julilili42/papers huggingface dataset:
Pigment Epithelium‐Derived Factor (PEDF)‐Based Therapy Induced Photoreceptor Survival by Stabilizing Choroidal Neovessels in a VEGF Overexpression CNV Rat Model
2025-10-09

ABSTRACT Pathological choroidal neovascularization (CNV), characterized by abnormal leaky vessel formation, can lead to vision impairment or blindness. Current standard treatment, anti‐vascular endothelial growth factor (VEGF) therapy, while effective, can be associated with severe local and systemic side effects and resistance in some patients, necessitating novel therapeutic approaches. Evidence from wet age‐related macular degeneration (AMD) donor eyes and patients suggests that functional, quiescent CNV can aid photoreceptor survival. Therefore, stabilizing functional neovessels rather than removing them could offer an effective alternative for treating pathological CNV. Pigment epithelium‐derived factor (PEDF), a multifunctional protein with antiangiogenic, neuroprotective, and vessel‐stabilizing properties, is a promising candidate for this approach. The efficacy of intravitreally injected PEDF protein, alone or in combination with bevacizumab, was investigated and compared to bevacizumab monotherapy in a VEGF overexpression‐induced CNV rat model using in vivo imaging and histology. Following PEDF + bevacizumab treatment, a significant reduction in CNV thickness was observed, comparable to bevacizumab monotherapy. Notably, only PEDF and PEDF + bevacizumab treatments significantly preserved retinal thickness and enhanced photoreceptor survival at the CNV site. Ultrastructural analysis revealed that PEDF and PEDF + bevacizumab treatments increased CNV vessel lumina, stabilized these vessels by reducing the thickness of the extracellular matrix and refining its structure, and enhanced vessel fenestration and pericyte coverage, making PEDF‐based therapy more effective than bevacizumab monotherapy. These findings suggest that supporting the maintenance of functional CNV vessels using PEDF may represent a novel and innovative strategy for the treatment of wet AMD.
Dynamic neutrophil lipidome remodeling during induction of NETosis
2025-10-09

Neutrophil Extracellular Trap formation (NETosis) affects a wide variety of clinically relevant human diseases. Although lipid remodeling is essential for neutrophil function and membrane rupture during NETosis, the neutrophil lipidome and its dynamics have not been characterized. Thus, we establish the first quantitative lipidome of human neutrophils comprising 1,039 species across nine orders of magnitude and map its remodeling during NETosis. NET formation caused profound alterations in the phosphatidylinositol, phosphatidic acid, diacylglycerol and lysoglycerophospholipid levels. Calcium- and reactive oxygen species-dependent NETosis pathways displayed distinct lipidomic trajectories, yet converged on the significance of phospholipid lipase networks. Pharmacological inhibition of this networks altered lipid composition and markedly impaired NETosis, while diacylglycerol (DG) treatment revoked the effect. Altogether our findings reveal lipid remodeling as a fundamental determinant of NETosis and identify interconnected and dependent phospholipid lipase networks with downstream DG-dependent signaling as a potential therapeutic target in NET-associated diseases.
Efficacy of Preoperative Chemotherapy in Patients With Nephroblastoma and Imaging Findings Suggestive of Preoperative Tumor Rupture
2025-10-09

