In this functional magnetic resonance imaging study, we investigated whether language production and understanding recruit similar phoneme-specific networks. We did so by comparing the brain’s response to different phoneme categories in minimal pairs: Bilabial-initial words (eg “monkey”) were contrasted to alveolar-initial words (eg “donkey”) in 37 participants performing both language production and comprehension tasks. Individual-specific region-of-interest analyses showed that the same sensorimotor networks were activated across the language modalities. In motor regions, word production and comprehension elicited the same phoneme-specific topographical activity patterns, with stronger haemodynamic activations for alveolar-initial words in the tongue cortex and stronger activations for bilabial-initial words in the lip cortex. In the posterior and middle superior temporal cortex, production and comprehension likewise resulted in similar activity patterns, with enhanced activations to alveolar- compared to bilabial-initial words. These results disagree with the classical asymmetry between language production and understanding in neurobiological models of language, and instead advocate for a cortical organization where phonology is carried by similar topographical activations in motor cortex and distributed activations in temporal cortex across the language modalities.

This study investigates the expression of predicative possession in Argentinian Spanish, focusing on the alternation between two constructions: tener (‘have’) + NP and estar con (‘be with’) + NP. Building on previous research, we explore the factors that determine speakers’ choices between these constructions, particularly the influence of temporal context and the presence of adverbs. Using a forced-choice experimental design, participants were presented with vignettes varying in temporal duration (durative vs. non-durative) and adverbial modification (extending, limiting, or none). Results show a strong overall preference for the tener + NP construction, particularly in durative contexts. However, the estar con + NP construction is more likely to be selected in non-durative contexts, especially when a limiting adverb is present. These findings suggest that the distinction between the two constructions is not purely semantic but also pragmatically modulated by temporal and contextual factors. We argue that this pattern reflects a subset-superset relationship between the two constructions, where tener + NP can cover a broader temporal scope than estar con + NP. This overlap mirrors cross-linguistic findings on possessive constructions and aspectual distinctions, with implications for understanding grammaticalization processes in Romance languages.

The Hadamard test is one of the pillars on which quantum algorithm development rests and, at the same time, is naturally suited for the intermediate regime between the current era of noisy quantum devices and complete fault tolerance. Its applications use measurements of the auxiliary qubit to extract information but disregard the system register completely. Concomitantly, but independently of this development, advances in quantum learning theory have enabled the efficient representation of quantum states via classical shadows. This Letter shows that, strikingly, putting both lines of thought into a new context results in substantial improvements to the Hadamard test on a single auxiliary readout qubit, by suitably exploiting classical shadows on the remaining 𝑛 -qubit work register. We argue that this combination inherits the best of both worlds and discuss statistical phase estimation as a vignette application. At the same time, the framework is more general and applicable to a wide range of other algorithms. There, we can use the Hadamard test to estimate energies on the auxiliary qubit, while classical shadows on the system register provide access to additional features such as (i) the fidelity of the initial state with certain pure quantum states, (ii) the initial state’s energy, and (iii) how pure and how close the initial state is to an eigenstate of the Hamiltonian. Finally, we also discuss how anticontrolled unitaries can further augment this framework and explain how this Letter settles the exploitation of the Hadamard test for intermediate applications.

New designs for molecular switches are essential for driving the development of nanoelectronics. The effect of quantum interference in cross-conjugated structures such as anthracene have already been thoroughly explored. A similar structural motif can be found in diboracenes, whose unsubstituted variants could only be synthesized recently. In this contribution, we explore the potential of these structures to produce similar quantum interference effects varying with substitution and how these could be used to produce a spin-filtering device. We investigate the eletronic properties of diboracenes through density functional theory and the global and local transport properties at the quasi-stationary limit using nonequilibrium Green’s function methods. Our findings show how the current may be tuned through the substituent and that larger unsubstituted diboracenes favor a triplet ground state with a destructive quantum interference effect for one of the spin channels.

