julilili42/papers huggingface dataset:
Changes in Gray Matter Morphology and White Matter Microstructure Across the Adult Lifespan in People With Temporal Lobe Epilepsy
2025-08-22

This study highlights that patients with TLE exhibit more pronounced and widespread gray and white matter atrophy across the lifespan. The cross-sectional nature of our study limits definitive conclusions on whether the atrophy shown is progressive but emphasizes the importance of prompt diagnosis and intervention in patients. Collectively, our results motivate future longitudinal studies to clarify consequences of drug-resistant epilepsy.
Determining the Dipole Orientation of Second Harmonic Generation in 3R-MoS2 for Enhanced Nonlinear Susceptibility
2025-08-22

As an efficient two-dimensional nonlinear optical crystal, 3R-MoS<sub>2</sub> exhibits intrinsic bulk second-order nonlinearity with substantial second harmonic generation (SHG) due to the interfacial charge transfer induced interlayer dipole and intralayer intrinsic asymmetric dipole. However, how these dipoles determine the SHG emission dipole orientation and intensity in 3R-MoS<sub>2</sub> has not been clearly resolved. Here, we accurately determine the coexistence of in-plane and out-of-plane SHG emission dipoles in few-layer 3R-MoS<sub>2</sub> through radial-/azimuthal-polarization excitation SHG measurements and back focal plane (BFP) imaging combined with numerical simulations, where the SHG emission dipole orientation (<i>Θ</i>) in real space for 3L, 4L, 5L, and 6L 3R-MoS<sub>2</sub> is determined to be ∼8°, ∼16°, ∼20°, and ∼32°, respectively. The layer-dependent <i>Θ</i> arises from the significant decrease in SHG susceptibility <i>χ</i><sub>16</sub><sup>(2)</sup> with an increasing layer number, which weakens the contribution of the in-plane SHG emission dipole component to the overall SHG response. Moreover, by tailoring the interlayer charge transfer induced dipole <i>via</i> hydrostatic pressure, more than 1 order of magnitude enhancement of SHG susceptibility in few-layer 3R-MoS<sub>2</sub> has been achieved, which originates from the strengthened interlayer charge transfer and interfacial charge rearrangement upon compression. Our findings not only optimize phase-matching conditions via aligning the emission dipoles but also provide a strategy for fine-tuning the nonlinear optical responses in nanophotonic applications.
Privacy-preserving federated unsupervised domain adaptation with application to age prediction from DNA methylation data
2025-08-22

Abstract Motivation Generalizing machine learning models across small, high-dimensional, and heterogeneous biological datasets remains a critical challenge due to domain shifts caused by variations in data collection, population differences, and privacy constraints that restrict data sharing. Existing federated domain adaptation (FDA) approaches primarily rely on deep learning and focus on classification tasks, making them unsuitable for privacy-sensitive, small-scale regression problems in biomedical research. We introduce a privacy-preserving federated method for unsupervised domain adaptation in regression, enabling robust learning across distributed, high-dimensional datasets while maintaining full data privacy. Results Our method is the first to enable distributed training of Gaussian processes for domain adaptation, ensuring complete privacy through randomized encoding and secure aggregation. Unlike deep learning-based FDA approaches, our method is specifically designed for small-scale, high-dimensional biological data, overcoming prior limitations in scalability and generalization. We evaluate our approach on age prediction from DNA methylation data, demonstrating that it achieves performance comparable to non-private state-of-the-art methods while fully preserving data privacy. This work enables secure and effective cross-institutional collaboration in biomedical research without requiring raw data sharing. Availability and implementation The source code for our method is available at https://github.com/mdppml/FREDA.
Repeated theta burst stimulation of the right ventrolateral prefrontal cortex reveals strong habituation in the context of stress and rumination
2025-08-23

Abstract Prefrontal hypoactivation under stress has been consistently observed in individuals with high trait rumination and in patients with depression. However, no study has yet investigated the mechanisms of modulating activity of the Ventrolateral Prefrontal Cortex (VLPFC) by using excitatory and inhibitory Theta Burst Stimulation (TBS) in this context. To address this, we recruited 89 healthy participants (44 low trait ruminators and 45 high trait ruminators) who attended two lab sessions, each including stress induction via the Trier Social Stress Test (TSST). Participants received either excitatory intermittent TBS (iTBS) or inhibitory continuous TBS (cTBS). One session involved active TBS, while the other used sham TBS (sTBS), with the order randomized and balanced across stimulation conditions and groups. In high ruminators, we observed a significant impact of iTBS in the hypothesized direction when considering cortical oxygenation in the right VLPFC. We found higher subjective stress following iTBS and cTBS compared to sTBS during recovery of the TSST but only at the first appointment. No stimulation-dependent effects were found for other measures (state rumination, positive and negative affect, and heart rates). In our discussion, we draw conclusions concerning repeated-measures designs in TBS-studies.
PRISM: Privacy-preserving Rare Disease Analysis using Fully Homomorphic Encryption
2025-08-23

