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Abstract Aging affects the 12-lead electrocardiogram (ECG) and correlates with cardiovascular disease (CVD). AI-ECG models estimate aging effects as a novel biomarker but have only been evaluated on single ECGs—without utilizing longitudinal data. We validated an AI-ECG model, originally trained on Brazilian data, using a German cohort with over 20 years of follow-up, demonstrating similar performance (r 2 = 0.70) to the original study (0.71). Incorporating longitudinal ECGs revealed a stronger association with cardiovascular risk, increasing the hazard ratio for mortality from 1.43 to 1.65. Moreover, aging effects were associated with higher odds ratios for atrial fibrillation, heart failure, and mortality. Using explainable AI methods revealed that the model aligns with clinical knowledge by focusing on ECG features known to reflect aging. Our study suggests that aging effects in longitudinal ECGs can be applied on population level as a novel biomarker to identify patients at risk early.

Deep learning models for the classification of electrocardiograms (ECGs) are able to learn disease-specific patterns, but they are rarely implemented in medical practice due to their "black box" nature. Post-hoc explainable artificial intelligence (XAI) methods compute regions of interest (ROI) which are of importance for a model’s decision making. However, it needs to be further analyzed whether a model focuses on the morphological or rhythmical information within the ROIs. We evaluate a pre-trained ResNet for sinus bradycardia (SB) and sinus tachycardia (ST) classification on the PTBXL dataset using the XAI method Integrated Gradients. We compare the confidence of the model predictions to ECG features used by clinicians using correlation analysis. Correlation is highest for RR intervals (SB: 0.44) and atrial as well as ventricular heart rates (ST: 0.51), with the majority exceeding clinical thresholds for both disorders, indicating that the model learned rhythmical features. Except for QT intervals in ST classification, morphological features such as duration and amplitudes of P-/T-waves do not show any correlation.

Introduction: Preoperative electrically auditory evoked potentials (= eAEP, i.e., eABR for brainstem, eAMLR for midbrain, and eALR for cortex) can be performed under local anesthesia, achieving subjective sensation and hearing in patients having a functional auditory nerve. For intraoperative eAEP, we stimulate the auditory nerve with an intra-cochlear test electrode like a cochlear implant (= CI) and stimulate basally when using an extra-cochlear electrode. These measurements aim to confirm preoperative findings (e.g. uncertain preoperative eABR) or intraoperative decisions (e.g. vestibular schwannoma resection). Methods: Preoperative eAEP can be performed with the trans-tympanic stimulation electrode and a neurological EP system for recording the responses. In addition, eAEP under local anesthesia allows for preoperative diagnostics of subjective sensation. For intraoperative eAEP, the intra-cochlear auditory nerve test system (= ANTS) system is preferable showing similar results to the gold standard CI-eABR (i.e., eABR using a CI for stimulation). The eAMLR can be used only preoperatively in case of ambiguous EABR or for extended analysis of the auditory pathway. Results: During preoperative eAEP in local anesthesia, an eABR is essential. eAMLR and eALR are optional. The subjective sensation can be recorded in parallel. A reliable response often avoids eAEP under general anesthesia. eAEP under general anesthesia should be performed as rarely as possible preoperatively to avoid unnecessary intraoperative eAEP, performed usually directly before cochlear implantation. Extra-cochlear stimulation avoids mechanical trauma and possible intra-cochlear infections. However, intra-cochlear stimulation is usually recommended due to larger response amplitudes; in fact, the ANTS electrode provides more stable monitoring. Conclusion: eAEP can be diagnostically useful preoperatively and intraoperatively with the concept presented here. Since not all clinics are familiar with these methods, a learning curve may be necessary.

Anatomy-based fitting (ABF) has the potential to lead to better outcomes than conventional clinically-based fitting (CBF). It has already been shown that anatomy-based fitting based on postoperative imaging (postopABF) can improve speech understanding. Moreover, it was demonstrated that patients preferred anatomy-based fitting maps based on preoperative imaging (preop ABF) over CBF. The goal of this study was to examine if a difference between preopABF and postopABF could be observed. Via the software OTOPLAN4 (CAScination, MED-EL) the electrode position was calculated based on preoperatively, as part of the clinical routine, obtained imaging (CT or MRI). If necessary, after the cochlear implantation surgery the selected electrode array was adapted if a different array was chosen intraoperatively. This data was exported into the fitting software MAESTRO to enable a preopABF. The same process was done based on postoperative imaging (CT) so that 1) the frequency bands were compared between preopABF and postopABF data and 2) the difference was displayed in semitones. 27 Patients could be included who got a postoperative CT scan. In addition, subjective tinnitus and dizziness or imbalance issues did not significantly change from the pre-operative appointment over the first fitting to the control fitting one month later. In this study, we could show that there is no significant difference between apical to medial and a significant difference for medial to basal electrode contacts between the preopABF and postopABF regarding the frequency bands. Thus, preopABF is an easy, clinically practicable way to implement ABF, which is promising to lead to better outcomes without extra costs and the radiation burden that comes with postopABF. If patients subjectively prefer either preopABF or postopABF is still to be examined.

