julilili42/papers huggingface dataset:
Hyperactive-impulsive behavior does not moderate the association between executive function and physical activity in preschoolers
2025-04-21

Abstract Experimental research suggests a positive association between executive function (EF) and physical activity (PA). Observational research examining PA in everyday life does not consistently support this positive association, with findings yielding negative or no associations. Hyperactive-impulsive behavior could act as a possible moderator, explaining inconsistent findings. In this observational study, we examined the relation between EF and everyday PA as well as hyperactive-impulsive behavior as a potential moderator in a sample of 68 German preschoolers (3–5 yrs). As performance-based measured of EF and PA, participants performed a computerized EF test battery in two sessions and wore an accelerometer for 7 days. Parental questionnaires of EF, PA, and hyperactive-impulsive behavior were further implemented. Accelerometer-assessed moderate-to-vigorous PA was negatively related to EF performance, and hyperactive-impulsive behavior did not moderate this association. Neither time spent in any other PA intensity nor parental PA reports were related to EF. The present study represents the first study to investigate if hyperactive-impulsive behavior moderates the association between everyday PA and preschoolers’ EF. Thus, the findings yield new insight into the relation between PA in everyday life and preschoolers’ EF, as the unexpected negative relation could not be explained through hyperactive-impulsive behavior.
Abstract 4592: TERT expression predicts progression-free survival in meningiomas
2025-04-21

Abstract Background: TERT promoter mutation (TPM) is a rare but established biomarker in meningiomas associated with aberrant TERT expression, reduced progression-free survival (PFS), and reduced overall survival. While TERT is highly expressed in tumors with promotor mutations, its expression has also been observed even in tumors with wildtype TERT promoters (TP-WT). This study aimed to assess the prevalence of TERT expression and its association with clinical outcome in meningiomas. Methods: Bulk RNA sequencing (n=604), Sanger sequencing of the TERT promoter (n=1095), and methylation profiling (n=1218) of a multi-institutional cohort of meningiomas (total n=1241) were performed to determine TERT expression, TERT promoter mutation status, and TERT promoter methylation. A cohort of 380 meningiomas from Toronto was used for discovery, and 861 meningioma samples from external institutions were compiled as a validation cohort. Results: TERT expression was significantly higher in meningiomas with TPMs compared to TP-WT. However, TERT was still expressed in 30.4% of meningiomas that lacked TPM. TERT expression increased with higher WHO grades and was associated with shorter progression-free survival, even among TP-WT tumors. WHO grade 1 tumors that expressed TERT had PFS similar to those of WHO grade 2, while WHO grade 2 meningiomas expressing TERT had a PFS similar to those of WHO grade 3 meningiomas. Among grade 3 meningiomas, tumors expressing TERT had PFS similar to those with TPMs. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients at greater risk of rapid progression. These results support the inclusion of TERT expression in risk stratification models and management strategies, including future WHO classification and cIMPACT-NOW molecular testing criteria. Citation Format: Chloe Gui, Justin Z. Wang, Vikas Patil, Andrew Ajisebutu, Jeff Liu, Zeel Patel, Rebeca Yakubov, Ramneet Kaloti, Yosef Ellenbogen, Christopher Wilson, Aaron Cohen-Gadol, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Eric C. Holland, Jill S. Barnholtz-Sloan, Andrew E. Sloan, Craig Horbinski, Silky Chotai, Lola B. Chambless, Andrew Gao, Serge Makarenko, Stephen Yip, Kenneth Aldape, Farshad Nassiri, Gelareh Zadeh. TERT expression predicts progression-free survival in meningiomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4592.
Abstract 6419: Stress-induced intratumoral senescence matrix shifts cancer evolution towards metastasis
2025-04-21

