Background

Porcine cytomegalovirus (PCMV) is a porcine roseolovirus (PCMV/PRV) which is widely distributed in pigs. Transmission of PCMV/PRV in preclinical xenotransplantations was shown to significantly reduce the survival time of the pig transplants in non-human primates. PCMV/PRV was also transmitted in the first transplantation of a pig heart into a human patient. To analyze how PCMV/PRV could be introduced into pig breeds, especially considering cloned transgenic pigs, and subsequently spread in breeding facilities, we screened ovaries and derived materials which are used to perform somatic cell nuclear transfer (SCNT).

Methods

DNA was isolated from ovarian tissues, follicular fluids, oocytes with cumulus cells, denuded oocytes and parthenotes. A real-time PCR with PCMV/PRV-specific primers and a probe was performed to detect PCMV/PRV. Furthermore, a Western blot assay using a recombinant fragment of the gB protein of PCMV/PRV was performed to screen for virus-specific antibodies in the follicular fluids.

Results

PCMV/PRV was found by real-time PCR in ovarian tissues, in the follicular fluid and in oocytes. In parthenotes the virus could not be detected, most-likely due to the low amount of DNA used. By Western blot assay specific antibodies against PCMV/PRV were found in 19 of 20 analyzed follicular fluids.

Conclusion

PCMV/PRV was found in ovarian tissues, in the follicular fluids and also in denuded oocytes, indicating that the virus is present in the animals of which the oocytes were taken from. Despite several washing steps of the denuded oocytes, which are subsequently used for microinjection or SCNT, the virus could still be detected. Therefore, the virus could infect oocytes during genetic modifications or stay attached to the surface of the oocytes, potentially infecting SCNT recipient animals.

Obtaining accurate ground and low-lying excited states of electronic systems is crucial in a multitude of important applications. One ab initio method for solving the Schrödinger equation that scales favorably for large systems is variational quantum Monte Carlo (QMC). The recently introduced deep QMC approach uses ansatzes represented by deep neural networks and generates nearly exact ground-state solutions for molecules containing up to a few dozen electrons, with the potential to scale to much larger systems where other highly accurate methods are not feasible. In this paper, we extend one such ansatz (PauliNet) to compute electronic excited states. We demonstrate our method on various small atoms and molecules and consistently achieve high accuracy for low-lying states. To highlight the method’s potential, we compute the first excited state of the much larger benzene molecule, as well as the conical intersection of ethylene, with PauliNet matching results of more expensive high-level methods.

Porcine cytomegalovirus (PCMV), a porcine roseolovirus (PRV) that is closely related to human herpesviruses 6 and 7, is commonly found in commercial pigs. PCMV/PRV is important in xenotransplantation, because in preclinical trials in which pig organs were transplanted into non-human primates, transmission of PCMV/PRV was shown to be associated with significantly reduced survival of the xenotransplants. PCMV/PRV was also transmitted in the first transplantation of a pig heart into a human patient worldwide and apparently contributed to the death of the patient. The prevalence of PCMV/PRV in wild boars is largely unknown. In this study, we screened wild boars from several areas of northern Italy and Germany to test for the presence of PCMV/PRV using PCR-based and Western blot assays. By Western blot analysis, 54% and 82% of Italian and German wild boars, respectively, were found to be PCMV/PRV positive, while 36% and 60%, respectively, tested positive by real-time polymerase chain reaction (PCR). These data indicate that the virus is common in German and Italian wild boars and that the Western blot assay detected a PCMV/PRV infection more often than did real-time PCR. The data also indicate that pigs raised for xenotransplantation should be protected from contact with materials from wild boars and commercial pigs.

Batrachochytrium salamandrivorans (Bsal), a species related to the destructive pathogen Batrachochytrium dendrobatidis (Bd), was found and identified in Europe in 2013. Now, a decade later, a large amount of information is available. This includes data from studies in the field, reports of infection in captive amphibians, laboratory studies testing host susceptibility, and data from prospective studies that test for Bsal’s presence in a location. We conducted a systematic review of the published literature and compiled a dataset of Bsal tests. We identified 67 species that have been reported positive for Bsal, 20 of which have a threatened conservation status. The distribution of species that have been found with infection encompasses 69 countries, highlighting the potential threat that Bsal poses. We point out where surveillance to detect Bsal have taken place and highlight areas that have not been well monitored. The large number of host species belonging to the families Plethodontidae and Salamandridae suggests a taxonomic pattern of susceptibility. Our results provide insight into the risk posed by Bsal and identifies vulnerable species and areas where surveillance is needed to fill existing knowledge gaps.

