Introduction: There is a lack of real-world data directly comparing different valve prostheses for transaortic valve replacement (TAVR). We aimed to compare early clinical outcomes at 30-days between the self-expandable Portico valve (Abbott) with the balloon-expandable Edwards Sapien 3 valve (Edwards Lifesciences) (ES3).

Methods: Out of 1,901 patients undergoing TAVR between January 2018 and December 2021, all patients who received either Portico valve or ES3 valve via transfemoral TAVR were matched using nearest-neighbor (1:1) propensity scoring. Primary endpoints were single safety endpoints and early safety composite endpoints defined by Valve Academic Research Consortium-2 (VARC-2) criteria. The secondary endpoint was to analyze risk predictors for new permanent pacemaker (PPM) implantation in TAVR.

Results: Out of 661 complete cases, a total of 434 patients were successfully matched based on age, sex, Euro Score II and STS-score. In the matched cohort, 217 received either a Portico or valve and 217 received an ES3 valve. The VARC-2 early safety composite scores indicated a significantly greater overall 30-day safety risk in the Portico group at 9.2% (n = 20) compared to 3.7% (n = 8) in the ES3 group (p = 0.032). The requirement for new permanent pacemaker (PPM) implantation was also higher in the Portico group, at 21.2% (n = 46) vs. 13.4% (n = 29) in the ES3 group (p = 0.042). 30-day mortality was higher was 3.7% (n = 8) in Portico group compared to 0.9% in ES3 group (p = 0.11). Furthermore, implantation of the Portico valve was identified as a significant risk predictor for new PPM implantation, alongside higher age, preprocedural atrioventricular block (AVB) and longer total procedure duration.

Conclusion: This study shows significantly higher rates of early clinical complications for Portico valve prostheses compared to ES3. These findings should be especially taken into consideration when selecting valve prosthesis for high-risk patients.

Purpose: Passive tibiofemoral anterior-posterior (AP) laxity has been extensively investigated after posterior cruciate ligament (PCL) single-bundle reconstruction. However, the PCL also plays an important role in providing rotational stability in the knee. Little is known in relation to the effects of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity. Gait biomechanics after PCL reconstruction are even less understood. The aim of this study was a comprehensive prospective biomechanical in vivo analysis of the effect of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity, passive anterior-posterior laxity, and gait pattern.

Methods: Eight patients undergoing PCL single-bundle reconstruction (seven male, one female, mean age 35.6 ± 6.6 years, BMI 28.0 ± 3.6 kg/m2) were analyzed preoperatively and 6 months postoperatively. Three of the eight patients received additional posterolateral corner (PLC) reconstruction. Conventional stress radiography was used to evaluate passive translational tibiofemoral laxity. A previously established rotometer device with a C-arm fluoroscope was used to assess passive tibiofemoral rotational laxity. Functional gait analysis was used to examine knee kinematics during level walking.

Results: The mean side-to-side difference (SSD) in passive posterior translation was significantly reduced postoperatively (12.1 ± 4.4 mm vs. 4.3 ± 1.8 mm; p < 0.01). A significant reduction in passive tibiofemoral rotational laxity at 90° knee flexion was observed postoperatively (27.8° ± 7.0° vs. 19.9° ± 7.5°; p = 0.02). The range of AP tibiofemoral motion during level walking was significantly reduced in the reconstructed knees when compared to the contralateral knees at 6-month follow-up (16.6 ± 2.4 mm vs. 13.5 ± 1.6 mm; p < 0.01).

Conclusion: PCL single-bundle reconstruction with optional PLC reconstruction reduces increased passive tibiofemoral translational and rotational laxity in PCL insufficient knees. However, increased passive tibiofemoral translational laxity could not be fully restored and patients showed altered knee kinematics with a significantly reduced range of tibiofemoral AP translation during level walking at 6-month follow-up. The findings of this study indicate a remaining lack of restoration of biomechanics after PCL single-bundle reconstruction in the active and passive state, which could be a possible cause for joint degeneration after PCL single-bundle reconstruction.

