julilili42/papers huggingface dataset:
Investigating PRDM8 DNA Methylation in Peripheral Tissues in Borderline Personality Disorder: Association with Symptom Severity but Not Adverse Childhood Experiences
2025-08-30

Background: Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. DNAm is increasingly being investigated as a molecular link between environmental exposures such as ACE and psychiatric outcomes. Differential DNAm of the gene PR domain zinc finger protein 8 (PRDM8), a histone methyltransferase, has recently been reported to be sensitive to early life trauma. Its role in BPD, especially in the context of ACE, remains to be elucidated. Methods: This study investigated DNAm patterns of PRDM8 in peripheral blood and saliva obtained from BPD patients undergoing Dialectic Behavioral Therapy (DBT) compared to healthy control (HC) participants. Associations with ACE and BPD symptom severity were assessed, and therapy-related changes in DNAm were examined. Results: At baseline, BPD patients demonstrated significant hypomethylation of PRDM8 in blood relative to the HC group. Following DBT, a nominally significant increase in DNAm was observed, aligning with inversely correlated symptom severity. No significant differences in saliva were detected. ACE was not associated with PRDM8 DNAm. Conclusions: Our findings suggest that PRDM8 DNAm might be associated with BPD and therapeutic intervention but not with ACE. Together with prior research, the results underscore the importance of future investigation of gene–environment interactions and the functional significance of PRDM8 regulation in the pathophysiology of BPD.
Graft Arteritis Due to Candida Spp. After Kidney Transplant: A Systematic Review of Individual Cases
2025-08-30

Abstract Background Graft arteritis due to Candida species (GAC) is a rare but life-threatening complication in kidney transplant recipients. This systematic review examines its clinical profile and outcomes. Methods A PRISMA-compliant systematic review was conducted. Cases of GAC in kidney transplant recipients were identified and analyzed for clinical characteristics and outcomes. Results Sixty-one patients from 31 studies were included. Median time to infection was 30 days (IQR: 12–60 days) post-transplant. Common symptoms included fever (41.5%) and abdominal pain (33.9%). Aneurysmal rupture occurred in 49.1%, often linked to early presentation. Surgical intervention, mainly external iliac artery ligation, was required in most cases. Mortality was 22.9% and was associated with candidemia and a significantly shorter interval between transplantation and clinical presentation. Conclusions GAC typically occurs early after kidney transplantation, with high rates of aneurysmal rupture and mortality.
The Phoneme as a Cognitive Tool
2025-08-31

Abstract All of the world's spoken languages make consistent use of a relatively narrow set of contrastive speech sounds—phonemes. Here, we argue that phonemes constitute cognitive tools, supporting, guiding, and extending speaker cognitive capacities. We outline commonalities between phonemes and other cognitive tools, which include tendencies in their usage based on biological constraints, their extensive variation across cultural lineages, their criticality to the efficient transmission of information, and their importance in the scaffolding of various cognitive capacities. Studies of the commonalities of phonological systems reveal the physical and biological underpinnings upon which the tools of phonemes are necessarily predicated, and the constraints on their cross‐cultural refinement. Our view complements cognitive linguistic perspectives on other cognitive tools, and on human perception and consciousness more broadly, by emphasizing the sounds of speech themselves.
IDEAL GENOM: Integrated Downstream Analytical Pipeline for Genomic Analysis
2025-08-31

Background: Since the release of the first human genome draft, there has been an exponential increase in the development of technologies that have offered unprecedented opportunities to unravel the genetic underpinnings of rare and complex diseases. However, despite the progress, the challenge persists. This includes the need for developing efficient computational tools to analyse large genomic datasets. The availability of clinical information, along with the development of cost-effective arrays that can scan hundreds of thousands of patients and healthy subjects to identify underlying risk variants, necessitates the development of tools that can streamline and automate the processing of millions of genetic markers. Results: To address this challenge, we present IDEAL-GENOM (Integrated Downstream Analytical Pipeline for Genomic Analysis), a Python-based framework designed to streamline the analytical workflow commonly implemented in genome-wide association studies (GWAS) settings. IDEAL-GENOM integrates widely used tools such as PLINK and GCTA along with custom-developed functionalities, enabling reproducible results through parameter sharing. Initial testing demonstrates that our framework reduces quality control processing time by 10\\%, requiring minimal user intervention. Additionally, IDEAL-GENOM supports both local and cloud-based environments, enhancing its accessibility and scalability. Conclusions: IDEAL-GENOM pipeline offers a simplified GWAS pipeline that will allow beginners and advanced users to leverage the in-built functionalities to perform GWAS analysis for complex diseases.
Unravelling the Link Between Body Mass Index and Cognitive Performance in Individuals With Bipolar Disorder and Exploration of PRS Moderation Effect: Findings From the PsyCourse Study
2025-08-31

