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Purpose: To provide a navigator-based run-time motion and first-order field correction for three-dimensional human brain imaging with high precision, minimal calibration and acquisition, and fast processing., Methods: A complex-valued linear perturbation model with feedback control is extended to estimate and correct for gradient shim fields using orbital navigators (2.3 ms). Two approaches for sensitizing the model to gradient fields are presented, one based on finite differences with three additional navigators, and another projection-based approximation requiring no additional navigators. A mechanism for noise decorrelation of the matrix and the data is proposed and evaluated to reduce unwanted parameter biases., Results: The rigid motion and first-order field control achieves robust motion and gradient shim corrections improving image quality in a series of phantom and in vivo experiments with varying field conditions. In phantom scans, magnet drifts, forced gradient field perturbations and field distortions from shifts of a second bottle phantom are successfully corrected. Field estimates of the magnet drifts are in good agreement with concurrent field probe measurements. For in vivo scans, the proposed method mitigates field variations from torso motions while being robust to head motion. In vivo gradient field precisions were 30   nT / m $$ 30\;\mathrm{nT}/\mathrm{m} $$ along with single-digit micrometer and millidegree rigid precisions., Conclusion: The navigator-based method achieves accurate, high-precision run-time motion and field corrections with low sequence impact and calibration requirements., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

A highly stereoselective Brønsted-acid catalyzed synthesis of densely substituted spiroisoindolinones from enamides and 3-hydroxy-isoindolinones is described. With simple Brønsted-acids, such as para-toluene sulfonic acid, spiroisoindolinones with three contiguous stereogenic centers are formed in high yields (up to 97 %) and diastereoselectivities (up to >98 : <2 : 0 : 0 dr) under mild reaction conditions. With the use of a chiral phosphoric acid catalyst, a diastereo- and enantioselective synthesis of the corresponding spiroisoindolinones was achieved. Mechanistic investigations indicate a step-wise mechanism via an initial addition of the enamide to an electrophilic N-acylimine species followed by an intramolecular aza-Friedel-Crafts reaction. Addition of a strong Lewis acid can be used to facilitate the second step for less reactive substrates., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Japanese species of the genus Syzeuctus Förster, 1869 are revised, with a total of 12 species recorded from Japan. Five species, S. brevicaudus sp. nov., S. flavitarsis sp. nov., S. nigrus sp. nov., S. rufiapicalis sp. nov., and S. yamatonis sp. nov., are newly described. Three species, S. flavofacialis Kang & Lee, 2020, S. laoticus Riedel, 2022, and S. maculatus Sheng, 2009, are newly recorded from Japan. Male of S. maculatus is newly described. A key for Japanese species is also provided.

Purpose: Treatment of patients undergoing prolonged weaning from mechanical ventilation includes repeated spontaneous breathing trials (SBTs) without respiratory support, whose duration must be balanced critically to prevent over- and underload of respiratory musculature. This study aimed to develop a machine learning model to predict the duration of unassisted spontaneous breathing., Materials and Methods: Structured clinical data of patients from a specialized weaning unit were used to develop (1) a classifier model to qualitatively predict an increase of duration, (2) a regressor model to quantitatively predict the precise duration of SBTs on the next day, and (3) the duration difference between the current and following day. 61 features, known to influence weaning, were included into a Histogram-based gradient boosting model. The models were trained and evaluated using separated data sets., Results: 18.948 patient-days from 1018 individual patients were included. The classifier model yielded an ROC-AUC of 0.713. The regressor models displayed a mean absolute error of 2:50 h for prediction of absolute durations and 2:47 h for day-to-day difference., Conclusions: The developed machine learning model showed informed results when predicting the spontaneous breathing capacity of a patient in prolonged weaning, however lacking prognostic quality required for direct translation to clinical use., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Speckle-based X-ray imaging (SBI) is a phase-contrast method developed at and for highly coherent X-ray sources, such as synchrotrons, to increase the contrast of weakly absorbing objects. Consequently, it complements the conventional attenuation-based X-ray imaging. Meanwhile, attempts to establish SBI at less coherent laboratory sources have been performed, ranging from liquid metal-jet X-ray sources to microfocus X-ray tubes. However, their lack of coherence results in interference fringes not being resolved. Therefore, algorithms were developed which neglect the interference effects. Here, we demonstrate phase-contrast computed tomography employing SBI in a laboratory-setting with an inverse Compton X-ray source. In this context, we investigate and compare also the performance of the at synchrotron conventionally used phase-retrieval algorithms for SBI, unified modulated pattern analysis (UMPA) with a phase-retrieval method developed for low coherence systems (LCS). We successfully retrieve a full computed tomography in a phantom as well as in biological specimens, such as larvae of the greater wax moth (Galleria mellonella), a model system for studies of pathogens and infections. In this context, we additionally demonstrate quantitative phase-contrast computed tomography using SBI at a low coherent set-up.

The Omicron variants boast the highest infectivity rates among all SARS-CoV-2 variants. Despite their lower disease severity, they can reinfect COVID-19 patients and infect vaccinated individuals as well. The high number of mutations in these variants render them resistant to antibodies that otherwise neutralize the spike protein of the original SARS-CoV-2 spike protein. Recent research has shown that despite its strong immune evasion, Omicron still induces strong T Cell responses similar to the original variant. This work investigates the molecular basis for this observation using the neural network tools NetMHCpan-4.1 and NetMHCiipan-4.0. The antigens presented through the MHC Class I and Class II pathways from all the notable SARS-CoV-2 variants were compared across numerous high frequency HLAs. All variants were observed to have equivalent T cell antigenicity. A novel positive control system was engineered in the form of spike variants that did evade T Cell responses, unlike Omicron. These evasive spike proteins were used to statistically confirm that the Omicron variants did not exhibit lower antigenicity in the MHC pathways. These results suggest that T Cell immunity mounts a strong defense against COVID-19 which is difficult for SARS-CoV-2 to overcome through mere evolution.

Purpose: Navigator-based correction of rigid-body motion reconciling high precision with minimal acquisition, minimal calibration and simple, fast processing., Methods: A short orbital navigator (2.3 ms) is inserted in a three-dimensional (3D) gradient echo sequence for human head imaging. Head rotation and translation are determined by linear regression based on a complex-valued model built either from three reference navigators or in a reference-less fashion, from the first actual navigator. Optionally, the model is expanded by global phase and field offset. Run-time scan correction on this basis establishes servo control that maintains validity of the linear picture by keeping its expansion point stable in the head frame of reference. The technique is assessed in a phantom and demonstrated by motion-corrected imaging in vivo., Results: The proposed approach is found to establish stable motion control both with and without reference acquisition. In a phantom, it is shown to accurately detect motion mimicked by rotation of scan geometry as well as change in global B 0 . It is demonstrated to converge to accurate motion estimates after perturbation well beyond the linear signal range. In vivo, servo navigation achieved motion detection with precision in the single-digit range of micrometers and millidegrees. Involuntary and intentional motion in the range of several millimeters were successfully corrected, achieving excellent image quality., Conclusion: The combination of linear regression and feedback control enables prospective motion correction for head imaging with high precision and accuracy, short navigator readouts, fast run-time computation, and minimal demand for reference data., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

During a survey of the family Ichneumonidae in northwestern Iran, a total of 17 species belonging to the subfamilies Banchinae, Cryptinae, Ichneumoninae, Mesochorinae, Metopiinae, Orthopelmatinae, Phygadeuontinae and Tersilochinae were identified. Two species, Lissonota (Lissonota) rufofacies Riedel nov. sp. and Orthopelma mukriyana Riedel nov. sp. are new to science and are described and illustrated. Their diagnostic characters are provided. We also provide collecting details for the fifteen species recorded for the first time from Iran.