The utilization of numerical methods, such as computational fluid dynamics (CFD), has been widely established for modeling patient-specific hemodynamics based on medical imaging data. Hemodynamics assessment plays a crucial role in treatment decisions for the coarctation of the aorta (CoA), a congenital heart disease, with the pressure drop (PD) being a crucial biomarker for CoA treatment decisions. However, implementing CFD methods in the clinical environment remains challenging due to their computational cost and the requirement for expert knowledge. This study proposes a deep learning approach to mitigate the computational need and produce fast results. Building upon a previous proof-of-concept study, we compared the effects of two different artificial neural network (ANN) architectures trained on data with different dimensionalities, both capable of predicting hemodynamic parameters in CoA patients: a one-dimensional bidirectional recurrent neural network (1D BRNN) and a three-dimensional convolutional neural network (3D CNN). The performance was evaluated by median point-wise root mean square error (RMSE) for pressures along the centerline in 18 test cases, which were not included in a training cohort. We found that the 3D CNN (median RMSE of 3.23 mmHg) outperforms the 1D BRNN (median RMSE of 4.25 mmHg). In contrast, the 1D BRNN is more precise in PD prediction, with a lower standard deviation of the error (+/- 7.03 mmHg) compared to the 3D CNN (+/- 8.91 mmHg). The differences between both ANNs are not statistically significant, suggesting that compressing the 3D aorta hemodynamics into a 1D centerline representation does not result in the loss of valuable information when training ANN models. Additionally, we evaluated the utility of the synthetic geometries of the aortas with CoA generated by using a statistical shape model (SSM), as well as the impact of aortic arch geometry (gothic arch shape) on the model's training. The results show that incorporating a synthetic cohort obtained through the SSM of the clinical cohort does not significantly increase the model's accuracy, indicating that the synthetic cohort generation might be oversimplified. Furthermore, our study reveals that selecting training cases based on aortic arch shape (gothic versus non-gothic) does not improve ANN performance for test cases sharing the same shape.

While there are many studies on psychotherapy and its efficacy - in terms of desired outcomes - there is comparatively little evidence on the possible negative effects of psychotherapy. The aim of this study was to investigate the possible negative effects of a multi-professional psychiatric day hospital treatment for patients with mental health disorders based on Acceptance and Commitment Therapy (ACT), including possible confounding factors. Fifty-one patients with a range of psychiatric diagnoses were assessed three months after an ACT-based psychiatric day hospital treatment. Questionnaires were used to measure negative effects of psychotherapy (INEP), subjective quality of life (WHOQOL-BREF), and symptomatology (BDI-II and SCL-90-R). Correlational analyses and group comparisons were performed to determine the relationship between the sum of reported negative effects on the one hand and symptomology, quality of life, and sociodemographic variables (gender, age, diagnosis, education) on the other hand. At least one negative effect out of a list of 18 possible effects was reported by 45% of participants, and 10% reported more than two. The number of negative effects reported correlates positively with symptomology and negatively with quality of life. The sum of reported negative effects does not correlate with age or gender and does not vary by education level and primary diagnosis. In the light of previous findings, patients included in this study showed lower rates of negative effects, both overall and at item level. Practical implications of these findings are discussed.

