External post-mortem examination in virtual reality-scalability of a monocentric application.

Conducting external post-mortem examinations is an essential skill required of physicians in various countries, regardless of their specialization. However, the quality of these examinations has been a subject of continuous debates, and notable errors were reviled. In response to these shortcomings, a virtual reality (VR) application was developed at Halle's medical department in Germany, focusing on the scene of discovery and the completion of death certificates. The initial trial of this VR application in 2020 involved 39 students and 15 early-career professionals. Based on the feedback, the application underwent improvements and was subsequently introduced to the medical department in Dresden, Germany, in 2022. Its primary objective was to showcase the VR training's adaptability and scalability across various educational structures and levels of medical expertise. Out of 73 students who participated, 63 completed the evaluation process. 93.1% (n = 58) of the evaluators reported increased confidence in conducting external post-mortem examinations, and 96.8% (n = 61) felt more assured in filling out death certificates, crediting this progress to the VR training. Additionally, 98.4% (n = 62) believed that repeating forensic medical aspects in their coursework was crucial, and 96.8% (n = 61) viewed the VR examination as a valuable addition to their academic program. Despite these positive responses, 91.6% (n = 55) of participants maintained that training with real corpses remains irreplaceable due to the insufficiency of haptic feedback in VR. Nevertheless, the potential for enhancing the VR content and expanding the training to additional locations or related disciplines warrants further exploration.

CoNIC Challenge: Pushing the frontiers of nuclear detection, segmentation, classification and counting.

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

Effect of a One-Time Communication Training Session on Dental Students' Self-Efficacy Expectancy.

An implementation of training units that provide evidence for improving students' communication skills in the dental curriculum is now more than ever of utmost importance. This study aimed to investigate how students assess their skills after communication training and whether this training also increased students' self-efficacy expectancy. A total of 32 male and 71 female students with a mean age of 25.6 ± 3.9 years participated in the study. Self-assessment of communication skills and self-efficacy expectancies were collected at two time points using Likert scales. Our study shows that the communication training, consisting of a practical exercise with actors and an online theory module, significantly improved the students' self-assessment of their communication skills and also improved some aspects of self-efficacy expectancy. These results indicate that, in addition to the practical and technical-theoretical training of students, communication training is essential in the dental curriculum. In summary, this study showed that a one-time practical exercise with actors together with an online theory module could improve both the self-assessment of communication competence and some aspects of self-efficacy expectancy, which demonstrates the importance of training communication skills alongside practical and technical-theoretical training.

Fusobacterium Necrophorum Septicemia Secondary to an Ovarian Abscess: A Case Report.

Fusobacterium necrophorum is part of the normal oropharyngeal flora and can result in a life-threatening systemic infection known as Lemierre's syndrome. A rare presentation of F. necrophorum infection is seen in the female genital tract and is typically due to obstetric infections. Here we present a unique case of F. necrophorum without traditional features of Lemierre's syndrome with the female genital tract as a primary site. A 50-year-old female presents with a two-month history of nausea, vomiting, abdominal pain, and weight loss. She ultimately developed bilateral lower extremity necrotizing fasciitis, colonic perforation, and a left chest wall abscess. Blood and wound cultures were found to be positive for Fusobacterium necrophorum. Imaging revealed a left ovarian mass along with a left upper lobe nodule. She had no history of oropharyngeal infections or symptoms. Imaging was also negative for deep neck space abscesses or thrombophlebitis. The patient was treated with ceftriaxone and metronidazole and clinically improved. In conclusion, F. necrophorum is a potentially life threatening infection and should be considered when dealing with ovarian abscesses or masses.

Light-Mediated Reduction in Photosynthesis in Closed Greenhouses Can Be Compensated for by CO2 Enrichment in Tomato Production.