Background: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown., Methods: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years., Results: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040)., Conclusions: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future., Competing Interests: Declaration of Competing Interest GN, YA, CS, HR, LS, DM, LSi, JM, TG, MR, URK, AH, DS, HD, FK,TT, MK, JK have no conflicts of interest to declare. CSk reports a grant from DFG Sk 276/3–1. BS has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme, and research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, the B. Braun Foundation, Boston Scientific, and Edwards Lifesciences. DL received lecture honoraria from Amgen, Abott Vascular, AstraZeneca, and Novo Nordisk. MJ received consulting fees from Biotronik, TriCares, Veryan and Shockwave; he is in the steering committee of Biotronik and Edwards lifesciences. UL reports lecture and advisory honorary from Abott., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments., (© 2024. The Author(s).)

Here, we report a comparative study of different sum parameter analysis methods for the extraction of per- and polyfluoroalkyl substances (PFAS) from manufactured consumer products, which can be measured by combustion ion chromatography (CIC). Therefore, a hydrolysis-based extraction method was further developed, which accounts for the addition of hydrolyzable covalently bound polyfluoroalkylated side-chain polymers (SFPs) to the extractable organic fluorine portion of the mass balance proposed as "hydrolyzable organically bound fluorine" (HOF). To test this hypothesis, the method was applied to 39 different consumer products containing fluoropolymers or monomeric PFAS taken from four different categories: outdoor textiles, paper packaging, carpeting, and permanent baking sheets. We also evaluated the method's efficiency by extracting four synthesized fluorotelomer polyacrylate reference compounds. The total fluorine (TF) and extractable organically bound fluorine (EOF) values were measured through CIC using established protocols. The TF values ranged from sub-ppb to %-levels, depending on the compound class. All samples showed results for hydrolyzed organofluorine (HOF) between 0.03 and 76.3 μg/g, while most EOF values were lower (

Background: Obstetrics and gynecology (OB/GYN) is an essential medical field that focuses on women's health. Universities aim to provide high-quality healthcare services to women through comprehensive education of medical students. In Germany, medical education is undergoing a phase of restructuring towards the implementation of competency-based learning. The objective of the current survey was to gain insights into the teaching methods, resources, and challenges at German medical universities in the field OB/GYN. This aims to document the current state of medical education and derive potential suggestions for improvements in the era of competency-based learning. The survey was conducted with teaching coordinators from the majority of OB/GYN departments at German universities., Methods: A questionnaire was sent to the teaching coordinators in all 41 OB/GYN departments at German university hospitals. The survey was delivered via email with a link to an online survey platform., Results: The study received 30 responses from 41 universities. Differences were observed in the work environment of teaching coordinators concerning release from clinical duties for teaching purposes and specialized academic training. Overall, medical education and student motivation were perceived positively, with noticeable gaps, particularly in practical gynecological training. Deficiencies in supervision and feedback mechanisms were also evident. Subfields such as urogynecology and reproductive medicine appear to be underrepresented in the curriculum, correlating with poorer student performance. E-learning was widely utilized and considered advantageous., Conclusion: The present study provides valuable insights into the current state of medical education in OB/GYN at German universities from the perspective of teaching experts. We highlight current deficits, discuss approaches to overcome present obstacles, and provide suggestions for improvement., (© 2024. The Author(s).)

Bias in neural network model training datasets has been observed to decrease prediction accuracy for groups underrepresented in training data. Thus, investigating the composition of training datasets used in machine learning models with healthcare applications is vital to ensure equity. Two such machine learning models are NetMHCpan-4.1 and NetMHCIIpan-4.0, used to predict antigen binding scores to major histocompatibility complex class I and II molecules, respectively. As antigen presentation is a critical step in mounting the adaptive immune response, previous work has used these or similar predictions models in a broad array of applications, from explaining asymptomatic viral infection to cancer neoantigen prediction. However, these models have also been shown to be biased toward hydrophobic peptides, suggesting the network could also contain other sources of bias. Here, we report the composition of the networks' training datasets are heavily biased toward European Caucasian individuals and against Asian and Pacific Islander individuals. We test the ability of NetMHCpan-4.1 and NetMHCpan-4.0 to distinguish true binders from randomly generated peptides on alleles not included in the training datasets. Unexpectedly, we fail to find evidence that the disparities in training data lead to a meaningful difference in prediction quality for alleles not present in the training data. We attempt to explain this result by mapping the HLA sequence space to determine the sequence diversity of the training dataset. Furthermore, we link the residues which have the greatest impact on NetMHCpan predictions to structural features for three alleles (HLA-A*34:01, HLA-C*04:03, HLA-DRB1*12:02)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Atkins, Solanki, Vasmatzis, Cornette and Riedel.)