Abstract Despite intensive efforts to improve early cancer detection, to date 30% of all solid tumors are still diagnosed at a metastasized and incurable stage. Molecular mechanisms underlying early metastasis are poorly understood, and thus far there are no strategies to suppress it. Here, using high-plex spatial protein profiling of human and murine tumours as well as functional studies in mouse models, we show that intratumoral microenvironmental stress factors induce senescence of apoptosis resistant tumor cells, resulting in a tumor-interlacing senescence matrix. Single cell RNA sequencing analyses revealed that matrix building cells, designated as stress-induced senescent tumor cells (SITC), harbour a distinct secretory phenotype, which fails to induce a full paracrine senescence phenotype in adjacent cancer cells but instead induces a hybrid senescence/invasion phenotype characterized by intermediate p16 levels and the upregulation of gene sets known to increase invasion and metastasis. Frequency of SITC in human therapy-naïve tumours was found to correlate with their metastatic stage at diagnosis and pharmacological or genetic depletion of SITC markedly reduced metastasis in orthotopic mouse models of colorectal cancer and intrahepatic cholangiocarcinoma. Our data harbours important translational potential, as recurrent pharmacological senolytic or senomorphic treatments hold the promise to eradicate SITC from occult tumors and this way prevent their early metastatic spread, allowing to diagnose more cancers at earlier and potentially curative stages. Clinical trials to address this hypothesis are warranted. Citation Format: Omelyan Trompak, Svenja A. Schütte, Jorge Abreu Macedo, Sophia Scheuermann, Zexi Hu, Igor Minia, Artür Manukyan, Thales Kronenberger, Marcello Zago, Rosanna Krebs, Alice Nuernbergk, Tae-Won Kang, Carlotta Schieler, Liudmyla Taranets, Angel M. Cuesta, Michael Forster, Kristin Bieber, Wolfgang Albrecht, Elke Rist, Can Yurttas, Daniel Dauch, Bettina Weigelin, Bence Sipos, Thomas Longerich, Stephan Singer, Markus W. Löffler, Manfred Claassen, Florian Wimmers, Markus Landthaler, Alfred Königsrainer, Saskia Biskup, Stefan Laufer, Christian M. Seitz, Lars Zender. Stress-induced intratumoral senescence matrix shifts cancer evolution towards metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6419.
Integrative analysis of miRNA expression profiles reveals distinct and common molecular mechanisms underlying broad diagnostic groups of severe mental disorders
2025-04-22

Micro RNAs (miRNAs) play a crucial role as regulators of various biological processes and have been implicated in the pathogenesis of mental disorders such as schizophrenia and bipolar disorders. In this study, we investigate the expression patterns of miRNAs in the PsyCourse Study (n = 1786), contrasting three broad diagnostic groups: Psychotic (Schizophrenia-spectrum disorders), Affective (Bipolar Disorder I, II and recurrent Depression), and neurotypic healthy individuals. Through comprehensive analyses, including differential miRNA expression, miRNA transcriptome-wide association study (TWAS), and predictive modelling, we identified multiple miRNAs unique to Psychotic and Affective groups as well as shared by both. Furthermore, we performed integrative analysis to identify the target genes of the dysregulated miRNAs and elucidate their potential roles in psychosis. Our findings reveal significant alterations of multiple miRNAs such as miR-584-3p and miR-99b-5p across the studied diagnostic groups, highlighting their role as molecular correlates. Additionally, the miRNA TWAS analysis discovered previously known and novel genetically dysregulated miRNAs confirming the relevance in the etiology of the diagnostic groups. Importantly, novel factors and putative molecular mechanisms underlying these groups were uncovered through the integration of miRNA-target gene interactions. This comprehensive investigation provides valuable insights into the molecular underpinnings of severe mental disorders, shedding light on the complex regulatory networks involving miRNAs.
Therapy of early breast cancer: current status and perspectives
2025-04-22