Introduction: In auditory evoked potentials (= AEP), auditory brainstem response (= ABR) is the gold standard for objective analysis of the auditory pathway using acoustical stimulators like headphones during hearing screening and patient assessment. Where no response can be recorded, electrical stimulation can be used in pre-, intra-, or postoperative scenarios to confirm the excitability of the auditory nerve (= eAEP). In eAEP, the recording of brainstem response (= eABR) is mostly the method of choice. Sometimes in eABR, the stimulation artifact can not only harden but even prevent the detection of the response waveforms. Methods: Many factors can influence the stimulation artifact when recording an eAEP. Neurological recording systems are recommended as well as some approved AEP systems traditionally used in ENT for amplification to avoid large stimulation artifacts in the response waveforms, but able to recover in

Abstract Background Body composition parameters provide relevant prognostic significance in critical care cohorts and cancer populations. Published results regarding polytrauma patients are inconclusive to date. The goal of this study was to analyse the role of body composition parameters in severely injured trauma patients. Methods All consecutive patients requiring emergency tracheal intubation and mechanical ventilation before initial computed tomography (CT) at a level‐1 trauma centre over a 12‐year period (2008–2019) were reanalysed. The analysis included CT‐derived body composition parameters based upon whole‐body trauma CT as prognostic variables for 30‐day mortality, intensive care unit length of stay (ICU LOS) and mechanical ventilation duration. Results Four hundred seventy‐two patients (75% male) with a median age of 49 years, median injury severity score of 26 and 30‐day mortality rate of 22% (104 patients) met the inclusion criteria and were analysed. Regarding body composition parameters, 231 patients (49%) had visceral obesity, 75 patients had sarcopenia (16%) and 35 patients had sarcopenic obesity (7.4%). After adjustment for statistically significant univariable predictors age, body mass index, sarcopenic obesity, visceral obesity, American Society of Anesthesiologists classification ≥3, injury severity score and Glasgow Coma Scale ≤ 8 points, the Cox proportional hazard model identified sarcopenia as significant prognostic factor of 30‐day mortality (hazard ratio 2.84; 95% confidence interval 1.38–5.85; P = 0.004), which was confirmed in Kaplan–Meier survival analysis (log‐rank P = 0.006). In a subanalysis of 363 survivors, linear multivariable regression analysis revealed no significant associations of body composition parameters with ICU LOS and duration of mechanical ventilation. Conclusions In a multivariable analysis of mechanically ventilated trauma patients, CT‐defined sarcopenia was significantly associated with 30‐day mortality whereas no associations of body composition parameters with ICU LOS and duration of mechanical ventilation were observed.

With the call for reformed teaching practices in STEM education, there is a need to spread effective teaching practices to classrooms. Affective drivers can lead an instructor to improve their teaching practices, but they are infrequently addressed or recognized. This case study followed one instructor through her General Chemistry course over a summer and fall semester to gain a detailed understanding of the affective drivers that impacted her teaching practices. Semi-structured interviews, based on classroom observations and field notes, revealed that the instructor had self- and student-focused factors that influenced her affective drivers. The self-focused factors included feeling basic emotional needs, feeling intrinsically motivated towards self-improvement, and feeling self-efficacy regarding instruction and chemistry. The student-focused factors included feeling like a supportive faculty to students, feeling empathy towards students, and having expectations for students' personal successes. Considering the difficulty of long-term change in faculty, the affective drivers are rich sources of motivation. Understanding these affective drivers, particularly if they are common to other instructors, could allow for targeted instructor self-reflection and guidance. The authors suggest that approaching self-reflection through an affective lens will allow for more effective support to change and adopt effective teaching practices.

Social media (SoMe) is an important part of how young people socialize and communicate with each other and there are concerns that this may negatively impact peer relationships. The aim of this article was to explore how high school students experience the impact of SoMe on their peer relationships and the quality of these relationships. We performed qualitative semi-structured interviews with 12 Norwegian high-school students. Results showed that SoMe changed the quality of peer relationships as well as online and offline communication. The impact of SoMe on peer relationships depended on whether the students had both online and offline peer relations. Unlike offline relationships, where the youth experienced real friendships, online relationships were primarily described as contacts. The results suggest that online peer relationships often resemble affiliations rather than attachments. This may negatively impact social competence, especially among students whose peer relationships are mainly online-based.

