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Crystal growth of 2-(3,4,5-triphenylphenyl)acetic acid (1) from acetonitrile yields a monosolvate, C26H20O2·CH3CN, of the space group P1. In the crystal, the title molecule adopts a conformation in which the three phenyl rings are arranged in a paddlewheel-like fashion around the central arene ring and the carboxyl residue is oriented nearly perpendicular to the plane of this benzene ring. Inversion-symmetric dimers of O—H...O-bonded molecules of 1 represent the basic supramolecular entities of the crystal structure. These dimeric molecular units are further linked by C—H...O=C bonds to form one-dimensional supramolecular aggregates running along the crystallographic [111] direction. Weak Caryl—H...N interactions occur between the molecules of 1 and acetonitrile.

BackgroundPegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven noncirrhotic NASH are not well established.MethodsIn this phase 2b, multicenter, double-blind, 24-week, randomized, placebo-controlled trial, we randomly assigned patients with biopsy-confirmed NASH and stage F2 or F3 (moderate or severe) fibrosis to receive subcutaneous pegozafermin at a dose of 15 mg or 30 mg weekly or 44 mg once every 2 weeks or placebo weekly or every 2 weeks. The two primary end points were an improvement in fibrosis (defined as reduction by ≥1 stage, on a scale from 0 to 4, with higher stages indicating greater severity), with no worsening of NASH, at 24 weeks and NASH resolution without worsening of fibrosis at 24 weeks. Safety was also assessed.ResultsAmong the 222 patients who underwent randomization, 219 received pegozafermin or placebo. The percentage of patients who met the criteria for fibrosis improvement was 7% in the pooled placebo group, 22% in the 15-mg pegozafermin group (difference vs. placebo, 14 percentage points; 95% confidence interval [CI], -9 to 38), 26% in the 30-mg pegozafermin group (difference, 19 percentage points; 95% CI, 5 to 32; P = 0.009), and 27% in the 44-mg pegozafermin group (difference, 20 percentage points; 95% CI, 5 to 35; P = 0.008). The percentage of patients who met the criteria for NASH resolution was 2% in the placebo group, 37% in the 15-mg pegozafermin group (difference vs. placebo, 35 percentage points; 95% CI, 10 to 59), 23% in the 30-mg pegozafermin group (difference, 21 percentage points; 95% CI, 9 to 33), and 26% in the 44-mg pegozafermin group (difference, 24 percentage points; 95% CI, 10 to 37). The most common adverse events associated with pegozafermin therapy were nausea and diarrhea.ConclusionsIn this phase 2b trial, treatment with pegozafermin led to improvements in fibrosis. These results support the advancement of pegozafermin into phase 3 development. (Funded by 89bio; ENLIVEN ClinicalTrials.gov number, NCT04929483.).

This article explores the micro dimension within the field of intercultural family studies. The ethnographic study focuses on Chinese elements in transcultural upbringing practices within families with Chinese mothers and German fathers raising their children in Germany. It builds on the notion of family figuration practice in transnational grandparents-grandchildren relations, particularly Confucian-based transnational grandparenting, and the development of a ‘third space’ for transcultural family upbringing within intercultural families. Additionally, it incorporates the concepts of discourse perspective of culture and assemblage to explore how Chinese culture and identity converge in a transcultural family upbringing context. The findings show that families have varied experiences with transnational intergenerational communication influenced by their life stage, language abilities, and socio-economic factors.

Robin Schmidt,1,2 Charlie Alexander Hamm,1,3 Christopher Rueger,1 Han Xu,1 Yubei He,1,2 Luzie Alexandra Gottwald,4 Bernhard Gebauer,1 Lynn Jeanette Savic1– 3 1Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiology, Berlin, 13353, Germany; 2Experimental Clinical Research Center (ECRC) at Charité - Universitätsmedizin Berlin and Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, 13125, Germany; 3Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, 10117, Germany; 4Vivantes Humboldt-Klinikum, Berlin, 13509, GermanyCorrespondence: Lynn Jeanette Savic, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Radiologie, Augustenburger Platz 1, Berlin, D-13353, Germany, Email lynn-jeanette.savic@charite.dePurpose: Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE).Patients and Methods: Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher’s exact and t-test, Kaplan–Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson’s correlation.Results: OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed.Conclusion: The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.Keywords: cancer imaging, hepatocellular carcinoma, microvascular invasion, magnetic resonance tomography, predictive imaging biomarkers