ABSTRACT Background and aims If Wilms tumor (WT) rupture is suspected preoperatively, it is unclear whether preoperative chemotherapy (preop‐CT) can be safely given and whether such patients need to be treated according to local stage III postoperatively. Methods We retrospectively analyzed characteristics, treatment, and outcome of patients with preoperative rupture suspected by imaging and clinical symptoms in 119 patients from Germany, Austria, and Switzerland with unilateral WT treated within SIOP studies. Results There was no difference in age and gender distribution compared with the overall cohort of patients with WT. The general health condition was characterized at least severely impaired (37.8%). Eighty‐nine patients 89 (74.8%) received preop‐CT and 30 (25.2%) had upfront surgery. The mean tumor volume at diagnosis undergoing preop‐CT was 605 mL compared with 312 mL at primary surgery. Metastases were found in 20 out of 89 (22.5%) and two out of 30 (6.7%) patients, respectively. After preop‐CT, 31 patients (34.8%) had local histological stage I, 16 (18.0%) had stage II, 41 (46.1%) had stage III, and one (1.1%) had unknown. Low risk histology was diagnosed in seven (7.9%), intermediate risk in 65 (73.0%), and high risk in 17 (19.1%) patients. After preop‐CT, nine patients relapsed (10.1%), compared with four (13.3%) after primary surgery. Relapses were independent of local radiotherapy. Altogether seven patients died. A total of 14 out of 31 patients (45.2%) with overall local stage I of intermediate risk after preop‐CT received only 4 weeks AV without radiotherapy after surgery with 100% relapse‐free survival. Conclusions Preop‐CT can be given safely, and postoperative treatment can follow the histological staging and risk group, given that a thorough review of the specific situation is done.
Clinical course up to 20 years after hantavirus infection
2025-10-09

ABSTRACT Background The long-term consequences of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome caused by Puumala virus (PUUV), remain incompletely understood. Previous studies suggested possible kidney and cardiovascular complications, but large-scale, long-term data are lacking. Methods In this study, we evaluated n = 156 individuals with a history of NE-associated acute kidney injury, up to 20 years after confirmed PUUV infection. Participants were followed up and underwent clinical and laboratory assessments including blood pressure measurement, kidney parameters, urinalysis and PUUV-specific serology. Participants with abnormalities in their kidney function during the first long-term follow-up were re-evaluated after 1 year. Results Median time since NE was 156 (interquartile range 137–168) months. Chronic kidney disease (CKD) was diagnosed in 8% of participants. Hematuria was present in 6% of participants. Hypertension at follow-up was observed in 78% of individuals. PUUV-specific immunoglobulin G (IgG) antibodies remained detectable in all participants, although three individuals had levels below the positive ratio threshold. No IgM antibodies or cases of reinfection were identified. Conclusion This is the largest and longest follow-up study of NE patients to date. Our findings do not support long-term kidney pathologies, or increased CKD incidence following acute NE. IgG antibodies persisted in all participants irrespective of duration of follow-up, with no evidence of reinfection. While hypertension was frequent, causality with prior hantavirus infection remains uncertain. These results suggest that long-term kidney complications after NE are uncommon.
Searching for long-lived light neutralinos from B-meson decays with baryonic R-parity violation at Belle II
2025-10-09

A bstract In a supersymmetry scenario with R-parity violation (RPV), neutralinos with GeV-scale mass, which are necessarily bino-like, are allowed by all constraints and can be produced in association with a baryon in B -meson decays via certain <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mover> <mml:mi>U</mml:mi> <mml:mo> ̄</mml:mo> </mml:mover> <mml:mover> <mml:mi>D</mml:mi> <mml:mo> ̄</mml:mo> </mml:mover> <mml:mover> <mml:mi>D</mml:mi> <mml:mo> ̄</mml:mo> </mml:mover> </mml:math> operators. In this work, we investigate this scenario with two non-vanishing RPV couplings at the low-energy scale. With one RPV coupling governing the neutralino production rate and another determining its lifetime, this scenario can lead to observable signals with displaced-vertex signatures in the tracking volume of B -factories. To maximize the sensitivity to such signals, we develop a new partial-reconstruction technique that yields high efficiency and utilizes most of the decays of relatively heavy, long-lived particles, achieving much better sensitivity than standard full reconstruction. We consider potential background sources and devise selection criteria to suppress their event yields to very low levels. Using a parameterized model of the detector, we estimate in detail the displaced-vertex reconstruction efficiency as a function of neutralino lifetime and mass. For squark masses beyond the LHC limits, we calculate the signal sensitivity of Belle II, showing that the experiment can probe the RPV couplings well beyond the present bounds, obtained from searches for dinucleon decays, baryon-antibaryon oscillations, and B + → p + missing.
Islamische Militärseelsorge in Deutschland zwischen Kriegs- und Friedensethik
2025-10-09

Abstract This article provides a fundamental reflection on Islamic military chaplaincy (IMS) in Germany. It explains who can provide this service, how it is structured, and the value it adds, while acknowledging that there are no easy answers. The argument centers on four key questions: 1) The juridical-legal basis of Islamic military chaplaincy; 2) The theological foundation of the new research and working field of IMS; 3) Peace ethics in Islam and its contribution to the German military; and 4) The challenges and future prospects of IMS. Through this multifaceted approach, the article highlights the potential of the emerging field of IMS in Germany.
Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators
2025-10-10

Individual variability in cortisol stress responses is shaped by multiple physiological factors. Yet the interaction with metabolic and hormonal states remains poorly understood. Therefore, we conducted a systematic review and meta-analysis to examine how metabolic factors (particularly glucose) and sex hormone levels (progesterone and estradiol) influence cortisol reactivity to acute stress. We identified 21 studies (<i>N</i> = 1216 participants) and conducted random-effects meta-analyses for metabolic and hormonal states. Across studies, glucose administration was associated with a significant increase in cortisol responses to acute stress compared to fasting or non-glucose control conditions (<i>d</i> = 0.30, 95 % CI = [0.05, 0.60], BF<sub>10</sub> = 2.42, NNT = 10.63). In contrast, the effects of sex hormones on cortisol responses were smaller and more variable, with both progesterone and estradiol showing weak and inconsistent associations. Our results highlight a robust modulatory role of metabolic state, specifically glucose availability, on HPA axis reactivity, while evidence for sex hormone effects remains inconclusive. Future research should focus on better harmonization of designs concerning sex hormones and systematically examine interactions between metabolic and hormonal states to better explain sex differences in the prevalences of metabolic and stress-related disorders.
Bridging Complexity and Accessibility in Metabolomics with MetaboApps
2025-10-10

Untargeted metabolomics is a powerful approach for exploring the chemical diversity and dynamics of biological systems. However, the types of questions that can be addressed depend not only on experimental design but also on the data processing and analysis workflows employed, many of which require advanced computational expertise. GNPS1, now transitioning to its second major implementation (GNPS2), has evolved into an expandable platform that supports the integration of modular web applications designed to simplify and enhance downstream analysis. These apps, named MetaboApps, facilitate the post-processing of outputs of several GNPS workflows and help make repository-scale metabolomics knowledge and other areas of metabolomics more accessible to a broader community.
Analysis of a Modified Version of the Inventory of Non‐Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study
2025-10-10

Abstract Background Friedreich's ataxia is a rare, neurodegenerative, multisystem disorder. While ataxia is a hallmark, non‐ataxia signs, including muscle weakness, spasticity, and dysphagia are equally disabling. The Inventory of Non‐Ataxia Signs (INAS) is a symptom list transformable to a 16‐item count. Objective To evaluate the responsiveness of a modified INAS in this population. Methods Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). The modified INAS count (presence/absence, 0–16 scale) and modified INAS sum (severity‐weighted, 0–84 scale) were evaluated using linear mixed‐models and standardized response means ( SRMs ). Items rare (&lt;5%) and uncharacteristic in Friedreich's ataxia were excluded (chorea, myoclonus, fasciculations, resting tremor, rigidity) Results A total of 1129 participants (mean age, 32.3 years) were assessed for up to 12 years. The mean modified INAS count was 4.6 (±2.2) and modified INAS sum 15.1 (± 9.9). Both correlated strongly with existing outcome measures. Longitudinally, the modified INAS count increased by 0.13 points/year (95% CI 0.12, 0.14; P &lt; 0.001) and modified INAS sum by 0.68 points/year (95% CI 0.64, 0.72; P &lt; 0.001). The modified INAS sum demonstrated greater responsiveness, with SRMs of 0.26, 0.38, 0.53, and 0.80 at 1, 2, 3, and 5 years, respectively, compared with 0.16, 0.27, 0.31, and 0.46 for the modified INAS count. In non‐ambulatory patients and children, responsiveness of the modified INAS sum was higher (SRM 0.82 and 1.7 at 5 years, respectively). Conclusions The modified INAS sum showed good responsiveness over 5 years but not over 1–3 years. It may supplement existing outcome measures, contributing to holistic assessment of this multisystem disease, especially in non‐ambulatory patients, in whom ataxia‐focused measures may show ceiling effects, and children, who typically progress faster. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Prevalence and epidemiological factors associated with urogenital schistosomiasis amongst school children in three health districts of Cameroon; Lagdo (North), Loum and Njombe-Penja (Littoral): a cross-sectional study
2025-10-10

Urinary eggs of Schistosoma haematobium were present in 28.3% of samples at Lagdo HD, 12.0% at Loum HD, and nil at Njombe-Penja HD. HDs and sex were epidemiological factors associated with UgS infection. This necessitates disease education, improvement of water, sanitation, and hygiene (WaSH) infrastructures, and snail vector control in at-risk localities, to improve schistosomiasis control/elimination efforts.
Multi- and Transgenerational Effects of Silver Ions (Ag+) in the ng/L Range on Life Cycle Parameters and Population Growth of the Midge Chironomus riparius (Diptera, Chironomidae)
2025-10-10

Silver (Ag) is widely released into aquatic environments through industrial and municipal discharges, with concentrations often reaching toxic levels for aquatic organisms. Its further extensive use in antimicrobials, especially during the COVID-19 pandemic, has increased environmental inputs. As Ag+ is the most toxic form of Ag, understanding its ecological risks remains critical for environmental regulation and ecosystem protection. Thus, we investigated multigenerational and transgenerational toxicity of Ag+ as AgNO3 on the ecologically important species midge Chironomus riparius using two complementary long-term life-cycle experiments. Experiment 1 simulated exposures with pulsed high environmentally relevant concentrations and recovery phases (nominal 3 μg/L), while Experiment 2 assessed continuous low environmentally relevant concentrations (nominal 0.01, 0.1, 1 and 3 μg/L) across four exposed generations of C. riparius followed by three recovery generations. Endpoints included survival, development, reproduction, growth as well as the population growth rate (PGR). Continuous Ag+ exposure produced cumulative increases in mortality and declines in emergence, reduced fertility and eggs per rope, delayed development (especially in females), and progressive reductions in PGR. Notably, adverse effects emerged or intensified over generations and were detectable at very low concentrations: some reproductive and survival endpoints showed significant impairment at the European Union’s environmental quality standard (EU-EQS) level (0.01 μg/L) by the fourth generation, while transgenerational effects persisted at ≥0.1 μg/L. Partial recovery occurred after removal of contamination at the lowest concentrations but not after higher exposures. The present study not only indicates that chronic, low-level Ag+ contamination can produce persistent, population-level adverse impacts on C. riparius, but also underscores the necessity for long-term ecological assessments to establish more protective standards and maintain ecosystem stability.
One-day repeat pass interferometry highlights the role of temporal baseline on digital elevation models retrieved from Sentinel-1
2025-10-10

Abstract. Digital Elevation Models (DEMs) derived from Synthetic Aperture Radar (SAR) interferometry are a key data source for numerous geospatial applications, from hydrological modelling to environmental monitoring. The launch of Sentinel-1C in late 2025 introduces a new sensor into the Sentinel-1 constellation. This study evaluates the vertical accuracy of DEMs generated from interferometric image pairs acquired during the satellite’s calibration phase. The analysis uses a set of image pairs with temporal baselines of 1, 6, and 12 days, over a test site in Angola, validated against ICESat-2 elevation measurements. The workflow includes interferometric processing, coherence assessment, and statistical error evaluation. Results indicate high accuracy for the 1-day pair (RMSE ≈ 14.7 m) and moderate degradation for the 6-day pair (RMSE ≈ 16.4 m), but a pronounced loss of accuracy for the 12-day pair (RMSE ≈ 49.4 m), primarily linked to coherence loss in vegetated areas. Coherence and elevation error distributions reveal clear land cover and slope dependencies, with lower performance in forested and steep terrain. These findings should be regarded as indicative due to the limited number of suitable image pairs for the calibration phase. However, this early assessment provides an important reference point for future Sentinel-1A/C DEM generation studies, informing both methodological refinement and application planning in SAR-based topographic mapping.
Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
2025-10-10

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) are mitochondrial disorders most commonly caused by a m.3243A>G variant in mitochondrial tRNA<sup>Leu</sup>. To investigate the pathophysiology of MELAS, we generated brain organoids from multiple induced pluripotent stem cell (iPSC) lines derived from a patient with MELAS carrying the m.3243A>G variant. These lines share an identical nuclear genetic background but differ in their heteroplasmy levels involving the m.3243A>G variant. We observed significant differences in organoid size, morphology, and neural induction efficiency, which correlated with the degree of heteroplasmy. Dissociated neurons from the organoids were transferred into a 2D-culture system, which is convenient and suitable for high-throughput drug screening. The organoids also exhibited significant differences in the formation of neural networks, depending on heteroplasmy levels. Our results suggest that patient-derived iPSC-based organoid models represent a useful platform for studying MELAS mechanisms and for drug screening. This video presents comprehensive and user-friendly methods, including protocols for generating organoids and evaluating phenotypes.
Which Imputation Fits Which Feature Selection Method? A Survey-Based Simulation Study
2025-10-11

Tree-based learning methods, such as Random Forest and XGBoost, remain the gold standard for prediction in tabular data. Feature importance measures are frequently employed in feature selection and to evaluate the influence of features on the outcome variables within the model. This approach extends to survey data, which are prevalent in social sciences and official statistics, presenting a significant challenge related to missing values. A typical strategy is to impute missing data before applying the learning method. However, with the sheer number of possible imputation techniques, determining the optimal method to best reflect feature importance and feature selection in subsequent analyses is a complex question. In this paper, we investigate this issue using a survey-based simulation study for eight state-of-the-art imputation methods and three tree-based learners. The imputation methods encompass listwise deletion, three MICE options, four missRanger options, and the recently proposed mixGBoost imputation approach. As learners, we evaluate the performance of the two most widely used tree-based methods–Random Forest and XGBoost–alongside an interpretable, regularized linear model (Elastic Net).
A pivotal, dermal, in-vivo bioequivalence study performed by confocal Raman spectroscopy (CRS)
2025-10-11

The EMA guideline on quality and equivalence of locally applied, locally acting cutaneous products, endorses the use of the stratum corneum (SC) sampling technique (Tape Stripping, TS) in lieu of an expensive and resource-intensive clinical endpoint study. However, alternative methods, like CRS are not yet approved. As we have already shown the correlation of TS and CRS results, we consider non-invasive CRS with its microscale resolution for fully quantifiable API data and its ease of use, as the superior method for future dermal bioequivalence studies for products with Raman-active drug substances. To provide pivotal data and demonstrate the suitability CRS for dermal bioequivalence assessment, we conducted an in-vivo study using four formulations containing salicylic acid(SA). The study design included a reference, a test, and a control formulation to validate discriminatory power. CRS measurements were performed in 12healthy volunteers at two defined time points - 1 h (uptake, that is in diffusional steady-state) and 4 h after product removal (clearance) - using a 785 nm laser to acquire SC penetration profiles down to a depth of 15 μm. We could demonstrate that the penetration data meet all EMA bioequivalence requirements. Thus, the supposedly bioequivalent products were confirmed to be bioequivalent, as their 90 % confidence intervals (CIs) fell entirely within the acceptance range of 80.00---125.00 %, in accordance with the average bioequivalence (ABE) approach. As this was, to our knowledge, the first dermal, in-vivo bioequivalence study conducted with the advantageous CRS method, fully following the recommendations of the EMA guideline. The pivotal data obtained thus shows the suitability of the CRS method. This should help with its establishment as a means to obtain bioequivalence data, also with reference to recognition in a subsequent guideline update.