BACKGROUND: Childhood cancer survivors (CCS) experience many long-term health problems that can be mitigated with recommended survivorship care. However, many CCS do not have access to survivorship care nor receive recommended survivorship care. We reviewed the empirical evidence of disparities in survivorship care for CCS. METHODS: This systematic review searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS (PROSPERO: CRD42021227965) and abstracted the reported presence or absence of disparities in care. We screened 7945 citations, and of those, we reviewed 2760 publications at full text. RESULTS: A total of 22 studies reported in 61 publications met inclusion criteria. Potential disparities by cancer treatment (N = 14), diagnosis (N = 13), sex (N = 13), and current age (N = 13) were frequently studied. There was high quality of evidence (QOE) of survivorship care disparities associated with non-White race, Hispanic ethnicity, and being uninsured. Moderate QOE demonstrated disparities among CCS who were unemployed and older. Lower QOE was found for disparities based on cancer diagnosis, cancer treatment, age at diagnosis, time since diagnosis, sex, insurance type, income, educational attainment, and geographic area. CONCLUSIONS: We found strong empirical evidence of disparities in survivorship care for CCS associated with race, ethnicity, and insurance status. Multiple other disparate groups, such as those by employment, income, insurance type, education, cancer diagnosis, age at diagnosis, time since diagnosis, cancer treatment, geographic area, sex, and self-identified gender warrant further investigation. Prospective, multilevel research is needed to examine the role of other patient characteristics as potential disparities hindering adequate survivorship care in CCS.

IntroductionThe first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.MethodsAn aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.ResultsSera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.DiscussionThese results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.

Objectives The objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.Methods Patients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.Results 121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.Conclusion Serum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.

Die Humangenetik ist ein sehr junges medizinisches Fachgebiet. Dies ist begründet in den über lange Zeit limitierten Untersuchungsmöglichkeiten des Erbmaterials und daraus resultierend, dem begrenzten Wissen über genetische Ursachen von Erkrankungen. Jetzt jedoch, mit der (R)Evolution der Analysemethoden (Hochdurchsatz-DNA-Sequenzierungsansätze) ist die Untersuchung des individuellen Erbmaterials für Patienten im Rahmen der Regelversorgung möglich. Das hat Auswirkungen auf nahezu alle medizinischen Fachbereiche. Nicht nur, dass wir heute Erkrankungen, die durch einzelne Genveränderungen verursacht werden, einen Namen geben können. Wir verstehen jetzt die komplexen Interaktionen von genetisch-determinierten Vulnerabilitäten bzw. Resilienzen und externen Faktoren immer besser. Ermöglichen nun die umfassenden und schnellen Analysemethoden, der enorme Zuwachs an zur Verfügung stehenden hochqualitativen klinisch-genetischen Daten und der explosionsartige Informationsgewinn eine bessere Prognoseabschätzung für Gesundheit und Krankheit? Ja und Nein. Für eine Vielzahl von genetischen Erkrankungen ist eine evidenzbasierte Prognoseabschätzung möglich, auch wenn in der Regel der konkrete Verlauf der Erkrankung für das einzelne Individuum nicht vorhergesagt werden kann. Erfreulich ist, dass mit zunehmender Kenntnis Krankheits-modifizierender genetischer und nicht-genetischer Faktoren unsere Prognoseabschätzung immer präziser wird.Für vorhersagende (prädiktive) genetische Untersuchungen an Gesunden ist die Einschätzung der Prognose schwieriger. Dabei spielt diese vorhersagende Untersuchung asymptomatischer Personen eine immer wichtiger werdende Rolle: zum Beispiel in der Testung hinsichtlich einer Anlageträgerschaft für bestimmte Erkrankungen oder in der Bestimmung von genetischen Risikofaktoren für Erkrankungen. Das Wissen über individuelle Erkrankungswahrscheinlichkeiten auf Grundlage eines genetischen Befundes bietet die einzigartige Möglichkeit der präventiven Anpassung des klinischen Managements. Hierdurch lässt sich die Prognose dieser Erkrankungen wesentlich beeinflussen. So umfasst das Spektrum klinischer Implikationen einer prädiktiven Testung unter anderem die Möglichkeit von risikoreduzierenden Operationen, die Aufnahme in intensivierte Früherkennungsprogramme sowie Lebensstilmodifikationen zur Vermeidung risikobehafteter Umweltfaktoren. Somit dient die Bestimmung einer genetischen Konstellation nicht nur einer reinen Prognoseabschätzung, sondern ist vielmehr von wesentlicher prognostischer Relevanz.