Concepts of semi-closed greenhouses can be used to save energy, whereas their technical equipment often causes a decrease in the light received by the plants. Nevertheless, higher yields are achieved, which are presumably triggered by a higher CO2 concentration in the greenhouse and associated higher photosynthesis because of the technical cooling and the longer period of closed ventilation. Therefore, we examined the effects of photosynthetic photon flux density (PPFD) and CO2 concentration on plant photosynthesis and transpiration in tomato using a multiple cuvette gas exchange system. In a growth chamber experiment, we demonstrated that a light-mediated reduction in photosynthesis can be compensated or even overcompensated for by rising CO2 concentration. Increasing the CO2 concentration from 400 to 1000 µmol mol-1 within the PPFD range from 303 to 653 µmol m-2 s-1 resulted in an increase in net photosynthesis of 51%, a decrease in transpiration of 5 to 8%, and an increase in photosynthetic water use efficiency of 60%. Estimations showed that light reductions of 10% can be compensated for via increasing the CO2 concentration by about 100 µmol mol-1 and overcompensated for by about 40% if CO2 concentration is kept at 1000 instead of 400 µmol mol-1.

EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization.

Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 µm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine spatially and molecularly defined subregions. EASI-FISH also facilitates iterative reanalysis of scRNA-seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.

Reactions of diborenes with terminal alkynes: mechanisms of ligand-controlled anti-selective hydroalkynylation, cycloaddition and C[triple bond, length as m-dash]C triple bond scission.

The reactions of terminal acetylenes with doubly Lewis base-stabilised diborenes resulted in different outcomes depending on the nature of the ligands at boron and the conformation of the diborene (cyclic versus acyclic). N-heterocyclic carbene (NHC)-stabilised diborenes tended to undergo anti-selective hydroalkynylation at room temperature, whereas [2 + 2] cycloaddition was observed at higher temperatures, invariably followed by a C-N bond activation at one NHC ligand, leading to the ring-expansion of the initially formed BCBC ring and formation of novel boron-containing heterocycles. For phosphine-stabilised diborenes only [2 + 2] cycloaddition was observed, followed by a rearrangement of the resulting 1,2-dihydro-1,2-diborete to the corresponding 1,3-isomer, which amounts to complete scission of both the B[double bond, length as m-dash]B double and C[triple bond, length as m-dash]C triple bonds of the reactants. The elusive 1,2-isomer was finally trapped by using a cyclic phosphine-stabilised diborene, which prevented rearrangement to the 1,3-isomer. Extensive density functional theory (DFT) calculations provide a rationale for the selectivity observed.

Development and testing of a summative video-based e-examination in relation to an OSCE for measuring communication-related factual and procedural knowledge of medical students.

Objective: In the context of educating medical students, testing of competence in medical communication is carried out primarily with the Objective Structured Clinical Examination [1]. This makes it possible to assess practical performance, but it is resource-intensive and has a negative impact on test quality. The project "Digital test tool for measuring communication skills in medical studies" (digiRole) was funded by the BMBF (Federal Ministry of Education and Research) and its objective was to develop digital formats as electronic versions of an OSCE in order to test the communication competency of medical students. Such digital forms of examination should be cost-effective, be relevant to clinical practice and have high psychometric quality. In terms of content, the examination questions should incorporate factual and procedural knowledge as components of communication competency, although we assumed that procedural knowledge is more relevant than facutal knowledge to OSCE performance. This article describes the development and testing of a video-based, communication-related e-examination that is relevant to passing the test, which is the first milestone of the overall project. Methodology: We produced videos and related exam questions in the form of a situational judgement test [2] related to medical psychology and medical sociology, based on the educational content of a preclinical course on doctor-patient communication at the Mainz University Medical Center. In the summer semester of 2018, 226 students sat for this video-based single-choice e-examination (VSE). In the winter semester of 2018/2019, a different cohort of 192 students participated in the VSE as well as a tried-and-tested communication OSCE with five stations [3]. Results: The internal consistencies for the VSE in the summer semester of 2018 were α=.55, in the winter semester 2018/19 with α=.62 and for the OSCE with α=.60. There was a positive correlation between the performance of the students with the VSE and that with the OSCE (r=.21, p≤.01). Principal Axis Analyses did not reveal any dimensioning in terms of factual and procedural knowledge. In the evaluation, the majority of the students stated that the VSE was quite relevant to the practise of medical communication and were in favour of retaining this form of examination. Conclusion: The correlation between the VSE and the OSCE is relatively low, so that the VSE in this form is not a satisfactory predictor of an OSCE result. In terms of internal consistency, the VSE and the OSCE produced an almost identical result. It can also be assumed that the VSE can achieve a high degree of objectivity with the use of standardised video-based examinations as well as greater resource efficiency than OSCEs.

