julilili42/papers huggingface dataset:
Prospective associations between diabetes and depressive symptoms across European regions: a secondary analysis of ELSA, TILDA, and SHARE datasets
2025-09-29

Abstract This article investigates predictive associations between diabetes and depressive symptoms across Ireland, the United Kingdom, and four European regions. The data were obtained by merging datasets from three large prospective cohort studies—the English Longitudinal Study on Ageing, The Irish Longitudinal study on Ageing, and the Survey on Health, Ageing and Retirement in Europe. We first applied a survival analysis design to two samples of 43 061 and 35 993 participants, investigating elevated depressive symptoms as a risk factor for diabetes, and diabetes as a risk factor for elevated depressive symptoms, respectively. We next applied a multilevel modeling approach to examine depressive symptoms before, during, and after diabetes onset across 101 799 participants. We found a bidirectional association between diabetes and depressive symptoms; however, the strength of these associations did not significantly differ between the regions (P &amp;gt; .01). The results also showed that individuals with newly diagnosed diabetes consistently reported higher depressive symptoms than those without diabetes, even before diagnosis. However, we observed no country-specific differences in the gradual changes in depressive symptoms regardless of participants’ diabetes status. Diabetes at baseline was associated with higher risk of developing depression; and vice versa. These associations were not moderated by geographical location. Therefore, the risks of diabetes and depressive symptoms comorbidity seem to be equal across all observed geographic regions.
Intraoperative Techniques for Language Mapping in Brain Surgery: A Comparison Between Direct Electrical Stimulation (DES) and Electrocorticography (ECoG)
2025-09-29

ABSTRACT Purpose The purpose of this overview is to compare Direct Electrical Stimulation (DES) and Electrocorticography (ECoG) techniques, assessing their respective strengths, limitations, and roles in ensuring successful language mapping during awake brain surgeries. Method This overview aims to compare two techniques used in intraoperative language mapping during awake brain surgery: Direct Electrical Stimulation (DES) and Electrocorticography (ECoG). By summarizing recent advances in both methods, we highlight their respective mechanisms, applications, and roles in improving surgical outcomes. DES is widely considered the gold standard for cortical brain mapping and is applicable in both awake and anesthetized surgeries for treating epilepsy and brain tumors. In contrast, ECoG involves monitoring the brain's electrical activity with or without direct stimulation, as it provides valuable insight into high gamma activity (70–150 Hz), which is strongly associated with speech production. Finding ECoG offers a high‐resolution approach to language mapping by detecting high‐gamma activity, reducing the risk of intraoperative seizures, and serving as a complementary or alternative tool to DES in specific clinical scenarios. While DES continues to be the most reliable technique for identifying functional brain areas, it does carry a higher risk of inducing seizures. Furthermore, recent advancements in ECoG‐based speech decoding and brain–computer interfaces (BCIs) underscore the growing potential of ECoG in restoring communication in patients with severe language impairments, extending its applications beyond surgical mapping. Conclusion In conclusion, while DES remains the gold standard for intraoperative language mapping, ECoG is emerging as a promising complementary or alternative technique in some clinical cases. This overview highlights the evolving role of ECoG, particularly in the context of speech decoding and BCIs, offering new possibilities for improving surgical outcomes and postoperative quality of life in patients.
The Exploitation of Cultivated and Wild Plants during the Kingdom of Dongola (14th–18th Centuries CE): Archaeobotanical Evidence from Old Dongola, Northern Sudan
2025-09-29

