University of Cologne

Zusammenfassung Forschendes Lernen in den Naturwissenschaften intendiert, dass Lernende den wissenschaftlichen Erkenntnisprozess selbst durchlaufen, um ihre Problemlösefähigkeiten zu schulen und ein Verständnis von Naturwissenschaft als Disziplin zu entwickeln. Wie sich die Gruppenarbeitsprozesse von Lernenden beim Experimentieren im Vergleich zu den programmatischen Erwartungen an das Forschende Lernen gestalten, ist die Fragestellung der vorliegenden Studie. Untersucht werden Experimentierprozesse von Lehramtsstudierenden des Faches Biologie. Bereits im Studium sind curriculare Angebote Forschenden Lernens vorgesehen, um angehenden Lehrpersonen eigene Erfahrungen und deren systematische Reflexion im Hinblick auf die spätere Anleitung forschungsbasierter Lernformen zu ermöglichen. Mittels der Dokumentarischen Methode streben wir an, die in-situ-Prozesse des Experimentierens – im Verhältnis zu mit der Aufgabenbearbeitung intendierten fachdidaktischen Zielen – zu rekonstruieren. Untersucht werden die handlungsleitenden Orientierungen der Studierendengruppen sowohl hinsichtlich der fachlichen Erkenntniswege als auch in Bezug auf ihre Interaktionsmodi. Im Ergebnis zeigen die Analysen für die Gruppen unterschiedliche Zugänge zur gestellten Aufgabe, die sich kontrastiv als hypothesen- und materialbasiert unterscheiden lassen. Hinsichtlich der Gruppeninteraktion können einvernehmliche und aushandlungsorientierte Modi rekonstruiert werden. Diskutiert werden die vorliegenden Befunde im Hinblick auf die Zielsetzungen Forschenden Lernens in den Naturwissenschaftsdidaktiken sowie den institutionellen Kontext der universitären Lehrer*innenbildung.

This article explores the effect of one's body representation on time perception. Time Perception is modulated by a variety of factors including, e.g., the current situation or activity, it can display significant disturbances caused by psychological disorders, and it is influenced by emotional and interoceptive states, i.e., “the sense of the physiological condition of the body”. We investigated this relation between one's own body and the perception of time in a novel Virtual Reality (VR) experiment explicitly fostering user activity. Forty-Eight participants randomly experienced different degrees of embodiment: i) without an avatar (low), ii) with hands (medium), and iii) with a high-quality avatar (high). Participants had to repeatedly activate a virtual lamp and estimate the duration of time intervals as well as judge the passage of time. Our results show a significant effect of embodiment on time perception: time passes slower in the low embodiment condition compared to the medium and high conditions. In contrast to prior work, the study provides missing evidence that this effect is independent of the level of activity of participants: In our task, users were prompted to repeatedly perform body actions, thereby ruling-out a potential influence of the level of activity. Importantly, duration judgements in both the millisecond and minute ranges seemed unaffected by variations in embodiment. Taken together, these results lead to a better understanding of the relationship between the body and time.

1. E i n l e i t u n g.1 Es ist ein schon seit Längerem bekannter Zug einiger ost- und südaukštaitischer Dialekte des Litauischen, dass sie Langformen der 3. Person des Konjunktivs (auch Konditional, Irrealis oder Optativ genannt) neben entsprechenden Kurzformen zeigen:2 So begegnen z. B. im ostaukštaitischen Inseldialekt von Lazūnai (wruss. Lazduny, heutiges Weißrussland) Formen des Typs 3 cond. dúotų neben solchen des Typs 3 cond. dúot.3 Diese Erscheinung zeigt sich in neuerer Zeit im Wesentlichen auf östliches ostaukštaitisches und südaukštaitisches Gebiet beschränkt,4 ist aber historisch auch für den Rest des litauischen Sprachgebiets – d. i. das Westaukštaitische und das Žemaitische – nachzuweisen.5 Die Langformen des Typs dúotų, btų, die heute in der Standardsprache alleinige Geltung beanspruchen, entsprechen insofern der sprachhistorischen Erwartung, als sie das dem Konjunktiv zugrundeliegende Supinum direkt lautlich fortsetzen: 3 cond. lit. dúotų, btų, lett. duôtu, bûtu < sup. urbsl. *ˈdṓ-tuñ, *ˈb-tuñ (vgl. aksl. datъ, bytъ, apr. dātun, būton). Im Gegensatz hierzu sind Kurzformen wie dúot, bt unerwartet; ihnen fehlt das für den Konjunktiv und das Supinum eigentlich charakteristische auslautende -ų, das normalerweise im Sprachsystem erhalten ist, wie Formen des Typs acc. sg. m. snų, gen. pl. m./f. balt, pron. pers. 1 pl. gen. msų, pron. pers. 2 pl. gen. jsų zeigen.6

