Scientific reasoning (SR) skills and nature of science (NOS) beliefs represent important characteristics of biology teachers’ professional competence. In particular, teacher education at university is formative for the professionalization of future teachers and is thus the focus of the current study. Our study aimed to examine the development of SR skills and NOS beliefs and their mutual relationship during teacher education. We applied paper-and-pencil tests to measure SR skills and NOS beliefs of 299 preservice biology teachers from 25 universities in Germany. The results of linear mixed models and planned comparisons revealed that both SR skills and NOS beliefs develop over the course of the study. Nevertheless, the development of SR skills and multiple aspects of NOS beliefs proceeds in different trajectories. Cross-lagged models showed a complex picture concerning the mutual relationship between SR skills and NOS beliefs during their development (both positive and negative). The current study contributes to the existing research because it is based on longitudinal data and allows—in contrast to cross-sectional research—conclusions about the development of SR skills and NOS beliefs.

While the hypothetico-deductive approach, which includes inductive and deductive reasoning, is largely recognized in scientific reasoning, there is not much focus on abductive reasoning. Abductive reasoning describes the theory-based attempt of explaining a phenomenon by a cause. By integrating abductive reasoning into a framework for modeling competence, we strengthen the idea of modeling being a key practice of science. The framework for modeling competence theoretically describes competence levels structuring the modeling process into model construction and model application. The aim of this theoretical paper is to extend the framework for modeling competence by including abductive reasoning, with impact on the whole modeling process. Abductive reasoning can be understood as knowledge expanding in the process of model construction. In combination with deductive reasoning in model application, such inferences might enrich modeling processes. Abductive reasoning to explain a phenomenon from the best fitting guess is important for model construction and may foster the deduction of hypotheses from the model and further testing them empirically. Recent studies and examples of learners’ performance in modeling processes support abductive reasoning being a part of modeling competence within scientific reasoning. The extended framework can be used for teaching and learning to foster scientific reasoning competences within modeling processes.

The aim of this study was continuous monitoring of the presence of mcr-1 to mcr-5 genes in Enterobacterales isolated from cattle, pigs, and domestic poultry at intensive breeding facilities in Northern Vojvodina, Serbia, from 1 January 1 to 1 October 2020. Out of 2167 examined samples, mcr-1 was observed in five E. coli isolates originating from healthy turkeys. Four isolates belonged to the phylogenetic group B1, and one isolate to the phylogenetic group A. Detected E. coli serogenotypes (somatic O and flagellar H antigens) were O8:H25 and O29:H25. Core-genome multi-locus sequence typing (cgMLST) revealed three ST58 isolates clustering together in Clonal Complex (CC) 155 and two singletons of ST641-CC86 and ST410-CC23, respectively. Clonotyping revealed CH4-32 (n = 3), CH6-53 (n = 1) and CH4-24 (n = 1). In all isolates, the mcr-1 gene was located on a large IncX4 replicon type plasmid. Eight virulence-associated genes (VAGs) typical of avian pathogenic E. coli (APEC) (fyuA, fimH, hlyF, iss, ompT, sitA, traT, iroN) were detected in four isolates. These isolates were investigated for susceptibility to four biocides and revealed MIC values of 0.125% for glutardialdehyde, of 0.00003–0.00006% for chlorohexidine, of 4–6% for isopropanol and of 0.001–0.002% for benzalkonium chloride. All obtained MIC values of the tested biocides were comparable to the reference strain, with no indication of possible resistance. This is the first report of mcr-1.1-carrying E. coli from Serbia. Although only samples from turkeys were mcr-positive in this study, continuous monitoring of livestock samples is advised to prevent a spill-over from animals to humans.

Precision dosing of piperacillin/tazobactam in obese patients is compromised by sparse information on target-site exposure. We aimed to evaluate the appropriateness of current and alternative piperacillin/tazobactam dosages in obese and nonobese patients. Based on a prospective, controlled clinical trial in 30 surgery patients (15 obese/15 nonobese; 0.5-h infusion of 4 g/0.5 g piperacillin/tazobactam), piperacillin pharmacokinetics were characterized in plasma and at target-site (interstitial fluid of subcutaneous adipose tissue) via population analysis. Thereafter, multiple 3–4-times daily piperacillin/tazobactam short-term/prolonged (recommended by EUCAST) and continuous infusions were evaluated by simulation. Adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target-attainment (PTA ≥ 90%) based on time unbound piperacillin concentrations exceed the minimum inhibitory concentration (MIC) during 24 h (%fT>MIC). Lower piperacillin target-site maximum concentrations in obese versus nonobese patients were explained by the impact of lean (approximately two thirds) and fat body mass (approximately one third) on volume of distribution. Simulated steady-state concentrations were 1.43-times, 95%CI = (1.27; 1.61), higher in plasma versus target-site, supporting targets of %fT>2×MIC instead of %fT>4×MIC during continuous infusion to avoid target-site concentrations constantly below MIC. In all obesity and renally impairment/hyperfiltration stages, at MIC = 16 mg/L, adequate PTA required prolonged (thrice-daily 4 g/0.5 g over 3.0 h at %fT>MIC = 50) or continuous infusions (24 g/3 g over 24 h following loading dose at %fT>MIC = 98) of piperacillin/tazobactam.

