julilili42/papers huggingface dataset:
Alien Acts in the Age of Emancipation: Mobility Control and Executive Power in the British Caribbean, 1820s–1830s
2025-08-06

Abstract In reaction to revolutionary upheaval in the 1790s and 1800s, the British parliament at home and colonial legislatures in the Americas passed their first statutory provisions to govern migration and aliens as such. As this paper argues, in their sustained and varied uses, these “alien acts” were much more than about border and migration controls. In a period of fundamental restructuring of imperial rule and of social statuses within the colonies, they increasingly turned into flexible tools of imperial governance. Taking the British Caribbean in the 1820s and 1830s as a case, the paper examines how alien legislation was reused, and reinvented, in two crucial arenas of imperial reconfiguration: the push for political equality by free people of color and the abolition of the slave trade. By their emphasis on sweeping executive power, various actors on the ground but also in the metropole regarded alien acts as an appropriate legal tool to respond to, to avert or subvert what they regarded as challenges or legal complexities of the age of emancipation. In this way, the alien acts also became a central factor in the reconfiguration of British subjecthood—with far-reaching consequences that their creators and users could never fully anticipate or control.
Prefrontal Cortex Recruitment to Food Stimuli Differs in Overweight/Obesity and Binge Eating Disorder
2025-08-06

ABSTRACT Background At a phenotypical level, the repeated occurrence of binge eating episodes clearly differentiates individuals with binge eating disorder (BED) from individuals with overweight but without BED. Their neural profiles during food‐related inhibition, however, indicate prefrontal hypoactivation in both groups. The present study investigated differential neural activations in upper lateral (right dorsolateral prefrontal cortex [DLPFC]) and inferior (right inferior frontal gyrus [IFG]) control regions during food‐related inhibition by functional near‐infrared spectroscopy (fNIRS). In addition, activity in reward‐related brain regions (orbitofrontal cortex [OFC]) during stimulus processing was measured. Method Individuals with BED ( n = 32), a control group of individuals with overweight and without BED (OWC, n = 21), and a control group of individuals with normal weight and without BED (NWC; n = 31) underwent a Go/No‐Go (GNG) and a stimulus degradation task during fNIRS, both with food and non‐food stimuli in counterbalanced order. Results Most predicted outcomes were not significant. Neural recordings during GNG underscore prefrontal hypoactivation in both BED and OWC relative to NWC, however, with differential alterations: In the Food‐NoGo condition, the BED group displayed hypoactivation in the IFG, while the OWC showed hypoactivation in the DLPFC. Conclusions The results suggest differential requirements for DLPFC and IFG recruitment during food‐related inhibition in individuals with BED and overweight.
Ultra-high-scale cytometry-based cellular interaction mapping
2025-08-07

Abstract Cellular interactions are of fundamental importance, orchestrating organismal development, tissue homeostasis and immunity. Recently, powerful methods that use single-cell genomic technologies to dissect physically interacting cells have been developed. However, these approaches are characterized by low cellular throughput, long processing times and high costs and are typically restricted to predefined cell types. Here we introduce Interact-omics, a cytometry-based framework to accurately map cellular landscapes and cellular interactions across all immune cell types at ultra-high resolution and scale. We demonstrate the utility of our approach to study kinetics, mode of action and personalized response prediction of immunotherapies, and organism-wide shifts in cellular composition and cellular interaction dynamics following infection in vivo. Our scalable framework can be applied a posteriori to existing cytometry datasets or incorporated into newly designed cytometry-based studies to map cellular interactions with a broad range of applications from fundamental biology to applied biomedicine.
Safety, tolerability, pharmacokinetics and pharmacodynamic effects of desmoglein 3 peptide-coupled tolerizing nanoparticles in pemphigus
2025-08-07