TGFβs, BMPs and Activins regulate numerous developmental and homeostatic processes and signal through hetero-tetrameric receptor complexes composed of two types of serine/threonine kinase receptors. Each of the 33 different ligands possesses unique affinities towards specific receptor types. However, the lack of specific tools hampered simultaneous testing of ligand binding towards all BMP/TGFβ receptors. Here we present a N-terminally Halo- and SNAP-tagged TGFβ/BMP receptor library to visualize receptor complexes in dual color. In combination with fluorescently labeled ligands, we established a Ligand Surface Binding Assay (LSBA) for optical quantification of receptor-dependent ligand binding in a cellular context. We highlight that LSBA is generally applicable to test (i) binding of different ligands such as Activin A, TGFβ1 and BMP9, (ii) for mutant screens and (iii) evolutionary comparisons. This experimental set-up opens opportunities for visualizing ligand-receptor binding dynamics, essential to determine signaling specificity and is easily adaptable for other receptor signaling pathways.

Citizen Science (CS) is a research approach that has become popular in recent years and offers innovative potential for dialect research in ornithology. As the scepticism about CS data is still widespread, we analysed the development of a 3-year CS project based on the song of the Common Nightingale (Luscinia megarhynchos) to share best practices and lessons learned. We focused on the data scope, individual engagement, spatial distribution and species misidentifications from recordings generated before (2018, 2019) and during the COVID-19 outbreak (2020) with a smartphone using the ‘Naturblick’ app. The number of nightingale song recordings and individual engagement increased steadily and peaked in the season during the pandemic. 13,991 nightingale song recordings were generated by anonymous (64%) and non-anonymous participants (36%). As the project developed, the spatial distribution of recordings expanded (from Berlin based to nationwide). The rates of species misidentifications were low, decreased in the course of the project (10–1%) and were mainly affected by vocal similarities with other bird species. This study further showed that community engagement and data quality were not directly affected by dissemination activities, but that the former was influenced by external factors and the latter benefited from the app. We conclude that CS projects using smartphone apps with an integrated pattern recognition algorithm are well suited to support bioacoustic research in ornithology. Based on our findings, we recommend setting up CS projects over the long term to build an engaged community which generates high data quality for robust scientific conclusions.

Class imbalance poses a major challenge for machine learning as most supervised learning models might exhibit bias towards the majority class and under-perform in the minority class. Cost-sensitive learning tackles this problem by treating the classes differently, formulated typically via a user-defined fixed misclassification cost matrix provided as input to the learner. Such parameter tuning is a challenging task that requires domain knowledge and moreover, wrong adjustments might lead to overall predictive performance deterioration. In this work, we propose a novel cost-sensitive boosting approach for imbalanced data that dynamically adjusts the misclassification costs over the boosting rounds in response to model’s performance instead of using a fixed misclassification cost matrix. Our method, called AdaCC, is parameter-free as it relies on the cumulative behavior of the boosting model in order to adjust the misclassification costs for the next boosting round and comes with theoretical guarantees regarding the training error. Experiments on 27 real-world datasets from different domains with high class imbalance demonstrate the superiority of our method over 12 state-of-the-art cost-sensitive boosting approaches exhibiting consistent improvements in different measures, for instance, in the range of [0.3–28.56%] for AUC, [3.4–21.4%] for balanced accuracy, [4.8–45%] for gmean and [7.4–85.5%] for recall.

Splicing is one key mechanism determining the state of any eukaryotic cell. Apart from linear splice variants, circular splice variants (circRNAs) can arise via non-canonical splicing involving a back-splice junction (BSJ). Most existing methods only identify circRNAs via the corresponding BSJ, but do not aim to estimate their full sequence identity or to identify different, alternatively spliced circular isoforms arising from the same BSJ. We here present CYCLeR, the first computational method for identifying the full sequence identity of new and alternatively spliced circRNAs and their abundances while simultaneously co-estimating the abundances of known linear splicing isoforms. We show that CYCLeR significantly outperforms existing methods in terms of F score and quantification of transcripts in simulated data. In a in a comparative study with long-read data, we also show the advantages of CYCLeR compared to existing methods. When analysing Drosophila melanogaster data, CYCLeR uncovers biological patterns of circRNA expression that other methods fail to observe.