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG. 200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits. PRSs for BMI (β = 3.78; p = 0.0041), schizophrenia (β = 5.38; p = 0.021) and diabetes type 2 (β = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10 -6 . Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples., Competing Interests: Declaration of competing interest SP was supported by the European Union's Horizon Europe research and innovation programme (Psych-STRATA, grant agreement No 101057454). UH was supported by the European Union's Horizon 2020 research and innovation programme (PSY-PGx, grant agreement No 945151) outside the submitted work. MF, MSS, BBB, CG, IS, MR, PZ, TGS, RM declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Multi-shot diffusion-weighted EPI allows an increase in image resolution and reduced geometric distortions and can be combined with chemical-shift encoding (Dixon) to separate water/fat signals. However, such approaches suffer from physiological motion-induced shot-to-shot phase variations. In this work, a structured low-rank-based navigator-free algorithm is proposed to address the challenge of simultaneously separating water/fat signals and correcting for physiological motion-induced shot-to-shot phase variations in multi-shot EPI-based diffusion-weighted MRI., Theory and Methods: We propose an iterative, model-based reconstruction pipeline that applies structured low-rank regularization to estimate and eliminate the shot-to-shot phase variations in a data-driven way, while separating water/fat images. The algorithm is tested in different anatomies, including head-neck, knee, brain, and prostate. The performance is validated in simulations and in-vivo experiments in comparison to existing approaches., Results: In-vivo experiments and simulations demonstrated the effectiveness of the proposed algorithm compared to extra-navigated and an alternative self-navigation approach. The proposed algorithm demonstrates the capability to reconstruct in the multi-shot/Dixon hybrid space domain under-sampled datasets, using the same number of acquired EPI shots compared to conventional fat-suppression techniques but eliminating fat signals through chemical-shift encoding. In addition, partial Fourier reconstruction can also be achieved by using the concept of virtual conjugate coils in conjunction with the proposed algorithm., Conclusion: The proposed algorithm effectively eliminates the shot-to-shot phase variations and separates water/fat images, making it a promising solution for future DWI on different anatomies., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Chat Generative Pre-Trained Transformer (ChatGPT) is an artificial learning and large language model tool developed by OpenAI in 2022. It utilizes deep learning algorithms to process natural language and generate responses, which renders it suitable for conversational interfaces. ChatGPT's potential to transform medical education and clinical practice is currently being explored, but its capabilities and limitations in this domain remain incompletely investigated. The present study aimed to assess ChatGPT's performance in medical knowledge competency for problem assessment in obstetrics and gynecology (OB/GYN)., Methods: Two datasets were established for analysis: questions (1) from OB/GYN course exams at a German university hospital and (2) from the German medical state licensing exams. In order to assess ChatGPT's performance, questions were entered into the chat interface, and responses were documented. A quantitative analysis compared ChatGPT's accuracy with that of medical students for different levels of difficulty and types of questions. Additionally, a qualitative analysis assessed the quality of ChatGPT's responses regarding ease of understanding, conciseness, accuracy, completeness, and relevance. Non-obvious insights generated by ChatGPT were evaluated, and a density index of insights was established in order to quantify the tool's ability to provide students with relevant and concise medical knowledge., Results: ChatGPT demonstrated consistent and comparable performance across both datasets. It provided correct responses at a rate comparable with that of medical students, thereby indicating its ability to handle a diverse spectrum of questions ranging from general knowledge to complex clinical case presentations. The tool's accuracy was partly affected by question difficulty in the medical state exam dataset. Our qualitative assessment revealed that ChatGPT provided mostly accurate, complete, and relevant answers. ChatGPT additionally provided many non-obvious insights, especially in correctly answered questions, which indicates its potential for enhancing autonomous medical learning., Conclusion: ChatGPT has promise as a supplementary tool in medical education and clinical practice. Its ability to provide accurate and insightful responses showcases its adaptability to complex clinical scenarios. As AI technologies continue to evolve, ChatGPT and similar tools may contribute to more efficient and personalized learning experiences and assistance for health care providers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Riedel, Kaefinger, Stuehrenberg, Ritter, Amann, Graf, Recker, Klein, Kiechle, Riedel and Meyer.)

In this study, new distributional records are given for 98 species and subspecies of Darwin wasps of the subfamily Ichneumoninae (Hymenoptera, Ichneumonidae) from Maritime Southeast Asia, namely from Indonesia and Malaysia: Sabah. Four genera, 31 species and three subspecies are described as new. The new genera are: Atanyjoppoides n. gen., Moluccarches n. gen., Orientodromus n. gen. and Platylaboides n. gen. The new species are: Achaius sabahensis n. sp., Allonotus rufiventris n. sp., Amblyjoppa nigra n. sp., Amblyjoppa striata n. sp., Atanyjoppoides mandibulator n. sp., Benyllus mesonotator n. sp., Benyllus rufostriatus n. sp., Benyllus sundaensis n. sp., Celebarches albifrons n. sp., Celebarches nigritor n. sp., Celebarches sabahensis n. sp., Celebarches tricolor n. sp., Coelichneumon (Exephanides) nigropropodealis n. sp., Compsophorus (Xenojoppa) quadrimaculatus n. sp., Deniya scutellaris n. sp., Eccoptosage nigrifemur n. sp., Eccoptosage sabahensis n. sp., Heresiarches simile n. sp., Lareiga nigrita n. sp., Lissosculpta albifrons n. sp., Lissosculpta malucuensis n. sp., Lissosculpta seramensis n. sp., Losgna baliensis n. sp., Losgna rufobasalis n. sp., Moluccarches albimaculatus n. sp., Orientodromus thyridialis n. sp., Platylaboides javanicus n. sp., Pseudoplatylabus rufoniger n. sp., Setanta albimaculata n. sp., Stirexephanes albicoxis n. sp., and Stirexephanes rufopetiolaris n. sp. The new subspecies are: Allonotus rufus sumatrensis n. ssp., Amblyjoppa rufobalteata sumatera n. ssp., and Anisobas vietnamensis sabahensis n. ssp. Vulgichneumon stegemanni (Heinrich, 1934) is transferred to the genus Virgichneumon Heinrich, 1977, n. stat.. For the following species the hitherto unknown are described: Barichneumonites properans (Tosquinet, 1903), Celebarches unicus Heinrich, 1934, Celebichneumon egregius Heinrich, 1934, Coelichneumon (Coelichneumon) lineiscutis Heinrich, 1966, Eccoptosage quadridentata (Cameron, 1905), Menkokia major (Heinrich, 1934), Nesostenodontus formosanus Cushman, 1937, Stenichneumonopsis albifasciatus Heinrich, 1934, Stirexephanes impictus Heinrich, 1934, Ulesta plagiata Heinrich, 1934, and Virgichneumon stegemanni (Heinrich, 1934). All new species are described in detail and illustrated. For the known species of Celebarches Heinrich, a determination key is provided.

DNA has been discussed as a potential medium for data storage. Potentially it could be denser, could consume less energy, and could be more durable than conventional storage media such as hard drives, solid-state storage, and optical media. However, performing computations on the data stored in DNA is a largely unexplored challenge. This paper proposes an integrated circuit (IC) based on microfluidics that can perform complex operations such as artificial neural network (ANN) computation on data stored in DNA. We envision such a system to be suitable for highly dense, throughput-demanding bio-compatible applications such as an intelligent Organ-on-Chip or other biomedical applications that may not be latency-critical. It computes entirely in the molecular domain without converting data to electrical form, making it a form of in-memory computing on DNA. The computation is achieved by topologically modifying DNA strands through the use of enzymes called nickases. A novel scheme is proposed for representing data stochastically through the concentration of the DNA molecules that are nicked at specific sites. The paper provides details of the biochemical design, as well as the design, layout, and operation of the microfluidics device. Benchmarks are reported on the performance of neural network computation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Solanki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic necessitated wide-ranging adaptations to the organisation of health systems, and primary care is no exception. This article aims to collate insights on the role of primary care during the pandemic. The gained knowledge helps to increase pandemic preparedness and resilience., Methods: The role of primary care during the pandemic in five European countries (Austria, Denmark, France, Hungary, Italy) was investigated using a qualitative approach, namely case study, based on document analysis and semi-structured interviews. In total, 31 interviews were conducted with primary care providers between June and August 2022. The five country case studies were subjected to an overarching analysis focusing on successful strategies as well as gaps and failures regarding pandemic management in primary care., Results: Primary care providers identified disruptions to service delivery as a major challenge emerging from the pandemic which led to a widespread adoption of telehealth. Despite the rapid increase in telehealth usage and efforts of primary care providers to organise face-to-face care delivery in a safe way, some patient groups were particularly affected by disruptions in service delivery. Moreover, primary care providers perceived a substantial propagation of misinformation about COVID-19 and vaccines among the population, which also threatened patient-physician relationships. At the same time, primary care providers faced an increased workload, had to work with insufficient personal protective equipment and were provided incongruous guidelines from public authorities. There was a consensus among primary care providers that they were mostly sidelined by public health policy in the context of pandemic management. Primary care providers tackled these problems through a diverse set of measures including home visits, implementing infection control measures, refurbishing used masks, holding internal meetings and relying on their own experiences as well as information shared by colleagues., Conclusion: Primary care providers were neither well prepared nor the focus of initial policy making. However, they implemented creative solutions to the problems they faced and applying the learnings from the pandemic could help in increasing the resilience of primary care. Attributes of an integrated health system with a strong primary care component proved beneficial in addressing immediate effects of the pandemic., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity., Methods: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales., Results: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression., Conclusions: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression., (© 2023. The Author(s).)