TOI-2015 is a known exoplanetary system around an M4 dwarf star, consisting of a transiting sub-Neptune planet in a 3.35-day orbital period, TOI-2015 b, accompanied by a non-transiting companion, TOI-2015 c. High-precision radial-velocity measurements were taken with the MAROON-X spectrograph, and high-precision photometric data were collected, primarily using the SPECULOOS, MUSCAT, TRAPPIST and LCOGT networks. We collected 63 transit light curves and 49 different transit epochs for TOI-2015 b. We recharacterized the target star by combining optical spectra obtained by the MAROON-X, Shane/KAST and IRTF/SpeX spectrographs, Bayesian model averaging (BMA) and spectral energy distribution (SED) analysis. The TOI-2015 host star is a K = 10.3 mag M4-type dwarf with a subsolar metallicity of [Fe/H] = −0.31 ± 0.16, and an effective temperature of Teff ≈ 3200 K. Our photodynamical analysis of the system strongly favors the 5:3 mean-motion resonance and in this scenario the planet b (TOI-2015 b) has an orbital period of Pb = 3.34 days, a mass of Mp = 9.02-0.36+0.32M⊕ , and a radius of Rp = 3.309-0.011+0.013R⊕ , resulting in a density of ρp = 0.25 ± 0.01 ρ⊕ = 1.40 ± 0.06 g cm−3; this is indicative of a Neptune-like composition. Its transits exhibit large (> 1 hr) timing variations characteristic of an outer perturber in the system. We performed a global analysis of the high-resolution radial-velocity measurements, the photometric data, and the TTVs, and inferred that TOI-2015 hosts a second planet, TOI-2015 c, in a non-transiting configuration. Our analysis places it near a 5:3 resonance with an orbital period of Pc = 5.583 days and a mass of Mp = 8.91-0.40+0.38M⊕. The dynamical configuration of TOI-2015 b and TOI-2015 c can be used to constrain the system’s planetary formation and migration history. Based on the mass-radius composition models, TOI-2015 b is a water-rich or rocky planet with a hydrogen-helium envelope. Moreover, TOI-2015 b has a high transmission-spectroscopic metric (TSM=149), making it a favorable target for future transmission spectroscopic observations with the JWST to constrain the atmospheric composition of the planet. Such observations would also help to break the degeneracies in theoretical models of the planet’s interior structure.

Mediterranean cyclones can trigger severe weather hazards, including convective precipitation, lightning and hail, with implications for operational forecasting, risk assessment in the insurance industry, and societal preparedness. This work examines the climatological link between Mediterranean cyclones and atmospheric conditions conducive to severe convection. Using ATDnet lightning detections we find that, from autumn to spring, 20%–80% of lightning hours over the Mediterranean basin and adjacent land regions are associated with nearby cyclones. Based on reanalysis data, we demonstrate that severe convective environments and associated hazards predominantly occur in the warm sector of Mediterranean cyclones and to the north-east of their centres. Convective processes and hazards exhibit a peak approximately 6 h prior to the time of minimum pressure of the cyclone centre, consistent with previous studies. Additionally, we find a strong seasonal dependence of severe convection within cyclones. Severe convective environments are often detected in cyclone types typical of transition seasons (autumn especially) and summer, while they are rarer in deep baroclinic cyclones characteristic of winter. Finally, we provide novel insights regarding the dependence of convective activity on the presence of dynamical features around Mediterranean cyclones. Warm conveyor belts, characterised by large-scale ascent and high thermodynamic instability, emerge as the most favourable regions for lightning activity, with lightning potential being twice as high compared to cyclone cold fronts. These results advance our understanding of the interplay between cyclone dynamics and severe convection, offering valuable guidance for improving hazard prediction and for elaborating weather emergency strategies in the Mediterranean region.