Increase of Yield, Lycopene, and Lutein Content in Tomatoes Grown Under Continuous PAR Spectrum LED Lighting.

Light emitting diodes (LEDs) are an energy efficient alternative to high-pressure sodium (HPS) lighting in tomato cultivation. In the past years, we have learned a lot about the effect of red and blue LEDs on plant growth and yield of tomatoes. From previous studies, we know that plants absorb and utilize most of the visible spectrum for photosynthesis. This part of the spectrum is referred to as the photosynthetically active radiation (PAR). We designed a LED fixture with an emission spectrum that partially matches the range of 400 to 700 nm and thus partially covers the absorption spectrum of photosynthetic pigments in tomato leaves. Tomato plants grown under this fixture were significantly taller and produced a higher fruit yield (14%) than plants grown under HPS lighting. There was no difference in the number of leaves and trusses, leaf area, stem diameter, the electron transport rate, and the normalized difference vegetation index. Lycopene and lutein contents in tomatoes were 18% and 142% higher when they were exposed to the LED fixture. However, the ß-carotene content was not different between the light treatments. Transpiration rate under LED was significantly lower (40%), while the light use efficiency (LUE) was significantly higher (19%) compared to HPS lighting. These data show that an LED fixture with an emission spectrum covering the entire PAR range can improve LUE, yields, and content of secondary metabolites in tomatoes compared to HPS lighting.

Tree rings reveal signs of Europe's sustainable forest management long before the first historical evidence.

To satisfy the increasing demand for wood in central Europe during medieval times, a new system of forest management was developed, one far superior to simple coppicing. The adoption of a sophisticated, Coppice-with-Standards (CWS) management practice created a two-storey forest structure that could provide fuelwood as well as construction timber. Here we present a dendrochronological study of actively managed CWS forests in northern Bavaria to detect the radial growth response to cyclical understorey harvesting in overstorey oaks (Quercus sp.), so-called standards. All modern standards exhibit rapid growth releases every circa 30 years, most likely caused by regular understorey management. We further analyse tree-ring width patterns in 2120 oak timbers from historical buildings and archaeological excavations in southern Germany and north-eastern France, dating between 300 and 2015 CE, and succeeded in identifying CWS growth patterns throughout the medieval period. Several potential CWS standards even date to the first millennium CE, suggesting CWS management has been in practice long before its first mention in historical documents. Our dendrochronological approach should be expanded routinely to indentify the signature of past forest management practices in archaeological and historical oak wood.

Tuneable reduction of cymantrenylboranes to diborenes or borylene-derived boratafulvenes.

Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr2Cym, in benzene results in the formation of the corresponding diborenes (NHC)2B2Cym2, a change of solvent to THF yields a borylene analogue of the form (NHC)2BCym, stabilised through a boratafulvene/borafulvenium conformation.

Practical sensorless aberration estimation for 3D microscopy with deep learning.

Estimation of optical aberrations from volumetric intensity images is a key step in sensorless adaptive optics for 3D microscopy. Recent approaches based on deep learning promise accurate results at fast processing speeds. However, collecting ground truth microscopy data for training the network is typically very difficult or even impossible thereby limiting this approach in practice. Here, we demonstrate that neural networks trained only on simulated data yield accurate predictions for real experimental images. We validate our approach on simulated and experimental datasets acquired with two different microscopy modalities and also compare the results to non-learned methods. Additionally, we study the predictability of individual aberrations with respect to their data requirements and find that the symmetry of the wavefront plays a crucial role. Finally, we make our implementation freely available as open source software in Python.

Closed mitosis requires local disassembly of the nuclear envelope.

