julilili42/papers huggingface dataset:
Extracellular Vesicles Derived From the Feces of Pregnant Women Modulate T Cells Toward a Pregnancy‐Supportive Phenotype In Vitro
2025-09-01

ABSTRACT Pregnancy requires immune tolerance to a semi‐allogeneic fetus, involving profound adaptations, particularly in the T helper (Th) cell response. The intestinal microbiome plays a crucial role in health, but its influence on immune adaptation to pregnancy remains unclear. Bacterial extracellular vesicles (BEVs), released by gut bacteria, can cross the intestinal barrier and modulate immune responses. In our study we investigated the effect of fecal EVs (fEVs) from pregnant women on Th cell composition in vitro . fEVs were purified from preserved stool samples, characterized, and their uptake by immune cells was analyzed. Using an in vitro T cell culture model, we examined Th cell phenotypes, intracellular cytokine expression, and proteomic changes after stimulation with fEVs from pregnant and non‐pregnant women. We demonstrate that fEVs from preserved stool samples are rapidly taken up by T cells and modulate their phenotype. Stimulation with fEVs from pregnant women shifts Th cells toward a regulatory profile favorable for pregnancy, increasing Th2 cells while reducing Th17 cells compared to fEVs from non‐pregnant controls. This study provides the first in vitro evidence that fecal‐derived EVs influence immune adaptation to pregnancy and may offer a basis for microbiome‐targeted strategies to prevent or treat immunological pregnancy complications.
Delineating the pathogenic threshold and phenotypic spectrum of SCA27B: findings from a large French–Canadian cohort
2025-09-01

This large cohort demonstrates that (GAA•TTC)<sub>200-249</sub> alleles are enriched in patients with ataxia compared to controls and can be pathogenic for SCA27B, supporting the need to define a lower pathogenic threshold in the presence of specific clinical criteria.
Cover Crop Root Channels Promote Bacterial Adaptation to Drought in the Maize Rhizosphere
2025-09-01

ABSTRACT Increasing drought frequency poses a significant threat to agricultural productivity. A promising strategy to enhance crop resilience against drought is the utilisation of root channels left by winter cover crops, which can improve access to subsoil water and nutrients for subsequent cash crops like maize ( Zea mays L.). The impact of drought on bacterial communities inhabiting these root channels remains largely unknown. Here, we investigated drought‐induced shifts in maize rhizosphere bacterial communities and their functional adaptation in cover crop root channels across three soil types in northern Germany (Luvisol, Podzol, and Phaeozem) using a multi‐omics approach (16S rRNA gene amplicon sequencing, qPCR, and metaproteomics). Our results reveal a preference towards bacterial K ‐strategists under drought conditions, indicating a shift towards stress‐tolerant populations. Under drought stress, the relative abundances of Acidobacteriota , Actinomycetota , Planctomycetota , and Pseudomonadota increased, while Chloroflexota , Methylomirabilota , Ca . Patescibacteria, and Verrucomicrobiota declined. Metaproteomics analyses revealed that drought‐stressed aerobic taxa among the Pseudomonadota and Verrucomicrobiota upregulated the glyoxylate cycle, potentially enhancing carbon and energy conservation, and increased antioxidant defences (catalase–glutathione peroxidase and methionine cycle–transsulfuration pathway). These drought‐mitigating strategies were especially pronounced in root channels formed by Brassicaceae and Poaceae cover crops in the Luvisol and Podzol soils. These findings demonstrate the functional plasticity of rhizosphere bacterial communities in reused root channels in response to drought, highlighting the potential to leverage microbiome‐mediated resilience for agricultural practices.
Time Course of Motor Improvement by Epidural Stimulation After Spinal Cord Injury: An Interim Analysis of a Phase II Trial
2025-09-01

Background Epidural spinal cord stimulation (EES) is a promising intervention for motor rehabilitation after spinal cord injury (SCI), but the extent and trajectory of motor recovery remain unclear. Objective This phase II trial evaluates the acquisition of voluntary movements in paraplegic patients (ASIA A or B) following SCI, assessed by the Fugl-Meyer Lower Extremity (FMA-LE) score and electromyography (EMG). Methods This interim analysis includes five patients implanted with EES and followed for 12 months. The primary outcome was motor recovery, measured by FMA-LE and EMG. Secondary outcomes included balance (Berg Balance Scale), spasticity (Modified Ashworth Scale), pain, autonomic functions, mood, quality of life (WHO-QOL), and safety. Adverse events were monitored. Results The FMA-LE score improved from 36 ± 9 (SD) to 55 ± 2 at 3 months ( P &lt; 0.05), 59 ± 2 at 6 months ( P &lt; 0.05), and 64 ± 4 at 12 months ( P &lt; 0.05). EMG confirmed increased voluntary activation. Balance and spasticity improved, while pain and autonomic functions remained unchanged. Motor gains plateaued after 5 months, reaching 68% above baseline. No serious adverse events occurred, though minor complications included transient nociceptive pain and a self-resolving pressure ulcer. Conclusions These findings support the role of EES in facilitating early motor recovery in SCI patients, consistent with prior studies. However, the plateau effect suggests a limit to long-term gains. Future research should explore strategies to sustain improvements, including regenerative therapies or optimized neuromodulation protocols. Trial registration number: NCT06847295
The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology
2025-09-01

Abstract BACKGROUND Tau‐derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid‐beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long‐term anti‐Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them. METHODS A post‐hoc analysis of the DIAN‐TU‐001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab ( n = 50), gantenerumab ( n = 52), or placebo ( n = 40). High‐resolution mass spectrometry quantified CSF tau species over four years. RESULTS Phosphorylated tau (p‐tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab‐mediated Aβ plaque reduction. Nearly a decade later, MTBR‐tau243 and p‐tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION Initially changing soluble p‐tau species track Aβ plaque reduction, while ptau205 and MTBR‐243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. Highlights p‐tau217 and p‐tau231 correlate with Aβ‐PET and respond to Aβ‐plaque lowering therapies. Aβ immunotherapy trials support a direct link between p‐tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT‐related biomarkers. Blood‐based p‐tau217 assays may provide a non‐invasive tool to monitor Aβ therapies. MTBR‐tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT‐targeting therapies.
HLA-A*01:01-B*08:01-C*07:01 is linked to early-onset immune checkpoint inhibitor-induced myositis and myocarditis
2025-09-01

Background Immune-related myotoxicity (irM), including irMyocarditis and irMyositis, is a severe complication of immune checkpoint inhibitors (ICIs). Markers to identify patients at risk are missing. In this retrospective multicenter cohort study, we aimed to determine whether specific human leukocyte antigen (HLA) variants are associated with irM. Methods Twenty patients with irMyocarditis and/or irMyositis (median age (IQR), 67 (60–73) years; 7/20 female) and 60 cancer controls (CC) without immune-related adverse events (median age (IQR), 68 (62–74) years; 26/60 female) presenting to Charité - Universitätsmedizin Berlin, Germany, or Kantonsspital St. Gallen, Switzerland, between September 2017 and June 2024, were included. As a second control cohort, we used HLA data from a historic dataset of 5.1×106 German healthy donors (G-HD). Allele frequencies (AF) of two-field HLA types were compared between patients with irM, CC, and G-HD using logistic regression and two-sided z-tests of odds ratios (OR). Results Comparison of single HLA AF between patients with irM and G-HD revealed moderate associations for irM with B*07:02 (OR 2.29; 95% CI 1.12 to 4.69; p=0.023), B*40:01 (OR 2.75; 95% CI 1.08 to 7.02; p=0.035), C*03:04 (OR 2.46; 95% CI 1.09 to 5.56; p=0.031), DPB1*04:02 (OR 2.37; 95% CI 1.16 to 4.85; p=0.018), and DQB1*06:02 (OR 2.28; 95% CI 1.12 to 4.67; p=0.024). No statistically significant differences were observed between patients with irM and CC. By contrast, multi-allelic HLA analysis identified a strong association between HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 ancestral haplotype (8.1 AH), and early-onset irM (onset ≤3 months after ICI initiation, n=11), compared with G-HD (22.7% vs 7.6%; OR 3.59; 95% CI 1.33 to 9.74; p=0.012) and CC (22.7% vs 7.5%; OR 3.62; 95% CI 1.09 to 12.12; p=0.036). Intriguingly, early-onset irM was linked to higher troponin T levels compared with late-onset irM (p=0.005, Cohen’s r=0.63). Conclusions Our results provide first evidence that early-onset irM with myocardial injury is linked to HLA-A*01:01-B*08:01-C*07:01, a component of the 8.1 AH, which is associated with various autoimmune diseases including idiopathic myopathies. If validated in larger cohorts, pretreatment screening for HLA-A*01:01-B*08:01-C*07:01 may help identify patients at risk of early-onset and severe irM.
Longitudinal associations of structural and functional brain connectivity with dimensions of psychopathology in adolescence
2025-09-01

These findings highlight the dynamic interplay between brain connectivity development and psychopathology in adolescence, with potential implications for identifying neural markers of risk and resilience during sensitive windows of development.
R-Spondin1 Regulates Fate of Enteric Neural Progenitors via Differential LGR4/5/6 Expression in Mice and Humans
2025-09-01

LGR receptor expression therefore might represent a previously unknown mechanism influencing the fate decision of ENS progenitor cells between proliferation and neuronal differentiation. Thus, our study is essential for our understanding of regenerative aspects of the postnatal ENS in health and disease.
Persistence of anti-platelet factor 4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis for 3 years
2025-09-01

Our findings demonstrate that VITT antibodies can persist for nearly 3 years in some patients, and a proportion of those maintain the ability to activate platelets in vitro. The complete duration of VITT antibody persistence remains unknown, and whether this has clinical implications requires ongoing surveillance with further evaluation.
Sensory neurons drive pancreatic cancer progression through glutamatergic neuron-cancer pseudo-synapses
2025-09-01

Cancers thrive on neuronal input. Here, we demonstrate the presence of pseudo-synaptic connections between sensory nerve endings and cancer cells in an extracerebral cancer, i.e., pancreatic ductal adenocarcinoma (PDAC). These synaptic sites exhibit a selective enrichment of the glutamatergic N-methyl-D-aspartate receptor (NMDA) receptor subunit NMDAR2D (GRIN2D) on the cancer cells, which turns PDAC cells responsive to neuron-derived glutamate and promotes tumor growth and spread. Intriguingly, neurons transform a subset of co-cultured PDAC cells into calcium-responsive cells via GRIN2D-type glutamate receptors at the neuron-cancer pseudo-synapses. We found that the expression of this subunit is due to the increased glutamate availability provided by sensory innervation in a neurotrophic feedforward loop. Moreover, interference with the glutamate-GRIN2D signaling at these neuron-cancer pseudo-synapses markedly improved survival in vivo. This discovery of peripheral cancer-neuron pseudo-synapses may provide an opportunity for cancer-neuroscience-instructed oncological therapies.
Biogeochemistry of an Iron‐ and Manganese‐Rich Stratified Lake: Tasik Biru, Malaysia, as a Modern Model Habitat for the Ancient Ocean
2025-09-01

ABSTRACT Tasik Biru is a ~70 m‐deep tropical lake in Malaysia, originating from a water‐filled open pit mine. We investigated the biogeochemistry and microbial community of the lake as a modern model habitat to the stratified ancient ocean. We found that a sharp redoxcline exists at around 50 m depth, related to the decrease of O 2 and pH (7.2–6.8) going down into the monimolimnion. Despite being relatively sulfate‐rich (~320 μM), only a slight decrease of sulfate (to ~240 μM) was observed coupled with an increase of dissolved sulfide to 4 μM, attributed to microbial sulfate reduction in the monimolimnion. Comparatively, dissolved Fe and total Mn rose to ~50 μM in the anoxic layer with an unusual 1:1 concentration ratio. Other nutrients (PO 4 3− , Si) and trace metal(loid)s (As, Mo, Sb, Co, U, and V) depth profiles increased or decreased across the chemocline, indicating controls via cycling of redox‐sensitive elements. Microbial community analysis based on 16S rRNA amplicon sequencing reflects various metabolisms, from aerobic metabolisms in the mixolimnion to putative nitrite‐dependent methane oxidation (e.g., by Methylomirabilis ) at the chemocline, to sulfate reduction, methanogenesis, and fermentation in the monimolimnion. Tasik Biru is not in steady‐state, and its anoxic water is predicted to shift from being Fe/Mn‐rich to sulfide‐rich, perhaps lending it as a model habitat to investigate biogeochemical changes from the metal‐rich Archean to the Proterozoic oceans with expanding zones of sulfide‐rich margins. An overview of the current biogeochemical cycles in the lake is presented, and open questions regarding partial sulfate consumption, methane, and Mn cycling and mineralogical distribution are highlighted to guide future studies.
Physical activity interventions and musculoskeletal health in surgeons: a systematic review and meta-analysis
2025-09-01

Surgeons face a significant risk of work-related musculoskeletal disorders due to the demands of their profession. However, the effects of physical activity interventions (eg, exercises or active and passive microbreaks) remain unclear. This study aimed to evaluate the effects of physical activity interventions on musculoskeletal health in the surgical population. A systematic literature search was conducted between 15 April 2024 and 30 May 2024, using six databases. We only included experimental studies, and meta-analyses were conducted for active microbreaks, while we narratively synthesised the results for other physical activity interventions due to small number of studies. The level of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation. Among 5576 identified articles, a total of 9 articles were included. For active microbreaks, the meta-analyses showed pooled estimates between −0.24 (95% CI −0.36 to –0.11) and −0.62 (95% CI −0.87 to –0.37) for pain in body regions related to the spine, upper extremity and lower extremity. For passive microbreaks, significantly lower levels of musculoskeletal pain and strain were found in the spine, neck, arms and knees at the end of the procedure compared with no intervention. For exercise with and without ergonomic counselling, a significant decrease in pain was found from baseline to 3, 6 and 12 months in most body parts. For all intervention types, the level of evidence ranged from very low to low. We found that physical activity interventions have positive effects on the musculoskeletal health of surgeons. However, the low level of evidence highlights the need for high-quality research.
Discovery of potent and selective inhibitors of human NLRP3 with a novel mechanism of action
2025-09-02

The NLRP3 inflammasome is an intracellular protein complex that causes inflammation via the release of IL-1β and pyroptosis. NLRP3 activation is associated with many age-related inflammatory diseases, and NLRP3 inhibition is a promising therapeutic strategy. We previously performed a DNA-encoded library screen to identify novel NLRP3-binding molecules. Herein we describe the characterization of BAL-0028 as a potent and specific inhibitor of NLRP3 signaling. Notably, BAL-0028 is a poor inhibitor of mouse NLRP3 but inhibits human and primate NLRP3 with nanomolar potency. Using cellular and biochemical analyses, we demonstrate that BAL-0028 binds to the NLRP3 NACHT domain at a site that is distinct from the MCC950-binding pocket. Using humanized NLRP3 mice, we show that a derivative of BAL-0028, BAL-0598, inhibits NLRP3 activation in vivo in a peritonitis model. Finally, we demonstrate that both BAL-0028 and BAL-0598 inhibit select hyperactive NLRP3 mutations associated with autoinflammatory diseases more potently than MCC950. BAL-0028 and BAL-0598 thus represent a new modality for NLRP3 inhibition in inflammatory diseases.
General-relativistic magnetar magnetospheres in 3D with physics-informed neural networks
2025-09-02

ABSTRACT Magnetar phenomena are likely intertwined with the location and structure of magnetospheric currents. General-relativistic effects are important in shaping the force-free equilibria describing static configurations, though most studies have quantified their impact only in cases of axial symmetry. Using a novel methodology based on physics-informed neural networks, fully three-dimensional configurations of varying stellar compactness are constructed. Realistic profiles for surface currents, qualitatively capturing the geometry of observed hotspots, are applied as boundary conditions to deduce the amount of free energy available to fuel outburst activity. It is found that the lowest energy solution branches permit only a excess relative to current-starved solutions in axisymmetric cases with global twists, regardless of compactness, reducing to in 3D models with localized spots. Accounting for redshift reductions to their inferred dipole moments from timing data, explaining magnetar burst energetics therefore becomes more difficult unless the field hosts non-negligible multipoles. Discussions on other aspects of magnetar phenomena are also provided.
Birth weight and prematurity for predicting type 2 diabetes mellitus: a prognostic review
2025-09-02

This is a protocol for a Cochrane Review (prototype). The objectives are as follows: Primary objective To determine the prognostic value of birth weight (BW) and prematurity in predicting the incidence of type 2 diabetes mellitus (T2DM) later in life (among adults, adolescents, and children) compared to normal BW and full-term birth. Secondary objectives To determine the prognostic value of BW and prematurity in predicting the incidence rates of diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy, later in life (among adults, adolescents, and children) compared to normal BW and full-term birth.
Adaptive Feedback in Digital Educational Games: An Explanatory Item Response Theory Approach
2025-09-02

ABSTRACT Background The potential of adaptive feedback in digital educational games remains largely unexplored. Fractions are a suitable topic for investigating the effectiveness of adaptive feedback, as the complexity of this domain highlights the need for adequate feedback. Objectives This study examines the effectiveness of explanatory adaptive feedback in a digital educational game to address two particular misconceptions regarding fractions (i.e., Natural Number Bias and Unit of Reference). Methods A total of 197 4th graders were randomly assigned to two different conditions, each playing a different version of a digital educational game: one with corrective feedback and one with explanatory adaptive feedback. During gameplay, we collected log data of students' item‐wise correctness and misconception errors. Results Explanatory item response analyses indicated that correctness improved in both game versions, with a more pronounced increase for the game with explanatory adaptive feedback compared to the game with corrective feedback. However, no decrease in misconception errors was observed in either game version. Moreover, neither the type of misconception nor students' prior fraction knowledge were moderating factors. These results suggest that adaptive feedback can support students in learning fractions; however, to reduce misconception errors concrete feedback should be optimised.
Return-to-work after acetabular fractures: the impact of injury severity on the post-rehabilitation working capacity and workload
2025-09-02

Objective: Acetabular fractures are among the most severe injuries in trauma surgery. In younger patients, they typically result from high-energy trauma and are often associated with polytrauma. Treatment complexity and rehabilitation outcomes are influenced by overall injury severity. This study aimed to evaluate return to work (RTW) after acetabular fracture in relation to the overall injury severity score (ISS). Design/subjects/patients: A retrospective study included 22 patients treated for acetabular fractures at a Level I Trauma Centre spanning a period from January 2009 – December 2020. Methods: Patients completed a questionnaire assessing work-related factors and workload before (PRE) and after (POST) trauma (median [MD] = 126.4 ± 46.4 months POST). Based on ISS, patients were categorized as &lt; 16 = “no polytrauma” (n = 8) and ≥ 16 = “polytrauma” (n = 14). Results: The RTW rate was 75% in both groups. However, descriptively the median workload reduction was greater in the “polytrauma” group (–50%) compared to the “no polytrauma” group (–33.3%). A shift toward sedentary work was seen in both groups, more prominently in the “polytrauma” subgroup (+40%) compared to the “no polytrauma” group (+11.4%). Conclusion: Possible workload was reduced after acetabular fracture. Despite similar RTW rates, polytrauma patients descriptively returned to less physically demanding work. Thus, ISS significantly predicts the outcome of the rehabilitations process after acetabular fractures.
A brain-wide map of neural activity during complex behaviour
2025-09-03

Abstract A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with previous expectations to initiate movements and make decisions 1 . It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here we report a comprehensive set of recordings from 621,733 neurons recorded with 699 Neuropixels probes across 139 mice in 12 laboratories. The data were obtained from mice performing a decision-making task with sensory, motor and cognitive components. The probes covered 279 brain areas in the left forebrain and midbrain and the right hindbrain and cerebellum. We provide an initial appraisal of this brain-wide map and assess how neural activity encodes key task variables. Representations of visual stimuli transiently appeared in classical visual areas after stimulus onset and then spread to ramp-like activity in a collection of midbrain and hindbrain regions that also encoded choices. Neural responses correlated with impending motor action almost everywhere in the brain. Responses to reward delivery and consumption were also widespread. This publicly available dataset represents a resource for understanding how computations distributed across and within brain areas drive behaviour.