At the 6th International Conference of the Global Bioequivalence Harmonisation Initiative (GBHI), co-organised by the European Federation of Pharmaceutical Sciences (EUFEPS) and the Product Quality Research Institute (PQRI), critical bioequivalence (BE) topics were discussed by pharmaceutical scientists from academia, industry and regulatory agencies, revealing the following main conclusions: (1) Physiologically based pharmacokinetic/biopharmaceutic modelling (PBPK/PBBM) for solid oral drugs: PBPK/PBBM gains increasing recognition for generic drug development, e.g. waivers of fed studies and drug interaction studies with proton pump inhibitors. However, especially for complex formulations containing low-solubility compounds, more data are needed for modelling-based conclusion regarding BE in fed state. (2) Narrow therapeutic index drugs: A progress towards harmonisation of BE criteria from US-FDA and EMA speakers was made as there is consensus in the usefulness of applying a mixed scale for BE acceptance range depending on variability, via either fully or partially replicated design. Differences still remain regarding variability comparison and the selection of regulatory constant (0.760 vs. 1.05361). All parties confirmed the importance of controlling type-I error. (3) Single- vs. multiple-dose studies for BE demonstration of modified-release (MR) products: To circumvent multiple-dose studies, model-informed approaches were discussed based on real-life data, e.g. to simulate steady-state profiles from single-dose data. To reduce the burden in patient trials for long-acting injectables promising modelling approaches were presented, extrapolating from incomplete steady-state scenarios. (4) BE demonstration for additional dose strengths of solid oral MR products: For multiple-unit dosage forms where strengths differ in number of units only, testing BE of the highest dose was considered sufficient. In addition, there was some consensus that, whenever extrapolation from one strength to the others is not easily established, the “bracket-approach” of the EMA focusing on the intake conditions in the label claim (fasted or fed), can help mitigating risks without adding significant cost and effort. (5) Partial AUC for BE demonstration: Clinical relevance is key to decide on the relevant PK metrics for BE assessment whenever possible. There was consensus that the BE criteria and evaluation strategy may be best specified in product-specific guidances – preferably with international harmonisation. (6) BE of orally inhaled drug products (OIDPs): The “weight-of-evidence” approach of US-FDA and the stepwise approach of EMA largely differ. The auditorium was in favour of combining data on in-vitro characteristics and PK exposure. For prediction of comparable efficacy of two OIDPs, there is good trust in PK exposure data whenever they present concentrations being absorbed via the lung. GBHI has a strong role in scientifically supporting official harmonisation efforts including the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use since the first conference in 2015.

Cyanobacteria oxygenated the atmosphere of early Earth and continue to be key players in global carbon and nitrogen cycles. A phylogenetically diverse subset of extant cyanobacteria can perform photosynthesis with far-red light through a process called far-red light photoacclimation, or FaRLiP. This phenotype is enabled by a cluster of ∼20 genes and involves the synthesis of red-shifted chlorophylls d and f, together with paralogs of the ubiquitous photosynthetic machinery used in visible light. The FaRLiP gene cluster is present in diverse, environmentally important cyanobacterial groups, but its origin, evolutionary history, and connection to early biotic environments have remained unclear. This study takes advantage of the recent increase in (meta)genomic data to help clarify this issue: sequence data mining, metagenomic assembly, and phylogenetic tree networks were used to recover more than 600 new FaRLiP gene sequences, corresponding to 51 new gene clusters. These data enable high-resolution phylogenetics and—by relying on multiple gene trees, together with gene arrangement conservation—support FaRLiP appearing early in cyanobacterial evolution. Sampling information shows that considerable FaRLiP diversity can be observed in microbialites to the present day, and we hypothesize that the process was associated with the formation of microbial mats and stromatolites in the early Paleoproterozoic. The ancestral FaRLiP cluster was reconstructed, revealing features that have been maintained for billions of years. Overall, far-red-light-driven oxygenic photosynthesis may have played a significant role in Earth’s early history.

Bentonite is a key barrier material in deep geological facilities for spent nuclear fuel, where it may be exposed to temperatures >100 °C because of radiogenic heating. Understanding how prolonged heating affects its physicochemical properties and radionuclide retention capacity is critical for ensuring long-term repository safety. This study investigated the impacts of dry heating (unconfined, evaporation allowed) at 150 °C for 36 months on the mineralogical and geochemical stability of a Wyoming bentonite, chosen for the Finnish geological disposal facility, and its subsequent sorption behavior with 90Sr. Although the bentonite mineralogy remained mostly stable, combined X-ray diffraction, cation exchange capacity, titrations, demonstrated partial Na to Ca exchange within montmorillonite's interlayer following heating, and specific surface area analyses revealed a > 50 % reduction in specific surface area (30 to 14 m2/g). Colloid stability tests revealed that bentonite colloids did not form under repository-relevant saline conditions (I = 0.2 M), and heat treatment did not significantly impact colloid formation in reduced ionic-strength systems. Sorption isotherms demonstrated that Sr sorption was strongly pH-dependent, increasing from ∼40 % at pH 8 to ∼90 % at pH 13, and heating slightly enhanced Sr retention at pH 8. Two-site protolysis non-electrostatic surface complexation and cation exchange modelling suggested that in unheated bentonite, Sr was bound via a combination of surface complexation (∼30 %) and cation exchange (∼70 %) at pH 8, while at pH 13, sorption shifted towards surface complexation. However, after heating, cation exchange dominated at both pH values. Extended X-ray absorption fine structure analysis confirmed outer-sphere Sr sorption at pH 8 and increasing inner-sphere complexation at pH 13. Together, these findings highlight that despite minor physicochemical alterations, bentonite retained its Sr sorption potential, supporting its continued suitability as a buffer material in the ONKALO® repository.