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, μCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with rhBMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

Florida citrus production from 1980-2021 was examined and modeled to determine the impacts associated with weather events and disease introductions.  Specifically, the study examined the effects of North Atlantic hurricanes, freezes events and two disease introductions -- Asiatic citrus canker (ACC), and Huanglongbing (HLB) -- on productions levels and on the structure of the Florida citrus industry.  The models estimated quantified the effects on production associated with the weather events and disease introductions.  Using the deterministic model generated, forecasts were generated to identify future implications of HLB on Florida citrus production.  Theses generated forecasts were compared to actual production levels and the USDA Crop forecast to test and validate the model.  Whereas testing indicated a significant structural change in the Florida citrus industry resulting from adverse weather events and disease introductions, published economic impact studies were examined and reviewed to gage the resulting reduction in total economic impact.

Growers rely on broad-spectrum agrochemicals to manage one of the most economically important fruit tree diseases, huanglongbing (HLB, citrus greening disease), presumptively caused by the gram-negative bacterium ‘Candidatus Liberibacter asiaticus’ (CLas). Although genetic resistance would be an attractive alternative to chemical management, this option is not yet available for HLB. Here, we tested whether a single chain variable fragment (scFv) antibody targeting the predicted CLas outer membrane transporter NodT can inhibit CLas growth or HLB disease development when expressed in ‘Duncan’ grapefruit (Citrus × paradisi). CLas NodT is similar to TolC and could be involved in Type I secretion and virulence. The scFv antibody was expressed in grapefruit trees as a C-terminal translational fusion to the Flowering Locus T protein of Poncirus trifoliata (FT-scFv) to promote expression in the phloem. Wild-type and FT-scFv-expressing transgenic lines were challenged with CLas using three inoculation approaches: psyllid-mediated inoculation, vegetative graft inoculation, and natural exposure in grove-like conditions. With the first two approaches, HLB symptom expression and CLas bacterial titers in FT-scFv grapefruit lines were not significantly different from wild-type controls. In the grove trial, one FT-scFv line exhibited a slight, but significant, reduction in canopy chlorosis compared to wild-type controls. Wild-type and FT-scFv lines were similar in all other metrics. We conclude that the expression of anti-NodT FT-scFv antibody in grapefruit did not decrease HLB susceptibility. Although our approach was unsuccessful, we hope that documenting our results will be useful for those seeking to develop HLB-resistant citrus germplasm in the future. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Accurately monitoring the extent of freezing in biological tissue is an important requirement for cryoablation, a minimally invasive cancer treatment that induces cell death by freezing tissue with a cryoprobe. During the procedure, monitoring is required to avoid unnecessary harm to the surrounding healthy tissue and to ensure the tumor is properly encapsulated. One commonly used monitoring method is attenuation-based computed tomography (CT), which visualizes the ice ball by utilizing its hypoattenuating properties compared to unfrozen tissue. However, the contrast between frozen and unfrozen tissue remains low. In a proof-of-principle experiment, we show that the contrast between frozen and unfrozen parts of a porcine phantom mimicking breast tissue can be greatly enhanced by acquiring X-ray dark-field images that capture the increasing small-angle scattering caused by the ice crystals formed during the procedure. Our results show that, compared to X-ray attenuation, the frozen region is detected significantly better in dark-field radiographs and CT scans of the phantom. These findings demonstrate that X-ray dark-field imaging could be a potential candidate for improved monitoring of cryoablation procedures.

