no association to acute kidney injury., (© 2024. The Author(s).)

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy ( n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy.

Background: Women developing preeclampsia (PE) or fetal growth restriction (FGR) during pregnancy are at higher risk for cardiovascular diseases (CVD) later in life. We aimed to analyse cardiovascular health of women 10-20 years after affected pregnancies in comparison to women after uneventful pregnancies. In addition, we assessed a potential long-term effect of the NO-donor pentaerythrityl tetranitrate (PETN)., Methods: Women 10-20 years after severe PE, including women receiving PETN during pregnancy and matched controls were recruited and assessed for baseline clinical data and cardiovascular function by transthoracic echocardiography, VICORDER and USCOM. SPSS was used for statistical analysis., Results: 53 participants after PE/FGR (13 with former PETN intake) and 51 controls were recruited for follow-up at an average of 14 years after index pregnancies. Compared to controls, women after PE/FGR had a significantly higher incidence of arterial hypertension (13.7% vs. 41.5%, p<0.001), and were more likely to be hypertensive (41.2% vs. 67.30%, p = 0.008). There were no differences in cardiovascular function observed. Affected women with PETN intake during pregnancy showed lower mean values for right atrial area and ventricle in comparison to controls and also to affected women without former medication., Conclusions: In conclusion, our study results confirm that the risk of CVD is increased in women after PE/FGR compared to women after uneventful pregnancies. Contrary to our expectations, no major cardiovascular changes were observed in our cohort 10-20 years post pregnancy. The observed differences found in right heart dimensions were within reference ranges, and should be interpreted with caution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lößner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Pulmonary vascular and right ventricular (RV) remodelling processes are important for development and progression of pulmonary hypertension (PH). The current study analysed the functional role of the extra domain A-containing fibronectin (ED-A+ Fn) for the development of PH by comparing ED-A+ Fn knockout (KO) and wild-type (WT) mice as well as the effects of an antibody-based therapeutic approach in a model of monocrotaline (MCT)-induced PH, which will be validated in a model of Sugen 5416/hypoxia-induced PH., Methods and Results: PH was induced using MCT (PH mice). Sixty-nine mice were divided into the following groups: sham-treated controls (WT: n = 7; KO: n = 7), PH mice without specific treatment (WT: n = 12; KO: n = 10), PH mice treated with a dual endothelin receptor antagonist (macitentan; WT: n = 6; KO: n = 11), WT PH mice treated with the F8 antibody, specifically recognizing ED-A+ Fn, (n = 8), and WT PH mice treated with an antibody of irrelevant antigen specificity (KSF, n = 8). Compared to controls, WT&#95;PH mice showed a significant elevation of the RV systolic pressure (P = 0.04) and RV functional impairment including increased basal RV (P = 0.016) diameter or tricuspid annular plane systolic excursion (P = 0.008). In contrast, KO PH did not show such effects compared to controls (P = n.s.). In WT&#95;PH mice treated with F8, haemodynamic and echocardiographic parameters were significantly improved compared to untreated WT&#95;PH mice or those treated with the KSF antibody (P < 0.05). On the microscopic level, KO&#95;PH mice showed significantly less tissue damage compared to the WT&#95;PH mice (P = 0.008). Furthermore, lung tissue damage could significantly be reduced after F8 treatment (P = 0.04). Additionally, these findings could be verified in the Sugen 5416/hypoxia mouse model, in which F8 significantly improved echocardiographic, haemodynamic, and histologic parameters., Conclusion: ED-A+ Fn is of crucial importance for PH pathogenesis representing a promising therapeutic target in PH. We here show a novel therapeutic approach using antibody-mediated functional blockade of ED-A+ Fn capable of attenuating and partially reversing PH-associated tissue remodelling., Competing Interests: Conflict of interest: M.M. is an employee of Philochem AG (www.philochem.ch), daughter company of Philogen. M.F. obtained financial support from Philogen (www.philogen.com). A.B., P.C.S., and M.F. have transferred IP rights to Philogen (www.philogen.com) concerning antibody–cytokine fusions. D.N. is CEO and shareholder of Philogen (www.philogen.com), a company working on the discovery and development of targeted therapeutics, including antibody–cytokine fusions. The remaining co-authors did not declare any conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The influence of the electron density of a bridge connecting two redox centers on both the intervalence hole transfer and the magnetic superexchange was investigated in a series of bridged bis-triarylamine mono- and dications. In this series, the bridge was 2,7-fluorenyl, where the bridge electron density was modified by substituents at the 9-position. For the mixed-valence monocations, the observation of both an intervalence charge transfer (IVCT) band and an absorption band associated with an electron transfer from the bridging fluorene to the triarylamine radical cation centers allowed determination of the electron transfer couplings in the framework of the three-state generalized Mulliken-Hush theory. Comparison of the derived couplings with those obtained from a classical two-state approach demonstrates an enhancement of the electronic coupling which increases with decreasing bridge state energy. For the dicationic diradical counterparts, the singlet-triplet gap (exchange interaction) was determined both experimentally and by quantum chemical methods. Hereby, an increase of antiferromagnetic coupling with a lowering of the bridge state energy by electron donating substituents was observed. Analysis of the involved molecular orbitals suggests that the ferromagnetic coupling is inversely proportional to the square of the bridge energy, which is also supported by the experimental findings. This influence of the bridge state energy on both types of interactions, electron transfer and magnetic exchange, provides a design guideline for fine-tuning the properties of electronically coupled organic redox dyads by variation of the bridge electron density.