Abstract Background Pemphigus vulgaris (PV) is a CD4+ T-cell-dependent autoantibody-mediated blistering disease associated with human leucocyte antigen (HLA) class II molecules. IgG autoantibodies against the primary autoantigen desmoglein 3 (Dsg3), a desmosomal adhesion protein on epidermal keratinocytes, cause loss of epidermal cell adhesion. Objectives To assess the clinical applicability of an innovative nanoparticle platform for the induction of immune tolerance exploiting the natural tolerance potential of liver sinusoidal endothelial cells. An open-label first-in-human study was conducted with TPM203, a mixture of four nanoparticle-coupled immunodominant Dsg3 T-cell peptides. Methods The efficacy and mechanism of action of TPM203 were first tested in a humanized HLA-DRB1*0402-transgenic PV mouse model. In the clinical phase I trial, TPM203 was administered intravenously in patients with PV with no-to-moderate disease activity in single ascending and multiple doses (three doses of TPM203 two weeks apart). Primary endpoints included safety and tolerability. As a secondary endpoint, pharmacokinetics were assessed. Exploratory endpoints comprised changes in Dsg3-specific and bulk T- and B-cell frequencies, anti-Dsg3 IgG levels and autoantibody-induced keratinocyte dissociation. The trial was registered with EudraCT (2019-001727-12). Results In the PV mouse model, two administrations of TPM203 significantly reduced anti-Dsg3 IgG. On the cellular level, TPM203 led to a significant decrease in CD4+ T cells in the spleen, accompanied by increased frequencies of regulatory T (Treg) cells. In the clinical trial, the 17 patients with PV enrolled across single- and multiple-dose groups did not experience any serious or severe adverse events, or treatment-related PV worsening. Pharmacokinetics confirmed rapid TPM203 clearance from the circulation. Significant TPM203-induced modulations in bulk lymphocyte subsets included an increase in Treg cells, and reductions in T helper 17.1 and CD27+ memory B cells, when dose groups were combined for analysis. Dsg3-specific T cells were found to be significantly reduced at week 8 following single administration of TPM203. Anti-Dsg3 IgG levels trended downward in the three lower single ascending dose groups, while IgG-induced keratinocyte-dissociating capacity was significantly reduced after multiple doses. Conclusions Administered for the first time in humans, TPM203 was shown to be a safe and well-tolerated nanoparticle-based therapeutic approach with the potential to promote tolerance induction in PV, justifying further clinical development in this and other autoimmune diseases.
Bifunctional Cysteine-Engineered CAR-T Cells Enable Thiol-Mediated Targeting to Overcome Antigen Escape in B Cell Lymphoma
2025-08-07

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies; however, durable remissions remain limited due to antigen-negative cancer relapse, where tumor cells downregulate or lose the targeted antigen to evade immune recognition. To address this challenge, we developed cysteine-engineered CAR (CysCAR) T cells that redirect T cells to target cancer cells based on extracellular redox imbalances and the altered thiol/disulfide ratios, a marker we identified on B cell lymphomas. Here, we show that CysCAR-T cells, engineered with different cysteine-modified antibody fragments, exhibit a potent and specific cytotoxicity <i>in vitro</i> across various B cell lymphoma (BCL) subtypes, even in antigen escape models. Moreover, by integrating cysteine engineering with clinically used anti-CD19 CAR-T cells, we enabled simultaneous targeting of CD19 and altered redox states on BCL, potentially reducing the risk of antigen escape. In a pilot <i>in vivo</i> study, these bifunctional CD19-CysCAR-T cells suppressed tumor growth and prolonged survival of BCL-bearing mice without inducing systemic toxicity. Given that aberrant exofacial redox states are a hallmark of multiple cancers, our findings suggest a promising strategy to enhance the efficacy of anti-CD19 CAR-T cell therapy, overcome antigen escape, and reduce tumor relapse in BCL, with potential applicability to other malignancies.
Mechanisms of an inhibitory control training to reduce binge eating behaviours: study protocol of the randomized controlled proof-of-principle MIND BINGES trial
2025-08-07