This paper brings together two very topical and important themes. The first is the issue of the environmental footprint of transport consumption and the second is the current educational challenges of Generation Z representatives. The paper focuses on a combination of both topics, respectively addressing the education of Generation Z on the topic of the environmental footprint of transport consumption. The paper is prepared using a primary representative survey method based on an online questionnaire survey of representatives of Generation Z (secondary school students in the Czech Republic). The aim of the paper is to identify the educational challenges of the generation Z (studying at secondary schools in the Czech Republic) in the thematic area of the environmental footprint of transport consumption. The results clearly show the necessity of using audio-visual educational content and linking theory and practice, for example in the form of case studies. Generation Z wants quick, concise, up-to-date, interesting, and interactive information. Generation Z representatives clearly confirm the need to address human environmental impacts in education, adding that not enough time is devoted to them. They also confirm that there is a lack of study materials in this subject area and that they are not developed in a user-friendly way. Representatives of Generation Z are interested in further education on the environmental footprint of transport consumption. The findings of this paper can help both secondary school teachers, as well as school and curriculum developers and educational policy and strategy makers.

Abstract In response to the pressing challenges of the ongoing biodiversity crisis, the protection of endangered species and their habitats, as well as the monitoring of invasive species are crucial. Habitat suitability modeling (HSM) is often treated as the silver bullet to address these challenges, commonly relying on generic variables sourced from widely available datasets. However, for species with high habitat requirements, or for modeling the suitability of habitats within the geographic range of a species, variables at a coarse level of detail may fall short. Consequently, there is potential value in considering the incorporation of more targeted data, which may extend beyond readily available land cover and climate datasets. In this study, we investigate the impact of incorporating targeted land cover variables (specifically tree species composition) and vertical structure information (derived from LiDAR data) on HSM outcomes for three forest specialist bat species (Barbastella barbastellus, Myotis bechsteinii, and Plecotus auritus) in Rhineland‐Palatinate, Germany, compared to commonly utilized environmental variables, such as generic land‐cover classifications (e.g., Corine Land Cover) and climate variables (e.g., Bioclim). The integration of targeted variables enhanced the performance of habitat suitability models for all three bat species. Furthermore, our results showed a high difference in the distribution maps that resulted from using different levels of detail in environmental variables. This underscores the importance of making the effort to generate the appropriate variables, rather than simply relying on commonly used ones, and the necessity of exercising caution when using habitat models as a tool to inform conservation strategies and spatial planning efforts.

Abstract Background Prediabetes management is a priority for policymakers globally, to avoid/delay type 2 diabetes (T2D) and reduce severe, costly health consequences. Countries moving from low to middle income are most at risk from the T2D “epidemic” and may find implementing preventative measures challenging; yet prevention has largely been evaluated in developed countries. Methods Markov cohort simulations explored costs and benefits of various prediabetes management approaches, expressed as “savings” to the public health care system, for three countries with high prediabetes prevalence and contrasting economic status (Poland, Saudi Arabia, Vietnam). Two scenarios were compared up to 15 y: “inaction” (no prediabetes intervention) and “intervention” with metformin extended release (ER), intensive lifestyle change (ILC), ILC with metformin (ER), or ILC with metformin (ER) “titration.” Results T2D was the highest‐cost health state at all time horizons due to resource use, and inaction produced the highest T2D costs, ranging from 9% to 34% of total health care resource costs. All interventions reduced T2D versus inaction, the most effective being ILC + metformin (ER) “titration” (39% reduction at 5 y). Metformin (ER) was the only strategy that produced net saving across the time horizon; however, relative total health care system costs of other interventions vs inaction declined over time up to 15 y. Viet Nam was most sensitive to cost and parameter changes via a one‐way sensitivity analysis. Conclusions Metformin (ER) and lifestyle interventions for prediabetes offer promise for reducing T2D incidence. Metformin (ER) could reduce T2D patient numbers and health care costs, given concerns regarding adherence in the context of funding/reimbursement challenges for lifestyle interventions.

