Goethe University Frankfurt

Psoriatic disease, encompassing psoriasis (PsO) and psoriatic arthritis (PsA), affects approximately 2 % of the global population. In the majority of cases, skin alterations occur first, followed by musculoskeletal disorders. The transition from cutaneous to synovio-entheseal disease reflects a gradual immune-driven progression from localized to systemic manifestations in most cases. Subclinical or non-specific symptoms often precede demonstrable synovitis or enthesitis, which further delays diagnosis and increases the risk of irreversible structural damage. Despite the critical importance of early detection, established risk factors for PsA are largely nonspecific, presenting challenges for precision medicine. Key amongst these is the presence of arthralgia, which usually precedes PsA development but is also common in degenerative and biomechanical problems. Recent advancements, encompassing cutting-edge imaging modalities, hold the potential to facilitate earlier and more precise detection of PsA, while groundbreaking therapeutic innovations are redefining treatment paradigms and may further integrate advanced imaging into personalized therapeutic strategies. This review explores the molecular and clinical complexity of psoriatic disease, highlights the latest developments in imaging and treatment, and considers their potential to revolutionize patient outcomes. Novel strategies promise advances in precision medicine and may pave the way for customized interventions that not only enhance the diagnosis and prognosis of psoriatic disease but also refine therapeutic decision-making. Innovative imaging techniques are essential to distinguishing psoriatic disease-related pain from alternative causes such as osteoarthritis, thereby guiding treatment continuation and optimization.

The infrageneric classification of the genus Lepiota has a long history of continuous refinement. Nevertheless, recent studies demonstrated that some of the widely used sections are not monophyletic in their current circumscription. In addition, the genus Echinoderma , or L. sect. Echinatae in the traditional sense, was shown to be polyphyletic. In this work, the phylogeny and taxonomy of the sections of Lepiota and the species attributed to Echinoderma /sect. Echinatae are analysed based on morphological investigation and a multilocus phylogeny (ITS, LSU, mtSSU, RPB2 ). Barcode ITS-sequences are provided for 11 type specimens for the first time. The genus Echinoderma is confirmed as a phylogenetically distinct clade. However, species so far treated in Echinoderma /sect. Echinatae form two further clades in Lepiota , one as basal clade in sect. Lepiota and the other as a section on its own, for which the new combination L. sect. Eriophorae is introduced. Lepiota sect. Stenosporae is validated as a result of a nomenclatural re-assessment. Lectotypes and epitypes are designated for Lepiota carinii and Echinoderma perplexum . Echinoderma asperum as currently circumscribed is shown to be a complex formed by at least four distinct clades. The re-assessment and emendation of the sections in Lepiota confirm that the microstructure of the pileus covering is the taxonomically most significant character, while the shape of the basidiospores is less uniform within the sections.

Functional neuroimaging studies have identified distributed brain networks involved in arithmetic problem-solving. However, it is still poorly understood to what extent microstructural properties of the underlying white matter contribute to mathematical performance. We investigate microstructural characteristics of one of the least studied white matter tracts, the bilateral middle longitudinal fasciculus (MdLF), reconstructed from diffusion-weighted MRI data, and their relations with mathematical performance in arithmetic tasks of varying complexity, in 56 individuals aged 10–29 years (22 children: 10–13 years; 20 adolescents: 14–17 years; 14 adults: 18–29 years). We identify group differences in math performance and diffusivity measures. We highlight linear relations with age in left fractional anisotropy and right radial diffusivity, which can serve as developmental markers. Further, we document for the first time that diffusivity values in the right MdLF are significantly lower than in the left MdLF for all groups, suggesting hemispheric asymmetry. Importantly, associations between math performance in the right MdLF favoured easier tasks and in the left MdLF favoured harder tasks. This finding is a deviation from the classic hemisphere dominance hypothesis. We propose that the observed patterns may be explained by the right-left-right hemispheric dominance hypothesis proposed by a theory of cognitive development. Our results provide new insights into the microstructural properties of the MdLF and their role in mathematical ability, with implications for understanding brain-behaviour relations.

Background Liposomal amphotericin B (LAmB) is widely used for prophylaxis in paediatric patients at high risk of invasive fungal diseases (IFD) but its use is off-label and there is significant variability in dosage and frequency. This systematic review was conducted to evaluate the published data on prophylactic LAmB use in the paediatric population and to present the reported proportions of breakthrough IFD and the associated toxicity profile. Methods EMBASE, Medline, Web of Science and the Cochrane Database were systematically searched for primary research reporting on the use of LAmB as prophylaxis for IFD in the paediatric population up to 7 December 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Twenty studies, comprising three clinical trials, 12 cohort studies, two point-prevalence surveys and three pharmacokinetic (PK) studies, with 2015 patients were included. A total of 717 cases presented individual patient data. Breakthrough IFD occurred in 7.2% (49/676). The most recognized side effects were hypokalaemia in 23.2% (125/538) and derangement of liver function tests in 15.0% (49/327). Discontinuation due to toxicity occurred in 6.0% (30/503) of patients. Of the four studies reporting PK data, two examined serum levels of LAmB, one analysed CSF levels and the remaining study peritoneal levels. Conclusions Despite widespread use of prophylactic LAmB, this systematic review highlights the paucity of paediatric data supporting its use. The heterogeneity observed in populations, dosing regimens and study design prevents conclusions being reached on its efficacy or the superiority of one dosing regimen. Overall, there is a clear need for further high-quality robust clinical data and targeted PK studies.

The authors offer a model for curriculum for education and training in substance-assisted psychotherapy (SAP), that is, psychedelic, psycholytic, and entactogen/MDMA (3,4-methylenedioxymethamphetamine)-assisted psychotherapy, addressing both the detailed contents of training and the question of experiential training. All authors of this model have an abiding interest and extensive experience in both the theory and practical aspects of SAP and questions relating to training. The model curriculum has been written through an international consensus building process and represents a consensus statement about the topic. The model includes an enumeration of theoretical themes and topics, which we suggest for inclusion in an SAP curriculum. The practical part of the curriculum includes experiential training with the following components: (1) apprenticeship observation: learning from observing experienced therapists, (2) ongoing clinical supervision: conducting treatment under direct supervision of experienced SAP therapists, and (3) a proposal for the inclusion of self-experiences for the trainees. Other parts address the use of peer supervision and conventional supervision. The authors are aware of the abiding need for respect of intercultural differences. We are conscious that the proposed model is one largely adapted to western industrialized countries with established graduate level education and training procedures for psychotherapists. However, the model curriculum includes teachings about the use of related substances and treatment techniques in indigenous cultures and traditions. This curriculum model may be valuable to psychedelic researchers, those endeavoring to train therapists for research studies, and those preparing for the clinical work to follow, once SAP is conducted outside of research settings.

Background Muscle fatigue has long been identified as a potential risk factor for muscle overuse injuries, frequently occurring due to rapid eccentric contractions. Traditionally, muscle fatigue was thought to arise mainly to metabolic stress, whereas muscle damage was considered a consequence of mechanical overload. However, this binary approach fails to capture the complex physiological mechanisms, including prolonged-force depression, enzyme leakage or inflammatory responses, which overlap between both entities. Main Text This narrative review synthesizes evidence regarding physiological and mechanical overlaps between muscle fatigue and muscle damage. It elaborates on the concept of a muscle injury continuum, including forms of muscle fatigue, possibly leading to mechanical tissue damage, and potentially culminating in severe muscle injuries. Additionally, the relevance of the overlaps for load monitoring and injury prevention in professional sports are discussed. Conclusion Understanding and recognizing the interplay between muscle fatigue and muscle damage is crucial for developing individualized prevention strategies, minimizing injury risk, and enhancing performance. This comprehensive approach is vital for improving load management and ensuring the long-term health and efficiency of athletes.

In groundwater depletion (GWD) regions, negative trends in groundwater storage (GWS) are problematic for groundwater drought detection, since they mask climate‐induced drought signals. As this is not yet considered in any large‐scale drought early warning system (LDEWS), we used GWS from the global hydrological model WaterGAP 2.2e to investigate, for the first time at the global scale, how groundwater drought can best be quantified in GWD regions. We analyzed two methods: (a) Linear detrending of monthly GWS time series and (b) analysis of naturalized GWS computed by assuming no human water use. We found that linear detrending is unsuitable for global‐scale groundwater drought monitoring and forecasting as even small deviations from a pronounced linear trend can lead to a systematic over‐ and underestimation of the drought hazard. In contrast, indicators from naturalized GWS can identify climate‐induced GWS anomalies. We recommend to provide, in LDEWS, indicators of the magnitude, duration, and severity of groundwater drought that are based on monthly time series of model‐derived GWS simulated with (“ant” variant) and without water use (“nat” variant). In both GWD and non‐GWD regions, the “nat” variants inform about the occurrence of climate‐induced droughts. In GWD regions, they specify periods in which the negative GWS trend is either exacerbated or alleviated by climate‐induced variations of groundwater recharge, while “ant” variants are of very limited informative value. In non‐GWD regions, the joint analysis of “nat” and “ant” variants informs whether a climate‐induced drought is aggravated or alleviated due to human activities.

The impact that the stories of Algernon Blackwood (1869-1951) have had on the literature of the uncanny can hardly be overestimated. However, there is almost no research on Blackwood's life and work. Against the background of a presentation of themes and motifs of Blackwood's narrative oeuvre, this article develops a characteristic of his poetics. It consists in first calling up conventions of narrative, which are also conventions of thought, and conventions of thought, which are also conventions of narrative, and then reversing them from within. This is shown in detail in The Willows (1907)-a story that has decisively shaped the entire tradition of uncanny tales because it solves the tasks of the poetics of the "strange" or "weird" uncanny in an exemplary manner. Yet this is also precisely what makes it so difficult to grasp what is actually going on in it, what it is actually telling us about and, above all, how. The events narrated are uncanny , even disturbing-but how can that be when there is no discernible actual event and the perceived threat remains absolutely intangible throughout the story? A precise narrative analysis shows that what was suspense in traditional ghost or horror genre tales becomes atmosphere here, and what was uncanny becomes thinking in as well as of fear.

The decomposition of plant material is a key driver of the global carbon cycle, traditionally attributed to fungi and bacteria. However, some invertebrates also possess orthologs to bacterial or fungal cellulolytic enzymes, likely acquired via horizontal gene transfer. This reticulated mode of evolution necessitates ortholog searches in large taxon sets to comprehensively map the repertoire of plant cell wall degrading enzymes (PCDs) across the tree of life, a task surpassing capacities of current software. Here, we use fDOG, a novel profile-based ortholog search tool to trace 235 potential PCDs across more than 18,000 taxa. fDOG allows to start the ortholog search from a single protein sequence as a seed, it performs on par with state-of-the-art software that require the comparison of entire proteomes, and it is unique in routinely scoring protein feature architecture differences between the seed protein and its orthologs. Visualizing the presence-absence patterns of PCD orthologs using a UMAP highlights taxa where recent changes in the enzyme repertoire indicate a change in lifestyle. Three invertebrates have a particularly rich set of PCD orthologs encoded in their genome. Only few of the orthologs show differing protein feature architectures relative to the seed that suggest functional modifications. Thus, the corresponding species represent lineages within the invertebrates that may contribute to the global carbon cycle. This study shows how fDOG can be used to create a multi-scale view on the taxonomic distribution of a metabolic capacity that ranges from tree of life-wide surveys to individual feature architecture changes within a species.

Background Learning analytics dashboards (LAD) have been developed as feedback tools to help students self‐regulate their learning (SRL) by using the large amounts of data generated by online learning platforms. Despite extensive research on LAD design, there remains a gap in understanding how learners make sense of information visualised on LADs and how they self‐reflect using these tools. Objectives We address this gap through an experimental study where a LAD delivered personalised SRL feedback based on interactions and progress to a treatment group, and minimal feedback based on the average scores of the lecture to a control group. Methods After receiving feedback, students were asked to write down how they planned to adjust their study habits. These reflection texts are the target of this study. Three human coders analysed 1251 self‐reflection texts from 417 students at three different times, using a coding system that categorised learning strategies, metacognitive strategies and learning materials. Results and Conclusions Our results show that learners who received personalised feedback intend to focus on different aspects of their learning in comparison to the learners who received minimal feedback and that the content of the LAD influences how students formulate their self‐reflection texts. Furthermore, the extent to which students incorporated suggested behavioural changes into their reflections was predicted by state measures like perceived helpfulness of the feedback. Our findings outline areas where support is needed to improve learners' sense‐making of feedback on LADs and self‐reflection.

Purpose A common side effect from cancer and anti-cancer treatment is cancer-associated cachexia (CAC), a multifactorial syndrome characterized by the loss of bodyweight, skeletal muscle and adipose tissue. Recommended therapeutic options are multidimensional, including nutritional, pharmacological and exercise interventions. A novel therapeutic approach is the use of low-load resistance training combined with blood-flow-restriction to the trained limbs (LL-BFR). It has been shown to induce adaptations in muscle mass and strength despite low training load in various clinical populations and might be a suitable training modality for cancer patients suffering from CAC. Methods A 56-year-old female patient diagnosed with stage IV gallbladder cancer, suffering from CAC performed LL-BFR training twice weekly for twelve weeks and received a guideline-based nutritional intervention. All outcome measures (maximal strength (8-RM), handgrip strength, body mass, lean body mass, body cell mass, quality of life and symptom burden) were evaluated before and directly after the training period. Results Adherence was moderate (67% of all training sessions completed) and no adverse events were noted. All measures of physical capacity and body composition improved between 19-55% and 9-11%, respectively. Quality of life decreased in 5/6 subscales while symptom burden increased in 2/4 subscales. Conclusions Treatment of CAC requires a multitargeted and interdisciplinary approach. This is the first case study using LL-BFR training in an oncological patient during active therapy. Our results show that LL-BFR was feasible and, despite no positive effect on quality of life and symptom burden, could induce relevant changes of muscle strength and muscle mass in a relatively short training period. Further research is necessary to confirm the results of this case study in randomised controlled trials.

Cannabinoids comprise a large class of bioactive compounds found primarily in the plant species Cannabis sativa and are of interest due to their pharmacological and therapeutic potential. The aromatic polyketide, olivetolic acid (OA), is a major precursor in the cannabinoid biosynthesis pathway and is derived from hexanoyl‐CoA and malonyl‐CoA by the action of olivetol synthase (OLS) and olivetolic acid cyclase (OAC). To date, most microbial cannabinoid production systems rely on the external supplementation of hexanoic acid together with the overexpression of acyl‐activating enzyme 1 from C. sativa (CsAAE1) to provide hexanoyl‐CoA. Here, we implement a heterologous OA biosynthesis pathway into the yeast Saccharomyces cerevisiae and describe various biochemical and metabolic engineering strategies to overcome the need for external hexanoic acid supplementation. We ensured a sufficient endogenous supply of hexanoyl‐CoA and further optimized OA production by enhancing precursor supply. Moreover, we present a mutant phenylacetate‐CoA ligase derived from Penicillium chrysogenum (PcPCL‐K) which displayed superior hexanoyl‐CoA ligase activity to CsAAE1. Together, these strategies enabled the production of 180 mg/L OA using shake flask cultures. Our results provide details of key metabolic engineering steps required for the biosynthetic production of cannabinoids and their precursors in S. cerevisiae.

Background Artificial intelligence (AI) will have a lasting and drastic impact on medical research and healthcare. In addition to the benefits, the associated risks are also the subject of controversial debate and there are fears of serious consequences. There is an urgent need for action, which must be underpinned by scientific information. Methods By analyzing temporal and geographic patterns, including national readiness for access to AI, we therefore identified incentives and barriers to global research under socioeconomic conditions. Results The explosive increase in annual publications started in 2017. The main players in AImed research were the USA, China, the UK, Germany, and South Korea. There was a significant correlation between the publication output on AI in medicine (AImed) and the metrics for economy and innovation. Additionally, citation patterns show the disadvantage of the Global South compared to the North American and European countries. In several weaker economies: Jordan, Pakistan, Egypt, Bangladesh, and Ethiopia, a more positive position was found in relation to the number of articles suggesting a better ranking in AImed research in the future. Conclusion The results show the need for advanced global networking to ensure all relevant aspects for equitable development and the beneficial use of AImed without promoting racial or regional inequities and to enforce this not only in the AI systems of economically strong countries but also for the participation of economically weaker countries.

Along with their ability to redefine the chemical and physical properties of surfaces and interfaces, self‐assembled monolayers (SAMs) may serve as versatile resists and templates for lithography, providing chemical, morphological, and biological patterns. A particularly useful approach in this context is photolithography with UV light. Applied to thiolate‐anchored SAMs on coinage metal substrates, UV light induces the oxidation of the anchoring groups and damage to the SAM matrix, with the rates and extent depending strongly on the wavelength. Here, these processes for different types of thiolate SAMs are discussed, and it is shown that the potential of UV lithography with SAM templates can be noticeably extended if it is combined with the subsequent exchange reaction with a molecular substituent capable of assembling on the given substrate. Since the extent of the substitution can be controlled by the irradiation dose, the final chemical composition can be flexibly tuned, allowing the preparation of functional binary SAMs and the creation of complex gradient‐like patterns. Using primary bioinert monolayers, templates for nonspecific and specific adsorption of biomolecules and biopolymer brushes are fabricated. The combination of electrostatic engineering of interfaces and promoted exchange reaction allows location‐selective work function modification for organic electronics devices in a circuit.

The International Criminal Court (ICC) was established to deliver impartial and universal justice, yet its operations are shaped by geopolitical interests and legal formalism, limiting its inclusivity and effectiveness. This commentary draws on feminist geopolitics to critically examine how the ICC's structural ambiguities constrain but also create opportunities for rethinking justice. By foregrounding intersectionality, structural violence and alternative legal frameworks, we propose ways to make international justice mechanisms more responsive to local contexts and marginalised communities. Moving beyond critique, we outline concrete reforms, including expanding the ICC's mandate, decentralising justice processes, and integrating survivor‐led approaches. In doing so, we call for a more geographically attuned and socially equitable approach to global justice. We also argue that geographers—especially those working in legal, political and feminist subfields—can play a critical role in illuminating the spatialities of international justice, uncovering power asymmetries, and advancing more inclusive legal imaginaries. Their interventions help expose and challenge the uneven geographies of accountability that shape institutions like the ICC.

Purpose Ample research exists on the association of migration status and health-related quality of life (HRQoL). Specific personality traits linked to the Big Five such as neuroticism, have been found to be predictive of migrants’ intercultural success. This study aimed to analyze the moderating effect of neuroticism on migration status and HRQoL in a representative German sample. Methods Data from the German Socioeconomic Panel (GSOEP) (N = 29,968) were analyzed. The sample included Germans without migration background (n = 19,749), immigrants (n = 3,491), foreigners residing in Germany (n = 2,460), and refugees (n = 4,268). Gender-stratified moderation analyses were performed using General Linear Models with HRQoL (SF-12; mental and physical health) as outcome, migration status as predictor, and neuroticism (BFI-S) as moderator. Results Refugees reported the lowest HRQoL (F(3, 29192) = 27.54, p <.001). Refugees also displayed the lowest neuroticism scores. Significant moderation effects of neuroticism on the relationship between migration status and SF-12 mental HRQoL scores were observed, especially for refugees (β = 0.05, CI [0.01 – 0.10], p =.03) and immigrants (β = 0.04, CI [0.00 – 0.08], p =.03; R² = 0.064). Women had lower SF-12 scores compared to men across all groups. Additionally, there was a significant three-way interaction effect for female refugees with neuroticism on mental HRQoL (β = − 0.24; CI [-0.34 – − 0.14]; p <.001). Conclusion The results corroborated research pointing out differences in HRQoL depending on migration status and gender. Refugees seem to benefit particularly from low neuroticism, in terms of emotional stability, as a psychological resource.