julilili42/papers huggingface dataset:
Exceptional tumor-free survival of a patient with metastatic intrahepatic cholangiocarcinoma after surgery and personalized peptide vaccination: revisiting a striking case
2025-10-01

Cholangiocarcinomas are rare but aggressive liver tumors of high lethality with scarce treatment options. Here we report on the follow-up of a patient diagnosed with an intrahepatic cholangiocarcinoma who experienced repeated tumor recurrences including distant metastasis, therefore facing a dismal prognosis. At present, this patient is tumor-free for more than 8 years following repeated surgery and application of two successive personalized vaccines. In-depth functional immune cell analyses revealed a dominant CD4 + T-cell response against the vaccine antigens with infiltration of the tumor site and immune responses prevailing for years following the last vaccine administration. Additionally, spontaneous tumor neoantigen-specific CD4 + and CD8 + T-cell responses have been detected, which might have contributed to the outstanding outcome witnessed in this patient. This case report highlights vaccination strategies targeting non-mutated antigens as well as the increasingly recognized central role of antitumor CD4 + T cells.
Pruritus in primary biliary cholangitis: insights from the German PBC registry across secondary and tertiary care
2025-10-01

Pruritus in patients with PBC is common and under-treated in the real-world scenario. Assessment and management vary by healthcare level, highlighting the need for standardized care and greater awareness of treatment options across all settings.
Cross‐country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia
2025-10-01

Abstract INTRODUCTION We investigated international differences in facial emotion recognition (FER) across stages of frontotemporal dementia (FTD). Previous studies may have missed early decline by combining data and masking variations in FER across countries. METHODS An FER test was administered to 159 individuals with behavioral variant FTD, 521 presymptomatic pathogenic variant carriers, and 583 controls from 16 countries of residence. Linear mixed models assessed age, sex, education, and country effects on FER. Voxel‐based morphometry examined neural correlates across countries. REULTS Country accounted for 18%–18.3% of FER variance in presymptomatic carriers and controls and 9.9% in individuals with behavioral variant of FTD (bvFTD). Cross‐country differences interacted with the effects of sex, age, and education. Neural correlates involving the frontal lobe and basal ganglia were identified in individuals with bvFTD, but no cross‐country differences were found. DISCUSSION These results underscore the need for culturally sensitive FER tools in research and clinical practice, especially as global multinational clinical trials emerge. Highlights Performance on a test for facial emotion recognition (FER) varies between countries. The percentage of variance is lower in the behavioral variant of frontotemporal dementia (bvFTD) compared to presymptomatic pathogenic variant carriers and healthy controls. Cross‐country differences interacted with the effects of sex, age, and education. There were no differences in brain correlates of FER across countries.
Redefining dopaminergic synapses beyond the classical paradigm
2025-10-01

Synapses are traditionally defined by the presence of presynaptic vesicle pools and postsynaptic densities. Dopaminergic neurons, however, frequently form bouton-like structures that lack these conventional postsynaptic specializations. Recently, high-resolution imaging techniques such as electron microscopy and correlative light and electron microscopy, along with nanosensors and in vitro models, have revealed the molecular identities and spatial organization of distinct vesicle pools in dopaminergic terminals. In this review, we discuss how recent findings have reshaped current understanding of dopamine vesicles, revealing a structural continuum that includes non-classical architectures. We highlight emerging concepts such as dopamine hub synapses and vesicle heterogeneity in dopaminergic terminals. Finally, we examine how dysfunction in Parkinson's disease-associated proteins affects synaptic integrity and predisposes dopaminergic neurons to selective vulnerability.
Evaluating the Evolvability of Paranthropus Cranial Morphology in Relation to Feeding Biomechanics
2025-10-01

ABSTRACT Objective Although disagreement persists as to the precise nature of the diet of Paranthropus , there is a consensus that the food resources consumed by Paranthropus were in some way mechanically challenging to process (i.e., by being “hard” and/or “tough”). While the highly derived feeding apparatus of Paranthropus likely conferred biomechanical performance advantages while consuming certain types of foods, it may also have limited the ability of these early hominins to respond to selection and evolve rapidly toward new adaptive peaks (i.e., reduced their evolvability). Materials and Methods We employed viability selection modeling to test this hypothesis. Viability selection simulations were performed using Paranthropus boisei (OH 5), Australopithecus afarensis (A.L. 444‐2), and Homo habilis (KNM‐ER 1813) specimens. We simulated the generation‐to‐generation evolution of biomechanically informative linear dimensions in a population where an individual's probability of survival (i.e., viability) was determined by its distance to a predetermined adaptive peak. The number of generations required for an evolving population to reach a new adaptive peak was used as a measure of evolvability. Results The results showed that the mean number of generations from P. boisei to H. habilis was larger than in the reverse direction when modeled using either chimpanzee or human estimates of population variance/covariance. It took longer for P. boisei to evolve toward Au. afarensis than in the reverse direction, but only with the chimpanzee estimates of population variance/covariance. Discussion The results suggest that P. boisei faced limitations in cranial evolvability, particularly if selection favored a cranial morphology similar to H. habilis .
Cortisol as a Mediator of Prenatal Distress and Difficult Infant Temperament: A Systematic Review and Meta‐Analysis Protocol
2025-10-01

ABSTRACT Background and Aims Exposure to prenatal distress is associated with a risk of developing difficult temperament in infants, an indicator for a higher likelihood of later adverse developmental outcomes, including behavioral and mental health problems. The underlying biological mechanisms of this association are still unclear, but many support the idea of fetal programming, which postulates the influence of environmental factors on the fetus during pregnancy. Evidence points to the role of cortisol as a mediator of stress, but the results are inconsistent. In this systematic review and meta‐analysis, the association between prenatal distress and difficult infant temperament will be assessed, focusing on cortisol exposure as a possible mediator and including subgroup analyses. Methods Literature research will be performed in PubMed, Web of Science, MEDLINE, PSYNDEX, APA PsycArticles, APA PsycInfo, and CINAHL. Inclusion criteria are the availability of (self‐) assessment of maternal prenatal distress, maternal prenatal cortisol levels, and (parental) assessment of difficult infant temperament up to the age of 2 years. Screening and selection of peer‐reviewed English (or German) articles and assessment of article quality will be done by two independent reviewers, with a third one included in the case of disagreement. Effect sizes will be extracted and subgroup analyses will be performed not only for covariables but also for the methods of assessing prenatal distress, cortisol, and temperament. This protocol follows the PRISMA‐P checklist. Conclusion This systematic review and meta‐analysis will contribute to the ongoing discussion of whether and how cortisol mediates the association between prenatal maternal distress and difficult infant temperament. Identifying sensitive subgroups is an integral part of this study, as results might guide further research to vulnerable population groups.
Comparison of amyloid chronicity and EYO in autosomal dominant Alzheimer's disease
2025-10-01

Abstract INTRODUCTION Preclinical Alzheimer's disease (AD) can be described relative to biomarker positivity onset time. METHODS We estimated time from amyloid positivity (A+) using sampled iterative local approximation (SILA) in a longitudinal autosomal dominant AD (ADAD) sample ( N = 379) with amyloid positron emission tomography. We compared (1) predicted age at A+ to imputed age, (2) estimated age at A+ to estimated age at symptom onset, and (3) variance in cognitive performance explained. RESULTS Mean error between imputed and SILA‐estimated age at A+ ( N = 26) was 1.15 years. Age at A+ explained 39% of estimated years to symptom onset (EYO) variance. Time from A+ explained 19% of cognitive composite variance and 14% of Clinical Dementia Rating Sum of Boxes CDR‐SB variance; EYO explained 43% and 57%, respectively. DISCUSSION SILA estimates A+ age in ADAD with reasonably good accuracy. SILA‐estimated time from A+ describes the start of pathology, but the time from A+ onset to symptoms is variable in ADAD and better described by EYO. Highlights Amyloid chronicity predicts a 14‐year preclinical AD phase in ADAD. SILA accurately estimates age at A+ (MAE &lt; 2 years). EYO outperforms chronicity in predicting symptom onset. APP mutation carriers show atypical amyloid accumulation. Chronicity models help reveal AD heterogeneity in preclinical stages.
Evidence-based diabetes prevention programmes in the public health sector
2025-10-01

Abstract Relevance Type 2 diabetes mellitus (T2DM) is a prevalent non-communicable disease caused by lifestyle factors such as inadequate diet and physical inactivity. Public health systems must prioritise early prevention through evidence-based interventions to reduce the growing burden of T2DM. In BW, Germany, the KNPM is focussing to enhance diabetes prevention in the public health sector. Activities in the WG The working group pursues two main objectives: (a) to examine existing diabetes prevention interventions at the community level in BW and internationally to identify best practices, and (b) to analyse enabling factors and barriers in the development and implementation of prevention programmes. Based on these findings, evidence-based recommendations for action will be developed in collaboration with public health professionals, local authorities, and KNPM researchers. Impact For prevention efforts to be effective and sustainable, programmes must be both scientifically sound and practically feasible. One challenge is the gap between research, practice and policy, which can hinder the development and implementation of these programmes. A participatory approach helps to bridge this gap by encouraging collaboration between different stakeholders. In our presentation, we will demonstrate how participatory approaches can be strategically structured and how interdisciplinary collaborations can contribute to the translation of research findings into practical prevention strategies. Key messages Community-based diabetes prevention requires a holistic approach that integrates scientific evidence with local feasibility. Strengthening collaboration between researchers, practitioners, and policymakers is crucial to improving implementation and ensuring long-term public health benefits.
Why sediments matter for mountain biogeomorphology
2025-10-01

Abstract In mountain regions, present and future climate warming affects the spatio‐temporal distribution, magnitude and frequency of geomorphic processes and vegetation response. Mountain biogeomorphology investigates the feedback between vegetation and geomorphic components and dynamics in alpine landscapes. Though sediment properties are known to provide important controls on vegetation colonization, species composition and provision of mountain microhabitats, they often receive considerably less attention than landform types and geomorphic processes. In this study, we aim to (i) elucidate biogeomorphic relationships between sediments and vegetation across landforms, (ii) identify key sediment and linked soil properties in mountain biogeomorphic systems and (iii) develop a workflow for routinely including sedimentological observations into mountain biogeomorphic research. We do so by investigating sediment granulometry and chemistry at four localities in the Swiss Alps, each dominated by different geomorphic processes (debris flow, soil erosion, solifluction, rock glacier creep), and integrating these data with vegetation information. Using multivariate statistics, we show that sediment properties, geomorphic processes and species composition are closely related across landforms, with different vegetation classes on stable terrain, coarse carbonate‐rich sediments, active solifluction and active soil erosion. Our data suggest that these relationships can be explained by previously described geomorphic activity‐related thresholds for biogeomorphic feedbacks, as well as possible thresholds related to sediment texture, with coarse grain sizes limiting plant colonization and biogeomorphic feedbacks. Sediment properties matter most for vegetation where geomorphic disturbances are low or absent. Based on our results, we propose that the median grain size of both coarse (&gt;2 mm) and fine (≤2 mm) sediments, bulk P, K, Fe, Ca and N concentrations and total organic carbon (TOC) are key sediment and linked soil variables for mountain biogeomorphic research. We propose a workflow to effectively incorporate sediment data into mountain biogeomorphology and suggest directions for further research into sediment‐vegetation interactions.
The influence of lip reconstruction on mother-infant bonding during the perioperative phase
2025-10-01

