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Wastewater treatment plants (WWTPs) have been identified as important point sources for microplastics (MPs) in the environment; monitoring MP emissions in the WWTP effluent is therefore essential for contamination control. The aim of this study is to acquire a large number of samples (320) over a period of two years and three months to determine the temporal variations in microplastic contamination in the outlet of the municipal WWTP Landau-Mörlheim. The effluent of the third cleaning stage is sampled with a 10 µm filter cartridge, processed in the laboratory using a hydrogen peroxide treatment, and MPs are then detected by fluorescence staining. The results show high temporal variations in the microplastic concentrations in the effluent of the WWTP. This indicates that high numbers of samples are necessary to obtain a representative assessment of the microplastic emissions; single samples are not representative. The average microplastic concentration in the effluent was 27.8 ± 29.8 MP/L, ranging from 0.6 MP/L to 194.0 MP/L. This leads to a yearly emission of 1.5 × 1011 MP for the WWTP Landau-Mörlheim, corresponding to an emission of 2.8 × 106 MP/inhabitant and year. Statistically significant seasonal variations could not be observed, although there is a trend towards lower MP concentrations in summer. Further, no correlations with other wastewater or weather parameters could be found.

The environmental impacts of the postindustrial era, which rely on fossil fuels, have compelled a reconsideration of the future of energy and chemical industries. Fungi are a valuable resource for improving a circular economy through the enhanced valorization of biomass and plant waste. They harbor a great diversity of oxidative enzymes, especially in their secretome. Enzymatic breakdown of the plant cell wall complex and lignocellulosic biomass yields sugars for fermentation and biofuel production, as well as aromatic compounds from lignin that can serve as raw materials for the chemical industry. To harness the biocatalytic potential, it is essential to identify and explore wild-type fungi and their secretomes. This study successfully combined genome mining and activity screening to uncover the oxidative potential of a collection of underexploited ascomycetes and basidiomycetes. The heme peroxidase and laccase activities of four promising candidates, Bipolaris victoriae, Colletotrichum sublineola, Neofusicoccum parvum and Moesziomyces antarcticus, were investigated to gain a deeper insight into their enzyme secretion. Furthermore, a plant-based medium screening with the phytopathogen C. sublineola revealed that soybean meal is a beneficial component to trigger the production and secretion of enzymes that catalyze H2O2-dependent oxidations. These results demonstrate that understanding fungal secretomes and their enzymatic potential opens exciting avenues for sustainable biotechnological applications across various industries.

Neural radiance fields have emerged as a dominant paradigm for creating complex 3D environments incorporating synthetic novel views. However, 3D object removal applications utilizing neural radiance fields have lagged behind in effectiveness, particularly when open set queries are necessary for determining the relevant objects. One such application area is in architectural heritage preservation, where the automatic removal of non-architectural objects from 3D environments is necessary for many downstream tasks. Furthermore, when modeling occupied buildings, it is crucial for modeling techniques to be privacy preserving by default; this also motivates the removal of non-architectural elements. In this paper, we propose a pipeline for the automatic creation of cleaned, architectural structure only point clouds utilizing a language embedded radiance field (LERF) with a specific application toward generating suitable point clouds for the structural integrity assessment of occupied buildings. We then validated the efficacy of our approach on the rooms of the historic Sion hospital, a national historic monument in Valais, Switzerland. By using our automatic removal pipeline on the point clouds of rooms filled with furniture, we decreased the average earth mover’s distance (EMD) to the ground truth point clouds of the physically emptied rooms by 31 percent. The success of our research points the way toward new paradigms in architectural modeling and cultural preservation.

Microplastic (MP) has emerged as a significant environmental challenge due to increased plastic production and its widespread presence in the environment. This study aimed to assess MP concentrations throughout the treatment process at nine wastewater treatment plants (WWTPs) in Germany, from influent to effluent. A customized sampling technique was employed, followed by field and laboratory preparation and the quantification of polymers (PE, PP, PS, PMMA, and PET) using TED-GCMS. MP concentrations decreased progressively in the WWTPs, with influent concentrations ranging from 2.5 to 13.6 mg/L. Effluent concentrations in the conventional WWTPs ranged from 0.001 to 0.051 mg/L, while advanced treatment via filtration yielded concentrations below the limit of quantification at 0.005 mg/L. All tested of the WWTPs demonstrated an over 99% removal efficiency for microplastics. Despite effective retention by the WWTPs, a critical evaluation of the results is necessary. There is a need to optimize existing technologies and enhance the standardization of sampling, processing, and measurement methods, as well as intensify efforts towards creating preventive measures to reduce plastic emissions.

The mesial piriform region plays a central role in olfaction. Its small size and complex geometry, however, make it a difficult target in functional neuroimaging studies, while histological maps often represent schematic drawings, which are not compatible with requirements for modern imaging. To bridge this gap, cytoarchitectonic analysis and mapping of the region was performed in serial histological sections over their full extent in 10 postmortem brains. The temporobasal areas PirTBd and PirTBv and temporal areas PirTu and PirTit were identified and analyzed. Probabilistic cytoarchitectonic maps of the piriform areas in MNI reference space and high-resolution maps of the amygdala-piriform region on the BigBrain model were calculated as part of the Julich-Brain. Differences in the cytoarchitectonic “texture” of the region were quantified based on the Gray Level Co-Occurrence Matrix. Results showed that allocortical areas were not consistently associated with the rostral Limen insulae, although it was often suggested as a landmark in neuroimaging protocols. PirTu was associated with the uncal tip. PirTit was the largest area, reaching to the temporal pole, with a “temporal” (caudal) and a “temporopolar” (rostral) part having complex neighborhood relationships. The probabilistic maps reflect interindividual variability; they are openly available via the digital EBRAINS platform to serve as an anatomical reference for studies related to olfaction.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the implementation of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs. (2) Methods: Single-center retrospective study in patients with ADRs after mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines). (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculopapular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular predominantly lymphocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred after the second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% of patients and maculopapular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients. (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. Interestingly, in about half of our patients, ADRs were self-limited, whereas ADRs extended beyond a month in the other half.