The development of several unique strategies and tactics for the synthesis of α-pinene isotopologues that has culminated in access to all eight possible isomers with deuterium incorporated selectively at each available carbon atom is described. Access to this library of isotopologues provides new tools to more fully investigate the atmospheric autoxidation of α-pinene, a complex process that plays a major role in the formation of secondary organic aerosol in the Earth's atmosphere.

Photogenerated three-spin systems show great potential for applications in the field of molecular spintronics. In these systems, the exchange interaction in the electronically excited state dictates their magnetic properties. To design such molecules for specific applications, it is thus important to understand how the sign and magnitude of the exchange interaction can be controlled. For this purpose, we developed a perturbational approach, based on previous work by the groups of de Loth and Malrieu, that allows for the direct calculation of the exchange interaction and its individual contributions up to the second order and implemented it within the ORCA program package. Within this manuscript, we present the derivation of the individual second-order contributions, provide an overview of the implementation of the code and illustrate its performance. We show that, using this perturbational approach in combination with state-averaged orbitals from minimal active space calculations, accurate values for the exchange interaction can be computed for organic nitroxides. Further, we demonstrate that the weight of the ionic determinants in the orbital optimisation of the CASSCF procedure is crucial for the computation of accurate exchange couplings. In the case of photoexcited chromophore-radical systems, we find that the dynamic spin polarisation effect constitutes the most important contribution to the exchange interaction, whereby the sign of this contribution determines the sign of the exchange interaction.

Introduction: Animal models play a vital role in pharmaceutical research and development by supporting the planning and design of later clinical studies. To improve confidence and reliability of first in human dose estimates it is essential to assess the comparability of animal studies with the human situation. In the context of large molecules, it is particularly important to evaluate the cross-species-translatability of parameters related to neonatal fragment crystallizable receptor (FcRn) binding and target mediated drug disposition (TMDD), as they greatly influence distribution and disposition of proteins in the body of an organism., Methods: Plasma pharmacokinetic data of the therapeutic protein efalizumab were obtained from literature. Physiologically based pharmacokinetic (PBPK) models were built for three different species (rabbit, non-human primate (NHP), human). Target binding was included in the NHP and human models. The assumption of similar target turnover and target-binding in NHP and human was explored, to gain insights into how these parameters might be translated between species., Results: Efalizumab PBPK models were successfully developed for three species and concentration-time-profiles could be described appropriately across different intravenously administered doses. The final NHP and human models feature a common set of parameters for target turnover and drug-target-complex internalization, as well as comparable target-binding parameters. Our analyses show that different parameter values for FcRn affinity are crucial to accurately describe the concentration-time profiles., Discussion: Based on the available data in rabbits, NHP and humans, parameters for FcRn affinity cannot be translated between species, but parameters related to target mediated drug disposition can be translated from NHP to human. The inclusion of additional pharmacokinetic (PK) data including different efalizumab doses would further support and confirm our findings on identifying TMDD and, thus, binding kinetics of efalizumab in NHPs. Furthermore, we suggest that information on target expression and internalization rates could make it possible to develop comprehensive human PBPK models with minimal animal testing. In this project, we compared the pharmacokinetics of a therapeutic protein in rabbit, NHP and human using an open PBPK modeling platform (Open Systems Pharmacology Suite, http://www.open-systems-pharmacology.org). Our findings could support similar translatory studies for first in human dose predictions in the future., Competing Interests: Authors MF and NH were employees of Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach, Germany, at the time of the research project. Author LK received research grants from Boehringer Ingelheim Pharma GmbH and Co. KG. The remaining 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 Franz, Jairam, Kuepfer and Hanke.)

Amputation as a life-saving measure for earthquake-trapped patients is supported by WHO and INSARAG guidelines. However, implementing these guidelines in highly stressful contexts can complicate decision-making. This report presents a case of life-saving amputation during the 2023 Turkey earthquake, adhering to recommended guidelines. The 16-year-old patient was trapped for 55 hours in a narrow corridor. Extensive interdisciplinary discussions led to the decision for a field amputation after alternative rescue attempts failed. Consent was obtained from the family, given the patient's delirium. Meticulous planning and anesthesia using midazolam and ketamine ensured successful amputation with minimal blood loss. Challenges encountered during the disaster response were discussed. Delays in administering antibiotics, a lack of cervical protection, ethical dilemmas, psychological concerns, and legal implications were highlighted. Continued improvement and addressing ethical, legal, and psychological aspects are essential for optimal disaster response outcomes.

Marine heatwaves have caused massive mortality in coastal benthic ecosystems, altering community composition. Here, we aim to understand the effects of single and sequential sublethal heatwaves in a temperate benthic ecosystem, investigating their disturbance on various levels of ecological hierarchy, i.e. individual physiology, trophic groups' biomass and ecosystem carbon fluxes. To do so, we performed a near-natural experiment using outdoor benthic mesocosms along spring/summer, where communities were exposed to different thermal regimes: without heatwaves (0HW), with one heatwave (1HW) and with three heatwaves (3HWs). Gastropods were negatively impacted by one single heatwave treatment, but the exposure to three sequential heatwaves caused no response, indicating ecological stress memory. The magnitude of ecosystem carbon fluxes mostly decreased after 1HW, with a marked negative impact on mesograzers' feeding, while the overall intensity of carbon fluxes increased after 3HWs. Consumers' acclimation after the exposure to sequential heatwaves increased grazing activity, representing a threat for the macroalgae biomass. The evaluation of physiological responses and ecological interactions is crucial to interpret variations in community composition and to detect early signs of stress. Our results reveal the spread of heatwave effects along the ecological hierarchical levels, helping to predict the trajectories of ecosystem development.This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