Old Dongola in northern Sudan, with a history dating back to the 5th century, was the capital of the Christian Kingdom of Makuria, one of the three medieval Nubian kingdoms. Following the collapse of Makuria in the 14th century, the city underwent significant cultural and social transformations, marked by migration of Arab tribes and the rise of new power structures. during the 16th and 17th centuries, Old Dongola served as the seat of a local ruler under the Funj Sultanate, reflecting its integration into wider Islamic governance. This period saw the emergence of diverse communities, shaped by the interplay of religious conversion, migration, and political changes. Here we present new archaeobotanical findings obtained through the application of a systematic sampling by collecting sediments from each excavated context, and a recovery strategy which combined flotation and dry sieving at the citadel of Old Dongola in northern Sudan. Our archaeobotanical results, spanning the Kingdom of Dongola and the Funj periods (14th–18th centuries), shed light on the development of dietary habits of the inhabitants of the city, which primarily revolved around cereals like sorghum, pearl millet, barley, and wheat, supplemented by crops such as purslane and fruits including watermelon, dates, grapes, and figs. Furthermore, the analysis of plant remains provided insights into the consumption of pulses such as cowpea and grass pea. Importantly, the discovery of imported plants, including tobacco seeds, underscores the significance of Old Dongola in the ancient world’s trade networks. These findings greatly enhance our understanding of subsistence practices and the utilisation of economic and medicinal plants in the region.
Effects of therapy with local anesthetics (TLA) on heart rate variability (HRV) over 24 hours
2025-09-29

Therapy with local anesthetics (TLA) is known to provide long-lasting pain relief, raising the question of whether these effects are mediated by changes in autonomic nervous system (ANS) regulation. To address this, we examined alterations in 24-h heart rate variability (HRV) following TLA treatment. Twenty-four patients undergoing TLA and 11 controls were monitored with Holter-ECG over 24 h. HRV parameters including mean heart rate (HR), root mean square of successive differences (RMSSD), stress index (SI), low- and high-frequency power, and total power were calculated in 15-min epochs. Changes were analyzed separately for the day and subsequent night, and the standard deviation of change between consecutive 15-min intervals was introduced as an additional parameter. TLA was associated with significant shifts in HRV within 24 h: HR and SI decreased, whereas RMSSD and low-frequency power increased, with effects most pronounced during the night. Moreover, the variability of changes between epochs was reduced across several parameters, particularly HR, RMSSD, and SI, suggesting a "smoothing" effect in HRV dynamics. These findings indicate that 24-h HRV monitoring can capture autonomic effects of TLA beyond its immediate analgesic action. The reduction of variability in HRV changes introduces a novel metric for assessing ANS modulation, offering new insight into the mechanisms and therapeutic potential of TLA.
Designing Limes Text: Adapting an Educational Video Game into a Text-Based Format for Controlled Experimental Comparisons
2025-09-29

Comparing educational video games and text-based learning presents a significant challenge when trying to ensure a fair comparison between the two formats. Their distinct natures, particularly in terms of engagement and interactivity, introduce uncontrolled variables that are often not directly comparable between a video game and a text. Many prior studies rely on static text conditions that do not account for reader engagement, decision-making, or interaction patterns. This paper therefore proposes a structured game design approach to developing a text-based application that enables a more precise and controlled comparison with video game-based learning. Limes is a 2D educational video game set in Roman frontier Germany, designed to teach historical knowledge through exploration and interactive learning elements. The game features a structured narrative, Codex entries with historical information, and secondary missions, all contributing to the player's engagement and learning experience. The text version of Limes is not a game but replicates key gameplay characteristics in a structured text-based format, providing an alternative to traditional text conditions in experimental research. Unlike passive reading conditions, this Text-app is designed to be interactive and engaging in the same ways as its video game counterpart. Moreover, like the video game, the Text-app tracks player behaviour, such as time spent reading, engagement with Codex entries, and whether secondary mission texts have been read, using a five-star rating system mirroring the game’s assessment mechanics. The present paper discusses the development of the Limes Text-app and presents a game design framework for adapting educational games into experimentally viable text-based counterparts. The contribution is particularly relevant to research on video game effects in education adopting experimental designs. However, beyond its experimental utility, the newly developed text-app offers promising opportunities for other research areas, and we discuss how it can, for example, be used to assess and explore digital traces of learner characteristics and behaviours. To conclude, by ensuring structural comparability and capturing interaction data across formats, the Limes Text-app addresses a key methodological challenge in video game-based learning research: the difficulty of creating valid text-based control conditions that enable meaningful comparisons. While Limes has been developed in the context of history education, the impact is much broader as our design framework is adaptable and could be extended to other domains and narrative-based games.
Insights into plant-microbe interactions in urban rhizosphere: feedback from Quercus cerris L. root morphology, soil zymography, and microbial community composition in rhizobox system
2025-09-29

Urbanization can have a substantial impact on rhizosphere activity by generating a hostile environment that hinders plant resource uptake. To study the effects of urbanization on plant-microbe interactions, Quercus cerris L. seedlings were cultivated in rhizoboxes with soil collected from non-urban, peri-urban, and urban forest sites in Campobasso, Italy. Urban and peri-urban soils showed higher enzyme activity, attributable to their nutrient content, that also caused root structural changes, modeling microbial communities. In particular, an increase in root diameter was found in urban and peri-urban soils while plants developed a root system ideal for exploring and/or exploiting the non-urban soil. Microbial community analysis revealed a higher number of phyla associated with cellular processes in non-urban soils while peri-urban and urban soils were dominated by phyla involved in metabolic pathways. This approach provides a framework for studying plant-microbe interactions, offering valuable insights to enhance urban area health and resilience.
High-Dimensional Spatiotemporal Single-Cell and 3D Atlas of the Bone Marrow Microenvironment during Leukemic Progression
2025-09-29

Abstract The bone marrow microenvironment (BMME) is essential for hematopoiesis and immunity, yet spatiotemporal single-cell analysis during leukemogenesis remains challenging. We characterized the BMME in femurs from wild-type and chronic myeloid leukemia (CML) mice at 7, 14 and 21 days post-induction by highly multiplexed and 3D microscopy. Using a 54-marker CODEX panel, we profiled 2,033,725 cells in 55 tissue regions of interest and identified 41 cell types through unsupervised clustering and supervised annotation. During leukemic progression, we observed an expansion of myeloid and progenitor cell populations, increased PD-L1 + leukemic cells, the upregulation of PD-1 on CD4 + and CD8 + T cells, and a profound loss of B cells, plasma cells and bone cells. Advanced CML exhibited a striking expansion of immature, pericyte-deficient vasculature that disrupted vascular niches and impaired hematopoietic stem/progenitor cell positioning. Spatial mapping revealed leukemia-specific cellular neighborhoods enriched in PD-1 + CD8 + T cells, suggesting localized immune cell exhaustion. Early-stage CML showed increaseds between plasmacytoid dendritic cells and megakaryocytes, whereas advanced CML featured heightened megakaryocyte emperipolesis of non-leukemic granulocytes. Megakaryocytes were morphologically irregular in CML mice and BM trephine biopsies from CML patients. Laser-capture microdissected megakaryocytes from newly diagnosed CML patients had reduced expression of cytoskeleton genes, which was reversed in advanced cases treated with tyrosine kinase inhibitors. 3D imaging revealed vascular disorganization and depleted megakaryocytes in the diaphysis, underscoring region-specific pathology. Together, this study provides a spatiotemporal single-cell atlas of the BMME during leukemic progression, showing how leukemic cells reprogram the niche to support their expansion and immune evasion.
IgM, IgG, and IgG Subclass Antibody Responses to Plasmodium falciparum Proteins in Naïve, Malaria-Vaccinated and Semi-Immune Volunteers after Controlled Human Malaria Infection
2025-09-30

The immune response to malaria vaccines is generally stronger in malaria-naive individuals than in those with lifelong exposure. The immunological basis for this is unclear. IgM, total IgG, and IgG subclass (IgG1, IgG2, IgG3, and IgG4) antibody responses against 21 pre-erythrocytic and erythrocytic Plasmodium falciparum proteins before and after controlled human malaria infection (CHMI) via the direct venous inoculation of 3,200 P. falciparum sporozoites (PfSPZ) were compared in three groups of volunteers: 1) malaria-naïve ( n = 22); 2) malaria-naïve immunized with a PfSPZ chemoattenuated vaccine (PfSPZ-CVac) ( n = 27); and 3) lifelong malaria-exposed individuals from Africa ( n = 20), including those with normal hemoglobin ( n = 11) or sickle cell trait ( n = 9). Before and after CHMI, PfSPZ-CVac-immunized individuals exhibited higher levels of IgM and IgG to CSP and SSP-2/TRAP than the other two groups. Malaria-experienced Africans exhibited more intense and broader antibody responses to blood-stage (BS) antigens than naïve and vaccinated individuals, longer pre-patent periods (PPPs), and fewer symptoms. Among confirmed malaria cases, cytophilic IgG1 and IgG3 antibodies to BS antigens were positively associated with longer PPPs, whereas IgG2, IgG4, and IgM were not. IgG2 and IgG4 (noncytophilic) P. falciparum -specific antibodies were higher in the semi-immune group, including elevated anti-CSP IgG4 (regulatory) levels. The IgM response in African volunteers post-CHMI was stronger than that in malaria-naïve and vaccinated individuals and had the hallmark of a secondary memory response. Cytophilic immunoglobulins controlled parasitaemia better than noncytophilic immunoglobulins. However, elevation of the latter in lifelong malaria-exposed individuals could be associated with regulatory responses and hamper vaccine efficacy.
Sealing and the Root kh-t-m in the Qurʾān and pre-Islamic Christian Literature: On the “Seal of the Prophets” and Disbelievers Having “Seals on Their Hearts and Hearing”
2025-09-30