This study suggests that cleft lip reconstruction plays a crucial role in strengthening the mother-child bond. Cleft malformations can adversely affect maternal well-being by complicating the interpretation of a child's needs. A secure maternal attachment style appears to offer protective benefits during the cleft repair hospitalization period. Preoperative consultations are essential for addressing concerns and providing reassurance to caregivers.
Epidemiological situation of hepatitis E in Africa
2025-10-01

Hepatitis E virus (HEV) belongs to the Hepeviridae family, Orthohepevirinae subfamily, Paslahepevirus genus which includes eight genotypes. HEV genotype 1 (HEV-1) and genotype 2 (HEV-2) are specific to humans, while genotype 3 (HEV-3) and genotype 4 (HEV-4) circulate mainly in pigs, wild boars and deer, but have also a zoonotic potential. HEV genotype 5 (HEV-5) and 6 (HEV-6) viruses circulate in wild boars in Japan and genotype 7 (HEV-7) and 8 (HEV-8) viruses circulate in camelids. The worldwide distribution of HEV is influenced by ecological and socioeconomic factors. In developing countries in Africa, transmission of the virus through fecally contaminated water accounts for a high proportion of epidemics. Direct human-to-human transmission is less frequent, although cases of infection through blood transfusion have been reported in several countries. Thanks to the "One Health" approach, zoonotic transmissions of HEV from pig to human have been more recently observed. These zoonotic infections are mainly due to the handling or consumption of pork meat or contact with pig manure, contaminating the environment. They alert on professions or populations at-risk, such as livestock farmers or butchers. In addition, HEV infection is particularly severe in pregnant women, leading to fetal and maternal death due to acute liver failure. Finally, the development and application of serological or molecular detection tests in Africa indicates that HEV can be incriminated in symptoms without etiology or falsely attributed to other hepatic viruses or to the yellow fever virus. This review updates studies on the epidemiology of HEV in Africa, a crucial step to better understand the virus and develop surveillance strategies to prevent and better control epidemics.
Tracking real-world persistence and adherence to anti-VEGF intravitreal therapy with prefilled syringes: a German prescription sales analysis
2025-10-01

Objective Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration and other retinal vascular diseases. Despite proven efficacy in clinical trials, real-world data suggest suboptimal persistence and adherence. This study aimed to assess therapy continuity in routine practice using pharmacy-based dispensing data in Germany, focusing on treatment with prefilled syringes (PFS). Methods and analysis This retrospective cohort study used anonymised nationwide pharmacy sales data from Germany to evaluate patients who initiated anti-VEGF therapy with PFS between 2020 and 2023. Patient trajectories were followed from treatment initiation for up to 12 months. 46 546 therapy beginners with 297 454 anti-VEGF PFS purchases were included. Discontinuation of treatment was defined by not purchasing a relevant medication for &gt;6 months. Results Mean time on therapy for all patients was 8.1±8.2 months (median=5.5) with 6.9±6.1 purchases (median=5). 20.5% of patients initiating anti-VEGF treatment stopped therapy before completing the loading phase (first three injections), and more than half of all patients discontinued treatment after 6 months. 49.4% of the patients who completed the loading phase (n all=34 895) adhered to the recommended monthly regimen. Non-adherence significantly decreased the number of injections later on (average of 7.5 vs 8.7 injections). Further, patients who stayed longer on therapy bought more PFSs within the first 6 and 12 months. Conclusions Real-world adherence and persistence to intravitreal anti-VEGF therapy in Germany are suboptimal, even with the use of PFS formulation. The high rate of early treatment discontinuation, especially during the loading phase, underscores the need for improved patient support, education and flexible treatment approaches to sustain long-term outcomes. A ‘breaking point’ or sensitive phase already seems to exist right at the beginning of therapy.
Microbiota-derived aromatic amino acid decarboxylases: linking microbial fitness and host neurochemical communication
2025-10-02

ABSTRACT The human microbiota produces a diverse array of bioactive molecules, including classic neurotransmitters (dopamine and serotonin) and trace amines (tryptamine, tyramine, and phenylethylamine). Although long considered products of host metabolism, these aromatic monoamines are now also known to originate in part from the microbiota, where they are synthesized by bacterial aromatic L-amino acid decarboxylases (AADCs). This review explores the distribution, biochemical diversity, and host interactions of microbiota-encoded AADCs, highlighting their roles in gut and skin ecosystems. Bacterial AADCs vary in gene organization, substrate range, and expression patterns across taxa like Ruminococcus gnavus , Clostridium sporogenes , Enterococcus spp., and Staphylococcus spp. These enzymes contribute to microbial fitness through acid stress resistance, energy generation via proton motive force, epithelial adherence and internalization, and niche dominance. Critically, their products modulate host physiology via trace amine-associated receptors (TAARs) and other signaling pathways, influencing neurotransmission, immune response, barrier integrity, and metabolism. Microbiota-derived monoamines can enter systemic circulation and cross the blood–brain barrier, implicating them in disorders ranging from irritable bowel syndrome to neurodegeneration. Emerging data also reveal their impact on wound healing and drug efficacy, notably in Parkinson’s disease. By positioning microbial AADCs as key players in host-microbe chemical communication, this review underscores their relevance for health and disease and highlights them as potential therapeutic targets.
mzPeak: Designing a Scalable, Interoperable, and Future-Ready Mass Spectrometry Data Format
2025-10-02

Advances in mass spectrometry (MS) instrumentation, including higher resolution, faster scan speeds, and improved sensitivity, have dramatically increased the data volume and complexity. The adoption of imaging and ion mobility further amplifies these challenges in proteomics, metabolomics, and lipidomics. Current open formats such as mzML and imzML struggle to keep pace due to large file sizes, slow data access, and limited metadata support. Vendor-specific formats offer faster access but lack interoperability and long-term archival guarantees. We here lay the groundwork for mzPeak, a next-generation community data format designed to address these challenges and support high-throughput, multidimensional MS workflows. By adopting a hybrid model that combines efficient binary storage for numerical data and both human- and machine-readable metadata storage, mzPeak will reduce file sizes, accelerate data access, and offer a scalable, adaptable solution for evolving MS technologies. For researchers, mzPeak will support complex workflows and regulatory compliance through faster access, improved metadata, and interoperability. For vendors, it offers a streamlined, open alternative to proprietary formats. mzPeak aims to become a cornerstone of MS data management, enabling sustainable, high-performance solutions for future data types and fostering collaboration across the mass spectrometry community.
Combination of App-Based Ultrasound Simulation and Conventional Learning Methods in Medical Education for Fetal Echocardiography
2025-10-02

Purpose: This study examines whether combining conventional textbook materials with the app-based ultrasound simulator Scanbooster enhances learning outcomes in fetal echocardiography, compared to using either method alone. It also evaluates the impact of the learning sequence. Materials and Methods: 210 medical students were randomized into two groups: • PDF→App Group (n=103): Textbook study followed by the Scanbooster ultrasound simulator app • App→PDF Group (n=107): Scanbooster ultrasound simulator app followed by textbook study Knowledge was assessed before and after by identifying marked structures in ultrasound videos. Results: There were no significant differences between the groups regarding age (p=0.564) and prior ultrasound experience (p=0.746). Both groups showed a significant improvement in identifying sonographic structures after the learning phase (p&lt;0.001), with a mean learning effect of 104.96% and 102.16%, respectively, for fetal echocardiography- specific knowledge. The order of learning materials had no significant effect on learning success (p&gt;0.05). In comparison with our previous study, we found that the combination of app-based simulation and textbooks led to the best learning outcomes in fetal echocardiography. This approach resulted in significantly higher performance compared to pure PDF learning (p&lt;0.001) and was slightly, yet still significantly better than pure simulation (p=0.031). Conclusion: The combination of conventional textbook material and app-based ultrasound simulation is the most effective approach for teaching fetal echocardiography. The learning sequence does not significantly impact the outcome.