ABSTRACT Introduction Bipolar disorder (BD) is a severe mental disorder characterized by extreme mood swings, often accompanied by metabolic comorbidities, such as cardiovascular disease, which increase mortality and reduce quality of life. Both metabolic dysfunctions and BD are associated with cognitive dysfunction. Body mass index (BMI) is closely linked to metabolic health and cognitive performance. This study examined the link between BMI and cognitive function in individuals with BD and how genetic factors, namely polygenic risk scores (PRS) for BD and BMI, might influence this link. Methods Genetic (PRS scores) and phenotypic data (sociodemographic factors, clinical symptoms and cognitive function) of 341 adult patients with BD diagnosis from the PsyCourse Study, a large, multi‐site, and naturalistic longitudinal study, were utilized for this study. First, we performed univariate and multivariate regression analyses to investigate associations between BMI and cognitive performance. Second, moderation analyses were conducted to examine the potential moderator effects of BD‐PRS or BMI‐PRS in the relationship between BMI and different cognitive outcomes. Results BMI was associated with processing speed (TMT‐A) and executive function (TMT‐B), with individuals with higher BMI showing poorer performance. Moderation analyses revealed that the effect of BMI on cognition was moderated by BD‐PRS only regarding the processing speed. BMI‐PRS did not moderate the association between BMI and cognitive variables. Conclusions Our findings indicate that the relationship between BMI and cognitive impairment in BD is partially moderated by BD genetic liability but not by BMI genetic load.
Brain-wide organization of intrinsic timescales at single-neuron resolution
2025-08-31

Variations in intrinsic neural timescales across the mammalian forebrain reflect the anatomical structure and functional specialization of brain areas and individual neurons. Yet, the organization of timescales beyond the forebrain remains unexplored. We analyzed intrinsic timescales of single neurons across the entire mouse brain. Median timescales were up to fivefold longer in the midbrain and hindbrain than in the forebrain. Spatial patterns of gene expression predicted timescale variation at a resolution finer than brain-area boundaries. Across neurons, the diversity of timescales revealed a multiscale architecture, in which fast timescales determined regional differences in medians, while slow timescales universally followed a power-law distribution with an exponent near 2, indicating a shared dynamical regime across the brain consistent with the edge of instability or chaos. These organizing principles for the dynamics of single neurons across the brain provide a foundation for linking cellular activity with regional specialization and brain-wide computation.
Gender in elections: The consequences of killing women activists
2025-09-01

Violence against social activists is a global phenomenon, increasingly prevalent in democratic and conflict-affected states. Violence targeting women activists, in particular, highlights the intersection of gender-based discrimination and the risks associated with activism. We theorize that the killings of women activists reduce both women’s motivation to run for office and voters’ willingness to elect women candidates, driven by fears of further retaliation from armed groups and a demand for protective masculine norms in politics. Using novel fine-grained data on violence against activists, we demonstrate that the killings of women activists in Colombia decrease women’s candidacies and lower voter support for women in mayoral elections. Additional analyses suggest that women’s visibility during peace negotiations and prior territorial control by left-wing FARC rebels mitigated this effect, emphasizing how variation in gender norms can alter the political consequences of violence. Our findings reveal that considering the gender of victims offers important insights into how exposure to political violence influences democratic elections.
The Diverse Reactions of Butterflies and Zygaenids (Lepidoptera) to Climate Change—A Large Scale, Multi‐Species Study
2025-09-01

ABSTRACT Aim An extensive dataset was used to decipher the different responses of 46 species of butterflies and Zygaenids (Lepidoptera) to climate change. The study included more than 1.5 million observations from four databases in Europe, with a south–north extension of about 1200 km from south‐eastern France, via Switzerland and Baden‐Württemberg (Germany) to Brandenburg (Germany). Altitude information was only available for France and Switzerland. Location Europe. Time Period 1894 to 2022. Taxa Studied Lepidoptera, 46 species. Methods Linear models were used to investigate the change over time of the beginning, median, and end of the flight period, as well as the change in altitude. The length of the flight period and the altitudinal range of two time periods were compared. Distribution curves were interpreted with respect to changes in voltinism. Results The beginning and the median of the flight period were increasingly earlier in 100% of the significant changes, while the end of the flight period was later in 69%. Below a mean altitude of about 1000 m, species were more likely to change phenology, while above 1500 m, altitude shift was more likely. In terms of voltinism, 47% of the distribution curves showed no change, 27% a major shift from one generation to another, 20% an additional generation, and 6% a merging of generations. Main Conclusion Four major responses to climate change were identified: no response (6 species in France, 5 in Switzerland), change in phenology (19 in France, 13 in Switzerland), change in altitude (11 in France, 21 in Switzerland) and change in both (2 in France and 7 in Switzerland). This study provides evidence that the response of Lepidoptera to climate change is variable and that these responses differ not only between species but also between regions. Ecological traits are used to discuss these differences in the species considered here.
Enhanced Lieb-Robinson bounds for commuting long-range interactions
2025-09-01