This systematic review aimed to assess the effectiveness of pre-harvest interventions to control the main foodborne pathogens in pork in the European Union. A total of 1180 studies were retrieved from PubMed® and Web of Science for 15 pathogens identified as relevant in EFSA’s scientific opinion on the public health hazards related to pork (2011). The study selection focused on controlled studies where a cause–effect could be attributed to the interventions tested, and their effectiveness could be inferred. Altogether, 52 studies published from 1983 to 2020 regarding Campylobacter spp., Clostridium perfringens, Methicillin-resistant Staphylococcus aureus, Mycobacterium avium, and Salmonella spp. were retained and analysed. Research was mostly focused on Salmonella (n = 43 studies). In-feed and/or water treatments, and vaccination were the most tested interventions and were, overall, successful. However, the previously agreed criteria for this systematic review excluded other effective interventions to control Salmonella and other pathogens, like Yersinia enterocolitica, which is one of the most relevant biological hazards in pork. Examples of such successful interventions are the Specific Pathogen Free herd principle, stamping out and repopulating with disease-free animals. Research on other pathogens (i.e., Hepatitis E, Trichinella spiralis and Toxoplasma gondii) was scarce, with publications focusing on epidemiology, risk factors and/or observational studies. Overall, high herd health coupled with good management and biosecurity were effective to control or prevent most foodborne pathogens in pork at the pre-harvest level.

Sphingosine 1-phosphate (S1P) is an extensively studied signaling molecule that contributes to cell proliferation, survival, migration and other functions through binding to specific S1P receptors. The cycle of S1P1 internalization upon S1P binding and recycling to the cell surface when local S1P concentrations are low drives T cell trafficking. S1P1 modulators, such as fingolimod, disrupt this recycling by inducing persistent S1P1 internalization and receptor degradation, which results in blocked egress of T cells from the secondary lymphoid tissues. The approval of these compounds for the treatment of multiple sclerosis has placed the development of S1PR modulators in the focus of pharmacological research, mostly for autoimmune indications. Here, we report on a novel anellated bismorpholino derivative of oxy-fingolimod, named ST-2191, which exerts selective S1P1 agonist and functional antagonist potency. ST-2191 is also effective in reducing the lymphocyte number in mice, and this effect is not dependent on phosphorylation by sphingosine kinase 2 for activity. These data show that ST-2191 is a novel S1P1 modulator, but further experiments are needed to analyze the therapeutic impact of ST-2191 in animal models of autoimmune diseases.

Due to changing distemper issues worldwide and to inadequate results of an inter-laboratory study in Germany, it seems sensible to adapt and optimize the diagnostic methods for the detection of the canine distemper virus (CDV) to the new genetic diversity of virus strains. The goal of the project was the development, establishment and validation of two independent one-step reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) methods for the safe detection of CDV in domestic and wild animals. For this purpose, an existing CDV-RT-qPCR was decisively adapted and, in addition, a completely new system was developed. Both CDV-RT-qPCR systems are characterized by a very high, comparable analytical and diagnostic sensitivity and specificity and can be mutually combined with inhibition or extraction controls. The reduction in the master mix used allows for the parallel implementation of both CDV-RT-qPCR systems without significant cost increases. For validation of the new CDV-RT-qPCR duplex assays, a panel comprising 378 samples derived from Germany, several European countries and one African country were tested. A sensitivity of 98.9% and a specificity of 100% were computed for the new assays, thus being a reliable molecular diagnostic tool for the detection of CDV in domestic and wild animals.

