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Abstract The university student population is particularly vulnerable to depression, which was identified during the COVID-19 pandemic. Understanding how depressive symptoms are interrelated with mental and physical health in students is essential. The aim of this study was to reveal the network of depressive and anxiety symptoms with respect to well-being (life satisfaction, physical health, physical activity, and perceived stress) during a difficult situation—the COVID-19 pandemic—at two measurement points of different pandemic severities. A repeated cross-sectional study was conducted in June 2020 (T1) (lower pandemic severity) and March 2021 (T2) (higher pandemic severity) among 592 and 1230 Czech university students, respectively. The measurements used were the PHQ-9, GAD-7, PSS-10, SWLS, self-rated physical health (SRH), and sociodemographic survey. The network analysis approach was utilized. For the significance of differences, the χ2 test, Student’s t test, and ANOVA were performed. The results revealed that scale-level depression, stress, and worse SRH increased over time, whereas life satisfaction decreased. Scale-level anxiety and physical activity were stable over time. PHQ2 Sad mood was the most central and influential node at T1 and T2. PHQ9 Suicidal Ideation was closely related to other variables at T1, whereas PHQ1 Anhedonia was closely related to other variables at T2. The most influential risk factors were the PHQ-2 score and the GAD-2 score, which are associated with uncontrollable worrying, whereas life satisfaction, physical health, and physical activity were the most protective factors. It is crucial to recognize and decrease the PHQ2 score and increase life satisfaction to improve the mental health of university students.

Abstract Background Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease. Methods This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used. Results Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p

ABSTRACT Pt‐based electrocatalysts for glycerol oxidation reaction (GOR) exhibit low durability due to the inactivation of Pt through rapid poisoning under oxidative conditions. Thus, bimetallic PtBi was strategically synthesized using BiOI as a photoactive intermediate for the uniform photoelectrodeposition of Pt. The nanostructured Pt–Bi was electrochemically reduced from a Pt/BiOI medium, and the GOR‐activated Pt–Bi electrocatalysts (G–Pt–Bi) were obtained via a subsequent electrochemical activation process. Here, abundant Bi sites in PtBi can prevent Pt poisoning and effectively provide adsorbed OH− for the GOR on Pt sites. Consequently, it allows the operation in low onset potential for GOR with a high mass activity of 13.35 A mgPt −1 at 0.85 VRHE in alkaline solution. The GOR products obtained using G–Pt–Bi were identified as glycolate and formate by 1H‐nuclear magnetic resonance without the interruption of the hydrogen evolution reaction, and it finally enables the operation of a membrane‐free two‐electrode system. In situ electrochemical impedance spectroscopy demonstrates that the G–Pt–Bi exhibit superior GOR kinetics and higher resistance to Pt inactivation compared with conventional Pt/C. This study suggests a novel design for a G–Pt–Bi architecture in developing durable and high‐mass‐activity Pt catalysts for the GOR.

IntroductionAdvanced glycation end-products (AGEs) are capable of stimulating oxidative stress and inflammation. This study investigates the synthesis of medium crosslinked AGEs (the most optimal form of AGEs because of soluble in water, used in many assays as markers) and their biochemical properties.MethodsOne of model protein–myoglobin from horse heart muscle (MB) and a chosen respective glycation factor – D-melibiose (mel), acrolein (ACR), D-glucose (glc), 4-hydroksynonenal (4HNE), trans-2-nonenal (T2N), methylglyoxal (MGO) – were subjected to high temperature water synthesis (HTWS) and high temperature microwave synthesis in anhydrous conditions (HTMS). The syntheses were deliberately carried out in two different conditions to check whether adding an additional energy source (microwaves) while lowering the temperature and shortening the reaction time would allow for more effective obtaining of medium-cross-linked AGEs, monitored with SDS-PAGE. Products were analyzed using fluorescence measurements, Enzyme-Linked Immunosorbent Assay (ELISA) and immunoblotting tests and electrophoretic mobility shift assay to evaluate their ability to activate nuclear factor kappa-light-chain-enhancer (NF-κB).ResultsMedium cross-linked AGEs were more efficiently obtained in HTMS. Fluorescence was high for MB-ACR, MB-T2N and MB-glc products. Anti-MAGE antibodies showed reactivity towards MB-mels of HTMS and HTWS, and the MB-4HNEs from HTMS. HTWS products, apart from MB-ACR, did not activate NF-κB, whereas MB-ACR, MB-4HNE, MB-mel, and MB-T2N products of HTMS strongly activated this factor that indicates their strong pro-inflammatory properties.ConclusionHTMS is a fast and efficient method of synthesizing medium cross-linked AGEs.

