Social exclusion contributes to alcohol consumption, whereas the development of alcohol dependence (AD) can in turn lead to the social exclusion of people with AD. Previous research observed altered neural responses to experimentally induced social exclusion (i.e., Cyberball game) in patients with AD. In addition, inflammation has been associated with both social behaviours and AD. Our study aimed to investigate the dynamic behavioural response and the inflammatory effects of social exclusion in male patients with a history of AD. To this end, we analysed dynamic changes in ball tossing during a partial exclusion Cyberball game and the cytokine interleukin (IL)-1b in saliva in 31 male patients who had a history of AD and 29 gender-matched healthy controls without AD. Participants were included in the first 2 min of the Cyberball game and then excluded by one of the two co-players in the proceeding 5 min. Saliva was collected three times: one before and two after the Cyberball game. Across groups, participants passed the ball more often to the excluder during the partial exclusion period. Analysis using piece-wise linear mixed models showed that patients rapidly increased ball tosses to the excluder upon exclusion, which lasted to the late response phase, whereas the early behavioural response to exclusion took longer for controls. There was no significant change of salivary IL-1b level to exclusion in either patients or controls. The results indicate a distinct dynamic behavioural response to social exclusion in male patients with a history of AD.

Objective Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life. Nevertheless, overlap with objective cognitive impairment (OCI) is often weak. One reason may be a domain-specific mismatch between subjective reports and objective tests. We aimed to evaluate relations between SCI and OCI of corresponding domains and to assess whether these differ between persons who over- or underestimate their performance.Methods In this prospective, cross-sectional sample of 104 adult inpatients with epilepsy, we performed multiple regression analyses predicting SCI in the domains attention, memory, and executive functions. We tested relationships with measures of psychomotor speed, short-term memory, verbal learning, verbal delayed recall, and word fluency while controlling for age, sex, seizure frequency, structural lesions, mono- versus polytherapy and adverse events of antiseizure medication (ASM), depressive and anxiety symptoms, level of education, and employment status. Furthermore, we tested whether these relationships differed between realistic raters and over- and underestimators.Results We found domain-specific relations for attention and executive functions for the full sample, explaining a small proportion of variance of SCI (general dominance index = .03 and .004), whereas ASM adverse events and psychological variables were more important predictors. When dividing the sample according to the concordance of SCI and OCI, we found high frequencies of both over- (23%-46%) and underestimation (31%-35%) depending on the domain. The explanatory power of OCI for SCI was stronger within the subgroups compared to the full sample, suggesting nonlinear relationships and different underlying mechanisms for realistic raters, underestimators, and overestimators.Significance Domain-specific SCI and OCI are related, and both should be assessed with standardized instruments. These relationships differ between over- and underestimators as well as realistic raters. Based on the concordance of self-ratings and objective measures, tailored counseling and treatment should be offered.

Illness anxiety may amplify vulnerability to psychopathological symptoms during the COVID-19-pandemic-perhaps especially at the beginning of the pandemic and during high infection waves, but empirical evidence on this is lacking. In addition, considering a potentially functional facet of it, illness anxiety might be associated with higher vaccine willingness. We analyzed data of a nine-wave longitudinal online-survey (March 2020-October 2021) with 8148 non-probability sampled adults of the general population in Germany (: NCT04331106). Using multilevel analysis, we investigated longitudinal associations of dimensionally assessed illness anxiety (worry about illness, bodily preoccupation) with mental strain and vaccine willingness and considered the dynamic of the pandemic (i.e., duration and infection rates). Higher worry about illness and bodily preoccupation were associated with higher COVID-19-related fears, unspecific anxiety, depressive symptoms, and vaccine willingness. Vaccine willingness increased over time and in parallel to higher infection rates. Symptoms of mental strain decreased with continuing duration of the pandemic but increased when infection rates inclined. This decrease and increase, respectively, was steeper in individuals with higher illness anxiety. Our findings suggest that individuals with higher illness anxiety are more vulnerable to experience psychopathological symptoms during the ongoing pandemic, particularly at its beginning and during times of high infection rates. Thus, illness anxiety and associated symptoms should be targeted by adaptive measures. The fluctuation of symptoms parallel to the pandemic situation implies that support should be particularly issued at the beginning of extraordinary situations as well as during phases of high infection rates.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.

Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced astrocytic Phd2/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases.

Ultraviolet (UV) exposure induces cross-linked pyrimidine dimers in nucleic acids, primarily forming cyclobutane pyrimidine dimers and 6–4 pyrimidine–pyrimidone adducts. These photoproducts exist in multiple isomeric forms, and various dimeric combinations involving thymine, cytosine, and uracil have been documented since the 1960s. Mass spectrometry (MS) has been pivotal in identifying these species, although condensed-phase spectroscopy remains essential for full structural elucidation. This study integrates MS with gas-phase infrared (IR) spectroscopy to obtain vibrational spectra (800–1900 cm–1) of UV-induced photoproducts from mono- and dinucleotides. Following nanoelectrospray ionization and in-source collision-induced dissociation, fragment ions─commonly used in tandem MS experiments to identify the photoproducts─are embedded in superfluid helium clusters at 0.37 K to measure high-resolution IR action spectra. These spectra are then compared with density functional theory-calculated spectra of various candidate isomers to facilitate structural assignment without reference standards. This combined approach enables detailed characterization of complex, low-abundance biomolecules beyond the reach of conventional MS.

