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Multiple jejunal diverticulosis, from an anatomical and histological view : a case report
(2025) Schmidt, Patricia; Perniss, Alexander; Nassenstein, Christina; Keller, Hanno; Deckmann, Klaus
BACKGROUND: Here, we report a case of jejunal diverticulosis from an anatomical and histological view. During the “Gross Anatomy course,” we found multiple jejunal diverticula along a total length of 208 cm of intestine. CASE SUMMARY: After opening the intestinal tract, we counted 232 jejunal diverticulum entry points with a diameter of up to 2 cm and observed connections between the diverticula that created shortcuts between two distinct intestinal parts. Interestingly, we observed an extreme longitudinal striation on the intestinal parts hosting diverticula. Thorough vessel preparation utilizing a dissecting microscope confirmed that all investigated arteriae rectae ended in a diverticulum. Histological and immunohistochemical investigations revealed that intestinal villi of diverticula were smaller and less prominent than control tissue and that the stratum longitudinale, as well as the stratum circular, were much thinner in the diverticula compared to control tissue. Neither submucosal nor mesenteric plexus could be detected in the diverticula. However, vasoactive intestinal peptide-positive nerve fibers and villin-positive brush border could only be detected in control tissue. This indicates that jejunal diverticulosis is associated with abnormalities of the smooth muscles and a disorder of innervation. CONCLUSION: Jejunal diverticulosis originates from mesenteric vessels, featuring smooth muscle changes, absent innervation, and thinning of tissue layers.
Histology-driven tailoring of surgical approaches in retroperitoneal soft tissue sarcoma : retrospective cohort study
(2025) Musa, Julian; Willis, Franziska; Rompen, Ingmar F; Harnoss, Julian-Camill; Grünewald, Thomas G P; Al-Saeedi, Mohammed; Büchler, Markus W; Schneider, Martin
Background: Histology-driven tailoring of surgical approaches for retroperitoneal soft tissue sarcoma is currently under debate. Compelling evidence assessing the role of histology-dependent extent of resection is lacking. The aim of this study was to assess outcomes of patients with primary retroperitoneal liposarcoma (LPS) or leiomyosarcoma (LMS) according to whether comprehensive (formerly ‘compartmental’) resection (CR) was performed. Methods: A retrospective study was conducted on data from patients undergoing surgical resection for LPS and LMS at Heidelberg University Hospital (2002–2019). Parameters were compared between groups with and without CR, with subgroup analyses for grading (LPS). Kaplan–Meier and Cox regression analyses were used to identify predictors of disease-specific survival (DSS), local recurrence-free survival, and distant metastasis-free survival. Results: In total, 119 patients with primary LPS and 46 patients with primary LMS were identified. DSS was improved in patients with LPS with CR (P = 0.049), and both DSS (P = 0.040) and distant metastasis-free survival (P = 0.041) were improved in the subgroup of patients with primary G3 LPS. In contrast, CR in patients with LMS was not associated with improved DSS, local recurrence-free survival, or distant metastasis-free survival. CR was associated with more severe postoperative complications (P = 0.021) and a longer hospital stay (P = 0.013) in patients with LPS, longer operation times (P < 0.010) in both patients with LPS and LMS, and increased blood loss (P = 0.008) in patients with LMS. Conclusion: CR is associated with improved DSS in patients with primary LPS, which is not the case in patients with primary LMS. Given the association between CR and increased perioperative morbidity, surgical strategies for retroperitoneal soft tissue sarcoma should be individualized according to the underlying histology.