Abstract Current guidelines recommend psychotherapy as first-line treatment for eating disorders. Many individuals with eating disorders characterized by binge eating episodes benefit from psychotherapy. However, a substantial subgroup does not achieve abstinence from binge eating. Bulimia Nervosa (BN) and Binge eating disorder (BED), along with other Specified/Unspecified Feeding or Eating Disorders (OSFED/UFED) with regular binge eating behaviour can be clustered on a continuum of eating disorders which is characterized by elevated impulsivity. Elevated impulsivity, and especially decreased inhibitory control, seem to be key factors in developing and maintaining binge eating behaviour. To target and modify these proposed underlying altered processes of binge eating, cognitive training approaches promise to achieve an amelioration of eating disorder-related psychopathology. Feedback is thought to play a crucial role in cognitive training approaches to increase learning and maintain motivation but its exact role has not been examined yet. MIND BINGES is a prospective, randomized controlled proof-of-principle trial investigating a food-modified inhibitory control training (ICT) and in particular the role of feedback on each individual’s performance. 63 patients with regular binge eating (BN, BED, OSFED, UFED) will be randomly assigned to receive either ICT with feedback after each session, ICT without feedback, or be assigned to a waitlist-control group (WL). The ICT is based on an antisaccade paradigm consisting of six training sessions over the course of two weeks. As the role of individual feedback provided to patients is unclear, the core aims are to investigate: (1) whether ICT without feedback is non-inferior to ICT with feedback in reducing binge eating episodes, and (2) whether ICT without feedback is superior to WL in reducing binge eating episodes. Thus, the primary endpoint is binge eating frequency in terms of changes in binge eating episodes four and 12 weeks after ICT/WL termination compared to baseline. Secondary outcomes include eating disorder psychopathology, general psychopathology, inhibitory control capacities, impulsivity, quality of life, self-esteem, and self-efficacy. Lastly, regression analyses will be conducted to explore the impact of secondary outcomes on the likelihood of a positive treatment effect. The results of the present trial will help to disentangle different elements of ICT, in particular the role of feedback. Based on the secondary outcomes, this trial might contribute to a better understanding of pathways and underlying mechanisms of an ICT. In sum, this helps developing possible individually tailored and effective treatment approaches for individuals suffering from regular binge eating. Findings might also inform cognitive trainings targeting symptoms of other mental health disorders.
The genetic history of the Southern Caucasus from the Bronze Age to the Early Middle Ages: 5,000 years of genetic continuity despite high mobility
2025-08-07

The Caucasus was a hub for cultural and technological innovation in prehistory, yet the population history between the Greater and Lesser Caucasus remains insufficiently understood. We present genome-wide data of 205 individuals from modern Georgia and 25 from Armenia, spanning the period from the Bronze Age (BA) to the "Migration Period" (c. 3500 BCE-700 CE). Our results reveal a persisting local gene pool that, during the Middle-Late BA, absorbed additional ancestry from Anatolia and the neighboring Eurasian Steppe. In subsequent periods, we document population growth and increasing genetic diversity, supported by a high rate of individual ancestry outliers, particularly in urban centers of eastern Georgia. Among 20 Medieval individuals with artificially deformed skulls, 15 were part of local mating networks and five derived ancestry from the Eurasian Steppe, suggesting that cranial modification arrived with nomadic groups but became a locally adopted cultural practice.
Multidisciplinary, Clinical Assessment of Accelerated Deep-Learning MRI Protocols at 1.5 T and 3 T After Intracranial Tumor Surgery and Their Influence on Residual Tumor Perception
2025-08-07