At the end of mitosis, eukaryotic cells must segregate the two copies of their replicated genome into two new nuclear compartments1. They do this either by first dismantling and later reassembling the nuclear envelope in an 'open mitosis' or by reshaping an intact nucleus and then dividing it into two in a 'closed mitosis'2,3. Mitosis has been studied in a wide variety of eukaryotes for more than a century4, but how the double membrane of the nuclear envelope is split into two at the end of a closed mitosis without compromising the impermeability of the nuclear compartment remains unknown5. Here, using the fission yeast Schizosaccharomyces pombe (a classical model for closed mitosis5), genetics, live-cell imaging and electron tomography, we show that nuclear fission is achieved via local disassembly of nuclear pores within the narrow bridge that links segregating daughter nuclei. In doing so, we identify the protein Les1, which is localized to the inner nuclear envelope and restricts the process of local nuclear envelope breakdown to the bridge midzone to prevent the leakage of material from daughter nuclei. The mechanism of local nuclear envelope breakdown in a closed mitosis therefore closely mirrors nuclear envelope breakdown in open mitosis3, revealing an unexpectedly high conservation of nuclear remodelling mechanisms across diverse eukaryotes.

Crop Photosynthetic Performance Monitoring Based on a Combined System of Measured and Modelled Chloroplast Electron Transport Rate in Greenhouse Tomato.

Combining information of plant physiological processes with climate control systems can improve control accuracy in controlled environments as greenhouses and plant factories. Through that, resource optimization can be achieved. To predict the plant physiological processes and implement them in control actions of interest, a reliable monitoring system and a capable control system are needed. In this paper, we focused on the option to use real-time crop monitoring for precision climate control in greenhouses. For that, we studied the processes and external factors influencing leaf net CO2 assimilation rate (AL , µmol CO2 m-2 s-1) as possible variables of a plant performance indicator. While measured greenhouse environmental variables such as light, temperature, or humidity showed a direct relation between AL and light-quantum yield of photosystem II (Φ2), we defined three objectives: (1) to explore the relationship between climate variables and AL , as well as Φ2; (2) create a simple and reliable method for real-time prediction of AL with continuously Φ2 measurements; and (3) calibrate parameters to predict chloroplast electron transport rate as input in AL modelling. Due to practical obstacles in measuring CO2 gas-exchange in commercial production, we explored a method to predict AL by measuring Φ2 of leaves in a commercial hydroponic greenhouse tomato crop ("Pureza"). We calculated AL with two different approaches based on either the negative exponential response model with simplified biochemical equations (marked as Model I) or the non-rectangular hyperbola full biochemical photosynthetic models (marked as Model II). Using Model I can only be used to predict AL with large uncertainty (R2 0.64; RMSE 2.21), while using Φ2 as input to Model II could be used to improve the prediction accuracy of AL (R2 0.71; RMSE 1.98). Our results suggests that (1) Φ2 light signals can be used to predict net photosynthesis rate with high accuracy; (2) a parameterized photosynthetic electron transport rate model is suitable predicting measured electron transport rate (J) and AL . The system can be used as decision support system (DSS) for plant and crop performance monitoring when leaf-dynamics are up-scaled to the plant or crop level.

Live Imaging of a Hyperthermophilic Archaeon Reveals Distinct Roles for Two ESCRT-III Homologs in Ensuring a Robust and Symmetric Division.

Live-cell imaging has revolutionized our understanding of dynamic cellular processes in bacteria and eukaryotes. Although similar techniques have been applied to the study of halophilic archaea [1-5], our ability to explore the cell biology of thermophilic archaea has been limited by the technical challenges of imaging at high temperatures. Sulfolobus are the most intensively studied members of TACK archaea and have well-established molecular genetics [6-9]. Additionally, studies using Sulfolobus were among the first to reveal striking similarities between the cell biology of eukaryotes and archaea [10-15]. However, to date, it has not been possible to image Sulfolobus cells as they grow and divide. Here, we report the construction of the Sulfoscope, a heated chamber on an inverted fluorescent microscope that enables live-cell imaging of thermophiles. By using thermostable fluorescent probes together with this system, we were able to image Sulfolobus acidocaldarius cells live to reveal tight coupling between changes in DNA condensation, segregation, and cell division. Furthermore, by imaging deletion mutants, we observed functional differences between the two ESCRT-III proteins implicated in cytokinesis, CdvB1 and CdvB2. The deletion of cdvB1 compromised cell division, causing occasional division failures, whereas the ΔcdvB2 exhibited a profound loss of division symmetry, generating daughter cells that vary widely in size and eventually generating ghost cells. These data indicate that DNA separation and cytokinesis are coordinated in Sulfolobus, as is the case in eukaryotes, and that two contractile ESCRT-III polymers perform distinct roles to ensure that Sulfolobus cells undergo a robust and symmetrical division.