Introduction

Despite the high prevalence of chronic low back pain (cLBP), its underlying mechanisms remain poorly understood. Addressing modifiable psychosocial resources and health behaviours such as physical activity offers a promising avenue for reducing the impact of cLBP. Furthermore, although the relationship between physical activity and pain is theorised as a within-person process, previous research has primarily focused on between-person differences. In this article, we present the protocol for the prospective observational study PRIA (Psychologie und Rückengesundheit im Alltag), which is part of a larger interdisciplinary research consortium investigating preventive, diagnostic and therapeutic aspects of cLBP. Drawing on theories from health and pain psychology, the outlined study examines the interplay between different dimensions of cLBP and back health, physical activity and their psychosocial determinants within individuals in their everyday lives.

Methods and analysis

This prospective longitudinal study combines online questionnaires with ecological momentary assessment of health behaviours, cognitions, affect, social support and pain using a smartphone-based app (movisensXS) and continuous measurement of physical activity by accelerometry (movisens Move 4). Parameters will be recorded at baseline (T0), daily for the following 14 days (five times per day at 09:00, 12:00, 15:00, 18:00 and 21:00, resulting in up to 70 measurement occasions), 3 and 6 months later (T1 and T2). A total of 230 participants (115 individuals with cLBP and 115 without cLBP) aged 18–64 years will be enrolled. The associations between cLBP and the measured parameters will be examined using multilevel models.

Ethics and dissemination

The university’s ethics committee at the MSB Medical School Berlin approved the study on 8 March 2021 (approval number MSB-2021/59, amendment approved on 10 November 2023, amendment number MSB-2023/145). Ethical approval for the FOR 5177 initial screening was granted by Charité – Universitätsmedizin Berlin (EA1/058/21). All participants provided written informed consent. The results of this research will be published in peer-reviewed international journals, presented at national and international conferences, and reported to the German Research Foundation.

Trial registration number

DRKS00032978.

Quite frequently, it is the progression of initial crystallographic fragment screening hits into more potent binders to their target, which constitutes the major bottleneck in many academic compound or drug development projects. While high quality starting points are critical to the success of a drug development project, it is equally important to have accessible pathways for further compound development. Here, we present two crystallographic fragment screening campaigns using a 96 fragment sub-selection of the European Fragment Screening Library (EFSL) provided by EU-OPENSCREEN. The two campaigns against the targets endothiapepsin and the NS2B–NS3 Zika protease, yielded hit rates of 31% and 18%, respectively. Further, we present how within the framework of the EU-OPENSCREEN European Research Infrastructure Consortium (ERIC) fast identification of follow-up compounds can be realized. With just one round of testing related compounds from the European Chemical Biology Library, two follow-up binders for each of the two targets could be identified proving the feasibility of this approach.

Autoimmune disorders are heterogeneous dynamic conditions characterized by dysregulated immune responses and caused by interruption of tolerogenic circuits. Although immunosuppressive drugs, including biological agents, are effective therapeutic options, several patients do not respond to these treatment or develop resistance mechanisms. Galectins, a family of soluble glycan-binding proteins, play central roles in the modulation of autoimmune inflammation. Galectin-1 (Gal-1), a prototype member of this family, interacts with specific N-acetyllactosamine (LacNAc) ligands present in N- and O-glycans via its conserved carbohydrate recognition domain (CRD). The immunomodulatory activity of Gal-1 involves regulation of T cell effector populations, inducing apoptosis of Th1 and Th17 cells, differentiation of tolerogenic dendritic cells and induction of myeloid-derived suppressor cells. To develop a rational galectin-based therapeutic strategy, we evaluated whether Gal-1 retains its function upon multivalent presentation on nanoparticles. Specifically, we report the design strategy, synthesis and characterization of galectin-1-conjugated glucose-stabilized gold nanoparticles, and compare their activities with unconjugated galectin-1. This formulation offers novel opportunities for treating a variety of autoimmune diseases, as well as chronic inflammatory disorders.

Ionizing radiation damage to biomolecules plays a crucial role in radiotherapy as a cancer treatment. Among these, DNA-binding proteins are of particular interest due to their pivotal roles in shielding DNA and facilitating its repair. Hence, in this study, we present first-ever recorded data of radiation damage to a protein monitored directly with near-ambient pressure (NAP) X-ray photoelectron spectroscopy (XPS) under a water atmosphere. This surface sensitive technique was used to in situ damage and probe gene-V protein (G5P, a model DNA-binding protein) under wet NAP conditions and dry vacuum (UHV) conditions to determine the effect of water on the radiation response. In addition, the X-ray radiation damage to selected pure amino acids and short homopeptides was determined to better understand the variety of damage mechanisms within the complex protein. In dry samples, drastic chemical changes were detected in all biomolecules dominated by fragmentation processes. Here, the breakage of peptide bonds in the peptides and the protein are dominant. Surprisingly, hydration – despite introducing additional indirect damage pathways via water radiolysis – led to a reduction in overall radiation damage. This behaviour was attributed to hydration-dependent changes in reaction rates and respective deexcitation and damaging channels within the molecules and secondary species such as low-energy (LEE), (pre)-hydrated/(pre)-solvated electrons and radical species such as hydroxyl radicals.

Experiences shape preferences. This is particularly the case when they deviate from our expectations and thus elicit prediction errors. Here we show that prediction errors do not only occur in response to actual events – they also arise endogenously in response to merely imagined events. Specifically, people repeatedly chose between different acquaintances and then imagined interacting with them. Our results show that they acquired a preference for acquaintances with whom they had pictured unexpectedly pleasant events. This learning can best be accounted for by a computational model that calculates prediction errors based on these rewarding experiences. Using functional MRI, we show that the prediction error is mediated via striatal activity. This activity, in turn, seems to update preferences about the individuals by updating their cortical representations. Our findings demonstrate that imaginings can violate our own expectations and thus drive endogenous learning by coopting a neural system that implements reinforcement learning.

Domestication has shaped animal vocal behaviour, increasing flexibility and responsiveness to humans. In domestic cats ( Felis catus ), two vocalisations, meows and purrs, have distinct communicative roles. Meows are context-dependent signals primarily directed at humans; purrs are stereotyped, low-frequency sounds produced in affiliative contexts. Vocal individuality, key in mammalian communication, supports social recognition and interaction, but its presence across cats’ call types remains poorly understood. We examined whether cats encode individual identity in meows and purrs, hypothesising that meows might show stronger signatures due to their human-directed nature. We analysed 276 meows from 14 cats and 557 purrs from 21 cats. Both call types carried sufficient individual information, but purrs had significantly higher classification accuracy (84.6%) and encoded more information content (4.47 bit) than meows (63.2%, 2.65 bit). To place individuality in a domestication framework, we compared domestic cat meows with those of five wild relatives: African wildcat, European wildcat, jungle cat, cheetah, and cougar. Domestic cat meows showed greater acoustic dispersion than those of wild cats, reflecting increased vocal plasticity through domestication. These findings demonstrate how domestication has shaped feline vocalisations, with purrs acting as stable identity cues and meows emphasising flexibility over recognisability.

Background

The interconnectedness of human, animal, and environmental health drives emerging threats, such as antimicrobial-resistant pathogens. The widespread use of the same antimicrobials in both human and livestock may play a role in interspecies bacterial transmission by disrupting natural microbial communities and creating an environment favouring resistant bacteria. Pigs and poultry receive high levels of antimicrobials and are reservoirs of multidrug-resistant bacteria, including Streptococcus suis, a zoonotic pig pathogen. S. suis detection in non-porcine hosts, particularly poultry, raises a critical question: is this due to transient spillover or does it represent sustained host jumps and adaptation?

Results

Analysing over 3000 S. suis genomes from a diverse range of hosts—including pigs, wild boar, humans, cats, dogs, cattle, fish, otter, and birds—we identify a multidrug-resistant lineage, distinct from the lineage responsible for most zoonoses, that has undergone multiple host jump events into birds. Unlike transmission to humans, which is exclusively derived through contacts with pigs, we find evidence of S. suis adaptation to birds. This includes phylogenetic persistence, independent acquisition of bird-specific mobile genomic islands, enhanced survival in chicken versus pig blood, and subsequent transmission from poultry to wild birds.

Conclusions

While chickens may not be a source of zoonotic S. suis infections, shared antibiotic usage in pigs and poultry may have promoted host jumps of multidrug-resistant S. suis, leading to onward transmission to wild bird populations. Our results suggest that antibiotic use in livestock production may promote transmission of antimicrobial-resistant bacteria to other hosts, thereby expanding the ecological range of bacterial pathogens.

Information extraction (IE) is a transformative process that converts unstructured text data into a structured format by employing entity and relation extraction (RE) methodologies. Identifying the relation between a pair of entities plays a crucial role within this framework. Despite the availability of various techniques for RE, their efficacy heavily depends on access to labeled data and substantial computational resources. To address these challenges, large language models (LLMs) have emerged as promising solutions; however, they are prone to generating hallucinated responses due to the limitations of their training data. To overcome these shortcomings, this work proposes a retrieval-augmented generation-based relation extraction (RAG4RE) approach to enhance RE performance. We evaluate the effectiveness of RAG4RE using various LLMs. By leveraging established benchmarks such as TACRED, TACREV, Re-TACRED and SemEval RE datasets, we aim to comprehensively assess the efficacy of our methodology. Specifically, we employ prominent LLMs, including Flan T5, Llama2, and Mistral, in our investigation. The results of our work demonstrate that RAG4RE outperforms traditional RE methods based solely on LLMs, with significant improvements observed in the TACRED dataset and its variations. Furthermore, our approach exhibits remarkable performance compared to previous RE methodologies across both TACRED and TACREV datasets, underscoring its efficacy and potential for advancing RE tasks in natural language processing.