Acute type A aortic dissection (ATAAD) is a dramatic emergency exhibiting a mortality of 50% within the first 48 hours if not operated. This study found an absolute value of cosine-like seasonal variation pattern for Germany with significantly fewer ATAAD events (Wilcoxon test) for the warm months of June, July, and August from 2005 to 2015. Many studies suspect a connection between ATAAD events and weather conditions. Using ERA5 reanalysis data and an objective weather type classification in a contingency table approach showed that for Germany, significantly more ATAAD events occurred during lower temperatures (by about 4.8 K), lower water vapor pressure (by about 2.6 hPa), and prevailing wind patterns from the northeast. In addition, we used data from a classification scheme for human-biometeorological weather conditions which was not used before in ATAAD studies. For the German region of Berlin and Brandenburg, for 2006 to 2019, the proportion of days with ATAAD events during weather conditions favoring hypertension (cold air advection, in the center of a cyclone, conditions with cold stress or thermal comfort) was significantly increased by 13% (Chi-squared test for difference of proportions). In contrast, the proportion was decreased by 19% for conditions associated with a higher risk for patients with hypotension and therefore a lower risk for patients with hypertension (warm air advection ahead of warm fronts, conditions with no thermal stress or heat stress, in the center of a cyclone with thermal stress). As many studies have shown that hypertension is a risk factor for ATAAD, our findings support the hypothesized relation between ATAAD and hypertension-favoring weather conditions.

The Corpus Callosum (CC) is a bundle of axons connecting the cerebral hemispheres. It is the most recent structure to have appeared during evolution of placental mammals. Its development is controlled by a very complex interplay of many molecules. In humans it contains almost 80% of all commissural axons in the brain. The formation of the CC can be divided into four main stages, each controlled by numerous intracellular and extracellular molecular factors. First, a newborn neuron has to specify an axon, leave proliferative compartments, the Ventricular Zone (VZ) and Subventricular Zone (SVZ), migrate through the Intermediate Zone (IZ), and then settle at the Cortical Plate (CP). During the second stage, callosal axons navigate toward the midline within a compact bundle. Next stage is the midline crossing into contralateral hemisphere. The last step is targeting a defined area and synapse formation. This review provides an insight into these four phases of callosal axons development, as well as a description of the main molecular players involved.

Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are postoperative neurocognitive disorders (PNDs) that frequently occur in the aftermath of a surgical intervention. Cognitive reserve (CR) is a concept posited to explain why cognitive health varies between individuals. On this qualitative understanding of cognitive health, factors like IQ, education level, and occupational complexity can affect the impact of neuropathological processes on cognitive outcomes.

Methods: We investigated the association between CR and POD and CR and POCD on data from 713 patients aged≥65 years with elective surgery. Peak pre-morbid IQ was estimated from vocabulary. Occupational complexity was coded according to the Dictionary of Occupational Titles (DOT). Education level was classed according to the International Standard Classification of Education (ISCED). These three factors were used as proxies of CR. In a series of regression models, age, sex, depression, site of surgery, and several lifestyle and vascular factors were controlled for.

Results: Patients with a higher IQ had lower odds of developing POD. We found no significant association between the other two CR markers with POD. None of the CR markers was associated with POCD.

Conclusion: The significant association of a higher IQ with lower POD risk allows for the stratification of elderly surgical patients by risk. This knowledge can aid the prevention and/or early detection of POD. Further research should attempt to determine the lack of associations of CR markers with POCD in our study.

Purpose: Stereotactic radiosurgery (SRS) has been increasingly used to treat intracranial pathologies in elderly patients. The treatment efficiency of SRS has been demonstrated in meningiomas, with excellent local control. We aimed to analyze the safety of robotic SRS in elderly patients with meningiomas.

Methods: We searched for patients with suspected WHO °I meningioma ≥ 60 years old, who underwent CyberKnife (CK) SRS from January 2011 to December 2021. Tumor localization was categorized using the “CLASS” algorithmic scale. Tumor response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for meningiomas. Adverse effects were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and a cox regression was performed to investigate possible predictors.

