Initial experience on abdominal photon-counting computed tomography in clinical routine: general image quality and dose exposure.

OBJECTIVES: Photon-counting computed tomography has lately found its way into clinical routine. The new technique could offer substantial improvements regarding general image quality, image noise, and radiation dose reduction. This study evaluated the first abdominal examinations in clinical routine and compared the results to conventional computed tomography. METHODS: In this single-center retrospective study, 66 patients underwent photon-counting and conventional abdominal CT. Four radiologists assessed general image quality, image noise, and image artifacts. Signal-to-noise ratio and dose properties of both techniques within the clinical application were compared. An ex vivo phantom study revealed the radiobiological impact by means of DNA double-strand break foci in peripheral blood cells by enumerating γ-H2AX+53BP1 foci. RESULTS: General image quality in accordance with the Likert scale was found superior for photon-counting CT (4.74 ± 0.46 vs. 4.25 ± 0.54; p < 0.001). Signal-to-noise ratio (p < 0.001) and also dose exposure were higher for photon-counting CT (DLP: 419.2 ± 162.2 vs. 372.3 ± 236.6 mGy*cm; p = 0.0435). CT exposure resulted in significantly increased DNA damage in comparison to sham control (p < 0.001). Investigation of the average foci per cell and radiation-induced foci numbers revealed significantly elevated numbers (p = 0.004 and p < 0.0001, respectively) after photon-counting CT. CONCLUSION: Photon-counting CT in abdominal examinations showed superior results regarding general image quality and signal-to-noise ratio in clinical routine. However, this seems to be traded for a significantly higher dose exposure and corresponding double-strand break frequency. Optimization of standard protocols in further clinical applications is required to find a compromise regarding picture quality and dose exposure. KEY POINTS: • Photon-counting computed tomography promises to enhance the diagnostic potential of medical imaging in clinical routine. • Retrospective single-center study showed superior general image quality accompanied by higher dose exposure in initial abdominal PCCT protocols compared to state-of-the-art conventional CT. • A simultaneous ex vivo phantom study revealed correspondingly increased frequencies of DNA double-strand breaks after PCCT.

High-power continuous-wave Tm3+:Ho3+-codoped fiber laser operation from 2.1 µm to 2.2 µm.

A Tm3+:Ho3+-codoped free-space single-oscillator fiber laser is under investigation with special focus on the power scalability of emission wavelengths from 2.1 µm to 2.2 µm. Using a tunable diffraction grating, a 200-nm tunable laser source is built. Laser output powers above 10 W are delivered from 1990 nm up to 2190 nm, demonstrating the range for stable high-power laser operation. By replacing the diffraction grating by a highly reflective, narrow linewidth volume Bragg grating, power scaling is performed at 2.1 µm and is even enabled at a wavelength of 2.2 µm. Using a volume Bragg grating (VBG) at 2.1 µm, a slope efficiency of 49% is measured with an output power of 262 W. Using another VBG with a center wavelength of 2.2 µm, the fiber laser delivers a record power of 77 W with a slope efficiency of 29%.

Fluorescent Zn(II)-Based Metal-Organic Framework: Interaction with Organic Solvents and CO2 and Methane Capture.

Adsorption of carbon dioxide (CO2), as well as many other kinds of small molecules, is of importance for industrial and sensing applications. Metal-organic framework (MOF)-based adsorbents are spotlighted for such applications. An essential for MOF adsorbent application is a simple and easy fabrication process, preferably from a cheap, sustainable, and environmentally friendly ligand. Herein, we fabricated a novel structural, thermally stable MOF with fluorescence properties, namely Zn [5-oxo-2,3-dihydro-5H-[1,3]-thiazolo [3,2-a]pyridine-3,7-dicarboxylic acid (TPDCA)] • dimethylformamide (DMF) •0.25 H2O (coded as QUF-001 MOF), in solvothermal conditions by using zinc nitrate as a source of metal ion and TPDCA as a ligand easy accessible from citric acid and cysteine. Single crystal X-ray diffraction analysis and microscopic examination revealed the two-dimensional character of the formed MOF. Upon treatment of QUF-001 with organic solvents (such as methanol, isopropanol, chloroform, dimethylformamide, tetrahydrofuran, hexane), interactions were observed and changes in fluorescence maxima as well as in the powder diffraction patterns were noticed, indicating the inclusion and intercalation of the solvents into the interlamellar space of the crystal structure of QUF-001. Furthermore, CO2 and CH4 molecule sorption properties for QUF-001 reached up to 1.6 mmol/g and 8.1 mmol/g, respectively, at 298 K and a pressure of 50 bars.