Abstract Motivation Rare diseases affect millions of people worldwide, yet their genomic foundations remain poorly understood due to limited patient data and strict privacy regulations, such as the General Data Protection Regulation (GDPR) (https://gdpr.eu/tag/gdpr/) in March 2025. These restrictions can hinder the collaborative analysis of genomic data necessary for uncovering disease-causing variants. Results We present PRISM, a novel privacy-preserving framework based on fully homomorphic encryption (FHE) that facilitates rare disease variant analysis across multiple institutions without exposing sensitive genomic information. To address the challenges of centralized trust, PRISM is built upon a threshold FHE scheme. This approach decentralizes key management across participating institutions and ensures no single entity can unilaterally decrypt sensitive data. Our method filters disease-causing variants under recessive, dominant, and de novo inheritance models entirely on encrypted data. We propose two algorithmic variants: a multiplication-intensive (MUL-IN) approach and an addition-intensive (ADD-IN) approach. The ADD-IN algorithms minimize the number of costly multiplication operations, enabling up to a 17× improvement in runtime for recessive/dominant filtering and 22× for de novo filtering, compared to MUL-IN methods. While ADD-IN produces larger ciphertexts, efficient parallelization via SIMD and multithreading allows it to handle millions of variants in reasonable time. To the best of our knowledge, this is the first study that utilizes FHE for privacy-preserving rare disease analysis across multiple inheritance models, demonstrating its practicality and scalability in a single-cloud setting. Availability The source code and the data used in this work can be found in https://github.com/mdppml/PRISM.git Supplementary information Supplementary data are available at Bioinformatics online.
CD8+ T cells regulate the bioenergetic reprogramming of lymphoid organs and the heart during viral infection
2025-08-23

SUMMARY The activation of the immune system is a bioenergetically-costly process 1 . Yet, essential bodily functions require a continuous energy supply, imposing energy constraints and trade-offs between competing processes 2 . Our understanding of the underlying bioenergetic adaptations reconciling rapid immune activation with other vital processes remains scarce. 3–6 Here, by using experimental models of viral infections, we identified an unexpected CD8 + T cell-driven redistribution of energy substrates between lymphoid organs and the heart. Viral infection promoted systemic hypoglycaemia and ketogenesis, together with systemic reallocation of energy substrates. Across organs analysed, secondary lymphoid organs and the heart showed the most dramatic changes. The former increased glucose uptake and oxidation while the heart showed the opposite, switching to preferential fatty acid utilization. These bioenergetic adaptations were absent in infected mice lacking CD8 + T cells or with T cells lacking the glucose transporter GLUT1. Pharmacological inhibition of fatty acid oxidation forced a systemic switch to glucose oxidation. This was associated with metabolic decompensation, reduced cardiac energetics, left ventricular stress, and mortality in otherwise nonlethal viral infections. Our results reveal how the energetic cost of immune cell activation imposes bioenergetic adaptations on non-lymphoid organs, posing a major challenge for the heart by completely relying on fatty acids.
DSPy-based neural-symbolic pipeline to enhance spatial reasoning in LLMs
2025-08-24

Spatial reasoning is crucial for Large Language Models (LLMs) but remains a persistent challenge. Existing neural-symbolic approaches offer partial solutions but suffer from inflexible design and limited effectiveness. We present a neural-symbolic framework that integrates LLMs with Answer Set Programming (ASP) through an iterative feedback loop, enabling precise and reliable refinement of generated logic programs. Evaluated on two benchmark datasets across multiple reasoning tasks and LLMs, our DSPy-based pipeline achieves 82-93 % and 71-80 % accuracy, surpassing direct prompting, Chain-of-Thought, and a two-stage "Facts+Rules" method by up to 43 % and 25 %, respectively. The lightweight "Facts+Rules" alternative we proposed also improves baseline performance by 9-27 % while reducing computational overhead. Key innovations driving these gains include (1) modular separation of semantic parsing and logical reasoning, (2) iterative error-handling feedback between LLMs and ASP solvers, and (3) domain-specific symbolic representations for efficient reasoning. The system offers strong interpretability and generalizability, allowing application across diverse and complex tasks. Moreover, our proposed system could substantially advance AI architectures capable of human-like, multi-component reasoning, contributing to the development of artificial general intelligence.
P2Y14 Receptor Antagonists: Piperidine Bioisosteres and Mutagenesis-Supported Molecular Modeling
2025-08-25