Recent works have revealed the intricate effect of long-range interactions on information transport in quantum many-body systems: In D spatial dimensions, interactions decaying as a power-law r−α with α &amp;gt; 2D + 1 exhibit a Lieb-Robinson bound (LRB) with a linear light cone and the threshold 2D + 1 is sharp in general. Here, we observe that mutually commuting, long-range interactions satisfy an enhanced LRB of the form t r−α for any α &amp;gt; 0, and this scaling is sharp. In particular, the linear light cone occurs at α = 1 in any dimension. Part of our motivation stems from quantum error-correcting codes. As applications, we derive enhanced bounds on ground state correlations and an enhanced local perturbations perturb locally principle for which we adapt a recent subharmonicity argument of Wang-Hazzard. Similar enhancements hold for commuting interactions with stretched exponential decay.
Digital Outcomes of Upper Limb Ataxia Capture Meaningful Longitudinal Change and Treatment Response
2025-09-01

Abstract Background Digital‐motor outcomes promise better responsiveness than clinician‐reported outcomes in ataxia trials. However, their patient meaningfulness and sensitivity to change remain to be demonstrated, particularly in the upper limb domain. Objectives Validation of quantitative motor (Q‐Motor) assessment for upper limb ataxia against patient‐reported outcomes and regarding sensitivity to both longitudinal and treatment‐induced change, the latter in n‐of‐1 treatment settings. Methods Single‐center longitudinal assessment of finger tapping, diadochokinesia, grip‐lift, spiral drawing, and target reaching in (1) 36 cross‐genotype ataxia patients and 20 controls, validating digital measures for correlations with patient‐reported outcome measure (PROM)‐ataxia, 2‐weeks test–retest reliability, and sensitivity to change within a trial‐relevant 1‐year follow‐up, anchored in Patient Global Impression of Change (PGI‐C); and (2) two patients with spinocerebellar ataxia type 27B (SCA27B) on versus off treatment with 4‐aminopyridine. Results Twenty‐four digital measures correlated with the PROM‐ataxia upper‐limb composite (|ρ| = 0.4–0.7) and had excellent test–retest reliability (ICC = 0.91–0.99). Correlations to individual PROM‐ataxia items were specific for functional impairment the respective measure was hypothesized to capture. Speed of finger tapping and diadochokinesia, and smoothness of target reaching (spectral arc length of movement in three dimensions [SPARC 3D ]) captured 1‐year progression in ataxia patients (| r prb | = 0.38–0.51), and specifically in patients with worsening PGI‐C. Estimated sample sizes to detect longitudinal change were lower for digital than clinical outcomes (SPARC 3D : n = 33, Scale for the Assessment and Rating of Ataxia (SARA): n = 79, nine‐hole peg‐test: n = 214). Speed of diadochokinesia, stability of grip‐lift, and variability of target reaching captured treatment responses to 4‐aminopyridine in SCA27B, exceeding minimal detectable and minimal important change. Conclusion Digital upper limb measures capture patient‐meaningful 1‐year longitudinal and treatment‐induced change, and are therefore promising outcomes for upcoming ataxia trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Hominin glacial-stage occupation 712,000 to 424,000 years ago at Fordwich Pit, Old Park (Canterbury, UK)
2025-09-01

Abstract Few high-latitude archaeological contexts are older than marine isotope stage (MIS) 15 and even fewer provide evidence of early human occupation during a glacial period. New discoveries at Old Park, Canterbury (UK), provide evidence of both the oldest accessible artefact-bearing sediment in northern Europe and cold-stage adaptation. Radiometric and palaeomagnetic dating places the earliest suggested occupation of this site between 773 thousand years ago (ka) and 607 ka, with hominin presence inferred during MIS 17–16. Two additional artefact-bearing stratigraphic units, dated to around 542 ka and 437 ka, strongly align with the MIS 14 and 12 cold stages, respectively. The latter unit contains convincing evidence of glacial-stage occupation by Acheulean hominins; fresh, unabraded flakes (including biface-thinning) between clearly defined glacial-aged sediments displaying mixed grassland palaeoenvironmental evidence. An historically collected assemblage of more than 330 handaxes is argued to be derived from both the MIS 17–16 and MIS 12 sediments, providing evidence of the earliest known Acheulean bifaces in northern Europe, and re-occupation by Acheulean populations 200,000 years later. Together, Old Park provides evidence for Lower Palaeolithic hominins reoccupying a location over several mid-Pleistocene MIS cycles, early human presence above 51° latitude during a glacial stage and handaxe production in northern Europe from MIS 17 to 16.
Minimum Compliance in Local Policy Implementation in Contemporary China: The Case of Municipal Solid Waste Management
2025-09-01