Objective: To determine if the receipt of occupational performance coaching (OPC) by adults living with multiple sclerosis (MS) improves participants' satisfaction with performance in daily activities (primary outcome); improves perceived performance in daily activities, resilience, autonomy, and participation; and reduces illness intrusiveness and effect of MS (secondary outcomes)., Design: Two-group randomized clinical trial with a waitlist control., Setting: Community., Participants: Convenience sample of adults with MS were recruited through a research registry. Eighty-three individuals were approached; 35 were assessed for eligibility and 31 were enrolled and 30 completed baseline assessment (Final sample size, N=30). Participants were English-speaking, were without serious cognitive impairment or severe depression, and were not receiving other coaching interventions., Interventions: Six telephone sessions of OPC were delivered by a trained facilitator over 10 weeks. Initial sessions focused on goal setting, prioritization, and action planning. Subsequent sessions involved goal and action plan review, discussion of facilitators and barriers, and goal and plan refinement., Main Outcome Measures: Primary outcome was participants' satisfaction with performance in daily activities, as measured by the Canadian Occupational Performance Measure (COPM). Secondary outcome measures included the COPM performance rating, Connor-Davidson Resilience Scale, Impact on Participation and Autonomy Questionnaire, Adapted Illness Intrusiveness Rating Scale, and MS Impact Scale. Measures were administered by a blinded assessor at baseline, 10 weeks, and 2 months., Results: Participants in the intervention and waitlist control groups were equivalent on demographic and outcome measures at baseline. At 10 weeks, the intervention group had significantly higher COPM ratings for both satisfaction (P<.001) and performance (P=.002). No other outcomes were significantly different. For the intervention group, the benefits of OPC were maintained at 2 months., Conclusions: OPC led to improved satisfaction with performance and performance in daily activities. Future research with a larger sample is needed to determine other effects and who benefits most from OPC., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Physiologically based pharmacokinetic (PBPK) modelling is an important tool to predict drug disposition in the body. Rabbits play a pivotal role as a highly valued small animal model, particularly in the field of ocular therapeutics, where they serve as a crucial link between preclinical research and clinical applications. In this context, we have developed PBPK models designed specifically for rabbits, with a focus on accurately predicting the pharmacokinetic profiles of protein therapeutics following intravenous administration. Our goal was to comprehend the influence of key physiological factors on systemic disposition of antibodies and their functional derivatives. For the development of the systemic PBPK models, rabbit physiological factors such as gene expression, body weight, neonatal fragment crystallizable receptor (FcRn) binding, target binding, target concentrations, and target turnover rate were meticulously considered. Additionally, key protein parameters, encompassing hydrodynamic radius, binding kinetic constants (KD, k off ), internal degradation of the protein-target complex, and renal clearance, were represented in the models. Our final rabbit models demonstrated a robust correlation between predicted and observed serum concentration-time profiles after single intravenous administration in rabbits, covering IgG, Fab, F(ab) 2 , Fc, and Fc fusion proteins from various publications. These pharmacokinetic simulations offer a promising platform for translating preclinical findings to clinical settings. The presented rabbit intravenous PBPK models lay an important foundation for more specific applications of protein therapeutics in ocular drug development., Competing Interests: MF and NH were employees of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, at the time of the research project. LK received research grants from Boehringer Ingelheim Pharma GmbH & Co. KG. The remaining 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 Jairam, Franz, Hanke and Kuepfer.)

We examine a class of Hamiltonians characterized by interatomic, interorbital even-odd parity hybridization as a model for a family of topological insulators without the need for spin-orbit coupling. Non-trivial properties of these materials are exemplified by studying the topologically-protected edge states of s - p hybridized alkali and alkaline earth atoms in one and two-dimensional lattices. In 1D the topological features are analogous to the canonical Su-Schrieffer-Heeger model but, remarkably, occur in the absence of dimerization. Alkaline earth chains, with Be standing out due to its gap size and near particle-hole symmetry, are of particular experimental interest since their Fermi energy without doping lies directly at the level of topological edge states. Similar physics is demonstrated to occur in a 2D honeycomb lattice system of s - p bonded atoms, where dispersive edge states emerge. Lighter elements are predicted using this model to host topological states in contrast to spin-orbit coupling-induced band inversion favoring heavier atoms., (Creative Commons Attribution license.)

The "Robotic Curriculum for young Surgeons" (RoCS) was launched 03/2020 to address the increasing importance of robotics in surgical training. It aims to provide residents with foundational robotic skills by involving them early in their training. This study evaluated the impact of RoCS' integration into clinical routine on patient outcomes. Two cohorts were compared regarding the implementation of RoCS: Cohort 1 (before RoCS) included all robot-assisted procedures between 2017 and 03/2020 (n = 174 adults) retrospectively; Cohort 2 (after RoCS) included all adults (n = 177) who underwent robotic procedures between 03/2020 and 2021 prospectively. Statistical analysis covered demographics, perioperative parameters, and follow-up data, including mortality and morbidity. Subgroup analysis for both cohorts was organ-related (upper gastrointestinal tract (UGI), colorectal (CR), hepatopancreaticobiliary system (HPB)). Sixteen procedures were excluded due to heterogeneity. In-hospital, 30-, 90-day morbidity and mortality showed no significant differences between both cohorts, including organ-related subgroups. For UGI, no significant intraoperative parameter changes were observed. Surgery duration decreased significantly in CR and HPB procedures (p = 0.018 and p < 0.001). Estimated blood loss significantly decreased for CR operations (p = 0.001). The conversion rate decreased for HPB operations (p = 0.005). Length of hospitalization decreased for CR (p = 0.015) and HPB (p = 0.006) procedures. Oncologic quality, measured by histopathologic R0-resections, showed no significant changes. RoCS can be safely integrated into clinical practice without compromising patient safety or oncologic quality. It serves as an effective training pathway to guide robotic novices through their first steps in robotic surgery, offering promising potential for skill acquisition and career advancement., (© 2024. The Author(s).)

A 69-year-old male patient with seropositive erosive rheumatoid arthritis (RA) presented to our clinic due to progressive dyspnea. High-resolution computed tomography (HRCT) and immunological bronchioalveolar lavage revealed ground-glass opacities and a lymphocytic alveolitis caused by interstitial lung disease (ILD) in RA. Considering previous forms of treatment, disease-modifying antirheumatic drug (DMARD) treatment was switched to tofacitinib. Tofacitinib treatment demonstrated a 33% reduction in ground-glass opacities by artificial intelligence-based quantification of pulmonary HRCT over the course of 6 months, which was associated with an improvement in dyspnea symptoms. In conclusion, tofacitinib represents an effective anti-inflammatory therapeutic option in the treatment of RA-ILD., (© 2023. The Author(s).)

Objectives: Inflammatory rheumatic diseases (IRD) are often associated with interstitial lung disease (ILD). The aim of the present study was to establish a correlation between the findings on HRCT and the immunological bronchoalveolar lavage (BAL)., Methods: The study included 74 patients with newly diagnosed IRD and evidence of ILD on HRCT with the following pattern: ground-glass opacities (GGO), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Patients with other HRCT pattern were excluded. No patient received any immunosuppressive therapy. In addition to HRCT, immunological BAL was performed and the American Thoracic Society clinical practice guideline were used to define BAL patterns (lymphocytic cellular pattern, neutrophilic cellular pattern, eosinophilic cellular pattern and unspecified pattern)., Results: The main HRCT patterns were NSIP (47.3%), GGO (33.8%), and UIP (18.9%). BAL patterns showed the following distribution: 41.9% lymphocytic cellular pattern, 23.0% neutrophilic cellular pattern, 18.9% eosinophilic cellular pattern, and 16.2% unspecific cellular pattern. Placing these data in the context of the HRCT findings, the lymphocytic cellular BAL pattern (48%) was most commonly BAL pattern associated with GGO pattern in HRCT, whereas neutrophilic and lymphocytic cellular BAL patterns were the dominant feature in NSIP and UIP., Conclusion: In patients with new-onset IRD and ILD, inflammatory pulmonary changes are predominate, reflected by GGO on HRCT and a mainly lymphocytic cell profile in the immunological BAL. In NSIP or UIP on HRCT, the percentages of lymphocytes and neutrophils were higher in BAL fluid, representing a fibrotic component in addition to the inflammation. Consequently, patients with evidence of GGO on HRCT should primarily be treated with anti-inflammatory/immunosuppressive therapy, whereas in patients with NSIP and UIP a combination of anti-inflammatory and anti-fibrotic agents would be the appropriate treatment., (© 2024. The Author(s).)

Background : Minimally invasive mitral valve surgery (MIMVS) is a treatment for severe mitral valve pathologies. In redo cases, especially after coronary artery bypass grafting (CABG) surgery with patent mammary bypass grafts, establishing aortic clamping followed by antegrade cardioplegia application might be challenging. Here, we present the outcome of hypothermic ventricular fibrillation as an alternative to conventional cardioprotection. Methods : Patients who underwent MIMVS either received hypothermic ventricular fibrillation (study group, n = 48) or antegrade cardioprotection (control group, n = 840) and were observed for 30 postoperative days. Data were retrospectively analyzed and collected from January 2011 until December 2022. Results : Patients in the study group had a higher preoperative prevalence of renal insufficiency ( p = 0.001), extracardiac arteriopathy ( p = 0.001), insulin-dependent diabetes mellitus ( p = 0.001) and chronic lung disease ( p = 0.036). Furthermore, they had a longer surgery time and a lower repair rate ( p < 0.001). No difference, however, was seen in postoperative incidences of stroke ( p = 0.26), myocardial infarction ( p = 1) and mitral valve re-operation ( p = 1) as well as 30-day mortality ( p = 0.1) and postoperative mitral valve insufficiency or stenosis. Conclusions : The patients who underwent redo MIMVS with hypothermic ventricular fibrillation did not have worse outcomes or more serious adverse events compared to the patients who received routine conventional cardioprotection. Therefore, the use of hypothermic ventricular fibrillation appears to be a promising cardioprotective technique in this challenging patient population requiring redo MIMVS.

Background : Mitral valve infective endocarditis (IE) still has a high mortality. Minimally invasive mitral valve surgery (MIMVS) is technically more challenging, especially in patients with endocarditis. Here, we compare the early postoperative outcome of patients with endocarditis and other indications for MIMVS. Methods : Two groups were formed, one consisting of patients who underwent surgery because of mitral valve endocarditis (IE group: n = 75) and the other group consisting of patients who had another indication for MIMVS (non-IE group: n = 862). Patients were observed for 30 postoperative days. Data were retrospectively reviewed and collected from January 2011 to September 2023. Results : Patients from the IE group were younger (60 vs. 68 years; p < 0.001) and had a higher preoperative history of stroke (26% vs. 6%; p < 0.001) with neurological symptoms (26% vs. 9%; p < 0.001). No difference was seen in overall surgery time (211 vs. 206 min; p = 0.71), time on cardiopulmonary bypass (137 vs. 137 min; p = 0.42) and aortic clamping time (76 vs. 78 min; p = 0.42). Concerning postoperative data, the IE group had a higher requirement of erythrocyte transfusion (2 vs. 0; p = 0.041). But no difference was seen in the need for a mitral valve redo procedure, bleeding, postoperative stroke, cerebral bleeding, new-onset dialysis, overall intubation time, sepsis, pacemaker implantation, wound healing disorders and 30-day mortality. Conclusions : Minimally invasive mitral valve surgery in patients with mitral valve endocarditis is feasible and safe. Infective endocarditis should not be considered as a contraindication for MIMVS.