Results: We identified 82 patients with 102 CK-treated lesions that matched the criteria for the first SRS. The median age was 70 [IQR 64-75] years, and 24.3% of the patients were aged > 75 years. Multiple lesions (up to six) were treated in 14.1% of the SRS-sessions. A previous surgery was performed in 57.3% of lesions, with a median time interval of 41 [IQR 10 – 58] months between the initial surgical procedure and the SRS treatment. In 47.9% of cases, CLASS 3 meningiomas at high-risk locations were irradiated. Single fraction radiosurgery was applied to 62.5% of the lesions, while in the remaining cases multi-session SRS with three to five fractions was used. During the median follow-up period of 15.9 months, lesion size progression was observed in 3 cases. Karnofsky Performance Status (KPS) declined by ≥ 20 points in four patients. Adverse effects occurred in 13 patients, while only four patients had CTCAE ≥2 toxicities. Hereby only one of these toxicities was persistent. The occurrence of complications was independent of age, planned target volume (PTV), high-risk localization, and surgery before SRS.

Conclusion: The data indicates that SRS is a safe, efficient, and convenient treatment modality for elderly patients with meningioma, even at high-risk locations

Objective: Aquaporin-4-antibody-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) are relapsing neuroinflammatory diseases, frequently leading to chronic pain. In both diseases, the spinal cord (SC) is often affected by myelitis attacks. We hypothesized that regional SC volumes differ between AQP4-IgG + NMOSD and MOGAD and that pain intensity is associated with lower SC volumes. To evaluate changes in the SC white matter (WM), gray matter (GM), and pain intensity in patients with recent relapses (myelitis or optic neuritis), we further profiled phenotypes in a case series with longitudinal imaging and clinical data.

Methods: Cross-sectional data from 36 participants were analyzed in this retrospective study, including 20 AQP4-IgG + NMOSD and 16 MOGAD patients. Pain assessment was performed in all patients by the Brief Pain Inventory and painDETECT questionnaires. Segmentation of SC WM, GM, cervical cord volumes (combined volume of WM + GM) was performed at the C2/C3 cervical level. WM% and GM% were calculated using the cervical cord volume as a whole per patient. The presence of pain, pain severity, and clinical disability was evaluated and tested for associations with SC segmentations. Additionally, longitudinal data were deeply profiled in a case series of four patients with attacks between two MRI visits within one year.

Results: In AQP4-IgG + NMOSD, cervical cord volume was associated with mean pain severity within 24 h (β = −0.62, p = 0.009) and with daily life pain interference (β = −0.56, p = 0.010). Cross-sectional analysis showed no statistically significant SC volume differences between AQP4-IgG + NMOSD and MOGAD. However, in AQP4-IgG + NMOSD, SC WM% tended to be lower with increasing time from the last attack (β = −0.41, p = 0.096). This tendency was not observed in MOGAD. Our case series including two AQP4-IgG + NMOSD patients revealed SC GM% increased by roughly 2% with either a myelitis or optic neuritis attack between visits. Meanwhile, GM% decreased by 1–2% in two MOGAD patients with a myelitis attack between MRI visits.

Conclusion: In AQP4-IgG + NMOSD, lower cervical cord volume was associated with increased pain. Furthermore, cord GM changes were detected between MRI visits in patients with disease-related attacks in both groups. Regional SC MRI measures are pertinent for monitoring disease-related cord pathology in AQP4-IgG + NMOSD and MOGAD.

Background: The question of the utility of face masks in preventing acute respiratory infections has received renewed attention during the COVID-19 pandemic. However, given the inconclusive evidence from existing randomized controlled trials, evidence based on real-world data with high external validity is missing.

Objective: To add real-world evidence, this study aims to examine whether mask mandates in 51 countries and mask recommendations in 10 countries increased self-reported face mask use and reduced SARS-CoV-2 reproduction numbers and COVID-19 case growth rates.

Methods: We applied an event study approach to data pooled from four sources: (1) country-level information on self-reported mask use was obtained from the COVID-19 Trends and Impact Survey, (2) data from the Oxford COVID-19 Government Response Tracker provided information on face mask mandates and recommendations and any other nonpharmacological interventions implemented, (3) mobility indicators from Google’s Community Mobility Reports were also included, and (4) SARS-CoV-2 reproduction numbers and COVID-19 case growth rates were retrieved from the Our World in Data—COVID-19 data set.