The coefficients of elastic and dissipative operators in a linear hyperbolic SPDE are jointly estimated using multiple spatially localised measurements. As the resolution level of the observations tends to zero, we establish the asymptotic normality of an augmented maximum likelihood estimator. The rate of convergence for the dissipative coefficients matches rates in related parabolic problems, whereas the rate for the elastic parameters also depends on the magnitude of the damping. The analysis of the observed Fisher information matrix relies upon the asymptotic behaviour of rescaled M, N-functions generalising the operator cosine and sine families appearing in the undamped wave equation. In contrast to the energetically stable undamped wave equation, the M, N-functions emerging within the covariance structure of the local measurements have additional smoothing properties similar to the heat kernel, and their asymptotic behaviour is analysed using functional calculus.

Objective

Chronic stress is a risk factor for developing stress-induced mental disorders like major depression and post-traumatic stress disorder. Low-grade inflammatory processes seem to mediate this association. The sphingolipid metabolism with its most important lipid messengers ceramide and sphingosine-1-phosphate (S1P) was shown to play an important role in the pathophysiology of affective disorders and inflammation.

Method

We conducted an exploratory trial to investigate the effect of intensive psychosomatic - psychotherapeutic treatment of stress-induced disorders on the biological level. Before and after eight weeks of treatment, blood plasma of 67 patients was analyzed for sphingolipid levels and their metabolizing enzymes. Symptom severity of depression (PHQ-9), anxiety (GAD-7), and somatization (PHQ-15) was assessed in parallel.

Results

During psychosomatic - psychotherapeutic treatment, symptom severity of depression, anxiety, and somatization decreased significantly. Levels of the stress molecule cortisol decreased upon treatment. Enzymatic activities of secreted acid sphingomyelinase (S-ASM) and neutral sphingomyelinase (NSM) increased significantly upon treatment, as well as of neutral ceramidase (NC). Regarding the lipid level, the molar ratio of ceramide species Cer16:0 and Cer18:0 decreased upon treatment, whereas sphingosine and S1P levels increased.

Conclusions

Psychosomatic – psychotherapeutic treatment was associated with a reduction in specific ceramide ratios and an increase in sphingosine and S1P levels potentially resulting from increased activity of sphingolipid metabolizing enzymes. Stress-induced mental disorders might be associated with disturbed sphingolipid levels that seem to be balanced during psychosomatic treatment. This study offers a further piece of evidence that the sphingolipid metabolism could be involved in the pathophysiology of stress-induced disorders, and its analysis could be helpful for treatment monitoring.

A series of bidentate quinoline/quinoxaline-NHC ligands were coordinated to an iron(II) metal centre with the aim of taking advantage of the combined effect of NHC σ-donor and quinoline/quinoxaline π-acceptors on the excited-state stabilization of the resulting Fe(II) complexes. Excitation of these complexes at 530 nm promoted excited state formation with lifetimes of up to 74 ps. A detailed study combining spectroelectrochemistry, UV/VIS transient absorption spectroscopy as well as steady-state and time-resolved luminescence concludes that these long-lived triplet states display spectroscopic properties compatible with both MC and MLCT character, with a degree of mixing that depends on the precise ligand structure.

Data show that the presence of women in quantum science is affected by a number of detriments and their percentage decreases even further for higher positions. Beyond data, from our shared personal experiences as female tenured quantum physics professors, we believe that the current model of scientific leadership, funding, and authority fails to represent many of us. Women for quantum calls for a joint effort and aims with this initiative to contribute to such a transformation. It is time for a real change that calls for a different kind of force and for the participation of everyone.

Biodiversity knowledge, from genes to ecosystems, is crucial for addressing the biodiversity crisis. However, even in well-explored countries like Germany, much biodiversity remains unknown. Therefore, several research institutions are joining forces to conduct a comprehensive biodiversity inventory, combining broad taxonomic expertise with advanced technologies. By consolidating data across many organismic groups, the Unknown Germany initiative will significantly enhance conservation strategies and may serve as a model for similar efforts worldwide.