Background: Lung transplantation is the only curative treatment for patients with end-stage pulmonary fibrosis. It is still under debate whether over- or undersizing of lung allografts is preferably performed regarding the postoperative outcome. We therefore analyzed our data using predicted total lung capacity to compare size mismatches., Methods: Patient records were retrospectively reviewed. Three groups were formed, 1 including patients with a donor-recipients pTLC ratio (DRPR) of <1.0 (undersized group), the second with a DRPR of ≥1.0 and <1.1 (size-matched group), and the third group with a DRPR of ≥1.1 (oversized group). Outcomes were evaluated using chi-square test and Kruskall-Wallis test as well as Kaplan-Meier analysis, competing risk analysis, and multivariable analysis, respectively., Results: Between January 2010 and May 2023, among the 1501 patients transplanted at our institution, 422 (28%) patients were included, 26 (2%) patients forming the oversized group (median DRPR: 1.14), 101 (7%) patients forming the size-matched group (median DRPR: 1.03), and 296 (20%) patients forming the undersized group (median DRPR: 0.92). Patients from the oversized group had a higher PGD grade 3 rate at 24 (p < 0.001), 48 (p < 0.001), and 72 (p = 0.039) hours after transplantation as well as a higher in-hospital mortality compared to the undersized group (p = 0.033). The long-term survival was also better in the undersized group compared to the oversized group (p = 0.011) and to the size-matched group (p = 0.01)., Conclusions: Oversizing lung allografts more than 10% deteriorated early postoperative outcomes and long-term survival in patients with pulmonary fibrosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Solid-water interfaces are crucial for clean water, conventional and renewable energy, and effective nuclear waste management. However, reflecting the complexity of reactive interfaces in continuum-scale models is a challenge, leading to oversimplified representations that often fail to predict real-world behavior. This is because these models use fixed parameters derived by averaging across a wide physicochemical range observed at the molecular scale. Recent studies have revealed the stochastic nature of molecular-level surface sites that define a variety of reaction mechanisms, rates, and products even across a single surface. To bridge the molecular knowledge and predictive continuum-scale models, we propose to represent surface properties with probability distributions rather than with discrete constant values derived by averaging across a heterogeneous surface. This conceptual shift in continuum-scale modeling requires exponentially rising computational power. By incorporating our molecular-scale understanding of solid-water interfaces into continuum-scale models we can pave the way for next generation critical technologies and novel environmental solutions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: We established the most commonly used clinician and patient-reported hip fracture outcome measures as of 2022, assessed their content validity using an International Classification of Functioning, Disability and Health (ICF) framework, and operationalized these results to contribute to an updated hip fracture core set., Materials and Methods: A literature search was conducted to identify articles utilizing outcome measures related to hip fracture. A total of five outcome measures were identified, linked to the ICF, and assessed for content validity via bandwidth percent, content density, and content diversity., Results: Outcome measures were linked to 191 ICF codes, most of which were associated with Activities and Participation. Notably, no outcome measure contained concepts linked to Personal Factors and Environmental Factors were underrepresented across all outcome measures. The modified Harris Hip Score had the highest content diversity (0.67), the Hip Disability and Osteoarthritis Outcome Score had the highest bandwidth of ICF content coverage (2.48), and the Oxford Hip Score had the highest content density (2.92)., Conclusions: These results clarify the clinical applicability of outcome measures and guide development of hip fracture outcomes that allow providers to assess the complex role of social, environmental, and personal factors in patient rehabilitation.IMPLICATIONS FOR REHABILITATIONHip fracture is a complex and disabling pathology predominantly affecting older adults and represents a public health problem.There are a variety of outcome measures used to assess a patient's recovery following a hip fracture, each with distinctive objectives and modes of administration.Content validity metrics associated with the Harris Hip Score suggest it would be a suitable outcome measure during early-stage recovery, whereas the modified Harris Hip Score may be more suitable for tracking long-term recovery tracking.Choosing an outcome measure most appropriate for a hip fracture patient is an individualized decision that must consider aspects such as age, activity level, needs, and environmental factors.

Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces. The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA Platform and successfully integrated 14 AI-based image analysis apps from eight different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes. Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Schmell and Falk Zakrzewski are employed by an AI vendor of which one app was included in the evaluation. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2024 The Author(s).)

Stacking ferroelectricity (SFE) has been discovered in a wide range of van der Waals materials and holds promise for applications, including photovoltaics and high-density memory devices. We show that the microscopic origin of out-of-plane stacking ferroelectric polarization can be generally understood as a consequence of a nontrivial Berry phase borne out of an effective Su-Schrieffer-Heeger model description with broken sublattice symmetry, thus elucidating the quantum-geometric origin of polarization in the extremely nonperiodic bilayer limit. Our theory applies to known stacking ferroelectrics such as bilayer transition-metal dichalcogenides in 3R and T&#95;{d} phases, as well as general AB-stacked honeycomb bilayers with staggered sublattice potential. Our explanatory and self-consistent framework based on the quantum-geometric perspective establishes quantitative understanding of out-of-plane SFE materials beyond symmetry principles.