Results: Mandates increased mask use by 8.81 percentage points (P=.006) on average, and SARS-CoV-2 reproduction numbers declined on average by −0.31 units (P=.008). Although no significant average effect of mask mandates was observed for growth rates of COVID-19 cases (−0.98 percentage points; P=.56), the results indicate incremental effects on days 26 (−1.76 percentage points; P=.04), 27 (−1.89 percentage points; P=.05), 29 (−1.78 percentage points; P=.04), and 30 (−2.14 percentage points; P=.02) after mandate implementation. For self-reported face mask use and reproduction numbers, incremental effects are seen 6 and 13 days after mandate implementation. Both incremental effects persist for >30 days. Furthermore, mask recommendations increased self-reported mask use on average (5.84 percentage points; P<.001). However, there were no effects of recommendations on SARS-CoV-2 reproduction numbers or COVID-19 case growth rates (−0.06 units; P=.70 and −2.45 percentage points; P=.59). Single incremental effects on self-reported mask use were observed on days 11 (3.96 percentage points; P=.04), 13 (3.77 percentage points; P=.04) and 25 to 27 (4.20 percentage points; P=.048 and 5.91 percentage points; P=.01) after recommendation. Recommendations also affected reproduction numbers on days 0 (−0.07 units; P=.03) and 1 (−0.07 units; P=.03) and between days 21 (−0.09 units; P=.04) and 28 (−0.11 units; P=.05) and case growth rates between days 1 and 4 (−1.60 percentage points; P=.03 and −2.19 percentage points; P=.03) and on day 23 (−2.83 percentage points; P=.05) after publication.

Conclusions: Contrary to recommendations, mask mandates can be used as an effective measure to reduce SARS-CoV-2 reproduction numbers. However, mandates alone are not sufficient to reduce growth rates of COVID-19 cases. Our study adds external validity to the existing randomized controlled trials on the effectiveness of face masks to reduce the spread of SARS-CoV-2.

Increased suicide rates in prison are a serious concern. Early identification of inmates at risk is a component of effective suicide prevention. The present study examined two suicide screening instruments in a sample of men in the Berlin, Germany, prison system (n = 289). The Screening for Initial Risk Assessment (SIRAS) identified significantly more high-risk inmates than the Vienna Instrument for Suicidality in Correctional Institutions (VISCI) (66 vs. 24). The results further show that the agreement in the classification was evident only in inmates with suicidal ideation, but was otherwise quite low. This can be explained by the fact that the instruments differ in terms of the risk factors taken into account. Finally, it was found that inmates classified as high risk received more monitoring and psychiatric or psychological support, which supports the construct validity of the instruments. As there were no deaths by suicide in the sample, no statistical information on the predictive validity of the instruments could be provided. Although research in this area is challenging, methodologically sound studies are needed to inform practice.

Aims: The majority of patients with severe aortic stenosis (AS) planned for transcatheter aortic valve implantation (TAVI) are elective outpatients. During the COVID-19 pandemic, the time between the heart team’s decision and TAVI increased due to limited healthcare resources. We therefore implemented telemedical approaches to identify AS patients at risk for clinical deterioration during the waiting time. The purpose of the prospective, randomized, controlled ResKriVer-TAVI study (DRKS00027842) is to investigate whether a digital concept of telemedical interventional management (TIM) in AS patients waiting for TAVI improves the clinical outcomes. In the present article, we report the study protocol of the ResKriVer-TAVI trial.

Methods: ResKriVer-TAVI will enroll AS patients planned for elective TAVI. Randomization to the TIM group or standard care will be made on the day of the heart team’s decision. TIM will include a daily assessment of weight, blood pressure, a 2-channel electrocardiogram, peripheral capillary oxygen saturation, and a self-rated health status until admission for TAVI. TIM will allow optimization of medical therapy or an earlier admission for TAVI if needed. Standard care will not include any additional support for patients with AS. All patients of the TIM group will receive a rule-based TIM including standard operating procedures when a patient is crossing prespecified values of a vital sign.

