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Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems‐wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)‐based proteomics workflow for the in‐depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature. Synopsis A robust proteomic workflow quantifies more than 1,000 proteins in cerebrospinal fluid and reveals an Alzheimer's Disease‐associated signature of more than 20 proteins across three independent cohorts. These include tau, superoxide dismutase 1, PARK7, YKL‐40 and novel biomarker candidates. Proteomics workflow for quantification of more than 1,000 proteins from microliters of cerebrospinal fluid. More than 20 proteins consistently associated with Alzheimer's Disease across three cohorts comprising about 200 individuals in total. Alzheimer's Disease CSF signature of Tau, SOD1, PARK7, YKL‐40, and glycolysis‐related proteins. Graphical Abstract A robust proteomic workflow quantifies more than 1,000 proteins in cerebrospinal fluid and reveals an Alzheimer's Disease‐associated signature of more than 20 proteins across three independent cohorts. These include tau, superoxide dismutase 1, PARK7, YKL‐40 and novel biomarker candidates.

Photon‑counting detector CT (PCD‑CT) enables ultra‑high resolution (UHR, 0.2 mm) and may improve visualization of coronary stents compared with standard‑resolution (SR, 0.4 mm). In this ex- vivo study, we utilized a phantom heart model to simulate physiological attenuation and imitated the most common coronary bifurcation stenting techniques by creating multiple stent layers and stent- crush situations (single layer, crushed, two‑ and three‑layer). We compared UHR and SR PCD‑CT using Bv72 and Bv56 kernels. Objective endpoints were in‑stent lumen visibility, signal-to-noise ratio, and percentage change in stent attenuation; subjective image quality was rated on a 5‑point Likert scale (1 = excellent to 5 = non‑diagnostic). Depending on distribution, two‑sided t‑tests (mean ± SD) or Mann–Whitney U tests (median[IQR]) were applied, p‑values were Bonferroni‑corrected for multiple comparisons. In the pooled Crush cohort, UHR Bv72 improved in‑stent lumen visibility when compared with both, SR Bv72 (single-layer: 68.08 ± 4.30% vs. 79.03 ± 3.79%; crushed: 63.62 ± 4.97% vs. 74.73 ± 2.51%) and SR Bv56 (single-layer: 63.63 ± 4.47% vs. 79.03 ± 3.79%; crushed: 62.18 ± 3.55% vs. 74.73 ± 2.51%), all p < 0.01. The effect was even more pronounced in small stents (single‑layer 65.45 ± 1.91% (SR) vs. 77.11 ± 2.55% (UHR) and crushed 60.67 ± 2.67% vs. 74.00 ± 2.67%), both p < 0.01. Regarding subjective image quality, UHR was associated with better sharpness and less blooming, e.g., UHR Bv72 vs. SR Bv56 (multilayer: sharpness 1[0] vs. 2[0], blooming 1[0] vs. 2[0]; crush: sharpness 1[0] vs. 2[0], blooming 1[0] vs. 2[1]; all p ≤ 0.01) and UHR Bv72 vs. SR Bv72 (multilayer: sharpness 1[0] vs. 1[1], blooming 1[0] vs. 1[1]; crush: sharpness 1[0] vs. 1[1]; all p ≤ 0.05). These findings indicate that UHR PCD‑CT with Bv72 might enable assessment of complex stents in a phantom setting; even though clinical studies are warranted.

Objectives We evaluated the influence of image reconstruction kernels on the diagnostic accuracy of CT-derived fractional flow reserve (FFR CT ) compared to invasive FFR in patients with coronary artery disease. Methods Sixty-nine patients, in whom coronary CT angiography was performed and who were further referred for invasive coronary angiography with FFR measurement via pressure wire, were retrospectively included. CT data sets were acquired using a third-generation dual-source CT system and rendered with medium smooth (Bv40) and sharp (Bv49) reconstruction kernels. FFR CT was calculated on-site using prototype software. Coronary stenoses with invasive FFR ≤ 0.80 were classified as significant. Agreement between FFR CT and invasive FFR was determined for both reconstruction kernels. Results One hundred analyzed vessels in 69 patients were included. Twenty-five vessels were significantly stenosed according to invasive FFR. Using a sharp reconstruction kernel for FFR CT resulted in a significantly higher correlation with invasive FFR ( r  = 0.74, p  < 0.01 vs. r  = 0.58, p  < 0.01; p  = 0.04) and a higher AUC in ROC curve analysis to correctly identify/exclude significant stenosis (AUC = 0.92 vs. AUC = 0.82 for sharp vs. medium smooth kernel, respectively, p  = 0.02). A FFR CT value of ≤ 0.8 using a sharp reconstruction kernel showed a sensitivity of 88% and a specificity of 92% for detecting ischemia-causing lesions, resulting in a diagnostic accuracy of 91%. The medium smooth reconstruction kernel performed worse (sensitivity 60%, specificity 89%, accuracy 82%). Conclusion Compared to invasively measured FFR, FFR CT using a sharp image reconstruction kernel shows higher diagnostic accuracy for detecting lesions causing ischemia, potentially altering decision-making in a clinical setting. Key Points • Image reconstruction parameters influence the diagnostic accuracy of simulated fractional flow reserve derived from coronary computed tomography angiography. • Using a sharp kernel image reconstruction algorithm delivers higher diagnostic accuracy compared to medium smooth kernel image reconstruction (gold standard invasive fractional flow reserve).