Acute Respiratory Distress Syndrome (ARDS) is a condition that endangers the lives of many Intensive Care Unit patients through gradual reduction of lung function. Due to its heterogeneity, this condition has been difficult to diagnose and treat, although it has been the subject of continuous research, leading to the development of several tools for modeling disease progression on the one hand, and guidelines for diagnosis on the other, mainly the "Berlin Definition". This paper describes the development of a deep learning-based surrogate model of one such tool for modeling ARDS onset in a virtual patient: the Nottingham Physiology Simulator. The model-development process takes advantage of current machine learning and data-analysis techniques, as well as efficient hyperparameter-tuning methods, within a high-performance computing-enabled data science platform. The lightweight models developed through this process present comparable accuracy to the original simulator (per-parameter R 2 > 0.90). The experimental process described herein serves as a proof of concept for the rapid development and dissemination of specialised diagnosis support systems based on pre-existing generalised mechanistic models, making use of supercomputing infrastructure for the development and testing processes and supported by open-source software for streamlined implementation in clinical routines.

This article provides datasets containing three years worth of solar spectra for the optimum installation angle of 35° and the building-integrated-photovoltaics relevant vertical angle of 90°. These datasets were obtained by measuring the spectrally resolved solar spectra using a five minute interval, where two sets of spectrometers, which measure different ranges of the solar spectrum, were employed. In addition, a merged dataset of these two spectral measurements, related to every specific five minute interval measurement, is provided. An analysis and interpretation of the data using only year the 2020 is provided in "Measurement and analysis of annual solar spectra at different installation angles in central Europe" [1]., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

At the northern Cascadia subduction zone, the subducting Explorer and Juan de Fuca plates interact across a transform deformation zone, known as the Nootka fault zone (NFZ). This study continues the Seafloor Earthquake Array Japan Canada Cascadia Experiment to a second phase (SeaJade II) consisting of nine months of recording of earthquakes using ocean-bottom and land-based seismometers. In addition to mapping the distribution of seismicity, including an M W 6.4 earthquake and aftershocks along the previously unknown Nootka Sequence Fault, we also conducted seismic tomography, which delineates the geometry of the shallow subducting Explorer plate (ExP). We derived hundreds of high-quality focal mechanism solutions from the SeaJade II data. The mechanisms manifest a complex regional tectonic state, with normal faulting of the ExP west of the NFZ, left-lateral strike-slip behaviour of the NFZ, and reverse faulting within the overriding plate above the subducting Juan de Fuca plate. Using data from the combined SeaJade I and II catalogs, we have performed double-difference hypocentre relocations and found seismicity lineations to the southeast of, and oriented 18° clockwise from, the subducted NFZ, which we interpret to represent less active small faults off the primary faults of the NFZ. These lineations are not optimally oriented for shear failure in the regional stress field, which we inferred from averaged focal mechanism solutions, and may represent paleo-configurations of the NFZ. Further, active faults interpreted from seismicity lineations within the subducted plate, including the Nootka Sequence Fault, may have originated as conjugate faults within the paleo-NFZ., (© 2023. The Author(s).)

This paper presents a novel strategy for computing mathematical functions with molecular reactions, based on theory from the realm of digital design. It demonstrates how to design chemical reaction networks based on truth tables that specify analog functions, computed by stochastic logic. The theory of stochastic logic entails the use of random streams of zeros and ones to represent probabilistic values. A link is made between the representation of random variables with stochastic logic on the one hand, and the representation of variables in molecular systems as the concentration of molecular species, on the other. Research in stochastic logic has demonstrated that many mathematical functions of interest can be computed with simple circuits built with logic gates. This paper presents a general and efficient methodology for translating mathematical functions computed by stochastic logic circuits into chemical reaction networks. Simulations show that the computation performed by the reaction networks is accurate and robust to variations in the reaction rates, within a log-order constraint. Reaction networks are given that compute functions for applications such as image and signal processing, as well as machine learning: arctan, exponential, Bessel, and sinc. An implementation is proposed with a specific experimental chassis: DNA strand displacement with units called DNA "concatemers"., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Solanki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Phase-contrast computed tomography can visualize soft tissue samples with high contrast. At coherent sources, propagation-based imaging (PBI) techniques are among the most common, as they are easy to implement and produce high-resolution images. Their downside is a low degree of quantitative data due to simplifying assumptions of the sample properties in the reconstruction. These assumptions can be avoided, by using quantitative phase-contrast techniques as an alternative. However, these often compromise spatial resolution and require complicated setups. In order to overcome this limitation, we designed and constructed a new imaging setup using a 2D Talbot array illuminator as a wavefront marker and speckle-based imaging phase-retrieval techniques. We developed a post-processing chain that can compensate for wavefront marker drifts and that improves the overall sensitivity. By comparing two measurements of biomedical samples, we demonstrate that the spatial resolution of our setup is comparable to the one of PBI scans while being able to successfully image a sample that breaks the typical homogeneity assumption used in PBI., (© 2023. The Author(s).)

In this taxonomical study, one new genus and 41 new species of the subfamily Mesochorinae (Hymenoptera, Ichneumonidae) are described from Southeast Asia, namely from Indonesia, Malaysia, Thailand and Vietnam. The new genus is Orientochorus n. gen., the new species are Orientochorus tonkinensis n. sp., Astiphromma bicoloratus n. sp., Mesochorus achterbergi n. sp., Mesochorus anamnesis n. sp., Mesochorus brevipunctatus n. sp., Mesochorus cariniscuta n. sp., Mesochorus controversus n. sp., Mesochorus diversidens n. sp., Mesochorus flavator n. sp., Mesochorus flavopronotalis n. sp., Mesochorus fuscomaculatus n. sp., Mesochorus halmaherae n. sp., Mesochorus harlequinus n. sp., Mesochorus kinabaluensis n. sp., Mesochorus lamdongensis n. sp., Mesochorus longimurus n. sp., Mesochorus longistylus n. sp., Mesochorus longivalvator n. sp., Mesochorus malaysiacus n. sp., Mesochorus malucutus n. sp., Mesochorus nigripleuris n. sp., Mesochorus nigrofemur n. sp., Mesochorus nigromaculatus n. sp., Mesochorus paratenebris n. sp., Mesochorus pictiloides n. sp., Mesochorus pterostigmator n. sp., Mesochoprus rufator n. sp., Mesochorus sabahensis n. sp., Mesochorus sapaensis n. sp., Mesochorus semifuscus n. sp., Mesochorus semipunctatus n. sp., Mesochorus siamensis n. sp., Mesochorus stigmaticolor n. sp., Mesochorus striatofacies n. sp., Mesochorus sulaensis n. sp., Mesochorus sumaterae n. sp., Mesochorus templator n. sp., Mesochorus tenebris n. sp., Mesochorus tonkinensis n. sp., Mesochorus train n. sp., and Mesochorus vietnamensis n. sp. All species are illustrated and described in detail. In addition, a key for the females of the known Mesochorus species of Southeast Asia is presented.