Introduction

Handling sexual interactions in a competent manner is a key skill for young adults, which is linked to positive aspects of sexual and general well-being. Several research conceptualizations of sexual competence have been proposed in the literature, but little is known about how young adults define sexual competence and what consequences they consider low sexual competence may have.

Methods

In this qualitative study conducted in 2019, 571 university students (365 women, 206 men) from Germany with a mean age of 22.6 years provided open-ended answers to two questions: (Q1) What do you consider to be sexual competence? (Q2) What consequences can low sexual competence have? Combining thematic analysis and qualitative content analysis, responses were coded into 264 categories that were then condensed into 30 latent themes, with 14 themes referring to Q1 and 16 themes referring to Q2. All categories showed strong inter-coder agreement.

Result

Participants defined sexual competence in a multi-faceted way and in partial overlap with research definitions. Gender differences emerged in four themes (needs/desires, communication, skills/abilities, and setting boundaries/limits). Participants’ statements about the consequences of low sexual competence corresponded closely with their definitions of sexual competence. Gender differences emerged in five themes (risk of sexual victimization and sexual aggression, problems in sexual communication, problematic [sexual] risk behavior, negative influence on [sexual] satisfaction, and lack of skills).

Conclusions and Policy Implications

The implications of the findings for research conceptualizations of sexual competence, for designing interventions to promote sexual competence, and for policy measures designed to reduce sexual aggression are discussed.

According to the United Nations, an estimated 26.6 million people worldwide were refugees in 2021. Experiences before, during, and after flight increase psychological distress and contribute to a high prevalence of mental disorders. The resulting high need for mental health care is generally not reflected in the actual mental health care provision for refugees. A possible strategy to close this gap might be to offer smartphone-delivered mental health care. This systematic review summarizes the current state of research on smartphone-delivered interventions for refugees, answering the following research questions: (1) Which smartphone-delivered interventions are available for refugees? (2) What do we know about their clinical (efficacy) and (3) nonclinical outcomes (e.g., feasibility, appropriateness, acceptance, and barriers)? (4) What are their dropout rates and dropout reasons? (5) To what extent do smartphone-delivered interventions consider data security? Relevant databases were systematically searched for published studies, gray literature, and unpublished information. In total, 456 data points were screened. Twelve interventions were included (nine interventions from 11 peer-reviewed articles and three interventions without published study reports), comprising nine interventions for adult refugees and three for adolescent and young refugees. Study participants were mostly satisfied with the interventions, indicating adequate acceptability. Only one randomized controlled trial (RCT; from two RCTs and two pilot RCTs) found a significant reduction in the primary clinical outcome compared to the control group. Dropout rates ranged from 2.9 to 80%. In the discussion, the heterogeneous findings are integrated into the current state of literature.

Various drug samples (N = 249; drug substances, tablets, capsules, solutions, crèmes, and more) from the European pharmaceutical market were collected since 2019 and analyzed for 16 nitrosamines (NAs). In 2.0% of the cases, NAs were detected. These findings included four active pharmaceutical ingredients already known for potential NA contamination: losartan (N-nitrosodimethylamine [NDMA] and N-nitrosodiethylamine, simultaneously), valsartan (NDMA), metformin (NDMA) and ranitidine (NDMA). The fifth new finding, which has not been reported yet, discovered contamination of a molsidomine tablet sample with N-nitrosomorpholine (NMor). The tablet contained 144% of the toxicological allowable intake for NMor. NMor was included in our screening from the beginning and is currently the focus of regulatory authorities, but was added to the guidelines only last year. Thus, it may not have been the focus of regulatory investigations for too long. Our results indicate that the majority of drug products in the market are nonhazardous in terms of patient safety and drug purity. Unfortunately, the list of individual affected products keeps growing constantly and new NA cases, such as molsidomine or nitrosated drug substances (nitrosamine drug substance-related impurities [NDSRI]), continue to emerge. We therefore expect nitrosamine screenings to remain a high priority.