At the present state of discourse, the issue of incomprehensibility is clouded by unresolved problems. We propose that this confusion stems from three distinct sources. In the following, we elaborate on each of them and advance a schema for structuring the discourse on schizophrenic incomprehensibility (see table 1): 1. Overreliance on delusional beliefs. The problem of incomprehensibility is ill-posed, biasing the discourse towards the delusional beliefs as is evidenced by their characterization in the ICD and DSM. Consequently, the origin and the experience of delusions are overlooked. Since they lie at the root of the psychopathology of schizophrenia, the discourse on the origin and experiential structure of incomprehensibility must be revisited. 2. False threat of irrationalism. Acknowledging the clinical reality of schizophrenic incomprehensibility is misevaluated as endangering the scientific status of psychopathology by pushing it towards irrationalism. Such an evaluation ultimately hinders the project of determining the possibilities and limits of psychopathological knowledge, which is essential to establishing it as a strict science: In light of the phenomenological approach, schizophrenic incomprehensibility does not mark the endpoint of our understanding of schizophrenia but is a starting point for developing a psychopathological agnotology (i.e., the scientific investigation of the production and experience of incomprehensibility). 3. Equivocations. The discourse on incomprehensibility is riddled with equivocations. This means that conflating concepts such as un-understandability, oddity, schizophrenic alterity or the praecox feeling is the norm rather than the exception. In order to distinguish these related concepts, it is helpful to consider their intellectual origins and to systematically classify competing approaches to schizophrenic incomprehensibility. Considering incomprehensibility can aid in enriching the discourse by moving beyond the classical framing in terms of the understanding-explanation dichotomy to the more adequate and encompassing trichotomy of un-understandability (“Unverständlichkeit”), obscurity (“Uneinfühlbarkeit”) and inexplicability (“Unerklärbarkeit”).

Darwinian evolution is driven by random mutations, genetic recombination (gene shuffling) and selection that favors genotypes with high fitness. For systems where each genotype can be represented as a bitstring of length L, an overview of possible evolutionary trajectories is provided by the L-cube graph with nodes labeled by genotypes and edges directed toward the genotype with higher fitness. Peaks (sinks in the graphs) are important since a population can get stranded at a suboptimal peak. The fitness landscape is defined by the fitness values of all genotypes in the system. Some notion of curvature is necessary for a more complete analysis of the landscapes, including the effect of recombination. The shape approach uses triangulations (shapes) induced by fitness landscapes. The main topic for this work is the interplay between peak patterns and shapes. Because of constraints on the shapes for L=3\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$L=3$$\end{document} imposed by peaks, there are in total 25 possible combinations of peak patterns and shapes. Similar constraints exist for higher L. Specifically, we show that the constraints induced by the staircase triangulation can be formulated as a condition of universal positive epistasis, an order relation on the fitness effects of arbitrary sets of mutations that respects the inclusion relation between the corresponding genetic backgrounds. We apply the concept to a large protein fitness landscape for an immunoglobulin-binding protein expressed in Streptococcal bacteria.

Background Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient’s pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow. Methods A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab. Results At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00). Conclusion This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.

In a nanowire (NW) of a three-dimensional topological insulator (TI), the quantum confinement of topological surface states leads to a peculiar sub-band structure that is useful for generating Majorana bound states. Top-down fabrication of TINWs from a high-quality thin film would be a scalable technology with great design flexibility, but there has been no report on top-down-fabricated TINWs where the chemical potential can be tuned to the charge neutrality point (CNP). Here we present a top-down fabrication process for bulk-insulating TINWs etched from high-quality (Bi1-xSbx)2Te3 thin films without degradation. We show that the chemical potential can be gate-tuned to the CNP, and the resistance of the NW presents characteristic oscillations as functions of the gate voltage and the parallel magnetic field, manifesting the TI-sub-band physics. We further demonstrate the superconducting proximity effect in these TINWs, preparing the groundwork for future devices to investigate Majorana bound states.

Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of C. acnes were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that C. acnes subsp. acnes IA1 was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, C. acnes subsp. acnes IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, C. acnes subsp. elongatum (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no P values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of C. acnes, possibly with the exception of C. acnes subsp. elongatum, are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by C. acnes. IMPORTANCE Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) C. acnes isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all C. acnes subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.