We present a newly developed instrument for 22Na-based positron-annihilation lifetime spectroscopy, designed to facilitate the simultaneous control of temperature, gas atmosphere, and humidity in a single experimental system. The spectrometer operates within a temperature range of 50–480 K and pressures from 10−6 mbar to 1.5 bars. It features a novel gas dosing chamber that allows in situ adsorption studies with gases such as but not limited to CO2, N2, Ar, O2, and their mixtures, with precise control over mixing ratios. Additionally, the device supports in situ humidity exposure, allowing for comprehensive studies of sample interactions with both humidity and humid gases. Fully automated, the system provides seamless data acquisition and environmental control, including pressure and temperature regulation. We demonstrate the instrument’s capability to elucidate alterations in the free volume of maltodextrin under humidity exposure. Additionally, we illustrate the instrument’s efficacy through case studies on CPO-27 metal-organic frameworks (MOFs), highlighting its versatility in analyzing adsorption phenomena across diverse gas adsorbates and temperatures. This state-of-the-art spectrometer stands as an indispensable tool for probing the physicochemical attributes of materials under varying conditions, providing pivotal insights into gas adsorption mechanisms and material dynamics.

Background and objectives: This study quantified the ‘distance to LDL-C goal’ in patients at very high cardiovascular risk with uncontrolled hyperlipidaemia. ‘Distance to LDL-C goal’ was defined as the percentage by which low-density lipoprotein cholesterol (LDL-C) levels needed to be reduced to achieve the LDL-C goals specified in the 2016 or 2019 European Society of Cardiology/European Atherosclerosis Society guidelines. Design and methods: This retrospective analysis using data from the IQVIA Disease Analyzer database included patients who were predominantly treated by a primary care physician, diabetologist or cardiologist between 2014 and 2018, with a diagnosis of hyperlipidaemia and an initial LDL-C measurement (index event) and one or more cardiovascular risk factors. The primary outcome was to assess the proportion of patients with uncontrolled hyperlipidaemia and to classify the ‘distance to LDL-C goal’ in these patients. Results: Data from 32,963 patients were analysed ( n = 27,159, n = 3873 and n = 1931 patients in the primary care physician, diabetology and cardiology cohorts, respectively). Most patients had uncontrolled LDL-C levels (⩾70 mg/dL; ⩾1.8 mmol/L) at index (91.0%, 86.4% and 94.0% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Analysis of the ‘distance to LDL-C goal’ indicated that approximately one-third of patients in each cohort required an LDL-C level reduction of up to 50% relative to index to achieve their LDL-C goal (35.8%, 43.7% and 28.4% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). LDL-C control was not achieved at 36 months post-index in most patients with uncontrolled LDL-C levels (86.8%, 81.7% and 90.2% of patients in the primary care physician, diabetology and cardiology cohorts, respectively). Conclusion: LDL-C levels were uncontrolled in most patients with hyperlipidaemia. Analysis of the ‘distance to LDL-C goal’ showed that most patients required a substantial LDL-C level reduction to achieve their LDL-C goal.

Summary: Background: Statin intolerance is associated with increased cardiovascular risk. Symptoms and patients’ characteristics are incompletely known. We aimed to analyse the health-related quality of life (QOL) associated with statin intolerance. Methods: The Statin Intolerance Registry (SIR) is an observational, prospective, multicentre study that included 1111 patients, with intolerance to at least two different statins, between 2021 and 2023 in Germany. SIR baseline data were compared to individuals with and without statin therapy of the population-based LIFE-Adult Study (n = 9983). Findings: The mean age in SIR was 66.1 years (standard deviation (SD) 9.9). The cohort was characterized by a higher proportion of women compared to patients on statins in LIFE-Adult (57.7% vs. 38.2%). SIR patients had impaired QOL (mean EQ VAS score of 64.9 (SD 18.1)) as measured by EuroQol (EQ-5D-5L)), which further deteriorated with age. Muscle symptoms were frequent (95.8%) and were associated with severe pain in 43.2% and intake of pain medication in 32.3% of statin intolerant patients. 10.3% had a diagnosis of depression. Women reported more pronounced symptoms than men. A data-driven k-means analysis, based on variables predicting severity of pain while on statin therapy, identified five clusters of SIR patients. The clusters differed in sex, prevalence of depression, QOL, comorbidities, and expectations to tolerate statin therapy. Interpretation: Statin intolerance is associated with impaired QOL. Women are more frequently and severely affected. The identified clusters may help to identify patients at risk and to develop individualized strategies to improve patient trajectories and outcomes. Funding: Leipzig University, research grants from Daiichi Sankyo, Novartis, and Amgen to Leipzig University.