The human P2Y<sub>14</sub> receptor (hP2Y<sub>14</sub>R) has emerged as a promising target for inflammation and pain treatment, but its zwitterionic antagonists have low bioavailability. We extended the naphthalene-based antagonist series' structure-activity relationship (SAR) by replacing an outward-facing piperidine moiety with small heteroaromatics. Notably, <i>C</i>-linked 1,2,3-triazol-4-yl (<b>10</b>, MRS4916) and pyrazol-3-yl (<b>11</b>, MRS4917) substitutions yielded antagonists with IC<sub>50</sub> values of 3.69 and 2.88 nM, respectively. In contrast, incorporation of a second triazole in the phenyl-triazolyl series (<b>16</b>) significantly reduced affinity. Charged phosphate groups were strategically placed at two positions of potent triazole derivative <b>7</b> to explore the ligand's binding site vicinity and detect potential proximity to cationic side chains but neither increased affinity. Site-directed mutagenesis was used to probe the antagonist binding site vicinity. However, residues that were previously predicted to participate in the binding of antagonist <b>1</b> were found to be nonessential. Molecular dynamics based on SAR and mutagenesis identified a critical interaction between the ligand's carboxylate and R253, defining a binding pose where the aromatic core inserts into a hydrophobic cleft between TM6 and TM7. This interaction supports a minimally orthosteric antagonist mechanism. Compound <b>11</b> demonstrated oral efficacy in reversing mechanoallodynia in mice. Additionally, a selective P2Y<sub>14</sub>R agonist, 2-thiouridine-5'-<i>O</i>-(α,β-methylene)-diphosphate (MRS2905), caused acute hypothermia in mice, likely via mast cell activation, while antagonists <b>1</b> and <b>11</b> had no such effect. Our study refines the P2Y<sub>14</sub>R antagonist binding model and introduces new drug-like scaffolds with improved solubility and CNS penetration. This work provides a platform for future SAR optimization and virtual screening campaigns targeting P2Y<sub>14</sub>R.
EHPS Conference Grant Report
2025-08-25

In September 2024, the EHPS conference took place in Cascais, Portugal. This report captures the experiences of early career researchers who were awarded grants to attend. We reflect on how the conference expanded our understanding of health psychology, enhanced our confidence in networking, provided opportunities to present our research, and inspired ideas for future projects and collaborations. The conference also allowed us to engage with the latest developments in health psychology from around the world, highlighting the value of international perspectives and building connections across borders. Our experiences demonstrate not only how attending the conference supported our professional growth, but also how the EHPS fosters an inclusive and accessible environment for early career researchers.
Structure and function of the ovipositor of the encyrtid wasp Microterys flavus
2025-08-25

Abstract Background Oviposition is crucial for the reproductive success of parasitoid insects and, hence, ovipositor structure and oviposition behaviour have probably played a central role in their adaptive evolution. However, various mechanical and functional aspects of the musculoskeletal ovipositor system are still not fully understood, especially within the enormously diverse parasitoid wasps, e.g. the minute and understudied Encyrtidae (Chalcidoidea). Some encyrtid wasps are specialized in parasitising insect plant pests and thus play an important ecological and economic role. We have examined all inherent cuticular elements and muscles of the ovipositor of the encyrtid wasp Microterys flavus to improve our understanding of its mechanics and mode of function. We provide a detailed 3D model based on a synchrotron X-ray phase-contrast microtomography (SR-μCT) dataset and have analysed microstructures on the cuticular ovipositor elements by using scanning electron microscopy (SEM). We have also conducted an in vivo documentation of the oviposition process of female M. flavus wasps on their host, the scale insect Coccus hesperidum . Results Based on morphological analyses, we have identified all elements of the musculoskeletal ovipositor system in M. flavus , consisting of two pairs of valvifers, three pairs of valvulae, the female T9 (9th abdominal tergum), and a set of nine paired ovipositor muscles. Three of these muscles (1st valvifer-genital membrane muscle, ventral 2nd valvifer-venom gland reservoir muscle, T9-genital membrane muscle) have only recently been discovered in pteromalid wasps but have not yet been described for encyrtids. Our behavioural analysis of the motion patterns during the various phases of parasitization has elucidated the oviposition process, which consists of penetration of the host’s body, assessment of the host’s internal organs, envenomation, egg deposition, and potential host feeding. Conclusions Based on our studies of the structure of the ovipositor system of the encyrtid wasp M. flavus , we have developed a functional model of the underlying working mechanism of all ovipositor movements observed during the oviposition process, thereby improving our understanding of a possible key trait contributing to the evolutionary success of a highly diverse group of chalcidoid wasps.
A Warm Welcome to MedChem: The Frontiers in Medicinal Chemistry 2025
2025-08-25

The Frontiers in Medicinal Chemistry (FiMC), which represents the largest international Medicinal Chemistry conference in Germany, took place from April 1 st to 4 th , 2025, in Erlangen. The conference was a great success, bringing together more than 200 participants from around 20 countries. The outstanding program of the 4 day conference included 41 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 91 posters were presented in a highly interactive poster session.
Exercise therapy innovations in outpatient mental health care
2025-08-25