Female rhinoceroses have an ovarian reserve that consists of immature oocytes in primordial follicles. Establishing methods to grow and culture these oocytes from those follicles in the laboratory might fuel efforts towards in vitro embryo production in this species without the need for repeated in vivo oocyte collection. In depth understanding of the biology behind and improvement of assisted reproductive techniques (ARTs) is the only option for preventing the disappearance of functionally extinct species such as the northern white rhinoceros. In vitro follicle development can only be obtained by in depth knowledge on rhinoceros ovarian histology. In addition to known ovarian features, we identified numerous undescribed structural and molecular ovarian characteristics from adult southern white rhinoceros (n=3). Ovarian sections were stained with H&E, PAS or Masson Trichrome and molecular analyses (hyaluronic acid detection, immunohistochemistry and TUNEL assay) were performed to identify proliferation, extracellular matrix, pluripotency markers, hormones, enzymes, markers for inflammation or endocrine glands, blood vessel presence, oocyte markers and apoptosis. Besides degenerating, deformed, or luteinized follicles, analysis revealed several ‘follicle-like structures’ (FLS) that deviated from the expected follicle appearance. Most importantly, the majority of FLS did not contain any oocyte and were comprised of a collection of cells organised around fluid islands with or without an antral cavity. The discovery and description of FLS in aged southern white rhinoceroses may play a role in poor oocyte recovery rates in ovum pick-up (OPU) in older rhinoceroses. It remains to be investigated whether FLS might be present on ovaries from other rhinoceros species and whether they might serve as a general indicator for oocyte recovery success in aged females.

Claudin polymers constitute the tight junction (TJ) backbone that forms paracellular barriers, at least for bigger solutes. While some claudins also seal the barrier for small electrolytes, others form ion channels. For cation-selective claudin-15 and claudin-10b, structural models of channels embedded in homo-polymeric strands have been suggested. Here, we generated a model for the prototypic anion-selective claudin-10a channel. Based on previously established claudin-10b models, dodecamer homology models of claudin-10a embedded in two membranes were analyzed by molecular dynamics simulations. The results indicate that both claudin-10 isoforms share the same strand and channel architecture: Sidewise unsealed tetrameric pore scaffolds are interlocked with adjacent pores via the beta 1 beta 2 loop of extracellular segment 1. This leads to TJ-like strands with claudin subunits arranged in four joined rows in two opposing membranes. Several but not all cis- and trans-interaction modes are indicated to be conserved among claudin-10a, -10b, and -15. However, pore-lining residues that differ between claudin-10a and -10b (i.e., R33/I35, A34/D36, K69/A71, N54/D56, H60/N62, R62/K64) result in opposite charge selectivity of channels. This was supported by electric field simulations for both claudins and is consistent with previous electrophysiological studies. In summary, for the first time, a structural and mechanistic model of complete and prototypic paracellular anion channels is provided. This improves understanding of epithelial paracellular transport.

Objective: Cold-inducible RNA binding Protein (CIRBP) has been shown to be a potent inflammatory mediator and could serve as a novel biomarker for inflammation. Systemic inflammatory response syndrome (SIRS) and capillary leak syndrome (CLS) are frequent complications after pediatric cardiac surgery increasing morbidity, therefore early diagnosis and therapy is crucial. As CIRBP serum levels have not been analyzed in a pediatric population, we conducted a clinical feasibility establishing a customized magnetic bead panel analyzing CIRBP in pediatric patients undergoing cardiac surgery.