Synergistic Effects of Forensic Medicine and Traumatology: Comparison of Clinical Diagnosis Autopsy Findings in Trauma-Related Deaths.

BACKGROUND: Trauma is the third leading cause of death worldwide after cardiovascular and oncologic diseases. Predominant causes of trauma-related death (TD) are severe traumatic brain injury (sTBI), hemorrhagic shock, and multiple organ failure. An analysis of TD is required in order to review the quality of trauma care and grasp how well the entire trauma network functions, especially for the most severely injured patients. Furthermore, autopsies not only reveal hidden injuries, but also verify clinical assumed causes of death. MATERIAL: During the study period of 3 years, a total of 517 trauma patients were admitted to our supraregional University Centre of Orthopaedics and Traumatology in Dresden. 13.7% (71/517) of the patients died after trauma, and in 25 cases (35.2%), a forensic autopsy was instructed by the federal prosecutor. The medical records, death certificates, and autopsy reports were retrospectively evaluated and the clinical findings matched to autopsy results. RESULTS: The observed mortality rates (13.7%) were 4.2% less than expected by the calculated RISC II probability of survival (mortality rate of 17.9%). The most frequent trauma victims were due to falls >3 m (n = 29), followed by traffic accidents (n = 28). The median ISS was 34, IQR 25, and the median New ISS (NISS) was 50, IQR 32. Locations of death were in emergency department (23.9%), ICU (73.2%), OR and ward (1.4%, respectively). Clinicians classified 47.9% of deaths due to sTBI (n = 34), followed by 9.9% thoracic trauma and multiple organ failure (n = 7), 8.4% multiple trauma (n = 6), and 2.8% hypoxia and exsanguination (n = 2). In 18.3%, cases were unspecific or other causes of death recorded on the death certificates. Evident differences with evident clinical consequences were ascertained in 4% (n = 1) and marginal clinical consequences in 24% (6/25). In 16% (4/25), marginal differences with minor forensic consequences were revealed. CONCLUSIONS: Even in a supraregional trauma center, specialized in multiple trauma management (4.2% survival benefit), room for improvement exists in more than a quarter of all casualties. This underlines the need for higher autopsy rates to uncover missed injuries and to understand the pathomechanism in each trauma fatality. This would also help to uncover potential insufficiencies in clinical routines with regard to diagnostics. The interdisciplinary cooperation of trauma surgeons and forensic pathologists can increase the quality of trauma patient care.

trans-Selective Insertional Dihydroboration of a cis-Diborene: Synthesis of Linear sp3 -sp2 -sp3 -Triboranes and Subsequent Cationization.

The reaction of aryl- and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3-trans-dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis-1,2-µ-H-3-hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base-stabilized B3 H4 + analogues.

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome ß5 Subunit.

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome ß5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1' by a 3-phenoxy group to increase ß5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.

Spontaneous trans-Selective Transfer Hydrogenation of Apolar Boron-Boron Double Bonds.

The transfer hydrogenation of N-heterocyclic carbene (NHC)-supported diborenes with dimethylamine borane proceeds with high selectivity for the trans-1,2-dihydrodiboranes. DFT calculations, supported by kinetic studies and deuteration experiments, suggest a stepwise proton-first-hydride-second reaction mechanism via an intermediate µ-hydrodiboronium dimethylaminoborate ion pair.