Protocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial).

Introduction: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade.

Clinical, biographical and healthcare-related factors associated with accelerated health decline in persons with multimorbidity: an evidence mapping review protocol.

Introduction: Multimorbidity contributes significantly to poor population health outcomes while straining healthcare systems. Although some multimorbid patients experience an accelerated health decline (a decline in well-being or functional status that cannot be attributed to the natural ageing-related health deterioration), others can remain stable for years. Identifying risk factors for accelerated health decline in persons with multimorbidity could help prevent complications and reduce unnecessary interventions.

Autophosphorylation of conserved yeast and human casein kinase 1 isozymes regulates Elongator-dependent tRNA modifications.

Casein kinase 1 (CK1) family members are crucial for ER-Golgi trafficking, calcium signalling, DNA repair, transfer RNA (tRNA) modifications, and circadian rhythmicity. Whether and how substrate interactions and kinase autophosphorylation contribute to CK1 plasticity remains largely unknown. Here, we undertake a comprehensive phylogenetic, cellular, and molecular characterization of budding yeast CK1 Hrr25 and identify human CK1 epsilon (CK1ϵ) as its ortholog.

WarpDemuX-tRNA: barcode multiplexing for nanopore tRNA sequencing.

Transfer RNA (tRNA) plays an essential role in protein translation, and tRNA modifications are important to their function. Recently, nanopore direct RNA sequencing (dRNA-seq) has shown promising results in the detection of complex tRNA modifications. However, its wider adoption in the tRNA field has been limited by a lack of (de)multiplexing solutions.

Deep analysis of desmoglein-3-reactive CD4 T cells in pemphigus vulgaris reveals a type 17/type 2 T cell signature.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder, which is caused by the loss of desmosomal cell-cell adhesion, initiated by the binding of IgG antibodies against the desmosomal components desmoglein (Dsg)1 and Dsg3. Dsg3-reactive CD4 T helper (Th) cells, in particular follicular Th (Tfh) cells, play a central role in autoantibody production by Dsg3-specific B cells. In this study, we challenged the concept that distinct Dsg3-reactive CD4 T cell subsets are critical in PV pathogenesis utilizing phenotypical and functional state-of-the-art ex vivo assays.

Daptomycin membrane activity is modulated by the localized interplay between calcium ions and phospholipids in monolayers and bilayers containing a lysyl-phosphatidylglycerol analogue.

Using the stable synthetic analogue 3-aza-dehydroxylysyl-phosphatidylglycerol (3adLPG), the putative role of native staphylococcal LPG in inhibiting the antibiotic daptomycin from binding to its target phosphatidylglycerol (PG), was investigated with respect to interfacial interactions between these lipids, daptomycin, and calcium ions. The influence of lipid monolayer/bilayer composition and interfacial ion concentrations upon the structure and integrity of model membranes were probed after daptomycin challenge using a combination of surface x-ray scattering techniques and fluorescence assays. In models representing the membrane composition of the daptomycin susceptible phenotype consisting of PG/3adLPG in a 7:3 M ratio, calcium ions drive the formation of two separate phases; Ca cross-linked PG/PG pairs and PG/3adLPG ion pairs.

International Multicentre Study on the Treatment of Infrarenal Penetrating Aortic Ulcers.

Objective: This study aimed to evaluate treatment indications, compare therapeutic approaches, and assess outcomes in patients with infrarenal penetrating aortic ulcers (iPAUs).

Methods: This was a retrospective, multicentre, observational study of patients with iPAUs treated between January 2018 and December 2022 across 12 European centres. Treatment strategies included open surgical repair (OSR) and endovascular techniques, including balloon expandable stent grafts (BESGs), covered endovascular reconstruction of the aortic bifurcation (CERAB), and endovascular aortic repair (EVAR) using bifurcated or tube grafts.

Neural foundations of creativity: A voxel-based meta-analysis of the activations and deactivations underlying creativity across linguistic, musical, and visual domains.