Methods: A prospective hypothesis generating observational clinical study was conducted at the German Heart Center Berlin during a period of 9 months starting in May 2020 (DRKS00020885, https://drks.de/search/de/trial/DRKS00020885). Serum samples were obtained before the cardiac operation, upon arrival at the pediatric intensive care unit, 6 and 24 h after the operation in patients up to 18 years of age with congenital heart disease (CHD). Customized multiplex magnetic bead-based immunoassay panels were developed to analyze CIRBP, Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Monocyte chemotactic protein 1 (MCP-1), Syndecan-1 (SDC-1), Thrombomodulin (TM), Vascular endothelial growth factor (VEGF-A), Angiopoietin-2 (Ang-2), and Fibroblast growth factor 23 (FGF-23) in 25 µl serum using the Luminex MagPix® system.

Results: 19 patients representing a broad range of CHD (10 male patients, median age 2 years, 9 female patients, median age 3 years) were included in the feasibility study. CIRBP was detectable in the whole patient cohort. Relative to individual baseline values, CIRBP concentrations increased 6 h after operation and returned to baseline levels over time. IL-6, IL-8, IL-10, and MCP-1 concentrations were significantly increased after operation and except for MCP-1 concentrations stayed upregulated over time. SDC-1, TM, Ang-2, as well as FGF-23 concentrations were also significantly increased, whereas VEGF-A concentration was significantly decreased after surgery.

Discussion: Using customized magnetic bead panels, we were able to detect CIRBP in a minimal serum volume (25 µl) in all enrolled patients. To our knowledge this is the first clinical study to assess CIRBP serum concentrations in a pediatric population.

1. In recent years, seismic sensors, traditionally used in geophysical studies, have been utilized to record seismic waves generated by wildlife locomotion, providing new ways to monitor wildlife non-invasively and continuously. Given the novelty of this approach, numerous research questions, unexplored potentials, and methodological challenges remain. 2. In this study, we investigate the seismic signal properties of African savanna species during locomotion and employ machine learning techniques to classify wildlife based on these footfall signals. We utilize the SeisSavanna dataset, which contains over 70,000 three-component seismograms paired with labelled images from co-located camera traps. To create a graphical overview of the entire seismic dataset, we combine a scattering transform with uniform manifold approximation and projection (UMAP). While the different wildlife categories display different footfall patterns, local geological conditions known as site effects significantly alter the frequency content of those signals. To address the issue of the site effect, we trained machine learning models on data recorded on various sites. 3. For a multi-class classification task involving signals from elephants, giraffes, hyenas, and zebras, the models achieved a balanced accuracy of 87% at a maximum animal-sensor distance of 50 m. The accuracy decreases to 77% when the maximum distance is extended to 150 m due to decreasing signal and label quality. We demonstrate that the models can generalize to new seismic stations if similar site conditions are present in the training data. 4. Our results indicate the potential for using seismic signals in wildlife monitoring and conservation, complementing other existing passive monitoring sensors such as camera traps or acoustic loggers with new observables about silent species. However, further methodological advancements and larger datasets are essential for this approach to become a reliable tool in wildlife monitoring.

(1) Background: Surgical site infections (SSIs) are a relevant problem with a 25% incidence rate after elective laparotomy due to inflammatory bowel disease (IBD). The aim of this study was to evaluate whether stricter hygienic measures during the COVID-19 pandemic influenced the rate of SSI. (2) Methods: This is a monocentric, retrospective cohort study comparing the rate of SSI in patients with bowel resection due to IBD during COVID-19 (1 March 2020-15 December 2021) to a cohort pre-COVID-19 (1 February 2015-25 May 2018). (3) Results: The rate of SSI in IBD patients with bowel resection was 25.8% during the COVID-19 pandemic compared to 31.8% pre-COVID-19 (OR 0.94; 95% CI 0.40-2.20; p = 0.881). There were seventeen (17.5%) superficial and four (4.1%) deep incisional and organ/space SSIs, respectively, during the COVID-19 pandemic (p = 0.216). There were more postoperative intra-abdominal abscesses during COVID-19 (7.2% vs. 0.9%; p = 0.021). The strictness of hygienic measures (mild, medium, strict) had no influence on the rate of SSI (p = 0.553). (4) Conclusions: Hygienic regulations in hospitals during COVID-19 did not significantly reduce the rate of SSI in patients with bowel resection due to IBD. A ban on surgery, whereby only emergency surgery was allowed, was likely to delay surgery and exacerbate the disease, which probably contributed to more SSIs and postoperative complications.