Two-thirds of human infectious diseases are zoonotic diseases and routine data collections exist for each sector (human, veterinary, environmental). However, these operate separately and the collected data are not integrated across sectors. Publicly available information on these routine data collections in terms of metadata and the information collected is sparse. The aim was to create an inventory of routine data collections in the Federal State of Lower Saxony, Germany. A systematic screening of existing routine data collections from the human and veterinary sectors on zoonotic infectious diseases was carried out on the basis of expert interviews. A standardised template was used to collect relevant metadata on data collections and pathogens they contain. The template was transferred to Research Electronic Data Capture tools. We recorded metadata for 19 veterinary, 16 human and 2 other data collections, and for 69 different zoonotic pathogens. The frequencies of a selection of metadata were analysed descriptively. The data collections, which served different purposes, differed, e.g., in underlying population and sampling strategy, export format and access to the original data. We identified challenges for integrated analyses of data from different collections, which need to be addressed to develop a One Health monitoring and surveillance system.

Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid–protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

The bacterium Zymomonas mobilis is investigated as a model organism for the cultivation and separation of ethanol as a product by in situ extraction in continuous flow microreactors. The considered microreactor is the Coiled Flow Inverter (CFI), which consists of a capillary coiled onto a support structure. Like other microreactors, the CFI benefits from a high surface-to-volume ratio, which enhances mass and heat transfer. Compared to many other microreactors, the CFI offers the advantage of operating without internal structures, which are often used to ensure good mixing. The simplicity of the design makes the CFI particularly suitable for biochemical applications as cells do not get stuck or damaged by internal structures. Despite this simplicity, good mixing is achieved through flow vortices caused by Taylor and Dean vortices. The reaction system consists of two phases, in which the aqueous phase carries the bacterium and an oleyl alcohol phase is used to extract the ethanol produced. Key parameters for evaluation are bacteria growth and the amount of ethanol produced by the microorganism. The results show the suitability of the CFI for microbial production of valuable compounds. A maximum ethanol concentration of 1.26 g L−1 was achieved for the experiment in the CFI. Overall, the cultivation in the CFI led to faster growth of Z. mobilis, resulting in 25% higher ethanol production than in conducted batch experiments.

To meet today’s requirements, new active catalysts with reduced noble metal content are needed for hydrogen sensing. A palladium-functionalized nanostructured Ni0.5Co2.5O4 catalyst with a total Pd content of 4.2 wt% was synthesized by coprecipitation to obtain catalysts with an advantageous sheet-like morphology and surface defects. Due to the synthesis method and the reducible nature of Ni0.5Co2.5O4 enabling strong metal-metal oxide interactions, the palladium was highly distributed over the metal oxide surface, as determined using scanning transmission electron microscopy and energy-dispersive X-ray investigations. The catalyst tested in planar pellistor sensors showed high sensitivity to hydrogen in the concentration range below the lower flammability limit (LFL). At 400 °C and in dry air, a sensor response of 109 mV/10,000 ppm hydrogen (25% of LFL) was achieved. The sensor signal was 4.6-times higher than the signal of pristine Ni0.5Co2.5O4 (24.6 mV/10,000 ppm). Under humid conditions, the sensor responses were reduced by ~10% for Pd-functionalized Ni0.5Co2.5O4 and by ~27% for Ni0.5Co2.5O4. The different cross-sensitivities of both catalysts to water are attributed to different activation mechanisms of hydrogen. The combination of high sensor sensitivity to hydrogen and high signal stability over time, as well as low cross-sensitivity to humidity, make the catalyst promising for further development steps.

Innovative tools suitable for chemical risk assessment are being developed in numerous domains, such as non-target chemical analysis, omics, and computational approaches. These methods will also be critical components in an efficient early warning system (EWS) for the identification of potentially hazardous chemicals. Much knowledge is missing for current use chemicals and thus computational methodologies complemented with fast screening techniques will be critical. This paper reviews current computational tools, emphasizing those that are accessible and suitable for the screening of new and emerging risk chemicals (NERCs). The initial step in a computational EWS is an automatic and systematic search for NERCs in literature and database sources including grey literature, patents, experimental data, and various inventories. This step aims at reaching curated molecular structure data along with existing exposure and hazard data. Next, a parallel assessment of exposure and effects will be performed, which will input information into the weighting of an overall hazard score and, finally, the identification of a potential NERC. Several challenges are identified and discussed, such as the integration and scoring of several types of hazard data, ranging from chemical fate and distribution to subtle impacts in specific species and tissues. To conclude, there are many computational systems, and these can be used as a basis for an integrated computational EWS workflow that identifies NERCs automatically.

Early endosomes represent first-line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes, for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platforms to initiate or prolong distinct signaling pathways. Accordingly, early endosomes have to be recognized as either part of a degradation or recycling pathway. The physical proximity of many ligand-binding receptors with other membrane-bound proteins or complexes such as NADPH oxidases may result in an interaction of second messengers, like reactive oxygen species (ROS) and early endosomes, that promote the correct recognition of individual early endosomes. In fact, redoxosomes comprise an endosomal subsection of signaling endosomes. One example of such potential interaction is epidermal growth factor receptor (EGFR) signaling. Here we summarize recent findings on EGFR signaling as a well-studied example for receptor trafficking and trans-activation and illustrate the interplay between cellular and endosomal ROS.

Background: Monochorionic (MC) twins are at risk for severe twin-to-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). In the case of preterm delivery, cesarean section (CS) with immediate umbilical cord clamping (ICC) of both twins is usually performed. While the recipient is at risk for polycythemia and may benefit from ICC, this procedure may result in aggravation of anemia with increased morbidity in the anemic donor. The purpose of this study was to demonstrate that the novel approach of selective extrauterine placental perfusion (EPP) with delayed umbilical cord clamping (DCC) in the donor infant is feasible in neonatal resuscitation of MC twins and may prevent severe anemia in donor and polycythemia in the recipient. Methods: Preterm MC twins with antenatal suspected severe anemia of the donor as measured by Doppler ultrasound, born with birthweights < 1500 g by CS, were transferred to the neonatal resuscitation unit with placenta and intact umbilical cords. In the donor, the umbilical cord was left intact to provide DCC with parallel respiratory support (EPP approach), while the cord of the recipient was clamped immediately after identification. Results: Selective EPP was performed in three cases of MC twins with TAPS and acute peripartum TTTS. All donor twins had initial hemoglobin levels ≥ 13.0 g/dL, and none of them required red blood cell transfusion on the first day after birth. Conclusions: Selective EPP may be a feasible strategy for neonatal resuscitation of MC preterm twins with high stage TAPS and TTTS to prevent anemia-related morbidities and may improve infant outcome.