Abstract For successful implementation of healthcare interventions, attitudes of healthcare professionals are a key factor. Research in the field of psychological treatment suggests that attitude towards evidence-based practice (EBP) may play a crucial role. However, little research has been conducted on the extent to which this applies to the field of exercise therapy, where there is a strong need for development regarding the dissemination of EBP. A recent pragmatic multisite randomized controlled trial (ImPuls) can serve as an innovative example for the implementation of an evidence-based exercise intervention including behavior change techniques within the outpatient mental health care system in Germany. The aim of the current study was to explore the role of exercise therapists’ attitude towards EBP for an implementation process by identifying relationships with other factors of importance for implementing innovations (e.g., motivation or self-efficacy). Exercise therapists ( n = 26) completed online surveys pre- (week 0) and postintervention (week 24+). Correlation analyses and linear regressions were performed considering a total score for attitude towards EBP as well as mean scores for its subdimensions. The total score was rather positive (mean = 2.58, standard deviation = 0.43) and significantly related to program-specific motivation ( r = 0.64, p &lt; 0.001), self-efficacy ( r = 0.42, p &lt; 0.034), and acceptance ( r = 0.56, p &lt; 0.003) at baseline. Exercise therapists’ education and further training should therefore have an increased focus on EBP, including the usage of scientific findings, the integration into routine practice and the scopes and obligations that come along with it.
The Circulation of Yersinia pestis in Central Eurasia before and during the First Plague Pandemic (Second to Eighth Century CE): Palaeogenetic and Historical Evidence and Sociopolitical, Ecological, and Climatic Factors
2025-08-25

Abstract Modern Yersinia pestis genomes show the greatest diversity of the plague pathogen in Central Eurasia. This region is now widely linked to the origins of the Y. pestis lineages responsible for two historic plague pandemics: one starting with the so-called “Justinianic Plague” of the mid-sixth century and the other with the “Black Death” of the mid-fourteenth century. These pandemics have mostly been studied in the Mediterranean region and Europe. Although the beginning of the latter is clearly defined both geographically and temporally, the early spread of the former has received less attention, despite being the focus of several competing hypotheses. Here, we build on recent discoveries of Y. pestis in late antique human remains from Central Eurasia and Europe. These findings identified an early victim of the Y. pestis lineage in Central Eurasia, centuries before it appeared in Europe during the Justinianic Plague. We contextualize these analyses with (I) what we can reconstruct from archaeological, written, and paleoclimate evidence about the demographic, economic, environmental, and mobility (human and animal) histories of the region in the earliest centuries CE, and (II) written evidence for epidemic disease from the region and neighboring areas, which may be linked to the spread of the plague before, during, and after the Justinianic Plague. Specifically, we examine sources to establish and evaluate hypotheses about how, why, and if the plague spread from Central Eurasia, ultimately causing the Justinianic Plague and the “First Plague Pandemic,” and how significantly Eurasian populations were impacted over these centuries. Despite extensive source analysis, limited information, especially palaeogenomic data, prevents us from definitively pinpointing the immediate origin of the First Plague Pandemic. Still, most evidence strongly suggests that the Y. pestis lineage originated from Central Eurasia.
CRISPR/Cas9 TCR-Edited NKp30 CAR T Cells Exhibit Superior Anti-Tumor Immunity to B7H6-Expressing Leukemia and Melanoma
2025-08-25

Chimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens on normal hematopoietic stem cells or tissues. As the stress-induced B7H6 molecule is rarely found on normal tissues but expressed on many cancers including AML and melanoma, the NKp30-ligand B7H6 emerges as a promising target for NKp30-based CAR T therapy for these tumors. In this study, we report a comprehensive B7H6 expression analysis on primary AML and melanoma as well as on different tumor cell-lines examined by RT-qPCR and flow cytometry, and efficient anti-tumor reactivity of NKp30-CAR T cells to AML and melanoma. To overcome limitations of autologous CAR T-cell fitness-dependent efficacy and patient-tailored production, we generated CRISPR/Cas9-mediated TCR-knockout (TCRKO) NKp30-CAR T cells as an off-the-shelf approach for CAR T therapy. Functional studies comparing NKp30-CD28 CAR or NKp30-CD137 CAR TCR+ and TCRKO T lymphocytes revealed superior anti-tumoral immunity of NKp30-CD28 CAR TCRKO T cells to AML and melanoma cell lines in vitro, and effective control of tumor burden in an NSG melanoma-xenograft mouse model. In conclusion, these findings highlight the therapeutic potential of NKp30 CAR TCRKO T cells for adoptive T-cell therapy to B7H6-expressing cancers, including melanoma and AML.