Progress in predictive medicine has increased the challenges to navigating complex risk information for patients and healthcare professionals. This contribution investigates how people facing the risk of developing Alzheimer’s dementia perceive risk, what aspects are relevant to their health literacy, and how to promote individual health literacy in predictive medicine. We conducted a qualitative study analyzing narrative interviews, body maps, and sociodemographic data from persons who had undergone early predictive procedures in a memory clinic. We understand the promotion of health literacy as an ethical task in predictive medicine and argue for (1) emphasizing personal resources to promote subjective health literacy, (2) reframing communication and decision-making about disease risk, and (3) teaching skills for value-sensitive, individualized risk communication.

Background: Differentiated thyroid cancer (DTC) in adolescents is a rare disease with favorable outcome, despite higher rates of cervical lymph node and pulmonary metastasis compared to adults. Aim of this study was to critically evaluate its treatment. Methods: Patients receiving postoperative radiojodine treatment (RAIT) for DTC between 2005 and 2020 at our institution were screened to identify adolescents according to the WHO definition (10-19 years of age). Demographics, clinico-pathologic characteristics, treatment and outcome were analyzed. Results: Among 1897 DTC patients 23 (1.3%) were adolescents (median age 16 years, range 10-18). The female to male ratio was 3.6:1. Classic papillary thyroid cancer was seen in 60%, follicular variant in 40% of cases, which is higher than reported in the literature (15-25%) for this age group. pT-status was pT1 in 9 (39.2%), pT2 in 8 (34.8%), pT3 in 3 (13%) and pT4 status in 3(13%) patients. In 19 (82.6%) patients, central lymphadenectomy was performed revealing metastasis in 57%. All patients received RAIT with an initial activity of 1.2 (n=1, 4.3%), 2 (n=12, 52.2%) or 3.7 GBq (n=10, 43.5%). Eighteen (78.2%) patients are free of biochemical and radiologic disease in a median follow-up of 60.7 months. Second-line surgery of lymph nodal relapse was necessary in 3 (13%) cases. There was one disease-associated death. Conclusion: Despite high rates of metastasis, most patients were cured, and second-line surgery was rarely required. Further prospective studies are needed to determine whether less aggressive surgical management or omitting adjuvant RAIT are feasible in limited stages.

In modern information societies, evaluating information, data, or knowledge claims is crucial. As these activities are influenced by epistemological beliefs, such beliefs are a key element of education in the sense that educational institutions intend to prepare students for professional and social life. Hence, this study aims to examine the development of students' epistemological beliefs about mathematics in the course of studying mathematics at university level. In a sequential cohort study, 1774 responses of mathematics students were surveyed in three consecutive years. The participants rated claims about the nature of mathematical knowledge in a spontaneous manner-a research procedure stimulating their connotative aspects of epistemological beliefs. Analyses showed that students hold different epistemological beliefs regarding 'mathematics as a scientific discipline' and 'mathematics as a school subject'-with mathematics major students and future upper secondary school teachers rating 'mathematics as a school subject' to be relatively simple and superficial compared to future primary school and lower secondary school teachers. Nonetheless, all student groups find 'mathe-matics as a scientific discipline' to be significantly more complex and profound than 'mathematics as a school subject'. Interestingly, the domain-specific beliefs remain rather stable in the course of studies regardless of the students' study programme. ARTICLE HISTORY

Cartilaginous fishes are renowned for a keen sense of smell, a reputation based on behavioral observations and supported by the presence of large and morphologically complex olfactory organs. At the molecular level, genes belonging to the four families coding for most olfactory chemosensory receptors in other vertebrates have been identified in a chimera and a shark, but it was unknown whether they actually code for olfactory receptors in these species. Here we describe the evolutionary dynamics of these gene families in cartilaginous fishes using genomes of a chimera, a skate, a sawfish and eight sharks. The number of putative OR, TAAR and V1R/ORA receptors is very low and stable whereas the number of putative V2R/OlfC receptors is higher and much more dynamic. In the catshark Scyliorhinus canicula, we show that many V2R/OlfC receptors are expressed in the olfactory epithelium in the sparsely distributed pattern characteristic for olfactory receptors. In contrast, the other three vertebrate olfactory receptor families are either not expressed (OR) or only represented with a single receptor (V1R/ORA and TAAR). The complete overlap of markers of microvillous olfactory sensory neurons with panneuronal marker HuC in the olfactory organ suggests the same cell type specificity of V2R/OlfC expression as for bony fishes, i.e. in microvillous neurons. The relatively low number of olfactory receptors in cartilaginous fishes compared to bony fishes could be the result of an ancient and constant selection in favor of a high olfactory sensitivity at the expense of a high discrimination capability.