The sensitivity of therapeutic proteins is a challenge for their use in biomedical applications, as they are prone to degradation and opsonization, thus limiting their potential. This demands for the development of drug delivery systems shielding proteins and releasing them at the site of action. Here, we describe the synthesis of novel polyglycerol-based redox-responsive nanogels and report on their potential as nanocarrier systems for the delivery of cytochrome C (CC). This system is based on an encapsulation protocol of the therapeutic protein into the polymer network. NGs were formed via inverse nanoprecipitation using inverse electron-demand Diels–Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. Coprecipitation of CC led to high encapsulation efficiencies. Applying physiological reductive conditions of l-glutathione (GSH) led to degradation of the nanogel network, releasing 80% of the loaded CC within 48 h while maintaining protein functionality. Cytotoxicity measurements revealed high potency of CC-loaded NGs for various cancer cell lines with low IC50 values (up to 30 μg·mL−1), whereas free polymer was well tolerated up to a concentration of 1.50 mg·mL−1. Confocal laser scanning microscopy (CLSM) was used to monitor internalization of free and CC-loaded NGs and demonstrate the protein cargo’s release into the cytosol.

Within the current SARS-CoV-2 pandemic, personal protective equipment, including face masks, is one important tool to interrupt virus transmission chains within the community. In this context, the quality of different face masks is frequently discussed and should, therefore, be evaluated. In this study, nanofleece textiles with a particle filtering effect and textiles with a self-disinfecting treatment were examined, which may be combined in face masks. Firstly, newly developed nanofleece textiles were tested regarding their filtration efficiency against airborne coronavirus, using feline coronavirus (FCoV) as a surrogate for SARS-CoV-2. The tested nanofleece textiles showed filtration efficiencies of over 95% against FCoV when used as a double layer and were, therefore, almost on par with the FFP-2 mask material, which was used as a reference. Secondly, eight treated, self-disinfecting textiles, which may increase the safety in the handling of potentially contaminated masks, were tested against SARS-CoV-2. Three out of eight treated textiles showed significant activity against SARS-CoV-2 and achieved about three LOG10 (99.9%) of virus titer reduction after twelve hours of incubation. Since all possible transmission paths of SARS-CoV-2, as well as the minimal infection doses, remain unknown, both investigated approaches seem to be useful tools to lower the virus spread within the community.

Escherichia (E.) coli is the main causative pathogen of neonatal and post-weaning diarrhea and edema disease in swine production. There is a significant health concern due to an increasing number of human infections associated with food and/or environmental-borne pathogenic and multidrug-resistant E. coli worldwide. Monitoring the presence of pathogenic and antimicrobial-resistant E. coli isolates is essential for sustainable disease management in livestock and human medicine. A total of 102 E. coli isolates of diseased pigs were characterized by antimicrobial and biocide susceptibility testing. Antimicrobial resistance genes, including mobile colistin resistance genes, were analyzed by PCR and DNA sequencing. The quinolone resistance-determining regions of gyrA and parC in ciprofloxacin-resistant isolates were analyzed. Clonal relatedness was investigated by two-locus sequence typing (CH clonotyping). Phylotyping was performed by the Clermont multiplex PCR method. Virulence determinants were analyzed by customized DNA-based microarray technology developed in this study for fast and economic molecular multiplex typing. Thirty-five isolates were selected for whole-genome sequence-based analysis. Most isolates were resistant to ampicillin and tetracycline. Twenty-one isolates displayed an ESBL phenotype and one isolate an AmpC β-lactamase-producing phenotype. Three isolates had elevated colistin minimal inhibitory concentrations and carried the mcr-1 gene. Thirty-seven isolates displayed a multi-drug resistance phenotype. The most predominant β-lactamase gene classes were blaTEM-1 (56%) and blaCTX-M-1 (13.71%). Mutations in QRDR were observed in 14 ciprofloxacin-resistant isolates. CH clonotyping divided all isolates into 51 CH clonotypes. The majority of isolates belonged to phylogroup A. Sixty-four isolates could be assigned to defined pathotypes wherefrom UPEC was predominant. WGS revealed that the most predominant sequence type was ST100, followed by ST10. ST131 was detected twice in our analysis. This study highlights the importance of monitoring antimicrobial resistance and virulence properties of porcine E. coli isolates. This can be achieved by applying reliable, fast, economic and easy to perform technologies such as DNA-based microarray typing. The presence of high-risk pathogenic multi-drug resistant zoonotic clones, as well as those that are resistant to critically important antibiotics for humans, can pose a risk to public health. Improved protocols may be developed in swine farms for preventing infections, as well as the maintenance and distribution of the causative isolates.

Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses.