High pulse energy ZnGeP2 OPO directly pumped by a Q-switched Tm3+-doped single-oscillator fiber laser.

A mid-infrared ${{\rm ZnGeP}_2}$ optical parametric oscillator pumped by a ${{\rm Tm}^{3 +}}$-doped fiber laser is reported, providing pulse energies of $230 \;\unicode{x00B5}{\rm J}$, pulse widths of 40 ns, and peak powers of ${\sim}6\;{\rm kW} $ with excellent efficiency and beam quality. The pump source is an actively $Q$-switched single oscillator optimized to generate high pulse energies.

A Building Brick Principle to Create Transparent Composite Films with Multicolor Emission and Self-Healing Function.

A cellulose paper is used impregnated with light-emitting CdTe nanocrystals and carbon dots, and filled with a polyurethane to fabricate uniform transparent composite films with bright photoluminescence of red (R), green (G), and blue (B) (RGB) colors. A building brick-like assembly method is introduced to realize RGB multicolor emission patterns from this composite material. By sectioning out individual pixels from monochrome-emissive composite sheets, the advantage of the self-healing properties of polyurethane is taken to arrange and weld them into a RGB patterned fabric by brief exposure to ethanol. This provides an approach to form single layer RGB light-emitting pixels, such as potentially required in the display applications, without the use of any lithographic or etching processing. The method can utilize a wide range of different solution-based kinds of light-emitting materials.

Rho-inhibiting C2IN-C3 fusion toxin inhibits chemotactic recruitment of human monocytes ex vivo and in mice in vivo.

Bacterial protein toxins became valuable molecular tools for the targeted modulation of cell functions in experimental pharmacology and attractive therapeutics because of their potent and specific mode of action in human cells. C2IN-C3lim, a recombinant fusion toxin (~50 kDa) of the Rho-inhibiting C3lim from Clostridium (C.) limosum and a non-toxic portion of the C. botulinum C2 toxin (C2IN), is selectively internalized into the cytosol of monocytic cells where C3lim specifically ADP-ribosylates Rho A and -B, thereby inhibiting Rho-mediated signaling. Thus, we hypothesized that these unique features make C2IN-C3lim an attractive molecule for the targeted pharmacological down-regulation of Rho-mediated functions in monocytes. The analysis of the actin structure and the Rho ADP-ribosylation status implied that C2IN-C3lim entered the cytosol of primary human monocytes from healthy donors ex vivo within 1 h. Moreover, it inhibited the fMLP-induced chemotaxis of human monocytes in a Boyden chamber model ex vivo. Similarly, in a 3-dimensional ex vivo model of extravasation, single cell analysis revealed that C2IN-C3lim-treated cells were not able to move. In a clinically relevant mouse model of blunt chest trauma, the local application of C2IN-C3lim into the lungs after thorax trauma prevented the trauma-induced recruitment of monocytes into the lungs in vivo. Thus, C2IN-C3lim might be an attractive lead compound for novel pharmacological strategies to avoid the cellular damage response caused by monocytes in damaged tissue after trauma and during systemic inflammation. The results suggest that the pathophysiological role of clostridial C3 toxins might be a down-modulation of the innate immune system.

Photoinduced Micropattern Alignment of Semiconductor Nanorods with Polarized Emission in a Liquid Crystal Polymer Matrix.

Photoalignment technology provides high alignment quality with an exceptional control over the local director of liquid crystals. Because of the reorientation ability of sulfonic azo dye molecules, they offer high azimuthal and polar anchoring energy with a low pretilt angle for the orientation of liquid crystals and liquid crystal composites. In this work, we make use of this approach to align thin film composites of light-emitting semiconductor nanorods dispersed in a liquid crystal polymer into both one-dimensional and two-dimensional microscale patterns. After unidirectional alignment, the patterns are fabricated by a second irradiation with different polarization azimuth and the employment of a photomask. Fluorescence micrographs reveal the nanorod pattern alignment in domain sizes down to 2 µm. Apart from demonstrating the possibility of controlling the orientation of anisotropic nanocrystals with strongly polarized emission on microscopic scale, our results are promising for the fabrication of complex nanostructures for photonic applications.

Tracking the Source of Carbon Dot Photoluminescence: Aromatic Domains versus Molecular Fluorophores.

