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S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood–brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22–47 pg/mL). Higher S100B levels were linked to longer HF duration (p = 0.014) and increased left atrial volume index (p = 0.041), but also with a higher prevalence of mild cognitive impairment (p = 0.023) and lower visual/verbal memory scores (p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99–1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00–1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B's value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption. [ABSTRACT FROM AUTHOR]

Factor XIII is a transglutaminase enzyme that plays a crucial role in hemostasis and wound healing. It crosslinks fibrin strands, stabilizing clots and promoting clot resistance to fibrinolysis. Additionally, Factor XIII has been found to have multiple other functions that extend beyond coagulation, including the regulation of inflammation and tissue repair processes. Emerging evidence suggests that Factor XIII may also have differential roles in acute myocardial infarction and ischemic stroke, two common cardiovascular events with significant morbidity and mortality. In acute myocardial infarction, Factor XIII has been implicated in promoting clot stability and reducing the risk of re-occlusion. In ischemic stroke, Factor XIII may also contribute to the pathogenesis of cerebral ischemia by promoting clot formation and exacerbating neuronal damage. Several studies have investigated the association between Factor XIII and these cardiovascular events, using various approaches such as genetic polymorphism analysis, animal models, and clinical data analysis. These studies have provided important insights into the role of Factor XIII in acute myocardial infarction and ischemic stroke, highlighting its potential as a therapeutic target for interventions aimed at improving outcomes in these conditions. In this review, we will summarize the current understanding of Factor XIII's role in acute myocardial infarction and ischemic stroke. [ABSTRACT FROM AUTHOR]

Ultrasonic sensors are one of the most common automatic monitoring methods in operational snow depth monitoring with reliable results. On the other hand, there is significant uncertainty when measuring small snow depths (<2 cm), thus it cannot provide binary snow presence (on/off) information. The use of webcams in monitoring snow cover has proven to be successful in recent studies and applications. In this study, we applied an adaptive thresholding technique on images from webcams to obtain reliable snow on/off information to complement the ultrasonic snow depth measurements. Camera and ultrasonic sensor data from two weather stations in Finland were studied. The webcam data was processed using FMIPROT (Finnish Meteorological Institute Image Processing Tool) software, operating in a cloud computing environment, which can generate near real-time data. Our results indicate that webcam-derived data can be successfully used for quality control or as auxiliary data to support operational ultrasonic sensor measurements and provide a cost-effective improvement to operational monitoring capabilities. Webcam monitoring is especially useful during the melting season when the snow depth is below 15 mm, with accuracy values between 72% and 94%. [ABSTRACT FROM AUTHOR]

Anhedonia, a central depression symptom, is associated with impairments in reward processing. However, it is not well understood which sub-components of reward processing (anticipation, motivation, consummation, and learning) are impaired in association with anhedonia in depression. In particular, it is unclear how learning about different rewards and the effort needed to obtain them might be associated with anhedonia and depression symptoms. Therefore, we examined learning in young people (N = 132, mean age 20, range 17–25 yrs.) with a range of depression and anhedonia symptoms using a probabilistic instrumental learning task. The task required participants to learn which options to choose to maximize their reward outcomes across three conditions (chocolate taste, puppy images, or money) and to minimize the physical effort required to obtain the rewards. Additionally, we collected questionnaire measures of anticipatory and consummatory anhedonia, as well as subjective reports of "liking", "wanting" and "willingness to exert effort" for the rewards used in the task. We found that as anticipatory anhedonia increased, subjective liking and wanting of rewards decreased. Moreover, higher anticipatory anhedonia was significantly associated with lower reward learning accuracy, and participants demonstrated significantly higher reward learning than effort learning accuracy. To our knowledge, this is the first study observing an association of anhedonia with reward liking, wanting, and learning when reward and effort learning are measured simultaneously. Our findings suggest an impaired ability to learn from rewarding outcomes could contribute to anhedonia in young people. Future longitudinal research is needed to confirm this and reveal the specific aspects of reward learning that predict anhedonia. These aspects could then be targeted by novel anhedonia interventions. [ABSTRACT FROM AUTHOR]

Acute and chronic cardiac disorders predispose to alterations in cognitive performance, ranging from mild cognitive impairment to overt dementia. Although this association is well-established, the factors inducing and accelerating cognitive decline beyond ageing and the intricate causal pathways and multilateral interdependencies involved remain poorly understood. Dysregulated and persistent inflammatory processes have been implicated as potentially causal mediators of the adverse consequences on brain function in patients with cardiac disease. Recent advances in positron emission tomography disclosed an enhanced level of neuroinflammation of cortical and subcortical brain regions as an important correlate of altered cognition in these patients. In preclinical and clinical investigations, the thereby involved domains and cell types of the brain are gradually better characterized. Microglia, resident myeloid cells of the central nervous system, appear to be of particular importance, as they are extremely sensitive to even subtle pathological alterations affecting their complex interplay with neighboring astrocytes, oligodendrocytes, infiltrating myeloid cells, and lymphocytes. Here, we review the current evidence linking cognitive impairment and chronic neuroinflammation in patients with various selected cardiac disorders including the aspect of chronic neuroinflammation as a potentially druggable target. [ABSTRACT FROM AUTHOR]