Results: The primary endpoint consists of days lost due to cardiovascular hospitalization and death of any cause within 180 days after the heart team’s decision. Major secondary endpoints include all-cause mortality within 365 days, the number of telemedical interventions, and adherence to TIM. Follow-up visits will be conducted at admission for TAVI as well as 6 and 12 months after the heart team’s decision.

Conclusions: ResKriVer-TAVI will be the first randomized, controlled trial investigating a telemedical approach before TAVI in patients with AS. We hypothesize that primary and secondary endpoints of AS patients with TIM will be superior to standard care. The study will serve to establish TIM in the clinical routine and to increase the resilience of TAVI centers in situations with limited healthcare resources.

In recent decades, robotic-assisted minimally invasive esophagectomy (RAMIE) has been increasingly adopted for patients with esophageal cancer (EC) or cancer of the gastroesophageal junction (GEJ). However, concerns regarding its costs compared to conventional minimally invasive esophagectomy (MIE) have emerged. This study examined outcomes and costs of RAMIE versus total MIE in 128 patients who underwent Ivor Lewis esophagectomy for EC/GEJ at our department between 2017 and 2021. Surgical costs were higher for RAMIE (EUR 12,370 vs. EUR 10,059, p < 0.001). Yet, median daily (EUR 2023 vs. EUR 1818, p = 0.246) and total costs (EUR 30,510 vs. EUR 29,180, p = 0.460) were comparable. RAMIE showed a lower incidence of postoperative pneumonia (8% vs. 25%, p = 0.029) and a trend towards shorter hospital stays (15 vs. 17 days, p = 0.205), which may have equalized total costs. Factors independently associated with higher costs included readmission to the intensive care unit (hazard ratio [HR] = 7.0), length of stay (HR = 13.5), anastomotic leak (HR = 17.0), and postoperative pneumonia (HR = 5.4). In conclusion, RAMIE does not impose an additional financial burden. This suggests that RAMIE may be considered as a valid alternative approach for esophagectomy. Attention to typical cost factors can enhance postoperative care across surgical methods.

In multiple sclerosis (MS), mitochondrial alterations appear to contribute to disease progression. The sphingosine-1-phosphate receptor modulator siponimod is approved for treating secondary progressive MS. Its preceding compound fingolimod was shown to prevent oxidative stress-induced alterations in mitochondrial morphology. Here, we assessed the effects of siponimod, compared to fingolimod, on neuronal mitochondria in oxidatively stressed hippocampal slices. We have also advanced the model of chronic organotypic hippocampal slices for live imaging, enabling semi-automated monitoring of mitochondrial alterations. The slices were prepared from B6.Cg-Tg(Thy1-CFP/COX8A)S2Lich/J mice that display fluorescent neuronal mitochondria. They were treated with hydrogen peroxide (oxidative stress paradigm) +/- 1 nM siponimod or fingolimod for 24 h. Afterwards, mitochondrial dynamics were investigated. Under oxidative stress, the fraction of motile mitochondria decreased and mitochondria were shorter, smaller, and covered smaller distances. Siponimod partly prevented oxidatively induced alterations in mitochondrial morphology; for fingolimod, a similar trend was observed. Siponimod reduced the decrease in mitochondrial track displacement, while both compounds significantly increased track speed and preserved motility. The novel established imaging and analysis tools are suitable for assessing the dynamics of neuronal mitochondria ex vivo. Using these approaches, we showed that siponimod at 1 nM partially prevented oxidatively induced mitochondrial alterations in chronic brain slices.

Although university education in Germany is without tuition fees, the parental educational background influences the decision to study as well as the choice of subjects, and is linked to challenges that students face during the course of study. However, little is known about these aspects in veterinary medicine. In this study, the differences between the first-generation students (FGS) and continuing-generation students (CGS) in veterinary medicine, as well as the challenges (study entrance, financial situation, concerns about the future), are examined in order to identify any need for supportive action.