Abstract Medical advancements in breast cancer are truly remarkable. Especially in recent years, numerous new therapeutics have been approved and surgical strategies have been de-escalated for specific patient groups. In the therapeutic setting, CDK4/6 inhibitors as oral maintenance therapy in early breast cancer and immune checkpoint inhibitors (Pembrolizumab) for triple-negative breast cancer (BC) are noteworthy. In the surgical field, prospective randomized controlled trials have currently explored the possibility to deescalate axillary surgery by omitting sentinel lymph node excision (INSEMA, SOUND). As a result, there have been significant improvements in prognosis and a reduction in surgical morbidity for patients. Many exciting trials are underway, and it remains to be seen whether antibody–drug conjugates beyond trastuzumab emtansine, will find their way into the treatment lines for early-stage BC. Furthermore, the integration of artificial intelligence in both diagnostics and treatment recommendation evaluation is a promising area with great potential.
Embolization of Middle Meningeal Artery in Patients with Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis of Randomized-Controlled Clinical Trials
2025-04-22

Background: Chronic subdural hematoma (cSDH) is a common neurosurgical condition, particularly among elderly patients. Middle meningeal artery (MMA) embolization has emerged as a minimally invasive adjunctive treatment aimed at reducing recurrence. However, its comparative efficacy and safety remain under investigation. Methods: In this systematic review and meta-analysis, randomized-controlled clinical trial (RCT) data evaluating MMA embolization combined with best medical therapy (BMT) versus BMT alone in adult patients with symptomatic cSDH were pooled. The primary efficacy outcome was recurrence or progression of hematoma at follow-up. Secondary efficacy outcomes included good functional outcome [modified Rankin Scale (mRS) score ≤ 2], independent ambulation (mRS score ≤ 3), and hematoma thickness at follow-up. The primary safety outcome was all-cause mortality. Procedure-related complications were assessed as a secondary safety outcome. Results: Six RCTs were included, comprising 760 patients treated with MMA embolization and 788 patients treated with BMT alone. MMA embolization significantly reduced recurrence compared to BMT alone (RR: 0.50; 95% CI: 0.37–0.69; six studies; I2 = 0%; number-needed-to-treat = 13). No significant differences were observed in good functional outcome (RR: 1.01; 95% CI: 0.97–1.05; three studies; I2 = 0%), independent ambulation (RR: 1.01; 95% CI: 0.99–1.04; three studies; I2 = 0%), or hematoma thickness at follow-up (SMD: −0.1; 95% CI: −0.3 to 0; four studies; I2 = 42%). All-cause mortality was similar between the two groups (RR: 1.01; 95% CI: 0.42–2.40; five studies; I2 = 44%). The pooled rate of procedure-related adverse events in the MMA embolization-group was 1% (95% CI: 0–3%; two studies; I2 = 35%). Conclusions: MMA embolization significantly reduced cSDH recurrence when used as an adjunct to BMT. However, it did not demonstrate a significant impact on functional outcomes or mortality in this meta-analysis. Further research is needed to identify patient subgroups that benefit most from MMA embolization and to evaluate its impact on cognitive function and quality of life using longer follow-up periods.
Benefits of Explorative Saccade Training in Patients with Advanced Glaucomatous Visual Field Defects—A Randomized, Placebo-Controlled Study
2025-04-22

Purpose: Patients with advanced glaucoma have visual field defects that impair mobility and quality of life (QoL). We aim to determine the effects of exploratory saccade training (EST) in such patients with bilateral overlapping scotomas that affect at least one visual field quadrant. Patients and Methods: This study was approved by the Ethics Committee of the Medical Faculty of the University of Tuebingen, Germany, and was registered in the German Clinical Trials Register (DRKS DRKS00031082, date of approval: 2 February 2023). We randomly assigned 27 patients to two groups, one of which trained with a computer-based EST (group 1). A control group (group 2) first used reading training (rapid serial visual presentation, RSVP, a single-word presentation to minimize eye movements) as placebo training (PRT) in regard to EST, which trains eye movements and, in a later phase, also used EST. Each training method required 6 weeks of home training. Main outcome variables were reaction time (RT) during the EST training sessions, RT during a natural search task (table test), reading speed (RS) during training on the screen, and during reading printed paragraphs aloud. QoL was assessed by a questionnaire. Results: Reaction times during EST and the table test improved significantly, which indicated transfer of the training effect to daily life. RS and QoL were reduced at baseline. Reading training improved RS significantly and reached normal median values. QoL improved significantly in the sub-categories regarding mobility problems in group 1. Patients with inferior field defects were more impaired and improved more than those without inferior field defects. Conclusions: As a supplement to the necessary treatment for glaucoma, EST is an effective home training method for rehabilitation by improving reaction time in daily living tasks for patients with advanced glaucoma. Reading training improved RS while reading from a screen as well as reading printed text.
Self-Other Generalisation Shapes Social Interaction and Is Disrupted in Borderline Personality Disorder
2025-04-22