The α-Gal epitope is an immunogen trisaccharide structure consisting of N-acetylglucosamine (GlcNAc)β1,4-galactose (Gal)α1,3-Gal. It is presented as part of complex-type glycans on glycoproteins or glycolipids on cell surfaces of non-primate mammalians. About 1% of all antibodies in human sera are specific toward α1,3-Gal and are therefore named as anti-α-Gal antibodies. This work comprises the purification and characterization of anti-α-Gal antibodies from human immunoglobulin G (IgG). A synthetically manufactured α Gal epitope affinity resin was used to enrich anti-α-Gal antibodies. Selectivity experiments with purified antibodies were carried out using enzyme-linked immunosorbent assays (ELISA), Western blotting, and erythrocyte agglutination. Furthermore, binding affinities toward α-Gal were determined by surface plasmon resonance (SPR) and the IgG distribution of anti α Gal antibodies (83% IgG2, 14% IgG1, 2% IgG3, 1% IgG4) was calculated applying ELISA and immunodiffusion. A range of isoelectric points from pH 6 to pH 8 was observed in 2D gel electrophoresis. Glycan profiling of anti α Gal antibodies revealed complex biantennary structures with high fucosylation grades (86%). Additionally, low amounts of bisecting GlcNAc (15%) and sialic acids (13%) were detected. The purification of anti-α-Gal antibodies from human IgG was successful, and their use as detection antibodies for α Gal-containing structures was evaluated.

Auxiliary reins are commonly used for the training of riders and horses as well as in daily training. They are often criticized when used incorrectly, as they will not help and can harm the horse by causing overwork, accidents, and injuries, which harm the horse in the long term. They also often conceal causal rider problems while trying to achieve quick success. The aim of this paper was to investigate, with an online horse-owner questionnaire, which and how often auxiliary reins were used and whether they were used appropriately. Only participants who were currently using auxiliary reins were selected. Consequently, 823 participants were questioned, of which 362 were currently using auxiliary reins at least every two weeks. Auxiliary reins were mainly used according to their discipline: the running side rein was the most popular when working from the ground and the sliding ring martingale was the most popular for ridden equestrian activities. Most of the test subjects only attached the auxiliary reins after the warm-up phase, but half of the participants did not change them during the entire training session. Most participants (75%) could at least identify what the correct head position of the horse should look like. However, there were still too many (50%) who adjusted their horse too tightly and did not change anything at that time despite the related breathing problems. The study found that most participants used the reins responsibly, but there is still a need for clarification and information relating to the functions of the different auxiliary reins among horse owners.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc.

Background: While potentially timesaving, there is no program to automatically transform diagnosis codes of the ICD-10 German modification (ICD-10-GM) into the injury severity score (ISS).

Objective: To develop a mapping method from ICD-10-GM into ICD-10 clinical modification (ICD-10-CM) to calculate the abbreviated injury scale (AIS) and ISS of each patient using the ICDPIC-R and to compare the manually and automatically calculated scores.

Methods: Between January 2019 and June 2021, the most severe AIS of each body region and the ISS were manually calculated using medical documentation and radiology reports of all major trauma patients of a German level I trauma centre. The ICD-10-GM codes of these patients were exported from the electronic medical data system SAP, and a Java program was written to transform these into ICD-10-CM codes. Afterwards, the ICDPIC-R was used to automatically generate the most severe AIS of each body region and the ISS. The automatically and manually determined ISS and AIS scores were then tested for equivalence.

Results: Statistical analysis revealed that the manually and automatically calculated ISS were significantly equivalent over the entire patient cohort. Further sub-group analysis, however, showed that equivalence could only be demonstrated for patients with an ISS between 16 and 24. Likewise, the highest AIS scores of each body region were not equal in the manually and automatically calculated group.

Conclusion: Though achieving mapping results highly comparable to previous mapping methods of ICD-10-CM diagnosis codes, it is not unrestrictedly possible to automatically calculate the AIS and ISS using ICD-10-GM codes.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and potentially irreversible adverse event of cytotoxic chemotherapy. We evaluate whether sensory neurons derived from induced pluripotent stem cells (iPSC-DSN) can serve as human disease model system for chemotherapy induced neurotoxicity. Sensory neurons differentiated from two established induced pluripotent stem cell lines were used (s.c. BIHi005-A https://hpscreg.eu/cell- line/BIHi005-A and BIHi004-B https://hpscreg.eu/cell-line/BIHi004-B, Berlin Institute of Health Stem Cell Core Facility). Cell viability and cytotoxicity assays were performed, comparing susceptibility to four neurotoxic and two non-neurotoxic drugs. RNA sequencing analyses in paclitaxel vs. vehicle (DMSO)treated sensory neurons were performed. Treatment of iPSC-DSN for 24 h with the neurotoxic drugs paclitaxel, bortezomib, vincristine and cisplatin led to a dose dependent decline of cell viability in clinically relevant IC50 ranges, which was not the case for the non-neurotoxic compounds doxorubicin and 5-fluorouracil. RNA sequencing analyses at 24 h, i.e. before paclitaxel-induced cell death occurred, revealed the differential expression of genes of neuronal injury, cellular stress response, and sterol pathways in response to 1 mu M paclitaxel. Neuroprotective effects of lithium chloride co-incubation, which were previously shown in rodent dorsal root ganglia, could be replicated in human iPSC-DSN. Cell lines from the two different donors BIHi005-A and BIHi004-B showed different responses to the neurotoxic treatment in cell viability and cytotoxicity assays.