Objective

To describe open reduction and surgical stabilization of a coxofemoral luxation in a pony using a modified toggle pin technique and prosthetic joint capsule reconstruction without osteotomy of the greater trochanter.

Animal

A 2-year-old Shetland pony with a bodyweight of 167 kg.

Study design

Case report.

Methods

Radiographic examination confirmed craniodorsal luxation of the left coxofemoral joint. An open reduction with the aid of a pulley system was performed. A toggle pin was inserted through a bone tunnel extending from the level of the femoral shaft through the femoral head and the center of the acetabulum for the pin to be positioned on the medial wall of the acetabulum. FiberWire was subsequently passed through the cranial and caudal aspects of the acetabulum as well as a transverse tunnel in the femoral neck in a figure of 8 to facilitate capsular reconstruction. The pony was placed in a sling for 8 weeks and gradually returned to normal activity over 2 months.

Results

Postoperative radiographic examination confirmed the position of the femoral head in the acetabulum with the implants in place. On 2-year follow-up the pony was sound at walk and trot.

Conclusion

A combined intra- and extra-articular stabilization technique for coxofemoral luxation in a pony resulted in successful long-term reduction and excellent outcome.

The crux of this paper is to provide a concentrated critical evaluation of Galen Strawson's innovative approach to the self. To that end, I will first attempt to concisely introduce his general thesis, which seems appropriate to be broken up into two major pieces: the phenomenology (experience) of the self, what the self would have to be; and the metaphysics of the self (i.e., a query refers to its metaphysics [its existence and nature]: whether there is any). Explaining and discussing Strawson's twofold account of the self is my first target in this paper. And it is with these two parts that I take issues. Accordingly, I shall determinedly try to develop a counterargument according to which Strawson's establishment of his entire enterprise of the self is based merely on unjustified intuitive generalisation. Next, I will put more effort into making some more argumentative points, mainly to show how his metaphysics does not give much thought to some vital matters of the self in comparison with the systems of metaphysics of his forebears of Western philosophers. What all this means is that Strawsonian metaphysical analysis of the self so conceived and so described appears philosophically to drive itself to justly be placed in an ahistorical context.

Mercuric oxide is a well-known and stable solid, but the diatomic molecule Hg-O is very fragile and do not survive detection in the gas phase. However, laser ablation of Hg atoms from a dental amalgam target into argon or neon containing about 0.3% of 16 O 2 or of 18 O 2 during their condensation into a cryogenic matrix at 4 K allows the formation of O atoms which react on annealing to make ozone and new IR absorptions in solid argon at 521.2 cm –1 for Hg- 16 O or at 496.4 cm –1 for Hg- 18 O with the oxygen isotopic frequency ratio 521.2/496.4 = 1.0500. Solid neon gives a 529.0 cm –1 absorption with a small 7.8 blue shift. CCSD(T) calculations found 594 cm –1 for Hg 16 O and 562 cm –1 for Hg 18 O (frequency ratio = 1.0569). Such calculations usually produce harmonic frequencies that are slightly higher than the anharmonic (observed) values, which supports their relationship. These observed frequencies have the isotopic shift predicted for Hg-O and are within the range of recent high-level frequency calculations for the Hg-O molecule. Spectra for the related mercury superoxide and ozonide species are also observed for the first time.

The one-sided Möbius strip with its characteristic 180° twist in the loop has inspired philosophers, artists and scientists since hundreds of years and continues to do so. On the molecular level, only in the last 15 years have some groups succeeded in synthesizing new expanded porphyrin compounds large enough to adopt Möbius-strip topology and Möbius aromaticity, the first being Lechosław Latos-Grażyński and collaborators in Wroclaw (2007) and Atsuhiro Osuka and collaborators in Kyoto (2008). We report on new studies of expanded porphyrins with either Möbius topology or Hückel topology that were synthesized in these laboratories. In this minireview, we focus on recent continuous-wave and time-resolved EPR, ENDOR and DFT MO studies on open-shell states of di-p-benzi[28]hexaphyrin(1.1.1.1.1.1), specifically, on the ground-state radical cation doublet state (total electron spin S = 1/2) and the first excited triplet state (S = 1). The review is largely based on the results and discussions of two previous publications: Möbius et al. (Appl Magn Reson 47:757–780, 2016) and Ema et al. (J Phys Chem Lett 9:2685–2690, 2018). In the open-shell systems, besides the electron-nuclear hyperfine couplings also the zero-field interaction tensor turned out to be a viable sensor for electronic structure changes between Möbius and Hückel topologies. In the Outlook section, we address the cyclotides, a new class of natural circular mini-proteins, usually less than 100 amino acids long. They are distinguished by exceptional chemical and biological stability. This is due to topological constraints imposed by threefoil knot and Möbius-strip formation. As a result, their physical qualities are “topologically protected”. This makes them highly interesting for medical or agricultural applications, for example as novel active ingredients against autoimmune diseases, viral infections, or as agents against insect damage to crops.