Abstract Environmental governance, often characterized as a tug-of-war between central ambitions and local reluctance, provides a valuable lens for examining the dynamics of China’s central–local relations and their impact on policy processes, enhancing our understanding of both the changes and continuities of the Xi Jinping era. By analysing the eco-transformation of waste management through the framework of political steering theory, this article presents a nuanced avoidance strategy used by local governments, which we term minimum compliance. This strategy allows local authorities to cope with and sidestep centrally mandated policies while avoiding the consequences of policy failure. This study enriches the discourse on China’s central–local relations by exploring why top-level design has not reduced policy implementation deviations. It also highlights how local governments in the Xi era evade policy responsibilities in their daily operations and hedge against political pressure.
C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC‐Derived Microglia and Modulates Glial‐Neuronal Crosstalk
2025-09-01

ABSTRACT The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type‐specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)‐derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single‐cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC‐derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia‐driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.
Metareference in Videogames
2025-09-01

Taking an original, in-depth approach, this book investigates the forms and functions of metareference in videogames. Drawing on a rich body of research in game studies, transmedial narratology, and neighbouring disciplines, the author combines detailed close-reading-style analyses of the indie games <i>What Remains of Edith Finch</i>, <i>The Magic Circle</i> and <i>OneShot</i> with a breadth of examples and systematic analyses that span multiple genres as well as several decades of videogaming. In doing so, the book maps different metareferential elements that can be found in videogames and proposes an original model for their analysis, while showcasing the complex interrelations among different metareferential elements in contemporary videogames. This book will appeal to videogame researchers and transmedial narratologists as well as to those interested in metaization in media and popular culture across disciplines.
Bifidobacteria-derived exopolysaccharide promotes anti-tumor immunity
2025-09-01

While several phylogenetically distinct bacterial taxa can predict responses to or improve cancer immunotherapies, the underlying mechanisms remain poorly understood. The use of microbes for microbial therapeutics is currently under intense research, yet safety and regulatory hurdles remain challenging. Thus, non-replicative bacterial-derived molecules or extracts provide promising alternatives. We have identified exopolysaccharides (EPSs) from two bacterial species-Bifidobacterium pseudolongum and Bifidobacterium pseudocatenulatum-that promote anti-tumor immunity. EPS improved Th1 T cell immunity, which was further boosted by the metabolite inosine. Mechanistically, EPS was sensed by dendritic cells in a Tlr2-MyD88-dependent manner, which induced interleukin (IL)-12 and tumor necrosis factor (TNF)-α. Both cytokines were required for T cell-dependent killing of tumor cells in murine colon cancer models. EPS stimulated IL-12 production through Toll-like receptor 2 (TLR2) in human dendritic cells and promoted cell death in patient-derived colon cancer organoids through immune cells. Collectively, our study identifies microbe-derived EPS as an adjuvant immunotherapy in cancer.
Competing Modes of Hydrogen Activation in Singlet Pyridinylidenes: π-Approach vs σ*-Approach Reaction Pathways
2025-09-01

Carbenes are promising reagents for the transition metal-free activation of molecular hydrogen. Depending on their multiplicity and electron configuration, carbenes can access different hydrogenation reaction mechanisms, with singlet carbenes usually leading to geminal hydrogenation products <i>via</i> a π-approach trajectory. Our group has recently prepared 1-iodopyridine-2-ylidene, <b>1-I</b>, introducing a new class of singlet <i>N</i>-heterocyclic carbenes featuring σ/σ* instead of the usually encountered σ/π frontier orbitals. Carbene <b>1-I</b> reacts with H<sub>2</sub> <i>via</i> a unique sideways σ*-approach, leading to pyridinium iodide formation with N-I bond cleavage. This study investigates how nitrogen substituents with varying bond strengths (I < Br < Cl < OCF<sub>3</sub> < OMe < NMe<sub>2</sub> < F < Me) influence the electronic structure of the carbene and its preference for σ*- or π-approach hydrogenation. Using high-accuracy DLPNO-CCSD(T) and NEVPT2 computations, we find that I-, Br-, Cl-, and OCF<sub>3</sub>-substituted pyridinylidenes adopt a σ<sup>2</sup>σ<sup>*0</sup> configuration and favor σ*-approach hydrogenation. In contrast, OMe-, NMe<sub>2</sub>-, and Me-substituted carbenes exhibit a σ<sup>2</sup>π<sup>0</sup> configuration and lower barriers for the π-approach hydrogenation. Interestingly, the fluorine-substituted carbene assumes a σ<sup>2</sup>π<sup>0</sup> electron configuration yet still preferentially undergoes σ*-approach hydrogenation.