The pharmaceutical medicine course at the Semmelweis University of Budapest, Hungary, was initiated as part of the Innovative Medicines Initiative (IMI is the main program, IMI-PharmaTrain is one of the IMI projects) Pharmaceutical Medicine Training Programs (16 IMI Call 2008/1/16). The aim was to extend training in the development of pharmaceutical medicine to those EU member states where no such education was present. The final program envisaged the development of a cooperative education supported by universities located in Central and Eastern Europe. It was considered to be the economically and scientifically most viable approach to combine the expertise from these countries to form a united teaching staff and provide education jointly for young professionals of the region. Semmelweis University was selected to manage this coordinated program. In this report, we describe the organization and functioning of this international university-based pharmaceutical medicine education project called the Cooperative European Medicines Development Course (CEMDC) and evaluate its successes and shortcomings. During the pandemic, the educational course was interrupted. The follow-on program is reorganized as a postgraduate MSc course named “Semmelweis Pharma MBA” and will be started in 2025. It will continue the established PharmaTrain educational tradition. However, it will deal in more detail with the transition from basic pharmacological to industrial research, as well as biopharmaceutical formulation and manufacturing and marketing aspects of medicines development.

Job satisfaction is a highly relevant topic across all sectors of the national economy worldwide. A contented employee significantly enhances a company’s performance compared to a dissatisfied one. Simultaneously, a contented employee increases the human capital value of the company, which has a substantial impact on its overall value. However, employee satisfaction is not a static state; it can be influenced by various factors, one of which is perceived workload resulting from the nature of the job. The aim of this article is to investigate whether there is a demonstrable impact of perceived workload on employee satisfaction. This relationship is examined within the context of subway train drivers in the Czech Republic. In exploring this relationship, we also delve into the psychological factor of whether there is a connection between perceived workload and the satisfaction of subway train drivers based on their personality types according to the MBTI test. These dependencies are assessed through correlation analysis using a comprehensive dataset obtained. In the course of the research, data were collected from the entire basic sample of respondents, namely from 654 subway train drivers. The results confirmed the existing influence of perceived workload on employee satisfaction and, concurrently, the influence of perceived workload on employee satisfaction based on the personality typology determined by the MBTI test. These findings are undoubtedly beneficial for the management of transportation companies, particularly those involved in passenger transportation, specifically in the provision of subway services.

For millennia humans have benefitted from application of the acute canine sense of smell to hunt, track and find targets of importance. In this report, canines were evaluated for their ability to detect the severe exotic phytobacterial arboreal pathogen Xanthomonas citri pv. citri (Xcc), which is the causal agent of Asiatic citrus canker (Acc). Since Xcc causes only local lesions, infections are non-systemic, limiting the use of serological and molecular diagnostic tools for field-level detection. This necessitates reliance on human visual surveys for Acc symptoms, which is highly inefficient at low disease incidence, and thus for early detection. In simulated orchards the overall combined performance metrics for a pair of canines were 0.9856, 0.9974, 0.9257 and 0.9970, for sensitivity, specificity, precision, and accuracy, respectively, with 1-2 s/tree detection time. Detection of trace Xcc infections on commercial packinghouse fruit resulted in 0.7313, 0.9947, 0.8750, and 0.9821 for the same performance metrics across a range of cartons with 0-10% Xcc-infected fruit despite the noisy, hot and potentially distracting environment. In orchards, the sensitivity of canines increased with lesion incidence, whereas the specificity and overall accuracy was >0.99 across all incidence levels; i.e., false positive rates were uniformly low. Canines also alerted to a range of 1-12-week-old infections with equal accuracy. When trained to either Xcc-infected trees or Xcc axenic cultures, canines inherently detected the homologous and heterologous targets, suggesting they can detect Xcc directly rather than only volatiles produced by the host following infection. Canines were able to detect the Xcc scent signature at very low concentrations (10,000× less than 1 bacterial cell per sample), which implies that the scent signature is composed of bacterial cell volatile organic compound constituents or exudates that occur at concentrations many fold that of the bacterial cells. The results imply that canines can be trained as viable early detectors of Xcc and deployed across citrus orchards, packinghouses, and nurseries.