Preserving biodiversity is a global challenge. Censuses of marine biodiversity are indispensable for monitoring the responses of marine life to environmental changes induced by human activities. Ongoing extinction events affect both species and populations amid unprecedented environmental changes induced by climate shifts and habitat degradation. These changes result in substantial declines in biodiversity. In addition, our understanding of oceanic life remains incomplete, especially regarding elusive, rare, delicate, or understudied organisms. One example for this is the biodiversity of the Red Sea which remains largely unexplored and poorly understood. In an attempt to evaluate the current status of known versus COI-barcoded marine animal species in the Red Sea we used online taxonomic and genetic databases to provide a comprehensive analysis of the region's described marine life, focusing on the occurrence data of marine animal species to identify disparities in COI barcoding coverage at the phylum level. Our analysis reveals that barcoding coverage varies significantly among phyla, with Nematoda, Platyhelminthes, Bryozoa, and Porifera being highly underrepresented compared to Chordata. While over 6000 metazoan species from 22 phyla are known to inhabit the Red Sea, only 49.77 % appear to be barcoded. COI barcoding helps preserve biodiversity by providing a reliable and standardized method for accurately identifying and monitoring species, including those that are cryptic or newly discovered, thereby informing and enhancing conservation efforts and guiding future research efforts toward understudied regions and organisms.

No data are currently available on the functional role of small conductance Ca2+‐activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non‐cell‐permeant SK2 inhibitor Lei‐Dab7, we identified functional SK2 channels at the plasma membrane, regulating store‐operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei‐Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei‐Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro‐migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression‐free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination.

As technology advances, the field of electrical and computer engineering continuously demands the introduction of innovative new tools and methodologies to facilitate the effective learning and comprehension of fundamental concepts. This research addresses an identified gap in technology-augmented education capabilities and researches the integration of virtual reality (VR) technology with real-time electronic circuit simulation to enable and enhance the visualization of non-observable concepts such as voltage distribution and current flow within these circuits. In this paper, we describe the development of our immersive educational platform, which makes understanding these abstract concepts intuitive and engaging. This research also involves the design and development of a VR-based circuit simulation environment. By leveraging VR’s immersive capabilities, our system enables users to physically interact with electronic components, observe the flow of electrical signals, and manipulate circuit parameters in real-time. Through this immersive experience, learners can gain a deeper understanding of fundamental electronic principles, transcending the limitations of traditional two-dimensional diagrams and equations. Furthermore, this research focuses on the implementation of advanced and novel visualization techniques within the VR environment for non-observable electrical and electromagnetic properties, providing users with a clearer and more intuitive understanding of electrical circuit concepts. Examples include color-coded pathways for current flow and dynamic voltage gradient visualization. Additionally, real-time data representation and graphical overlays are researched and integrated to offer users insights into the dynamic behavior of circuits, allowing for better analysis and troubleshooting.

ObjectiveFor large, integrated healthcare delivery systems, coordinating patient care across delivery systems with providers external to the system presents challenges. We explored the domains and requirements for care coordination by professionals across healthcare systems and developed an agenda for research, practice and policy.DesignThe modified Delphi approach convened a 2-day stakeholder panel with moderated virtual discussions, preceded and followed by online surveys.SettingThe work addresses care coordination across healthcare systems. We introduced common care scenarios and differentiated recommendations for a large (main) healthcare organisation and external healthcare professionals that contribute additional care.ParticipantsThe panel composition included health service providers, decision makers, patients and care community, and researchers. Discussions were informed by a rapid review of tested approaches to fostering collaboration, facilitating care coordination and improving communication across healthcare systems.Outcome measuresThe study planned to formulate a research agenda, implications for practice and recommendations for policy.ResultsFor research recommendations, we found consensus for developing measures of shared care, exploring healthcare professionals' needs in different care scenarios and evaluating patient experiences. Agreed practice recommendations included educating external professionals about issues specific to the patients in the main healthcare system, educating professionals within the main healthcare system about the roles and responsibilities of all involved parties, and helping patients better understand the pros and cons of within-system and out-of-system care. Policy recommendations included supporting time for professionals with high overlap in patients to engage regularly and sustaining support for care coordination for high-need patients.ConclusionsRecommendations from the stakeholder panel created an agenda to foster further research, practice and policy innovations in cross-system care coordination.