Abstract Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task – the Intentions Game. We involved individuals with (n=50) and without (n=53) a diagnosis of borderline personality disorder and assessed whether infractions to self-other generalisation may explain interpersonal (in)stability. Healthy controls initially used their preferences to predict others and were influenced by their partners, leading to self-other convergence. In contrast, individuals with borderline personality disorder maintained distinct self-other representations, generating a new neutral prior when learning about others. This allowed for equal predictive performance compared to controls despite reduced updating sensitivity. Furthermore, we explored theory-driven individual differences underpinning contagion. Overall, the findings provide a clear explanation of how self-other generalisation constrains and assists learning and how childhood adversity is associated with separation of internalised beliefs. Our model makes clear causal predictions about the mechanisms of social information generalisation concerning both joint and individual reward.
Exploration of fluorinated peptoid-based histone deacetylase inhibitors as dual-stage antiplasmodial agents
2025-04-22

this study, we investigated the antiplasmodial properties of a series of fluorinated peptoid-capped histone deacetylase inhibitors (HDACi) against the drug-sensitive 3D7 and drug-resistant Dd2 strains of Plasmodium falciparum, as well as the exo-erythrocytic liver stages and mature gametocytes. Among the series, compound 1h emerged as the most potent derivative, showing strong activity against both P. falciparum strains (Pf 3D7 and Dd2 IC50: 0.010 μM) and pronounced efficacy against P. berghei liver stages (IC50: 0.74 μM), while lacking activity against mature gametocytes. Compound 1j was identified as a second hit compound with slightly lower activity against asexual blood and liver stages (Pf 3D7 IC50: 0.015 μM; Pf Dd2 IC50: 0.018 μM; Pb EEF IC50: 3.69 μM) but showed excellent parasite selectivity (SIHepG2/3D7: 2053; SIHepG2/Dd2: 1711) and notable activity against mature gametocytes (IC50: 1.92 μM). Compared to our previous hit compound MAHA-022, both 1h and 1j exhibited improved activity against asexual blood stages and enhanced parasite selectivity, albeit with reduced efficacy against liver stage parasites. Taken together, compounds 1h and 1j represent promising multi-stage antiplasmodial HDACi scaffolds for further development and optimization.
Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study
2025-04-22