Midterm Outcomes and Surgical Approaches for Osteochondral Lesions of the Talus
(2025) Biehl, Christoph; Fritzsche, Carina; Walter, Nike; Biehl, Lotta; El Khassawna, Thaqif; Heiss, Christian; Rupp, Markus
Background: Osteochondral lesions (OCL) of the talus are a significant cause of chronic ankle pain and functional impairment, typically following trauma. Despite advancements in diagnostic imaging and surgical interventions, long-term outcomes vary, and no gold standard treatment has been established. Methods: This retrospective study evaluated the outcomes of n=64 patients undergoing OCL-related surgery. Inclusion criteria: an OCL of the talus, patients without OCL, with osteoarthritis, or infection were excluded. The cohort was categorized primarily based on the stage of OCL and the surgical technique used: bone marrow stimulation by retrograde or anterograde drilling and microfracturing, transplantation of autologous cancellous bone, and acellular cartilage replacement and other procedures. Postoperative outcomes were assessed using the visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, and the Foot and Ankle Outcome Score (FAOS). Statistical significance was determined using χ2 tests, with P <.05 considered significant. Results: A total of 97 operations were performed on 64 patients. Fifty-six percent of patients reported complete resolution of symptoms, 25% experienced partial improvement, and 19% showed no improvement. Patients aged ≤30 years had a higher success rate (62.5%) compared with older patients (45.8%, P = .227). Success rates were significantly better for patients with stage II and III lesions (50% and 59%, respectively) than for those with stage IV lesions (P = .043). Material substitution had a success rate of 44.4%, bone marrow stimulation 37.8%, and other procedures 18.8%. Conclusion: Surgical techniques for treating OCL of the talus provide moderate success, but a significant proportion of patients, especially those with advanced lesions, remain symptomatic.
AMPK and CAMKK activation participate in early events of Toxoplasma gondii-triggered NET formation in bovine polymorphonuclear neutrophils
(2025) Conejeros, Iván; Velásquez, Zahady D.; Espinosa, Gabriel; Rojas-Baron, Lisbeth; Grabbe, Magdalena; Hermosilla, Carlos; Taubert, Anja
Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects humans, eventually causing severe diseases like prenatal or ocular toxoplasmosis. T. gondii also infects cattle but rarely induces clinical signs in this intermediate host type. So far, the innate immune mechanisms behind the potential resistance of bovines to clinical T. gondii infections remain unclear. Here, we present evidence on sustained activation of bovine polymorphonuclear neutrophils PMN by T. gondii tachyzoites, which is linked to a rise in cytoplasmic calcium concentrations, an enhancement of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK) and AMP-activated protein kinase (AMPK). NETosis is a specific form of programmed cell death, characterized by the release chromatin from the nucleus to the extracellular space resulting in formation of neutrophil extracellular traps (NETs). NETs can kill and entrap pathogens. In our experiments, NETosis was triggered by T. gondii, and this effector mechanism was enhanced by pre-treatments with the AMPK activator AICAR. Moreover, tachyzoite-mediated bovine neutrophil DNA release depended on MAPK- and store operated calcium entry- (SOCE) pathways since it was diminished by the inhibitors UO126 and 2-APB, respectively. Overall, we here provide new insights into early polymorphonuclear neutrophils responses against T. gondii for the bovine system.
Dietary Protein Levels in Isoenergetic Diets Affect the Performance, Nutrient Utilization and Retention of Nitrogen and Amino Acids of Hermetia illucens (L.) (Diptera: Stratiomyidae) Larvae
(2025) Schneider, Laura; Kisinga, Benson; Stoehr, Nathalie; Cord-Landwehr, Stefan; Schulte-Geldermann, Elmar; Moerschbacher, Bruno M.; Eder, Klaus; Jha, Rajesh; Dusel, Georg
Black soldier fly, H. illucens larvae, efficiently convert low-value organic substrates into high-value products, offering solutions to global challenges in sustainable food production and biotechnology. This study investigated the impact of dietary protein levels (10%, 14%, 16%, and 20% crude protein, CP) on BSFL growth, nutrient utilization, and energy retention using isoenergetic diets (18.5 ± 0.3 MJ/kg dry matter) under commercial-scale conditions. Larvae were harvested after 8 days of feeding, with 5 replicates per treatment. Optimal growth performance and feed conversion ratios were observed in larvae fed 14% CP diet, with a quadratic relationship between dietary CP and biomass gain (p < 0.001, R² = 0.870). Ash and calcium deposition peaked in CP20-fed larvae and were lowest in CP14-fed larvae. Phosphorus and glucosamine deposition remained unaffected, while chitin deposition correlated positively with larval weight. Nitrogen and amino acid retention were highest in CP14-fed larvae but reduced in CP20-fed larvae (p < 0.001, R² = 0.573–0.902). CP10-fed larvae showed impaired growth and nitrogen deposition but increased fat deposition. These findings establish the CP14 diet as the optimal formulation for scalable BSFL production, providing critical insights into dietary protein effects on BSFL physiology and enabling the development of efficient feeding strategies for industrial-scale farming.