Objective: To establish a deep learning model for the detection of hypoxic–ischemic encephalopathy (HIE) features on CT scans and to compare various networks to determine the best input data format.

Methods: 168 head CT scans of patients after cardiac arrest were retrospectively identified and classified into two categories: 88 (52.4%) with radiological evidence of severe HIE and 80 (47.6%) without signs of HIE. These images were randomly divided into a training and a test set, and five deep learning models based on based on Densely Connected Convolutional Networks (DenseNet121) were trained and validated using different image input formats (2D and 3D images).

Results: All optimized stacked 2D and 3D networks could detect signs of HIE. The networks based on the data as 2D image data stacks provided the best results (S100: AUC: 94%, ACC: 79%, S50: AUC: 93%, ACC: 79%). We provide visual explainability data for the decision making of our AI model using Gradient-weighted Class Activation Mapping.

Conclusion: Our proof-of-concept deep learning model can accurately identify signs of HIE on CT images. Comparing different 2D- and 3D-based approaches, most promising results were achieved by 2D image stack models. After further clinical validation, a deep learning model of HIE detection based on CT images could be implemented in clinical routine and thus aid clinicians in characterizing imaging data and predicting outcome.

Background: Takotsubo syndrome is, by definition, a reversible form of acute heart failure. If cardiac output is severely reduced, Takotsubo syndrome can cause cardiogenic shock, and mechanical circulatory support can serve as a bridge to recovery. To date, there are no recommendations on when to use mechanical circulatory support and on which device is particularly effective in this context. Our aim was to determine the best treatment strategy. Methods: A systematic literature research and analysis of individual patient data was performed in MEDLINE/PubMed according to PRISMA guidelines. Our research considered original works published until 31 July 2023. Results: A total of 93 publications that met the inclusion criteria were identified, providing individual data from 124 patients. Of these, 62 (50%) were treated with veno-arterial extracorporeal life support (va-ECLS), and 44 (35.5%) received a microaxial left ventricular assist device (Impella). Eighteen patients received an Impella CP and twenty-one an Impella 2.5. An intra-aortic balloon pump (IABP) without other devices was used in only 13 patients (10.5%), while other devices (BiVAD or Tandem Heart) were used in 5 patients (4%). The median initial left ventricular ejection fraction was 20%, with no difference between the four device groups except for the IABP group, which was less affected by cardiac output failure (p = 0.015). The overall survival was 86.3%. Compared to the other groups, the time to cardiac recovery was shorter with Impella (p < 0.001). Conclusions: Though the Impella treatment is new, our analysis may show a significant benefit of Impella compared to other MCS strategies for cardiogenic shock in Takotsubo syndrome.

(1) Background: Around 50% of hemophilia patients develop severe arthropathy, with even subclinical hemorrhage in childhood potentially leading to intra-articular iron deposition, synovia proliferation, neoangiogenesis, and eventual damage to articular cartilage and subchondral bone. Treatments typically include coagulation factor substitution, radiosynoviorthesis, and joint replacement for advanced cases. This study aims to elucidate programmed cell death mechanisms in hemophilic arthropathy (HA) to identify novel treatments. (2) Methods: Human chondrocytes were exposed to lysed/non-lysed erythrocytes, ferroptosis inducer ML-162, cytokines (IL-1ss, TNF alpha), and ferric citrate, then assessed for metabolic activity, DNA content, and cell death using Alamar Blue, cyQUANT, and Sytox assays. Three-dimensional spheroids served as a cartilage model to study the effects of erythrocytes and ML-162. (3) Results: Erythrocytes caused significant cell death in 2D cultures (p < 0.001) and damaged 3D chondrocyte spheroids. Iron citrate and erythrocytes reduced chondrocyte DNA content (p < 0.001). The ferroptosis pathway was implicated in cell death, with no effects from apoptosis and necroptosis inhibitors. (4) Conclusions: This study offers insights into HA's cell death pathway, suggesting ferroptosis inhibitors as potential therapies. Further studies are needed to evaluate their efficacy against the chronic effects of HA.