Adverse alcohol consumption is a major public health concern, which might have been further increased by the COVID-19 pandemic. In this study we investigated the impact of a lockdown stage on the association between alcohol consumption, loneliness, and COVID-19-related worries. We used smartphone-based Ecological Momentary Assessment (EMA) conducted during the COVID-19 pandemic in Germany. We recruited 280 participants from the general population, who experienced at least mild loneliness and distress due to the COVID-19 pandemic. We assessed daily alcohol intake, loneliness, and COVID-19-related worries every evening for 7 consecutive days across a no-lockdown [8th August 2020–1st November 2020] and lockdown stage [2nd November 2020–11th March 2021]. We did not find that a lockdown stage, compared to a no-lockdown stage, is associated with increased alcohol consumption. We found that loneliness, previous day drinking, and COVID-19-related worries were not associated with increased, but with decreased alcohol consumption. Moreover, COVID-19-related worries were more negatively associated with alcohol consumption during a no-lockdown stage compared to a lockdown stage. We found that the effect of COVID-19 related worries on alcohol consumption is mediated by loneliness. Our study suggests that heightened levels of worry can decrease alcohol intake. This association can be explained by loneliness: individuals who worry more are lonelier and thus less likely to engage in social drinking. However, during a lockdown stage, the negative association between worrying and drinking diminishes.

The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (IKs) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT syndrome (LQTS) types 1 and 5 (LQT1/LQT5), accounting for over one-third of clinical LQTS cases. Despite prior structural work on KCNQ1 and KCNQ1 + KCNE3, the structural basis of KCNQ1 + KCNE1 remains unresolved. Using cryo-electron microscopy and electrophysiology, we determined high-resolution (2.5–3.4 Å) structures of human KCNQ1APO, and KCNQ1 + KCNE1 in both closed and open states. KCNE1 occupies a pivotal position at the interface of three KCNQ1 subunits, inducing six helix-to-loop transitions in KCNQ1 transmembrane segments. Three of them occur at both ends of the S4–S5 linker, maintaining a loop conformation during IKs gating, while the other three, in S6 and helix A, undergo dynamic helix-loop transitions during IKs gating. These structural rearrangements: (1) stabilize the closed pore and the conformation of the intermediate state voltage-sensing domain, thereby determining channel gating, ion permeation, and single-channel conductance; (2) enable a dual-PIP2 modulation mechanism, where one PIP2 occupies the canonical site, while the second PIP2 bridges the S4–S5 linker, KCNE1, and the adjacent S6’, stabilizing channel opening; (3) create a fenestration capable of binding compounds specific for KCNQ1 + KCNE1 (e.g., AC-1). Together, these findings reveal a previously unrecognized large-scale secondary structural transition during ion channel gating that fine-tunes IKs function and provides a foundation for developing targeted LQTS therapy.

Mothers with borderline personality disorder (BPD) are assumed to perceive difficulties in the relationship towards their children. However, a detailed and comprehensive investigation on how mothers with BPD reflect and speak about their children as an indicator for mental representations of the mother-child relationship is yet missing. In two articles drawing from a cross-sectional data set of a multi-center study, we examined these aspects in mothers with BPD compared with a healthy and a clinical control group comprising mothers with anxiety disorders, depression, or both. Using the Five Minute Speech Sample, we focused on Expressed Emotion (EE), Narrative Coherence (NC) – both in the primary data analysis – and an extended assessment of Mind-Mindedness (extended MM) in the secondary data analysis. This article mainly addresses the similarities and differences between the three constructs on a conceptual level and regarding the respective study results, and additionally discusses the overall results from both studies. When comparing the three constructs, we identified differences regarding the level of analyzed content (i.e., characteristics of speech vs. characteristics of representation) and the level of orientation (i.e., reference to the mother herself vs. reference to the child). Three aspects are assessed via all operationalizations: (1) reporting negatively about characteristics or behaviors of the child, (2) reporting weaknesses of the child, and (3) descriptions of relationship quality. Mothers with BPD were more likely to express overt criticism (EE) and express more mental attributes with negative valence (extended MM) than both the clinical and healthy control groups. Given that we found particularities in the parent-child relationship in mothers with BPD across all three coding systems, we assume the overlap to be grounded in a tendency towards greater disapproval of child characteristics and reports of challenges in relationship quality. Considering the results of both studies, this article provides the most a comprehensive examination of these relational aspects in mothers with BPD, including comparisons with both healthy and clinical control groups. These insights contribute to a deeper understanding of the complexities underlying mental representations of the mother-child relationship in the context of BPD.