Genome-Wide Association Study Reveals Single Nucleotide Polymorphisms Associated with Tail Length and Tail Kinks in Piglets
(2025) Gerhards, Katharina; Egerer, Christiane; Becker, Sabrina; Willems, Hermann; Engel, Petra; Koenig, Sven; Reiner, Gerald
Tail docking is still used in pigs to reduce the prevalence of tail biting, although it is purely symptomatic and contrary to animal welfare. Genetic selection for shorter tails might, however, help to avoid tail docking and has therefore been proposed. A genetic basis for tail length is known for many species. Variability in tail length, including moderate heritability, has also been demonstrated in pigs. The aim of the present study was to identify genetic markers for tail length and to define candidate genes. To this end, 140 piglets were phenotyped and genotyped at 3 days of age and a genome-wide association study was performed. Seven SNPs were mapped on chromosomes 1, 2, 6, 11, and 15. Two linked SNPs on chromosome 2 resulted in a functional amino acid exchange. The genotypes at the SNPs were only associated with small differences in relative tail length of up to 16.5% (short genotype versus long genotype at SSC15), but at the same time with the occurrence of malformations in the form of tail kinks. The small effect size and the association between tail length and tail kinks, together with the generally pure symptomatic effect on tail biting, argue against the applicability of selection for shorter tails in pigs.
Isoflurane vs. Propofol Sedation in Patients with Severe Stroke : A Clinical Proof-of-Concept-Study
(2025) Worm, André; Claudi, Christian; Braun, Svea R.; Schenker, Marisa; Meyer, Anneke; Moeller, Leona; Simon, Ole J.; Timmermann, Lars; Mrochen, Anne; Diel, Norma J.; Juenemann, Martin; Huttner, Hagen B.; Schramm, Patrick
Background: Severe strokes often require deep sedation, yet the optimal sedation regimen remains unclear. This comparative study compared the efficacy of achieving target sedation depth using inhaled (isoflurane) versus intravenous (propofol) sedation. Methods: This prospective, observational, proof-of-concept study was conducted between July 2022 and June 2023 at two University Hospitals with dedicated neurological intensive care units. We included conservatively treated patients with severe space-occupying strokes (ischemic or haemorrhagic) requiring deep sedation. Patients received either inhaled or intravenous sedation. Sedation targets were defined in the morning rounds using the Richmond-Agitation-Sedation-Scale and were assessed at two subsequent time points (7 p.m. and 7 a.m.) during hospital stay. The primary outcome was the number of days where the predefined sedation target was achieved at both time points, comparing between the two sedation regimens. Secondary and safety outcomes included the incidence of delirium, pneumonia, functional outcomes, mortality, and vasopressor doses. Results: Seventy-nine patients (age 71 [63–81] years, 31 female) were included. Patients sedated with isoflurane achieved the sedation target significantly more often, with 182/444 (41%) compared to 80/497 (16%) assessments in patients sedated with propofol (RR 1.4; 95%-CI: 1.3–1.6). This effect was consistent across all sedation stages, specifically in the deep sedation targets (RR 1.5; 95%-CI: 1.2–1.9) and no-sedation target (RR 5.1; 95%-CI: 2.8–9.4). Secondary and safety outcomes revealed no significant differences. Conclusions: Isoflurane sedation offers a benefit for invasively ventilated stroke patients with respect to sedation targets. Specifically, isoflurane facilitates faster awakening when transitioning from deep sedation to awakening. These data encourage further confirmatory studies for specific stroke-patient groups.
Dobutamine, epinephrine, and milrinone accelerate particle transport velocity in murine tracheal epithelium via Ca2+ release from caffeine-sensitive internal stores
(2025) Schmidt, Götz; Borchers, Frederic; Müller, Sabrina; Ali Akbari, Amir; Edinger, Fabian; Sander, Michael; Koch, Christian; Henrich, Michael
Mucociliary clearance, the ability of the respiratory tract to protect the integrity of the airways through the mechanical removal of potentially harmful substances, is of enormous importance during intensive care treatment. The present study aimed to evaluate the influence of clinically relevant inotropic agents on mucociliary clearance. The particle transport velocity (PTV) of isolated murine tracheae was measured as a surrogate for mucociliary clearance in the presence of dobutamine, epinephrine, and milrinone. Inhibitory substances were applied to elucidate the signal transduction cascades and the value and origin of calcium ions which provoke alterations in mucociliary clearance function. Dobutamine, epinephrine, and milrinone increased the PTV in a dose-dependent manner with half maximal effective concentrations of 75.7 nM, 87.0 nM, and 13.7 µM, respectively. After the depletion of intracellular calcium stores, no increase in PTV was observed after administering any of the three inotropic agents. While dobutamine and epinephrine activated β-adrenergic receptors, epinephrine used both the phospholipase C (PLC) and protein kinase A (PKA) pathway to promote the release of intracellular Ca2+. However, dobutamine primarily acted on the PKA pathway, having only a minor influence on the PLC pathway. The induced changes in PTV following milrinone administration required both the PKA and PLC pathway, although the PKA pathway was responsible for most of the induced changes. In conclusion, the common inotropic agents dobutamine, epinephrine, and milrinone increase murine PTV in a concentration-dependent manner and ultimately release Ca2+ from intracellular calcium stores, suggesting the function of changes in mucociliary clearance in the respiratory tract.
Genetic and epigenetic intersections in COVID-19-associated cardiovascular disease: emerging insights and future directions
(2025) Sabit, Hussein; Arneth, Borros; Altrawy, Afaf; Ghazy, Aysha; Abdelazeem, Rawan M.; Adel, Amro; Abdel-Ghany, Shaimaa; Alqosaibi, Amany I.; Deloukas, Panos; Taghiyev, Zulfugar T.
The intersection of COVID-19 and cardiovascular disease (CVD) has emerged as a significant area of research, particularly in understanding the impact of antiplatelet therapies like ticagrelor and clopidogrel. COVID-19 has been associated with acute cardiovascular complications, including myocardial infarction, thrombosis, and heart failure, exacerbated by the virus’s ability to trigger widespread inflammation and endothelial dysfunction. MicroRNAs (miRNAs) play a critical role in regulating these processes by modulating the gene expressions involved in platelet function, inflammation, and vascular homeostasis. This study explores the potential of miRNAs such as miR-223 and miR-126 as biomarkers for predicting resistance or responsiveness to antiplatelet therapies in COVID-19 patients with cardiovascular disease. Identifying miRNA signatures linked to drug efficacy could optimize treatment strategies for patients at high risk of thrombotic events during COVID-19 infection. Moreover, understanding miRNA-mediated pathways offers new insights into how SARS-CoV-2 exacerbates CVD, particularly through mechanisms like cytokine storms and endothelial damage. The findings of this research could lead to personalized therapeutic approaches, improving patient outcomes and reducing mortality in COVID-19-associated cardiovascular events. With global implications, this study addresses the urgent need for effective management of CVD in the context of COVID-19, focusing on the integration of molecular biomarkers to enhance the precision of antiplatelet therapy.
Description of Cohnella rhizoplanae sp. nov., isolated from the root surface of soybean (Glycine max)
(2025) Kämpfer, Peter; Glaeser, Stefanie P.; McInroy, John A.; Busse, Hans-Jürgen; Clermont, Dominique; Criscuolo, Alexis
A Gram-staining-positive, aerobic bacterium, designated strain JJ-181^T, was isolated from the root surface of soybean. Based on the 16S rRNA gene sequence similarities, strain JJ-181^T was grouped into the genus Cohnella, most closely related to Cohnella hashimotonis F6_2S_P_1^T (98.85%) and C. ginsengisoli GR21-5^T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridisation values of the JJ-181^T genome assembly against publicly available Cohnella type strain genomes were below 84% and 28%, respectively. The fatty acid profile from whole cell hydrolysates, the cell wall diaminoacid, the quinone system, the polar lipid profile, and the polyamine pattern supported the allocation of strain JJ-181^T to the genus Cohnella. In addition, the results of physiological and biochemical tests also allowed phenotypic differentiation of strain JJ-181^T from its closely-related Cohnella species. Functional analysis revealed that strain JJ-181^T has different gene clusters related to swarming motility, chemotaxis ability, and endospore and biofilm formations. The gene content also suggests the ability of strain JJ-181^T to synthesise biotin and riboflavin, as well as indole-3-acetic acid, an important phytohormone for plant growth. Based on polyphasic analyses, strain JJ-181^T can be classified as a new species of the genus Cohnella, for which we propose the name Cohnella rhizoplanae sp. nov., with strain JJ-181^T (= LMG 31678^T= CIP 112018^T = CCM 9031^T = DSM 110650^T) as the type strain.
A biocontrol perspective on mycoviruses in fungal pathogen management
(2025) Galli, Matteo; Sede, Ana; Heinlein, Manfred; Kogel, Karl-Heinz
Mycoviruses, viruses that infect fungi, have been identified across nearly every fungal taxon. Despite their widespread presence, the ecological effects of mycoviruses remain poorly understood. They can influence the biology of their hosts in various ways, including altering growth, reproduction, and pathogenicity. Their ability to induce either fungal hyper- or hypovirulence and thus regulate general fungal fitness by increasing fungal aggressiveness or, conversely, in extreme cases, converting harmful fungi into beneficial ones, has attracted increasing attention in recent years as a potential means of protecting plants from fungal diseases and pests. Increasing difficulties in controlling fungal diseases, pests and weeds with synthetic chemical pesticides, exacerbated by the emergence of resistance or tolerance to certain active ingredients, and stricter regulatory requirements due to environmental and health concerns, have stimulated interest in alternative approaches. In parallel with the introduction of double-stranded (ds)RNA-based products for crop protection and the fundamental knowledge generated in this field in recent years, the potential use of mycoviruses to control pathogenic fungi appears to be within reach. This review highlights recent advances in the field and emphasizes the potential of mycoviruses as biological control agents (BCAs), with the emphasis on the utilization of mycovirus-induced fungal hypovirulence to control fungi that cause plant diseases and mycovirus-induced fungal hypervirulence to protect plants from fungal hosts such insect pests or weeds.
Nirenberg problem on high dimensional spheres : blow up with residual mass phenomenon
(2025) Ahmedou, Mohameden; Ben Ayed, Mohamed; El Mehdi, Khalil
In this paper, we extend the analysis of the subcritical approximation of the Nirenberg problem on spheres recently conducted in Malchiodi and Mayer(J Differ Equ 268(5):2089–2124, 2020; Int Math Res Not 18:14123–14203, 2021). Specifically, we delve into the scenario where the sequence of blowing up solutions exhibits a non-zero weak limit, which necessarily constitutes a solution of the Nirenberg problem itself. Our focus lies in providing a comprehensive description of such blowing up solutions, including precise determinations of blow-up points and blow-up rates. Additionally, we compute the topological contribution of these solutions to the difference in topology between the level sets of the associated Euler-Lagrange functional. Such an analysis is intricate due to the potential degeneracy of the solutions involved. We also provide a partial converse, wherein we construct blowing up solutions when the weak limit is non-degenerate.
Transforming the feeding regime towards low-input increases the environmental impact of organic milk production on a case study farm in central germany
(2025) Eisert, Johannes; Sahraei, Amir; Knob, Deise Aline; Lambertz, Christian; Zollitsch, Werner; Hörtenhuber, Stefan; Kral, Iris; Breuer, Lutz; Gattinger, Andreas
Purpose: Despite the direct effect of the feeding regime on the environmental impacts of dairy farming systems, its level of intensity, particularly in organic systems, has rarely been investigated. This study compares the environmental impact of a high-input feeding regime with a grassland-based, low-input feeding regime scenario within an organic milk production system conducted on Gladbacherhof, the research farm of Justus Liebig University Giessen, in Central Germany. Methods: An integrated Life Cycle Assessment (LCA) analysis was performed from a cradle-to-farm gate perspective to quantify five environmental impacts, namely Global Warming (GW), Non-Renewable Energy Use (NREU), Land Use (LU), Terrestrial Acidification (TA), and Freshwater Eutrophication (FE). All agronomic data of the Gladbacherhof research farm, averaged over the years 2010–2017, were included. When not directly measured on the farm, ecoinvent data were included. Results and discussion: Contrary to our hypothesis, the results suggest that a grassland-based low-input system has a higher environmental impact as compared to a high-input system for each of the five impact categories when using fat and protein-corrected milk (FPCM) as the functional unit. A 50% reduction in concentrates and exclusion of maize silage from the feed ration in the modelled low-input production system lead to a 20% drop in milk yield. To balance the energy content in low-input feeding ration, longer grazing period and higher amount of hay, alfalfa, and grass silage are required. This in turn results in higher emissions from enteric fermentation, manure management, and feed production and hence in higher environmental impact, particularly for GW, TA, and FE. Conclusions: This study is one of the few that directly explores the environmental impact of feeding intensity in an organic milk production system. Nevertheless, there is a lack of research on consolidated emission factors for several greenhouse gas (GHG) sources in organic livestock and cropping systems to perform more robust carbon footprint calculations that comply with the Intergovernmental Panel on Climate Change (IPCC) Tier 3 GHG reporting guidelines. To generalize the results at the regional or national scale, direct comparisons with a larger number of organic farms representative of high-input and low-input intensities are still essential.
FIGO - GCH joint consensus statement on the current status and recommendations for the use of blind intrauterine procedures in the evaluation and management of women with suspected intrauterine pathologies
(2025) Villegas-Echeverri, Juan Diego; Pope, Rachel; Robert, Magali; Meinhold-Heerlein, Ivo; Haimovich, Sergio; Carugno, José; Pacheco, Luis A.; Sardo, Attilio Di Spiezio
Historically, blind intrauterine procedures such as dilation and curettage (D&C) and blind endometrial biopsies have been the primary approach for diagnosing and managing intrauterine pathologies. However, these techniques lack direct visualization, leading to diagnostic limitations, incomplete treatment, and increased complication rates. Despite substantial advances in hysteroscopic technology, including high-definition imaging and minimally invasive instruments, blind procedures remain widely used. This paper examines the limitations of blind intrauterine procedures, underscoring the advantages of hysteroscopy, which provides real-time visualization and allows for more accurate, targeted interventions. With the adoption of the “See and Treat” philosophy, hysteroscopy enables nearly 90% of procedures to be performed in an office setting, enhancing both patient convenience and outcomes. FIGO and GCH advocate for the gradual replacement of blind procedures with hysteroscopic approaches whenever feasible, noting that hysteroscopy improves diagnostic accuracy, reduces risks, and minimizes the need for repeat interventions. Recommendations include expanding access to hysteroscopy through targeted training, especially in low- and middle-income countries, where financial and logistical barriers limit access to advanced gynecological care. Furthermore, this paper emphasizes the importance of patient-centered care, encouraging transparent counseling to support informed decision-making.
Use of a new aiming compression device and technique for the repair of navicular bone fractures in horses: A cadaveric study
(2025) Pudert, Tanja; Fries, Giuletta Felicia; Lotz, Hannah; Röcken, Michael; Cruz, Antonio M.
Objective: To assess the use of a newly developed aiming compression device (ACD) for screw insertion in non-fractured navicular bones (NB) in cadavers. Study design: Cadaveric study. Sample Population: A total of 10 cadaveric front limbs of adult horses. Methods: Placement of a 3.5 mm cortical screw in non-fractured NB under radiographic guidance was performed in 10 cadaver limbs in a standing position. An ACD was used to stabilize the NB and to guide the drilling process. Preparation and surgical time as well as the number of radiographic images were noted. A postoperative scoring system was used to assess screw placement by cone beam computed tomography (CBCT) and gross examination by two evaluators. Results: The total procedure time was 25–62 min (median 33.5). During the procedure, 11–21 radiographs (median 18.5) were taken. The postoperative gross examination revealed an excellent screw placement in nine NB and poor in one. This could not be reliably assessed with post-procedure CBCT. Conclusion: The described technique achieves an excellent screw placement in 9/10 bones without disrupting the articular or flexural surface of the NB and with no protrusion of the screw head or tip, in a median procedure time of under 35 min. Clinical significance: Adequate screw placement is paramount for NB fracture repair. The described approach under radiographic guidance allows adequate screw placement using the ACD to stabilize the NB by lateral to medial compression. This technique facilitates adequate screw placement within the NB without the use of advanced imaging techniques.
Anti-inflammatory and remyelinating effects of fexagratinib in experimental multiple sclerosis
(2025) Gurski, Fynn; Shirvanchi, Kian; Rajendran, Vinothkumar; Rajendran, Ranjithkumar; Megalofonou, Fevronia-Foivi; Böttiger, Gregor; Stadelmann, Christine; Bhushan, Sudhanshu; Ergün, Süleyman; Karnati, Srikanth; Berghoff, Martin
Background and Purpose: FGF, VEGFR-2 and CSF1R signalling pathways play a key role in the pathogenesis of multiple sclerosis (MS). Selective inhibition of FGFR by infigratinib in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) prevented severe first clinical episodes by 40%; inflammation and neurodegeneration were reduced, and remyelination was enhanced. Multi-kinase inhibition of FGFR1-3, CSFR and VEGFR-2 by fexagratinib (formerly known as AZD4547) may be more efficient in reducing inflammation, neurodegeneration and regeneration in the disease model. Experimental Approach: Female C57BL/6J mice were treated with fexagratinib (6.25 or 12.5 mg·kg−1) orally or placebo over 10 days either from time of EAE induction (prevention experiment) or onset of symptoms (suppression experiment). Effects on inflammation, neurodegeneration and remyelination were assessed at the peak of the disease (Day 18/20 post immunization) and the chronic phase of EAE (Day 41/42). Key Results: In the prevention experiment, treatment with 6.25 or 12.5 mg·kg−1 fexagratinib prevented severe first clinical episodes by 66.7% or 84.6% respectively. Mice treated with 12.5 mg·kg−1 fexagratinib hardly showed any symptoms in the chronic phase of EAE. In the suppression experiment, fexagratinib resulted in a long-lasting reduction of severe symptoms by 91 or 100%. Inflammation and demyelination were reduced, and axonal density, numbers of oligodendrocytes and their precursor cells, and remyelinated axons were increased by both experimental approaches. Conclusion and Implications: Multi-kinase inhibition by fexagratinib in a well-tolerated dose of 1 mg·kg−1 in humans may be a promising approach to reduce inflammation and neurodegeneration, to slow down disease progression and support remyelination in patients.
European ILD registry algorithm for self-assessment in interstitial lung diseases (eurILDreg ASA-ILD)
(2025) Krauss, Ekaterina; Claas, Laurenz H.; Tello, Silke; Naumann, Jennifer; Wobisch, Sandra; Kuhn, Stefan; Majeed, Raphael W.; Moor, Karen; Molina-Molina, Maria; Byrne, Oisin; Borton, Rebecca; Wijsenbeek, Marlies S.; Hirani, Nik; Vancheri, Carlo; Crestani, Bruno; Guenther, Andreas
Background and aims: Predicting progression and prognosis in Interstitial Lung Diseases (ILD), especially Idiopathic Pulmonary Fibrosis (IPF) and Progressive Pulmonary Fibrosis (PPF), remains a challenge. Integrating patient-centered measurements is essential for earlier and safer detection of disease progression. Home monitoring through e-health technologies, such as spirometry and oximetry connected to smartphone applications, holds promise for early detection of ILD progression or acute exacerbations, enabling timely therapeutic interventions. Methods: The European ILD Registry Algorithm for Self-Assessment in ILD (eurILDreg ASA-ILD), developed by all eurILDreg principal investigators, includes questionnaires on symptom burden, respiratory infections, and quality of life (EQ5D VAS, K-BILD, LCQ). The algorithm also incorporates spirometry and oxygen saturation measurements, both at rest and during exercise (one-minute sit-to-stand test, 1STST). This ASA-ILD algorithm is integrated into the patientMpower Ltd. smartphone application, used for patient-led monitoring, research, and clinical care since 2016, and available on both Apple and Android platforms. Discussion: For patient-centered measurements, participants in the multicenter eurILDreg study will receive a patientMpower account, a handheld clinical-grade spirometer (Spirobank Smart, MIR, Italy), and a pulse oximeter (Nonin Medical, Inc. Plymouth, MN, USA), along with usage instructions. Artificial intelligence software (ArtiQ) will analyze spirometry maneuvers in real-time, ensuring compliance with recent ERS/ATS criteria and providing automated feedback. Pulse oximetry is integrated into the exercise testing within the application, following an automated in-app protocol developed with clinician involvement for safety and accuracy. The application will send reminders to participants to complete patient-reported outcome measures (PROMs) according to the study protocol. Conclusion: This study is designed to explore the potential of e-Health technologies, such as home monitoring via spirometry and oximetry, integrated with the eurILDreg ASA-ILD algorithm and patientMpower app, to improve early detection and management of ILD. A pilot trial showed promising adherence to spirometry, indicating that digital health interventions could enhance patient care and outcomes in ILD.
Human-like face pareidolia emerges in deep neural networks optimized for face and object recognition
(2025) Gupta, Pranjul; Dobs, Katharina
Decoding affect in emotional body language: valence representation in the action observation network
(2025) Keck, Johannes; Bachmann, Julia; Zabicki, Adam; Munzert, Jörn; Krüger, Britta
Humans are highly adept at inferring emotional states from body movements in social interactions. Nonetheless, it is under debate how this process is facilitated by neural activations across multiple brain regions. The specific contributions of various brain areas to the perception of valence in biological motion remain poorly understood, particularly those within the action observation network (AON) and those involved in processing emotional valence. This study explores which cortical regions involved in processing emotional body language depicted by kinematic stimuli contain valence information, and whether this is reflected either in the magnitude of activation or in distinct activation patterns. Results showed that neural patterns within the AON, notably the inferior parietal lobule (IPL), exhibit a neural geometry that reflects the valence impressions of the observed stimuli. However, the representational geometry of valence-sensitive areas mirrors these impressions to a lesser degree. Our findings also reveal that the activation magnitude in both AON and valence-sensitive regions does not correlate with the perceived valence of emotional interactions. Results underscore the critical role of the AON, particularly the IPL, in interpreting the valence of emotional interactions, indicating its essential function in the perception of valence, especially when observing biological movements.
Quantifying the spatial impact of an invasive Acacia on ecosystem functioning using remote sensing
(2025) Große-Stoltenberg, André; Werner, Christiane; Hellmann, Christine; Oldeland, Jens; Thiele, Jan
Remote sensing technology is increasingly applied to map the occurrence of invasive plant species, yet its use to map their ecological impact remains limited. Furthermore, invader-induced changes beyond the canopy, as well as the environmental context, are rarely considered. This study aimed to assess the impacts of an invasive tree on ecosystem functioning at the landscape scale using remote sensing, taking into account both spatial effects and environmental heterogeneity. Specifically, we investigated a coastal Mediterranean dune ecosystem invaded by the N-fixing tree Acacia longifolia (Andrews) Willd. (‘Acacia’). Four vegetation indices were calculated as proxies of ecosystem functions, and these indices were used to compute functional diversity in terms of spectral Rao’s Q for assessing impacts by Acacia based on airborne hyperspectral data. Vegetation cover and topographic indices derived from airborne LiDAR (Light Detection and Ranging) were used to account for spatial heterogeneity. For seven sites, we employed Generalized Linear Mixed Models to model the effects of environmental variables and Acacia-related variables on proxies of ecosystem functions. Significant impact of the invader was found beyond the invaded area augmenting to 50 % total impact on ecosystem functions. These spatial impacts are particularly prevalent at rather early stages of invasion (∼20 % invader cover at landscape level). Consequently, the impact of invaders is underestimated when spatial effects are ignored, but it is overestimated when environmental heterogeneity is neglected. Furthermore, functional diversity decreases due to invasion, though it reaches its maximum at the edges of invader stands, where Rao’s Q index captures spectral effects of both the invader and the native vegetation. Thus, we highlight that both 2D and 3D remote sensing data complement each other in remote sensing-driven impact assessments. We envision that advancements in remote sensing of ecosystem structure and functioning in terms of increasing availability of high spectral, spatial and temporal data as well as enhanced methods for data analysis will facilitate tracing the context-dependent and function-specific spatial effects of invasive species especially at early stages of invasion to enable timely management.

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