Throughout recent years, the implementation of nanoparticles into the microstructure of additively manufactured (AM) parts has gained great attention in the material science community. The dispersion strengthening (DS) effect achieved leads to a substantial improvement in the mechanical properties of the alloy used. In this work, an ex situ approach of powder conditioning prior to the AM process as per a newly developed fluidized bed reactor (FBR) was applied to a titanium-enriched variant of the NiCu-based Alloy 400. Powders were investigated before and after FBR exposure, and it was found that the conditioning led to a significant increase in the TiN formation along grain boundaries. Manufactured to parts via laser-based powder bed fusion of metals (PBF-LB/M), the ex situ FBR approach not only revealed a superior microstructure compared to unconditioned parts but also with respect to a recently introduced in situ approach based on a gas atomization reaction synthesis (GARS). A substantially higher number of nanoparticles formed along cell walls and enabled an effective suppression of dislocation movement, resulting in excellent tensile, creep, and fatigue properties, even at elevated temperatures up to 750 °C. Such outstanding properties have never been documented for AM-processed Alloy 400, which is why the demonstrated FBR ex situ conditioning marks a promising modification route for future alloy systems.

Background: Nodular fasciitis is a benign, singularly occurring nodular fibroblastic/myofibroblastic neoplasia. Due to the rapid growth and cellular atypia, this rare differential diagnosis in the head and neck region can be mistaken for malignant sarcomas. Methods: We present a 40-year-old female patient with an unclear, rough, and poorly displaceable supraclavicular swelling on the right as part of a medical check-up. Sonographically, the lump was poorly circumscribed with little vascularization. A consecutive core needle biopsy of the lesion yielded inconclusive results showing spindle-shaped tumor cells. 68Ga-FAPI-PET/CT showed an intensive uptake of the right supraclavicular lesion in addition to postoperative changes in the right tonsil. Subsequent operative partial excision of the lesion confirmed the histopathological diagnosis of nodular fasciitis. Results: Nodular fasciitis is the most prevalent pseudosarcoma found in soft tissues. This case is the first description of 68Ga-FAPI-PET/CT in nodular fasciitis. Surgical removal is advised; nevertheless, the tumor frequently diminishes on its own, and recurrence is rare. Extensive surgical therapy is not necessary. Conlcusions: The recognition of nodular fasciitis and its benign characteristics is crucial to prevent diagnostic errors and the subsequent unnecessary operative treatment of the patient.

Fragile X mental retardation protein (FMRP) is a translational repressor encoded by FMR1. It targets bone morphogenetic protein receptor type II (BMPR2), which regulates granulosa cell (GC) function and follicle development. However, whether this interaction affects folliculogenesis remains unclear. Therefore, this study investigated the potential effect of FMRP-BMPR2 dysregulation in ovarian reserves and infertility. COV434 cells and patient-derived GCs were used to evaluate FMRP and BMPR2 expression. Similarly, FMR1, BMPR2, LIMK1, and SMAD expression were evaluated in GCs with normal (NOR) and poor (POR) ovarian responses. FMRP and BMPR2 were expressed in both cell types. They were co-localized to the nuclear membrane of COV434 cells and cytoplasm of primary GCs. FMR1 silencing increased the mRNA and protein levels of BMPR2. However, the mRNA levels of FMR1 and BMPR2 were significantly lower in the POR group. FMR1 and BMPR2 levels were strongly positively correlated in the NOR group but weakly correlated in the POR group. Additionally, SMAD9 expression was significantly reduced in the POR group. This study highlights the crucial role of FMR1/FMRP in the regulation of BMPR2 expression and its impact on ovarian function. These findings indicate that the disruption of FMRP-BMPR2 interactions may cause poor ovarian responses and infertility.

In recent decades, inland water remote sensing has seen growing interest and very strong development. This includes improved spatial resolution, increased revisiting times, advanced multispectral sensors and recently even hyperspectral sensors. However, inland waters are more challenging than oceanic waters due to their higher complexity of optically active constituents and stronger adjacency effects due to their small size and nearby vegetation and built structures. Thus, bio-optical modeling of inland waters requires higher ground-truthing efforts. Large-scale ground-based sensor networks that are robust, self-sufficient, non-maintenance-intensive and low-cost could assist this otherwise labor-intensive task. Furthermore, most existing sensor systems are rather expensive, precluding their employability. Recently, low-cost mini-spectrometers have become widely available, which could potentially solve this issue. In this study, we analyze the characteristics of such a mini-spectrometer, the Hamamatsu C12880MA, and test it regarding its application in measuring water-leaving radiance near the surface. Overall, the measurements performed in the laboratory and in the field show that the system is very suitable for the targeted application.

Today, there is a continuous worldwide battle against antimicrobial resistance (AMR) and that includes vancomycin-resistant enterococci (VRE). Methods that can adequately and quickly detect transmission chains in outbreaks are needed to trace and manage this problem fast and cost-effectively. In this study, DNA-microarray-based technology was developed for this purpose. It commenced with the bioinformatic design of specific oligonucleotide sequences to obtain amplification primers and hybridization probes. Microarrays were manufactured using these synthesized oligonucleotides. A highly parallel and stringent labeling and hybridization protocol was developed and employed using isolated genomic DNA from previously sequenced (referenced) clinical VRE strains for optimal sensitivity and specificity. Microarray results showed the detection of virulence, resistance, and species-specific genes in the VRE strains. Theoretical predictions of the microarray results were also derived from the sequences of the same VRE strain and were compared to array results while optimizing protocols until the microarray result and theoretical predictions were a match. The study concludes that DNA microarray technology can be used to quickly, accurately, and economically detect specifically and massively parallel target genes in enterococci.

During the COVID-19 pandemic, wastewater surveillance was used to monitor community transmission of SARS-CoV-2. As new genetic variants emerged, the need for timely identification of these variants in wastewater became an important focus. In response to increased reports of Omicron transmission across the United States, the Oklahoma Wastewater Surveillance team utilized allele-specific RT-qPCR assays to detect and differentiate variants, such as Omicron, from other variants found in wastewater in Oklahoma. The PCR assays showed presence of the Omicron variant in Oklahoma on average two weeks before official reports, which was confirmed through genomic sequencing of selected wastewater samples. Through continued surveillance from November 2021 to January 2022, we also demonstrated the transition from prevalence of the Delta variant to prevalence of the Omicron variant in local communities. We further assessed how this transition correlated with certain demographic factors characterizing each community. Our results highlight RT-qPCR assays as a rapid, simple, and cost-effective method for monitoring the community spread of SARS-CoV-2 genetic variants in wastewater. Additionally, they demonstrate that specific demographic factors such as ethnic composition and household income can correlate with the timing of SARS-CoV-2 variant introduction and spread.