Current literature reveals no increased risk for adverse non-hereditary health outcomes in the offspring of childhood cancer survivors (CCS), yet survivors reported concerns regarding their offspring's health. To investigate how the fear of cancer development in offspring influences parental behavior related to health and prevention, survey reports from 256 European adult CCS and 256 age- and sex-matched siblings who participated in a multicenter study on offspring health were analyzed in the present study. Analyses of covariance and chi-square tests were conducted to test for differences between CCS and siblings in outcome variables (all related to healthy parenting behavior). CCS reported higher fear levels (p = 0.044, Partial eta(2) = 0.01) and less alcohol consumption (p = 0.011, Phi = 0.12) and smoking (p = 0.022, Phi = 0.11) during pregnancy than siblings. In survivor families, children were breastfed less often (p < 0.001, Phi = 0.18). Partial correlation analyses showed that CCS' fear levels decreased with increasing age (r = -0.16, p = 0.014), time since oncological therapy (r = -0.19, p = 0.003), and number of children (r = -0.21, p = 0.001). Overall, due to their own experiences with cancer, many CCS harbor misperceptions regarding the health outcomes of their offspring. Although the fear decreases with increasing distance from the active disease, any fear should be taken seriously, even if unfounded, and combated through targeted educational measures.

Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A suitable tumor antigen target on CRC is carcinoembryonic antigen (CEA), given its widespread expression and role in tumorigenesis and metastasis. CEA is known to be prolifically shed from tumor cells in a soluble form, thus hindering CAR recognition of tumors and migration through the TME. We have developed a next-generation CAR construct exclusively targeting cell-associated CEA, incorporating a PD1-checkpoint inhibitor and a CCR4 chemokine receptor to enhance homing and infiltration of the CAR-NK-92 cell line through the TME, and which does not induce fratricidal killing of CAR-NK-92-cells. To evaluate this therapeutic approach, we harnessed intricate 3D multicellular tumor spheroid models (MCTS), which emulate key elements of the TME. Our results demonstrate the effective cytotoxicity of CEA-CAR-NK-92 cells against CRC in colorectal cell lines and MCTS models. Importantly, minimal off-target activity against non-cancerous cell lines underscores the precision of this therapy. Furthermore, the integration of the CCR4 migration receptor augments homing by recognizing target ligands, CCL17 and CCL22. Notably, our CAR design results in no significant trogocytosis-induced fratricide. In summary, the proposed CEA-targeting CAR-NK cell therapy could offer a promising solution for CRC treatment, combining precision and efficacy in a tailored approach.

Artificial light at night (ALAN) is an omnipresent anthropogenic stressor disrupting ecological interactions, potentially driving rapid evolutionary change. However, evidence for genetic adaptation to ALAN remains limited, with ecological responses dominating observed effects. Here, we critically review current evidence for evolution under ALAN and propose that interactions between ecological and evolutionary processes—so-called eco-evolutionary feedbacks—may obscure direct evolutionary signals. We argue for more common-garden experiments to disentangle genetic adaptation from environmentally induced plasticity, for multiple study organisms. Using a conceptual framework of an urban freshwater pond and a key ecological interactor, the water flea Daphnia, we illustrate how ALAN may affect key ecological phenomena, including diel vertical migration, parasite infection, and top-down control of algae, and may impose complex and cascading selection pressures. Recognizing interactions between ecological and evolutionary processes provides new insights on how light pollution can influence ecosystem health and inform conservation strategies in increasingly illuminated environments.