Background/Objectives: Postoperative MRI is crucial for detecting residual tumor, identifying complications, and planning subsequent therapy. This study evaluates accelerated deep learning reconstruction (DLR) versus standard clinical protocols for early postoperative MRI following tumor resection. Methods: This study uses a multidisciplinary approach involving a neuroradiologist, neurosurgeon, neuro-oncologist, and radiotherapist to evaluate qualitative aspects using a 5-point Likert scale, the preferred reconstruction variant and potential residual tumor of DLR and conventional reconstruction (CR) of FLAIR, T1-weighted non-contrast and contrast-enhanced (T1), and coronal T2-weighted (T2) sequences for 1.5 and 3 T MRI. Quantitative analysis included the image quality metrics Structural Similarity Index (SSIM), Multi-Scale SSIM (MS-SSIM), Feature Similarity Index (FSIM), Noise Quality Metric (NQM), signal-to-noise ratio (SNR), and Peak SNR (PSNR) with CR as a reference. Results: All raters strongly preferred DLR over CR. This was most pronounced for FLAIR images at 1.5 and 3 T (91% at 1.5 T and 97% at 3 T) and least pronounced for T1 at 1.5 T (79% for non-contrast-enhanced and 84% for contrast-enhanced sequences) and for T2 at 3 T (69%). DLR demonstrated superior qualitative image quality for all sequences and field strengths (p &lt; 0.001), except for T2 at 3 T, which was observed across all raters (p = 0.670). Diagnostic confidence was similar at 3 T with better but non-significant differences for T2 (p = 0.134) and at 1.5 T with better but non-significant differences for non-contrast-enhanced T1 (p = 0.083) and only marginally significant results for FLAIR (p = 0.033). Both the SSIM and MS-SSIM indicated near-perfect similarity between CR and DLR. FSIM performs worse in terms of consistency between CR and DLR. The image quality metrics NQM, SNR, and PSNR showed better results for DLR. Visual assessment of residual tumor was similar at 3 T but differed at 1.5 T, with more residual tumor detected with DLR, especially by the neurosurgeon (n = 4). Conclusions: An accelerated DLR protocol demonstrates clinical feasibility, enabling high-quality reconstructions in challenging postoperative MRIs. DLR sequences received strong multidisciplinary preference, underscoring their potential to improve neuro-oncologic decision making and suitability for clinical implementation.
Frontocentral brain networks amplify action-oriented temporal prediction errors
2025-08-07

Successful sensorimotor behavior depends on anticipating when a tactile event will occur and translating it into rapid action, yet it remains unclear how action requirements shape temporal prediction in the human cortex. Here, we combined Magnetoencephalography (MEG), multivariate decoding and computational modeling to contrast temporally jittered finger stimulations under passive versus action-oriented conditions. We characterized a distributed frontal sensorimotor network that was linked to fast tactile-motor associations and predicted reaction-time variability. We found that trial-by-trial deviations from expected stimulus timing modulated behavior, with stronger frontocentral prediction-error encoding when an overt response was required. Temporal prediction errors were primarily encoded in a motor rather than sensory reference frame. These results reveal that action demands dynamically amplify temporal error signaling in sensorimotor circuits, in line with predictive coding frameworks postulating that the brain preferentially encodes task-relevant and goal-directed sensory prediction errors.
Robust spatial hearing beyond primary interaural cues in humans over deep neural networks
2025-08-07

Summary Spatial hearing allows humans to localize sound sources in the azimuth plane using interaural time (ITD) and level (ILD) differences, but the contribution of additional auditory features remains unclear. To investigate this, we measured human localization performance with natural and artificial stimuli that selectively included or excluded ITD and ILD as primary interaural cues. As expected, human listeners relied synergistically on ITD and ILD for accurate azimuth localization. Moreover, even when both primary cues were absent, localization performance remained above chance level. We compared human performance with state-of-the-art deep neural networks (DNN) optimized for sound localization to investigate possible computational mechanisms underlying this robust performance. In contrast to humans, DNNs demonstrated high accuracy only for stimuli that resembled their training regime but failed when primary interaural cues were absent. This human-DNN misalignment highlights a fundamental distinction in sensory processing strategies, potentially arising from the simplicity bias inherent in DNN training, with human reliance on a wider range of auditory features likely reflecting evolutionary pressures favoring adaptability across diverse acoustic environments. Together, our results demonstrate the robustness of human spatial hearing beyond primary interaural cues and point to promising directions for advancing artificial systems and informing clinical applications, such as cochlear implants and auditory prosthetics.
Comparison of Methods for Quantifying the Carbon Content of Carbonated Wood Ash
2025-08-07

Abstract To assess mineral carbonation as a negative emission technology, the reliable quantification of the sequestered carbon is crucial. This study evaluates four methods for quantifying carbon sequestration by wood ash, through analyses of ash samples before and after lab‐scale carbonation, and compares the results to the theoretical storage potential determined using the Steinour equation. Results show that CHN elemental analysis and total carbon quantification provided consistent values for total carbon content and for the amount of CO 2 sequestered. Inorganic carbon was effectively quantified using both total/inorganic carbon analysis (TC/IC) analysis and volumetric calcimetry. The findings highlight the importance of selecting analytical methods and demonstrate that oversimplified thermogravimetric analysis (TGA) can lead to misinterpretation of sequestration results.
Rapid and simple method for glyphosate, aminomethylphosphonic acid, and sarcosine pre-concentration and determination in environmental samples after molecularly imprinted solid-phase extraction
2025-08-08