Background

Arcobacter cryaerophilus is considered an emerging foodborne pathogen and is associated primarily with infectious gastrointestinal disease in humans. However, the underlying pathogenic mechanisms remain poorly understood. Therefore, the aim of the present study was to investigate the pathogenic potential of twelve A. cryaerophilus strains using various in vitro assays in two human colonic cell lines, HT-29/B6 and T84.

Results

All strains tested were able to adhere to and invade into both cell lines, with strain-dependent differences in their adhesion and invasion rates. In addition, two strains showed cytotoxic effects on both cell lines. The ability to disrupt the epithelial barrier function of T84 cell monolayers was shown for two strains by measurement of transepithelial electrical resistance. As structural factors correlate with the barrier dysfunction, immunofluorescence staining of the tight junction domain was performed, and revealed an altered distribution of claudin-5 in infected cells.

Conclusions

The results highlight the strain-dependent pathogenic mechanisms of A. cryaerophilus that may contribute to key symptoms such as diarrhoea. These findings also highlight the importance of further research into the pathogen A. cryaerophilus.

The aim of the present study was to test the replicability of the text generation effect for learning with expository texts while systematically varying contextual factors that—based on extant literature—can be assumed to affect the occurrence and magnitude of the text generation effect. Seven experiments were conducted in which participants either read (control condition) or unscrambled sentences (generation condition) in expository texts. The experiments varied systematically on intentionality of learning, learning time constraint, retention interval, and study design. Contrary to expectations, no text generation effect could be found. Instead, some of the experiments even revealed a learning disadvantage for text generation compared to the reading control condition. In only one experiment (Experiment 6) and for just one of the learning measures, learners performed better when they had generated the texts. In sum, the results indicate that a generation effect is most likely to occur when learning is intentional, when learning time is unrestricted, and for immediate testing. The findings suggest that the applications of text generation in educational contexts are rather limited.

Voltage imaging holds great potential for biomedical research by enabling noninvasive recording of the electrical activity of excitable cells such as neurons or cardiomyocytes. Camera-based detection can record from hundreds of cells in parallel, but imaging entire volumes is limited by the need to focus through the sample at high speeds. Remote focusing techniques can remedy this drawback, but have so far been either too slow or light-inefficient. Here, we introduce flipped image remote focusing, a remote focusing method that doubles the light efficiency compared to conventional beamsplitter-based techniques and enables high-speed volumetric voltage imaging at 500 volumes/s. We show the potential of our approach by combining it with light sheet imaging in the zebrafish spinal cord to record from >100 spontaneously active neurons in parallel.

[FeFe] hydrogenases are Nature's most efficient catalysts for the cleavage and evolution of molecular hydrogen. Despite decades of research, key aspects of the catalytic cycle and the underlying geometrical and electronic properties of the active-site cofactor, called the H-cluster, are not fully understood. Spectroscopic techniques have played a central role in establishing the current state of knowledge on [FeFe] hydrogenases, and further advances in the field depend critically on novel techniques that yield so-far inaccessible insights into structural and mechanistic aspects. Infrared (IR) absorption spectroscopy represents a well-established and versatile technique that can identify and characterize all active and inactive states of the H-cluster by means of structurally sensitive and spectrally isolated CO and CN stretching vibrations. However, the amount of information that can be extracted from these linear experiments is inherently limited. Here we introduce experimental and computational two-dimensional (2D-)IR spectroscopy for the characterization of [FeFe] hydrogenases. Utilizing the Hinact state of the H-cluster as a model system, we demonstrate that this nonlinear technique yields direct information about the nature and interactions of the CO and CN stretching vibrations. These insights allow, for the first time, to quantitatively describe the character of these widely used reporter vibrations, their spatial localization, and the way they change upon structural variation of the H-cluster. The strength of this approach is demonstrated by correctly identifying the proposed structure of the Hinact state, in solution and at ambient temperature. In conclusion, the introduced combination of experimental and computational 2D-IR spectroscopy represents a powerful approach for studying [FeFe] hydrogenases and other complex organometallic targets.