Carbon dots (CDs) are an intriguing fluorescent material; however, due to a plethora of synthesis techniques and precursor materials, there is still significant debate on their structure and the origin of their optical properties. The two most prevalent mechanisms to explain them are based on polycyclic aromatic hydrocarbon domains and small molecular fluorophores, for instance, citrazinic acid. Yet, how these form and whether they can exist simultaneously is still under study. To address this, we vary the hydrothermal synthesis time of CDs obtained from citric acid and ethylenediamine and show that in the initial phase molecular fluorophores, likely 2-pyridone derivatives, account for the blue luminescence of the dots. However, over time, while the overall size of the CDs does not change, aromatic domains form and grow, resulting in a second, faster decay channel at similar wavelengths and also creating additional lower energetic states. Electrophoresis provides further evidence that the ensemble of CDs consists of several subsets with different internal structure and surface charge. The understanding of the formation mechanism enables a control of the chemical origin of these emitters and the ensuing optical properties of the CDs through synthetic means.

Top-Down Fabrication of Stable Methylammonium Lead Halide Perovskite Nanocrystals by Employing a Mixture of Ligands as Coordinating Solvents.

A top-down method is demonstrated for the fabrication of CH3 NH3 PbBr3 and CH3 NH3 PbI3 perovskite nanocrystals, employing a mixture of ligands oleic acid and oleylamine as coordinating solvents. This approach avoids the use of any polar solvents, skips multiple reaction steps by employing a simple ultrasonic treatment of the perovskite precursors, and yields rather monodisperse blue-, green-, and red-emitting methylammonium lead halide nanocrystals with a high photoluminescence quantum yield (up to 72 % for the green-emitting nanocrystals) and remarkably improved stability. After discussing all relevant reaction parameters, the green-emitting CH3 NH3 PbBr3 nanocrystals are employed as a component of down-conversion white-light-emitting devices.

Open-atmosphere sustenance of highly volatile attoliter-size droplets on surfaces.

The controlled formation and handling of minute liquid volumes on surfaces is essential to the success of microfluidics in biology, chemistry, and materials applications. Even though current methods have demonstrated their potential in a variety of experimental assays, there remain significant difficulties concerning breadth of applicability, standardization, throughput, and economics. Here we introduce a unique microfluidic paradigm in which microscopic volatile droplets are formed, sustained, and manipulated in size and content at any desired spot on unpatterned substrates. Their sustainability is warranted by continuous replacement of the rapidly vaporizing sessile fluid through controlled equivalent volume deposition of smaller discrete liquid entities by an electrohydrodynamic nanodripping process. Using nanoparticle inks we show that the concentration of solutes in so-stabilized droplets can be linearly increased at isochoric conditions and user-defined rates. An intriguing insensitivity of the droplet shape toward surface heterogeneities ensures robustness and experimental reproducibility, even when handling attoliter quantities. The unique capabilities and technical simplicity of the presented method introduce a high degree of flexibility and make it pertinent to a diverse range of applications.

Exploring Spanish health social media for detecting drug effects.

BACKGROUND: Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. METHODS: In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. RESULTS: Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. CONCLUSIONS: The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English.

Computational prediction of circular dichroism spectra and quantification of helicity loss upon peptide adsorption on silica.

Circular dichroism (CD) spectroscopy is one of the few experimental techniques sensitive to the structural changes that peptides undergo when they adsorb on inorganic material surfaces, a problem of deep significance in medicine, biotechnology, and materials science. Although the theoretical calculation of the CD spectrum of a molecule in a given conformation can be routinely performed, the inverse problem of extracting atomistic structural details from a measured spectrum is not uniquely determined. Especially complicated is the case of oligopeptides, whose folding/unfolding energy landscapes are often very broad and shallow. This means that the CD spectra measured for either dissolved or adsorbed peptides arise from a multitude of different structures, each present with a probability dictated by their relative free-energy variations, according to Boltzmann statistics. Here we present a modeling method based on replica exchange with solute tempering in combination with metadynamics, which allows us to predict both the helicity loss of a small peptide upon interaction with silica colloids in water and to compute the full CD spectra of the adsorbed and dissolved states, in quantitative agreement with experimental measurements. In our method, the CD ellipticity Θ for any given wavelength λ is calculated as an external collective variable by means of reweighting the biased trajectory obtained using the peptide-SiO2 surface distance and the structural helicity as two independent, internal collective variables. Our results also provide support for the often-employed hypothesis that the Θ intensity at λ = 222 nm is linearly correlated with the peptides' fractional helicity.

Thermodynamics of surface defects at the aspirin/water interface.