Several studies have previously investigated the effects of sticky mittens training on reaching and grasping development. However, recent critique casted doubts on the robustness of the motor effect of this training. The current study presents a pre-registered report that aimed to generalize these effects to Swedish infants. Three-month-old infants N = 96, 51 females, mostly White middle class in Uppsala, received daily, parent-led sticky mittens or observational training for 2 weeks or no training in 2019. Reaching and grasping abilities were assessed before and after training, using motion tracking and a 4-step reaching task. Sticky mittens training did not facilitate successful reaching. These results indicate that beneficial motor effects of sticky mittens training did not generalize to this sample.

Abstract The most basic behavioural states of animals can be described as active or passive. While high‐resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which a combination of automatic radiotracking and machine learning is used to distinguish between active and passive behaviour in small vertebrates fitted with lightweight transmitters (3 million signals from very‐high‐frequency (VHF) telemetry from two forest‐dwelling bat species (Myotis bechsteinii [n = 52] and Nyctalus leisleri [n = 20]) to train and test a random forest model in assigning either active or passive behaviour to VHF‐tagged individuals. The generalisability of the model was demonstrated by recording and classifying the behaviour of tagged birds and by simulating the effect of different activity levels with the help of humans carrying transmitters. The model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F1 0.96–0.98). We provide an ecological case‐study demonstrating the potential of this automated monitoring tool. We used the trained models to compare differences in the daily activity patterns of two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night‐time activity of M. bechsteinii was relatively constant. These results show that subtle differences in the timing of species' activity can be distinguished using our method. Our approach can classify VHF‐signal patterns into fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radiotracking method, we provide the trained random forest models together with an R package that includes all necessary data processing functionalities. In combination with state‐of‐the‐art open‐source automated radiotracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.

Particulate matter (PM) largely consists of secondary organic aerosol (SOA) that is formed via oxidation of biogenic and anthropogenic volatile organic compounds (VOCs). Unambiguous identification of SOA molecules and their assignment to their precursor vapors are challenges that have so far only succeeded for a few SOA marker compounds, which are now well characterized and (partly) available as authentic standards. In this work, we resolve the complex composition of SOA by means of a top-down approach based on the newly created Aerosolomics database, which is fed by non-target analysis results of filter samples from oxidation flow reactor experiments. We investigated the oxidation products from the five biogenic VOCs α-pinene, β-pinene, limonene, 3-carene, and trans-caryophyllene and from the four anthropogenic VOCs toluene, o-xylene, 1,2,4-trimethylbenzene, and naphthalene. Using ultrahigh-performance liquid chromatography coupled to a high-resolution (Orbitrap) mass spectrometer, we determine the molecular formula of 596 chromatographically separated compounds based on exact mass and isotopic pattern. We utilize retention time and fragmentation mass spectra as a basis for unambiguous attribution of the oxidation products to their parent VOCs. Based on the molecular-resolved application of the database, we are able to assign roughly half of the total signal of oxygenated hydrocarbons in ambient suburban PM2.5 to one of the nine studied VOCs. The application of the database enabled us to interpret the appearance of diurnal compound clusters that are formed by different oxidation processes. Furthermore, by performing a hierarchical cluster analysis (HCA) on the same set of filter samples, we identified compound clusters that depend on sulfur dioxide mixing ratio and temperature. This study demonstrates how Aerosolomics tools (database and HCA) applied to PM filter samples can improve our understanding of SOA sources, their formation pathways, and temperature-driven partitioning of SOA compounds.

Abstract Knowledge of one’s own body size is a crucial facet of body representation, both for acting on the environment and perhaps also for constraining body ownership. However, representations of body size may be somewhat plastic, particularly to allow for physical growth in childhood. Here we report a developmental investigation into the role of hand size in body representation (the sense of body ownership, perception of hand position, and perception of own-hand size). Using the rubber hand illusion paradigm, this study used different fake hand sizes (60%, 80%, 100%, 120% or 140% of typical size) in three age groups (6- to 7-year-olds, 12- to 13-year-olds, and adults; N = 229). We found no evidence that hand size constrains ownership or position: participants embodied hands which were both larger and smaller than their own, and indeed judged their own hands to have changed size following the illusion. Children and adolescents embodied the fake hands more than adults, with a greater tendency to feel their own hand had changed size. Adolescents were particularly sensitive to multisensory information. In sum, we found substantial plasticity in the representation of own-body size, with partial support for the hypothesis that children have looser representations than adults.