Objective Restrictive foramen ovale (FO) in dextro-transposition of the great arteries (d-TGA) with intact ventricular septum may lead to severe life-threatening hypoxia within the first hours of life, making urgent balloon atrial septostomy (BAS) inevitable. Reliable prenatal prediction of restrictive FO is crucial in these cases. However, current prenatal echocardiographic markers show low predictive value, and prenatal prediction often fails with fatal consequences for a subset of newborns. In this study, we described our experience and aimed to identify reliable predictive markers for BAS. Methods We included 45 fetuses with isolated d-TGA that were diagnosed and delivered between 2010 and 2022 in two large German tertiary referral centers. Inclusion criteria were the availability of former prenatal ultrasound reports, of stored echocardiographic videos and still images, which had to be obtained within the last 14 days prior to delivery and that were of sufficient quality for retrospective re-analysis. Cardiac parameters were retrospectively assessed and their predictive value was evaluated. Results Among the 45 included fetuses with d-TGA, 22 neonates had restrictive FO postnatally and required urgent BAS within the first 24 h of life. In contrast, 23 neonates had normal FO anatomy, but 4 of them unexpectedly showed inadequate interatrial mixing despite their normal FO anatomy, rapidly developed hypoxia and also required urgent BAS (‘bad mixer’). Overall, 26 (58%) neonates required urgent BAS, whereas 19 (42%) achieved good O2 saturation and did not undergo urgent BAS. In the former prenatal ultrasound reports, restrictive FO with subsequent urgent BAS was correctly predicted in 11 of 22 cases (50% sensitivity), whereas a normal FO anatomy was correctly predicted in 19 of 23 cases (83% specificity). After current re-analysis of the stored videos and images, we identified three highly significant markers for restrictive FO: a FO diameter < 7 mm (p < 0.01), a fixed (p = 0.035) and a hypermobile (p = 0.014) FO flap. The maximum systolic flow velocities in the pulmonary veins were also significantly increased in restrictive FO (p = 0.021), but no cut-off value to reliably predict restrictive FO could be identified. If the above markers are applied, all 22 cases with restrictive FO and all 23 cases with normal FO anatomy could correctly be predicted (100% positive predictive value). Correct prediction of urgent BAS also succeeded in all 22 cases with restrictive FO (100% PPV), but naturally failed in 4 of the 23 cases with correctly predicted normal FO (‘bad mixer’) (82.6% negative predictive value). Conclusion Precise assessment of FO size and FO flap motility allows a reliable prenatal prediction of both restrictive and normal FO anatomy postnatally. Prediction of likelihood of urgent BAS also succeeds reliably in all fetuses with restrictive FO, but identification of the small subset of fetuses that also requires urgent BAS despite their normal FO anatomy fails, because the ability of sufficient postnatal interatrial mixing cannot be predicted prenatally. Therefore, all fetuses with prenatally diagnosed d-TGA should always be delivered in a tertiary center with cardiac catheter stand-by, allowing BAS within the first 24 h after birth, regardless of their predicted FO anatomy.

Purpose Rising incidence of pancreatic ductal adenocarcinoma (PDAC) bind with insufficient therapy options showcases a great medical challenge. Further biomarkers are required to identify patients, who will benefit from more aggressive therapy. Methods 320 patients were included by the PANCALYZE study group. Cytokeratin 6 (CK6) immunohistochemical staining as a putative marker for the basal-like subtype of PDAC was performed. The correlation between CK6 expression patterns and survival data, as well as various markers of the (inflammatory) tumor microenvironment, were analyzed. Results We divided the study population based on the expression pattern of CK6. Patients with a high CK6 tumor expression had a significantly shorter survival (p = 0.013), confirmed in a multivariate cox regression model. CK6-expression is an independent marker for a decreased overall survival (HR = 1.655, 95% CI 1.158–2.365, p = 0.006). In addition, the CK6-positive tumors showed significantly less plasma cell infiltration and more cancer-associated fibroblasts (CAFs) expressing Periostin and SMA. Conclusions CK6 could be considered as an independent biomarker for a shorter overall survival. CK6 is a clinically easily accessible biomarker for the identification of the basal-like subtype of PDAC. Therefore, it could be taken into consideration in deciding for the more aggressive therapy regimes. Prospectively, studies addressing the chemosensitive characteristics of this subtype are required.