This study analyzes the dynamics of short-term treatment response to the first intravitreal faricimab injection in eyes with diabetic macular edema (DME). This retrospective, single-center, clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich. Patients with treatment-naïve and pretreated DME were included. Patient chart data and imaging were analyzed. Safety and efficacy (corrected visual acuity (CVA), central subfield thickness (CST), and signs of intraocular inflammation (IOI)) of the first faricimab intravitreal therapy (IVT) were evaluated weekly until 4 weeks after injection. Forty-three eyes (81% pretreated) of 31 patients were included. Four weeks after the first faricimab IVT, CVA remained stable and median CST (µm) decreased significantly (p < 0.001) from 325.0 (293.5–399.0) at baseline to 304.0 (286.5–358.0). CVA at week 4 was only associated with baseline CVA (p < 0.001). CST was the only predictive variable (p = 0.002) between baseline and week 4 CST. Weekly safety assessments did not show any sign of clinically significant IOI. This study suggests faricimab is an effective treatment for (pretreated) DME, showing structural benefit 1 month following the first injection without short-term safety signals.

Including motivational variables such as interest in the cognitive load framework is an ongoing process. Of particular interest is the question of how motivational variables influence the investment of mental effort. In this study, we investigated how topic interest affects the investment of mental effort in simple tasks. A total of 1543 students’ judgments regarding invested mental effort, perceived task difficulty, and topic interest for 32 tasks of a chemistry test were analyzed at the task level based on item response theory parameters. Additionally, objective task difficulty was calculated. The Rasch parameters were used for correlation and moderated regression analyses. The results indicated that when perceived task difficulty was low, students invested more mental effort in solving tasks of low topic interest compared to tasks of high topic interest. With increasing perceived task difficulty, the amount of invested mental effort rose for tasks of low as well as high topic interest. However, the difference between tasks of low and high topic interest in the amount of invested mental effort decreased as perceived task difficulty increased and even vanished when perceived task difficulty roughly corresponded to students’ performance capability. These results are in line with flow theory and the expectancy-value-cost model of motivation. When solving tasks that match their performance capability, students can experience a flow situation. However, when solving rather easy tasks of low interest, students can experience motivational costs in terms of additional effort, such as an increased need for motivational self-regulation. The results of this study provide a basis for systematically investigating and better understanding the relationship between interest, task difficulty, invested mental effort, flow experience, and emotional costs.

Mammary tumors are one of the most common neoplasms in female dogs, and cytology represents a non-invasive diagnostic method. The protozoal pathogen Leishmania spp. was previously demonstrated in canine mammary glands. An eight-year-old, female-spayed Doberman was imported from Crete, Greece, three years before the first presentation. The dog was presented due to a mammary tumor two years after adoption. The clinical examination revealed fever and weight loss. Smears of the mammary secretion were investigated cytologically. Multiple atypical epithelial cells with moderate to marked criteria of malignancy were detected. Furthermore, amastigotes were visible intra- and extracellularly. The diagnosis of L. infantum infection was based on a positive PCR out of the cytological smear, and a positive serology. Mammary carcinoma and granulomatous inflammation with amastigotes were confirmed by histopathology. We aimed to provide a complete report of cytological, histopathological, hematological, and biochemistry findings in a dog with L. infantum in the mammary glands with focus on trans-mammary pathogen transmission as a potential alternative way of spreading Leishmania infections. Canine leishmaniasis should be a potential differential diagnosis in dogs with lesions and/or inflammation in the mammary glands and a history of presence in areas endemic for L. infantum, especially the Mediterranean in Europe.

Myrrh has a long tradition in the treatment of inflammatory diseases. However, many of its (active) constituents are still unknown. In the present study, secondary metabolites were isolated from an ethanolic extract by various separation methods (liquid–liquid partition, silica and RP18 flash chromatography, CPC, and preparative HPLC), their structures were elucidated with NMR spectroscopy and mass spectrometry, and the selected compounds were tested for their effect on LPS-induced NO production by RAW 264.7 murine macrophages. Among the isolated substances are 17 sesquiterpenes (1–17) including the first 4,8-cycloeudesmane (1), a triterpene (38), two phytosterols (39, 40) and one lignan (43), which were previously unknown as natural products. Numerous compounds are described for the first time for the genus Commiphora. Eight of the eleven compounds tested (1, 29, 31, 32, 34–37) showed a statistically significant, concentration-dependent weak to moderate anti-inflammatory effect on NO production in the LPS-stimulated RAW 264.7 macrophages in vitro. For the reference substance, furanoeudesma-1,3-diene, an IC50 of 46.0 µM was determined. These sesquiterpenes might therefore be part of the multi-target molecular principles behind the efficacy of myrrh in inflammatory diseases.

The Nox1-centered NADPH oxidase complex facilitates the transfer of electrons from intracellular NADPH across the cell membrane to extracellular molecular oxygen, resulting in the formation of superoxide. The complex is comprised of two membrane-bound subunits, namely Nox1 and p22phox, and the cytosolic subunits, namely NoxA1 and NoxO1. The presence of NoxO1 facilitates the proximity of all components, thereby enabling the complex to exhibit constitutive activity. Despite the theoretical sufficiency of all subunits in a 1:1 ratio, the precise composition of the Nox1-centered NADPH oxidase remains unknown. Analyses of mRNA expression in different cell lines revealed an unequal expression of the components, with an excess of NoxO1. Furthermore, plasmid-based overexpression of individual components of the Nox1-centered NADPH oxidase resulted in an excess of NoxO1 mRNA. The objective of this study was to analyze the ability of NoxO1 to control the level of ROS formation by the Nox1 complex. To this end, we generated Hek293 cells for constitutive expression of Nox1 and NoxA1, which were then transfected with increasing concentrations of NoxO1. The data presented herein suggests that ROS formation by the Nox1-centered NADPH oxidase is dependent on the concentration of NoxO1. A surplus of NoxO1 has been observed to exert control over the activity of the complex in accordance with a dose-dependent mechanism. We thus conclude that the ratio of Nox1, NoxA1, and NoxO1 complexes does not adhere to a 1:1 ratio. Conversely, the availability of NoxO1 serves to regulate the formation of ROS by the Nox1-centered NADPH oxidase.

Our study investigates the impact of FGF23 overexpression on SaOS-2 cells to elucidate its role in cellular stress and morphology, contributing to the understanding of skeletal pathologies like X-linked hypophosphatemia (XLH). Using transmission electron microscopy and protein analysis (Western blot), we analyzed the rough endoplasmic reticulum (rER) and mitochondria in SaOS-2 cells with FGF23 overexpression compared to controls. We found significant morphological changes, including enlarged and elongated rER and mitochondria, with increased contact zones, suggesting enhanced interaction and adaptation to elevated protein synthesis and secretion demands. Additionally, we observed higher apoptosis rates of the cells after 24–72 h in vitro and upregulated proteins associated with ER stress and apoptosis, such as CHOP, XBP1 (spliced and unspliced), GRP94, eIF2α, and BAX. These findings indicate a robust activation of the unfolded protein response (UPR) and apoptotic pathways due to FGF23 overexpression. Our results highlight the critical role of ER and mitochondrial interactions in cellular stress responses and provide new insights into the mechanistic link between FGF23 signaling and cellular homeostasis. In conclusion, our study underscores the importance of analyzing UPR-related pathways in the development of therapeutic strategies for skeletal and systemic diseases and contributes to a broader understanding of diseases like XLH.

Background: To establish dual-energy-derived iodine density reference values in abdominopelvic organs in a large cohort of healthy subjects. Methods: 597 patients who underwent portal venous phase dual-energy CT scans of the abdomen were retrospectively enrolled. Iodine distribution maps were reconstructed, and regions of interest measurements were placed in abdominal and pelvic structures to obtain absolute iodine values. Subsequently, normalization of the abdominal aorta was conducted to obtain normalized iodine ratios. The values obtained were subsequently analyzed and differences were investigated in subgroups defined by sex, age and BMI. Results: Overall mean iodine uptake values and normalized iodine ratios ranged between 0.31 and 6.08 mg/mL and 0.06 and 1.20, respectively. Women exhibited higher absolute iodine concentration across all organs. With increasing age, normalized iodine ratios mostly tend to decrease, being most significant in the uterus, prostate, and kidneys (p < 0.015). BMI was the parameter less responsible for variations in iodine concentrations; normal weighted patients demonstrated higher values of both absolute and normalized iodine. Conclusions: Iodine concentration values and normalized iodine ratios of abdominal and pelvic organs reveal significant gender-, age-, and BMI-related differences, underscoring the necessity to integrate these variables into clinical practice.

Background/Objectives: According to the guidelines of the EndoCert initiative, certified maximum-care arthroplasty centers (ACmax) are obliged to admit patients from certified arthroplasty centers (AC) if these patients need to be transferred to the more specialized ACmax due to difficult replacement and revision procedures as well as after complications in primary care that are beyond the expertise of the smaller centers. This study investigated whether the cohort of transferred patients differed from the patients directly recruited at the ACmax for factors such as severity of diagnosis, comorbidities or outcome. The aim was to determine whether transferred patients increased the resource requirements for the ACmax. Methods: A total of 136 patients were included in the retrospective study and analyzed in terms of case severity, length of hospital stays (LOS), Diagnosis-Related Group charges, readmission rate and concomitant diseases. All patients were followed for up to 12 months after the initial hospital stay. Results: There were significant differences between the groups of transferred and self-recruited patients. For example, transferred patients had a higher Patient Clinical Complexity Level (PCCL). Similarly, the increased Case Mix Index (CMI) of transferred patients indicated more intensive care during the inpatient stay. The higher values for the comorbidity indices also supported these results. This had an impact on the LOS and overall costs, too. The differences between the groups were also reflected by adverse events during the one-year follow-up. The higher percentage of patients with septic revisions, whose treatment is especially demanding, among transferred patients aggravated the differences even further. Thus, transferred patients were associated with increased resource requirements for the ACmax. Conclusions: While it serves patients’ safety to transfer them to an ACmax with specialized expertise and greater structural quality, the care of transferred patients ties up considerable resources at the ACmax that might only be insufficiently reimbursed by the generalized tariffs.

Intervertebral disc disease (IDD) is a debilitating spine condition that can be caused by intervertebral disc (IVD) damage which progresses towards IVD degeneration and dysfunction. Recently, human pluripotent stem cells (hPSCs) were recognized as a valuable resource for cell-based regenerative medicine in skeletal diseases. Therefore, adult somatic cells reprogrammed into human induced pluripotent stem cells (hiPSCs) represent an attractive cell source for the derivation of notochordal-like cells (NCs) as a first step towards the development of a regenerative therapy for IDD. Utilizing a differentiation method involving treatment with a four-factor cocktail targeting the BMP, FGF, retinoic acid, and Wnt signaling pathways, we differentiate CRISPR/Cas9-generated mCherry-reporter knock-in hiPSCs into notochordal-like cells. Comprehensive analysis of transcriptomic changes throughout the differentiation process identified regulation of histone methylation as a pivotal driver facilitating the differentiation of hiPSCs into notochordal-like cells. We further provide evidence that specific inhibition of histone demethylases KDM2A and KDM7A/B enhanced the lineage commitment of hiPSCs towards notochordal-like cells. Our results suggest that inhibition of KDMs could be leveraged to alter the epigenetic landscape of hiPSCs to control notochord-specific gene expression. Thus, our study highlights the importance of epigenetic regulators in stem cell-based regenerative approaches for the treatment of disc degeneration.

Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities. However, acute metabolic adaptation during epileptic activity and its relationship to chronic epilepsy remains poorly understood. We elicited seizure-like events (SLEs) in an in vitro model of status epilepticus for eight hours. Electrophysiological recording and tissue oxygen partial pressure recordings were performed. After eight hours of ongoing SLEs, we used proteomics-based kinetic modeling to evaluate changes in metabolic capacities. We compared our findings regarding acute metabolic adaptation to published proteomic and transcriptomic data from chronic epilepsy patients. Epileptic tissue acutely responded to uninterrupted SLEs by upregulating ATP production capacity. This was achieved by a coordinated increase in the abundance of proteins from the respiratory chain and oxidative phosphorylation system. In contrast, chronic epileptic tissue shows a 25–40% decrease in ATP production capacity. In summary, our study reveals that epilepsy leads to dynamic metabolic changes. Acute epileptic activity boosts ATP production, while chronic epilepsy reduces it significantly.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

The fast, affordable, and standardized detection of microplastics (MP) remains one of the biggest challenges in MP research. Comparable data are essential for appropriate risk assessments and the implementation of laws and limit values. The fluorescent staining of MP in environmental samples is a possible solution to this problem. This study investigates the optimization of a sample preparation process (hydrogen peroxide digestion) and the staining process (temperature, concentration, time, surfactants as staining aids) for using a specifically developed fluorescent dye for MP detection. The optimization is performed by comparing the sample preparation process and staining of MP from different polymers and natural particles. Further, the suitability of the optimized process for the detection of fluoropolymers and tire abrasion was tested. The results show that the optimized method (increased temperature and optimized stain concentration) can detect microplastics reliably with a total sample preparation and measurement time of 2.5–3 h per sample, reaching recovery rates of 93.3% (polypropylene) to 101.7% (polyester). Moreover, two of the three tested fluoropolymers could be detected reliably. Tire abrasion could not be detected with the here presented method, as the black color leads to strong quenching. A long-term study measuring the MP pollution in the effluent of a municipal wastewater treatment plant compared the optimized and original processes and confirmed the stability of the improved method for routine measurements and contamination control.

Adolescents and young adults (AYAs) with cancer face unique challenges. We aimed to describe (i) education, employment, and financial outcomes and (ii) determinants for adverse outcomes in AYA cancer survivors. We performed a systematic literature search. We included original research articles on AYA (15–39 years of age) cancer survivors (≥2 years after diagnosis) and our outcomes of interest. We narratively synthesized the results of the included articles. We included 35 articles (24 quantitative and 11 qualitative studies). Patients in education had to interrupt their education during cancer treatment, and re-entry after treatment was challenging. After treatment, most survivors were employed but started their employment at an older age than the general population. Overall, no disadvantages in income were found. Survivors reported more absent workdays than comparisons. We identified chemotherapy, radiotherapy, late effects or health problems, female sex, migration background, and lower education associated with adverse outcomes. Although most AYA cancer survivors were able to re-enter education and employment, they reported difficulties with re-entry and delays in their employment pathway. To facilitate successful re-entry, age-tailored support services should be developed and implemented.

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment guidelines rely mostly on non-randomized retrospective studies. We performed a systematic review of studies published within the last 15 years comparing pediatric-inspired regimens (PIR) versus adult-type regimens or performing an age-stratified analysis of outcomes in the AYA population. Due to the heterogeneity of data, a meta-analysis was not possible. However, the gathered data show a trend toward improvement in outcomes and an acceptable toxicity profile in patients treated with PIRs compared to conventional adult-type regimens. There is still room for further improvement, as older patients within the AYA population tend to perform poorly with PIR or conventional adult-type chemotherapy. Further randomized studies are needed to develop an optimal treatment strategy for AYA with ALL.

Modern power engine concepts and environmental restrictions demand oil-free lubrication of rotors, for example, by gas bearings. However, the stiffness and damping properties ruling the rotor’s dynamics are poorly documented for aerodynamic bearings and simple calculation methods are lacking. Based on the similarity between aerodynamic and hydrodynamic journal bearings, it is investigated to what extent the hydrodynamic bearing element types of the commercial FE program ANSYS are also suitable for air bearings. Within these elements, the compressibility of the gas is neglected. After verification of the ANSYS hydrodynamic element types with literature data for cylindrical hydrodynamic bearings, the stiffness and damping coefficients of a cylindrical aerodynamic bearing are calculated by using the ANSYS hydrodynamic element types. In the examined speed range, the results agree well with literature data that consider gas compressibility. Therefore, the FE elements designed for hydrodynamical journal bearings may also be used for simulating cylindrical aerodynamic bearings. The presented calculation approach provides a compact and easy-to-use method for rotordynamic simulations with cylindrical aerodynamic bearings in a single development environment.

Salivary gland cancer (SGC) is a rare cancer that can present a diagnostic challenge to pathologists, with emerging, but still limited options for the treatment of recurrent/metastatic disease. We aimed to characterize the cohort of salivary gland cancers in our institute and generate a tissue microarray (TMA) with clinical data available for immunohistochemical analysis. We extracted the cases of salivary gland cancers in our institute and generated a TMA with 72 patients between 2002 and 2017 with sufficient paraffin block material. Follow-up data were present for all cases. The TMA was stained with three p53 antibodies as well as MSH2, MSH6, PMS2 and MLH1 antibodies. Additionally, we applied fragment analysis based on the Bethesda panel, and the IdyllaTM MSI test to cases with expression loss of any of the mismatch repair proteins (MMR-P) according to our immunohistochemistry (IHC). The investigated cohort shows that pT and pN stage are the only factors independently associated with survival, according to our multivariate analysis (p = 0.037 and p = 0.014). In univariate analysis, risk factors identified in our cohort were also age (p = 0.015), (lympho-) vascular invasion (p = 0.002 and p = 0.003) and risk stratification (p = 0.037). The p53 protein investigated by three antibodies showed no statistically significant association with survival or other tumor characteristics in the investigated cohort. According to MMR-P IHC, six cases of SGC showed an aberrant IHC phenotype. Additional IdyllaTM MSI test and fragment length analysis failed to confirm microsatellite instability. The pT and pN stage are the most important factors for survival in our cohort. In our cohort, antibodies directed against the protein p53 did not contribute to clinical decision-making and were not correlated with any known clinical characteristics. MSI appears to be insignificant in SGCs. Larger cohorts are needed for verification.

Rapid digitalization and the fast rise of generative AI tools pose fresh challenges to educational institutions, teachers, and students. Teachers of all subjects are expected to pass on key digital competencies along with subject-related knowledge to facilitate students’ employability and navigation in a society characterized by the impact of digital technology in all areas of life. However, several studies have shown that there is still a lack of integration of digital competencies in teacher training programs. Hence, to add to these previous studies, this paper aims to find and explore strategies and measures to equip secondary-level pre-service teachers with digital competencies and support them in professionally promoting their students’ digital skills. This happens by investigating what advanced pre-service teachers at a large European university miss and suggest changing to become more confident in promoting digital competencies at secondary school levels (K5–K12). In this context, the authors deepened a previously conducted university-wide survey among advanced secondary-level pre-service teachers through two focus groups to sharpen insights into challenges and good practices from the perspective of pre-service teachers. A thematic analysis of these focus groups confirmed the presumption that most pre-service teachers are keen on actively acquiring relevant digital competencies and gave insights into how they wish to have digital skills integrated into their studies. Additionally, it became evident that even though pre-service teachers can acquire several digital skills through self-study, they longed for collaboration and guidance to reach a professional level for “teaching” them to their students.

While the analysis of gait and balance can be an important indicator of age- or disease-related changes, it remains unclear if repeated performance of gait and balance tests in healthy adults leads to habituation effects, if short-term gait and balance training can improve gait and balance performance, and whether the placement of wearable sensors influences the measurement accuracy. Healthy adults were assessed before and after performing weekly gait and balance tests over three weeks by using a force plate, motion capturing system and smartphone. The intervention group (n = 25) additionally received a home-based gait and balance training plan. Another sample of healthy adults (n = 32) was assessed once to analyze the impact of sensor placement (lower back vs. lower abdomen) on gait and balance analysis. Both the control and intervention group exhibited improvements in gait/stance. However, the trends over time were similar for both groups, suggesting that targeted training and repeated task performance equally contributed to the improvement of the measured variables. Since no significant differences were found in sensor placement, we suggest that a smartphone used as a wearable sensor could be worn both on the lower abdomen and the lower back in gait and balance analyses.

Infections with Anaplasma (A.) phagocytophilum in cats seem to be rare. The study aimed to determine whether infections in cats are underestimated and to identify the risk factors for infection. Blood samples of 1015 cats across Europe (2017–2022), sent to IDEXX Laboratories, Germany, were tested for A. phagocytophilum DNA. The influence of the cats’ origin on A. phagocytophilum infection was assessed by univariable analysis, while multivariable logistic regression evaluated associations with the cats’ sex and age, and the years, and seasonality of the samples’ submission. Furthermore, univariable linear regression was used to determine patterns in PCR orders. The number of submitted samples increased significantly during the 6 years (p = 0.042). Anaplasma phagocytophilum DNA was detected in 76/1015 of cats (7.5%, 95% CI 6.0–9.3%). Infections were significantly more common in Northern compared to Central (p < 0.001, OR: 8.70) and Southern Europe (p < 0.001, OR: 39.94). A significantly higher likelihood for infections during the summer compared with winter (p = 0.047, OR: 3.13) was found. Bacteremia with A. phagocytophilum in European cats is not uncommon. Anaplasma phagocytophilum infection should be considered an important risk, particularly in Northern Europe. Effective tick prevention is crucial for managing feline health across Europe, not just in the Mediterranean region.

Reducing side effects in non-cancerous tissue is a key aim of modern radiotherapy. Here, we assessed whether the use of the antioxidants hydroxytyrosol (HT) and thioredoxin-mimetic peptide CB3 (TMP) attenuated radiation-induced normal tissue toxicity in vitro. We used primary human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (HaCaT) as normal tissue models. Cells were treated with HT and TMP 24 h or immediately prior to irradiation. Reactive oxygen species (ROS) were assessed via luminescent- and fluorescence-based assays, migration was investigated using digital holographic microscopy, and clonogenic survival was quantified by colony formation assays. Angiogenesis and wound healing were evaluated via time-dependent microscopy. Secreted cytokines were validated in quantitative polymerase chain reaction (qPCR) studies. Treatment with HT or TMP was well tolerated by cells. The application of either antioxidant before irradiation resulted in reduced ROS formation and a distinct decrease in cytokines compared to similarly irradiated, but otherwise untreated, controls. Antioxidant treatment also increased post-radiogenic migration and angiogenesis while accelerating wound healing. HT or TMP treatment immediately before radiotherapy increased clonogenic survival after radiotherapy, while treatment 24 h before radiotherapy enhanced baseline proliferation. Both antioxidants may decrease radiation-induced normal tissue toxicity and deserve further pre-clinical investigation.

Experimental animal studies of hypoxic–ischemic injury of the hippocampus of pigs are limited due to the unprecise definition of hippocampal subfields, cornu ammonis 1 to 4, compared to humans. Given that the pig model closely mirrors human physiology and serves as an important model for critical care research, a more precise description is necessary to draw valid conclusions applicable to human diseases. In our study, we were able to precisely define the CA2 and its adjacent regions in a domestic pig model by arginine vasopressin receptor 1B (AVPR1B) and calbindin-D28K like (CaBP-Li) expression patterns. Our findings demonstrate that the histoarchitecture of the porcine cornu ammonis subfields closely resembles that of the human hippocampus. Notably, we identified unusually strong neuronal damage in regions of the pig hippocampus following global ischemia, which are typically not susceptible to hypoxic–ischemic damage in humans.

Chaga mushroom (Inonotus obliquus) is a pathogenic fungus that grows mostly on birch species (Betula pendula Roth and B. pubescens Ehrh.) and has traditionally been used as an anticancer medicine. This study aimed to compare the chemical composition and cytotoxic activity of chagas growing on both Betula spp. on various cancer cell lines. The freeze-dried extracts contained triterpenes inotodiol, lanosterol betulin, and betulinic acid typical to conks growing on Betula species. The cytotoxic activity of chaga growing on Betula pendula and B. pubescens 80% ethanolic extracts against 31 human cancer cell lines was evaluated by a sulforhodamine B assay. Chaga extract showed moderate activity against all cancer cell lines examined; it did not result in high cytotoxicity (IC50 ≤ 20 µg/mL). The strongest inhibitions were observed with chaga (growing on B. pendula) extract on the HepG2 and CAL-62 cell line and with chaga (from B. pubescens) extract on the HepG2 cell line, with IC50 values of 37.71, 43.30, and 49.99 μg/mL, respectively. The chaga extracts from B. pendula exert somewhat stronger effects on most cancer cell lines studied than B. pubescens extracts, which can be attributed to a higher content of inotodiol in B. pendula extracts. This study highlights the potential of chaga as a source of bioactive compounds with selective anticancer properties. To the best of our knowledge, this study is the first investigation of the chemical composition of I. obliquus parasitizing on B. pubescens.

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O’nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8–9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout.