Shailey Gale Twamley,1– 3 Niclas Gimber,4 Héctor Eduardo Sánchez-Ibarra,1,2 Tobias Christaller,1,2 Victoria Isakzai,1,2 Harald Kratz,5 Ronodeep Mitra,6 Lena Kampen,1– 3 Anke Stach,1,2 Heike Heilmann,7 Berit Söhl-Kielczynski,8 Eno Essien Ebong,6,9,10 Jan Schmoranzer,4 Agnieszka Münster-Wandowski,7,* Antje Ludwig1– 3,* 1Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany; 2Department of Cardiology, Angiology and Intensive Care Medicine, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany; 3DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; 4Advanced Medical Bioimaging Core Facility (AMBIO), Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 5Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 7Institute of Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 8Institute for Integrative Neurophysiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 9Department of Bioengineering, Northeastern University, Boston, MA, USA; 10Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA*These authors contributed equally to this workCorrespondence: Shailey Gale Twamley; Antje Ludwig, Tel +49-30-450-528455 ; +49-30-450-513196, Fax +49-30-450-528922 ; +49-30-450941, Email shailey.twamley@charite.de; antje.ludwig@dhzc-charite.dePurpose: To study whether the absence of laminar shear stress (LSS) enables the uptake of very small superparamagnetic iron oxide nanoparticles (VSOP) in endothelial cells by altering the composition, size, and barrier function of the endothelial surface layer (ESL).Methods and Results: A quantitative particle exclusion assay with living human umbilical endothelial cells using spinning disc confocal microscopy revealed that the dimension of the ESL was reduced in cells cultivated in the absence of LSS. By combining gene expression analysis, flow cytometry, high pressure freezing/freeze substitution immuno-transmission electron microscopy, and confocal laser scanning microscopy, we investigated changes in ESL composition. We found that increased expression of the hyaluronan receptor CD44 by absence of shear stress did not affect the uptake rate of VSOPs. We identified collagen as a previously neglected component of ESL that contributes to its barrier function. Experiments with inhibitor halofuginone and small interfering RNA (siRNA) demonstrated that suppression of collagen expression facilitates VSOP uptake in endothelial cells grown under LSS.Conclusion: The absence of laminar shear stress disturbs the barrier function of the ESL, facilitating membrane accessibility and endocytic uptake of VSOP. Collagen, a previously neglected component of ESL, contributes to its barrier function. Keywords: citrate coated nanoparticles, atherosclerosis, blood flow, endothelial barrier, permeability, internalization

Abstract Background Early-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation; and (2) pharmacologically treated early- or late-onset GDM. Methods HbA1c was measured at 8—14 weeks’ gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12—16 weeks’ gestation (OGTT1), and if normal, repeated at 24–28 weeks’ gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2. Results Maternal early-pregnancy HbA1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66). Conclusions In our population-based cohort, early-pregnancy HbA1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12—16 weeks’ gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

Abstract Background Appendicularia consists of approximately 70 purely marine species that belong to Tunicata the probable sister taxon to Craniota. Therefore, Appendicularia plays a pivotal role for our understanding of chordate evolution. In addition, appendicularians are an important part of the epipelagic marine plankton. Nevertheless, little is known about appendicularian species, especially from deeper water. Results Using µCT, scanning electron microscopy, and digital 3D-reconstruction techniques we describe three pairs of complex oral sensory organs in the mesopelagic appendicularian Bathochordaeus stygius. The oral sensory organs are situated at the anterior and lateral margin of the mouth and inside the mouth cavity. A single organ consists of 22–90 secondary receptor cells that project apical cilia through a narrow hole in the epidermis. The receptor cells are innervated by branches of the second brain nerve. Conclusions Based on position, morphology, and innervation we suggest that the oral sensory organs are homologues of the coronal organs in other tunicates. We discuss the hypothesized homology of coronal organs and the lateral line system of primary aquatic vertebrates. The complex oral sensory organs of B. stygius are unique in tunicates and could be adaptations to the more muffled environment of the mesopelagic.

Abstract In this big data era, multitudes of data are generated and collected which contain the potential to gain new insights, e.g., for enhancing business models. To leverage this potential through, e.g., data science and analytics projects, the data must be made available. In this context, data marketplaces are used as platforms to facilitate the exchange and thus, the provisioning of data and data-related services. Data marketplaces are mainly studied for the exchange of data between organizations, i.e., as external data marketplaces. Yet, the data collected within a company also has the potential to provide valuable insights for this same company, for instance to optimize business processes. Studies indicate, however, that a significant amount of data within companies remains unused. In this sense, it is proposed to employ an Enterprise Data Marketplace, a platform to democratize data within a company among its employees. Specifics of the Enterprise Data Marketplace, how it can be implemented or how it makes data available throughout a variety of systems like data lakes has not been investigated in literature so far. Therefore, we present the characteristics and requirements of this kind of marketplace. We also distinguish it from other tools like data catalogs, provide a platform architecture and highlight how it integrates with the company’s system landscape. The presented concepts are demonstrated through an Enterprise Data Marketplace prototype and an experiment reveals that this marketplace significantly improves the data consumer workflows in terms of efficiency and complexity. This paper is based on several interdisciplinary works combining comprehensive research with practical experience from an industrial perspective. We therefore present the Enterprise Data Marketplace as a distinct marketplace type and provide the basis for establishing it within a company.

Single-cell RNA sequencing (scRNA-seq) is an important tool for understanding disease pathophysiology, including airway diseases. Currently, the majority of scRNA-seq studies in airway diseases have used invasive methods (airway biopsy, surgical resection), which carry inherent risks and thus present a major limitation to scRNA-seq investigation of airway pathobiology. Bronchial brushing, where the airway mucosa is sampled using a cytological brush, is a viable, less invasive method of obtaining airway cells for scRNA-seq. Here we describe the development of a rapid and minimal handling protocol for preparing single-cell suspensions from bronchial brush specimens for scRNA-seq. Our optimized protocol maximizes cell recovery and cell quality and facilitates large-scale profiling of the airway transcriptome at single-cell resolution.

Abstract Systemic inflammation affects the whole vasculature, yet whether arterial and venous endothelial cells differ in their abilities to mediate inflammation and to return to homeostasis after an inflammatory stimulus has not been addressed thoroughly. We assessed gene-expression profiles in isolated endothelial cells from human umbilical arteries (HUAEC) or veins (HUVEC) under basal conditions, after TNF-α stimulation and various time points after TNF-α removal to allow reinstatement of homeostasis. TNF-α regulates the expression of different sets of transcripts that are significantly changed only in HUAEC, only in HUVEC or changed in both. We identified three types of gene regulation, i.e. genes that were significantly regulated after 24 h of TNF-α stimulation but no longer when TNF-α was removed (homeostatic regulation), genes that maintained significantly regulated after TNF-α removal (not homeostatic regulation) and genes that were only significantly regulated when TNF-α was removed (post-regulation). HUAEC and HUVEC quantitatively differed in these types of gene regulation, with relatively more genes being post-regulated in HUAEC. In conclusion our data demonstrate that HUAEC and HUVEC respond intrinsically different to an inflammatory insult. Whether this holds true for all endothelial cells and its relevance for inflammatory insults in different organs during systemic inflammation warrants further studies.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

Summary: Understanding the cell-type composition and spatial organization of brain regions is crucial for interpreting brain computation and function. In the thalamus, the anterior thalamic nuclei (ATN) are involved in a wide variety of functions, yet the cell-type composition of the ATN remains unmapped at a single-cell and spatial resolution. Combining single-cell RNA sequencing, spatial transcriptomics, and multiplexed fluorescent in situ hybridization, we identify three discrete excitatory cell-type clusters that correspond to the known nuclei of the ATN and uncover marker genes, molecular pathways, and putative functions of these cell types. We further illustrate graded spatial variation along the dorsomedial-ventrolateral axis for all individual nuclei of the ATN and additionally demonstrate that the anteroventral nucleus exhibits spatially covarying protein products and long-range inputs. Collectively, our study reveals discrete and continuous cell-type organizational principles of the ATN, which will help to guide and interpret experiments on ATN computation and function.