The neuroscience of creativity has proposed that shared and domain-specific brain mechanisms underlie creative thinking. However, greater nuance is needed in characterizing these mechanisms, and limited neuroimaging analyses, especially regarding the relationship between the Alternative Uses Task (AUT) and other linguistic tasks, have so far prevented a comprehensive understanding of the neural basis of creativity. This paper offers to fill these gaps with a closer examination of the contributions of the specific domains and the deactivations associated with creativity.

PROGESTERONE ATTENUATES THE EFFECTS OF COCAINE ON HYPERMOBILITY AND DOPAMINERGIC TRANSMISSION IN THE NUCLEUS ACCUMBENS.

Currently there is no pharmacological treatment for cocaine use disorder. Previous studies have shown that progesterone can mitigate the behavioral effects induced by cocaine in both animal models and humans. However, the underlying mechanisms through which progesterone exerts this effect remain poorly understood.

Effect of 3-hydroxisobutyrate in vivo administration on cardiometabolic disease in ApoE-/- mouse model.

The valine catabolite 3-hydroxyisobutyrate (3-HIB) is suggested to mediate the uptake of extracellular fatty acids into the cells, thus regulating intracellular lipid metabolism, although the direct mechanism remains unclear. In this study, we assessed the effects of long-term 3-HIB treatment on the development and progression of complex atherosclerotic lesions, lipid metabolism and liver injury in vivo in ApoE-/- mouse model fed Western Diet (WD). Results show that 3-HIB treatment is associated with a significant reduction in weight and serum lipid content, reduced aortic mean plaque area and improvement of liver functions.

Modelling challenges to unlock the power of phototrophic systems for wastewater valorization.

Phototrophic microorganisms are gaining prominence for their dual role in wastewater treatment and resource recovery, converting wastewater into valuable bioproducts. However, their effective deployment needs robust modelling frameworks capable of predicting performance across complex, real-world scenarios. Despite significant advances, key challenges hinder the development and application of such models.

Supplementary Material for Projected Global Clinical, Humanistic, and Economic Impact of Metabolic Dysfunction-Associated Steatohepatitis (MASH): The Cost of Inaction Based on Data from Nine Countries.

Background And Aim: Although the clinical burden of MASH is well known, its economic burden is less well described. We estimated MASH's economic burden in several regions of the world including the US, Germany, Spain, France, Italy, and United Kingdom (UK), Japan, Saudi Arabia, and Brazil over the next two decades.

Methods: A one-year cycle Markov model projected MASH progression from 2021 to 2040, incorporating 2020 prevalent cases and annual incident cases (2021-2040).

Real-world use of terlipressin in cirrhosis and acute kidney injury: frequent use beyond hepatorenal syndrome.

Background & Aims: Terlipressin is indicated to treat hepatorenal syndrome (HRS)-acute kidney injury (AKI), but is likely used outside this primary indication in clinical practice. We aimed to investigate real-world practice patterns on the use of terlipressin in AKI in cirrhosis.

Methods: International prospective study including patients hospitalized for decompensated cirrhosis.

Intraoperative radiotherapy for resectable brain metastases: a systematic review and meta-analysis.

Background: In recent years, intraoperative radiotherapy (IORT) with low-energy X-rays is emerging as an alternative to postoperative stereotactic radiotherapy (SRT) of the resection cavity in patients with resectable brain metastases (BMs).

Methods: We performed a systematic review of the MEDLINE, Embase, and Scopus databases, including all original articles on IORT for resectable BMs from 2015 to 2025. Data on safety, local control, and survival outcomes were collected.

Blood transcriptomic analysis reveals a distinct molecular subtype of treatment resistant depression compared to non-treatment resistant depression.

Treatment-resistant depression (TRD) is a severe condition characterized by chronic and recurrent depressive symptoms, leading to significant morbidity and a considerable socio-economic impact. Genetic and biological studies suggest that TRD is associated with distinct biological characteristics. In this study, we analysed whole-transcriptome differences in 293 patients with major depressive disorder (MDD) to compare TRD (N = 150) vs non-TRD (N = 143) cases.

Impaired social fear extinction in chronically stressed mice: Impact on inflammatory brain markers and the contribution of oxytocin.