Objectives Chronic renal failure is common in patients referred for transcatheter aortic valve implantation (TAVI). CT angiography is recommended and provides crucial information prior to TAVI. We evaluated the feasibility of a reduced contrast volume protocol for pre-procedural CT imaging. Methods Forty consecutive patients were examined with prospectively ECG-triggered high-pitch spiral acquisition using a novel third-generation dual-source CT system; 38 ml contrast agent was used. Image quality was graded on a visual scale (1–4). Contrast attenuation was measured at the level of the aortic root and at the iliac bifurcation. Results Mean patient age was 82 ± 6 years (23 males; 58 %). Mean attenuation/average image quality was 285 ± 60 HU/1.5 at the aortic annulus compared to 289 ± 74 HU/1.8 at the iliac bifurcation (p = 0.77/p = 0.29). Mean estimated effective radiation dose was 2.9 ± 0.3 mSv. A repeat acquisition was necessary in one patient due to image quality. Out of the 35 patients who underwent TAVI, 31 (89 %) patients had no or mild aortic regurgitation. Thirty-two (91 %) patients were discharged successfully. Conclusion Pre-procedural CTA with a total of 38 ml contrast volume is feasible and clinically useful, using third-generation dual-source CT, allowing comprehensive imaging for procedural success. Key points • Reduction of contrast agent volume is crucial in patients with chronic renal failure . • Novel third - generation computed tomography helps to reduce contrast agent volume . • Pre - procedural CT allows comprehensive imaging for procedural success before heart valve implantation . • A low - contrast CT protocol is feasible for pre - procedural TAVI planning .

The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.

A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.

Background Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Results Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. Conclusion The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Retention and detention basins are engineering constructions with multiple objectives; e.g., flood protection and irrigation. Their performance is highly location-dependent, and thus, optimization strategies are needed. LOCASIN (Location detection of retention and detention basins) is an open-source MATLAB tool that enables automated and rapid detection, characterization and evaluation of basin locations. The site detection is based on a numerical raster analysis to determine the optimal dam axis orientation, the dam geometry and the basin area and volume. After selecting a reasonable basin combination, the results are summarized and visualized. LOCASIN represents a user-friendly and flexible tool for policy makers, engineers and scientists to determine dam and basin properties of optimized positions for planning and research purposes. It can be applied in an automated way to solve small and large scale engineering problems. The software is available on GitHub.

The concept of systemic resilience, as it is understood in the context of climate change adaptation addressing systemic risks and polycrisis, is an inherently normative notion that carries ethical weight. To account for these implications, systemic resilience needs to be supplemented with ethical reflections on a system’s function, why it should be made resilient, and who the resilience serves. Crucially, considerations surrounding various forms of justice, such as participatory, procedural, distributive, and historical, need to be accounted for when making decisions about a community’s resilience in the face of increasing climate hazards. Resilience in the context of systemic risks and climate adaptation currently does not account for its ethical implications. This investigation builds on complexity science research and specifically the expanded concept of systemic resilience. In this article, the concept of systemic resilience is applied to the local level, highlighting its ethical underpinnings in the process. Specifically, a case-study explores the application of the ethically informed version of systemic climate resilience, exploring how the Rhine-Erft catchment in Germany could be assessed on this basis.

Objectives The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT). Methods Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months). Results In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm 3 /m 2 . We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score ( p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068–0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly. Conclusions Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification. Key Points • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD.