julilili42/papers huggingface dataset:
Risk Management in “Other Clinical Investigations” According to Art. 82 MDR — Lessons Learnt from the EDITh Project
2025-10-02

With the implementation of the EU Medical Device Regulation (MDR), clinical trials of clinical decision support systems (CDSS) now often fall under Article 82 of the MDR. This mandates systematic risk management even for academic feasibility studies. This article presents a risk management strategy based on the EDiTh project, which evaluated a CDSS for epilepsy treatment recommendations in accordance with the 2023 S2k guideline First epileptic seizure and epilepsy in adulthood. A Preliminary Hazard Analysis and System Failure Mode and Effects Analysis identified key error types such as incorrect diagnoses or dosing recommendations. Due to the potential for catastrophic harm, a dual-visit study design was implemented, including a second, blinded expert consultation via videoconference to independently confirm diagnosis and treatment decisions. This design supports both risk mitigation and assessment of guideline adherence as the primary endpoint. The risk matrix and study setup illustrate how safety and regulatory requirements can be met in academic environments, while offering insights for future MDR-compliant investigations of digital health technologies.
Preferred working time models and equal opportunities in gynecology and obstetrics: a sub-analysis of the trinational FARBEN survey focusing on German participants from Western and Eastern federal states
2025-10-03

Many family policy aspects of the former German Democratic Republic facilitated and continues to facilitate the compatibility of work and family life for mothers in the East. Historical perspectives can be helpful in implementing improvements for women in terms of work-family balance in a female-dominated medical field such as gynecology.
From state commodification to local reproduction of vulnerability: ethnographic insights from a Risk Zone Urban Renewal Project in Turkey
2025-10-03

Abstract This paper explores how vulnerability is not only defined by the state but also actively reshaped through policy implementation and lived experience. Drawing on ethnographic research in Eskişehir, Turkey, I propose an analytical distinction between the ‘commodification of vulnerability’—framing risk in technoscientific and moral terms to justify intervention—and the ‘reproduction of vulnerability’—capturing the emergent precarity produced by such action. Following the 2011 Van earthquakes, Turkey's central government advanced disaster prevention as a national imperative. In 2012, Law No. 6306 was enacted to facilitate large‐scale urban transformations in the name of risk prevention. Eskişehir's Metropolitan Municipality quickly adopted the ‘Renewal Law’, initiating the Risk Zone Urban Renewal Project with the stated aim of protecting lives and property. While official definitions of vulnerability centred on the structural durability of the built environment, residents of the designated area have encountered new and unanticipated vulnerabilities, ranging from housing insecurity and prolonged legal limbo to socioeconomic instability and emotional distress.
Quantifying and Utilizing Electroosmotic Flow for Mechanical Measurements with the Scanning Ion Conductance Microscope
2025-10-03

The scanning ion conductance microscope (SICM) is an emerging imaging technique for the investigation of delicate samples on the nanometer scale in liquid environments using ion current through a glass nanopipette. In recent years, the SICM has been increasingly applied to mechanical measurements, typically using a microfluidic flow in the nanopipette induced by hydrostatic pressure. Here, we introduce the use of electroosmotic flow (EOF) in mechanical SICM measurements. We show that the EOF in small SICM nanopipettes is comparable to the flow induced by commonly applied hydrostatic pressures. We quantify the electroosmotic mobility, which is a central parameter of EOF but strongly depends on experimental conditions, by measuring the streaming current independent of nanopipette geometry. Using decane microdroplets, we show that both EOF and hydrostatic pressure can be used to mechanically probe elastic samples on the nanometer scale. We then develop a numerical model to quantify the stiffness and the Young's modulus of elastic samples using EOF. Finally, we use EOF to map the Young's modulus of living cells, which gives similar results to the hydrostatic pressure method. We thereby demonstrate that EOF can be used to quantitatively probe sample stiffness with the SICM.
When Sex Hormones Shape Motivation: A Translational Perspective on Sex/Gender Differences in Reward Processing
2025-10-03

<title>Abstract</title> Females undergo hormonal fluctuations across every menstrual cycle, often experiencing mood changes or decreased motivation, indicating increased risk for affective disorders associated with altered motivation. To assess whether steroid hormone fluctuations and menstrual cycle phase modulate sex/gender-specific motivation, we examined 48 naturally cycling females and 46 males, aged 18-34, who performed a physical effort task while fasted (part 1, T0) and across four weeks (part 2, T1-T4). We obtained objective and subjective measures of motivation in response to food and monetary rewards, alongside plasma levels of estradiol, progesterone, and testosterone. Results revealed sex/gender specific reward sensitivity: Females showed more sustained effort, especially for small rewards, while males displayed opportunistic approaches seeking monetary rewards. Motivation decreased during periovulatory and luteal phases and high estradiol levels correlated with decreased motivation in females and males. Our findings emphasise the importance of integrating biological, psychosocial, and physiological factors in understanding and treating motivational deficits.
FLT3-ITD Induces CMTM6 and Enhances Immune Escape in Acute Myeloid Leukemia
2025-10-03

Abstract FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutations are frequent in acute myeloid leukemia (AML) and are associated with a high risk of relapse. CKLF-like MARVEL transmembrane domain containing member 6 (CMTM6) stabilizes PD-L1 surface expression and modulates tumor immunity in solid cancer. In this study, we found a role for FLT3-induced CMTM6 in hematological malignancies. FLT3 drove CMTM6 and PD-L1 expression in AML cells, while FLT3 inhibition reduced expression of CMTM6 and PD-L1. In three distinct allogeneic hematopoietic cell transplantation mouse models, transplantation of Cmtm6 deficient FLT3-ITD+ leukemia cells resulted in prolonged survival, reduced leukemia burden, enhanced T cell effector function, and decreased expression of T cell exhaustion markers compared to Cmtm6 proficient FLT3-ITD+ leukemia cells. Furthermore, combination therapy with anti-PD-L1 and tandutinib significantly improved survival, suppressed leukemia cell expansion, and augmented the anti-leukemia T cell response in mice bearing FLT3-ITD+ leukemia. Mechanistically, protein-protein interaction of FLT3 and CMTM6 within their transmembrane domains, which was not phosphorylation dependent, enhanced CMTM6 stability in leukemia cells, while FLT3-ITD did not increase CMTM6 and PD-L1 expression at the RNA level. Furthermore, CMTM6 upregulation and protein interaction with FLT3 was validated in primary leukemia cells from two independent cohorts of patients with FLT3-ITD+ AML. Collectively, these findings uncover FLT3-mediated stabilization of CMTM6 in AML cells, which results in enhanced PD-L1 cell surface expression and leukemia immune escape.
Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma
2025-10-03

<title>Abstract</title> <italic>BRCA</italic>-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with <italic>BRCA</italic>-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with <italic>BRCA</italic>-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one <italic>BRCA</italic>-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with <italic>BRCA1</italic>-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with <italic>BRCA2</italic>-deficient HGSC and loss of <italic>NF1</italic> survived twice as long as those without <italic>NF1</italic> loss, whereas <italic>PIK3CA</italic> or <italic>RAD21</italic> amplification defined <italic>BRCA2</italic>-deficient HGSC with exceptionally short survival. <italic>BRCA1</italic>-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline <italic>BRCA</italic> variants (g<italic>BRCA</italic>pv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in g<italic>BRCA</italic>pv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in <italic>BRCA</italic>-deficient HGSC.
Rooting for function: community‐level fine‐root traits relate to many ecosystem functions
2025-10-03

Summary Humans are driving biodiversity change, which also alters community functional traits. However, how changes in the functional traits of the community alter ecosystem functions—especially belowground—remains an important gap in our understanding of the consequences of biodiversity change. We test hypotheses for how the root traits of the root economics space (composed of the collaboration and conservation gradients) are associated with proxies for ecosystem functioning across grassland and forest ecosystems in both observational and experimental datasets from 810 plant communities. First, we assessed whether community‐weighted means of the root economics space traits adhered to the same trade‐offs as species‐level root traits. Then, we examined the relationships between community‐weighted mean root traits and aboveground biomass production, root standing biomass, soil fauna biomass, soil microbial biomass, decomposition of standard and plot‐specific material, ammonification, nitrification, phosphatase activity, and drought resistance. We found evidence for a community collaboration gradient but not for a community conservation gradient. Yet, links between community root traits and ecosystem functions were more common than we expected, especially for aboveground biomass, microbial biomass, and decomposition. These findings suggest that changes in species composition, which alter root trait means, will in turn affect critical ecosystem functions.
Accelerating probabilistic privacy-preserving medical record linkage: A three-party MPC approach
2025-10-04

Our novel PPRL method, based on secure 3-party computation, offers an efficient and scalable solution for large-scale record linkage while ensuring privacy protection. The approach demonstrates significant performance improvements, making it a promising tool for secure data integration in privacy-sensitive sectors.
Addressing Heterogeneity in Binge Eating Disorder: A Cluster Analysis Approach Based on Age of Onset, Clinical and Psychopathological Features
2025-10-04

ABSTRACT Objective This study investigates clinical heterogeneity in patients with binge eating disorder (BED) and its association with treatment outcomes. Methods A two‐step cluster analysis was conducted on a clinical sample of 196 BED patients, using an agglomerative hierarchical procedure based on both categorical and quantitative measures—psychopathological symptoms, personality traits, emotional dysregulation, body composition, and food addiction. A subsequent comparison between clusters assessed therapy outcomes. Results Two distinct clusters emerged: C1 ( n = 77) and C2 ( n = 119). C2 patients exhibited a more dysfunctional profile, marked by more frequent binge episodes, higher eating psychopathology, greater emotion regulation difficulties, higher impulsivity levels, worse psychopathological state, higher food addiction levels, and personality traits reflecting greater harm avoidance and lower self‐directedness and cooperativeness. While clusters did not differ by age, C2 had earlier age of onset and longer duration of the disorder. In contrast, C1 showed a more functional profile, later age of onset, lower total body fat mass, and better treatment outcomes. Conclusion These findings highlight heterogeneity in BED, particularly regarding age of onset and associated clinical features, which may influence treatment response. The results suggest the need for distinct treatment strategies and more personalised therapeutic approaches tailored to patient subtypes.
Rethinking ambiguity across species
2025-10-05

Ambiguity-the capacity for a signal to support multiple interpretations-has long been regarded as a hallmark of human language, linked to sophisticated syntax and pragmatics. Yet recent evidence shows that ambiguity is also widespread in non-human communication systems, especially among primates, where signals are routinely disambiguated through social and interactional context. We maintain that ambiguity is not a communicative flaw but an evolved strategy that enhances efficiency and flexibility across species. Drawing on cross-species data and probabilistic modelling, we argue that ambiguity offers adaptive benefits: balancing signal cost, informativeness, and interpretive flexibility. We propose that pragmatic ambiguity resolution likely predates language and reflects shared cognitive capacities for social inference. Recognising ambiguity as a comparative phenomenon reframes debates on language evolution and highlights shared adaptive pressures shaping communication systems.
Recipe for Hydrogels With Tunable Relaxation and Diffusion Properties for Use as MRI Test Materials
2025-10-05

ABSTRACT Purpose To develop and evaluate a preparation protocol (recipe) for hydrogels with specific relaxation times and ADC values to be used as tissue‐like test materials for MRI experiments at 3 Tesla. Methods Gd‐DTPA, agarose, and soy lecithin were used as modulators for T1, T2, and ADC. First, systematic measurements were performed to determine the relaxation‐ and diffusion‐modifying properties of the single substances and combinations of them. An algorithm was developed to determine the necessary concentrations of the ingredients to achieve predetermined sets of target values (T1, T2, and ADC). To validate this approach, hydrogels mimicking the relaxation and diffusion properties of different tissues (pancreas, white matter, fibroglandular tissue, liver, prostate) were prepared and evaluated. All measurements (relaxometry, diffusion‐weighted imaging) were performed on a 3 Tesla clinical scanner at 20°C. Results The proposed method allowed the preparation of hydrogels with specific diffusion and relaxation properties by adjusting the concentrations of Gd‐DTPA, agarose, and soy lecithin. Test phantoms containing hydrogels for simulation of various tissue types showed good agreement between targeted and measured properties, with deviations of less than 8% for T1, 7.5% for T2, and 11.5% for ADC. With the present approach, the properties (T1, T2, and ADC) of most known tissue classes could be well approximated; only the gray matter of the brain was slightly outside the selectable range. Temporal stability over 3 months was acceptable. Conclusion This work provides a relatively simple, inexpensive, and reproducible method for the preparation of hydrogels with independently adjustable T1, T2, and ADC values at 3 T.
Enhanced maximum intensity projection (eMIP) for improving the fidelity of optoacoustic images
2025-10-06

Abstract Three-dimensional (3D) image reconstructions are often rendered as two-dimensional images, using maximum intensity projections (MIPs). However, MIP’s rendering fidelity depends on the alignment of the individual slices along the projection direction. Also, the presence of noise and artifacts affects the contrast and the projected image elements. We introduce enhanced MIP (eMIP), a methodology that aligns the boundaries (e.g., skin boundary) of adjacent slices of the 3D volume onto the same coordinate system assumed by MIP (e.g., same depth) and applies robust contrast adjustment to normalize the intensities of the projected slices. We benchmark eMIP on 1725 clinical scans of human skin, using raster-scan optoacoustic mesoscopy (RSOM) that were assessed by 8 experts. Our results show that eMIP facilitates interpretability compared to conventional MIP and increases consistently the perceived image quality. The improved diagnostic ability of eMIP has the potential to replace MIP in RSOM and similar modalities.
Ethics at the Intersection of Intelligent Assistive Technology, Ageing, and the Home Environment: A Scoping Review
2025-10-06

Abstract Intelligent assistive technology (IAT) is being developed to enable safe and autonomous ageing at home and is associated with supporting quality of life. These anticipated benefits must be balanced against potential unintended negative effects. This scoping review aims to identify and summarize the key ethical dimensions and frameworks discussed in the relevant scholarly literature. Furthermore, we examine whether the ethical dimensions identified can be derived from the four principles of bioethics, suggesting that, when properly specified, principlism could serve as a systematic framework for evaluating IAT. Thus, our review has two aims: identifying the ethical dimensions and frameworks currently discussed and investigating whether these frameworks can be structured according to the four principles or if additional principles are necessary. A systematic search across the databases PubMed, Web of Science, EMBASE, Belit, and PhilPapers, plus a manual search identified 535 publications, from which twenty-three studies were included. The results show twenty-one heterogeneous ethical dimensions, with similar matters considered across different categories. The review shows that key expectations and promises of developing and using IAT in this context mostly relate to the possibility of safely ageing at home and reducing healthcare costs. While assigning these ethical dimensions to the four principles of bioethics, it became clear that although all aspects discussed could be subcategorized, some ethical concerns might lose visibility or be inadequately addressed. We, therefore, conclude that the four principles generally provide a sufficient basis for evaluating these technologies.
Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma
2025-10-06

Abstract Glioblastoma (GBM), an aggressive brain tumour associated with poor prognosis and high recurrence rate, has limited clinical treatment options. However, novel immunotherapeutics targeting over-presented epitopes of tumour-associated antigens (TAAs) represent a promising solution. Here we describe the preclinical development of CVGBM, an mRNA-based immunotherapeutic candidate for GBM consisting of a nucleotide-unmodified mRNA encapsulated in lipid nanoparticles (LNP). CVGBM mRNA encodes a fusion protein comprising eight TAA-derived epitopes that have previously induced T-cell responses in patients with GBM as peptide-based immunotherapeutics: five restricted to class I human leukocyte antigen (HLA) allele A*02:01 and three restricted to various class II HLA-DR alleles. Translation and processing of the mRNA-encoded fusion protein and presentation of derived epitopes on HLA molecules were confirmed in human cell lines after lipofection with CVGBM mRNA. Immunopeptidomics confirmed the presentation of four of the six HLA-A*02:01-restricted epitopes; however, HLA class II-bound epitopes were not detected. Administration of CVGBM to mice demonstrated functionality of the immunotherapeutic in vivo by inducing CD8 + and CD4 + T-cell responses. As CVGBM requires an intact immune system for its mode of action, it could not be tested in xenograft models. Instead, anti-tumoural efficacy was demonstrated for a surrogate mRNA-based immunotherapeutic, which has a similar mRNA and protein design as CVGBM but encodes a fusion protein comprising epitopes of the murine B16.F10 melanoma cell line. Administration of the surrogate immunotherapeutic prolonged median survival time of B16.F10 tumour-bearing mice relative to controls. Based on these results, a Phase I clinical trial with CVGBM was started in HLA-A*02:01-positive patients with surgically resected MGMT-unmethylated GBM (NCT05938387).
Evolution of the rostral vasculature in turtles
2025-10-06

Abstract The cephalic vasculature of turtles has been explored extensively for its evolutionary history. However, the rostral portion of the cephalic vasculature has rarely been investigated compared to that of the basicranial region, despite its unique morphology among diapsids and a wide range of variation within crown turtles. Here, a broad range of diapsid taxa were examined to explore the evolution of the rostral vasculature in turtles. We show that the arrangement of the rostral vasculature specific to extant turtles, bifurcation of the maxillary artery, and the caudally shifted foramen praepalatinum transmitting the palatine artery, could at least be traced back to the mesochelydians based on osteological evidence. Although one of the oldest testudinatans Proganochelys quenstedtii had a medially shifted maxillary artery as in crown turtles, its rostral vasculature likely retained the ancestral diapsid condition, consistent with the generally plesiomorphic morphology of the cranium. The crownward evolution of the rostral vascular patterning is likely related to associated rostral morphological changes, such as the keratinous beak, nasolacrimal duct, and medial nasal gland. In addition, variations of the osteological correlates for the maxillary and palatine arteries were found in crown turtles. Trionychians have a unique large opening termed foramen intermaxillaris instead of the paired foramina praepalatina on the floor of the nasal cavity, but they were shown to be homologous based on the shared palato-nasal neurovascular pattern. Chelonioids exhibited the most deviation from the generalized turtle rostral vascular patterning. Those deviations within crown turtles are likely associated with the relevant anatomical changes of the rostrum, such as the secondary palate of cheloniids.