In this paper we study the optimal control of a class of semilinear elliptic partial differential equations which have nonlinear constituents that are only accessible by data and are approximated by nonsmooth ReLU neural networks. The optimal control problem is studied in detail. In particular, the existence and uniqueness of the state equation are shown, and continuity as well as directional differentiability properties of the corresponding control-to-state map are established. Based on approximation capabilities of the pertinent networks, we address fundamental questions regarding approximating properties of the learning-informed control-to-state map and the solution of the corresponding optimal control problem. Finally, several stationarity conditions are derived based on different notions of generalized differentiability.

A dinuclear copper(I) complex Cu2L22 (L2 = 3,3-dimethyl-1-(1-methyl-1H-benzo[d]imidazole-2-yl)-N-(propan-2-ylidene)butan-2-amine) containing benzimidazole and imino donors was previously reported by some of us as an efficient catalyst for the aerobic oxidation of alcohols to aldehydes in presence of TEMPO (2,2,6,6-tetramethylpiperidinyloxyl) and an external base NMI (N-methyl imidazole). Cu(III)2(bis-μ-oxo) and Cu(II)2(bis-μ-hydroxo) cores were trapped as viable intermediates in the reaction, which provided deeper mechanistic insights. Here, we report two new ligand systems L3 (N-isopropyl-3,3-dimethyl-1-(1-methyl-1H-benzol[d]imidazole-2-yl)butane-2-amine) and L4 ((Z)-2,4-di-tert-butyl-6-(((3,3-dimethyl-1-(1-methyl-1H-benzol[d]imidazole-2-yl)butane-2-yl)imino)methyl)phenol), which are designed to perturb the overall electronics of the complexes and the resulting effects on their O2 activation mechanisms. The stronger donation of the secondary amine group stabilizes a mononuclear CuIL3 core, which nevertheless follows a dinuclear O2 activation mechanism as in Cu2L22. Notably, the CuIL3/TEMPO catalyst system performs the aerobic oxidation of alcohols to aldehydes with good yields and turnover numbers, even in the absence of NMI. The dinuclear CuI2L42 complex involving a non-innocent phenolate group, in contrast, exhibits depleted catalytic activity, because of the instability of the Cu(III)2(bis-μ-oxo) core against intramolecular H-atom abstraction to form an alkoxo bridged dicopper(II) complex.

The development of immunocompetent skin models marks a significant advancement in in vitro methods for detecting skin sensitizers while adhering to the 3R principles, which aim to reduce, refine, and replace animal testing. This study introduces for the first time an advanced immunocompetent skin model constructed entirely from induced pluripotent stem cell (iPSC)-derived cell types, including fibroblasts (iPSC-FB), keratinocytes (iPSC-KC), and fully integrated dendritic cells (iPSC-DC). To evaluate the skin model’s capacity, the model was treated topically with a range of well-characterized skin sensitizers varying in potency. The results indicate that the iPSC-derived immunocompetent skin model successfully replicates the physiological responses of human skin, offering a robust and reliable alternative to animal models for skin sensitization testing, allowing detection of extreme and even weak sensitizers. By addressing critical aspects of immune activation and cytokine signaling, this model provides an ethical, comprehensive tool for regulatory toxicology and dermatological research.

This article examines the condition of hybrid sovereignties in unstable borderlands characterised by conflict, crime and cross-border mobility as well as the competition and collusion between violent non-state actors and state authorities. While in political practice open borders are often associated with mobility (of people), closed borders are imagined as guarantors of security (of nation-states). This dichotomy, however, ignores porosity as a third dimension. The article theorises the link between the porosity of borders and complementary governance constellations and discusses its implications for hybrid sovereignty. We illustrate our argument with insights from the Colombian-Venezuelan borderlands.

This article investigates how social inequality is reproduced through the recontextualization of mathematics pedagogy, using Dowling’s social activity method as an analytical framework. The study identifies the selection and transmission of pedagogic messages as a potential pathway. Findings indicate that teachers in upper-stream schools favour abstract, context-independent messages and metonymically organize tasks to maintain their messages in esoteric mathematical domain. In contrast, their middle- and bottom-streams counterparts often select everyday, context-dependent tasks and assemble tasks metaphorically, limiting students’ access to the abstract mathematical system. These results suggest that class differences are transformed and legitimized through the differential selection and transmission of pedagogic messages, shaping students’ social consciousness in different ways and perpetuating social stratification.