Acid-base reactions are ubiquitous, easy to prepare, and execute without sophisticated equipment. Acids and bases are also inherently complementary and naturally map to a universal representation of "0" and "1." Here, we propose how to leverage acids, bases, and their reactions to encode binary information and perform information processing based upon the majority and negation operations. These operations form a functionally complete set that we use to implement more complex computations such as digital circuits and neural networks. We present the building blocks needed to build complete digital circuits using acids and bases for dual-rail encoding data values as complementary pairs, including a set of primitive logic functions that are widely applicable to molecular computation. We demonstrate how to implement neural network classifiers and some classes of digital circuits with acid-base reactions orchestrated by a robotic fluid handling device. We validate the neural network experimentally on a number of images with different formats, resulting in a perfect match to the in-silico classifier. Additionally, the simulation of our acid-base classifier matches the results of the in-silico classifier with approximately 99% similarity., (© 2023. The Author(s).)

The COVID-19 pandemic shed light on the need for quick diagnosis tools in healthcare, leading to the development of several algorithmic models for disease detection. Though these models are relatively easy to build, their training requires a lot of data, storage, and resources, which may not be available for use by medical institutions or could be beyond the skillset of the people who most need these tools. This paper describes a data analysis and machine learning platform that takes advantage of high-performance computing infrastructure for medical diagnosis support applications. This platform is validated by re-training a previously published deep learning model (COVID-Net) on new data, where it is shown that the performance of the model is improved through large-scale hyperparameter optimisation that uncovered optimal training parameter combinations. The per-class accuracy of the model, especially for COVID-19 and pneumonia, is higher when using the tuned hyperparameters (healthy: 96.5%; pneumonia: 61.5%; COVID-19: 78.9%) as opposed to parameters chosen through traditional methods (healthy: 93.6%; pneumonia: 46.1%; COVID-19: 76.3%). Furthermore, training speed-up analysis shows a major decrease in training time as resources increase, from 207 min using 1 node to 54 min when distributed over 32 nodes, but highlights the presence of a cut-off point where the communication overhead begins to affect performance. The developed platform is intended to provide the medical field with a technical environment for developing novel portable artificial-intelligence-based tools for diagnosis support.

The purpose of this study was to develop a self-navigation strategy to improve scan efficiency and image quality of water/fat-separated, diffusion-weighted multishot echo-planar imaging (ms-EPI). This is accomplished by acquiring chemical shift-encoded diffusion-weighted data and using an appropriate water-fat and diffusion-encoded signal model to enable reconstruction directly from k-space data. Multishot EPI provides reduced geometric distortion and improved signal-to-noise ratio in diffusion-weighted imaging compared with single-shot approaches. Multishot acquisitions require corrections for physiological motion-induced shot-to-shot phase errors using either extra navigators or self-navigation principles. In addition, proper fat suppression is important, especially in regions with large B 0 inhomogeneity. This makes the use of chemical shift encoding attractive. However, when combined with ms-EPI, shot-to-shot phase navigation can be challenging because of the spatial displacement of fat signals along the phase-encoding direction. In this work, a new model-based, self-navigated water/fat separation reconstruction algorithm is proposed. Experiments in legs and in the head-neck region of 10 subjects were performed to validate the algorithm. The results are compared with an image-based, two-dimensional (2D) navigated water/fat separation approach for ms-EPI and with a conventional fat saturation approach. Compared with the 2D navigated method, the use of self-navigation reduced the shot duration time by 30%-35%. The proposed algorithm provided improved diffusion-weighted water images in both leg and head-neck regions compared with the 2D navigator-based approach. The proposed algorithm also produced better fat suppression compared with the conventional fat saturation technique in the B 0 inhomogeneous regions. In conclusion, the proposed self-navigated reconstruction algorithm can produce superior water-only diffusion-weighted EPI images with less artefacts compared with the existing methods., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

With growing molecular evidence for correlations between spatial arrangement of blood vasculature and fundamental immunological functions, carried out in distinct compartments of the subdivided lymph node, there is an urgent need for three-dimensional models that can link these aspects. We reconstructed such models at a 1.84 µm resolution by the means of X-ray phase-contrast imaging with a 2D Talbot array in a short time without any staining. In addition reconstructions are verified in immunohistochemistry staining as well as in ultrastructural analyses. While conventional illustrations of mammalian lymph nodes depict the hilus as a definite point of blood and lymphatic vessel entry and exit, our method revealed that multiple branches enter and emerge from an area that extends up to one third of the organ's surface. This could be a prerequisite for the drastic and location-dependent remodeling of vascularization, which is necessary for lymph node expansion during inflammation. Contrary to corrosion cast studies we identified B-cell follicles exhibiting a two times denser capillary network than the deep cortical units of the T-cell zone. In addition to our observation of high endothelial venules spatially surrounding the follicles, this suggests a direct connection between morphology and B-cell homing. Our findings will deepen the understanding of functional lymph node composition and lymphocyte migration on a fundamental basis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwarzenberg, Schütz, Hammel, Riedel, Bartl, Bordbari, Frank, Walkenfort, Busse, Herzen, Lohr, Wülfing and Henne.)