Accessibility is commonly defined and operationalised through objective measurements, such as travel time and physical distance to destinations; however, there is a lack of empirical studies capturing perceived accessibility from individual perspectives. With the aim of sustainable transport for inclusive communities, it is crucial to investigate the impact of socio-economy and travel mode on perceived accessibility and key driving factors of perceived safety and service quality. Through the collection of primary data from one of the fastest-growing suburbs in Melbourne, this study examined variation of perceptions towards accessibility, safety, and service quality among diverse social groups and travellers using different modes of transport. The findings of this study would assist transport planners in making informed decisions in creating inclusive transport networks that can improve community health and well-being.

Obesity is an emerging public health problem. Chronic low-grade inflammation is considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, and several cancer entities. Most preliminary studies on obesity-induced immune responses have been conducted in male rodents. Sex-specific differences between men and women in obesity-induced immune dysregulation have not yet been fully outlined but are highly relevant to optimizing prevention strategies for overweight-associated complications. In this study, we fed C57BL/6 female vs. male mice with either standard chow or an obesity-inducing diet (OD). Blood and spleen immune cells were isolated and analyzed by flow cytometry. Lean control mice showed no sex bias in systemic and splenic immune cell composition, whereas the immune responses to obesity were significantly distinct between female and male mice. While immune cell alterations in male OD mice were characterized by a significant reduction in T cells and an increase in myeloid-derived suppressor cells (MDSC), female OD mice displayed preserved T cell numbers. The sex-dependent differences in obesity-induced T cell dysregulation were associated with varying susceptibility to body weight gain and fatty liver disease: Male mice showed significantly more hepatic inflammation and histopathological stigmata of fatty liver in comparison to female OD mice. Our findings indicate that sex impacts susceptibility to obesity-induced T cell dysregulation, which might explain sex-dependent different incidences in the development of obesity-associated secondary diseases. These results provide novel insights into the understanding of obesity-induced chronic inflammation from a sex-specific perspective. Given that most nutrition, exercise, and therapeutic recommendations for the prevention of obesity-associated comorbidities do not differentiate between men and women, the data of this study are clinically relevant and should be taken into consideration in future trials and treatment strategies.

Cellulose microspheres have a wide range of applications due to their unique properties and versatility. Various preparation methods have been explored to tailor these microspheres for specific applications. Among these methods, the acetate method using cellulose acetate is well known. However, replacement of the acetate group through the butyrate group significantly extends the variety of morphological properties. In the present work, microspheres based on cellulose acetate butyrate are being developed with modified characteristics in terms of particle size, porosity, surface morphology and the inner structure of the microspheres. While the inner structure of cellulose acetate microspheres is predominantly porous, microspheres prepared from cellulose acetate butyrate are mainly filled or contain several smaller microspheres. Carbon materials from cellulose acetate butyrate microspheres exhibit a high specific surface area of 567 m2 g−1, even without further activation. Activation processes can further increase the specific surface area, accompanied by an adaptation of the pore structure. The prepared carbons show promising results in symmetrical supercapacitors with aqueous 6 M KOH electrolytes. Activated carbons derived from cellulose acetate butyrate microspheres demonstrate an energy density of 12 Wh kg−1 at a power density of 0.9 kW kg−1.

Tunable laser spectroscopy (TLS) with infrared (IR) imaging is a powerful tool for gas leak detection. This study focuses on direct absorption spectroscopy (DAS) that utilizes wavelength modulation to extract gas information. A tunable interband cascade laser (ICL) with an optical power of 5 mW is periodically modulated by a sawtooth injection current at 10 Hz across the methane absorption around 3271 nm. A fast and sensitive thermal imaging camera for the mid-infrared range between 3 and 5.7 µm is operated at a frame rate of 470 Hz. Offline processing of image stacks is performed using different algorithms (DAS-F, DAS-f and DAS-2f) based on the Lambert–Beer law and the HITRAN database. These algorithms analyze various features of gas absorption, such as area (F), peak (f) and second derivative (2f) of the absorbance. The methane concentration in ppm*m is determined on a pixel-by-pixel analysis without calibration. Leak localization for methane leak rates as low as 0.25 mL/min is accurately displayed in a single concentration image with pixelwise sensitivities of approximately 1 ppm*m in a laboratory environment. Concentration image sequences represent the spatiotemporal dynamics of a gas plume with high contrast. The DAS-2f concept demonstrates promising characteristics, including accuracy, precision, 1/f noise rejection, simplicity and computational efficiency, expanding the applications of DAS.

Emotion dysregulation has long been considered a key symptom in multiple psychiatric disorders. Difficulties in emotion regulation have been associated with neural dysregulation in fronto-limbic circuits. Real-time fMRI-based neurofeedback (rt-fMRI-NFB) has become increasingly popular as a potential treatment for emotional dysregulation in psychiatric disorders, as it is able to directly target the impaired neural circuits. However, the clinical impact of these rt-fMRI-NFB protocols in psychiatric populations is still largely unknown. Here we provide a comprehensive overview of primary studies from 2010 to 2023 that used rt-fMRI-NFB to target emotion regulation. We assessed 41 out of 4001 original studies for methodological quality and risk of bias and synthesised concerning the frequency of significant rt-fMRI-NFB-related effects on the neural and behaviour level. Successful modulation of brain activity was reported in between 25 and 50 percent of study samples, while neural effects in clinical samples were more diverse than in healthy samples. Interestingly, the frequency of rt-fMRI-NFB-related behavioural improvement was over 75 percent in clinical samples, while healthy samples showed behavioural improvements between 0 and 25 percent. Concerning clinical subsamples, rt-fMRI-NFB-related behavioural improvement was observed in up to 100 percent of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) samples. Substance use samples showed behavioural benefits ranging between 50 and 75 percent. Neural effects appeared to be less frequent than behavioural improvements: most neural outcomes ranged between 25 and 50 percent for MDD and substance use and between 0 and 25 percent for PTSD. Using multiple individualised regions of interest (ROIs) for rt-fMRI-NFB training resulted in more frequent behavioural benefits than rt-fMRI-NFB solely based on the amygdala or the prefrontal cortex. While a significant improvement in behavioural outcomes was reported in most clinical studies, the study protocols were heterogeneous, which limits the current evaluation of rt-fMRI-NFB as a putative treatment for emotional dysregulation.

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors—major drivers of mucositis development—could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients. Methods: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. Results: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). Conclusions: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression.