The COVID-19 pandemic highlighted the essential role of disease modeling in shaping public health responses. However, models designed in high-resource settings often fail to capture disease dynamics accurately in lower-resource contexts like Ghana, where socio-ecological factors, infrastructure constraints, and data fragmentation complicate accurate predictions. In this Commentary, we examine the challenges of adapting global modeling approaches to Ghana’s context and propose strategies to improve their accuracy, relevance, and policy utility. These challenges were further compounded during the pandemic recovery period, when Ghana simultaneously faced outbreaks of Marburg virus and Mpox. These additional pressures—against a backdrop of rapid urbanization, increased human-wildlife interaction, shifting transmission dynamics, and environmental degradation—underscore the limitations of current modeling approaches. A key limitation lies in the difficulty of collecting raw, disaggregated data, accounting for sociocultural determinants, and capturing the complex interplay between disease dynamics and adaptive behaviors. Addressing these challenges requires valid, timely, and disaggregated data on social and epidemiological dynamics for model parameterization and validation. To examine the challenges faced in adapting global models for local use, we focus on Ghana’s unique context and argue for a rethinking of modeling approaches in this commentary. To mitigate potential harm, it is imperative to emphasize context-specific data, interdisciplinary input, and integration of social and economic factors, as foundational principles for future frameworks that can better support pandemic preparedness in Ghana and similar settings.

Soil microbes drive ecosystem function and play a critical role in how ecosystems respond to global change. Research surrounding soil microbial communities has rapidly increased in recent decades, and substantial data relating to phospholipid fatty acids (PLFAs) and potential enzyme activity have been collected and analysed. However, studies have mostly been restricted to local and regional scales, and their accuracy and usefulness are limited by the extent of accessible data. Here we aim to improve data availability by collating a global database of soil PLFA and potential enzyme activity measurements from 12,258 georeferenced samples located across all continents, 5.1% of which have not previously been published. The database contains data relating to 113 PLFAs and 26 enzyme activities, and includes metadata such as sampling date, sample depth, and soil pH, total carbon, and total nitrogen. This database will help researchers in conducting both global- and local-scale studies to better understand soil microbial biomass and function.

Objectives: Differentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-F-18-fluoroethyl)-l-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping. Methods: Fifty-nine participants with neuropathologically confirmed recurrent HGG (n=39) or PTRE (n=20) were investigated using static F-18-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80-100% and 60-75% areas of F-18-FET uptake) compartments were assessed. Comparative analysis was performed using Mann-Whitney U tests with Holm-Sidak multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations. Results: Compared to PTRE, recurrent HGG presented increased F-18-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p<.05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance - most pronounced for FA60 (AUC=0.86, p<.001), which presented similar benefit to F-18-FET PET (AUC=0.86, p<.001) and was negatively correlated with amino acid uptake (rs=-0.46, p<.001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax+FA60 showed highest diagnostic accuracy (AUC=0.93, p<.001), which improved the detection of relapse compared to PET alone (difference in AUC=0.069, p=.04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting. Conclusion: Detection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone.

Spinal cord injury (SCI) imposes a significant physical, social, and economic burden on millions of patients and their families worldwide. Although medical and surgical care improvements have decreased mortality rates, sustained recovery remains constrained. Cell-based therapies offer a promising strategy for neuroprotection and neuro-regeneration post-SCI. This article reviews the most promising preclinical approaches, encompassing the transplantation of embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), oligodendrocyte progenitor cells (OPCs), Schwann cells (SCs), and olfactory ensheathing cells (OECs), along with the activation of endogenous pluripotency cell banking strategies. We also outline key ancillary strategies to enhance graft cell viability and differentiation, such as trophic factor assistance, engineered biomaterials for supportive scaffolds, and innovative methods for a synergistic effect in treatment, including promoting neuronal regeneration and reducing glial scars. We highlight the key aspects of SCI pathophysiology, the fundamental biology of cell treatments, and the advantages and limitations of each approach. Graphical abstract There are several approaches to treating spinal cord injuries that show great promise: Cellular therapies, which utilize a range of cells such as embryonic, neural, and mesenchymal stem cells, along with astrocytes, Schwann cells, olfactory ensheathing cells, and reprogrammed cells; The use of innovative biomaterials, including hydrogels, collagen, polycaprolactone fibers, and advanced 3D-printing technologies, provides valuable support for tissue repair.

Background: Post-stroke heart rate (HR) and heart rate variability (HRV) changes have been proposed as outcome predictors after stroke. We used data lake-enabled continuous electrocardiograms to assess post-stroke HR and HRV, and to determine the utility of HR and HRV to improve machine learning-based predictions of stroke outcome.Methods: In this observational cohort study, we included stroke patients admitted to two stroke units in Berlin, Germany, between October 2020 and December 2021 with final diagnosis of acute ischemic stroke or acute intracranial hemorrhage and collected continuous ECG data through data warehousing. We created circadian profiles of several continuously recorded ECG parameters including HR and HRV parameters. The pre-defined primary outcome was short-term unfavorable functional outcome after stroke indicated through modified Rankin Scale (mRS) score of > 2.Results: We included 625 stroke patients, 287 stroke patients remained after matching for age and National Institute of Health Stroke Scale (NIHSS; mean age 74.5 years, 45.6% female, 88.9% ischemic, median NIHSS 5). Both higher HR and nocturnal non-dipping of HR were associated with unfavorable functional outcome (p < 0.01). The examined HRV parameters were not associated with the outcome of interest. Nocturnal non-dipping of HR ranked highly in feature importance of various machine learning models.Conclusions: Our data suggest that a lack of circadian HR modulation, specifically nocturnal non-dipping, is associated with short-term unfavorable functional outcome after stroke, and that including HR into machine learning-based prediction models may lead to improved stroke outcome prediction.

The use of multiple-choice (MC) instruments to assess pedagogical content knowledge (PCK) has advantages in terms of test economy and objectivity, but it also poses challenges, for example, in terms of adequately capturing the intended construct. To help address these challenges, we developed and evaluated a new instrument to assess science teachers’ PCK of scientific reasoning in biology contexts (PCKSR-bio), considering multiple sources of validity evidence. First, 12 MC items were developed to assess crucial PCK components for three scientific reasoning skills. Subsequently, the correlation of corresponding content knowledge (CK) with the PCKSR-bio score was tested with 67 master’s students. In addition, the instrument was used in a cross-sectional study with 165 students (n = 29 bachelor, n = 115 master, n = 21 school-based preservice teachers), and the internal consistency as well as the correlation of the test score with the educational level was determined. An analysis of the response processes of 10 bachelor’s students showed that they more often referred to PCK when selecting an attractor and more often (rather intuitively) to other knowledge when selecting a distractor. In the cross-sectional study, the internal consistency was relatively low but increased with higher educational level. A correlation was found between the test score and CK but not between the test score and the educational level. Our results show that considering multiple sources of validity evidence can help to address common challenges in developing MC–PCK instruments. The results and limitations are discussed, and recommendations are made for the development of MC instruments to assess PCK in general.

The Network University Medicine (NUM) consists of 36 university clinics in Germany. It was set up to coordinate COVID-19 university medicine research activities on a national level. This required, among other things, common infrastructures for the collection, storage, and use of medical research data. These infrastructures were not available in the required form when the NUM started in April 2020. Medical research data are extremely heterogeneous and reach far beyond "real world data " from patient care. There was no "one size fits all " solution, so NUM built five infrastructures for different types of data, different ways of obtaining data, and different data origination settings. To prevent the creation of new data silos, all five infrastructures operate based on FAIR principles (findable, accessible, interoperable, reusable). In addition, NUM is implementing an overarching governance framework to manage the evolution of these five infrastructures. The article describes the current state of development and possible perspectives with a strong focus on technical and organizational aspects.

Fusobacterium nucleatum is overrepresented in the colon microbiome of colorectal cancer patients and has been associated with tumor growth enhancement and metastasis. A pivotal pathogenic factor, the autotransporter adhesin Fap2, facilitates association to cancer and immune cells via the receptors Gal-GalNAc and TIGIT, respectively, leading to deactivation of immune cells. Mechanistic details of the Fap2/TIGIT interaction remain elusive as no structural data are available. Here, we report a system to recombinantly express functional Fap2 on the Escherichia coli surface, which interacts with Gal-GalNAc on cancer cells and with purified TIGIT with submicromolar affinity. Cryo-EM structures of Fap2, alone and in complex with TIGIT, show that the elongated ~50 nm long Fap2 extracellular region binds to TIGIT on its membrane-distal tip via an extension of a β-helix domain. Moreover, by combining structure predictions, cryo-EM, docking and molecular dynamics simulations, we identified a binding pit for Gal-GalNAc on the tip of Fap2.

How SARS-CoV-2 Omicron evolved remains obscure. T492I, an Omicron-specific mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, inferring potentials to drive evolution. Through evolve-and-resequence experiments of SARS-CoV-2 wild-type (hCoV-19/USA/WA-CDC-02982585-001/2020, A) and Delta strains (B.1.617) with or without T492I, this study demonstrates that the NSP4 mutation T492I confers accelerated phenotypic adaption and a predisposition to the emergence of SARS-CoV-2 Omicron-like variants. The T492I-driven evolution results in accelerated enhancement in viral replication, infectivity, immune evasion capacity, receptor-binding affinity and potential for cross-species transmission. Aside from elevated mutation rates and impact on deaminases, positive epistasis between T492I and adaptive mutations could potentially mechanistically facilitate the shifts in mutation spectra and indirectly determines the Omicron-predisposing evolution. These suggest a potentially important role of the driver mutation T492I in the evolution of SARS-CoV-2 Omicron variants. Our findings highlight the existence and importance of mutation-driven predisposition in viral evolution.

Background

Virtual reality (VR) technology has been increasingly employed to develop innovative treatments for Alcohol use disorder (AUD) and overcome limitations of currents therapies. However, previous research in this field has yielded inconclusive results. To improve the quality and comparability of studies, a critical analysis of the research methodology employed in this field is necessary.

Objectives

This scoping review aims to provide an overview of existing studies with a focus on their objectives, methodology, treatment paradigms, and VR design characteristics.

Methods

A systematic literature research was conducted in the electronic databases MEDLINE (PubMed), APA PsychInfo, APA PsychArticles, PSYINDEX (EBSCOhost), Scopus, Web of Science and by search in the reference list of included publication to identify relevant publications. Clinical studies and study protocols using VR for the assessment or treatment of patients with AUD were included.

Results

The literature search yielded 1.197 studies, of which 22 met the inclusion criteria. Completed trials (n = 16) and study protocols (n = 6) were included. The majority of the studies (n = 19) used a VR cue exposure paradigm to induce craving. The studies can be classified either as assessment (n = 9) or treatment studies (n = 13). The duration (7–60 min) and number of applied sessions (1–13) varied significantly depending on the type of study. Craving outcomes were based on subjective and physiological measurements. All studies used alcoholic beverages and VR scenarios such as bars, pubs, parties and restaurants, with additional scenarios varying, except for one study using a hospital and subway scenario as aversive scenarios. Moreover, synchronized olfactory stimuli were frequently used.

Conclusions

Despite the heterogeneity of VR software features and VR interventions, it was possible to identify a similarity within the main VR scenarios employed, as well as consistent positive results concerning the induction of subjective craving by alcohol-associated VR cues. While VR interventions for AUD show methodological progress, future research should adopt standardized protocols, include objective psychophysiological outcomes, and evaluate long-term efficacy and feasibility in clinical settings. Integration of emerging VR paradigms and technologies may further enhance the therapeutic potential.

Understanding allosteric communication in proteins remains a critical challenge for structure-based, rational drug design. We present MDPath, a Python toolkit for analyzing allosteric communication paths in molecular dynamics simulations using NMI-based analysis. We demonstrate MDPath’s ability to identify both established and novel GPCR allosteric mechanisms using the β2-adrenoceptor, adenosine A2A receptor, and μ-opioid receptor as model systems. The toolkit reveals ligand-specific allosteric effects in β2-adrenoceptor and MOR, illustrating how protein–ligand interactions drive conformational changes. Analysis of ABL1 kinase in complex with allosteric and orthosteric inhibitors demonstrates the broader applicability of the approach. Ultimately, MDPath provides an open-source framework for mapping allosteric communication within proteins, advancing structure-based drug design (https://github.com/wolberlab/mdpath).

Purpose: To analyse differences in the retinal microvasculature in eyes with cytomegalovirus (CMV)-positive Posner-Schlossman syndrome (PSS) compared to the non-affected eyes using optical coherence tomography angiography (OCTA). Methods: In this monocentric, observational prospective case series, 25 patients with unilateral CMV-positive PSS were included. We compared the vessel area densities (VAD) in the macula, optic disc, and peripapillary region in PSS-affected and non-affected eyes using OCTA. We compared the visual fields (VF) of the affected and healthy eyes of each patient. The mean deviation (MD) of the VF was analysed together with the retinal nerve fibre layer (RNFL) thickness to evaluate the strength of correlation with the VAD parameters. Results: The VAD of the peripapillary superficial vascular complex (SVC) is significantly reduced in CMV-positive PSS-affected eyes (46.1 +/- 9.3% versus 50.1 +/- 6.3%, p = 0.008, adjusted p = 0.048). The VAD of the deeper macular, papillary, and peripapillary layers showed no differences between the affected and non-affected eyes. The mean deviation and the retinal nerve fibre layer thickness had correlations with the VAD of the macula (r = 0.451, p = 0.001, r = 0.553, p < 0.001), the peripapillary SCV (r = 0.430, p = 0.002, r = 0.723, p < 0.001), and the papillary region (r = 0.512, p < 0.001, r = 0.292, p = 0.039). Patients receiving systemic antiviral therapy (SAT) showed better VAD of the peripapillary choriocapillary layer (p = 0.001, no therapy: 31.4 +/- 1.9%, SAT: 35.0 +/- 1.6%), and choroidal layer (p = 0.009, no therapy: 34.2 +/- 0.3%, SAT: 36.3 +/- 1.8%) compared to those with no SAT. Conclusion: A lower peripapillary VAD in the SVC might indicate vascular dysfunction as a sign of glaucomatous damage. SAT might have positive effects on the microcirculation in the deep retinal and choroidal layers.

We introduce a weak solution concept (called “rough weak solutions") for singular SDEs with additive alpha-stable Lévy noise (including the Brownian noise case) and prove its well-posedness and equivalence to martingale solutions from Kremp and Perkowski (Bernoulli 28(3):1757–1783, 2022. https://doi.org/10.3150/21-BEJ1394) in “Young” and “rough” regularity regimes. In the rough regime this requires to construct certain rough integrals with the help of the stochastic sewing lemma, which we use to prove a generalized Itô formula for rough weak solutions. Furthermore, we show that in the Young case our solutions are equivalent to a simpler notion of weak solution, while in the rough case this simpler formulation leads to non-uniqueness in law.

Background: This study assesses digital health literacy (DHL) among individuals with bipolar disorder (BD) in Germany, employing Sørensen’s Integrated Model of Health Literacy (SIMHL). According to SIMHL, health literacy is a dynamic construct influenced by demographic, structural, and situational factors. With increased adoption of digital health resources, often overlooked are the skills required to use these tools. This study aims to bridge this gap by examining overall patterns of DHL among individuals with BD and employing SIMHL to investigate DHL the role of associated structural, situational/clinical, and technical access factors.

Methods: A cross-sectional online survey was conducted comprising 212 individuals with self-reported BD. DHL was assessed using the HL-DIGI instrument in addition to SIMHL factors including: structural (gender, employment status), situational (manic and depressive symptomatology), and technology use factors (use of health-related websites). Structural Equation Modeling (SEM) was used to model DHL as a latent variable.

Results: DHL followed a bimodal distribution, with participants clustering at either low (33.5%) or high (31.6%) levels. Evaluating reliability of online health information and using it to solve health-related tasks proved to be the most challenging. SEM demonstrated overall adequate model fit with higher DHL significantly associated with male gender, being employed and use of health-related websites.

Discussion: In line with SIMHL, DHL in individuals with BD is shaped by structural and access-related factors rather than illness severity. Gender, employment status, and engagement with health-related websites emerged as key correlates.

Conclusion: DHL in BD is not uniformly lower compared to the general population, underlining the feasibility of digital interventions as a promising pillar of care. At the same time, substantial heterogeneity highlights the need for routine DHL screening and tailored support for subgroups with lower skills. Future interventions and studies should systematically stratify by DHL level and target higher-order skills such as evaluating reliability and decision-making, in order to ensure equitable access and maximize the benefits of digital mental health care.

Clathrin-mediated endocytosis is essential for membrane traffic, impacting a diverse range of cellular processes including cell signaling homeostasis, cell adhesion, and receptor recycling. During endocytosis, invagination of the plasma membrane is coordinated by a network of proteins that recruit and assemble the clathrin coat. Recent work demonstrated that clathrin accessory proteins which arrive early at endocytic sites, such as Eps15 and Fcho2, form phase-separated condensates that recruit downstream machinery, promoting maturation of clathrin-coated vesicles. However, the mechanisms by which protein condensates regulate and are regulated by clathrin assembly remain unclear. Using in vitro reconstitution and nuclear magnetic resonance spectroscopy, we demonstrate that protein condensates provide a platform for recruitment and assembly of clathrin triskelia. This condensate driven assembly is enhanced in the presence of the accessory protein, AP2, which is incorporated within condensates. In turn, clathrin assembly restricted condensate growth, exhibiting surfactant-like behavior that stabilized protein-protein interactions while imposing the preferred curvature of the clathrin lattice. This mutual regulation promotes assembly of clathrin-coated vesicles while preventing uncontrolled expansion of protein condensates. More broadly, reciprocal regulation of protein condensates and clathrin coats may provide a framework for understanding how disordered and structured protein assemblies can work together to build cellular architectures.

Different types of germline de novo SETBP1 variants cause clinically distinct and heterogeneous neurodevelopmental disorders: Schinzel-Giedion syndrome (SGS, via missense variants at a critical degron region) and SETBP1 -haploinsufficiency disorder. However, due to the lack of systematic investigation of genotype-phenotype associations of different types of SETBP1 variants, and limited understanding of its roles in neurodevelopment, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remains elusive. This imposes challenges for diagnosis. Here, we present a comprehensive investigation of the largest cohort to date of individuals carrying SETBP1 missense variants outside the degron region ( n  = 18). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS and SETBP1- haploinsufficiency disorder. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding, transcription, and neuronal differentiation capacity and morphologies. In contrast to SGS and SETBP1 haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care, and aetiology of SETBP1-related disorders.

Background

Marek’s disease virus (MDV) causes Marek’s disease (MD) in chickens, which is characterized by malignant lymphomas and neurological disorders. Although MD is currently controlled using live vaccines, the virulence of field strains has continuously increased in recent decades. Polymorphisms in the MDV-encoded oncoprotein Meq are shared among field strains according to their virulence. In particular, very virulent MDV strains harbor characteristic amino acid changes in the basic region of Meq at positions 77 and 80; however, the contribution of these polymorphisms to virulence remains unclear.

Methods

To assess the impact of these polymorphisms on MDV virulence, we generated recombinant MDV (rMDV) based on the very virulent RB-1B strain, harboring K77E and D80Y substitutions in Meq found in low-virulent strains (rRB-1B_Meq77/80). Chickens were challenged with rMDVs, and survival rates and tumor incidence were evaluated. Viral loads in major organs were quantified by quantitative PCR, and the dynamics of MDV-infected cells and T cells were analyzed using flow cytometry. In addition, histopathological analysis was performed to further examine differences in pathogenesis in detail. To elucidate the mechanisms underlying pathogenesis, we conducted reporter assays to assess the effect of these polymorphisms in the basic region on its transcriptional regulatory activity.

Results

rRB-1B_Meq77/80 exhibited a reduced virulence but unexpectedly caused other clinical signs, including open-mouth breathing, in infected chickens. Quantitative PCR analysis showed consistently lower viral loads across all examined organs in rRB-1B_Meq77/80-infected chickens. Flow cytometric analysis revealed a reduction in MDV-infected cells, accompanied by a notable increase in CD8⁺ T cell populations. Histopathological analysis showed bronchus-associated lymphoid tissue hyperplasia in the lungs. Reporter assays revealed that most amino acid substitutions in the basic region in low-virulence strains reduced transcriptional regulatory activity.

Conclusion

Our data indicate that polymorphisms at positions 77 and 80 in the Meq of low-virulence strains reduce MDV virulence and Meq-mediated transcription and possibly alter pathogenesis. This study improves our understanding of the mechanisms underlying MDV virulence.

Impaired working memory in response to social-evaluative stress might be a central cognitive mechanism underlying the persistence of mental health difficulties such as social anxiety. To investigate this, we developed the Socio-evaluative N-back Task (SENT), which can measure the impact of acute socio-evaluative stress on working memory (WM) performance. Moreover, we tested the SENT in a stratified sample with high (HSA) and low socially anxious (LSA) individuals (HSA = 30, LSA = 27, N  = 57). Of the highly anxious individuals, thirteen were diagnosed with social anxiety disorder (SAD). The socio-evaluative stress condition, compared to a control condition, increased psychophysiological stress reactions, and reduced WM performance. Moreover, people with low anxiety displayed faster reaction times under socio-evaluative stress compared to a control condition. Conversely, individuals with high social anxiety demonstrated consistent reaction times regardless of whether they encounter a non-evaluative or socio-evaluative situation. This suggests that social anxiety is associated with a lack of differentiation between neutral and socio-evaluative situations. Additionally, this study indicates that the socio-evaluative N-back Task can be used to induce socio-evaluative stress responses while simultaneously measuring working memory and physiological stress responses.

Quantum low-density parity-check codes are a promising candidate for fault-tolerant quantum computing with considerably reduced overhead compared to the surface code. However, the lack of a practical decoding algorithm remains a barrier to their implementation. In this work, we introduce localized statistics decoding, a reliability-guided inversion decoder that is highly parallelizable and applicable to arbitrary quantum low-density parity-check codes. Our approach employs a parallel matrix factorization strategy, which we call on-the-fly elimination , to identify, validate, and solve local decoding regions on the decoding graph. Through numerical simulations, we show that localized statistics decoding matches the performance of state-of-the-art decoders while reducing the runtime complexity for operation in the sub-threshold regime. Importantly, our decoder is more amenable to implementation on specialized hardware, positioning it as a promising candidate for decoding real-time syndromes from experiments.