Purpose Hematotoxicity is a common side-effect of cytotoxic gastrointestinal (GI) cancer therapies. An unsolved problem is to predict the individual risk therefore to decide on treatment adaptions. We applied an established biomathematical prediction model and primarily evaluated its predictive value in patients undergoing chemotherapy for GI cancers in curative intent.

Methods In a prospective, observational multicenter study on patients with gastro-esophageal or pancreatic cancer (n = 28) receiving myelosuppressive adjuvant or neoadjuvant chemotherapy (FLO(T) or FOLFIRINOX), individual model parameters were learned based on patients’ observed laboratory values during the first chemotherapy cycle and further external data resources. Grades of hematotoxicity of subsequent cycles were predicted by model simulation and compared with observed data.

Results The most common high-grade hematological toxicity was neutropenia [19/28 patients (68%)]. For the FLO(T) regimen, individual grades of thrombocytopenia and leukopenia could be well predicted for cycles 2–4, as well as grades of neutropenia for cycle 2. Prediction accuracy for neutropenia in the third and fourth cycle differed by one toxicity grade on average. For the FOLFIRINOX-regimen, thrombocytopenia predictions showed a maximum deviation of one toxicity grade up to the end of therapy (8 cycles). Deviations of predictions were less than one degree on average up to cycle 4 for neutropenia, and up to cycle 6 for leukopenia.

Conclusion The biomathematical model showed excellent short-term and decent long-term prediction performance for all relevant hematological side effects associated with FLO(T)/FOLFIRINOX. Clinical utility of this precision-medicine approach needs to be further investigated in a larger cohort.

Background Upper respiratory tract infections usually peak during winter months.

Objective The purpose of this study was to evaluate whether imaging of complicated upper airway infection in children increased during the winter season of 2022/2023.

Materials and methods In a retrospective study setting, pediatric magnetic resonance imaging (MRI) and computed tomography (CT) scans for evaluation of upper respiratory tract infection performed between October 2022 and April 2023 were analyzed regarding presence of the following complications: mastoiditis, abscess, phlegmon, meningitis, reactive vasculitis, and sinus vein thrombosis. Pathogen detection, surgery, and infection parameters were obtained. Data were compared with MRI and CT scans performed in the same months of the preceding five years, distinguishing between pandemic and pre-pandemic years.

Results During the 2022/2023 winter season, the number of MRI and CT scans in children with upper airway infections, the complication rate, the rate of detected streptococcal infections, and the rate of surgery increased significantly compared to expectations based on the five prior winter seasons (all P<0.05). During the first complete pandemic winter season in Europe (2020/2021), the number of MRI and CT scans in children with upper airway infection, the complication rate, and the rates of streptococcal detection and surgery decreased significantly compared to expectations based on the pre-pandemic, the second pandemic, and the post-pandemic winter seasons (all P<0.05).

Conclusion After a decline during the first pandemic winter season, there was a marked rebound in complicated upper airway infection in children, with a significant increase in cases during the 2022/2023 winter season compared to the pre-pandemic and pandemic years.

Aims We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period.

Methods From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years.

Results The median age of women was 72 years (IQR 61–81) compared to 61 years in men (IQR 51–71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12–1.68, p = 0.002), but not in patients < 75 years (p = 0.076).

Conclusion In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.

Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders. Using rs-fMRI, we studied functional connectivity alterations in (1) adult C57BL/6 J mice that were intrathecally injected with a recombinant human NR1 antibody over 14 days (n = 10) and in (2) a newly established mouse model with in utero exposure to a human recombinant NR1 antibody (NR1-offspring) at the age of (2a) 8 weeks (n = 15) and (2b) 10 months (n = 14). Adult NR1-antibody injected mice showed impaired functional connectivity within the left hippocampus compared to controls, resembling impaired connectivity patterns observed in human NMDAR encephalitis patients. Similarly, NR1-offspring showed significantly reduced functional connectivity in the hippocampus after 8 weeks, and impaired connectivity in the hippocampus was likewise observed in NR1-offspring at the age of 10 months. We successfully reproduced functional connectivity changes within the hippocampus in different experimental murine systems that were previously observed in human NMDAR encephalitis patients. Translational application of this method within a combined imaging and histopathological framework will allow future experimental studies to identify the underlying biological mechanisms and may eventually facilitate non-invasive monitoring of disease activity and treatment responses in autoimmune encephalitis.