Host-pathogen interactions can be influenced by the host microbiota, as the microbiota can facilitate or prevent pathogen infections. In addition, members of the microbiota can become virulent. Such pathobionts can cause co-infections when a pathogen infection alters the host immune system and triggers dysbiosis. Here we performed a theoretical investigation of how pathobiont co-infections affect the evolution of pathogen virulence. We explored the possibility that the likelihood of pathobiont co-infection depends on the evolving virulence of the pathogen. We found that, in contrast to the expectation from classical theory, increased virulence is not always selected for. For an increasing likelihood of co-infection with increasing pathogen virulence, we found scenario-specific selection for either increased or decreased virulence. Evolutionary changes, however, in pathogen virulence do not always translate into similar changes in combined virulence of the pathogen and the pathobiont. Only in one of the scenarios where pathobiont co-infection is triggered above a specific virulence level we found a reduction in combined virulence. This was not the case when the probability of pathobiont co-infection linearly increased with pathogen virulence. Taken together, our study draws attention to the possibility that host-microbiota interactions can be both the driver and the target of pathogen evolution. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

This narrative review summarizes a representative collection of electrophysiological and imaging studies on the neural processes and brain sources underlying hypnotic trance and the effects of hypnotic suggestions on the processing of experimentally induced painful events. It complements several reviews on the effect of hypnosis on brain processes and structures of chronic pain processing. Based on a summary of previous findings on the neuronal processing of experimentally applied pain stimuli and their effects on neuronal brain structures in healthy subjects, three neurophysiological methods are then presented that examine which of these neuronal processes and structures get demonstrably altered by hypnosis and can thus be interpreted as neuronal signatures of the effect of analgesic suggestions: (A) On a more global neuronal level, these are electrical processes of the brain that can be recorded from the cranial surface of the brain with magnetoencephalography (MEG) and electroencephalography (EEG). (B) On a second level, so-called evoked (EPs) or event-related potentials (ERPs) are discussed, which represent a subset of the brain electrical parameters of the EEG. (C) Thirdly, imaging procedures are summarized that focus on brain structures involved in the processing of pain states and belong to the main imaging procedures of magnetic resonance imaging (MRI/fMRI) and positron emission tomography (PET). Finally, these different approaches are summarized in a discussion, and some research and methodological suggestions are made as to how this research could be improved in the future., 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 Miltner, Franz and Naumann.)

Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH&#95;MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH&#95;MAC groups ( p = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH ( p < 0.05) but not the PH&#95;MAC group ( p = n.s.). The PH group showed elevated serum concentrations for IL-22 ( p = 0.04) and IL-17a ( p = 0.008). Compared to the PH group, the PH&#95;MAC group demonstrated a decrease in IL-22 ( p = 0.021) but not IL17a ( p = n.s.). In the PH patient collective ( n = 92), increased serum levels of IL-22 but not IL-17a could be shown ( p < 0.0001). This elevation remained significant across the different etiological groups ( p < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.

Background: Infective endocarditis represents a life-threatening disease with high mortality rates. A fraction of patients receives exclusively conservative antibiotic treatment due to their comorbidities and high operative risk, despite fulfilling criteria for surgical therapy. The aim of the present study is to compare outcomes in patients with infective endocarditis and indication for surgical therapy in those who underwent or did not undergo valve surgery., Methods and Results: Three databases were systematically assessed. A pooled analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies with longer follow-up comparing conservative and surgical treatment was performed. A landmark analysis to further elucidate the effect of surgical intervention on mortality was carried out. Four studies with 3003 patients and median follow-up time of 7.6 months were included. Overall, patients with an indication for surgery who were surgically treated had a significantly lower risk of mortality compared with patients who received conservative treatment (hazard ratio [HR], 0.27 [95% CI, 0.24-0.31], P <0.001). The survival analysis in the first year showed superior survival for patients who underwent surgery when compared with those who did not at 1 month (87.6% versus 57.6%; HR, 0.31 [95% CI, 0.26-0.37], P <0.01), at 6 months (74.7% versus 34.6%) and at 12 months (73.3% versus 32.7%)., Conclusions: Based on the findings of this study-level meta-analysis, patients with infective endocarditis and formal indication for surgical intervention who underwent surgery are associated with a lower risk of short- and long-term mortality when compared with conservative treatment.

This study investigates speech production under various room acoustic conditions in virtual environments, by comparing vocal behavior and the subjective experience of speaking in four real rooms and their audio-visual virtual replicas. Sex differences were explored. Males and females (N = 13) adjusted their voice levels similarly to room acoustic changes in the real rooms, but only males did so in the virtual rooms. Females, however, rated the visual virtual environment as more realistic compared to males. This suggests a discrepancy between sexes regarding the experience of realism in a virtual environment and changes in objective behavioral measures such as voice level., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

By virtue of the modularity of their structures, their tunable optical and magnetic properties, and versatile applications, photogenerated triplet-radical systems provide an ideal platform for the study of the factors controlling spin communication in molecular frameworks. Typically, these compounds consist of an organic chromophore covalently attached to a stable radical. After formation of the chromophore triplet state by photoexcitation, two spin centres are present in the molecule that will interact. The nature of their interaction is governed by the magnitude of the exchange interaction between them and can be studied by making use of transient electron paramagnetic resonance (EPR) techniques. Here, we investigate three perylene-nitroxide dyads that only differ with respect to the position where the nitroxide radical is attached to the perylene core. The comparison of the results from transient UV-vis and EPR experiments reveals major differences in the excited state properties of the three dyads, notably their triplet state formation yield, excited state deactivation kinetics, and spin coherence times. Spectral simulations and quantum chemical calculations are used to rationalise these findings and demonstrate the importance of considering the structural flexibility and the contribution of rotational conformers for an accurate interpretation of the data., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We employ amplitude- and phase-resolved second harmonic generation experiments to probe interactions of fused silica:aqueous interfaces with Al 3+ , Mg 2+ , and Na + cations at pH 4 and as a function of metal cation concentration. We quantify the second-order nonlinear susceptibility and the total interfacial potential in the presence and absence of a 10 mM screening electrolyte to understand the influence of charge screening on cation adsorption. Strong cation:surface interactions are observed in the absence of the screening electrolyte. The total potential is then employed to estimate the total number of absorbed cations cm -2 . The contributions to the total potential from the bound and mobile charges were separated using Gouy-Chapman-Stern model estimates. All three cations bind fully reversibly, indicating physisorption as the mode of interaction. Of the isotherm models tested, the K d adsorption model fits the data with binding constants of 3-30 and ∼300 mol -1 for the low (<0.1 mM) and high (0.1-3 mM) concentration regimes, corresponding to adsorption free energies of -13 to -18 and -24 kJ mol -1 at room temperature, respectively. The maximum surface coverages are around 10 13 cations cm -2 , matching the number of deprotonated silanol groups on silica at pH 4. Clear signs of decoupled Stern and diffuse layer nonlinear optical responses are observed and found to be cation-specific.