Background and Hypothesis: Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation., Study Design: In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5-20 mg/day) or amisulpride (200-800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the "non-improvers") were rerandomized double-blind to either staying on the same compound ("stayers") or to switching to the other antipsychotic ("switchers") for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined "switchers" and the "stayers" after 8 weeks of treatment, analyzed by logistic regression., Study Results: A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the 'stayers' compared to 41 (68.3 %) of the "switchers" reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. "Switchers" and "stayers" did not differ in safety outcomes., Conclusions: Switching "non-improvers" from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Rupture of the fibrous cap (RFC) represents the main pathophysiological mechanism causing acute coronary syndromes (ACS). Destabilization due to plaque biomechanics is considered to be importantly involved, exact mechanisms triggering plaque ruptures are, however, unknown. This study aims at characterizing the relation between plaque components and rupture points at ACS-causing culprit lesions in a large cohort of ACS-patients assessed by high-resolution intracoronary imaging., Methods and Results: Within the prospective, multicentric OPTICO-ACS study program, the ACS-causing culprit plaques of 282 consecutive patients were investigated following a standardized optical coherence tomography (OCT) imaging protocol. Each pullback was assessed on a frame-by-frame basis for the presence of lipid components (LC), calcium components (CC), and coexistence of both LC and CC (LCC) by two independent OCT-core labs. Of the 282 ACS-patients, 204 patients (72.3%) presented with ACS caused by culprit lesions with rupture of the fibrous cap (RFC-ACS) and 27.7% patients had ACS caused by culprit lesions with intact fibrous cap (IFC-ACS). When comparing RFC-ACS to IFC-ACS, a preferential occurrence of all three plaque components (LC, CC, and LCC) in RFC-ACS became apparent (P < 0.001). Within ruptured culprit lesions, the zone straight at the rupture point [extended rupture zone (RZ)] was characterized by similar (24.7% vs. 24.0%; P = ns) calcium content when compared with the proximal and distal border of the culprit lesion [border zone (BZ)]. The RZ displayed a significantly higher amount of both, LC (100% vs. 69.8%; P < 0.001) and LCC (22.7% vs. 6.8%; P < 0.001), when compared with the BZ. The relative component increase towards the RZ was particularly evident for LCC (+233.8%), while LC showed only a modest increase (+43.3%)., Conclusions: Calcified- and lipid-containing components characterize ruptured fibrous cap ACS-causing culprit lesions. Their coexistence is accelerated directly at the ruptured point, suggesting a pathophysiological contribution in the development of RFC-ACS., Competing Interests: Conflict of interest: The authors have nothing to declare., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Major Histocompability Complex (MHC) Class I molecules allow cells to present foreign and endogenous peptides to T-Cells so that cells infected by pathogens can be identified and killed. Neural networks tools such as NetMHC-4.0 and NetMHCpan-4.1 are used to predict whether peptides will bind to variants of MHC molecules. These tools are trained on data gathered from binding affinity and eluted ligand experiments. However, these tools do not track hydrophobicity, a significant biochemical factor relevant to peptide binding, in their predictions. A previous study had concluded that the peptides predicted to bind to HLA-A*0201 by NetMHC-4.0 were much more hydrophobic than expected. This paper expands that study by also focusing on HLA-B*2705 and HLA-B*0801, which prefer binding hydrophilic and balanced peptides respectively. The correlation of hydrophobicity of 9-mer peptides with their predicted binding strengths to these various HLAs was investigated. Two studies were performed, one using the data that the two neural networks were trained on, and the other using a sample of the human proteome. NetMHC-4.0 was found to have a statistically significant bias towards predicting highly hydrophobic peptides as strong binders to HLA-A*0201 and HLA-B*2705 in both studies. Machine Learning metrics were used to identify the causes for this bias: hydrophobic false positives and hydrophilic false negatives. These results suggest that the retraining the neural networks with biochemical attributes such as hydrophobicity and better training data could increase the accuracy of their predictions. This would increase their impact in applications such as vaccine design and neoantigen identification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Solanki, Riedel, Cornette, Udell and Vasmatzis.)

Introduction: Arthroplasty has become the standard of care for displaced femoral neck fractures in the geriatric cohort. However, details regarding optimal implant design and fixation strategy continue to be debated. We sought to determine whether cemented or press-fit hemiarthroplasties were more advantageous in terms of revision surgery, contralateral hip fractures, hospital length of stay, mortality rates, and survival., Methods: All geriatric fragility hip fractures at a level 1 trauma center (2014 to 2019) were retrospectively reviewed for the fracture pattern, fixation methodology, and outcome, yielding 707 femoral neck fractures treated with hemiarthroplasty (309 cemented and 398 press fit). The final follow-up was either date of death or final encounter. Major end points were revision surgery, contralateral fracture, and death. A Z-score test of two proportions was used for dichotomous variables, and a two-tailed t -test was used for continuous variables. Cox proportional hazard was used for revision surgery-free survival between groups, adjusting for age, sex, and American Society of Anesthesiologists status., Results: Patients who underwent press-fit hemiarthroplasty had a significantly higher rate of revision surgery (7.8% vs 3.9%; P = 0.006). Press-fit cases had a trend toward a decreased risk of contralateral fracture (13% vs 9.8%; P = 0.12), although this did not reach significance. Both groups had similar length of stay ( P = 0.08) and death rates ( P = 0.39). Of those who died, there was a trend toward longer survival in patients who received a press-fit hemiarthroplasty (413 vs 615 days; P < 0.001). There was a trend toward longer survival without repeat surgery in the cemented group without reaching significance (hazard ratio, 0.66 [0.34 to 1.23]; P = 0.201)., Conclusion: In this study, we found a markedly longer survival time after press-fit hemiarthroplasty, which we believe reflects surgeons' tendencies to cement the femoral prosthesis in patients with more comorbidities. However, press-fit hemiarthroplasties were more likely to result in repeat procedures on the same hip. Displaced geriatric femoral neck fractures may benefit from a cemented rather than press-fit hemiarthroplasty., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Objectives: The present sub-analysis from the randomized UDDC-Radial-Trial sought to compare one-catheter concepts (OCC) with two-catheter concepts (TCC) in different patient subgroups, particularly in those depending on gender and age., Background: There is an ongoing debate regarding potential performance differences of OCC compared to TCC for transradial coronary angiography in specific patient subgroups., Methods: The randomized UDDC-Radial-Trial enrolled a total of 300 patients planed for coronary angiography in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n = 100) or TCC by Judkins (n = 100) catheters. Predefined patient subgroups stratified for age, gender and patient constitution were analyzed with regard to the primary outcome measure of time required for a complete coronary angiography., Results: In male patients time for coronary angiography was significantly shorter in the TCC group compared to the OCC group (510 ± 37 s vs. 615 ± 35 s; p = 0.046). No difference between the catheter concepts was observed in the subset of female patients (525 ± 34 s vs. 583 ± 54 s; p = 0.43). TCC was associated with shorter coronary angiography time in patients aged <71 years compared to OCC (462 ± 23 s vs. 570 ± 38 s; p = 0.018). In patients ≥72 years of age no difference was detected (573 ± 41 s vs. 636 ± 45 s; p = 0.31). Other subgroups showed no relevant differences in angiography time among OCC and TCC., Conclusions: The present subgroup analysis from the UDDC-radial trial demonstrates the use of OCC in transradial diagnostic angiography to be inferior compared to TCC in terms of angiography time in younger and male patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study investigates basic features of a photoelectrochemical system based on CeO 2 nanoparticles fixed on gold electrodes. Since photocurrent generation is limited to the absorption range of the CeO 2 in the UV range, the combination with metal nanoparticles has been studied. It can be shown that the combination of silver nanoparticles with the CeO 2 can shift the excitation range into the visible light wavelength range. Here a close contact between both components has been found to be essential and thus, hybrid CeO 2 @Ag nanoparticles have been prepared and analyzed. We have collected arguments that electron transfer occurs between both compositional elements of the hybrid nanoparticles.The photocurrent generation can be rationalized on the basis of an energy diagram underlying the necessity of surface plasmon excitation in the metal nanoparticles, which is also supported by wavelength-dependent photocurrent measurements. However, electrochemical reactions seem to occur at the CeO 2 surface and consequently, the catalytic properties of this material can be exploited as exemplified with the photoelectrochemical reduction of hydrogen peroxide. It can be further demonstrated that the layer-by layer technique can be exploited to create a multilayer system on top of a gold electrode which allows the adjustment of the sensitivity of the photoelectrochemical system. Thus, with a 5-layer electrode with hybrid CeO 2 @Ag nanoparticles submicromolar hydrogen peroxide concentrations can be detected.