Anthropogenic disturbances pose a multitude of novel challenges to ecosystems. While many experiments have tested effects using abrupt treatment applications, most environmental changes in fact are gradual. Since ecosystem responses might be highly dependent on the temporal nature of stressors, it is crucial to differentiate the effects of abrupt vs gradual treatment application. Antifungal agents, which are widely used in disease control both for humans and in agriculture, are becoming a new class of environmental contaminants. In this study, we examined the effect of a sub-lethal application of one antifungal agent, amphotericin B. We applied different rates of delivery, e.g. gradual and abrupt, and monitored biomass and sporulation of the model fungus Neurospora crassa in a batch culture. Our results demonstrate that: (i) the effect size difference between abrupt and gradual treatments is fungal growth stage dependent and (ii) the gradual treatment clearly had a higher sporulation level compared with all types of abrupt treatments. Our findings highlight the importance of considering the rate of change in environmental change research and point to a new research direction for future global change studies. Furthermore, our results also have important implications for avoiding treatment-induced spore production in agriculture and medical practise.

Objectives: The present study examined the effects of a yoga and mindfulness-based programme on the autonomic nervous system of primary school children by using heart rate variability parameters.

Design: A two-arm non-randomised controlled trial compared an integrated yoga and mindfulness-based programme (16 weeks) to conventional primary school lessons.

Setting: Primary school classrooms and conference rooms. Interventions: Participants were allocated to a 16-week integrated yoga-based programme or conventional school lessons. A subgroup was randomised to receive 24h electrocardiogram-recordings.

Main outcome measures: Heart rate variability indices were measured, both linear (time and frequency domain) and non-linear (symbolic dynamics, compression entropy), calculated from 30-minute extracts of Holterelectrocardiogram-recordings. Assessments were conducted at baseline and at the end of intervention.

Results: 40 participants (42.5% female) were included into the analysis of HRV. No significant changes in heart rate variability parameters were observed between the groups after 16 weeks. In the intervention group, a trend towards increased parasympathetic activity could be seen over time, although not significantly enhanced compared to the control group.

Conclusion: Results obtained here do not clearly show that children in German primary school settings benefit from an integrated yoga-based intervention. However, exploratory post-hoc analyses point interestingly to an increased nocturnal parasympathetic activity in the intervention group. Further studies are required with highquality study designs, larger sample sizes and longer-term follow-ups.

Basophil testing is the most effective single approach for diagnosing type-IIb autoimmune chronic spontaneous urticaria (TIIbaiCSU). A positive basophil test has been linked to long disease duration, higher disease activity, a poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib. As of now it is unclear what other features are connected to a positive basophil test in chronic spontaneous urticaria (CSU). We aimed to identify features of basophil test-positive CSU patients. We performed a cross-sectional study of 85 CSU patients. Basophil testing was done with the basophil activation test (BAT) and the basophil histamine release assay (BHRA). Data were analysed using SPSS: Student's t-test, Chi-square test, Odds Ratio, Spearman's correlation test. Of 85 CSU patients, 44% and 28% tested positive with the BAT and BHRA, respectively. These patients showed higher disease activity and impact, lower levels of disease control and total serum IgE, as well as higher rates of having a positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms for >5 days/week, and thyroid autoantibodies. The ASST, by itself, was not a good predictor of basophil test results, but it predicted a positive basophil test in up to 100% of cases when combined with angioedema, thyroid autoantibodies or low IgE. In conclusion, a positive basophil test is linked to known features of TIIbaiCSU and novel characteristics including nocturnal symptoms. Further studies on basophil test-positive and -negative CSU patients can help to better understand CSU endotypes and to develop better management approaches.