Acute ischemic cardiac injury predisposes one to cognitive impairment, dementia, and depression. Pathophysiologically, recent positron emission tomography data suggest astroglial activation after experimental myocardial infarction (MI). We analyzed peripheral surrogate markers of glial (and neuronal) damage serially within 12 months after the first ST-elevation MI (STEMI). Serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using ultra-sensitive molecular immunoassays. Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11% female). The median (quartiles) of GFAP was 63.8 (47.0, 89.9) pg/mL and of NfL 10.6 (7.2, 14.8) pg/mL at study entry 0–4 days after STEMI. GFAP after STEMI increased in the first 3 months, with a median change of +7.8 (0.4, 19.4) pg/mL (p = 0.007). It remained elevated without further relevant increases after 6 months (+11.7 (0.6, 23.5) pg/mL; p = 0.015), and 12 months (+10.3 (1.5, 22.7) pg/mL; p = 0.010) compared to the baseline. Larger relative infarction size was associated with a higher increase in GFAP (ρ = 0.41; p = 0.009). In contrast, NfL remained unaltered in the course of one year. Our findings support the idea of central nervous system involvement after MI, with GFAP as a potential peripheral biomarker of chronic glial damage as one pathophysiologic pathway. [ABSTRACT FROM AUTHOR]

Considering the first ten years of Industrie 4.0 in Germany—the digital transformation of industry towards the goal of increased manufacturing productivity and mass customization—significant progress has been achieved. However, future efforts are required. This review first evaluates the status quo of implementation and research in Germany and finds that large-scale companies have proceeded faster than small- and middle-sized enterprises. Currently, regardless of their size, companies have in common a shortage of qualified specialists, coupled with a lack of adequate base technologies for Industrie 4.0 and an insufficient digital mindset. The creation of platform-based digital business models is particularly lagging behind, despite high research interest. This review subsequently identifies three research-driven fields of action that are particularly important for the future of Industrie 4.0: (1) resilience of value networks in the strategic area of sovereignty, (2) Open-Source as a driver for the strategic area of interoperability, and (3) the strategic combination of digitalization and sustainability as a basis for sustainable business models in the strategic area of sustainability. [ABSTRACT FROM AUTHOR]

Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice. [ABSTRACT FROM AUTHOR]

Simple Summary: Access to molecular cancer treatments outside of clinical trials is limited and the benefit of molecular-guided, individualized patient care in patients with cancer progression after standard treatment is unclear. We here present the four-year experience of one of Europe's first Molecular Tumor Boards and show that precision oncology in the era of affordable, extended genetic and phenotypic tumor profiling is feasible and effective for a small but relevant proportion of advanced cancer patients. We performed a comprehensive analysis of clinical follow-up data and report our workflow optimizations and upscaling processes. These could help other centers to establish similar structures to support molecular-guided treatment for patients with limited therapy options. Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field and second, to provide access to a broad patient population. Here, we report a four-year experience of the Molecular Tumor Board (MTB) of the Comprehensive Cancer Center Freiburg (Germany) including workflows and process optimizations. This retrospective single-center study includes data on 488 patients enrolled in the MTB from February 2015 through December 2018. Recommendations include individual molecular diagnostics, molecular stratified therapies, assessment of treatment adherence and patient outcomes including overall survival. The majority of MTB patients presented with stage IV oncologic malignancies (90.6%) and underwent an average of 2.1 previous lines of therapy. Individual diagnostic recommendations were given to 487 patients (99.8%). A treatment recommendation was given in 264 of all cases (54.1%) which included a molecularly matched treatment in 212 patients (43.4%). The 264 treatment recommendations were implemented in 76 patients (28.8%). Stable disease was observed in 19 patients (25.0%), 17 had partial response (22.4%) and five showed a complete remission (6.6%). An objective response was achieved in 28.9% of cases with implemented recommendations and for 4.5% of the total population (22 of 488 patients). By optimizing the MTB workflow, case-discussions per session increased significantly while treatment adherence and outcome remained stable over time. Our data demonstrate the feasibility and effectiveness of molecular-guided personalized therapy for cancer patients in a clinical routine setting showing a low but robust and durable disease control rate over time. [ABSTRACT FROM AUTHOR]

Climate services are becoming the backbone to translate climate knowledge, data & information into climate-informed decision-making at all levels, from public administrations to business operators. It is essential to assess the technical and scientific quality of the provided climate data and information products, including their value to users, to establish the relation of trust between providers of climate data and information and various downstream users. The climate data and information products (i.e., from satellite, in-situ and reanalysis) shall be fully traceable, adequately documented and uncertainty quantified and can provide sufficient guidance for users to address their specific needs and feedbacks. This paper discusses details on how to apply the quality assurance framework to deliver timely assessments of the quality and usability of Essential Climate Variable (ECV) products. It identifies an overarching structure for the quality assessment of single product ECVs (i.e., consists of only one single variable), multi-product ECVs (i.e., more than one single parameter), thematic products (i.e., water, energy and carbon cycles), as well as the usability assessment. To support a traceable climate service, other than rigorously evaluating the technical and scientific quality of ECV products, which represent the upstream of climate services, how the uncertainty propagates into the resulting benefit (utility) for the users of the climate service needs to be detailed. [ABSTRACT FROM AUTHOR]