Exome-wide sequencing studies recently described PTPN11 as a novel brain somatic epilepsy gene. In contrast, germline mutations of PTPN11 are known to cause Noonan syndrome, a multisystem disorder characterized by abnormal facial features, developmental delay, and sporadically, also brain tumors. Herein, we performed a deep phenotype-genotype analysis of a comprehensive series of ganglioglioma (GG) with brain somatic alterations of the PTPN11/KRAS/NF1 genes compared to GG with common MAP-Kinase signaling pathway alterations, i.e., BRAFV600E. Seventy-two GG were submitted to whole exome sequencing and genotyping and 84 low grade epilepsy associated tumors (LEAT) to DNA-methylation analysis. In 28 tumours, both analyses were available from the same sample. Clinical data were retrieved from hospital files including disease onset, age at surgery, brain localization, and seizure outcome. A comprehensive histopathology staining panel was available in all cases. We identified eight GG with PTPN11 alterations, copy number variant (CNV) gains of chromosome 12, and the commonality of additional CNV gains in NF1, KRAS, FGFR4 and RHEB, as well as BRAFV600E alterations. Histopathology revealed an atypical glio-neuronal phenotype with subarachnoidal tumor spread and large, pleomorphic, and multinuclear cellular features. Only three out of eight patients with GG and PTPN11/KRAS/NF1 alterations were free of disabling-seizures 2 years after surgery (38% had Engel I). This was remarkably different from our series of GG with only BRAFV600E mutations (85% had Engel I). Unsupervised cluster analysis of DNA methylation arrays separated these tumours from well-established LEAT categories. Our data point to a subgroup of GG with cellular atypia in glial and neuronal cell components, adverse postsurgical outcome, and genetically characterized by complex alterations in PTPN11 and other RAS-/MAP-Kinase and/or mTOR signaling pathways. These findings need prospective validation in clinical practice as they argue for an adaptation of the WHO grading system in developmental, glio-neuronal tumors associated with early onset focal epilepsy.

Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort (n = 100), and validate in an independent cohort (n = 86), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.

Sporotrichosis is an implantation mycosis caused by the dimorphic fungus Sporothrix and mostly involves cutaneous and subcutaneous tissues and the lymphatic vessels. Among more than 50 different species, only Sporothrix schenckii, Sporothrix globosa and Sporothrix brasiliensis are frequently reported to cause infections in humans. Sporothrix brasiliensis is remarkably virulent and has been spreading rapidly in Brazil and other Latin American countries. In this study, we aimed to determine the genetic relatedness and antifungal susceptibility of Sporothrix strains by analysing 89 isolates from humans and cats in Curitiba, Southern Brazil. Calmodulin sequencing identified 81 S. brasiliensis and seven S. schenckii isolates. Amplified fragment length polymorphism genotyping analysis showed feline and human isolates clustering together. In vitro susceptibility testing with seven antifungals demonstrated a broad activity against all tested S. brasiliensis isolates, with no significant differences in minimal inhibitory concentration (MIC) values between feline and human isolates. Resistance was solely observed in one human isolate against itraconazole and posaconazole, with MICs of ≥16 μg/mL against both antifungals. Whole genome sequencing (WGS) analysis on this isolate and two related susceptible isolates did not reveal any unique substitutions in resistance-associated genes, including cyp51, hmg and erg6, when compared to two related susceptible isolates. The novel antifungal olorofim exhibited excellent activity against this large isolate collection, with all isolates considered as susceptible. Altogether, we indicate zoonotic transmission based on genotyping and revealed a broad activity of seven common antifungals, including olorofim, against a large S. brasiliensis isolate collection.

In the “coal province” of Shanxi, residents grapple with tensions between caring for their families and caring about their environment. In creating ethical pathways through care, residents must navigate the paradox of livelihoods dependent on forms of development that endanger lives and pollute environments. This dilemma has crystallized over time, as the personal and particular demands of the present have become enmeshed with long-standing concerns over environmental degradation. Rather than characterizing family care as concrete and environmental care as abstract, acts of care in Shanxi link the reproductive crisis of the family with the reproductive crisis of the environment: the article presents instances under which the attention, empathy and recognition of care for concrete others are scaled up to the levels of ecology and planetary crisis.

Purpose In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group. Methods We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group. Results In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age ( R = − 74.04, T = − 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy ( p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses ( p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological. Conclusion NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.