Purpose Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2-specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients.

Methods We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pTFH) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine.

Results SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. One hundred percent of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen-specific CD4+CD154+CD137+CXCR5+ pTFH cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pTFH did not correlate with antibody response or avidity.

Conclusion Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.

Unstable interpersonal relationships and fear of abandonment are core symptoms of borderline personality disorder (BPD) that often intensify during stress. Psychosocial stress, which includes components of social exclusion and increases cortisol secretion, enhances emotional empathy in healthy individuals. Women with BPD, on the contrary, react with reduced emotional empathy. The aim of the present study was to investigate the effects of perceived social exclusion without accompanying cortisol increase on empathy in women with BPD and healthy women. To induce social exclusion, we randomized 98 women with BPD and 98 healthy women to either an exclusion or an overinclusion (control) condition of Cyberball, a virtual ball game. Subsequently, participants underwent the Multifaceted Empathy Test (MET), which assesses cognitive and emotional empathy. There was no increase in cortisol release after Cyberball. Cognitive empathy did not differ between groups or conditions. Women with BPD reported lower emotional empathy for positive emotions (group by valence interaction), but not for negative emotions. Exploratory analyses suggested that this effect might be more pronounced after social exclusion. Our results confirm previous findings that cognitive empathy does not differ between women with BPD and healthy women and extend this evidence to social exclusion. Emotional empathy in women with BPD seems to be more sensitive to the effects of stress or ambiguous social situations. Specifically, emotional empathy seems to be reduced for positive emotions, and might further decline after social exclusion. Empathic reactions to emotional stimuli of different valences and to specific emotions should be further investigated.

Purpose The study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

Methods Prospective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-naïve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman’s rank correlation coefficient.

Results Eighty eyes of 74 patients (mean age 72.7; SD ± 9.96) were included. BCVA improved significantly from 0.44 (SD ± 0.21) logMAR to 0.38 (SD ± 0.23) logMAR by 0.06 (SD ± 0.14) logMAR values (p < 0.001). CS measured by MLCS increased significantly from 1.27 (SD ± 0.25) logCS to 1.39 (SD ± 0.22) logCS (p < 0.001). CS measured by FrACT also improved significantly from 1.22 (SD ± 0.32) logCS to 1.30 (SD ± 0.29) logCS (p = 0.035). A positive correlation between MLCS and FrACT was found (r = 0.389; p < 0.001). Despite statistical significance, results for BCVA, MLCS, and FrACT failed clinical significance. Overall best test results were achieved with MLCS.

Conclusions Intravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology.

Objectives To identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA).

Methods MTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders. Genome-wide gene expression analysis was performed in CD4 + and CD14 + mononuclear cells sampled from whole blood at baseline to identify differentially expressed genes in responders versus non-responders. Gene selection methods and prediction modelling obtained the most relevant differentially expressed genes. A logistic regression prediction model was subsequently constructed and validated via bootstrapping. The area under the receiver operating characteristic (AUC) curve was calculated to judge model quality.

Results Seventy-nine patients with RA (53.4 ± 13.9 years, 74.7% females) were enrolled, and 70 finished the study with a documented treatment EULAR response (77.1% responders). Forty-six differentially expressed genes were found. The most promising genes were KRTAP4-11, LOC101927584, and PECAM1 in CD4 + cells and PSMD5 and ID1 in CD14 + cells. The final prediction model using these genes reached an AUC of 90%; the validation set’s AUC was 82%.

Conclusions Our prediction model constructed via genome-wide gene expression analysis in CD4 + and CD14 + mononuclear cells yielded excellent predictions. Our findings necessitate confirmation in other cohorts of MTX-naïve RA patients. Especially if used in conjunction with previously identified clinical and laboratory (bio)markers, our results could help predict response to MTX in RA to guide treatment decisions.