Chronic psychosocial stress is a frequent burden in modern societies and risk factor for numerous somatic and affective disorders, including social anxiety disorder (SAD). Traumatic experiences after prolonged periods of stress exposure often trigger these diseases. Although human and animal studies support the hypothesis of an over-reactive immune system being critically involved in the pathogenesis of psychopathologies, the underlying mechanisms are not fully understood.

Simulating Extractables and Leachables in Biopharmaceutical Manufacturing to Support Safety Assessment.

The use of single-use systems in the manufacturing of biopharmaceuticals raises concerns about the accumulation of process equipment-related leachables in their production and purification processes. However, this risk is mitigated by effective sinks in the manufacturing processes and dilution of product flow, for example, in tangential-flow-filtration. This paper presents a modeling approach that combines the release and adsorption of compounds with dynamic process conditions of biopharmaceutical processes.

Incidence of Tick-Borne Encephalitis in Unvaccinated Populations Across Europe (2020-2023).

Background: Tick-borne encephalitis (TBE) is a vaccine-preventable disease. While many European countries conduct TBE surveillance, resulting incidence estimates do not distinguish between vaccinated and unvaccinated populations. To understand TBE risk to unvaccinated individuals, we assessed incidence among unvaccinated populations in Europe.

Chronic medical diseases and depressive symptoms in Europe: A study using representative data from 275,009 individuals in the third wave of the European Health Interview Survey (EHIS-3).

Background: Depressive symptoms significantly increase physical morbidity, mortality, and healthcare demands, while chronic diseases can exacerbate depressive symptoms. This study aimed to: 1) determine the prevalence of depressive symptoms among individuals with and without chronic diseases; 2) compare the number of chronic diseases across age groups in those with and without depressive symptoms; and 3) analyze associations between depressive symptoms and chronic diseases, adjusting for sociodemographic, socioeconomic, lifestyle, and health-related variables.

Methods: In this cross-sectional study, data from 275,009 participants (126,642 men, 148,367 women) in the third wave of the European Health Interview Survey (2018-2020) across 30 European countries were analyzed.

Linear magnetic nanoparticle structures as key feature in magnetic particle imaging.

Objective: Magnetic particle imaging (MPI) opens huge possibilities in image-guided therapy. Its effectiveness is strongly influenced by the quality of the magnetic nanoparticles (MNP) used as tracers. Besides MNP optimization following different synthesis routes, MNP assembly into linear structures can significantly enhance their performance in MPI.

Recellularization of Scaffolds derived from precision-cut kidney slices.

The global rise in chronic kidney disease necessitates innovative solutions for end-stage renal dis-ease that can help to overcome the limitations of the only available treatment options, transplanta-tion and dialysis. Tissue engineering presents a promising alternative, leveraging decellularized scaffolds to retain the extracellular matrix (ECM). However, optimizing methods for decellularization and recellularization remains a challenge.

How big data analytics can strengthen large-scale food fortification and biofortification decision-making: A scoping review.

Big data analytics have shown great potential to improve decision-making in health, including disease surveillance and healthcare delivery. This scoping review explores how big data supports decision-making in large-scale food fortification (LSFF) and biofortification across the food value chain. Following PRISMA guidelines, we analyzed open-access peer-reviewed literature and gray literature from 2012 to 2022.

Sensitive dissection of a genomic regulatory landscape using bulk and targeted single-cell activation.

Enhancers are known to spatiotemporally regulate gene transcription, yet the identification of enhancers and their target genes is often indirect, low resolution, and/or assumptive. To identify and functionally perturb enhancers at their endogenous sites, we performed a pooled tiling CRISPR activation (CRISPRa) screen surrounding PHOX2B, a master regulator of neuronal cell fate and a key player in neuroblastoma, and found many CRISPRa-responsive elements (CaREs) that alter cellular growth. To determine CaRE target genes, we developed TESLA-seq (targeted single-cell activation), which combines CRISPRa screening with targeted single-cell RNA sequencing and enables the parallel readout of the effect of hundreds of enhancers on all genes in the locus.