We present a simulation scheme to calculate defect formation free energies at a molecular crystal/water interface based on force-field molecular dynamics simulations. To this end, we adopt and modify existing approaches to calculate binding free energies of biological ligand/receptor complexes to be applicable to common surface defects, such as step edges and kink sites. We obtain statistically accurate and reliable free energy values for the aspirin/water interface, which can be applied to estimate the distribution of defects using well-established thermodynamic relations. As a show case we calculate the free energy upon dissolving molecules from kink sites at the interface. This free energy can be related to the solubility concentration and we obtain solubility values in excellent agreement with experimental results.

Disulfiram Inhibits Opsonin-Independent Phagocytosis and Migration of Human Long-Lived In Vitro Cultured Phagocytes from Multiple Inflammatory Diseases.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects through its copper chelating derivatives and induction of oxidative stress in mitochondria. Since chronic/persistent borreliosis is characterized by increased amounts of pro-inflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration, and surface marker expression of in vivo activated and in vitro cultured human monocyte-derived phagocytes (macrophages and dendritic cells) with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24 h, imaging every 3.5 min. To simultaneously monitor phagocyte function, results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads. DSF decreased the phagocytic capacities exhibited by in vitro enriched and long-lived phagocytes. Although no chemotactic gradient was applied to the test system, vigorous spontaneous migration was observed. We therefore set up an algorithm to monitor and quantify both phagocytosis and migration simultaneously. DSF not only reduced phagocytosis in a majority of these long-lived phagocytes but also impaired their migration. Despite these selective effects by DSF, we found that DSF reduced the expression densities of surface antigens CD45 and CD14 in all of our long-lived phagocytes. In cells with a high metabolic activity and high mitochondrial contents, DSF led to cell death corresponding to mitochondrial oxidative stress, whereas metabolically inactive phagocytes survived our DSF treatment protocol. In conclusion, DSF affects the viability of metabolically active phagocytes by inducing mitochondrial stress and secondly attenuates phagocytosis and migration in some long-lived phagocytes.

NFDI4Health Workflow and Service for Synthetic Data Generation, Assessment and Risk Management.

Individual health data is crucial for scientific advancements, particularly in developing Artificial Intelligence (AI); however, sharing real patient information is often restricted due to privacy concerns. A promising solution to this challenge is synthetic data generation. This technique creates entirely new datasets that mimic the statistical properties of real data, while preserving confidential patient information. In this paper, we present the workflow and different services developed in the context of Germany's National Data Infrastructure project NFDI4Health. First, two state-of-the-art AI tools (namely, VAMBN and MultiNODEs) for generating synthetic health data are outlined. Further, we introduce SYNDAT (a public web-based tool) which allows users to visualize and assess the quality and risk of synthetic data provided by desired generative models. Additionally, the utility of the proposed methods and the web-based tool is showcased using data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Center for Cancer Registry Data of the Robert Koch Institute (RKI).

Privacy Risk Assessment for Synthetic Longitudinal Health Data.

INTRODUCTION: A modern approach to ensuring privacy when sharing datasets is the use of synthetic data generation methods, which often claim to outperform classic anonymization techniques in the trade-off between data utility and privacy. Recently, it was demonstrated that various deep learning-based approaches are able to generate useful synthesized datasets, often based on domain-specific analyses. However, evaluating the privacy implications of releasing synthetic data remains a challenging problem, especially when the goal is to conform with data protection guidelines. METHODS: Therefore, the recent privacy risk quantification framework Anonymeter has been built for evaluating multiple possible vulnerabilities, which are specifically based on privacy risks that are considered by the European Data Protection Board, i.e. singling out, linkability, and attribute inference. This framework was applied to a synthetic data generation study from the epidemiological domain, where the synthesization replicates time and age trends previously found in data collected during the DONALD cohort study (1312 participants, 16 time points). The conducted privacy analyses are presented, which place a focus on the vulnerability of outliers. RESULTS: The resulting privacy scores are discussed, which vary greatly between the different types of attacks. CONCLUSION: Challenges encountered during their implementation and during the interpretation of their results are highlighted, and it is concluded that privacy risk assessment for synthetic data remains an open problem.

Synthetic data generation for a longitudinal cohort study - evaluation, method extension and reproduction of published data analysis results.

Access to individual-level health data is essential for gaining new insights and advancing science. In particular, modern methods based on artificial intelligence rely on the availability of and access to large datasets. In the health sector, access to individual-level data is often challenging due to privacy concerns. A promising alternative is the generation of fully synthetic data, i.e., data generated through a randomised process that have similar statistical properties as the original data, but do not have a one-to-one correspondence with the original individual-level records. In this study, we use a state-of-the-art synthetic data generation method and perform in-depth quality analyses of the generated data for a specific use case in the field of nutrition. We demonstrate the need for careful analyses of synthetic data that go beyond descriptive statistics and provide valuable insights into how to realise the full potential of synthetic datasets. By extending the methods, but also by thoroughly analysing the effects of sampling from a trained model, we are able to largely reproduce significant real-world analysis results in the chosen use case.