The synthesis and the first structural characterization of the halogenated pyridinium salts [C 5 F 5 NH] + , [C 5 F 4 ClNH] + , [(C 5 F 5 N) 2 H] + , [(C 5 Cl 5 N) 2 H] + of the weakly coordinating anion (WCA) [Al(OTeF 5 ) 4 ] − , showing noncovalent interactions in the solid state, are presented. The salts were characterized by the multinuclear NMR and IR spectroscopy as well as X-Ray diffraction. Hirshfeld surface analysis and solid state structures reveal various intermolecular anion-π and σ-hole interactions between the corresponding halogenated pyridinium cations and the anion [Al(OTeF 5 ) 4 ] − .

p-Fluorophenylisocyanide (CNPhpF) reacts with [Re(CO)5Br] under stepwise exchange of the carbonyl ligands depending on the conditions applied. The reaction stops with the formation of fac-[Re(CO)3Br(CNPhpF)2] in boiling THF. An ongoing carbonyl exchange is observed at higher temperatures, e. g. in refluxing toluene, with the final formation of the [Re(CNPhpF)6]+ cation. The progress of the reactions has been studied by 19F NMR spectroscopy and the structures of [Re(CO)Br(CNPhpF)4] and [Re(CNPhpF)6](BPh4) have been elucidated by X-ray diffraction.

Many quantum information protocols require the implementation of random unitaries. Because it takes exponential resources to produce Haar-random unitaries drawn from the full n-qubit group, one often resorts to t-designs. Unitary t-designs mimic the Haar-measure up to t-th moments. It is known that Clifford operations can implement at most 3-designs. In this work, we quantify the non-Clifford resources required to break this barrier. We find that it suffices to inject O(t4log2(t)log(1/ε)) many non-Clifford gates into a polynomial-depth random Clifford circuit to obtain an ε-approximate t-design. Strikingly, the number of non-Clifford gates required is independent of the system size – asymptotically, the density of non-Clifford gates is allowed to tend to zero. We also derive novel bounds on the convergence time of random Clifford circuits to the t-th moment of the uniform distribution on the Clifford group. Our proofs exploit a recently developed variant of Schur-Weyl duality for the Clifford group, as well as bounds on restricted spectral gaps of averaging operators.

This work improves the characterization and knowledge of the surface wind climatology over Europe with the development of an observational database with unprecedented quality control (QC), the European Surface Wind Observational database (EuSWiO). EuSWiO includes more than 3,829 stations with sub-daily resolution for wind speed and direction, with a number of sites spanning the period of 1880–2017, a few hundred time series starting in the 1930s and relatively good spatial coverage since the 1970s. The creation of EuSWiO entails the merging of eight different data sets and its submission to a common QC. About 5% of the total observations were flagged, correcting a great part of the extreme and unrealistic values, which have a discernible impact on the statistics of the database. The daily wind variability was characterized by means of a classification technique, identifying 11 independent subregions with distinct temporal wind variability over the 2000–2015 period. Significant decreases in the wind speed during this period are found in five regions, whereas two regions show increases. Most regions allow for extending the analysis to earlier decades. Caution in interpreting long-term trends is needed as wind speed data have not been homogenized. Nevertheless, decreases in the wind speed since the 1980s can be noticed in most of the regions. This work contributes to a deeper understanding of the temporal and spatial surface wind variability in Europe. It will allow from meteorological to climate and climate change studies, including potential applications to the analyses of extreme events, wind power assessments or the evaluation of reanalysis or model-data comparison exercises at continental scales.