This study presents a selective and efficient analytical method for the simultaneous determination of glyphosate (GLY), aminomethylphosphonic acid (AMPA), and sarcosine (SAR) in environmental water and honey samples using commercial molecularly imprinted solid-phase extraction (MIP-SPE) coupled with tosyl chloride-based derivatization and high-performance liquid chromatography with UV detection (HPLC-UV). A central composite design (CCD) was employed to optimize key extraction parameters, including pH, sample volume, flow rate, and analyte concentration. Under optimized conditions, extraction recoveries exceeded 98 % for all analytes. Elution was optimized using 100 mM HCl, which provided superior recovery compared to basic eluents. The method showed excellent linearity (R<sup>2</sup> > 0.99), low detection limits (<0.4 μgL<sup>-1</sup>), and high precision (RSD<1.5 %). Application to real wastewater, river water, and honey samples confirmed high recoveries and minimal matrix interference. This validated MIP-SPE-HPLC-UV procedure provides a robust, cost-effective, and environmentally friendly solution for monitoring trace levels of polar contaminants in complex matrices.
Call for Standardization of C-Peptide Measurement
2025-08-08

Background: An impaired β-cell function is a key contributor to the pathophysiology of diabetes mellitus that can be estimated by the biomarker C-peptide. Measurement of C-peptide can therefore be used for prediction, diagnosis, and subclassification of diabetes. Furthermore, C-peptide assists in the prediction of therapeutic response and guiding therapeutic decisions. To support diabetes classification, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have recently introduced serum C-peptide cut-off values in their guidelines: &lt;0.2 nmol/L C-peptide levels suggest the presence of type 1 DM while C-peptide levels &gt;0.6 nmol/L indicate type 2 DM. However, analytical aspects limit the clinical utility of these defined cut-off values since standardization of C-peptide measurements has not been achieved. Results from different assay manufacturers still show significant variability. Results: This discrepancy can have significant consequences, as reliance on C-peptide testing for diabetes classification and therapeutic decisions has steadily increased in recent years. Although there have been growing calls to standardize C-peptide testing and a process for standardization has been established, standardization has unfortunately yet to be implemented in practice. Conclusion: It therefore seems appropriate for health care providers to advocate for standardized C-peptide measurements, which is more or less in the hands of the manufacturer of the C-peptide assays, to improve diagnostic accuracy and patient safety.
Cultivation in a Natural Microbial Community Enhances the Industrial Performance of a Genetically Engineered Cyanobacterium for Bioplastic Production
2025-08-08

Large-scale production of polyhydroxybutyrate (PHB), a biodegradable bioplastic, using genetically engineered cyanobacteria offers a sustainable alternative to petrochemical-derived plastics. However, monoculture-based phototrophic systems face major limitations, such poor resilience in large-scale reactors, hindering industrial upscaling. To address these challenges, we established a hybrid photosynthetic microbiome by replacing the native cyanobacterium of a natural microbial consortium with a genetically engineered Synechocystis strain optimized for PHB production. This new community retained the ecological structure and stability of the original microbiome while gaining synthetic production capacity. Compared to the axenic strain, the hybrid system exhibited enhanced robustness under abiotic stress, including light and temperature fluctuations, and improved tolerance to operational instability. These features made it suitable for upscaling and application in non-sterile environments. The hybrid microbiome sustained PHB production in scaled photobioreactors, reaching up to 32% PHB per cell dry weight (CDW) equal to ~230 mg L-1 under fully photoautotrophic conditions. Production was also achieved under dark conditions with acetate supplementation, highlighting the system metabolic flexibility. This work demonstrates the successful integration of an engineered phototroph into a stable native microbiome, positioning hybrid communities as powerful platform for industrial biotechnology.