Background: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe., Material and Methods: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature., Results: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m 2 . In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up., Conclusion: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Objectives: Multi-organ failure is one of the leading causes of mortality after cardiac surgery for infective endocarditis (IE). Although the randomized evidence does not support the use of haemoadsorption during cardiac surgery for IE, observational studies suggest a beneficial effect in selected patient groups. Staphylococcus aureus is the most common pathogen, and its presence is an independent mortality predictor. We aimed to analyse the effect of haemoadsorption in patients with IE caused by S. aureus., Methods: This is a post hoc analysis of the REMOVE trial that randomized 288 patients with IE who underwent cardiac surgery with haemoadsorption using CytoSorb® or control. The primary outcome was ΔSequential Organ Failure Assessment (SOFA), defined as the difference between the mean total postoperative and baseline SOFA score within 24 h of surgery., Results: Among the total of 282 patients included in the modified intention-to-treat analysis of the REMOVE trial, 73 (25.9%) had S. aureus IE (38 patients in the haemoadsorption group and 35 patients in the control group). The overall ΔSOFA did not differ between the intervention groups in patients with S. aureus IE (mead difference = -0.4, 95% confidence interval -2.3 to 1.4, P = 0.66) and neither did 30-day mortality (hazard ratios = 1.32, 95% confidence interval 0.53-3.28, P = 0.55). No differences were observed with regard to any of the other secondary outcomes., Conclusions: Based on a post hoc analysis from REMOVE trial, the intraoperative use of haemoadsorption in patients with S. aureus IE was not associated with reduction of postoperative organ dysfunction, 30-day mortality or other major clinical end points., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We propose a novel qubit architecture based on a planar c-axis Josephson junction between a thin flake d-wave superconductor, such as a high-T&#95;{c} cuprate Bi&#95;{2}Sr&#95;{2}CaCu&#95;{2}O&#95;{8+x}, and a conventional s-wave superconductor. When operated in the transmon regime the device-that we call "d mon"-becomes insensitive to offset charge fluctuations and, importantly, exhibits at the same time energy level spectrum with strong anharmonicity that is widely tunable through the device geometry and applied magnetic flux. Crucially, unlike previous qubit designs based on d-wave superconductors the proposed device operates in a regime where quasiparticles are fully gapped and can be therefore expected to achieve long coherence times.

Background: Pathogenesis of pulmonary hypertension (PH) is a multifactorial process driven by inflammation and pulmonary vascular remodeling. To target these two aspects of PH, we recently tested a novel treatment: Interleukin-9 (IL9) fused to F8, an antibody that binds to the extra-domain A of fibronectin (EDA + Fn). As EDA + Fn is not found in healthy adult tissue but is expressed during PH, IL9 is delivered specifically to the tissue affected by PH. We found that F8IL9 reduced pulmonary vascular remodeling and attenuated PH compared with sham-treated mice., Purpose: To evaluate possible F8IL9 effects on PH-associated inflammatory processes, we analysed the expression of genes involved in pulmonary immune responses., Methods: We applied the monocrotaline (MCT) model of PH in mice ( n = 44). Animals were divided into five experimental groups: sham-induced animals without PH (control, n = 4), MCT-induced PH without treatment (PH, n = 8), dual endothelin receptor antagonist treatment (dual ERA, n = 8), F8IL9 treatment ( n = 12, 2 formats with n = 6 each), or with KSFIL9 treatment (KSFIL9, n = 12, 2 formats with n = 6 each, KSF: control antibody with irrelevant antigen specificity). After 28 days, a RT-PCR gene expression analysis of inflammatory response (84 genes) was performed in the lung., Results: Compared with the controls, 19 genes exhibited relevant (+2.5-fold) upregulation in the PH group without treatment. Gene expression levels in F8IL9-treated lung tissue were reduced compared to the PH group without treatment. This was the case especially for CCL20, CXCL5, C-reactive protein, pentraxin related (CRP PR ), and Kininogen-1 (KNG1)., Conclusion: In accordance with the hypothesis stated above, F8IL9 treatment diminished the upregulation of some genes associated with inflammation in a PH animal model. Therefore, we hypothesize that IL9-based immunocytokine treatment will likely modulate various inflammatory pathways.