Objective: The attitudes about the usage of artificial intelligence in healthcare are controversial. Unlike the perception of healthcare professionals, the attitudes of patients and their companions have been of less interest so far. In this study, we aimed to investigate the perception of artificial intelligence in healthcare among this highly relevant group along with the influence of digital affinity and sociodemographic factors., Methods: We conducted a cross-sectional study using a paper-based questionnaire with patients and their companions at a German tertiary referral hospital from December 2019 to February 2020. The questionnaire consisted of three sections examining (a) the respondents' technical affinity, (b) their perception of different aspects of artificial intelligence in healthcare and (c) sociodemographic characteristics., Results: From a total of 452 participants, more than 90% already read or heard about artificial intelligence, but only 24% reported good or expert knowledge. Asked on their general perception, 53.18% of the respondents rated the use of artificial intelligence in medicine as positive or very positive, but only 4.77% negative or very negative. The respondents denied concerns about artificial intelligence, but strongly agreed that artificial intelligence must be controlled by a physician. Older patients, women, persons with lower education and technical affinity were more cautious on the healthcare-related artificial intelligence usage., Conclusions: German patients and their companions are open towards the usage of artificial intelligence in healthcare. Although showing only a mediocre knowledge about artificial intelligence, a majority rated artificial intelligence in healthcare as positive. Particularly, patients insist that a physician supervises the artificial intelligence and keeps ultimate responsibility for diagnosis and therapy., (© The Author(s) 2022.)

Purpose: The COVID-19 pandemic has imposed severe challenges on medical education at German university hospitals. In this first German nationwide expert survey, we addressed the responsible university teaching coordinators in obstetrics and gynecology departments and investigated their experiences during the pandemic as well as their opinions on future developments, especially with regard to the broader implementation of e-learning in the standard curriculum., Methods: The questionnaire included 42 items and was disseminated among teaching coordinators at all 41 departments of obstetrics and gynecology at German university hospitals via an email that included a weblink to the online survey provider. Responses were collected between 19 April and 7 June 2021., Results: In total, 30 responses were collected from 41 departments across Germany and their respective teaching coordinators in obstetrics and gynecology. The general opinion of the medical teaching provided during the pandemic was positive, whereas the teaching quality in practical skills was considered inferior and not equivalent to the standard face-to-face curriculum. Lectures and seminars had to be substituted by remote-learning alternatives, while clinical clerkships were reduced in length and provided less patient contact. Students in their final year experienced only a few differences in the clinical and teaching routine. Teaching coordinators in obstetrics and gynecology stated that they intend to incorporate more e-learning into the curriculum in the future., Conclusion: The medical educators' views presented here may help to complement the already-thoroughly investigated experiences of students under the restrictions of the COVID-19 pandemic. Medical educators in obstetrics and gynecology at German university hospitals have successfully established online and hybrid teaching alternatives to their standard face-to-face courses. Building on recent experiences, digitalization could help to improve future medical education., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following potential competing interests: Niklas Amann, Florian Recker, and Martin Weiss are members of the “Junges Forum in der DGGG” (i.e., the official German organization and interest group of physicians in training in OB/GYN within the German Society for Gynecology and Obstetrics). This does not alter our adherence to PLOS ONE policies on sharing data and material.

The updip limit of seismic rupture during a megathrust earthquake exerts a major control on the size of the resulting tsunami. Offshore Northern Chile, the 2014 Mw 8.1 Iquique earthquake ruptured the plate boundary between 19.5° and 21°S. Rupture terminated under the mid-continental slope and did not propagate updip to the trench. Here, we use state-of-the-art seismic reflection data to investigate the tectonic setting associated with the apparent updip arrest of rupture propagation at 15 km depth during the Iquique earthquake. We document a spatial correspondence between the rupture area and the seismic reflectivity of the plate boundary. North and updip of the rupture area, a coherent, highly reflective plate boundary indicates excess fluid pressure, which may prevent the accumulation of elastic strain. In contrast, the rupture area is characterized by the absence of plate boundary reflectivity, which suggests low fluid pressure that results in stress accumulation and thus controls the extent of earthquake rupture. Generalizing these results, seismic reflection data can provide insights into the physical state of the shallow plate boundary and help to assess the potential for future shallow rupture in the absence of direct measurements of interplate deformation from most outermost forearc slopes., (© 2022. The Author(s).)

Background: Research suggests that a low omega-3 index may contribute to the low heart rate variability and the increased risk of cardiovascular morbidity and mortality in bipolar disorders. However, so far, no intervention trial with EPA and DHA has been conducted in bipolar patients attempting to increase their heart rate variability., Methods: 119 patients with bipolar disorder according to DSM-IV were screened, with 55 euthymic bipolar patients-owing to inclusion criteria (e.g. low omega-3 index (< 6%), SDNN < 60 ms.)-being enrolled in a randomized, double-blind, 12-week parallel study design with omega-3 fatty acids (4 capsules of 530 mg EPA, 150 mg DHA) or corn oil as a placebo, in addition to usual treatment. Heart rate variability as well as the omega-3 index were measured at baseline and at the endpoint of the study., Results: A total of 42 patients (omega-3: n = 23, corn oil: n = 19) successfully completed the study after 12 weeks. There was a significant increase in the omega-3 index (value at endpoint minus value at baseline) in the omega-3 group compared to the corn oil group (p < 0.0001). However, there was no significant difference in the change of the SDNN (value at endpoint minus value at baseline) between the treatment groups (p = 0.22). In addition, no correlation between changes in SDNN and change in the omega-3 index could be detected in the omega-3 group (correlation coefficient = 0.02, p = 0.94) or the corn oil group (correlation coefficient =  - 0.11, p = 0.91). Similarly, no significant differences between corn oil and omega-3 group regarding the change of LF (p = 0.19), HF (p = 0.34) and LF/HF ratio (p = 0.84) could be demonstrated., Conclusions: In our randomized, controlled intervention trial in euthymic bipolar patients with a low omega-3 index and reduced heart rate variability no significant effect of omega-3 fatty acids on SDNN or frequency-domain measures HF, LF and LF/HF ratio could be detected. Possible reasons include, among others, the effect of psychotropic medication present in our trial and/or the genetics of bipolar disorder itself. Further research is needed to test these hypotheses. Trial registration ClinicalTrials.gov, NCT00891826. Registered 01 May 2009-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT00891826., (© 2022. The Author(s).)

Purpose: The onset of the COVID-19 pandemic posed an eminent challenge for medical teachers worldwide. Face-to-face lectures and seminars were no longer possible, and alternatives had to be found. E-learning concepts quickly emerged as the only practicable solutions and also offered the opportunity to evaluate whether traditional face-to-face lectures could be translated into an online format, independent of the COVID-19 pandemic., Methods: We offered an e-learning program consisting of lecture notes, screencasts with audio narration, and online webinars that covered topics normally taught in traditional lectures and seminars. To evaluate the learning behavior and quality of our e-learning program, we drafted a questionnaire that students completed at the end of the 2020 summer semester that had been designed to enable a comparative analysis of the different e-learning modules., Results: Voluntary participation in the online courses was high. Survey analysis revealed high satisfaction with and a distinctive preference for the format, even under regular, COVID-19-independent conditions. In general, a positive appraisal of e-learning-especially as a substitute for regular lectures-was found. Students also reported higher studying efficiency. Exam results were equal to those of previous semesters., Conclusion: Both acceptance of and satisfaction with our e-learning modules were high, and students displayed increased demand for this kind of e-learning format. We, therefore, conclude that e-learning offerings could serve as reasonable, efficient, student-orientated substitutes for certain medical courses, especially lectures. These curricular adaptations would correlate with the high digitalization seen in students' everyday lives. This correlation may also hold true independent of the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