Abstract Common variants within TMEM106B are associated with risk for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). The G allele of the top single nucleotide polymorphism, rs1990622, confers protection against FTLD-TDP, including genetic cases due to GRN mutations or C9orf72 hexanucleotide repeat expansions. However, the effects of interaction between TMEM106B-rs1990622 and frontotemporal dementia (FTD) mutations on disease endophenotypes in genetic FTD are unknown. This longitudinal cohort study was embedded within the GENetic Frontotemporal dementia Initiative (GENFI). We included 518 participants from 222 families [209 non-carriers; 222 presymptomatic carriers (C9orf72 = 79; GRN = 101, MAPT = 42); 87 symptomatic carriers (C9orf72 = 45; GRN = 29; MAPT = 13)] followed for up to 7 years. Using linear mixed-effects models, we examined the effects of a triple interaction between TMEM106B-rs1990622G allele dosage (additive model: 0, 1 or 2 alleles) and autosomal dominant FTD mutations with clinical status, and time from baseline on (i) grey matter volume using a voxel-based analysis; (ii) serum neurofilament light chain (NfL) levels; and (iii) cognitive and behavioural measures. Mean age of participants was 47.9 ± 13.8 years, 58.1% were female and 61% had at least one G allele. C9orf72: rs1990622G allele dosage was associated with less atrophy within the right occipital region in presymptomatic carriers at baseline, and reduced atrophy rate within putamen and caudate nucleus, right frontotemporal regions, left cingulate and bilateral insular cortices in symptomatic carriers over time; lower NfL levels in presymptomatic carriers at baseline; better executive functions and language abilities in presymptomatic carriers; and maintained overall cognitive functions and behaviour in symptomatic carriers over time. GRN: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right temporal and occipital regions in presymptomatic carriers, and within the right frontal cortex and insula over time in symptomatic carriers; lower serum NfL levels over time in presymptomatic carriers and lower NfL levels at both baseline and over time in symptomatic carriers; and better global cognitive performance at baseline and higher attention/processing speed scores over time in symptomatic carriers. MAPT: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right inferior frontal gyrus in symptomatic carriers, but no effects on serum NfL or cognitive/behavioural measures. TMEM106B-rs1990622G allele dosage showed protective effects on multiple endophenotypes predominantly in GRN and C9orf72 groups. Therefore, TMEM106B genotype should be assessed in clinical trials, particularly of GRN- and C9orf72-related genetic FTD, due to its modifying effects on biomarker, imaging, cognitive and clinical outcomes.
Exploration of the visual streak of the Mongolian gerbil as a model for the human central retina
2025-04-22

Introduction The Mongolian gerbil (MG), a day-active rodent, features a particular retinal region of high visual acuity, the visual streak (VS). Optimized for vision in desert-like environments, the VS allows for a perfect view of the horizon between the projection areas of the sky and the ground. Here, we assess the structural basis of this specialized region and compare the findings to the conditions at the human retinal center. Methods The VSs of MG retinas ( n = 5) were evaluated morphologically with immunohistochemistry for cone, rod, and RPE cell-specific markers in dorsoventral cross-sections, and the results were compared to data from the near (adjacent) and far periphery. Mass spectrometry of the VS and peripheral retina/RPE was used to analyze the proteomic differential expression between these regions. Results In the VS of the MG, we found an increased density of cones, elongated photoreceptor outer segments (OSs), and a rod-to-cone ratio lying within the zone of descent between the border of the macula and the fovea (macular shoulder). Similarly, the base area of retinal pigment epithelium (RPE) cells in the VS was significantly reduced, while cells were taller than those in the periphery. Accordingly, proteomic data provided evidence for an enhanced abundance of key proteins relevant to photoreceptor and RPE function and pathophysiology of macular diseases in the VS. Conclusion The high degree of conformance between the VS data of the MG and the human central retina renders the MG a promising rodent, non-primate model of the central human retina.
Effects of Annealing on Electrode/MoS2 Interfaces Studied by Photoelectron Spectroscopy
2025-04-22

For optoelectronic devices based on transition metal dichalcogenides (TMDCs) like molybdenum disulfide (MoS2), contacts with metal electrode materials are of great importance. However, the role of possible interactions at these interfaces for the device performance is often not sufficiently considered. We present an in-depth study of interface properties between MoS2 and Au, Cu and Ti using photoelectron spectroscopy (PES) and scanning electron microscopy (SEM). By post-deposition annealing, we simulate the potential long-term effects of slow metal diffusion into MoS2. A doping of the TMDC was observed at the Au and Cu containing interfaces, as well as the (partial) diffusion of metal atoms into the TMDC substrate after annealing. In the case of Ti, we observe profound changes in the electronic structure, indicating a chemical reaction. The deposition of cobalt(II)-hexadecafluorophthalocyanine (CoPcF16) on the metal covered surface was utilized as a probe for the presence of metal atoms on the topmost TMDC layer before and after annealing.