Facial mimicry is the automatic imitation of the facial affect expressions of others. It serves as an important component of interpersonal communication and affective co-experience. Facial mimicry has so far been measured by Electromyography (EMG), which requires a complex measuring apparatus. Recently, software for measuring facial expressions have become available, but it is still unclear how well it is suited for measuring facial mimicry. This study investigates the comparability of the automated facial coding software Affdex with EMG for measuring facial mimicry. For this purpose, facial mimicry was induced in 33 subjects by presenting naturalistic affect-expressive video sequences (anger, joy). The response of the subjects is measured simultaneously by facial EMG (corrugator supercilii muscle, zygomaticus major muscle) and by Affdex (action units lip corner puller and brow lowerer and affects joy and anger). Subsequently, the correlations between the measurement results of EMG and Affdex were calculated. After the presentation of the joy stimulus, there was an increase in zygomaticus muscle activity (EMG) about 400 ms after stimulus onset and an increase in joy and lip corner puller activity (Affdex) about 1200 ms after stimulus onset. The joy and the lip corner puller activity detected by Affdex correlate significantly with the EMG activity. After presentation of the anger stimulus, corrugator muscle activity (EMG) also increased approximately 400 ms after stimulus onset, whereas anger and brow lowerer activity (Affdex) showed no response. During the entire measurement interval, anger activity and brow lowerer activity (Affdex) did not correlate with corrugator muscle activity (EMG). Using Affdex, the facial mimicry response to a joy stimulus can be measured, but it is detected approximately 800 ms later compared to the EMG. Thus, electromyography remains the tool of choice for studying subtle mimic processes like facial mimicry., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Westermann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Many COVID-19 survivors suffer from persisting sequelae after acute disease. This is referred to as long COVID. The objectives of this study were to assess factors associated with long COVID and to analyze differences in persistent symptoms, findings on chest imaging, and pulmonary function between intensive care unit (ICU) and non-ICU hospitalized patients., Methods: We conducted a retrospective study including patients hospitalized with COVID-19. Patients were stratified into ICU patients and non-ICU patients. We analyzed the outcomes of patients who were in clinical follow-up 6 months after discharge with persistent symptoms, radiological and/or functional abnormalities. Logistic regression was used to examine the association between long COVID and patient characteristics., Results: A total of 549 patients were included. Eighty-one ICU patients (66%) and 146 (34%) non-ICU patients had persistent symptoms or abnormalities on chest imaging or lung function test minimally 6 months after discharge. Significantly more ICU patients had residual fibrotic abnormalities on chest CT and functional impairment. Female gender, myocardial infarction, OSAS, low PCO2 at admission, and longer hospital stay were associated with a higher risk of developing long COVID. Diabetes and treatment with tocilizumab were associated with a lower risk of developing long COVID., Conclusion: Of the patients hospitalized for COVID-19, 34-66% suffered from persistent symptoms, residual abnormalities on chest imaging, or reduced lung function at around 6 months after discharge. While persistent sequelae were more frequent in ICU patients, admission to the ICU was not found to be an independent risk factor for developing long COVID., (© 2024 S. Karger AG, Basel.)

Background: Metabolomics has become a valuable tool for identifying potential new biomarkers and metabolic profiles. It has the potential to improve the diagnosis and prognosis of different phenotypes of heart failure. To generate a distinctive metabolic profile, we assessed and compared the metabolic phenotypes of patients with acute decompensated heart failure (ADHF), patients with chronic heart failure (CHF), and healthy controls., Methods: Plasma metabolites were analyzed by liquid-chromatography mass spectrometry/mass spectrometry and the MxP Quant 500 kit in 15 patients with ADHF, 50 patients with CHF (25 with dilated cardiomyopathy, 25 with ischemic cardiomyopathy), and 13 controls., Results: Of all metabolites identified to be significantly altered, 3-indolepropionic acid and 1-methyl histidine showed the highest concentration differences in ADHF and CHF compared with control. Area under the curve-receiver operating characteristic analysis showed an area under the curve ≥0.8 for 3-indolepropionic acid and 1-methyl histidine, displaying good discrimination capabilities between control and patient cohorts. Additionally, symmetrical dimethylarginine (mean, 1.97±0.61 [SD]; P =0.01) was identified as a suitable biomarker candidate for ADHF and kynurenine (mean, 1.69±0.39 [SD]; P =0.009) for CHF when compared with control, both demonstrating an area under the curve ≥0.85., Conclusions: Our study provides novel insights into the metabolic differences between ADHF and CHF and healthy controls. We here identify new metabolites for potential diagnostic and prognostic purposes., Competing Interests: Disclosures Dr Schulze received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, Bristol Myers Squibb, Abiomed, Pharmacosmos, and Amgen not related to this article and research support for the department from Boehringer Ingelheim, Edwards, and Abiomed not related to this article.

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG. 200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits. PRSs for BMI (β = 3.78; p = 0.0041), schizophrenia (β = 5.38; p = 0.021) and diabetes type 2 (β = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10 -6 . Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples., Competing Interests: Declaration of competing interest SP was supported by the European Union's Horizon Europe research and innovation programme (Psych-STRATA, grant agreement No 101057454). UH was supported by the European Union's Horizon 2020 research and innovation programme (PSY-PGx, grant agreement No 945151) outside the submitted work. MF, MSS, BBB, CG, IS, MR, PZ, TGS, RM declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Twisted interfaces between stacked van der Waals (vdW) cuprate crystals present a platform for engineering superconducting order parameters by adjusting stacking angles. Using a cryogenic assembly technique, we construct twisted vdW Josephson junctions (JJs) at atomically sharp interfaces between Bi 2 Sr 2 CaCu 2 O 8+ x crystals, with quality approaching the limit set by intrinsic JJs. Near 45° twist angle, we observe fractional Shapiro steps and Fraunhofer patterns, consistent with the existence of two degenerate Josephson ground states related by time-reversal symmetry (TRS). By programming the JJ current bias sequence, we controllably break TRS to place the JJ into either of the two ground states, realizing reversible Josephson diodes without external magnetic fields. Our results open a path to engineering topological devices at higher temperatures.