Abstract This study examines two Qurʾānic concepts expressed through the root kh-t-m : “the seal of the prophets” and disbelievers “having seals on their hearts and hearing” in light of pre-Islamic Christian and particularly Syriac literature. It suggests that both concepts entered the Qurʾān via the Syriac cognate of kh-t-m , ḥ-t-m , albeit in different ways: whereas Syriac interpretations of Isaiah 8:16, Daniel 9:24, Matthew 5:17–18, and Luke 24:44, found in the Diatessaron, the Peshitta, and works of Syriac theologians, informed the Qurʾānic conception of “the seal of the prophets,” it was the Syro-Hexapla that inspired the concept of disbelievers being sealed by adopting a minority rendering of Isaiah 8:16 from the Septuagint. The study then proposes that the Qurʾānic notion of “sealing the prophets” has a legal dimension, and that the Qurʾān positions Muḥammad as the great lawgiver prophet, ending the line of the prophets who are the recipients of God’s covenants and “laws.” Muḥammad taking on such a role provides him a position comparable to Jesus’s role in the Syriac texts. Moreover, the study demonstrates that discussion of disbelievers “having seals on their hearts and hearing” with the Biblical precursor of disbelievers being sealed fits neatly into the broader context of the Qurʾān, when several phrases with Biblical antecedents become a part of the Qurʾānic discourse.
Poly(vinyl alcohol) cryogels: Effect size of polymer concentration, number of cycles and thawing rate on material properties and dermal drug delivery
2025-09-30

Poly(vinyl alcohol) (PVA) can be physically cross-linked by repeated freeze-thaw (F-T) cycles, resulting in a cryogel. Despite the growing prevalence of the cryogelation process in the scientific literature, its multivariable nature, particularly the individual and synergistic impact of process variables on material properties, remains under-explored. The present work is the first systematic analysis quantifying the effect sizes associated with the influence of the key process parameters polymer concentration, number of cycles and thawing rates within F-T-cycles on the material properties of PVA cryogels as a drug delivery system for dermal applications. The variables analysed showed both positive and negative correlations with Young's modulus, gel strength and calculated mesh sizes of the polymer network to varying degrees. Moreover, it uniquely demonstrates the synergistic combination effects between individual process parameters, revealing mutual influences, that had not been characterized systematically before. The excellent suitability as a dermal drug delivery system was also demonstrated by both comparative drug release and drug permeation through the skin using diclofenac sodium as a model drug. Overall, this study provides the first systematic understanding of the impact of cryogelation process parameters on material properties and introduces a new and simple approach to individual selection of specific cryogelation conditions.
New methods on the block: Taxonomic identification of archaeological bones in resin-embedded sediments through paleoproteomics
2025-09-30