HSV-1 and Cellular miRNAs in CSF-Derived Exosomes as Diagnostically Relevant Biomarkers for Neuroinflammation.

Virus-associated chronic inflammation may contribute to autoimmunity in a number of diseases. In the brain, autoimmune encephalitis appears related to fluctuating reactivation states of neurotropic viruses. In addition, viral miRNAs and proteins can be transmitted via exosomes, which constitute novel but highly relevant mediators of cellular communication. The current study questioned the role of HSV-1-encoded and host-derived miRNAs in cerebrospinal fluid (CSF)-derived exosomes, enriched from stress-induced neuroinflammatory diseases, mainly subarachnoid hemorrhage (SAH), psychiatric disorders (AF and SZ), and various other neuroinflammatory diseases. The results were compared with CSF exosomes from control donors devoid of any neuroinflammatory pathology. Serology proved positive, but variable immunity against herpesviruses in the majority of patients, except controls. Selective ultrastructural examinations identified distinct, herpesvirus-like particles in CSF-derived lymphocytes and monocytes. The likely release of extracellular vesicles and exosomes was most frequently observed from CSF monocytes. The exosomes released were structurally similar to highly purified stem-cell-derived exosomes. Exosomal RNA was quantified for HSV-1-derived miR-H2-3p, miR-H3-3p, miR-H4-3p, miR-H4-5p, miR-H6-3p, miR-H27 and host-derived miR-21-5p, miR-146a-5p, miR-155-5p, and miR-138-5p and correlated with the oxidative stress chemokine IL-8 and the axonal damage marker neurofilament light chain (NfL). Replication-associated miR-H27 correlated with neuronal damage marker NfL, and cell-derived miR-155-5p correlated with oxidative stress marker IL-8. Elevated miR-138-5p targeting HSV-1 latency-associated ICP0 inversely correlated with lower HSV-1 antibodies in CSF. In summary, miR-H27 and miR-155-5p may constitute neuroinflammatory markers for delineating frequent and fluctuating HSV-1 replication and NfL-related axonal damage in addition to the oxidative stress cytokine IL-8 in the brain. Tentatively, HSV-1 remains a relevant pathogen conditioning autoimmune processes and a psychiatric clinical phenotype.

Exerting Forces and Wall Load during Duodenoscopy for ERCP: An Experimental Measurement in an Artificial Model.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is crucial to the treatment of biliopancreatic diseases with iatrogenic perforation as a potential complication. As of yet, the wall load during ERCP is unknown, as it is not directly measurable during an ERCP in patients. METHODS: In a life-like, animal-free model, a sensor system consisting of five load cells was attached to the artificial intestines (sensors 1 + 2: pyloric canal-pyloric antrum, sensor 3: duodenal bulb, sensor 4: descending part of the duodenum, sensor 5: distal to the papilla). Measurements were made with five duodenoscopes (n = 4 reusable and n = 1 single use). RESULTS: Fifteen standardized duodenoscopies were performed. Peak stresses were found at the antrum during the gastrointestinal transit (sensor 1 max. 8.95 N, sensor 2 max. 2.79 N). The load reduced from the proximal to the distal duodenum and the greatest load in the duodenum was discovered at the level of the papilla in 80.0% (sensor 3 max. 2.06 N). CONCLUSIONS: For the first time, intraprocedural load measurements and exerting forces obtained during a duodenoscopy for ERCP in an artificial model were recorded. None of the tested duodenoscopes were classified as dangerous for patient safety.

Specific material recognition by small peptides mediated by the interfacial solvent structure.

We present evidence that specific material recognition by small peptides is governed by local solvent density variations at solid/liquid interfaces, sensed by the side-chain residues with atomic-scale precision. In particular, we unveil the origin of the selectivity of the binding motif RKLPDA for Ti over Si using a combination of metadynamics and steered molecular dynamics simulations, obtaining adsorption free energies and adhesion forces in quantitative agreement with corresponding experiments. For an accurate description, we employ realistic models of the natively oxidized surfaces which go beyond the commonly used perfect crystal surfaces. These results have profound implications for nanotechnology and materials science applications, offering a previously missing structure-function relationship for the rational design of materials-selective peptide sequences.