After the development of 3D cell culture methods in the middle of the last century and the plethora of data generated with this culture configuration up to date, it could be shown that a three-dimensional arrangement of cells in most of the cases leads to a more physiological behavior of the generated tissue. However, a major determinant for an organotypic function, namely, the dissolved oxygen concentration in the used in vitro-system, has been neglected in most of the studies. This is due to the fact that the oxygen measurement in the beginning was simply not feasible and, if so, disturbed the measurement and/or the in vitro-system itself. This is especially true for the meanwhile more widespread use of 3D culture systems. Therefore, the tissues analyzed by these techniques can be considered as the Schrödinger’s cat in 3D cell biology. In this perspective paper we will outline how the measurement and, moreover, the regulation of the dissolved oxygen concentration in vitro-3D culture systems could be established at all and how it may be possible to determine the oxygen concentration in organoid cultures and the respiratory capacity via mito stress tests, especially in spheroids in the size range of a few hundred micrometers, under physiological culture conditions, without disturbances or stress induction in the system and in a high-throughput fashion. By this, such systems will help to more efficiently translate tissue engineering approaches into new in vitro-platforms for fundamental and applied research as well as preclinical safety testing and clinical applications.

Abstract Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1‐13C]pyruvate based on parahydrogen‐induced polarization by side‐arm hydrogenation (PHIP‐SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d‐DNP) device. Purified, concentrated (≈70–160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate‐to‐pyruvate ratios, are equivalent for PHIP and d‐DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

Abstract Conventional practices in species distribution modeling lack predictive power when the spatial structure of data is not taken into account. However, choosing a modeling approach that accounts for overfitting during model training can improve predictive performance on spatially separated test data, leading to more reliable models. This study introduces spatialMaxent (https://github.com/envima/spatialMaxent), a software that combines state‐of‐the‐art spatial modeling techniques with the popular species distribution modeling software Maxent. It includes forward‐variable‐selection, forward‐feature‐selection, and regularization‐multiplier tuning based on spatial cross‐validation, which enables addressing overfitting during model training by considering the impact of spatial dependency in the training data. We assessed the performance of spatialMaxent using the National Center for Ecological Analysis and Synthesis dataset, which contains over 200 anonymized species across six regions worldwide. Our results show that spatialMaxent outperforms both conventional Maxent and models optimized according to literature recommendations without using a spatial tuning strategy in 80 percent of the cases. spatialMaxent is user‐friendly and easily accessible to researchers, government authorities, and conservation practitioners. Therefore, it has the potential to play an important role in addressing pressing challenges of biodiversity conservation.

Personnel evaluation and selection is an essential part of modern business. Appropriate candidate selection can significantly contribute to companies in terms of increased profit, good culture, reputation, reduced costs, etc. This paper addresses the personnel evaluation and selection problem at the University of Pardubice, Faculty of Transport Engineering (UPCE). Since this is a typical ranking alternative problem where multiple criteria affect the decision, the Z-numbers-based Alternative Ranking Order Method Accounting for the two-step Normalization (AROMAN) is applied. Four Ph.D. candidates are assessed, and the most appropriate is selected to be employed by the UPCE. The Z-numbers fuzzy AROMAN method ranks Ph.D. candidate number four as the most appropriate alternative. To investigate the stability and sensitivity of the Z-numbers fuzzy AROMAN method, the values of parameters β and λ used in the mathematical calculations of the method were changed. The results of sensitivity analysis revealed that the obtained solution is stable. To confirm the robustness of the proposed approach, a comparative analysis is performed. Simple Additive Weighting (SAW), Weighted Product Model (WPM), and Z-number fuzzy TOPSIS were applied. Besides, we applied the fuzzy inferior ratio method as well. The results confirm the high robustness of the proposed Z-numbers fuzzy AROMAN method.