julilili42/papers huggingface dataset:
Most L1CAM Is not Associated with Extracellular Vesicles in Human Biofluids and iPSC–Derived Neurons
2025-04-10

Abstract Transmembrane L1 cell adhesion molecule (L1CAM) is widely used as a marker to enrich for neuron-derived extracellular vesicles (EVs), especially in plasma. However, this approach lacks sufficient robust validation. This study aimed to assess whether human biofluids are indeed enriched for EVs, particularly neuron-derived EVs, by L1CAM immunoaffinity, utilizing multiple sources (plasma, CSF, conditioned media from iPSC-derived neurons [iNCM]) and different methods (mass spectrometry [MS], nanoparticle tracking analysis [NTA]). Following a systematic multi-step validation approach, we confirmed isolation of generic EV populations using size-exclusion chromatography (SEC) and polymer-aided precipitation (PPT)—two most commonly applied EV isolation methods—from all sources. Neurofilament light (NfL) was detected in both CSF and blood-derived EVs, indicating their neuronal origin. However, L1CAM immunoprecipitation did not yield enrichment of L1CAM in EV fractions. Instead, it was predominantly found in its free-floating form. Additionally, MS-based proteomic analysis of CSF-derived EVs also did not show L1CAM enrichment. Our study validates EV isolation from diverse biofluid sources by several isolation approaches and confirms that some EV subpopulations in human biofluids are of neuronal origin. Thorough testing across multiple sources by different orthogonal methods, however, does not support L1CAM as a marker to reliably enrich for a specific subpopulation of EVs, particularly of neuronal origin.
Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis
2025-04-10

Abstract Septic arthritis, primarily caused by Staphylococcus aureus , poses a significant risk of both mortality and morbidity due to its aggressive nature. The nuc1 -encoded thermonuclease NucA of S. aureus degrades extracellular DNA/RNA, allowing the pathogen to escape neutrophil extracellular traps (NETs) and maintain the infection unabated. Here we show that in the mouse model for hematogenous septic arthritis, the Δ nuc1 mutant is much less pathogenic and the severity of clinical septic arthritis is markedly reduced, including decreased weight loss, lower kidney bacterial load, reduced bone erosion, and much less IL-6 production. In vitro, S. aureus genomic DNA induces a robust TNF-α response in macrophage-like RAW 264.7 cells abrogated when the DNA is degraded by NucA. Moreover, the wild type induces high levels of TNF-α, IL-10, and IL-6 in neutrophils and osteoblast-like SAOS-2 cells, respectively. NucA exacerbates septic arthritis by increasing extracellular and intracellular survival of bacteria.
The impact of sleep in high-risk infants
2025-04-10

Abstract Most of an infant’s day is devoted to sleep – and normal sleep is vital to normal brain development. Sleep disruptions may impair overall health, well-being, and neurodevelopment. Disruptors of sleep and circadian health, such as noise, light, respiratory support, and clinical interventions, are highly prevalent in hospital and nursing care facilities. These factors particularly affect infants who already have an increased risk of sleep disorders and their consequences due to an underlying disease. Preterm infants and infants with disorders such as neonatal abstinence syndrome, craniofacial malformations, congenital heart disease, hypoxic-ischemic encephalopathy, Chiari-malformation/myelomeningocele, congenital musculoskeletal disease, and Down syndrome are all at high risk for impaired development of sleep-wake cycling and for sleep-disordered breathing. Since abnormal sleep is a potentially treatable risk factor for impaired neurodevelopment, there is an urgent need for effective monitoring, timely interventions, and treatment strategies to improve sleep physiology and thereby optimize overall neurodevelopment in these high-risk populations. Impact Healthy sleep plays a fundamental role in normal infant brain development. Many factors can disrupt sleep during a hospital stay. This is particularly important for infants who have an increased risk of sleep disorders due to neonatal disorders such as prematurity, congenital heart disease, or Chiari malformation. Sleep protective strategies are readily available and need to be systematically implemented into hospital care.
Why elusive expectancy × value interactions may be critical for theory and intervention: A simulated power analysis.
2025-04-10

According to expectancy-value theories of motivation, individuals choose to pursue tasks that they expect to succeed at and find personally valuable. Historically, researchers have often suggested that these two factors interact to motivate behavior. However, expectancy × value interactions are rarely observed in empirical research and, when detected, they are often small in magnitude. Does this mean they can safely be ignored in models of motivation? In this paper we conduct two power analyses with simulated data to argue that expectancy × value interactions are likely far more important than a straightforward interpretation of effect sizes would suggest, and that downplaying them risks oversimplifying theory and recommendations for intervention. Specifically, Study 1 demonstrates that a realistic combination of three constraints (measurement error, skew, and correlation) can negatively bias expectancy × value interaction estimates by more than 50%. Study 2 shows that these interactions can create meaningful variability in motivation interventions and may contribute to a better understanding of treatment heterogeneity.
Point-of-care ultrasound reveals extensive pathology in Gabonese preschool-age children with urogenital schistosomiasis
2025-04-10

Background Historically, urinary tract pathology caused by S. haematobium infection was thought to affect predominantly school-age children (SAC) and adults. Increasing availability of ultrasound data from endemic areas demonstrates that even younger children develop potentially irreversible pathology. Methodology/principal findings Point-of-care ultrasound for urinary schistosomiasis and urine microscopy were performed across age groups in 105 patients with symptomatic urogenital schistosomiasis in Lambaréné, Gabon. Of 96 ultrasound scans with sufficient image quality, bladder wall thickening &gt; 5mm was found in 9/20 (45%) preschool-age children (PSAC), 29/51 (57%) SAC and 7/25 (28%) adults. Upper urinary tract pathology was found in 19/90 (21%) patients across age groups, up from three years of age. Urine egg counts were highest in PSAC, with high-intensity infection (≥ 50 eggs/10 ml urine) in 19/24 (79%) and hyper-infection (≥ 500 eggs/10 ml urine) in 10/24 (42%). Bladder wall thickening &gt; 5mm and upper urinary tract pathology correlated significantly with high-intensity infection with crude odds ratios of 8.6 (95% CI 3.1-23.8; p&lt;0.001) and 6.6 (95% CI 1.4-30.7; p=0.02), respectively. Three months after praziquantel treatment, parasitology showed a cure rate of 51% and egg reduction rate of 95%, while bladder wall thickening and upper urinary tract pathology persisted in 12/41 (29%) and 7/12 (58%) patients. Conclusions/significance A high proportion of PSAC in areas endemic for urogenital schistosomiasis already have detectable urinary tract pathology. Our findings highlight the urgent need to include this age group in mass drug administration programs, as recommended now by WHO. Further, particular attention should be paid to individual patient care.
Application of a replicative targetable vector system for difficult-to-manipulate streptomycetes
2025-04-10

Abstract The low frequency of homologous recombination together with poor efficiency in introducing DNA into the cell are the main factors hampering genetic manipulation of some bacterial strains. We faced this problem when trying to construct mutants of Streptomyces iranensis DSM 41954, a strain in which conjugation is particularly inefficient, and suicidal vectors had failed to yield any exconjugants. In this work, we report the construction and application of a conjugative replicative vector, pDS0007, which allows selection of exconjugants even with poor conjugation efficiency. The persistence of the construct inside the cell for as long as required facilitates the homologous recombination events leading to single and double crossovers. While it was confirmed that the vector is frequently lost without selection, the recognition sequence for the I-SceI endonuclease was included in the backbone of pDS0007. The presence of a I-SceI recognition sequence would allow to force the loss of the vector and the appearance of double crossover recombinants by introducing a second construct (e.g. pIJ12742) that expresses a Streptomyces codon–optimised gene encoding the I-SceI endonuclease. To facilitate screening for vector-free clones, the construct also carries a Streptomyces codon–optimised gusA gene encoding the β-glucuronidase expressed from a constitutive promoter. We prove the usefulness of this vector and strategy with the strain S. iranensis DSM 41954, in which we could readily delete an essential gene of a newly discovered biosynthetic pathway for a phosphonate-containing natural product, which led to loss of phosphonate production according to 31 P NMR spectroscopy. Key points • pDS0007 is a new vector for gene-targeting in difficult-to-manipulate streptomycetes. • pDS0007 is self-replicative but easy to cure, targetable and allows visual screening. • pDS0007 was used to prove the discovery of a novel phosphonate biosynthetic pathway. Graphical Abstract
Multidimensional Functional Phenotyping Based on Photoreceptor-Directed Temporal Contrast Sensitivity Defects in Inherited Retinal Diseases
2025-04-10

LMDlow, SMD, and RMD were the most important parameters. Photoreceptor-directed tCSs allow sophisticated functional phenotyping of inherited retinal diseases and complement other structural and functional parameters for genotype-phenotype correlations.
TAPAS—A Prospective, Multicentre, Long-Term Cohort Study in Children, Adolescents and Adults with Seasonal Allergic Rhinitis—Design and Early Results
2025-04-10

Background/Objectives: The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year. Methods: The Combined Symptom and Medication Score was chosen as the primary endpoint of this therapy. Secondary endpoints include the Rhinoconjunctivitis Quality of Life Questionnaire, the retrospective Rhinoconjunctivitis score, the Asthma Control Test and the Rhinitis Control Test, as well as an analysis of adverse drug reactions. Results: A total number of 320 patients were enrolled into this study, with 129 of these patients in the age group between 5 and 17 years and 191 patients in the adult age group. Mean Combined Symptom and Medication Score values did not differ significantly between minors and adults in the first pollen season after treatment induction. The retrospective score showed a strong and significant reduction in rhinoconjunctivitis and asthma symptoms. Treatment was well tolerated, with more than 80% of patients reporting no adverse drug reactions. Conclusions: The validity of this study approach of a cohort study has been confirmed by this first interim analysis for the initial course of therapy in the first year.
Modeling PFAS Sorption in Soils Using Machine Learning
2025-04-11

In this study, we introduce PFASorptionML, a novel machine learning (ML) tool developed to predict solid-liquid distribution coefficients (<i>K</i><sub>d</sub>) for per- and polyfluoroalkyl substances (PFAS) in soils. Leveraging a data set of 1,274 <i>K</i><sub>d</sub> entries for PFAS in soils and sediments, including compounds such as trifluoroacetate, cationic, and zwitterionic PFAS, and neutral fluorotelomer alcohols, the model incorporates PFAS-specific properties such as molecular weight, hydrophobicity, and p<i>K</i><sub>a</sub>, alongside soil characteristics like pH, texture, organic carbon content, and cation exchange capacity. Sensitivity analysis reveals that molecular weight, hydrophobicity, and organic carbon content are the most significant factors influencing sorption behavior, while charge density and mineral soil fraction have comparatively minor effects. The model demonstrates high predictive performance, with RPD values exceeding 3.16 across validation data sets, outperforming existing tools in accuracy and scope. Notably, PFAS chain length and functional group variability significantly influence <i>K</i><sub>d</sub>, with longer chain lengths and higher hydrophobicity positively correlating with <i>K</i><sub>d</sub>. By integrating location-specific soil repository data, the model enables the generation of spatial <i>K</i><sub>d</sub> maps for selected PFAS species. These capabilities are implemented in the online platform PFASorptionML, providing researchers and practitioners with a valuable resource for conducting environmental risk assessments of PFAS contamination in soils.
Subphenotype-Dependent Benefits of Bariatric Surgery for Individuals at Risk for Type 2 Diabetes
2025-04-11

OBJECTIVE Bariatric surgery is an effective treatment option for individuals with obesity and type 2 diabetes (T2D). However, whether outcomes in subtypes of individuals at risk for T2D and/or comorbidities (Tübingen Clusters) differ, is unknown. Of these, cluster 5 (C5) and cluster 6 (C6) are high-risk clusters for developing T2D and/or comorbidities, while cluster 4 (C4) is a low-risk cluster. We investigated bariatric surgery outcomes, hypothesizing that high-risk clusters benefit most due to great potential for metabolic improvement. RESEARCH DESIGN AND METHODS We allocated participants without T2D but at risk for T2D, defined by elevated BMI, to the Tübingen Clusters. Participants had normal glucose regulation or prediabetes according to American Diabetes Association criteria. Two cohorts underwent bariatric surgery: a discovery (Lille, France) and a replication cohort (Rome, Italy). A control cohort (Tübingen, Germany) received behavioral modification counseling. Main outcomes included alteration of glucose regulation parameters and prediabetes remission. RESULTS In the discovery cohort, 15.0% of participants (n = 121) were allocated to C4, 22.3% (n = 180) to C5, and 62.4% (n = 503) to C6. Relative body weight loss was similar among all clusters; however, reduction of insulin resistance and improvement of β-cell function were strongest in C5. Prediabetes remission rate was lowest in low-risk C4 and highest in high-risk C5. Individuals from high-risk clusters changed to low-risk clusters in both bariatric surgery cohorts but not in the control cohort. CONCLUSIONS Participants in C5 had the highest benefit from bariatric surgery in terms of improvement in insulin resistance, β-cell function, and prediabetes remission. This novel classification might help identify individuals who will benefit specifically from bariatric surgery.
How variants in inflammatory mediator genes influence symptom severity of psychiatric disorders: Findings from the PsyCourse study
2025-04-11

Alterations in glial cell function and cytokine levels in the central nervous system may be influenced by neuroinflammatory processes, which have a pathogenic role in psychiatric disorders. Variability in genes that encode inflammatory mediators is associated with risk of developing mental disorders. Therefore, by analyzing data from the transdiagnostic PsyCourse Study, we aimed to investigate whether variations in inflammatory mediator genes are associated with current symptom severity. We used cross-sectional data from 1320 individuals with a psychiatric disorder and 466 neurotypical individuals. Outcome variables were the psychopathological data from various rating scales and questionnaires that measured depressive, psychotic, and manic symptoms. Furthermore, from a whole-genome SNP array dataset, we extracted single nucleotide polymorphisms (SNPs) in the loci of genes related to inflammatory mediators, and we performed an association analysis by considering covariates. False discovery rate (FDR) was used to adjust the results for multiple comparisons. A total of 1594 individuals and 1336 SNPs were included in the analyses. The results of regression analysis showed a significant positive association of six SNPs located on the interleukin (IL)-1 receptor type 1 (IL-1R1) gene locus with Altman Self-Rating Mania Scale scores (FDR-adjusted p value < 0.05). Our findings show that genetic variations in IL-1R1 may influence the pathophysiology of psychiatric disorders by affecting brain cytokine profiles associated with manic episodes. IL-1R1 encodes a membrane-bound receptor for IL-1. Several physiological functions, including inflammation, are linked to the IL-1/IL-1R1 signaling pathway. Replication of our findings is warranted.
Discovery of synthetic small molecules targeting the central regulator of Salmonella pathogenicity
2025-04-11

The enteric pathogen Salmonella enterica serovar Typhimurium relies on the activity of effector proteins to invade, replicate, and disseminate into host epithelial cells and other tissues, thereby causing disease. Secretion and injection of effector proteins into host cells is mediated by dedicated secretion systems, which hence represent major virulence determinants. Here, we report the identification of a synthetic small molecule with drug-like properties, C26, which suppresses the secretion of effector proteins and consequently hinders bacterial invasion of eukaryotic cells. C26 binds to and inhibits HilD, the transcriptional regulator of the major secretion systems. Although sharing the same binding pocket as the previously described long-chain fatty acid ligands, C26 inhibits HilD with a unique binding mode and a distinct mechanism. We provide evidence of intramacrophage activity and present analogs with improved potency and suitability as scaffolds to develop antivirulence agents against Salmonella infections in humans and animals.
Functional characterization of Phytophthora infestans RXLR effector AVR2
2025-04-11

The P. infestans RXLR effector AVR2 interacts with BSU1-like phosphatases, which are known to positive regulators of Brassinosteroid signaling. I have used a combination of biochemical, molecular biology and reverse genetic approaches to characterize the function of AVR2 in host N. benthamiana and non-host A. thaliana.The expression of AVR2 in Arabidopsis leads to dwarf phenotype and abnormal stomata density. This phenotype is consistent with a defect in brassinosteroid signaling pathway. However, the transcriptome change analysis and activation studies of key brassinosteroid transcription factor BES1 showed except stomata biogenesis no deregulation by AVR2. AVR2 did not interfere with MAMP induced immune signaling responses: oxidative burst, MAPK activation expression of MIT-induced marker genes in Arabidopsis and N. benthamiana. However AVR2 interfered with programmed cell death in N. benthamiana and caused higher susceptibility to biotrophic pathogens P. syringae and P. capsici and increased resistance to necrotrophic A. brassicicola.
Crows recognize geometric regularity
2025-04-11

The perception of geometric regularity in shapes, a form of elementary Euclidean geometry, is a fundamental mathematical intuition in humans. We demonstrate this geometric understanding in an animal, the carrion crow. Crows were trained to detect a visually distinct intruder shape among six concurrent arbitrary shapes. The crows were able to immediately apply this intruder concept to quadrilaterals, identifying the one that exhibited differing geometric properties compared to the others in the set. The crows exhibited a geometric regularity effect, showing better performance with shapes featuring right angles, parallel lines, or symmetry over more irregular shapes. This performance advantage did not require learning. Our findings suggest that geometric intuitions are not specific to humans but are deeply rooted in biological evolution.
The Early Neolithic Settlement of Movila lui Deciov in Romanian Banat
2025-04-11

Abstract Since 2018, excavation work at the well-known site of Movila lui Deciov has been resumed by an international excavation team from the University of Tübingen together with the National Museum of Banat in Timişoara. The site was discovered at the beginning of the 20 th century by Kisléghi Nagy Gyula, who also carried out the first excavations. Further excavations were undertaken between 2001 and 2004 by Banat Museum in Timișoara and a team from the University of Calgary, Canada. The Early Neolithic settlement is delimited by a circular ditch, which was made visible by geophysical measurements and confirmed by sounding excavations. So far, three successive Early Neolithic settlement horizons from the beginning of the 6 th millennium BCE could be proven. The archaeological finds from the Movila lui Deciov provide a good insight into the specific character of the oldest Neolithic in the eastern part of the Carpathian Basin. A large series of radiocarbon dates makes it possible to reconstruct the settlement sequence chronology at this site particularly well. The micromorphological analyses and evaluation of the bioarchaeological remains allow us to understand in detail the adaptation of the Neolithic immigrants to the natural conditions. In addition to the usual domestic animals like sheep, goat and cattle as well as cultivated plants such as emmer, einkorn and legumes, hunting, fishing and the gathering of wild plants still played significant role in the diet of the Early Neolithic settlers.
Worse recovery from acute attacks and faster disability accumulation highlights the unmet need for improved treatment in patients with late-onset neuromyelitis optica spectrum disorders (COPTER-LO study)
2025-04-11

Objective This study analyzed clinical characteristics, attack recovery and long-term disability accumulation in late-onset (LO ≥ 50 years at onset) versus early-onset (EO &amp;lt; 50 years) NMOSD. Methods This multicenter cohort study included demographic and clinical data from 446 NMOSD patients collected from 35 German Neuromyelitis Optica Study Group (NEMOS) centers. Time to disability milestones was estimated through Kaplan-Meier analysis and Cox proportional hazard regression models adjusted for sex, year of onset, immunotherapy exposure and antibody status. Generalized estimating equations (GEE) were used to compare attack outcomes. Results Of the 446 NMOSD patients analyzed (83.4% female, 85.4% AQP4-IgG-positive, median age at disease onset = 43 years), 153 had a late-onset (34.3%). AQP4-IgG+ prevalence was higher in LO- than in EO-NMOSD (94.1% vs. 80.9%, p &amp;lt;0.001). Optic neuritis at onset was more frequent in EO-NMOSD (27.4% vs. 42.6%, p &amp;lt;0.002), whereas myelitis was more common in LO-NMOSD (58.4% vs. 37.9%, p &amp;lt;0.001). Both groups had similar annualized attack rates (AAR, 0.51 vs. 0.54, p =0.352), but attack recovery was poorer (complete remission in 15.6% vs. 27.4%, p &amp;lt;0.001) and relapse-associated worsening (RAW) was higher in LO-NMOSD (RAW: 3 vs. 0.5, p &amp;lt;0.001). Long-term immunotherapy use was comparable. LO-NMOSD exhibited faster progression to disability endpoints (EDSS 4: HR = 2.64, 95% CI=1.81–3.84). Interpretation LO-NMOSD patients presented more often with myelitis, experienced worse attack outcomes and faster disability accumulation, despite comparable AAR, acute attack treatment and long-term treatment regimens. Accordingly, therapeutic strategies for attack and prophylactic treatment in LO-NMOSD have to be improved.