Abstract The integration of biomolecular studies of past organisms with geoarchaeological studies can significantly improve our understanding of the relative chronology and context of archaeologically (in)visible behaviors. However, the complexity and sedimentological heterogeneity of archaeological deposits at a microscopic scale is often not taken into consideration in biomolecular studies. Here, we investigate the preservation and retrieval of paleoproteomic data from bone fragments embedded in Pleistocene resin-impregnated sediment blocks. We show that resin impregnation has minimal effect on skeletal protein taxonomic identifications in modern skeletal material but observe an increase in oxidation of methionines. We then successfully retrieve proteins from resin-impregnated blocks from the Paleolithic sites of Bacho Kiro Cave, La Ferrassie, and Quinçay. The taxonomic identifications of minute bones encased in resin are in line with previous analyses of the faunal communities of these sites, with a diversity of taxa (Bos sp./Bison sp., Equus sp., Ursus sp., and Caprinae) observed at a microscale in Bacho Kiro. This differs from results from La Ferrassie where most of the samples are identified as a single taxon (Bos sp./Bison sp.) across different areas of the site. The block from Quinçay only provided taxonomic identification of two out of eleven bone-derived samples, likely due to diagenesis. Our work indicates that paleoproteomes can be retrieved from bone fragments at a microstratigraphic resolution, enabling the detailed study of faunal community composition at a scale that more closely matches that of past human occupations.
White matter hyperintensities precede other biomarkers in GRN frontotemporal dementia
2025-10-01

Abstract INTRODUCTION Increased white matter hyperintensities (WMHs) have been reported in genetic frontotemporal dementia (FTD) in small studies, but the sequence of WMH abnormalities relative to other biomarkers is unclear. METHODS Using a large dataset ( n = 763 GENFI2 participants), we measured WMHs and examined them across genetic FTD variants and stages. Cortical and subcortical volumes were parcellated, and serum neurofilament light chain (NfL) levels were measured. Biomarker progression was assessed with discriminative event‐based and regression modeling. RESULTS Symptomatic GRN carriers showed elevated WMHs, primarily in the frontal lobe, while no significant increase was observed in symptomatic C9orf72 or MAPT carriers. WMH abnormalities preceded NfL elevation, ventricular enlargement, and cortical atrophy. Longitudinally, baseline WMHs predicted subcortical changes, while subcortical volumes did not predict WMH changes, suggesting WMHs may precede neurodegeneration. DISCUSSION WMHs are elevated in a subset of GRN ‐associated FTD. When present, they appear early and should be considered in disease progression models. Highlights Elevated WMH volumes are found predominantly in symptomatic GRN . WMH accumulation is mostly observed in the frontal lobe. WMH abnormalities appear early in GRN ‐associated FTD, before NfL, atrophy, and ventriculomegaly. Longitudinally, WMH volumes can predict subcortical changes, but not vice versa. WMHs are key early markers in GRN ‐associated FTD and should be included in progression models.
The R&D productivity challenge: transforming the pharmaceutical ecosystem
2025-10-01

The persistent decline in pharmaceutical R&D productivity has been extensively analyzed and debated for over two decades, with profound implications for the structure and strategy of the pharmaceutical industry. This systemic challenge forced many leading companies to adapt their R&D models, influencing internal capabilities and external innovation strategies. In response, the industry has evolved into a complex, interdependent biopharmaceutical ecosystem encompassing large pharmaceutical corporations, biotech innovators and specialized service providers. Although R&D productivity affects all research-driven companies, its consequences are particularly pronounced for large pharmaceutical firms, because the scale and capital intensity of their R&D activities make productivity a crucial determinant of long-term competitiveness and sustainability. By contrast, other stakeholders are only partially adversely affected, whereas some can even obtain value from it.
Efficacy and tolerability of fenfluramine with concomitant potassium bromide in patients with Dravet syndrome.
2025-10-01

This study investigated the combination of fenfluramine (FFA) and potassium BR in treating Dravet syndrome. It was found that it is effective in reducing seizures, but BR levels often went up after starting FFA, which caused side effects like drowsiness in many patients. In some cases, these side effects were serious enough that physicians had to stop either BR or FFA. The study highlights the need for careful monitoring of BR levels when using this combination to avoid potential side effects by reducing the BR dose early if needed.
Time Course of Electrocortical Processing of Food Stimuli in Adolescent Anorexia Nervosa.
2025-10-01

The automated early avoidance indicates a decline in the positive incentive value of high-calorie food, which signals a loss of the appetitive character of these foods. The increased top-down attention towards food may be due to an increased negative emotional salience activating aversive motivational systems.