The application of artificial intelligence (AI) is often associated with the use of large amounts of data for the construction of AI models and algorithms. This data should ideally comply with the FAIR Data principles, i.e. being findable, accessible, interoperable and reusable. However, the handling of health data poses a particular challenge in this context. In this article, we highlight the challenges of the data usage for AI in medicine using the example of anaesthesia and intensive care medicine. We discuss the current situation but also the obstacles for a wider application of AI in medicine in Europe and give suggestions how to solve the different issues. The article covers different subjects like data protection, research data infrastructures and approval of medical products. Finally, this article shows how it can nevertheless be possible to establish a secure and at the same time effective handling of data for use in AI at the European level despite its unneglectable difficulties., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The distributional data on the Ukrainian Carpathian mesochorines are summarized. The list contains 64 species belonging to three genera. The genus Astiphromma Frster, 1869 numbering 14 species, of which A. albitarse (Brischke, 1880) and A. flagellator Riedel, 2015, are the first records for Ukraine. All three European species of the genus Cidaphus Frster, 1869 are distributed in the studied region and are the first records from the country. The genus Mesochorus Gravenhorst, 1829 is the most species-rich genus of the subfamily with 46 species found in the Ukrainian Carpathians, containing newly described M. (Mesochorus) genator sp. n. and 41 species recorded from the Ukrainian fauna for the first time. Taxonomic remarks and illustrations for most of the species are provided.

A new ichneumonid species, Syzeuctus flavocephalus Zardouei Riedel sp. nov. (Hymenoptera: Ichneumonidae: Banchinae) from the Eastern high mountains of Iran (Sistan-o Baluchestan province) is described and illustrated. Together with this new species, nine previously recorded species from Iran are reviewed, and a comprehensive key of the Iranian species of Syzeuctus is provided.

Background: Around 20% - 30% of depressed individuals experience a chronic form of depression lasting two or more years. This naturalistic study investigates the characteristics and the course of chronic depressed patients (CD) during standard antidepressant treatment in comparison to not chronically depressed (NCD) patients., Methods: Data of 954 patients were drawn from the prospective naturalistic, multicenter study of the German research network on depression, CD was met as classifier by 113 patients (11.8%), whereas 841 patients (88.2%) had non-chronic courses (NCD)., Results: CD was significantly associated with a low age at onset, use of benzodiazepines, psychotherapy at baseline, substance abuse, a depressive personality disorder and a low degree of extraversion. CD patients showed a longer hospital stay, lower remission rates, increased rates of suicidal ideation as well as higher depression scores at discharge. In addition, individuals with chronic depression continued to obtain higher neuroticism scores and lower extraversion scores at discharge., Limitation: Results were assessed by a post-hoc analysis, based on prospectively collected data., Conclusion: CD patients have an inferior outcome in clinical measures as well as personality dimensions (i.e. low extraversion) compared to non-CD patients. These findings support the notion that CD patients entering a setting of standard psychiatric inpatient care will show less benefit compared to non-CD patients, and that this difference as such may be used as a stratifying marker for providing specialized psychiatric treatment with optimized pharmacological and psychotherapeutic protocols., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: The field of obstetrics and gynecology (OB/GYN) is facing growing competition for young professionals in Germany, with high interest rates among female graduates and a declining proportion of male students who choose residency training in the field. The aim of this study is to analyze general and gender-dependent factors that influence the decision for or against specialty training in OB/GYN among medical students in Germany., Methods: Between February and November 2019, n = 346 medical students in their 5th and 6th year of undergraduate training at Heidelberg University received a questionnaire with 44 items., Results: n = 286 students (61.3 female; 38.7% male) participated in the study. 28% of the female students and 9% of the male students had considered OB/GYN for their specialty training. The students reported different general and gender-specific influencing factors in their choice of a specialty. Both genders desired a good work-life-balance, however, in comparison with their female colleagues, male students had heavily weighted factors related to their later careers and professional success, including competition among colleagues. Male students had gained little practical experience during compulsory internships (26.9% for females vs. 8.8% for males) or had chosen their final-year elective in OB/GYN (15.9% for females vs. 5.5% for males). Female students had worried about the negative effects of their sex on their career (35.4% for females vs. 5.9% for males)., Conclusion: OB/GYN must become more appealing and attractive to young female and male professionals alike. A better compatibility of career and family should go hand in hand with the implementation of differentiated, (extra) curricular teaching approaches that take the different preferences of female and male students into account., (© 2021. The Author(s).)

Two-dimensional (2D) Talbot array illuminators (TAIs) were designed, fabricated, and evaluated for high-resolution high-contrast x-ray phase imaging of soft tissue at 10-20 keV. The TAIs create intensity modulations with a high compression ratio on the micrometer scale at short propagation distances. Their performance was compared with various other wavefront markers in terms of period, visibility, flux efficiency, and flexibility to be adapted for limited beam coherence and detector resolution. Differential x-ray phase contrast and dark-field imaging were demonstrated with a one-dimensional, linear phase stepping approach yielding 2D phase sensitivity using unified modulated pattern analysis (UMPA) for phase retrieval. The method was employed for x-ray phase computed tomography reaching a resolution of 3 µm on an unstained murine artery. It opens new possibilities for three-dimensional, non-destructive, and quantitative imaging of soft matter such as virtual histology. The phase modulators can also be used for various other x-ray applications such as dynamic phase imaging, super-resolution structured illumination microscopy, or wavefront sensing., Competing Interests: The authors declare no conflicts of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Purpose: To develop a new water-fat separation and B 0 estimation algorithm to effectively suppress the multiple resonances of fat signal in EPI. This is especially relevant for DWI where fat is often a confounding factor., Methods: Water-fat separation based on chemical-shift encoding enables robust fat suppression in routine MRI. However, for EPI the different chemical-shift displacements of the multiple fat resonances along the phase-encoding direction can be problematic for conventional separation algorithms. This work proposes a suitable model approximation for EPI under B 0 and fat off-resonance effects, providing a feasible multi-peak water-fat separation algorithm. Simulations were performed to validate the algorithm. In vivo validation was performed in 6 volunteers, acquiring spin-echo EPI images in the leg (B 0 homogeneous) and head-neck (B 0 inhomogeneous) regions, using a TE-shifted interleaved EPI sequence with/without diffusion sensitization. The results are numerically and statistically compared with voxel-independent water-fat separation and fat saturation techniques to demonstrate the performance of the proposed algorithm., Results: The reference separation algorithm without the proposed spatial shift correction caused water-fat ambiguities in simulations and in vivo experiments. Some spectrally selective fat saturation approaches also failed to suppress fat in regions with severe B 0 inhomogeneities. The proposed algorithm was able to achieve improved fat suppression for DWI data and ADC maps in the head-neck and leg regions., Conclusion: The proposed algorithm shows improved suppression of the multi-peak fat components in multi-shot interleaved EPI applications compared to the conventional fat saturation approaches and separation algorithms., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, KCNQ1 R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins., (© 2021. The Author(s).)